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Biomedical subjects

G Gerstenblith

Publications and source records attributed to G Gerstenblith.

16 recordsLinked to original sources
PubMed1992

Treatment of unstable angina pectoris.

Unstable angina pectoris may be manifested as new-onset angina, a change in the anginal pattern, pain at rest with associated electrocardiographic (ECG) changes, or postinfarction angina. Of these, pain at rest with ischemic ECG changes is known to be associated with the poorest prognosis. The pathogenesis of unstable angina pectoris involves a combination of a fixed atherosclerotic obstruction and a dynamic component related to coronary vasoconstriction, thrombus formation, or both. Long-acting nitrates, inhibitors of platelet aggregation, beta blockers, and calcium antagonists are among the agents that have been shown to be effective in the medical management of unstable angina. A study now in progress is evaluating the routine use of thrombolytic therapy for this indication. Although alleviation of symptoms and prevention of death and myocardial infarction are important therapeutic goals, the overall efficacy of a particular medical therapy can best be assessed by objective evaluation of its ability to control ischemia, using such techniques as exercise scintigraphy and ambulatory ECG monitoring. Cardiac catheterization and revascularization are indicated for patients with unstable angina who continue to experience symptoms or who show evidence of silent ischemia despite medical therapy. A study is under way to determine the advisability of routine revascularization of such patients. Revascularization will provide symptomatic relief in most patients with unstable angina and may prolong survival and improve left ventricular function in certain subsets.

Angina, Unstable↗
PubMed1992

Contractile, metabolic and arrhythmogenic effects of ionic and nonionic contrast agents in the isolated rat heart.

Intracoronary administration of contrast agents may be associated with contractile dysfunction and arrhythmias. To further establish the mechanisms of these alterations, we studied high-energy phosphate metabolism, developed pressure, the occurrence of arrhythmias, and the effects of verapamil during infusion of ionic and nonionic agents in isovolumic, retrogradely perfused rat hearts using 31P nuclear magnetic resonance imaging (NMR). Diatrizoate meglumine (Renografin) infusion reduced developed pressure (DP) to 17.1 +/- 3.4% (p less than 0.001) of the control level, and immediately following termination of the infusion, sudden ventricular tachycardia (VT) was observed in four of six hearts. In the presence of verapamil, meglumine reduced DP to 13 +/- 1.9% of control values and none of these six hearts developed VT. Iopamidol infusion in the presence of verapamil (n = 6) and alone (n = 6) resulted in a decrease in DP to 87% of control value, and no arrhythmias, significant change in high-energy phosphate levels, or changes in pH were observed. These results suggest that contrast-induced contractile depression is not mediated by changes in high-energy phosphate metabolism or pH. Arrhythmias associated with meglumine administration alone and suppressed by verapamil are probably related to calcium loading.

Adenosine Triphosphate↗
PubMed1992

Age-related decline in left ventricular filling at rest and exercise.

To determine whether the age-associated decline in resting left ventricular diastolic filling persists during aerobic exercise, rest and bicycle exercise filling indexes were measured from gated radionuclide blood pool scans in 88 healthy men aged 22-82 yr. To evaluate the effect of physical conditioning status on these age-related changes, a subset of the subjects consisted of endurance-trained senior athletes with a maximal O2 consumption of 50.5 +/- 5 compared with 32.6 +/- 7 ml.kg-1 x min-1 in age-matched controls. The contribution of beta-adrenergic stimulation to exercise-induced changes in filling was also evaluated by the administration of intravenous propranolol to another subset before testing. Peak filling rate increased progressively at all ages with increasing exercise work loads. The peak filling rates at rest, 50% maximal exercise, and maximum exercise inversely correlated with age (r = -0.64, -0.53, -0.64, respectively). Rest and exercise filling indexes in senior athletes were similar to those of sedentary older subjects. Propranolol decreased exercise peak filling rates in young (37.2 +/- 7.5 yr) but not in older (62.1 +/- 6 yr) subjects. Therefore, filling rates increase with exercise in both young and older healthy men, but age differences persist at comparable relative work loads. This decline is not secondary to a decline in physical conditioning status but appears to be related to a decrease in beta-adrenergic responsiveness in older individuals.

Adrenergic beta-Antagonists↗
PubMed1992

Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.

Aged↗
PubMed1992

Indexing tricarboxylic acid cycle flux in intact hearts by carbon-13 nuclear magnetic resonance.

Although the tricarboxylic acid (TCA) cycle is the prime means of carbon metabolism for energy generation in normal myocardium, the noninvasive quantification of TCA cycle flux in intact cardiac tissues is difficult. A novel approach for estimating citric acid cycle flux using 13C nuclear magnetic resonance (NMR) is presented and evaluated experimentally by comparison with measured myocardial oxygen consumption over a wide range of cardiac contractile function in intact, beating rat hearts. Continuous series of 13C NMR spectra, obtained after the introduction of [2-13C]acetate as substrate, quantified the time course of 13C appearance in the carbon positions of myocardial glutamate, which are sequentially enriched via citric acid cycle metabolism. A TCA cycle flux parameter was calculated using the premise that TCA cycle flux is inversely proportional to the time difference between 13C appearance in the C-4 and C-2 positions of glutamate (glutamate delta t50 [minutes]), which are enriched in subsequent "turns" of the TCA cycle. This TCA cycle flux parameter, termed KT, correlated strongly with myocardial oxygen consumption over a range of developed pressures in hearts perfused with 5 mM acetate (r = 0.98, p less than 0.001), as well as in separate studies in hearts perfused with 5 mM glucose and 0.5-0.8 mM acetate (r = 0.94, p less than 0.001). Results of numerical modeling of 13C glutamate kinetics suggest that this TCA cycle flux parameter, KT, is relatively insensitive to changes in metabolite pool sizes that could occur during metabolism of other substrates or during conditions of altered oxygen availability. Additional studies in separate hearts indicated that the time course of 13C appearance in citrate, which is predominantly mitochondrial in the rat heart, is similar to that in glutamate, further supporting the premise that the described 13C NMR parameters reflect mitochondrial citric acid cycle activity in intact cardiac tissues.

Acetates↗
PubMed1992

Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure.

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle-1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.

Animals↗
PubMed1992

Left ventricular mass regression in elderly hypertensives.

It is now recognized that left ventricular hypertrophy (LVH), often associated with hypertension, is itself a risk factor for coronary disease in the elderly. Although many agents are capable of controlling blood pressure, the ability of these agents to induce regression of left ventricular (LV) mass, and the effect of regression on diastolic relaxation and contractile indices in the elderly are less well known. Our study compared the ability of the calcium blocker, verapamil, and the beta-blocker, atenolol, to both control blood pressure (BP) and to induce regression of LV mass in older hypertensives. In addition, the influence of regression on resting diastolic filling and on cardiac output and ejection fraction during rest and mild upright bicycle exercise were determined. Forty-two hypertensives 60 years of age or above, without evidence of ischemic disease underwent 2-D echocardiographic evaluation of LV mass and gated blood pool scan determination of early diastolic filling, cardiac output and ejection fraction. They were then randomized to receive verapamil or atenolol during a four-week titration period so as to achieve a BP of less than 160/90 mm Hg. If BP was not controlled with either agent, chlorthalidone was added. Individuals whose BP was controlled continued on the protocol for six months. At that time, the echocardiographic and gated blood pool studies were repeated both on and after subsequent withdrawal of the study medications. Twenty-one patients were randomized to receive verapamil and 21 patients to receive atenolol. Blood pressure control was achieved with verapamil alone in 18 patients, but with atenolol alone in only 8 patients (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Regulation of myocardial glycogenolysis during post-ischemic reperfusion.

Myocardial glycogen and the factors which primarily regulate its metabolism were studied during post-ischemic reperfusion. Myocardial [13C]glycogen was continuously monitored by 13C-NMR spectroscopy in beating rat hearts perfused with oxygenated solutions containing [1-13C]glucose (5 mM) and insulin, during normal flow at 15 ml/min (n = 5), and during reperfusion after 30 min of 1 ml/min (n = 5), or 0 ml/min (n = 4) ischemia. Mean myocardial [13C]glycogen fell during reperfusion from 1.1 +/- 0.6 at the end of zero-flow ischemia to 0.4 +/- 0.4 mumol of [13C]glucosyl units/g wet wt (P less than 0.02) over the first 7 min of reperfusion; it also fell during reflow following 1 ml/min ischemia, from 2.3 +/- 1.4 to 1.7 +/- 1.0 mumol (P less than 0.03) over the same interval. In parallel experiments, glycogen phosphorylase % a (GPA%) content was higher at the end of 30 min of 0 ml/min (37.3 +/- 7.3%, P less than 0.01), and trended higher after 1 ml/min flow (30.8 +/- 12.1%, P = 0.18) than under baseline conditions (20.1 +/- 7.4%). However GPA% returned to baseline values within 1 min of reflow after both 0 and 1 ml/min ischemic periods (20.6 +/- 3.0% and 19.0 +/- 8.0%, respectively). Inorganic phosphate, as determined by simultaneous 31P-NMR, remained elevated during early reperfusion relative to baseline, and significantly correlated with the extent of decline in [13C]glycogen during reperfusion (r = 0.79, P less than 0.01). Thus, glycogen breakdown continues to occur during early post-ischemic reperfusion, but the mechanism is not related to elevated GPA%, and may be due to persistently increased inorganic phosphate at that time.

Adenosine Monophosphate↗
PubMed1978

Effect of lidocaine on conduction in the ischemic His-Purkinje system of dogs.

The effect of lidocaine on His-Purkinje conduction in dogs with ischemic damage to the His bundle was compared with the effect of lidocaine in normal dogs. The anterior septal artery was ligated in 14 dogs, and 30 minutes later atrial pacing was performed to increase residual ischemic damage. Four to 6 days later, His bundle recordings were obtained during sinus rhythm and atrial pacing before and after the administration of lidocaine in a dose of 2 mg/kg and a total dose of 4 mg/kg. His bundle recordings were also obtained in nine control animals beofre and after the administration of lidocaine. Lidocaine significantly increased the H-V time in the animals with ischemic damage during sinus rhythm and at all packing rates. It also resulted in advanced His-Purkinje conduction defects including His bundle block and right bundle branch block in these animals. In contrast, the effect of lidocaine in the normal animals was negligible. It is concluded that lidocaine significantly depresses His-Purkinje conduction in the setting of preexisting ischemic damage. These results suggest that lidocaine may be used as a diagnostic tool to unmask latent His-Purkinje conduction defects due to ischemia.

Animals↗
PubMed1977

Ventricular ectopic activity after premature atrial beats in acute myocardial infarction.

Ventricular ectopic activity occurred only after premature atrial beats in a patient with an acute inferior wall myocardial infarction. The ventricular ectopic activity occurred only when the coupling interval between the premature atrial beats and preceding sinus beat was less than or equal to 0-44 s. The sinus cycle length, however, appeared to influence the form of expression of ventricular ectopic activity independent of coupling intervals, with single premature ventricular contractions occurring at cycle lengths greater than or equal to 0-72 s, couplets at cycle lengths of 0-68 to 0-71 s, and ventricular tachycardia at cycle lengths less than or equal to 0-67 s.

Aged↗
PubMed1977

Echocardiographic assessment of a normal adult aging population.

Echocardiograms were performed on 105 male participants in the National Institutes on Aging's volunteer Longitudinal Study Program. All subjects (25--84 years of age) were physically active and had no evidence of hypertension or cardiovascular disease. Measurements were made of the initial diastolic (E-F) slope of the anterior mitral valve leaflet, the aortic and left ventricular cavity dimensions, and the thickness of the posterior left ventricular wall. Fractional shortening of the minor semi-axis of the left ventricle and the velocity of circumferential fiber shortening were also determined. It was found that increasing age correlated with a decrease mitral valve E-F slope and increased aortic root diameter and left ventricular wall thickness. Aging did not affect left ventricular cavity dimension, fractional shortening of the minor semi-axis, and velocity of circumferential fiber shortening. These findings suggest that aging in the normal male is associated with altered left ventricular diastolic filling, increased aortic root diameter and left ventricle hypertrophy but little change in contractile ability in the resting state.

Adult↗
PubMed1975

Diminished inotropic response of aged myocardium to catecholamines.

The effect of advanced age on the response of active tension, maximal rate of tension development (dT/dt), and contraction duration to catecholamines and to calcium was evaluated in isometric trabeculae carneae from young adult (6-month-old), middle-aged (12-month-old), and aged (25-month-old) rats. Control values were not age dependent except for that for contraction duration which was prolonged in the aged group. At a norepinephrine concentration of 8 times 10-5M, dT/dt increased to 163.8 plus or minus 5.3% of control in the young adult group and to 125.9 plus or minus 6.3% of control in the aged group (P smaller than 0.001). Active tension increased to 121.3 plus or minus 4.0% of control in the young adult muscles but did not increase in the aged muscles (P smaller than 0.01). Contraction duration shortened proportionately in both age groups. Similar results were obtained with isoproterenol. In contrast to the response to catecholamines, there was no age difference in the response of active tension and dT/dt to increasing concentrations of calcium. It is concluded that the intrinsic inotropic response to catecholamines is diminished in the aged myocardium. This finding does not appear to result from differences in tachyphylaxis, tissue uptake of catecholamines, or the ability of the contractile proteins to respond to increasing concentrations of calcium but instead may result from a decreased ability of catecholamines to increase the intracellular calcium available for contraction.

Aging↗
PubMed1975

Prolonged contraction duration in aged myocardium.

Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content.

Action Potentials↗