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Biomedical subjects

G Gerstenblith

Publications and source records attributed to G Gerstenblith.

At least 37 records · Page 2Linked to original sources
PubMed1997

Intravascular magnetic resonance imaging of aortic atherosclerotic plaque composition.

Magnetic resonance imaging (MRI) may be an excellent tool to define atherosclerotic plaque composition, but surface MRI (SMRI) suffers from a low signal-to-noise ratio and low resolution of arterial images. Intravascular MRI (IVMRI) represents a potential solution for acquiring high-quality in vivo images of atherosclerotic plaques. Isolated segments of 11 thoracic human aortas obtained at autopsy were imaged by IVMRI using an intravascular receiver catheter coil designed and built at our institution. Images obtained by IVMRI were compared with corresponding images obtained by SMRI and with histopathological aortic cross sections. The intensity of intimal thickness and plaque components was graded by IVMRI and histopathology using a score of 1 for mild, 2 for moderate, and 3 for severe intensity. IVMRI had an agreement of 75% with histopathology in fibrous cap grading (37.5% expected, kappa = 0.60, P < 0.001) and of 74% in necrotic core grading (39% expected, kappa = 0.57, P < 0.001). Intraplaque calcification was correctly graded by IVMRI in six of the eight plaques in which histopathology recognized calcium. The analysis of intimal thickness showed 80% agreement between IVMRI and histopathology (52% expected, kappa = 0.59, P < 0.001). IVMRI image features were similar to those of SMRI. In addition, IVMRI accurately determined atherosclerotic plaque size in comparison with histopathology and SMRI (slope = 1.25 cm2, r = 0.99, P < 0.001 for luminal area by IVMRI vs histopathology; slope = 0.97 cm2, r = 0.996, P < 0.001 for luminal area by IVMRI vs SMRI). IVMRI has the potential to provide important prognostic information in patients with atherosclerosis because of its ability to accurately assess both plaque composition and size.

Adult↗
PubMed1997

Carcinoid heart disease with severe hypoxia due to interatrial shunt through patent foramen ovale.

Carcinoid heart disease occurs in approximately half of patients who have carcinoid syndrome and is the leading cause of death among these patients. It is typically manifest as right-sided valvular lesions, usually tricuspid insufficiency and pulmonary valve stenosis. This case report describes the unusual presentation of a patient with carcinoid heart disease and a large right-to-left shunt through a patent foramen ovale.

Adult↗
PubMed1996

Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.

Adult↗
PubMed1996

Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men.

BACKGROUND: Although it has become clear that habitual exercise in older individuals can partially offset age-associated cardiovascular declines, it is not known whether the beneficial effects of exercise training in older individuals depend on their prior fitness level. METHODS AND RESULTS: Ten sedentary men (S), age 60.0 +/- 1.6 years (mean +/- SEM), who were carefully screened to exclude cardiac disease underwent exercise training for 24 to 32 weeks, and eight age-matched endurance-trained men (ET) stopped their exercise training for 12 weeks. All underwent treadmill exercise and rest and maximal cycle exercise upright gated blood pool scans at baseline and after the lifestyle intervention. Before the intervention, the treadmill maximum rate of oxygen consumption (Vo2max) was 49.9 +/- 1.9 and 32.1 +/- 1.4 mL.kg-1.min-1 in ET and S, respectively. During upright cycle exercise at exhaustion, although heart rate did not differ between groups, cardiac index, stroke volume index, ejection fraction, and left ventricular contractility index (systolic blood pressure/end-systolic volume index) all were significantly higher, and end-systolic volume index, diastolic blood pressure, and total systemic vascular resistance all were significantly lower in ET versus S. After the partial deconditioning of ET men, Vo2max fell to 42 +/- 2.2 mL.kg-1.min-1, and training of S increased Vo2max to 36.2 +/- 1.6 mL.kg-1.min-1. Training of S had effects on cardiovascular function that were similar in magnitude but directionally opposite those of detraining ET. All initial differences in cardiovascular performance at peak work rate between S and ET were abolished with the intervention. Across the broad range of fitness levels encountered before and after change in training status (Vo2max of 26 to 58 mL.kg-1.min-1), cardiac index, stroke volume index, end-systolic volume index, ejection fraction, and the left ventricular contractility index were all linearly correlated with Vo2max. CONCLUSIONS: Exercise training or detraining of older men results in changes in left ventricular performance that are qualitatively and quantitatively similar, regardless of the initial level of fitness before the intervention.

Aging↗
PubMed1996

A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.

BACKGROUND: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction. METHODS: To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PlA genotype: reverse dot blot hybridization and allele-specific restriction digestion. RESULTS: The prevalence of PlA2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PlA2 was 50 percent, a value that was 3.6 times that among control subjects under 60 years of age (13.9 percent, P=0.002). Among subjects with the PlA2 polymorphism, the odds ratio for having a coronary event was 2.8 (95 percent confidence interval, 1.2 to 6.4). In the patients less than 60 years of age at the onset of disease, the odds ratio was 6.2 (95 percent confidence interval, 1.8 to 22.4). CONCLUSIONS: We observed a strong association between the PlA2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years.

Acute Disease↗
PubMed1996

Refining the treatment of women with unstable angina--a randomized, double-blind, comparative safety and efficacy evaluation of Integrelin versus aspirin in the management of unstable angina.

BACKGROUND: Although women typically develop coronary artery disease several years after men, once they have symptomatic disease their thromboembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unknown. We previously studied platelet functions in siblings from patients with premature coronary artery disease. We observed that platelets from women are responsive than their male counterparts. In particular, platelets from women stimulated ex vivo with various agonists bind more fibrinogen molecules than platelets from men. HYPOTHESIS: We hypothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men. METHODS: To test this hypothesis, we investigated retrospectively the results of a trial on Integrelin in unstable angina. RESULTS: We report that platelet aggregation and Holter-detected ischemic episodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggregation and Holter-detected ischemic events are well controlled in men with unstable angina treated with standard therapy including aspirin. CONCLUSION: Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data are consistent with the concept that the platelets from women require stronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery disease.

Aged↗
PubMed1996

Attenuated glycogenolysis reduces glycolytic catabolite accumulation during ischemia in preconditioned rat hearts.

Prior transient episodes of ischemia ("ischemic preconditioning") reduce lactate accumulation and attenuate acidosis during a subsequent prolonged ischemic insult. The mechanisms responsible for attenuated glycolytic catabolite accumulation have not been established but may include earlier exhaustion of glycogen stores, slowed glycogenolysis before complete glycogen depletion, and/or inhibition of glycolysis. Simultaneous repeated measures of myocardial glycogen and the rates of glycolysis, glycogenolysis, glucose utilization, and glycolytic ATP production were obtained during total ischemia by 13C nuclear magnetic resonance spectroscopy in control and ischemia-preconditioned isolated rat hearts. Both [13C]glycolytic and [13C]glycogenolytic rates were significantly lower during total ischemia in preconditioned compared with control hearts (0.77 +/- 0.04 versus 1.06 +/- 0.06 mumol/min per gram wet weight [P < .01] for glycolysis and 0.15 +/- 0.07 versus 0.78 +/- 0.12 mumol/ min per gram wet weight [P < .001] for glycogenolysis, respectively, at 2.5 minutes of ischemia). Slowed glycolysis was present even during the early minutes of ischemia, when significant amounts of available [13C]glycogen were still present. Importantly, the reduction in the rate of glycogenolysis was larger and out of proportion to the reduction in glycolysis and occurred despite an increase in glucose utilization in preconditioned hearts (2.23 +/- 0.15 versus 1.5 +/- 0.10 mumol/min per gram wet weight at 1.25 minutes, P < .01). During early ischemia, conversion of glycogen phosphorylase to the a or "active" form was less in preconditioned than in control hearts (29.1 +/- 2.6% versus 41.2 +/- 9.8%, respectively; P < .05). Taken together, these findings demonstrate that ischemic preconditioning significantly depresses glycolytic catabolite accumulation during sustained ischemia not by more severe glycolytic inhibition or exhaustion of glycogen stores but by depressed glycogenolysis from the onset of ischemia.

Animals↗
PubMed1995

Noninvasive measurement of tissue magnesium and correlation with cardiac levels.

BACKGROUND: Intracellular magnesium ([Mg]i) plays an important role in the regulation of myocardial metabolism, contractility, and the maintenance of transsarcolemmal and intracellular ionic gradients. An understanding of the role of magnesium in the clinical setting, however, is hampered by the lack of an assay of intracellular tissue magnesium levels. METHODS AND RESULTS: We used energy-dispersive x-ray analysis to measure [Mg]i in sublingual epithelial cells and to correlate the level with those in atrial biopsy specimens from the same patients during cardiopulmonary bypass. Levels were also measured in acute myocardial infarction (AMI) patients before and after intravenous magnesium sulfate administration and compared with those from intensive care unit (ICU) patients and healthy individuals. A strong correlation between sublingual epithelial cell (mean, 32.1 +/- 0.3 mEq/L) and atrial tissue (mean, 32.1 +/- 0.3 mEq/L) [Mg]i was present in 18 cardiac surgery patients (r = .68, P < .002). Epithelial and atrial [Mg]i levels were lower than in healthy individuals (33.7 +/- 0.5 mEq/L, P < .01) studied at that time and correlated poorly with serum magnesium. Mean [Mg]i in 22 AMI patients was 30.7 +/- 0.4 mEq/L, which was significantly lower than in 21 ICU patients and 15 healthy individuals (35.0 +/- 0.5 mEq/L and 34.5 +/- 0.7 mEq/L, respectively, P < .001). Intravenous magnesium sulfate was administered to most of the AMI patients (mean dose, 36 +/- 6 mmol). [Mg]i rose significantly in the AMI patients over the first 24 hours, and the magnitude of the increase was greater in those who received higher doses of intravenous magnesium sulfate. CONCLUSIONS: Sublingual epithelial cell [Mg]i correlates well with atrial [Mg]i but not with serum magnesium. [Mg]i levels are low in patients undergoing cardiac surgery and those with AMI. Intravenous magnesium sulfate corrects low [Mg]i levels in AMI patients. Energy-dispersive x-ray analysis determination of sublingual cell [Mg]i may expedite the investigation of the role of magnesium deficiency in heart disease.

Aged↗
PubMed1995

Consequences of altered aspartate aminotransferase activity on 13C-glutamate labelling by the tricarboxylic acid cycle in intact rat hearts.

The appearance of 13C label in glutamate has been used to quantify cellular tricarboxylic acid (TCA) cycle activity using 13C-NMR spectroscopy. Glutamate is linked to the TCA cycle by the amino-transferase reactions, however the consequences of alterations in amino-transferase activity on glutamate labelling kinetics, at a constant total tricarboxylic acid cycle activity, have not been investigated. Aspartate amino-transferase activity in [2-13C]acetate-perfused beating rat hearts was found to be similar to total TCA cycle flux in the presence of normal perfusion conditions and was reduced by more than 50% with the subsequent administration of amino-oxyacetic acid (AOA). AOA did not reduce contractile or kinetic measures of total TCA cycle flux, but did slow the 13C labelling of glutamate, in accord with current mathematical predictions. The impact of similar reductions in amino-transferase activity on estimates of total TCA cycle flux derived from several previously reported methods was also evaluated. Because total TCA cycle and the amino-transferase activities both affect the kinetics of 13C-glutamate labelling and because the amino-transferase activities are often unknown under physiologic conditions and can be reduced under pathologic conditions, the calculation of total TCA cycle flux from 13C-NMR data in the future is probably best accomplished either with a sufficiently sophisticated mathematical model that assesses amino-transferase activity or with an empiric model that is relatively insensitive to variations in amino-transferase activity.

Aminooxyacetic Acid↗
PubMed1995

Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women.

To examine whether age differentially modifies the physiological response to exercise in men and women, we performed gated radionuclide ventriculography with measurement of left ventricular volumes at rest and during peak upright cycle exercise in 200 rigorously screened healthy sedentary volunteers (121 men and 79 women) aged 22-86 yr from the Baltimore Longitudinal Study of Aging. At rest in the sitting position, age-associated declines in heart rate (HR) and increases in systolic blood pressure occurred in both sexes. Whereas resting cardiac index (CI) and total systemic vascular resistance (TSVR) in men did not vary with age, in women resting CI decreased 16% and TSVR increased 46% over the six-decade age span. Men, but not women, demonstrated an age-associated increase of approximately 20% in sitting end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume index over this age span. Peak cycle work rate declined with age approximately 40% in both sexes, but at any age it was greater in men than in women even after normalization for body weight. At peak effort, ejection fraction (EF), HR, and CI were reduced similarly with age while ESVI and TSVR were increased in both sexes; EDVI increased 35% with age and stroke work index (SWI) rose 19% in men, but neither was related to age in women; and stroke volume index did not vary with age in either sex. When hemodynamics were expressed as the change from rest to peak effort as an index of cardiovascular reserve function, both sexes demonstrated age-associated increases in EDVI and ESVI and reductions in EF, HR, and CI. However, the exercise-induced reduction in ESVI and the increases in EF, CI, and SWI from rest were greater in men than in women. Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise.

Adult↗
PubMed1994

Effect of body fat on exercise hemodynamics in sedentary older men.

Morbid obesity is often associated with cardiac dilatation and left ventricular dysfunction. The present study investigated whether a similar relationship exists between mild and moderate obesity and left ventricular reserve function in 28 middle aged and older men (58.6 +/- 6.1 years, mean +/- SD). Subjects had a body mass index of 26.4 +/- 2.9 kg/m2, a percent body fat determined by hydrodensitometry ranging from 9.5% to 33.8%, and were carefully screened to exclude cardiovascular disease. Left ventricular function was assessed by gated blood pool scans at rest and during exhaustive upright cycle exercise. There were no significant relationships between resting or exercise cardiac volumes or ejection fraction with percent body fat; however, peak work rate/kg correlated inversely with percent body fat (r = -0.68, p < 0.0001). Heart rate reserve, defined as heart rate at peak work rate minus resting heart rate, declined significantly with increasing percent body fat (r = -0.47, p = 0.01). End diastolic volume index reserve also tended to decline with increasing percent body fat, but stroke volume index and cardiac index reserve were maintained because the decrease in end systolic volume index from rest to maximal exercise was greatest in those subjects with highest percent body fat (r = -0.41, p = 0.03). Therefore, rest and exercise left ventricular function are not related to percent body fat in healthy older men. However, older more obese men have a smaller increase in heart rate and end diastolic volume and a greater decrease in end systolic volume from rest to peak effort as a mechanism to augment exercise cardiac output.

Body Mass Index↗
PubMed1994

Long-term function in the remote region after myocardial infarction: importance of significant coronary stenoses in the non-infarct-related artery.

BACKGROUND: Left ventricular (LV) function is the most important determinant of outcome after a myocardial infarction. Global LV function after a myocardial infarction is affected not only by wall motion in the infarct zone but also by regional function in the contralateral territory. It was hypothesised that the presence of significant stenoses in coronary arteries supplying the contralateral territory might influence the ability of this region to compensate for damaged myocardium after a myocardial infarction. METHODS AND RESULTS: 79 patients treated with thrombolysis for acute myocardial infarction had coronary and ventricular angiograms within 24 h and at a mean follow up of 12 months after myocardial infarction. Wall motion in the contralateral territory was analysed and scored by the centre line method and the change over time was correlated with the presence or absence of significant (> 70%) diameter stenoses in the non-infarct-related artery. Mean (SD) contralateral territory motion worsened, from 0.74 (1.78) to -1.55 (2.06) SD chord (p < 0.001) in 40 patients with stenoses, whereas contralateral territory motion improved from -0.02 (2.4) to 0.63 (2.21) SD chord (p < 0.05) in the 39 patients without coronary stenoses. The same pattern was present whether or not the infarct artery was patent. The global left ventricular ejection fraction at 12 months was also related to contralateral territory motion (r = 0.71, p < 0.001) and to the presence of coronary stenoses (54 (15)% in those with coronary stenoses and 62 (16)% in those without, p < 0.05). CONCLUSION: The results demonstrate that significant stenoses in arteries supplying the non-infarct territory adversely affect global and regional left ventricular function after a transmural infarction. Non-infarct artery anatomy should be considered in intervention strategies to improve left ventricular function after acute myocardial infarction.

Coronary Angiography↗
PubMed1994

Cardiovascular responses to exhaustive upright cycle exercise in highly trained older men.

It is unclear whether the markedly enhanced aerobic exercise capacity of older endurance-trained men relative to their sedentary age peers is mediated primarily by central or peripheral cardiovascular mechanisms. To address this question, we performed radionuclide ventriculography with respiratory gas exchange measurements during exhaustive upright cycle ergometry in 16 endurance-trained men aged 63 +/- 7 yr and in 35 untrained men of similar age. As expected, maximal O2 consumption during treadmill exercise was much higher in athletes than in controls. At rest and during fixed submaximal cycle work rates through 100 W, athletes demonstrated lower heart rates and greater stroke volume indexes than controls while maintaining similar cardiac indexes and O2 uptake (VO2). At exhaustion, athletes achieved 53% higher work rates and peak VO2 per kilogram body weight than the sedentary men. The higher peak VO2 in athletes was achieved by a 22.5% larger cardiac index and a 15.6% greater arteriovenous O2 difference. The larger peak cardiac index in the athletes than in sedentary controls was mediated entirely by a greater stroke volume index; peak heart rates were virtually identical. The athletes' greater stroke volume index was achieved through an 11% larger end-diastolic volume index and a 7% higher ejection fraction, both of borderline significance. At exhaustion, athletes demonstrated a lower systemic vascular resistance than controls, despite a higher value at rest. Athletes also showed greater exercise-induced increments in heart rate, stroke volume index, and cardiac index and a greater reduction in systemic vascular resistance from rest to maximal workload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1994

Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women.

BACKGROUND: Estrogen administration in postmenopausal women is associated with a 50% reduction in the clinical manifestations of coronary artery disease. The mechanisms are not known, although one potential explanation is estrogen-induced modulation of coronary vasoreactivity. Acetylcholine is an endothelium-dependent vasodilator that may be used to assess coronary vasoreactivity and elicits coronary responses that parallel those found with common daily vasomotor stimuli. Therefore, we tested whether estrogen attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. METHODS AND RESULTS: Acetylcholine-induced changes in coronary flow, resistance, and cross-sectional area were determined before and 15 minutes after intravenous administration of ethinyl estradiol (EE, 35 micrograms) in 15 postmenopausal women. The influence of estrogen on basal coronary flow, resistance, and epicardial cross-sectional area was also assessed by measuring these parameters before and after EE or placebo administration in 33 women. Estrogen altered basal coronary vasomotor tone in 22 women as manifested by an EE-induced 23.3 +/- 4.5% (mean +/- SEM) increase (P < .01) in coronary flow, a 15.0 +/- 3.2% decrease (P < .01) in resistance, and a 20.0 +/- 6.5% increase (P = .02) in epicardial cross-sectional area. Placebo administration in 11 women did not change these parameters. Estrogen also attenuated abnormal coronary vasomotor responses to acetylcholine. Seven women who exhibited a paradoxical acetylcholine-induced decrease in coronary flow (-33.5 +/- 12.3%, P < .01) and increase in resistance (38.9 +/- 14.1%, P = .05) and seven who had an abnormal acetylcholine-induced decrease in epicardial cross-sectional area (-14.2 +/- 4.4%; P = .04) did not have acetylcholine-induced changes in these parameters after EE administration. Acetylcholine-induced flow, resistance, and cross-sectional area responses before and after EE were significantly different (P < .01, P = .02, and P = .02, respectively). Normal coronary responses to acetylcholine were not affected by EE administration. CONCLUSIONS: EE attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. EE also decreases basal coronary vasomotor tone as manifested by increased coronary flow, decreased resistance, and increased epicardial cross-sectional area. These acute effects of estrogen on coronary vasoreactivity may explain, in part, the cardioprotective effects of estrogen in postmenopausal women.

Acetylcholine↗
PubMed1994

Effects of acute beta-adrenergic receptor blockade on age-associated changes in cardiovascular performance during dynamic exercise.

The cardiovascular response to beta-adrenergic stimulation is markedly blunted with advancing age, and this blunting may underlie some of the prominent age-associated changes in the hemodynamic profile during dynamic exercise. To examine this hypothesis, we administered the nonselective beta-adrenergic receptor blocker propranolol (0.15 mg/kg IV) to 25 healthy normotensive men ages 28 to 72 years from the Baltimore Longitudinal Study of Aging (BLSA) immediately before maximal upright cycle ergometry with 99mTc gated cardiac blood pool scintigraphy. Their hemodynamic responses to exercise were compared with those of 70 age-matched healthy unmedicated male BLSA control subjects. The maximal cycle work rate achieved was similar in propranolol-treated men (158 +/- 32 W) and control subjects (148 +/- 32 W) and declined similarly with age in both groups. Hemodynamics at seated rest were not age-related in either group; however, propranolol-treated men had lower heart rates (HR), systolic blood pressure (SBP), ejection fraction, and cardiac index than control subjects but higher end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) by covariance analysis. At maximal effort, several striking age-drug interactions were evident: Propranolol caused a greater reduction in HR and greater increases in EDVI and stroke volume index (SVI) in younger than in older men. Hence, at maximal work rate, HR declined less with age in the propranolol group (0.46 versus 1.09 beats per minute per year, P < .05 by covariance analysis); EDVI and SVI decreased with age (0.27 and 0.48 mL/m2 per year, respectively) after propranolol compared with increases of 0.47 and 0.16 mL/m2 per year in control subjects, respectively, each P < or = .05 by covariance analysis. The left ventricular contractility index, SBP/ESVI, at exhaustion was reduced by propranolol to a greater extent in younger than older men. Thus, acute beta-adrenergic blockade reverses the age-associated ventricular dilation at end diastole and end systole observed during upright cycle exercise and blunts the decline in maximal HR and myocardial contractility. These data suggest that the age-associated declines in maximal HR and left ventricular contractility during vigorous exercise are manifestations of reduced beta-adrenergic responsivity with advancing age which is partially offset by exercise-induced ventricular dilation.

Adrenergic beta-Antagonists↗
PubMed1994

Importance of metabolic inhibition and cellular pH in mediating preconditioning contractile and metabolic effects in rat hearts.

The pathophysiological mechanisms by which brief periods of flow interruption before a prolonged ischemic period, ischemic preconditioning (IPC), increase myocardial tolerance to ischemia and improve myocardial function during reperfusion are not completely understood. To test whether short periods of metabolic inhibition in the absence of a flow reduction induce similar protective effects, we studied cardiac function and metabolism using 31P nuclear magnetic resonance spectroscopy in isolated isovolumic rat hearts. Fifteen hearts underwent IPC, consisting of two 5-minute ischemia-reperfusion cycles (IPC group); 18 hearts underwent brief metabolic inhibition by exposure to two 5-minute infusions of 10 mmol/L sodium cyanide (CN group); and 15 hearts served as controls. Subsequently all hearts were subjected to 30 minutes of total global ischemia at 37 degrees C followed by reperfusion. At the end of the ischemic period, creatine phosphate and ATP levels did not differ among the groups. Cellular pH, however, plateaued at a higher level in the CN group (6.51 +/- 0.03) and IPC group (6.12 +/- 0.06) than in the control group (5.84 +/- 0.01, P < .001). IPC and CN hearts had better functional and metabolic recovery than the control hearts. Improved contractile recovery correlated with coronary flow rates at reperfusion (r = .7, P < .001) and with pHi values at 30 minutes of ischemia (r = .8, P < .001) but not with increased ATP levels during ischemia. Additional control hearts were reperfused at 15 mL/min so as to match the flow rates of IPC and CN groups, but this did not result in improved performance. To test the hypothesis that the preconditioning effect was related to pHi during ischemia, additional IPC and CN hearts underwent the same preconditioning protocol, except that the cellular pH at the end of the ischemic period was lowered by the use of hypercarbic superfusion during ischemia or by the use of bicarbonate-free perfusate just before sustained ischemia. Both of these interventions resulted in significantly lower contractile and metabolic recoveries than those observed in other IPC and CN hearts. Therefore, the preconditioning effect does not require reduced coronary flow but can be effectively elicited by metabolic inhibition per se in this model. The protective effect is not dependent on preservation of global myocardial energy stores but, rather, on reduced acidosis during the prolonged ischemic period.

Acidosis↗