Michael Artman, M.D.

beta2-Adrenergic receptor agonists stimulate L-type calcium current independent of PKA in newborn rabbit ventricular myocytes
Collis, Leon P; Srivastava, Shekhar; Coetzee, William A; Artman, Michael
2007 Nov;293(5):H2826-H2835, American journal of physiology. Heart & circulatory physiology
Selective stimulation of beta(2)-adrenergic receptors (ARs) in newborn rabbit ventricular myocardium invokes a positive inotropic effect that is lost during postnatal maturation. The underlying mechanisms for this age-related stimulatory response remain unresolved. We examined the effects of beta(2)-AR stimulation on L-type Ca(2+) current (I(Ca,L)) during postnatal development. I(Ca,L) was measured (37 degrees C; either Ca(2+) or Ba(2+) as the charge carrier) using the whole-cell patch-clamp technique in newborn (1 to 5 days old) and adult rabbit ventricular myocytes. Ca(2+) transients were measured concomitantly by dialyzing the cell with indo-1. Activation of beta(2)-ARs (with either 100 nM zinterol or 1 microM isoproterenol in the presence of the beta(1)-AR antagonist, CGP20712A) stimulated I(Ca,L) twofold in newborns but not in adults. The beta(2)-AR-mediated increase in Ca(2+) transient amplitude in newborns was due exclusively to the augmentation of I(Ca,L). Zinterol increased the rate of inactivation of I(Ca,L) and increased the Ca(2+) flux integral. The beta(2)-AR inverse agonist, ICI-118551 (500 nM), but not the beta(1)-AR antagonist, CGP20712A (500 nM), blocked the response to zinterol. Unexpectedly, the PKA blockers, H-89 (10 microM), PKI 6-22 amide (10 microM), and Rp-cAMP (100 microM), all failed to prevent the response to zinterol but completely blocked responses to selective beta(1)-AR stimulation of I(Ca,L) in newborns. Our results demonstrate that in addition to the conventional beta(1)-AR/cAMP/PKA pathway, newborn rabbit myocardium exhibits a novel beta(2)-AR-mediated, PKA-insensitive pathway that stimulates I(Ca,L). This striking developmental difference plays a major role in the age-related differences in inotropic responses to beta(2)-AR agonists
— id: 75449, year: 2007, vol: 293, page: H2826, stat: Journal Article,

Modulation of human cardiovascular outward rectifying chloride channel by intra- and extracellular ATP
Liu, Gong Xin; Vepa, Sanjay; Artman, Michael; Coetzee, William A
2007 Dec;293(6):H3471-H3479, American journal of physiology. Heart & circulatory physiology
The macroscopic volume-regulated anion current (VRAC) is regulated by both intracellular and extracellular ATP, which has important implications in signaling and regulation of cellular excitability. The outwardly rectifying Cl(-) channel (ORCC) is a major contributor to the VRAC. This study investigated the effects of intracellular and extracellular ATP on the ORCCs expressed in the human cardiovascular system. With inside-out single-channel patch-clamp techniques, ORCCs were recorded from myocytes isolated from human atrium and septal ventricle and from primary cells originating from human coronary artery endothelium and human coronary artery smooth muscle. ORCCs from all of these tissues had similar biophysical properties, i.e., they were outwardly rectifying in symmetrical Cl(-) solutions, exhibited a slope conductance of approximately 90-100 pS at positive potentials and approximately 22 pS at negative potentials, and had a high open probability that was independent of voltage or time. The presence of ATP at the cytosolic face of the membrane increased the number of patches that contained functional ORCC but had no effect on gating. In contrast, 'extracellular' ATP (in pipette solution) had no effect on the proportion of patches in which ORCC was detected but strongly reduced the open probability by increasing the closed dwell time. The potency order for nucleotides to affect gating was ATPgammaS > ATP = UTP > ADP > AMP, which suggests that a negatively charged phosphate group is involved in ORCC block. Our findings are consistent with a role of ORCC in the human cardiovasculature (atrium, ventricle, and coronary arteries). Regulation of ORCC by extracellular ATP suggests that this channel may have an important role in maintaining electrical activity and membrane potential under conditions in which extracellular ATP levels are elevated, such as with ATP release from nerve endings or during pathophysiological conditions
— id: 93831, year: 2007, vol: 293, page: H3471, stat: Journal Article,

Phospholemman expression is high in the newborn rabbit heart and declines with postnatal maturation
Srivastava, Shekhar; Cala, Steven E; Coetzee, William A; Artman, Michael
2007 Apr 6;355(2):338-341, Biochemical & biophysical research communications
Phospholemman (PLM) is a small sarcolemmal protein that modulates the activities of Na(+)/K(+)-ATPase and the Na(+)/Ca(2+) exchanger (NCX), thus contributing to the maintenance of intracellular Na(+) and Ca(2+) homeostasis. We characterized the expression and subcellular localization of PLM, NCX, and the Na(+)/K(+)-ATPase alpha1-subunit during perinatal development. Western blotting demonstrates that PLM (15kDa), NCX (120kDa), and Na(+)/K(+)-ATPase alpha-1 (approximately 100kDa) proteins are all more than 2-fold higher in ventricular membrane fractions from newborn rabbit hearts (1-4-day old) compared to adult hearts. Our immunocytochemistry data demonstrate that PLM, NCX, and Na(+)/K(+)-ATPase are all expressed at the sarcolemma of newborn ventricular myocytes. Taken together, our data indicate that PLM, NCX, and Na(+)/K(+)-ATPase alpha-1 proteins have similar developmental expression patterns in rabbit ventricular myocardium. Thus, PLM may have an important regulatory role in maintaining cardiac Na(+) and Ca(2+) homeostasis during perinatal maturation
— id: 71420, year: 2007, vol: 355, page: 338, stat: Journal Article,

Consequences of Cardiac Myocyte-Specific Ablation of KATP channels in Transgenic Mice expressing Dominant Negative Kir6 Subunits
Tong, XiaoYong; Porter, Lisa M; Liu, GongXin; Dhar-Chowdhury, Piyali; Srivastava, Shekhar; Pountney, David J; Yoshida, Hidetada; Artman, Michael; Fishman, Glenn I; Yu, Cindy; Iyer, Ramesh; Morley, Gregory E; Gutstein, David E; Coetzee, William A
2006 Aug;291(2):H543-H551, American journal of physiology. Heart & circulatory physiology
Cardiac KATP channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice which express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression with the alpha-myosin heavy chain promoter. Weight gain and development after birth of these mice were similar to wild-type mice, but an increased mortality was noted after the age of 4-5 months. Transgenic mice lacked cardiac KATP channel activity as assessed with patch clamp techniques. Consistent with a decreased current density observed at positive voltages, the action potential duration was increased in these mice. Some myocytes developed early afterdepolarizations following isoproterenol treatment. Hemodynamic measurements revealed no significant effects on ventricular function (apart from a slightly elevated heart rate) whereas in-vivo electrophysiological recordings revealed a prolonged ventricular effective refractory period in transgenic mice. The transgenic mice tolerated stress less well as evident from treadmill stress tests. The pro-arrhythmogenic features and lack of adaptation to a stress response in transgenic mice suggests that these features are intrinsic to the myocardium and that KATP channels in the myocardium have an important role in protecting the heart from lethal arrhythmias and adaptation to stress situations
— id: 63616, year: 2006, vol: 291, page: H543, stat: Journal Article,

Cardiovascular development and congenital malformations : molecular & genetic mechanisms
Artman, Micheal
Malden MA : Blackwell Futura, 2005,
— id: 2072, year: 2005, vol: , page: , stat: ,

Expression of ATP-sensitive K+ channel subunits during perinatal maturation in the mouse heart
Morrissey, Alison; Parachuru, Lavanya; Leung, Monika; Lopez, Gwendolyn; Nakamura, Tomoe Y; Tong, Xiaoyong; Yoshida, Hidetada; Srivastiva, Shekhar; Chowdhury, Piyali Dhar; Artman, Michael; Coetzee, William A
2005 Aug;58(2):185-192, Pediatric research
Prevailing data suggest that sarcolemmal ATP-sensitive (K(ATP)) channels in the adult heart consist of Kir6.2 and SUR2A subunits, but the expression of other K(ATP) channel subunits (including SUR1, SUR2B, and Kir6.1) is poorly defined. The situation is even less clear for the immature heart, which shows a remarkable resistance to hypoxia and metabolic stress. The hypoxia-induced action potential shortening and opening of sarcolemmal K(ATP) channels that occurs in adults is less prominent in the immature heart. This might be due in part to the different biophysical and pharmacological properties of K(ATP) channels of immature and adult K(ATP) channels. Because these properties are largely conferred by subunit composition, it is important to examine the relative expression levels of the various K(ATP) channel subunits during maturation. We therefore used RNAse protection assays, reverse transcription-PCR approaches, and Western blotting to characterize the mRNA and protein expression profiles of K(ATP) channel subunits in fetal, neonatal, and adult mouse heart. Our data indicate that each of the K(ATP) channel subunits (Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B) is expressed in the mouse heart at all of the developmental time points studied. However, the expression level of each of the subunits is low in the fetal heart and progressively increases with maturation. Each of the subunits seems to be expressed in ventricular myocytes with a subcellular expression pattern matching that found in the adult. Our data suggest that the K(ATP) channel composition may change during maturation, which has important implications for K(ATP) channel function in the developing heart
— id: 58895, year: 2005, vol: 58, page: 185, stat: Journal Article,

Developmental expression of NCS-1 (frequenin), a regulator of Kv4 K+ channels, in mouse heart
Nakamura, Tomoe Y; Sturm, Eron; Pountney, David J; Orenzoff, Barbara; Artman, Michael; Coetzee, William A
2003 Apr;53(4):554-557, Pediatric research
The channel proteins responsible for the cardiac transient outward K+ current (Ito) of human and rodent heart are composed, in part, of pore-forming Kv4.3 or Kv4.2 principal subunits. Recent reports implicate K+ channel interacting proteins (members of the neuronal Ca2+-binding protein family) as subunits of the Ito channel complex. We reported that another Ca2+-binding protein, frequenin [or neuronal calcium center protein-1 (NCS-1)], also functions as a Kv4 auxiliary subunit in the brain. By examining cardiac expression of NCS-1, the aim of this study was to examine the potential physiologic relevance of this protein as an additional regulator of cardiac Ito. Immunoblot analysis demonstrates NCS-1 protein to be expressed in adult mouse ventricle at levels comparable to that found in some brain regions. Cardiac NCS-1 protein expression levels are much higher in fetal and neonatal mouse hearts when compared with the adult. Immunocytochemical analysis of isolated neonatal mouse ventricular myocytes demonstrates co-localization of NCS-1 and Kv4.2 proteins at the sarcolemma. Given its high levels of expression in the heart, NCS-1 should be considered an important potential Kv4 regulatory subunit, particularly in the immature heart
— id: 39285, year: 2003, vol: 53, page: 554, stat: Journal Article,

Neonatal cardiology
Artman, Michael; Mahony, Lynn; Teitel, David F.
New York : McGraw-Hill, 2002,
— id: 650, year: 2002, vol: , page: , stat: ,

Measuring health-related quality of life in children with heart disease
Connolly, Dana; Rutkowski, Monika; Auslender, Marcelo; Artman, Michael
2002 May;15(2):74-80, Applied nursing research
This study tested an instrument for measuring health-related quality of life (HRQL) in children with heart disease. HRQL was measured using the New York University Children's Heart Health Survey in a sample of 0- to 20-year-old subjects with heart disease compared with a control group. Heart disease was associated with impairment on all subscales except psychological function. Adolescent self-reports did not differ significantly between the cardiac group and healthy controls in any of the subscales. This instrument may be useful in assessing the impact of various treatment strategies in this population
— id: 39651, year: 2002, vol: 15, page: 74, stat: Journal Article,

Impact of a clinical pathway on the postoperative care of children undergoing surgical closure of atrial septal defects
DeSomma, Michelle; Divekar, Abhay; Galloway, Aubrey C; Colvin, Stephen B; Artman, Michael; Auslender, Marcelo
2002 Nov;15(4):243-248, Applied nursing research
The purpose of this study was to impact of a clinical pathway on the postoperative management of children undergoing surgical closure of atrial septal defects (ASDs). Three groups of children were studied: group 1 (14 patients), before introduction of an intensive care team, minimally invasive surgery, and the clinical pathway; group 2 (17 patients), after the introduction of the intensive care team and minimally invasive surgical techniques but before the pathway; and group 3 (30 patients), after implementation of the clinical pathway. Average hospital length of stay fell from 118.52 +/- 19.83 hours (4.9 +/- 0.83 days) in group 1 to 95.92 +/- 66.48 hours (3.99 +/-2.77 days) in group 2 and declined further to 54.29 +/- 20.17 hours (2.26 +/- 0.84 days) in group 3 (p <.05). There were statistically significant decreases in laboratory resource utilization (p <.05). The addition of a dedicated intensive care team and utilization of minimally invasive surgical techniques reduced mean length of stay (by 20%) and resource utilization (by 50%). However, only the implementation of the pathway provided the consistency necessary for maximal quality management, cost saving, and reduction in length of stay (additional 44% reduction in mean length of stay and 40% reduction in resource utilization). These results show the incremental advantage of implementing a defined clinical pathway for postoperative management of children with atrial septal defects
— id: 32916, year: 2002, vol: 15, page: 243, stat: Journal Article,

The New York University Pediatric Heart Failure Index: A new method of quantifying chronic heart failure severity in children
Connolly D; Rutkowski M; Auslender M; Artman M
2001 May;138(5):644-648, Journal of pediatrics
OBJECTIVE: The assessment of the severity of heart failure in pediatric patients is handicapped by the subjectivity of diagnostic parameters. This study evaluated the feasibility of a new standardized heart failure index, the New York University Pediatric Heart Failure Index (NYU PHFI), to quantify the degree of heart failure in a selected pediatric population.Methods and Results: The index is a weighted, linear combination of scores based on symptoms, physical signs, and medical regimen. Overall, healthy children (n = 12) scored very low (0 to 2) on this index. Mean scores of children (<2 years; mean age, 4.8 months; n = 12) with a left-to-right shunt lesion declined from 11.4 (SD +/- 4.1, P <.001, 2-tailed test) before surgery to 1.8 (SD +/- 1.3) after surgical correction of their cardiac defects. The average inter-observer correlation coefficient was 0.95 (P <.001), despite a wide range of scores. CONCLUSIONS: The NYU PHFI appears to be a reliable and convenient instrument for measuring heart failure severity in children. These initial results support further testing in broader diagnostic and age groups and over longer periods
— id: 20680, year: 2001, vol: 138, page: 644, stat: Journal Article,

Abnormal right coronary artery flow and multiple right ventricular myocardial infarctions associated with severe right ventricular systolic hypertension
Divekar A; Auslender M; Colvin S; Artman M; Rutkowski M
2001 Jan;14(1):70-72, Journal of the American Society of Echocardiography
The impact of left ventricular hypertension on coronary flow patterns in adult patients has been well described. In contrast, few reports exist regarding the association of right coronary flow abnormalities with right ventricular hypertension. The observation of myocardial infarcts, right ventricular hypertension, and abnormal coronary flow pattern-as well as its normalization with relief of right ventricular hypertension-lends support to a causal relation between ventricular hypertension and coronary flow abnormalities
— id: 26806, year: 2001, vol: 14, page: 70, stat: Journal Article,

Different effects of the Ca(2+)-binding protein, KChIP1, on two Kv4 subfamily members, Kv4.1 and Kv4.2
Nakamura TY; Nandi S; Pountney DJ; Artman M; Rudy B; Coetzee WA
2001 Jun 22;499(3):205-209, FEBS letters
The Ca(2+)-binding protein, K(+) channel-interacting protein 1 (KChIP1), modulates Kv4 channels. We show here that KChIP1 affects Kv4.1 and Kv4.2 currents differently. KChIP1 slows Kv4.2 inactivation but accelerates the Kv4.1 inactivation time course. Kv4.2 activation is shifted in a hyperpolarizing direction, whereas a depolarizing shift occurs for Kv4.1. On the other hand, KChIP1 increases the current amplitudes and accelerates recovery from inactivation of both currents. An involvement of the Kv4 N-terminus in these differential effects is demonstrated using chimeras of Kv4.2 and Kv4.1. These results reveal a novel interaction of KChIP1 with these two Kv4 members. This represents a mechanism to further increase the functional diversity of K(+) channels
— id: 21167, year: 2001, vol: 499, page: 205, stat: Journal Article,

Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycan-deficient hamsters
Nakamura, T Y; Iwata, Y; Sampaolesi, M; Hanada, H; Saito, N; Artman, M; Coetzee, W A; Shigekawa, M
2001 Aug;281(2):C690-C699, American journal of physiology. Cell physiology
Deficiency of delta-sarcoglycan (delta-SG), a component of the dystrophin-glycoprotein complex, causes cardiomyopathy and skeletal muscle dystrophy in Bio14.6 hamsters. Using cultured myotubes prepared from skeletal muscle of normal and Bio14.6 hamsters (J2N-k strain), we investigated the possibility that the delta-SG deficiency may lead to alterations in ionic conductances, which may ultimately lead to myocyte damage. In cell-attached patches (with Ba(2+) as the charge carrier), an approximately 20-pS channel was observed in both control and Bio14.6 myotubes. This channel is also permeable to K(+) and Na(+) but not to Cl(-). Channel activity was increased by pressure-induced stretch and was reduced by GdCl(3) (>5 microM). The basal open probability of this channel was fourfold higher in Bio14.6 myotubes, with longer open and shorter closed times. This was mimicked by depolymerization of the actin cytoskeleton. In intact Bio14.6 myotubes, the unidirectional basal Ca(2+) influx was enhanced compared with control. This Ca(2+) influx was sensitive to GdCl(3), signifying that stretch-activated cation channels may have been responsible for Ca(2+) influx in Bio14.6 hamster myotubes. These results suggest a possible mechanism by which cell damage might occur in this animal model of muscular dystrophy
— id: 134936, year: 2001, vol: 281, page: C690, stat: Journal Article,

Thyroid hormone increases pacemaker activity in rat neonatal atrial myocytes
Sun ZQ; Ojamaa K; Nakamura TY; Artman M; Klein I; Coetzee WA
2001 Apr;33(4):811-824, Journal of molecular & cellular cardiology
The effects of thyroid hormone (3,3',5-triiodo- L -thyronine, T3) on pacemaker activity were studied with electrophysiological and pharmacological approaches using spontaneously beating neonatal atrial myocytes cultured from 2-day-old rats. Treatment with T3 (10(-8)m) for 24-48 h led to a positive chronotropic effect. The beating rate of T3-treated cells was 244+/-19 beats/min and for control cells it was 122+/-10 beats/min (P<0.05). Action potentials were recorded and showed that the predominant effect of T3 was to increase the diastolic depolarization rate (99.5+/-9.8 in T3-treated group v 44.0+/-7.8 mV/s in untreated group). Some cells that exhibited pacemaker activity lacked a pacemaker current (I(f)) under voltage clamp conditions I(f)was recorded in 5 of 12 spontaneously active control cells and in 6 of 10 T3-treated cells. In those cells exhibiting the pacemaker current, the I(f)density was significantly larger in T3-treated cells (-7.9+/-2.6 pA/pF v-1.8+/-0.5 pA/pF in control). The L-type Ca2+ current density was similar in the two groups (at -7 mV, -7.5+/-1.5 in treated group v-8.6+/-1.0 pA/pF in control). In the presence of T3, the Na+-Ca2+ exchanger current (I(Na/Ca)) density was larger (e.g. at +60 mV, it was 4.8+/-0.5 v 3.5+/-0.2 pA/pF in control cells, P<0.05). As intracellular Ca2+ is extruded from the cell, the electrogenic Na+-Ca2+ exchanger causes a declining inward current, which may contribute to the pacemaker potential-this declining inward current was demonstrated using the action potential voltage clamp technique and was shown to be larger in T3-treated myocytes. Our data demonstrate that thyroid hormone enhances pacemaker activity and that this may be due in part to an increased Na+-Ca2+ exchanger activity
— id: 21224, year: 2001, vol: 33, page: 811, stat: Journal Article,

Cellular basis for age-related differences in cardiac excitation-contraction coupling
Artman M; Henry G; Coetzee WA
2000 Sep 1;11(3):185-194, Progress in pediatric cardiology
Clinical experience indicates that infants and young children respond to a variety of cardiovascular pharmacological and physiological interventions differently than adults. What is less clear, however, are the cellular and molecular mechanisms that contribute to these age-related differences. Based largely upon results from animal models, it is apparent that developmental changes occur in numerous pathways and proteins involved in the regulation of contractile function and in the determinants of inotropic responsiveness. The purposes of this review are to provide a brief overview of cardiac excitation-contraction and to illustrate some of the important age-related differences in the mechanisms involved in calcium regulation in the heart. This scientific foundation may help to explain certain clinical observations in the very young. Furthermore, it is hoped that a better understanding of the fundamental processes involved in controlling cardiac contractile function will stimulate additional research in the search for more specific, rational and age-appropriate cardiovascular therapeutics
— id: 39556, year: 2000, vol: 11, page: 185, stat: Journal Article,

Overview of the management of pediatric heart failure
Auslender, M; Artman, M
2000 SEP ;11(3):231-241, Progress in pediatric cardiology
For the most part of this the century heart failure syndrome was understood as a pump failure disorder with hemodynamic consequences stemming from the same myocardial dysfunction. In addition supply and demand theories were used to explain the nature of symptoms. As a result, therapeutic strategies were directed at correcting the abnormal hemodynamic conditions and normalizing the delivery of the much needed nutrients. Improvement of cardiac pump function with inotropic drugs and abnormal circulatory conditions with afterload and preload modifications became therapeutic goals and standards of care. However, while vasodilators and inotropic drugs immediately improved symptoms, hemodynamics and functional status, in the long term they either did not affect or worsen the natural history of heart failure. In pediatrics, this is further complicated by the lack of large scale trials addressing issues pertinent to the particularities that affect heart failure in children. In the late 1980s and 1990s heart failure has evolved into a more complex, multiple and interactive pathophysiologic disorder. Today not only the abnormal hemodynamics but also the biological disorders are pharmacologic targets. The reversal or slowing of myocardial maladaptation has become one of the most important therapeutic goals. With this end in mind therapeutic strategies may seem counterintuitive and paradoxical, such as the use of P-blockers. This review will address the current thinking and therapeutic modalities used today in the treatment of heart failure syndrome in the adult population. We also discuss some of the issues why we think that these principles can be extrapolated to the pediatric population. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved
— id: 54513, year: 2000, vol: 11, page: 231, stat: Journal Article,

Management of heart failure in children
Balaguru D; Artman M; Auslender M
2000 Jan;30(1):1-35, Current problems in pediatrics
— id: 11853, year: 2000, vol: 30, page: 1, stat: Journal Article,

Effects of thyroid hormone on action potential and repolarizing currents in rat ventricular myocytes
Sun ZQ; Ojamaa K; Coetzee WA; Artman M; Klein I
2000 Feb;278(2):E302-E307, American journal of physiology. Endocrinology & metabolism
Thyroid hormones play an important role in cardiac electrophysiology through both genomic and nongenomic mechanisms of action. The effects of triiodothyronine (T(3)) on the electrophysiological properties of ventricular myocytes isolated from euthyroid and hypothyroid rats were studied using whole cell patch clamp techniques. Hypothyroid ventricular myocytes showed significantly prolonged action potential duration (APD(90)) compared with euthyroid myocytes, APD(90) of 151 +/- 5 vs. 51 +/- 8 ms, respectively. Treatment of hypothyroid ventricular myocytes with T(3) (0.1 microM) for 5 min significantly shortened APD by 24% to 115 +/- 10 ms. T(3) similarly shortened APD in euthyroid ventricular myocytes, but only in the presence of 4-aminopyridine (4-AP), an inhibitor of the transient outward current (I(to)), which prolonged the APD by threefold. Transient outward current (I(to)) was not affected by the acute application of T(3) to either euthyroid or hypothyroid myocytes; however, I(to) density was significantly reduced in hypothyroid compared with euthyroid ventricular myocytes
— id: 8549, year: 2000, vol: 278, page: E302, stat: Journal Article,

Congenital heart disease
Galloway AC; Artman M; Colvin SB
Principles of surgery New York : McGraw-Hill, 1999,
— id: 3834, year: 1999, vol: , page: ?, stat: Chapter,

Subcellular [Ca2+]i gradients during excitation-contraction coupling in newborn rabbit ventricular myocytes
Haddock PS; Coetzee WA; Cho E; Porter L; Katoh H; Bers DM; Jafri MS; Artman M
1999 Sep 3;85(5):415-427, Circulation research
The central role of T-tubule and sarcoplasmic reticulum (SR) diadic junctions in excitation-contraction (EC) coupling in adult (AD) ventricular myocytes suggests that their absence in newborn (NB) cells may manifest as an altered EC coupling phenotype. We used confocal microscopy to compare fluo-3 [Ca2+]i transients in the subsarcolemmal space and cell center of field-stimulated NB and AD rabbit ventricular myocytes. Peak systolic [Ca2+]i occurred sooner and was higher in the subsarcolemmal space compared with the cell center in NB myocytes. In AD myocytes, [Ca2+]i rose and declined with similar profiles at the cell center and subsarcolemmal space. Disabling the SR (10 micromol/L thapsigargin) slowed the rate of rise and decline of Ca2+ in AD myocytes but did not alter Ca2+ transient kinetics in NB myocytes. In contrast to adults, localized SR Ca2+ release events ('Ca2+ sparks') occurred predominantly at the cell periphery of NB myocytes. Immunolabeling experiments demonstrated overlapping distributions of the Na(+)-Ca2+ exchanger and ryanodine receptors (RyR2) in AD myocytes. In contrast, RyR2s were spatially separated from the sarcolemma in NB myocytes. Confocal sarcolemmal imaging of di-8-ANEPPS-treated myocytes confirmed an extensive T-tubule network in AD cells, and that T-tubules are absent in NB myocytes. A mathematical model of subcellular Ca2+ dynamics predicts that Ca2+ flux via the Na(+)-Ca2+ exchanger during an action potential can account for the subsarcolemmal Ca2+ gradients in NB myocytes. Spatial separation of sarcolemmal Ca2+ entry from SR Ca2+ release channels may minimize the role of SR Ca2+ release during normal EC coupling in NB ventricular myocytes
— id: 6195, year: 1999, vol: 85, page: 415, stat: Journal Article,

The role of Kir2.1 in the genesis of native cardiac inward-rectifier K+ currents during pre- and postnatal development
Nakamura TY; Lee K; Artman M; Rudy B; Coetzee WA
1999 Apr 30;868:434-437, Annals of the New York Academy of Sciences
Our results demonstrate that (a) the Kir2.1 gene encodes a native K+ channel protein with a 21-pS conductance; (b) this channel has an important role in the genesis of adult ventricular 1K1; and (c) the contribution of Kir2.1 channel proteins to 1K1 changes during development. The lack of contribution of Kir2.1 to fetal 1K1 channels is interesting from the point of view of possible future generation of knockout mice lacking Kir2.1, since cardiac abnormalities would not be expected to result in fetal lethality. These observations provide further support for a generalized hypothesis that different genes may code for 1K1 channel proteins at various developmental stages. However, the effects of these AS-oligos must first be examined on native 1K1 channels in cardiac myocytes before definite conclusions can be reached
— id: 6164, year: 1999, vol: 868, page: 434, stat: Journal Article,

Identification and cloning of TWIK-originated similarity sequence (TOSS): a novel human 2-pore K+ channel principal subunit
Pountney DJ; Gulkarov I; Vega-Saenz de Miera E; Holmes D; Saganich M; Rudy B; Artman M; Coetzee WA
1999 May 7;450(3):191-196, FEBS letters
We have identified and cloned a new member of the mammalian tandem pore domain K+ channel subunit family, TWIK-originated similarity sequence, from a human testis cDNA library. The 939 bp open reading frame encodes a 313 amino acid polypeptide with a calculated Mr of 33.7 kDa. Despite the same predicted topology, there is a relatively low sequence homology between TWIK-originated similarity sequence and other members of the mammalian tandem pore domain K+ channel subunit family group. TWIK-originated similarity sequence shares a low (< 30%) identity with the other mammalian tandem pore domain K+ channel subunit family group members and the highest identity (34%) with TWIK-1 at the amino acid level. Similar low levels of sequence homology exist between all members of the mammalian tandem pore domain K+ channel subunit family. Potential glycosylation and consensus PKC sites are present. Northern analysis revealed species and tissue-specific expression patterns. Expression of TWIK-originated similarity sequence is restricted to human pancreas, placenta and heart, while in the mouse, TWIK-originated similarity sequence is expressed in the liver. No functional currents were observed in Xenopus laevis oocytes or HEK293T cells, suggesting that TWIK-originated similarity sequence may be targeted to locations other than the plasma membrane or that TWIK-originated similarity sequence may represent a novel regulatory mammalian tandem pore domain K+ channel subunit family subunit
— id: 8510, year: 1999, vol: 450, page: 191, stat: Journal Article,

Recent advances in cardiovascular development: promise for the future
Baldwin HS; Artman M
1998 Dec;40(3):456-468, Cardiovascular research
— id: 7300, year: 1998, vol: 40, page: 456, stat: Journal Article,

Influence of postnatal changes in action potential duration on Na-Ca exchange in rabbit ventricular myocytes
Haddock PS; Artman M; Coetzee WA
1998 May;435(6):789-795, Pflugers archiv = European journal of physiology
Cardiac Na-Ca exchanger (NCX) expression and current density are significantly greater in newborn rabbit hearts compared with adults. However, the relatively short action potential (AP) at birth may limit the impact of increased NCX expression by diminishing Ca2+ entry via Na-Ca exchange current (INaCa). To address the interdependence of AP duration and NCX activity, we voltage-clamped newborn (NB, 1-5 day), juvenile (JV, 10-14 day) and adult (AD) rabbit myocytes with a series of APs of progressively increasing duration (APD90: 108-378 ms) under nominally chloride-free conditions. In each age group we quantified an increase in outward (QExout) and inward (QExin) Ni2+-sensitive charge movement in response to AP prolongation. QExout and QExin measured during age-appropriate APs declined postnatally [QEXout: NB (2 day) 0.19 +/- 0.02, JV (10 day) 0.10 +/- 0.01, AD 0.04 +/- 0.002; QEXin: NB -0. 2 +/- 0.01, JV -0.11 +/- 0.02; AD -0.04 +/- 0.003 pC/pF] despite the significantly shorter APD90 of newborn myocytes (NB 122 +/- 10; AD 268 +/- 22 ms). When Ca2+ fluxes by other transport pathways were blocked with nifedipine, ryanodine and thapsigargin, age-appropriate APs elicited contractions in NB and JV but not AD myocytes (NB 4.8 +/- 0.5, JV 1.2 +/- 0.3% resting length). These data demonstrate that a shorter AP does not negate the impact of increased NCX expression at birth
— id: 7590, year: 1998, vol: 435, page: 789, stat: Journal Article,

Inhibition of rat ventricular IK1 with antisense oligonucleotides targeted to Kir2.1 mRNA
Nakamura TY; Artman M; Rudy B; Coetzee WA
1998 Mar;274(3 Pt 2):H892-H900, American journal of physiology. Heart & circulatory physiology
The cardiac inward rectifying K+ current (IK1) is important in maintaining the maximum diastolic potential. We used antisense oligonucleotides to determine the role of Kir2.1 channel proteins in the genesis of native rat ventricular IK1. A combination of two antisense phosphorothioate oligonucleotides inhibited heterologously expressed Kir2.1 currents in Xenopus oocytes, either when coinjected with Kir2.1 cRNA or when applied in the incubation medium. Specificity was demonstrated by the lack of inhibition of Kir2.2 and Kir2.3 currents in oocytes. In rat ventricular myocytes (4-5 days culture), these oligonucleotides caused a significant reduction of whole cell IK1 (without reducing the transient outward K+ current or the L-type Ca2+ current). Cell-attached patches demonstrated the occurrence of multiple channel events in control myocytes (8, 14, 21, 35, 43, and 80 pS). The 21-pS channel was specifically knocked down in antisense-treated myocytes (fewer patches contained this channel, and its open frequency was reduced). These results demonstrate that the Kir2.1 gene encodes a specific native 21-pS K(+)-channel protein and that this channel has an essential role in the genesis of cardiac IK1
— id: 7702, year: 1998, vol: 274, page: H892, stat: Journal Article,

Noninvasive, in utero imaging of mouse embryonic heart development with 40-MHz echocardiography
Srinivasan S; Baldwin HS; Aristizabal O; Kwee L; Labow M; Artman M; Turnbull DH
1998 Sep 1;98(9):912-918, Circulation
BACKGROUND: The increasing number of transgenic and targeted mutant mice with embryonic cardiac defects has resulted in the need for noninvasive techniques to examine cardiac structure and function in early mouse embryos. We report the first use of a novel 40-MHz ultrasound imaging system in the study of mouse cardiac development in utero. METHODS AND RESULTS: Transabdominal scans of mouse embryos staged between 8.5 and 13.5 days of gestation (E8.5 to E13.5) were obtained in anesthetized mice. Atrial and ventricular contractions could be discerned from E9.5, and changes in cardiac morphology were observed from E9.5 to E13.5. Hyperechoic streaming patterns delineated flow through the umbilical, vitelline, and other major blood vessels. Diastolic and systolic ventricular areas were determined by planimetry of the epicardial borders, and fractional area change was measured as an index of contractile function. Significant increases in ventricular size were documented at each stage between E10.5 and E13.5, and the ability to perform serial imaging studies over 3 days of embryonic development is described. Finally, the detection of vascular cell adhesion molecule 1 (VCAM-1) homozygous null mutant embryos demonstrates the first example of noninvasive, in utero analysis of cardiac structure and function in a targeted mouse mutant. CONCLUSIONS: We used 40-MHz echocardiography to identify key elements of the early mouse embryonic cardiovascular system and for noninvasive dimensional analysis of developing cardiac ventricles. The ability to perform serial measurements and to detect mutant embryos with cardiac defects highlights the usefulness of the technique for investigating normal and abnormal cardiovascular development
— id: 7805, year: 1998, vol: 98, page: 912, stat: Journal Article,

Role of the sarcoplasmic reticulum in contraction and relaxation of immature rabbit ventricular myocytes
Balaguru D; Haddock PS; Puglisi JL; Bers DM; Coetzee WA; Artman M
1997 Oct;29(10):2747-2757, Journal of molecular & cellular cardiology
Previous indirect studies of newborn hearts have suggested a diminished functional role of the SR and a greater dependency upon trans-sarcolemmal Ca2+ fluxes to directly elicit contraction and promote relaxation. We tested the hypothesis that the SR in newborn rabbit hearts is functionally incompetent by measuring contraction and relaxation in ventricular myocytes isolated from the hearts of 1-2-day-old (newborn), 10-12-day-old (juvenile) and >150-day-old (adult) rabbits. Electrically stimulated twitch characteristics were compared to those elicited by the rapid application of 10 mm caffeine in the presence and absence of functional sarcolemmal Na-Ca exchange (disabled using a Na+- and Ca2+-free extracellular solution). During steady state, electrically-induced contractions were lower in amplitude in newborn and juvenile compared to adult myocytes (2.9+/-0.5 and 3.4+/-0.3 v 8.5+/-0.9% of resting cell length, respectively; n=24-29) and relaxation was slower in immature myocytes (t0.75 values: newborn 250+/-20; juvenile 240+/-10; adult 130+/-20 ms, n=14-21). Contrary to our hypothesis, caffeine triggered sufficient SR Ca2+ release from immature myocytes to elicit contractions of similar magnitude to adults (newborn 12.8+/-1. 1; juvenile 14.0+/-0.9; adult 15.0+/-1.6% of resting cell length, n=25-29). The amplitude of indo-1 Ca2+ transients during steady-state twitch was 36+/-12% of the maximal caffeine-induced Ca2+ transient in newborns (n=6) and 59+/-4% in adults (n=6). Caffeine slightly prolonged relaxation in adult myocytes (t0. 75=200+/-30 ms), but accelerated relaxation in newborn and juvenile myocytes (t0.75=180+/-20 and 150+/-30 ms, respectively). When both the SR and Na-Ca exchanger were disabled, the rate of relaxation (attributable to the sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uniporter) of newborn and juvenile myocytes was significantly faster than in the adults (1660+/-210 and 3030+/-180 v 4530+/-310 ms, respectively; n=14-21). We conclude that neonatal and adult rabbit ventricular myocytes have comparable SR Ca2+ load, but neonatal cells exhibit smaller fractional SR Ca2+ release during steady-state contractions and greater Ca2+ removal by sarcolemmal Na-Ca exchange during relaxation.
— id: 8376, year: 1997, vol: 29, page: 2747, stat: Journal Article,

Na+/Ca2+ exchange current and contractions measured under Cl(-)-free conditions in developing rabbit hearts
Haddock PS; Coetzee WA; Artman M
1997 Aug;273(2 Pt 2):H837-H846, American journal of physiology. Heart & circulatory physiology
Previous studies suggesting a greater functional role of cardiac Na+/Ca2+ exchange at birth were performed using tightly buffered free cytosolic Ca2+ concentration ([Ca2+]i). Because Na+/Ca2+ exchange current (INaCa) is influenced by physiological fluctuations in [Ca2+]i, we used conditions of minimally buffered [Ca2+]i to simultaneously record INaCa and cell contractions in single ventricular myocytes isolated from 1 to 27-day-old and adult rabbits. With conventional Cl(-)-containing solutions. Ni(2+)-sensitive outward and inward charge movements were unbalanced, suggesting the presence of a contaminating current (presumably the Ca(2+)-activated Cl- current). Removing Cl- abolished this discrepancy in all age groups and allowed for the accurate quantitation of INaCa. Under Cl(-)-free conditions, outward and inward charge movements were high at birth (4 days: 0.42 +/- 0.03 and -0.38 +/- 0.04 pC/pF, respectively) and decreased postnatally (adult: 0.08 +/- 0.01 and -0.07 +/- 0.01 pC/pF, respectively). Newborn but not adult myocytes contracted during depolarizations in the presence of nifedipine, ryanodine, and thapsigargin. The magnitudes of outward charge movement (Ca2+ influx) and cell shortening exhibited similar voltage dependence, consistent with INaCa-mediated contractions. These results indicate that INaCa can directly support contraction in newborn rabbit ventricular myocytes
— id: 7162, year: 1997, vol: 273, page: H837, stat: Journal Article,

Na-Ca exchange inhibitory peptide prevents apparent depolarization induced calcium release in rat ventricular myocytes
Haddock, PS; Artman, M; Coetzee, WA
1997 OCT 21 ;96(8):991-991, Circulation
— id: 105047, year: 1997, vol: 96, page: 991, stat: Journal Article,

Kir2.1 antisense oligonucleotides decrease inward rectifier K+ currents expressed in Xenopus oocytes by poly(A(+)) RNA from neonatal and adult, but not fetal mouse ventricles
Nakamura, TY; Artman, M; Rudy, B; Coetzee, WA
1997 OCT 21 ;96(8):2380-2380, Circulation
— id: 105048, year: 1997, vol: 96, page: 2380, stat: Journal Article,

Spotlight on cardiovascular development
Artman, Michael; Nakanishi, Toshio; Rosen, Michael R
New York : Elsevier, 1996,
— id: 2074, year: 1996, vol: , page: , stat: ,

Thyroid hormone regulates Na(+)-Ca2+ exchanger expression during postnatal maturation and in adult rabbit ventricular myocardium
Boerth SR; Artman M
1996 Feb;31 Spec No:E145-E152, Cardiovascular research
OBJECTIVES: Expression of the cardiac Na(+)-Ca2+ exchanger (NCX) is high at birth and declines rapidly to adult levels by approximately 21 days in rabbits. The aim was to evaluate the role of thyroid hormone in regulating cardiac NCX expression. METHODS: Adult New Zealand White rabbits were made hypothyroid by treatment with propylthiouracil or hyperthryoid by administration of sigma-thyroxine. Hypothyroidism was induced in immature rabbits by exposure to propylthiouracil from gestational day 25 through the first 21 days after birth. NCX steady-state mRNA levels were quantitated using Northern slot blots with poly(A+) RNA isolated from ventricular myocardium of treated and age-matched euthyroid animals. As a control, steady-state levels of cardiac sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) were measured in each group. Thyroid status was confirmed with serum T4, ventricular weight and body weight measurements. Immunoreactive NCX protein levels were assessed using Western blots. RESULTS: Compared with euthyroid controls, NCX steady-state mRNA levels increased to 189 +/- 20% in hypothyroid adults and decreased to 55 +/- 15% in hyperthyroid adults. Opposite effects were observed for SERCA2a expression (58 +/- 7% in hypothyroidism and 130 +/- 15% in hyperthyroidism). In hypothyroid 21-day-old rabbits, NCX steady-state mRNA levels were elevated to 205 +/- 30% of age-matched euthyroid controls. SERCA2a levels were unaffected in the immature animals, possibly due to inability to reduce thyroid levels sufficiently to affect SERCA2a expression in this model. Changes in NCX mRNA levels produced comparable changes in immunoreactive NCX protein levels. CONCLUSIONS: Thyroid hormone reciprocally regulates NCX and SERCA2a expression in the ventricles of adult rabbits. Hypothyroidism resulted in sustained high levels of NCX expression in 21-day-old rabbits. These results suggest that the postnatal thyroid hormone surge is important for the normal down-regulation of cardiac NCX expression during the first 3 weeks after birth in developing rabbits
— id: 7932, year: 1996, vol: 31 Spec No, page: E145, stat: Journal Article,

Na+/Ca2+ exchange current density in cardiac myocytes from rabbits and guinea pigs during postnatal development
Artman M; Ichikawa H; Avkiran M; Coetzee WA
1995 Apr;268(4 Pt 2):H1714-H1722, American journal of physiology. Heart & circulatory physiology
It has been proposed that the activity of the cardiac sarcolemmal Na+/Ca2+ exchanger may be greatest in developing animals before the sarcoplasmic reticulum (SR) reaches functional maturity. Experiments were performed in rabbits, which have a sparse SR at birth, and in newborn guinea pigs, which exhibit a more extensive SR. Whole cell voltage clamp techniques were used to characterize the Ni(2+)-sensitive Na+/Ca2+ exchange current in single freshly isolated cardiac myocytes. Na+/Ca2+ exchange current was measured from a holding potential of -40 mV by using a slow-ramp voltage protocol (-120 to +60 mV, 0.09 V/s) in the presence of Ba2+, Cs+, tetraethylammonia, D-600, and ouabain to block Ca2+, Na+, and K+ currents. Experiments in developing rabbits (1-22 days old) demonstrated that Na+/Ca2+ exchange current density was greatest at 1-4 days and declined rapidly over the first 3 wk of age. In contrast, Na+/Ca2+ exchange current density in newborn guinea pig myocytes did not differ from that recorded in adults. These results confirm that Na+/Ca2+ exchange is functional at birth in both rabbits and guinea pigs. The species-related difference in the ontogeny of Na+/Ca2+ exchange is consistent with the concept that Na+/Ca2+ exchange assumes a relatively greater role in newborn animals with a sparse SR
— id: 8294, year: 1995, vol: 268, page: H1714, stat: Journal Article,

NA+-CA2+ EXCHANGE CURRENT-DENSITY DECLINES DURING EARLY POSTNATAL MATURATION IN RABBIT VENTRICULAR MYOCYTES
ARTMAN, M; COETZEE, WA
1994 APR ;35(4):A29-A29, Pediatric research
— id: 105052, year: 1994, vol: 35, page: A29, stat: Journal Article,

Developmental changes in myocardial intropic responsiveness
Artman, Michael
Austin TX : R.G. Landes, 1994,
— id: 2073, year: 1994, vol: , page: , stat: ,

Steady-state mRNA levels of the sarcolemmal Na(+)-Ca2+ exchanger peak near birth in developing rabbit and rat hearts
Boerth SR; Zimmer DB; Artman M
1994 Feb;74(2):354-359, Circulation research
To functionally compensate for an underdeveloped sarcoplasmic reticulum in immature cardiomyocytes, it has been proposed that the sarcolemmal Na(+)-Ca2+ exchanger may assume a more predominant role for regulating cytosolic Ca2+. Previous studies using sarcolemma prepared from developing rabbit hearts demonstrated that Na(+)-dependent Ca2+ uptake and exchanger protein content were highest at birth and declined postnatally. To further investigate the significance of the Na(+)-Ca2+ exchanger during normal myocardial development, steady-state mRNA levels of the cardiac Na(+)-Ca2+ exchanger were quantitated by Northern blot and slot-blot analyses using poly(A+) RNA isolated from rabbit and rat ventricles at various fetal and postnatal ages. Northern analyses were performed with a 1.35-kb guinea pig cardiac Na(+)-Ca2+ exchanger cDNA probe. Exchanger mRNA levels were quantitated by densitometric scans of the slot blots, and results were normalized by reprobing the same blots with 32P 5'-end-labeled oligo(dT). In both species, exchanger mRNA levels peaked near birth and declined postnatally. Maximal levels were approximately sixfold greater in the late fetal rabbit (gestational day 29) and eightfold greater in the early newborn rat (postnatal day 1) compared with adults of the respective species. The parallel changes in exchanger mRNA and protein levels suggest that developmental regulation of cardiac Na(+)-Ca2+ exchanger expression involves pretranslational control mechanisms. These results support the concept that during normal cardiac development, Na(+)-Ca2+ exchanger expression is maximal near the time of birth and then declines postnatally as Ca2+ regulation by the sarcoplasmic reticulum reaches functional maturity
— id: 8426, year: 1994, vol: 74, page: 354, stat: Journal Article,

DEVELOPMENTAL-CHANGES IN THE ELECTROGENIC NA+-CA2+ EXCHANGE CURRENT-DENSITY IN VOLTAGE-CLAMPED, ISOLATED RABBIT VENTRICULAR MYOCYTES
COETZEE, WA; AVKIRAN, M; HEARSE, DJ; ARTMAN, M
1993 MAR ;473(3):P181-P181, Journal of physiology
— id: 105054, year: 1993, vol: 473, page: P181, stat: Journal Article,

Sarcolemmal Na(+)-Ca2+ exchange activity and exchanger immunoreactivity in developing rabbit hearts
Artman M
1992 Nov;263(5 Pt 2):H1506-H1513, American journal of physiology. Heart & circulatory physiology
It has been postulated that as a consequence of an underdeveloped sarcoplasmic reticulum, sarcolemmal Na(+)-Ca2+ exchange assumes relatively greater importance in modulating Ca2+ fluxes in the developing heart. To explore this concept, cardiac sarcolemmal vesicles were prepared from late fetal (28-day gestation), newborn (24-48 h), immature (14-16 days), and adult New Zealand White rabbits. Na(+)-dependent Ca2+ uptake was measured by diluting Na(+)-loaded (140 mM) vesicles into Na(+)-free buffer and measuring 45Ca2+ uptake (40 microM Ca2+) by timed quenching and rapid filtration. Vesicles from all four age groups demonstrated Ca2+ uptake curves characteristic of Na(+)-Ca2+ exchange with stimulation by valinomycin and inhibition by amiloride. Initial uptake velocity (measured at 2 s and corrected for the fraction of competent vesicles) was significantly higher in fetal (23.2 +/- 5.5 nmol/mg) and newborn (26.2 +/- 5.9 nmol/mg) than in adult sarcolemmal preparations (7.3 +/- 1.2 nmol/mg). Uptake was intermediate in the 2-wk-old group (13.7 +/- 1.7 nmol/mg). The relative amounts of exchanger protein were compared by quantitating immunoreactivity using a polyclonal antibody to the Na(+)-Ca2+ exchanger. Densitometric scanning of protein slot blots demonstrated approximately 2.5 times more exchanger protein in fetal and newborn sarcolemma than in adult preparations. The relative amount of exchanger protein detected immunologically corresponded with the age-related differences observed in exchanger activity. Thus the cardiac sarcolemmal Na(+)-Ca2+ exchanger is abundant and functionally well-developed in the late fetal/early newborn rabbit heart and appears to decline postnatally.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 8425, year: 1992, vol: 263, page: H1506, stat: Journal Article,

Effects of hemorrhagic shock and retransfusion on myocardial beta-adrenergic receptors and adenylate cyclase activity
Artman, Michael
[S.l.] : Ft. Belvoir Defense Technical Information Center, 1991,
Mechanisms for the myocardial dysfunction observed following hemorrhagic shock remain unclear. A well characterized rabbit model was utilized to determine the effects of shock and retransfusion on myocardial beta- adrenergic receptors and adenylate cyclase activity. Hemorrhagic shock was produced by rapid blood withdrawal to reduce mean arterial pressure to 35 mmHg in anesthetized rabbits instrumented for comprehensive hemodynamic monitoring. The shock state was maintained for 60 minutes and then the animals were transfused with the autologous warmed shed blood. Ventricular myocardium was analyzed for dihydroalprenolol binding and adenylate cyclase activity. There was no effect of shock or retransfusion on basal or stimulated adenylate cyclase activity
— id: 2075, year: 1991, vol: , page: , stat: ,

Effects of poloxamer 188 on hemodynamcis in survival in a rabbit model of hemorrhagic shock and retransfusion
Mayer, David C; Artman, Michael
[S.l.] : Ft. Belvoir Defense Technical Information Center, 1990,
The effects of an antithrombotic, rheologic agent (Poloxamer 188) were examined in an acute model of severe hemorrhagic shock in rabbits. Anesthetized rabbits were instrumented for comprehensive hemodynamic monitoring. Blood was withdrawn to reduce the mean arterial pressure to 35 mmHg. The shock state was maintained for 60 minutes, followed by transfusion with autologous warmed shed blood. At the time of transfusion, treated animals received an intravenous bolus of Poloxamer 188 (200 mg), followed by continued infusion of either 50 mg/kg/hr or 200 mg/kg/hr. No demonstrable effects on hemodynamics were observed. However, in animals treated with Poloxamer 188, 13 of 16 animals survived the entire 3 hour monitoring. In contrast, in the group of animals that received the autologous blood but were not treated with Poloxamer 188, only 6 of 16 animals survived. Although additional studies are needed, these results suggest that Poloxamer 188 may favorably affect early mortality when administered in the resuscitation phase of hemorrhagic shock. Keywords: Hemorrhagic shock; Reperfusion injury; Poloxamer 188. (jes)
— id: 2077, year: 1990, vol: , page: , stat: ,

Effects of hemorrhagic shock on antioxidant enzyme activities
Artman, Michael; Mayer, David C
[S.l.] : Ft. Belvoir Defense Technical Information Center, 1989,
A model of hemorrhagic shock has been developed using rabbits. Rabbits are anesthetized and instrumented for comprehensive hemodynamic monitoring. Blood is withdrawn to obtain a mean arterial pressure of 35 mmHg. Retransfusion with autologous warmed shed blood is performed either 30 or 60 minutes following blood withdrawal. Tissue samples are obtained at various time intervals for determination of antioxidant enzymes activities. Results to-date indicate that superoxide dismutase activity either declines or is unchanged in plasma, myocardium, brain, large and small intestines, liver, skeletal muscle, and lung. In contrast, catalase activity is induced with substantial increases in catalase activity in each of the aforementioned tissues. These results may have important implications for understanding the pathophysiology of hemorrhagic shock and consequently, in the design of therapeutic strategies for resuscitation from hemorrhagic shock. Keywords: Hemorrhagic shock. (KT)
— id: 2076, year: 1989, vol: , page: , stat: ,