Biomedical subjects

G Gerstenblith

Publications and source records attributed to G Gerstenblith.

At least 73 records · Page 4Linked to original sources

PubMed1990

Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Effects of amiloride on metabolism and contractility during reoxygenation in perfused rat hearts.

Myocardial recovery after hypoxia may be determined not only by the extent of metabolic depression during the hypoxic period but also by changes in cation contents as well. Calcium overload during reoxygenation, mediated in part by Na-Ca exchange and supported by the rise in cell sodium during hypoxia, may be one factor. The effects of amiloride (0.1 mM), a diuretic that inhibits Na(+)-H+ and Na-Ca exchanges in cardiac sarcolemma and mitochondria preparations, were studied during hypoxia-reoxygenation in the isovolumic, isolated rat heart. During hypoxia, cell sodium, measured using potassium ethylenediamine tetraacetate cobaltate as an extracellular marker, increased in amiloride and amiloride-free hearts, but there was no increase in cell calcium (3.3 +/- 0.3 vs. 3.6 +/- 0.9 mumol/g dry wt; p = NS). Amiloride did not alter developed pressure (DP), end-diastolic pressure (EDP), pH, or integrated areas of adenosine triphosphate (ATP) and phosphocreatine (PCr) (determined by phosphorus-31-nuclear magnetic resonance spectroscopy) during hypoxia or normal perfusion conditions. Forty minutes after reoxygenation, however, cell calcium was significantly lower in the amiloride (5.1 +/- 1.3 mumol/g dry wt) than in the amiloride-free group (10.4 +/- 1.8 mumol/g dry wt; p less than 0.001), and there was improved recovery of DP (percent of initial) (72 +/- 12% vs. 41 +/- 12%; p less than 0.001), PCr (99 +/- 9% vs. 70 +/- 14%; p less than 0.001), and pH (7.17 +/- 0.17 vs. 6.88 +/- 0.16; p less than 0.001) in the amiloride group. To determine whether this dose of amiloride inhibits the manifestations of sodium-mediated calcium gain in the same model during normoxia, the metabolic and functional sequelae of lithium-substituted low sodium (50 mM) perfusion were studied. Amiloride significantly limited the manifestations of sodium-mediated calcium gain as indexed (all expressed as percent of control) by a lower peak DP (221 +/- 25% vs. 284 +/- 20%) at 3 minutes, improved preservation of PCr (85 +/- 10% vs. 68 +/- 9%) and ATP (104 +/- 12% vs. 84 +/- 9%), lower rise in inorganic phosphate (201 +/- 74% vs. 332 +/- 106%), and a smaller fall in intracellular pH (7.01 +/- 0.04 vs. 6.70 +/- 0.15, p less than 0.05) for all metabolic parameters during a 20-minute period.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗

PubMed1990

Calcium oscillations index the extent of calcium loading and predict functional recovery during reperfusion in rat myocardium.

Delayed recovery of contractile function after myocardial ischemia may be due to prolonged recovery of high-energy phosphates, persistent acidosis, increased inorganic phosphate, and/or calcium loading. To examine these potential mechanisms, metabolic parameters measured by 31P nuclear magnetic resonance spectroscopy, and spontaneous diastolic myofilament motion caused by sarcoplasmic reticulum-myofilament calcium cycling indexed by the scattered light intensity fluctuations (SLIF) it produces in laser beam reflected from the heart, were studied in isolated atrioventricularly blocked rat hearts (n = 10) after 65 min of ischemia at 30 degrees C. All metabolic parameters recovered to their full extent 5 min after reperfusion. Developed pressure evidenced a small recovery but then fell abruptly. This was accompanied by an increase in end diastolic pressure to 37 +/- 5 mm Hg and a fourfold increase in SLIF, to 252 +/- 58% of baseline. In another series of hearts initial reperfusion with calcium of 0.08 mM prevented the SLIF rise and resulted in improved developed pressure (74 +/- 3% vs. 39 +/- 13% of control), and lower cell calcium (5.9 +/- 3 vs. 10.3 +/- 1.4 mumol/g dry wt). Thus, during reperfusion, delayed contractile recovery is not associated with delayed recovery of pH, inorganic phosphate, or high-energy phosphates and can be attributed, in part, to an adverse effect of calcium loading which can be indexed by increased SLIF occurring at that time.

Adenosine Triphosphate↗

PubMed1990

Influence of left ventricular mass regression on cardiac function in hypertensive elderly individuals.

A randomized, double-blind placebo controlled trial was conducted to compare the ability of verapamil and atenolol to induce regression of left ventricular mass in elderly hypertensive patients and the effects of regression on left ventricular filling, ejection fraction, and cardiac volumes. Forty-two individuals over 60 years of age were enrolled in the protocol. Eight of 21 patients assigned to atenolol and 18 to 21 assigned to verapamil achieved blood pressure control with single-agent therapy (p less than 0.05). The addition of chlorthalidone resulted in blood pressure control in the three remaining assigned to verapamil and in ten of the remaining patients assigned to atenolol. In the verapamil group left ventricular mass index decreased from 104 +/- 5 to 85 +/- 5 g/M2, while it was unchanged in the atenolol patients (109 +/- 9 to 112 +/- 10 g/M2). In the patients in whom the left ventricular mass regressed, the peak filling rate increased from 2.42 +/- 0.2 to 3.31 +/- 0.4 EDV/s, while it did not change in the patients who did not experience regression. Furthermore, ejection fraction and cardiac output were maintained in patients who had regression, both at rest and during mild upright bicycle exercise.

Aged↗

PubMed1990

Special considerations in the elderly patient.

Special considerations in the treatment of the elderly hypertensive include altered pathophysiology, the increasing likelihood of coexisting disease, and the question of whether reduction of left ventricular (LV) mass should be a therapeutic goal. The objective of our study was to compare the ability of a calcium blocker, verapamil, and a beta-blocker, atenolol, to induce reduction of LV mass and to determine the effects of any such reduction on LV filling and contractile performance. Forty-two hypertensive patients over 60 years of age were randomized to progressively increasing doses of long-acting verapamil or atenolol in a double-blind fashion and followed over a six-month period. Blood pressure decreased in both groups but atenolol-treated subjects more frequently required the addition of chlorthalidone. Despite similar blood pressure reductions, mean LV mass index, determined by two-dimensional echocardiography, was significantly reduced in the verapamil group magnitude of [104 +/- 5 g/m2 to 85 +/- 5 g/m2 (P less than 0.01)] but was not changed in the atenolol group. Following withdrawal of therapy, gated blood pool scan determined peak filling rate and the ratio of peak filling to peak ejection significantly increased in the group evidencing reduction (2.42 +/- 0.2 to 3.31 +/- 0.4 EDV/sec and 0.61 +/- 0.03 to 0.85 +/- 0.05, respectively) but did not change in the group which showed no reduction. Cardiac output and ejection fraction were maintained, both at rest and during mild upright exercise in the group evidencing reduction. Reduction of LV mass occurs more frequently with verapamil than with atenolol therapy in elderly hypertensives. Reduction improves diastolic filling and does not impair contractile performance.

Age Factors↗

PubMed1989

Frequency and significance of early postoperative silent myocardial ischemia in patients having peripheral vascular surgery.

Coronary disease causes the majority of perioperative complications after peripheral vascular surgery. Twenty-four patients with stable coronary disease undergoing peripheral revascularization were studied using continuous electrocardiographic monitoring to determine the incidence of perioperative asymptomatic myocardial ischemia and its relation to postoperative clinical ischemic events. Patients were monitored preoperatively (17 +/- 1 hours), intraoperatively and postoperatively (29 +/- 2 hours) using 4-channel calibrated amplitude-modulated units. Fifteen patients (63%) had early postoperative silent ischemia; 3 also had preoperative silent ischemia and 5 intraoperative transient ischemia. Patients with and without silent ischemia had similar clinical characteristics, perioperative antianginal medications and postoperative episodes of hemodynamic instability. However, 8 of 15 patients (53%) with silent ischemia had postoperative clinical ischemic events (2 had myocardial infarction, 2 had new congestive heart failure and 4 had new rest angina), versus only 1 of 9 patients (11%) without silent ischemia who had angina (p less than 0.05). Early postoperative silent myocardial ischemia occurs frequently after vascular surgery and is associated with postoperative clinical ischemic events.

Aged↗

PubMed1989

Fatty acid regulation of glucose metabolism in the intact beating rat heart assessed by carbon-13 NMR spectroscopy: the critical role of pyruvate dehydrogenase.

Although the myocardium is capable of utilizing both glucose and fatty acid substrates, glucose metabolism is inhibited in the presence of fatty acid during normal perfusion conditions. Fatty acid regulation of glucose utilization in intact beating rat hearts was studied with 13C-enriched substrates and 13C and 31P NMR spectroscopy at 8.5 T. During [1-13C]glucose and insulin perfusion, the 13C appeared in alanine, lactate and the glutamate isotopomers, indicating glycolytic flux through pyruvate and glucose-supported tricarboxylic acid (TCA) cycle oxidation, respectively. Following the addition of hexanoic acid, 1 mM, [1-13C]glucose metabolism proceeded through the hexokinase and phosphofructokinase reactions, as evidenced by continued production of [3-13C]alanine and [3-13C]lactate, but was completely inhibited at the pyruvate dehydrogenase (PDH) reaction as evidenced by a lack of appearance of the 13C label in the glutamate isotopomers. This inhibition of PDH was associated with increased PCr/ATP levels and was readily reversed by removal of hexanoic acid. Addition of dichloroacetate, 5 mM, which increases the active form of PDH, to fatty acid and glucose containing perfusate reinstituted carbon flux through the PDH reaction, indicating that the mechanism of fatty acid cessation of PDH flux is by reversible inactivation of the PDH enzyme complex. Thus the point of inhibition and mechanism of action of fatty acid modulation of glucose metabolism can be continuously and non-destructively studied in the intact beating heart with 13C and 31P NMR and is primarily attributable, in this model, to reversible PDH enzyme inactivation.

Animals↗

PubMed1989

Comparative 13C and 31P NMR assessment of altered metabolism during graded reductions in coronary flow in intact rat hearts.

13C NMR spectroscopy may offer a unique ability to characterize the metabolic response to graded reduction in coronary flow since it allows repeated, nondestructive identification of products of intermediary metabolism in the same heart. The sensitivity of 13C parameters of glucose metabolism was compared with changes in levels of phosphocreatine, ATP, and pH as determined by 31P NMR in the intact, beating rat heart model during graded reductions in coronary flow. Experiments were performed during 60 min of perfusion with [1-13C]glucose (5 mM) at normal flow (15 ml/min) and at the reduced flow rates of 5 and 2 ml/min. During flow at 5 ml/min, isovolumic developed pressure fell to 51 +/- 4% of control. Although phosphocreatine, ATP, and pH were not changed, [3-13C]lactate was increased (1.46 +/- 0.12 mumol/g of wet weight vs. 0.63 +/- 0.08 during normal flow). In addition, the time to 50% maximum enrichment of [2-13C]glutamate was prolonged (17 +/- 1 min vs. 9 +/- 1 min during normal flow), indicating that glucose-supported flux through the tricarboxylic acid (TCA) cycle was decreased. The relative anaplerotic contribution to citrate synthase-supported TCA flux was increased from 6% to 35%. These 13C metabolic changes could not be reproduced by reduced [1-13C]glucose delivery in the absence of ischemia, although similar reduced TCA flux indices were reproduced in additional hearts when workload was reduced by low calcium (0.7 mM) perfusion. Therefore, the information provided by 13C NMR spectroscopy can be a more sensitive indicator of flow-induced alterations in cardiac metabolism than that provided by the much more commonly used 31P NMR technique.

Adenosine Triphosphate↗

PubMed1989

Laser backscatter studies of intracellular Ca2+ oscillations in isolated hearts.

We measured intensity fluctuations of 633 nm laser light backscattered from the epicardial surface of isolated, perfused rat and rabbit hearts. Scattered light intensity fluctuations (SLIF) were detected from verapamil-arrested rat hearts. The frequency of SLIF was increased by maneuvers that raise intracellular calcium. SLIF were abolished by removal of extracellular calcium with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and by blockade of sarcoplasmic reticulum calcium release by ryanodine. SLIF were not accompanied by any surface electro-cardiogram and were not abolished by 144 mM extracellular potassium. SLIF were absent in rabbit hearts under base-line conditions but could be provoked by calcium loading using zero potassium and ouabain. We conclude that backscatter SLIF monitor the microscopic motion caused by intracellular calcium oscillations in the intact heart. We measured SLIF from rat hearts during 60 min of global ischemia at 30 degrees C, followed by reflow. Ischemia reduced SLIF frequency to zero within 30 min. Reflow caused an overshoot of SLIF frequency to as much as five times control, suggesting that reflow causes major calcium overload of cells that are at least transiently viable.

Animals↗

PubMed1988

Silent ischemia on Holter monitoring predicts mortality in high-risk postinfarction patients.

The relative prognostic significance of ischemic ST changes on two-lead continuous electrocardiographic (Holter) monitoring in 103 high-risk postinfarction patients was examined. Ischemic ST changes were detected in 30 patients, with a median number of five episodes per day and median total daily duration of 157 minutes. Only one third of these patients reported any angina in the hospital, and 28 of the 30 patients had silent ST changes on Holter monitoring. The remaining 73 patients had no ischemic ST changes on Holter monitoring. At one year, nine (30%) of 30 patients with ischemic ST changes were dead vs only eight (11%) of 73 patients without such changes. Multivariate Cox's hazard function analysis on 18 variables, including age, type of infarction, Lown and Killip class, ejection fraction, and medications, showed that the presence of ST changes on Holter monitoring was a significant predictive variable for one-year mortality in the overall study population and particularly in the subgroup of 59 patients who could not undergo early exercise treadmill testing. Thus, ischemic ST changes on Holter monitoring, the majority of which are silent, occur in nearly one third of high-risk postinfarction patients and are significantly associated with one-year mortality.

Actuarial Analysis↗

PubMed1988

Absence of acute doxorubicin-induced dysfunction of heart mitochondrial oxidative phosphorylation and creatine kinase activities.

Since reductions in cardiac high-energy phosphate content and dysfunction of mitochondrial activities have been demonstrated after doxorubicin exposure, one mechanism of doxorubicin cardiotoxicity has been thought to be an interference with mitochondrial energy metabolism. To determine whether mitochondrial dysfunction is induced by acute drug exposure, isolated rat hearts were perfused with 10(-5) M doxorubicin for 70 min followed by mitochondrial isolation. Rates of electron transport, creatine kinase activity, acceptor control, respiratory control, and ADP/O ratios were assayed and correlated to doxorubicin-induced abnormalities in left ventricular function. At doses of doxorubicin sufficient to cause a marked deterioration of left ventricular systolic pressure and a rise in end-diastolic pressure, no decreases were noted in the measured mitochondrial parameters with either glutamate plus malate or succinate as respiratory substrates. In fact, in some cases the rates of electron transport were higher in mitochondria isolated from the treated hearts. In addition, isolated heart mitochondria were directly incubated in doxorubicin at doses as high as 10(-4) M for up to 70 min at 0 and 20 degrees C and 1.5 min at 37 degrees C. Under these conditions functional impairment of mitochondrial respiration was also not detected. Therefore, it appears that acute doxorubicin cardiotoxicity cannot be related to primary mitochondrial defects in high-energy phosphate metabolism. These data lend further support to the notion that doxorubicin cardiotoxicity may be fundamentally related to changes in coronary vascular resistance and resultant damage induced by hypoperfusion.

Animals↗

PubMed1988

Silent myocardial ischemia in the elderly: current concepts.

The traditional approach to managing ischemic heart disease has been to reduce symptoms, eg, angina pectoris. However, recent studies demonstrate that myocardial ischemia often can be found in the absence of common symptoms, including in elderly patients. Since elderly patients may not complain about their symptoms, or may not get enough exercise to test their cardiovascular capabilities and, thus, bring out problems, the geriatrician needs to be highly suspicious of silent myocardial ischemia. A brief overview of diagnostic testing methods suitable for the elderly and medical and surgical management options is presented.

Aged↗

PubMed1987

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty.

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.

Angina Pectoris↗

PubMed1987

Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina.

Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in greater than 50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring. Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p less than 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p less than 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.

Angina Pectoris↗

PubMed1987

Negative inotropic effects of furosemide in the isolated rabbit heart: a prostaglandin-mediated event.

Furosemide is an effective diuretic that initiates a rapid diuresis and peripheral vasodilatation through renal adenylate cyclase inhibition and prostaglandin synthesis. Recently, it has been shown to be associated with activation of the neurohumoral vasoconstrictor mechanism and a further compromise of left ventricular function in patients with heart failure. The present study was performed to investigate the direct effects of furosemide on myocardial performance in the isolated perfused rabbit heart. Furosemide (10(-3) M) caused a significant decrease in developed pressure as well as a similar fall in coronary perfusion pressure. Furosemide also decreased myocardial contractility when the coronary perfusion pressure was kept constant. The change in developed pressure but not the decrease in coronary perfusion pressure could be blocked by treatment with indomethacin. Furosemide did not antagonize rabbit cardiac membrane adenylate cyclase. Therefore, furosemide has a direct inhibitory effect on cardiac contractility that is related to prostaglandin synthesis.

Adenylyl Cyclases↗

PubMed1987

Prolonged decrease in cardiac volumes after maximal upright bicycle exercise.

Sequential exercise-gated cardiac blood pool scintigrams provide a noninvasive technique for evaluating the effect of therapeutic interventions on cardiac volumes and function only if both exercise periods are equivalent in the absence of an intervention. To assess whether they are indeed equivalent, 14 healthy subjects underwent gated blood pool scintigraphy during two maximal upright exercise periods separated by 60 min without changing position. Although resting cardiac output and blood pressure returned to base-line values 60 min after the first exercise period, mean resting heart rate was markedly higher (89.4 +/- 2.7 vs. 66.5 +/- 2.5 beats/min, P less than 0.001) and upright cardiac volumes lower [39.1 +/- 4.9 vs. 56.3 +/- 6.0 ml, P less than 0.001, for end-systolic volume (ESV) and 112.6 +/- 8.0 vs. 144.9 +/- 9.0 ml, P less than 0.001, for end-diastolic volume (EDV)] than before the first exercise period. These differences persisted during low levels of the subsequent exercise but not at high and maximum work loads. Cardiac volumes and heart rate 60 min after an identical exercise protocol in a second group of 22 subjects who received propranolol, 0.15 mg/kg iv, after their initial exercise, however, were the same as those preexercise. Thus higher sympathetic tone may be responsible for the persistently higher heart rate and decreased cardiac volumes after exercise, and the assumption that cardiac volumes and function are similar during two closely spaced sequential exercise studies is not always valid.

Adult↗

PubMed1987

Prophylactic antiarrhythmic therapy of high-risk survivors of myocardial infarction: lower mortality at 1 month but not at 1 year.

To determine whether prophylactic antiarrhythmic therapy influences mortality in high-risk patients after acute myocardial infarction, 143 such patients were randomized in a double-blind individually dose-adjusted, placebo-controlled trial an average of 14 +/- 7 days after myocardial infarction and followed for 1 year. Patients were judged to be at high risk on the basis of (1) ejection fraction less than 40% (n = 60), (2) arrhythmias of Lown class 3 or higher (n = 26), or (3) both (n = 57). Aprindine was chosen because of its long half-life, few side effects, and antiarrhythmic efficacy. Baseline characteristics in the treatment arms did not differ. Holter-detected arrhythmias were reduced in aprindine-treated patients at 3 months (p less than .001) and at 1 year (p less than .001). One patient was lost to follow-up; in the remaining patients 1 year mortality was 20% (28/142; 12 aprindine and 16 placebo). There was no significant difference between the two study arms in overall mortality and sudden death. However, among those who died, median duration of survival was longer in aprindine-treated patients (86 vs 21.5 days) (p = .04). Although antiarrhythmic treatment with aprindine of high-risk patients after myocardial infarction does not affect 1 year survival, mortality appears to be delayed; thus there may be a role for short-term treatment before more definitive therapy such as surgery.

Aprindine↗

PubMed1987

Functional and metabolic consequences of vitamin B-6 deficiency in the rat heart.

The cardiac functional and metabolic consequences of pyridoxine deficiency were studied in rats maintained on a pyridoxine-deficient diet for 10 weeks. Because food intake was diminished in the pyridoxine-deficient rats, a second group of animals was fed a diet restricted to the intake of the pyridoxine-deficient animals. The inotropic response (developed pressure) to an isoproterenol or Ca2+ concentration response curve was measured simultaneously with high energy phosphate levels using a modified Langendorf apparatus and 31P nuclear magnetic resonance spectroscopy. The inotropic response to Ca2+ and isoproterenol was significantly decreased relative to controls in both the food-deprived and the pyridoxine-deficient groups. Developed pressure after adrenergic stimulation was significantly less in the pyridoxine-deficient than in the food-deprived animals. Phosphocreatine and ATP levels were maintained and did not differ among the control, pyridoxine-deficient, and food-deprived groups during isoproterenol and Ca2+ stress, implying that the diminished inotropy was not due to an abnormality in generation of high energy phosphate levels.

Adenosine Triphosphate↗