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Biomedical subjects

J N Weiss

Publications and source records attributed to J N Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Controlling cardiac chaos.

The extreme sensitivity to initial conditions that chaotic systems display makes them unstable and unpredictable. Yet that same sensitivity also makes them highly susceptible to control, provided that the developing chaos can be analyzed in real time and that analysis is then used to make small control interventions. This strategy has been used here to stabilize cardiac arrhythmias induced by the drug ouabain in rabbit ventricle. By administering electrical stimuli to the heart at irregular times determined by chaos theory, the arrhythmia was converted to periodic beating.

Action Potentials↗
PubMed1992

Fertility rates with delayed fibrin glue: vasovasostomy in rats.

OBJECTIVE: To determine if fibrin glued vasovasostomy had comparable fertility rates to sutured vasovasostomy. DESIGN: Twenty adult male Sprague-Dawley rats underwent bilateral vasectomy. Two weeks after vasectomy, 10 rats had a bilateral sutured vasal anastomosis consisting of four mucosal and four seromuscular sutures with 10-0 nylon. The second group of 10 rats underwent bilateral fibrin glue vasal anastomosis consisting of two transmural sutures with 10-0 nylon followed by application of fibrin glue. One month after vasectomy reversal, each male rat was mated with a female rat for a period of 2 weeks. SETTING: Animal laboratory. PATIENTS PARTICIPANTS: Twenty male Sprague-Dawley rats. INTERVENTIONS: Bilateral vasectomies in 20 male Sprague-Dawley rats. Two weeks after vasectomy, 10 rats had bilateral sutured vasal anastomosis, and 10 rats had bilateral glued vasal anastomosis. MAIN OUTCOME MEASURES: Pregnancy after vasectomy reversal. RESULTS: Ten of 10 rats in the sutured group produced offspring for a fertility rate of 100%. Eight of 10 rats in the fibrin glue group produced offspring for a fertility rate of 80%. There was no statistically significant difference in the pregnancy rates between the two groups at the 95% confidence interval. CONCLUSION: Fibrin glue-delayed vasectomy reversal produces comparable fertility rates compared with conventional sutured vasectomy reversal in the rat.

Adhesives↗
PubMed1992

ATP-sensitive K+ channels and cellular K+ loss in hypoxic and ischaemic mammalian ventricle.

1. The contribution of ATP-sensitive K+ (K+ATP) channels to the rapid increase in cellular K+ efflux and shortening of action potential duration (APD) during early myocardial ischaemia and hypoxia remains controversial, because for the first 10 min of ischaemia or hypoxia in intact hearts cytosolic [ATP] remains about two orders of magnitude greater than the [ATP] causing half-maximal blockade of K+ATP channels in excised membrane patches. The purpose of this study was to investigate this apparent discrepancy. 2. During substrate-free hypoxia, total, diastolic and systolic unidirectional K+ efflux rates increased by 43, 26 and 103% respectively after 8.3 min in isolated arterially perfused rabbit interventricular septa loaded with 42K+. APD shortened by 39%. From the Goldman-Hodgkin-Katz equation, the relative increases in systolic and diastolic K+ efflux rates were consistent with activation of a voltage-independent K+ conductance. 3. During total global ischaemia, [K+]o measured with intramyocardial valinomycin K(+)-sensitive electrodes increased at a maximal rate of 0.68 mM min-1, which could be explained by a less than 26% increase in unidirectional K+ efflux rate (assuming no change in K+ influx), less than the increase during hypoxia. APD shortened by 23% over 10 min. 4. During hypoxia and ischaemia, cytosolic [ATP] decreased by about one-third from 6.8 +/- 0.5 to 4.3 +/- 0.3 and 4.6 +/- 0.4 mM respectively, and free cytosolic [ADP] increased from 15 to 95 and approximately 63 microM respectively. 5. To estimate the percentage of activation of current through K+ATP channels (IK,ATP) necessary to double the systolic K+ efflux rate (comparable to the increase during hypoxia), K+ efflux during a single simulated action potential was measured by blocking non-K+ currents under control conditions and after IK,ATP was fully activated by metabolic inhibitors. Activation of 0.41 +/- 0.07% of maximal IK,ATP was sufficient to double the systolic K+ efflux rate. The equivalent amount of constant hyperpolarizing current also shortened the APD in the isolated myocytes by 41 +/- 5%, compared to the 39% APD shortening observed during hypoxia in the intact heart. 6. The degree of activation of IK,ATP expected to occur during hypoxia and ischaemia was estimated by characterizing the ATP sensitivity of K+ATP channels in the presence of 2 mM-free Mgi2+ and 0, 10, 100 and 300 microM-ADPi in inside-out membrane patches excised from guinea-pig ventricular myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Oxygen free radicals and cardiac reperfusion abnormalities.

Oxygen free radicals are highly reactive compounds causing peroxidation of lipids and proteins and are thought to play an important role in the pathogenesis of reperfusion abnormalities including myocardial stunning, irreversible injury, and reperfusion arrhythmias. Free radical accumulation has been measured in ischemic and reperfused myocardium directly using techniques such as electron paramagnetic resonance spectroscopy and tissue chemiluminescence and indirectly using biochemical assays of lipid peroxidation products. Potential sources of free radicals during ischemia and reperfusion have been identified in myocytes, vascular endothelium, and leukocytes. In several different experimental models exogenous free radical-generating systems have been shown to produce alterations in cardiac function that resemble the various reperfusion abnormalities described above. Injury to processes involved in regulation of the intracellular Ca2+ concentration may be a common mechanism underlying both free radical-induced and reperfusion abnormalities. Direct effects of free radicals on each of the known Ca(2+)-regulating mechanisms of the cell as well as the contractile proteins and various ionic membrane currents have been described. Free radicals also inhibit critical enzymes in anaerobic and aerobic metabolic pathways, which may limit the metabolic reserve of reperfused myocardium and contribute to intracellular Ca2+ overload. Inhibiting free radical accumulation during myocardial ischemia/reperfusion with free radical scavengers and inhibitors has been demonstrated to reduce the severity of myocardial stunning, irreversible injury, and reperfusion arrhythmias in many, but not all, studies. This evidence strongly implicates free radical accumulation during myocardial ischemia/reperfusion as an important pathophysiological mechanism of reperfusion abnormalities, although many issues remain unresolved.

Animals↗
PubMed1992

Activation of ATP-sensitive K+ channels by cromakalim. Effects on cellular K+ loss and cardiac function in ischemic and reperfused mammalian ventricle.

Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sensitive K+ channels, in isolated arterially perfused rabbit interventricular septa subjected to ischemia and reperfusion and, through use of the patch clamp technique, in inside-out membrane patches excised from guinea pig ventricular myocytes. During aerobic perfusion, 5 microM cromakalim shortened action potential duration (APD) from 217 +/- 7 to 201 +/- 10 msec, had no effect on [K+]o, and reduced tension by 17 +/- 3% (n = 11). During ischemia, pretreatment with 5 microM cromakalim resulted in 1) more rapid APD shortening (71 +/- 9 versus 166 +/- 7 msec at 10 minutes and 63 +/- 12 versus 122 +/- 8 msec at 30 minutes), 2) similar [K+]o accumulation after 10 minutes (8.9 +/- 0.3 versus 9.6 +/- 0.5 mM) but a trend toward increased [K+]o accumulation after 30 minutes (11.0 +/- 1.7 versus 9.6 +/- 1.0 mM), and 3) similar times for tension to decline to 50% of control (2.14 +/- 0.16 versus 2.14 +/- 0.19 minutes) but shorter time to fall to 20% of control (4.34 +/- 0.33 versus 4.90 +/- 0.22 minutes; p = 0.003). After 60 minutes of reperfusion following 30 minutes of ischemia, recovery of function was similar, with a trend toward better recovery of developed tension (to 58 +/- 9% versus 39 +/- 10% of control; p = 0.18) and tissue ATP levels in cromakalim-treated hearts but no differences in APD or rest tension. Thus, 5 microM cromakalim had mild effects in normal heart but greatly accelerated APD shortening during ischemia without markedly increasing [K+]o accumulation, possibly because the more rapid APD shortening reduced the time-averaged driving force for K+ efflux through ATP-sensitive K+ channels. A significant cardioprotective effect during 30 minutes of ischemia plus 60 minutes of reperfusion could not be demonstrated in this model. In excised membrane patches studied at room temperature, the ability of cromakalim to activate ATP-sensitive K+ channels was significantly potentiated by 100 microM but not 15 microM cytosolic ADP, suggesting that in addition to the modest fall in cytosolic ATP during early ischemia, the rapid increases in cytosolic ADP may further sensitize cardiac ATP-sensitive K+ channels to activation by cromakalim.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Benign lesions of the external genitalia.

Benign external genital lesions, being uncommon, can cause a significant diagnostic dilemma for the physician and anxiety for the patient. These lesions can be grouped into three categories: vascular lesions, nevi, and benign new growths.

Genital Diseases, Male↗
PubMed1991

Ventricular arrhythmias in ischemic heart disease.

Ventricular arrhythmias remain the leading cause of death from coronary artery disease. This review summarizes current thinking in several areas relating to the pathophysiology, prognosis, and therapy of ventricular arrhythmias associated with acute and chronic coronary artery disease syndromes. The experimental basis of arrhythmias in the setting of acute myocardial ischemia and chronic myocardial infarction is described, stressing the important pathophysiologic differences between these two conditions. The effects of the autonomic nervous system as a key modulator of ischemic arrhythmogenesis are discussed. Insights, derived from endocardial mapping studies, into the nature of ventricular tachycardia in humans with chronic myocardial infarction are described, including implications for risk stratification and therapy to prevent arrhythmia recurrence. Current therapeutic principles are discussed in the management of ventricular arrhythmias associated with coronary artery disease, including pharmacologic approaches, surgical and catheter ablation, and automatic implantable cardioverting and defibrillating devices.

Acute Disease↗
PubMed1991

Identification of a peptide inhibitor of the cardiac sarcolemmal Na(+)-Ca2+ exchanger.

The deduced amino acid sequence of the cardiac sarcolemmal Na(+)-Ca2+ exchanger has a region which could represent a calmodulin binding site. As calmodulin binding regions of proteins often have an autoinhibitory role, a synthetic peptide with this sequence was tested for functional effects on Na(+)-Ca2+ exchange activity. The peptide inhibits the Na(+)-dependent Ca2+ uptake (KI approximately 1.5 microM) and the Nao(+)-dependent Ca2+ efflux of sarcolemmal vesicles in a noncompetitive manner with respect to both Na+ and Ca2+. The peptide is also a potent inhibitor (KI approximately 0.1 microM) of the Na(+)-Ca2+ exchange current of excised sarcolemmal patches. The binding site for the peptide on the exchanger is on the cytoplasmic surface of the membrane. The exchanger inhibitory peptide binds calmodulin with a moderately high affinity. From the characteristics of the inhibition of the exchange of sarcolemmal vesicles, we deduce that only inside-out sarcolemmal vesicles participate in the usual Na(+)-Ca2+ exchange assay. This contrasts with the common assumption that both inside-out and right-side-out vesicles exhibit exchange activity.

Amino Acid Sequence↗
PubMed1991

Intracavernous pharmacotherapy in psychogenic impotence.

Twenty-five men with psychogenic impotence but without serious psychopathology were considered for intracavernosal therapy with papaverine hydrochloride and phentolamine mesylate. A total of 20 proved suitable and began self-injection in conjunction with sex therapy; 8 patients had return of spontaneous erections without pharmacotherapy, although one of them needs to keep the medication in his refrigerator. The other 12 patients are continuing self-injection therapy. Psychotherapy with self-injection may be helpful in the management of psychogenic erectile impotence.

Adult↗
PubMed1991

Mechanisms of excitation-contraction coupling failure during metabolic inhibition in guinea-pig ventricular myocytes.

1. The effects of complete metabolic inhibition on excitation-contraction coupling in heart were studied by exposing patch-clamped guinea-pig ventricular myocytes, loaded via the patch pipette with the Ca2+ indicator Fura-2 (0.1 mM), to carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP, 1 microM) and 2-deoxyglucose (2-DG, 10 mM) while simultaneously recording membrane current, Fura-2 fluorescence, and cell motion. The patch pipette solution contained Cs+ and TEA (tetraethylammonium) to partially block K+ currents. 2. During voltage clamps from a holding potential of -40 mV to a test potential of 0 mV, complete metabolic inhibition decreased the Ca2+ current (ICa), activated the ATP-sensitive K+ current, modestly elevated diastolic [Ca2+]i and markedly reduced the [Ca2+]i transient without altering its voltage dependence. Active shortening was impaired and diastolic cell length decreased prior to large increases in diastolic [Ca2+]i, consistent with rigor induced by ATP depletion. Return of the [Ca2+]i transient to baseline and relaxation upon repolarization were also delayed. 3. Despite the depression of the peak [Ca2+]i transient induced by membrane depolarization during metabolic inhibition, the [Ca2+]i transient induced by a rapid exposure to 5 mM-caffeine was greater than control. The Na(+)-Ca2+ exchange current during the caffeine-induced [Ca2+]i transient was not affected by metabolic inhibition. 4. [Ca2+]i transients depressed by metabolic inhibition could be enhanced by augmenting ICa with elevated [Ca2+]o (10 mM) and Bay K 8644 (5 microM). 5. To study the relationship between the magnitude of ICa and the amplitude of the [Ca2+]i transient, ICa was modulated either by (a) voltage clamping the cell to different membrane potentials at constant [Ca2+]o or by (b) rapidly altering [Ca2+]o immediately prior to a voltage clamp to a fixed membrane potential. Under control conditions, the relationship between the size of ICa and the magnitude of the [Ca2+]i transient was the same whether ICa was modulated by altering membrane potential or [Ca2+]o, suggesting that membrane potential does not significantly modulate the Ca(2+)-induced Ca2+ release mechanism of cardiac excitation-contraction coupling. 6. After metabolic inhibition, however, the same ICa released less Ca2+ than under control conditions, consistent with some impairment of the Ca2+ release mechanism. 7. These results suggest that under conditions in which excitability is maintained by controlling membrane voltage and minimizing metabolically sensitive K+ currents, the decreased [Ca2+]i transient observed during metabolic inhibition severe enough to induce rigor is caused primarily by depression of ICa and not by depletion of intracellular Ca2+ stores. Additional factors also modestly hinder Ca2+ release from intracellular stores during metabolic inhibition.

Animals↗
PubMed1991

Activation of cardiac ATP-sensitive K+ current during hypoxia: correlation with tissue ATP levels.

Although previous work has implicated activation of ATP-sensitive K+ currents (IK,ATP) in action potential duration (APD) shortening and increased cellular K+ efflux during hypoxia, ischemia, and metabolic inhibition, no prior study has directly assessed the tissue levels of ATP at which IK,ATP activates in intact cardiac muscle. Accordingly, we correlated changes in tissue high-energy phosphate levels during substrate-free hypoxia with activation of IK,ATP in intact voltage-clamped rabbit papillary muscles. During 10 min of hypoxia, the outward K+ current measured in response to a voltage-clamp pulse step from -50 to 0 mV increased from 8.57 +/- 0.27 to 15.67 +/- 1.41 microA (P less than 0.05, n = 6), and APD decreased from 452 +/- 54 to 292 +/- 56 ms (P less than 0.05, n = 6). Glibenclamide (10 microM), a specific IK,ATP blocker, prevented both of these changes. In a parallel set of experiments, papillary muscles were freeze-clamped and assayed for tissue ATP. In these muscles, 10 min of hypoxia resulted in a comparable degree of APD shortening (441 +/- 24 to 297 +/- 18 ms, P less than 0.05, n = 12), and tissue ATP levels fell from 13.2 +/- 1.3 to 9.7 +/- 0.7 mumol/g dry wt (P less than 0.05, n = 12). These results directly demonstrate that IK,ATP is activated and causes APD shortening during hypoxia in intact cardiac muscle despite only a modest (approximately 25%) decline in tissue ATP content.

Action Potentials↗
PubMed1991

Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.

Sulfonylurea derivatives glibenclamide and tolbutamide are selective blockers of ATP-sensitive K+ (KATP) channels. However, their ability to prevent cellular K+ loss and shortening of action potential duration during ischemia or hypoxia in the intact heart is modest compared with their efficacy at blocking KATP channels in excised membrane patches. In the isolated arterially perfused rabbit interventricular septum, the increase in unidirectional K+ efflux and shortening of action potential duration during substrate-free hypoxia were effectively blocked by glibenclamide, but only by very high concentrations (100 microM); during hypoxia with glucose present, glibenclamide was only partially effective at reducing K+ loss. During total global ischemia (10 minutes), up to 100 microM glibenclamide or 1 mM tolbutamide attenuated shortening of action potential duration but only reduced [K+]0 accumulation by a maximum of 32 +/- 6%. In isolated patch-clamped guinea pig ventricular myocytes in which the whole-cell ATP-sensitive K+ current was activated by exposure to the metabolic inhibitors, glibenclamide (up to 100 microM) and tolbutamide (10 mM) were only partially effective at blocking the whole-cell ATP-sensitive K+ current (maximum block, 51 +/- 10% and 50 +/- 9%, respectively), especially when ADP was included in the patch electrode solution. In inside-out membrane patches excised from these myocytes, glibenclamide blocked unitary currents through KATP channels with a Kd of 0.5 microM and a Hill coefficient of 0.5 in the absence of ADP at the cytosolic membrane surface, but block was incomplete when 100 microM ADP (+2 mM free Mg2+) was present. ADP had a similar effect on block of KATP channels by tolbutamide. These findings suggest that free cytosolic [ADP], which rises rapidly to the 100 microM range during early myocardial ischemia and hypoxia, may account for the limited efficacy of sulfonylureas at blocking ischemic and hypoxic cellular K+ loss under these conditions.

Action Potentials↗
PubMed1991

Effects of lysophosphatidylcholine on electrophysiological properties and excitation-contraction coupling in isolated guinea pig ventricular myocytes.

Lysophosphoglyceride accumulation in ischemic myocardium has been implicated as a cause of arrhythmias. We examined the effects of lysophosphatidylcholine (LPC) in isolated guinea pig ventricular myocytes. In paced myocytes loaded with the Ca2+ indicator Indo-1-AM and studied at room temperature, 20 microM LPC caused an initial positive inotropic effect followed by spontaneous automaticity, a decline in active cell shortening, and progressive diastolic shortening (contracture) leading to cell death. These changes were accompanied by a progressive increase in cytosolic [Ca2+]i. In patch-clamped myocytes dialyzed internally with high EGTA concentrations, LPC caused membrane depolarization, shortening of the action potential duration, and abnormal automaticity as seen in multicellular preparations. Voltage clamp experiments revealed the appearance of a nonselective leak conductance without significant changes in the delayed rectifier K+ current, inward rectifier K+ current, L-type Ca2+ current, and T-type Ca2+ current. Pretreatment with 20 mM caffeine and [Ca2+]o-free solution did not prevent the leak current. In patch clamped myocytes loaded with 0.1 mM Fura-2 salt, the [Ca2+]i transient induced by either voltage clamps or brief caffeine exposure remained normal until the nonselective leak current developed. The Na(+)-Ca2+ exchange current elicited during caffeine-induced [Ca2+]i transients also did not appear to be altered by LPC. Qualitatively similar results were obtained in myocytes studied at 35 degrees C. The membrane detergent saponin (0.005% wt/wt) mimicked all of the effects of LPC. We conclude that under these experimental conditions the effects of LPC are most compatible with a detergent action causing membrane leakiness with resultant depolarization, [Ca2+]i overload, and contracture.

Animals↗
PubMed1990

Treatment of catecholamine-sensitive right ventricular tachycardia by endocardial catheter ablation.

Endocardial catheter ablation with direct current high voltage shocks was performed in a patient with recurrent syncope due to a catecholamine-sensitive ventricular tachycardia that was drug refractory and occurred in the absence of identifiable heart disease. Pace mapping and catheter activation mapping of the spontaneous and isoproterenol-induced ventricular tachycardia located the tachycardia origin in the right ventricular outflow tract. Ablation dramatically reduced spontaneous ventricular tachycardia and ectopic activity (from 50,000 to less than 100 ectopic beats/24 h). The patient has remained symptom free and without ventricular tachycardia recurrence for 3 years. These observations and review of previous studies suggest that catheter mapping can easily locate the arrhythmia focus in the right ventricular outflow tract and that catheter ablation can be performed at low risk. Catheter ablation is a viable option for the treatment of right ventricular catecholamine-sensitive tachycardias that are unresponsive to antiarrhythmic drugs.

Adult↗
PubMed1990

Facioscapulohumeral muscular dystrophy: evidence for selective, genetic electrophysiologic cardiac involvement.

Facioscapulohumeral muscular dystrophy is an autosomal dominant disorder with an incidence of 3 to 10 cases per million. The only type of cardiac involvement ascribed to this neuromuscular disorder is a unique form of heart disease--permanent atrial paralysis. However, reported cases of facioscapulohumeral muscular dystrophy probably represented instead what is now recognized as phenotypically similar Emery-Dreifuss dystrophy. Cardiac involvement, therefore, has not been convincingly reported in facioscapulohumeral muscular dystrophy, but because of the clinical similarity of that disorder to Emery-Dreifuss dystrophy and its genetic variants, a prospective investigation of the electrophysiologic properties of the atria and atrioventricular (AV) node and infranodal conduction was undertaken in 30 rigorously documented cases of facioscapulohumeral muscular dystrophy. All patients had a 12 lead surface electrocardiogram (ECG), 22 had a 24 h ambulatory ECG, 15 patients had two-dimensional echocardiographic/Doppler studies and 10 patients underwent 12 intracardiac electrophysiologic investigations. Left atrial, right atrial or biatrial P wave abnormalities were present in 60% of the surface ECGs. Evidence of abnormal AV node or infranodal conduction was present on intracardiac electrophysiologic study or surface ECG in 27% of patients. Atrial flutter or fibrillation was induced by single atrial extra stimuli in 10 of the 12 intracardiac electrophysiologic studies. Sinus node function was abnormal in three patients. This investigation provides the first secure evidence of cardiac involvement in facioscapulohumeral muscular dystrophy. The involvement is represented by relatively high susceptibility to induced atrial flutter or fibrillation during electrophysiologic study, together with less frequent evidence of abnormal sinus node function and abnormal AV node or infranodal conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Frequency-dependent effects of quinidine on the ventricular action potential and QRS duration in humans.

We studied the frequency-dependent effects of quinidine on the right ventricular action potential and QRS duration in 10 patients (nine men and one woman; mean age, 57 +/- 14 years) undergoing electrophysiologic studies for clinical indications. The right ventricular monophasic action potential, electrocardiographic, and conventional intracardiac electrical signals from various sites were recorded at different pacing cycle lengths from 30 seconds to 1 minute before and after a 10-mg/kg i.v. quinidine infusion. We used the extrastimulus technique to determine the effects of quinidine on ventricular refractory periods at different pacing cycle lengths and on the abrupt changes of the action potential duration. The action potential duration progressively decreased as the ventricular pacing rate increased at baseline and after quinidine infusion. Quinidine significantly increased the action potential duration from that of control by 25 msec (p less than 0.02) at the relatively slow pacing cycle lengths of 600, 500, and 400 msec. Quinidine's effect on the action potential duration was attenuated at the pacing cycle length of 350 msec and became negligible at 300 msec. In contrast, quinidine progressively lengthened the QRS duration as the pacing rate increased (20, 18, 37, 46, and 34 msec at pacing cycle lengths of 600, 500, 400, 350, and 300 msec, respectively; p less than 0.05). There were no rate-dependent changes in the QRS duration during the control period. The relation between the ventricular refractory periods and the action potential duration at different pacing cycle lengths was also determined before and after quinidine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Enhanced utilization of exogenous glucose improves cardiac function in hypoxic rabbit ventricle without increasing total glycolytic flux.

The effects of elevated glucose on cardiac function during hypoxia were investigated in isolated arterially perfused rabbit interventricular septa. Rest tension, developed tension, intracellular potential, 42K+ efflux, lactate production, exogenous glucose utilization, and tissue high-energy phosphate levels were measured during a 50-min period of hypoxia with 4, 5, or 50 mM glucose present (isosmotically balanced with sucrose) and during reoxygenation for 60 min with perfusate containing 5 mM glucose/45 mM sucrose. At physiologic (4 or 5 mM) and supraphysiologic glucose (50 mM), lactate production and high-energy phosphate levels during hypoxia were equally well maintained, yet cardiac dysfunction was markedly attenuated by 50 mM glucose. Despite identical rates of total glycolytic flux, exogenous glucose utilization was enhanced by 50 mM glucose so that tissue glycogen levels remained normal during hypoxia, whereas glycogen became depleted with 4 or 5 mM glucose present during hypoxia. Most of the beneficial effects of 50 mM glucose occurred during the first 25 min of hypoxia. Prior glycogen depletion had no deleterious effects during hypoxia with 50 mM glucose present, but exacerbated cardiac dysfunction during hypoxia with 5 mM glucose present. These findings indicate that enhanced utilization of exogenous glucose improved cardiac function during hypoxia without increasing total glycolytic flux or tissue high-energy phosphate levels, suggesting a novel cardioprotective mechanism.

Animals↗