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G Gerstenblith

Publications and source records attributed to G Gerstenblith.

At least 73 records · Page 4Linked to original sources
PubMed1986

A phosphorus-31 nuclear magnetic resonance study of the metabolic, contractile, and ionic consequences of induced calcium alterations in the isovolumic rat heart.

Isolated adult rat hearts perfused in an isovolumic mode were used to study the effects of sodium-potassium pump inhibition and sodium-calcium exchange alterations on the tissue content of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH, all measured by phosphorus-31 nuclear magnetic resonance spectroscopy. Rates of oxygen consumption, contractile function, and the cell contents of calcium, sodium, and potassium also were determined. The inhibition of sodium-potassium adenosine triphosphatase, either by the reduction in perfusate potassium from 5.9 to 1 millimolar or less, or by the addition of 10(-4) molar ouabain, transiently increased systolic pressure. This was followed by a decrease in systolic pressure, an increase in diastolic pressure, and eventual inexcitability. This contractile profile was accompanied by a persistent increase in oxygen consumption, a monotonic decline in cellular adenosine triphosphate and phosphocreatine content, the development of marked intracellular acidosis, a gain in cell sodium and calcium content, and a reduction in cell potassium. Quite similar metabolic changes were also observed when cell calcium was increased after a reduction in perfusate sodium. These metabolic and contractile effects could be prevented or reversed by decreasing perfusate calcium. The results emphasize the profound role of calcium in modulating cell oxygen consumption, energy balance, pH, excitability, and force production. These data are discussed in light of changes in the myocardial energy supply/demand balance, as well as from the viewpoint of the known competition between mechanisms for mitochondrial calcium transport vs. high-energy phosphate production.

Animals↗
PubMed1986

Angina: current approaches to diagnosis, drug therapy, and surgical referral.

An abnormal resting ST segment renders the stress ECG impossible to interpret. Therefore, one must substitute a radionuclide stress evaluation in the presence of digitalis, left bundle-branch block, left ventricular hypertrophy, a paced rhythm, or any other condition that would cause abnormal baseline ST segments. All these are more common in the elderly. Beta-blocker therapy is useful in patients with demand-related ischemia because it decreases two of the major determinants of myocardial oxygen demand: heart rate and contractility. Propranolol, timolol, and metoprolol have been shown to decrease the reinfarction and mortality rates in patients who have had an infarction.

Adrenergic beta-Antagonists↗
PubMed1986

Hypertension in the elderly: treatment.

Hypertension in the elderly is a common problem confronting the practitioner today. The rationale for treating hypertensive elderly patients is presented in this article. Guidelines for the use of specific agents for the treatment of older patients are also discussed.

Adrenergic beta-Antagonists↗
PubMed1985

Safety of acute calcium antagonist withdrawal: studies in patients with unstable angina withdrawn from nifedipine.

The acute effects of nifedipine withdrawal were studied in 81 patients with angina at rest who had completed a prospective, double-blind, randomized trial of nifedipine versus placebo. Thirty-nine of the 81 patients (group 1) were withdrawn from nifedipine or placebo at the time of coronary artery bypass surgery for uncontrolled angina or left main coronary artery disease. When the patients withdrawn from nifedipine were compared with those withdrawn from placebo, no significant differences were seen in the incidence of hypotension, myocardial infarction, significant arrhythmias or vasopressor or vasodilator requirements during the perioperative period. Forty-two patients (group 2) completed 2 years on a protocol consisting of nitrates and propranolol, in addition to nifedipine or placebo. These patients were hospitalized for a controlled withdrawal of the study drug (nifedipine or placebo), and no significant difference was noted in either exercise performance on serial treadmill testing or the number or duration of episodes of ischemic ST-segment changes during continuous electrocardiographic monitoring. Eight patients continued to experience occasional episodes of angina at rest. Angina at rest recurred during the withdrawal period in 5 of these 8 patients. Four of these 5 patients were withdrawn from nifedipine. Of the 34 stable patients in group 2 who were not experiencing angina at rest before withdrawal, none had angina at rest during the withdrawal study period. Thus, there were no early untoward effects of acute nifedipine withdrawal either in patients undergoing coronary bypass surgery or in stable patients on long-term medical therapy. However, patients with persistent symptoms of angina at rest may experience early recurrent ischemia upon withdrawal from nifedipine.

Angina Pectoris↗
PubMed1985

Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty.

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.

Adult↗
PubMed1985

Results of a randomized prospective trial of intraaortic balloon counterpulsation and intravenous nitroglycerin in patients with acute myocardial infarction.

A randomized prospective clinical trial compared combined treatment with intraaortic balloon pumping and intravenous nitroglycerin for 4 to 5 days with routine clinical management in 20 patients with extensive myocardium at risk for infarction as evidenced by a thallium defect score of 7.0 units or greater. No significant differences in mortality or clinical outcome were observed between the 10 patients receiving the combined treatment and the 10 receiving routine management. In 14 patients two-dimensional echocardiograms obtained 6 to 24 hours after the onset of symptoms and at follow-up 6 to 16 days later (after completion of combined intraaortic balloon pumping plus nitroglycerin therapy) were analyzed to determine whether infarct segment or noninfarct segment lengths were affected by therapy. Among these 14 patients, 5 (3 receiving the combined therapy and 2 receiving routine management) demonstrated an increase in infarct segment length of greater than 1.0 cm. Mean infarct segment length increased 0.30 +/- 0.44 cm in patients receiving the combined therapy and 0.29 +/- 0.36 cm in patients on routine management (p = NS). In contrast, noninfarct segment length increased greater than 1.0 cm (mean increase 1.20 +/- 0.39) in five of seven patients on routine management but in none of 7 patients receiving intraaortic balloon pumping plus nitroglycerin therapy (mean decrease 0.22 +/- 0.20 cm) (p less than 0.05). No significant differences were noted in left ventricular ejection fraction, as measured by gated blood pool scintigraphy, or thallium perfusion defect score in a comparison of day 1 (pretreatment) with day 4 thallium or day 7 to 14 gated blood pool scintigrams. Thus, in patients with extensive myocardium at risk, it is unlikely that a reduction in mortality or a significant improvement in myocardial perfusion or ventricular function can be obtained by early intervention with intraaortic balloon pumping in combination with nitroglycerin. Although this combined therapy failed to prevent infarct segment lengthening (infarct expansion), the combined afterload-lowering effects of intraaortic balloon pumping and nitroglycerin did appear to prevent dilation or remodeling of noninfarcted segments during the first 2 weeks after acute myocardial infarction.

Adult↗
PubMed1985

Calcium-dependent enhancement of myocardial diastolic tone and energy utilization dissociates systolic work and oxygen consumption during low sodium perfusion.

The relationships and correlations among functional, metabolic, and ionic consequences of low sodium perfusion were studied in isovolumic, retrograde-aortic perfused working rat hearts by 31P nuclear magnetic resonance, oxygen consumption, and atomic absorption spectrometry. Reduction of perfusate sodium from 144 to 74, 51, 39, and 25 mM in four separate groups of hearts via lithium substitution for 15 minutes decreased cell sodium to mean values of 62, 51, 43, and 36 mumol/g dry weight, respectively (P less than 0.001 vs. control of 107). There was a transient rise and then a fall in developed pressure and a decline in phosphocreatine and adenosine triphosphate, all of which were graded and correlated with perfusate sodium (P less than 0.01 for all parameters vs. perfusate sodium). This was accompanied by a 2- to 7-fold elevation of diastolic pressure while oxygen consumption remained near control levels. All parameters except adenosine triphosphate returned toward baseline values when normal perfusate sodium was reintroduced. Although cell calcium as measured by atomic absorption spectrometry did not differ among the groups, the functional and metabolic changes did not occur if the sodium steps were performed in reduced perfusate calcium (0.08 mM). In hearts in which systolic function was obliterated by verapamil, exposure to zero sodium caused a 4-fold increase in oxygen consumption, an increase in diastolic pressure, and a reduction of high energy phosphates. In the presence of ryanodine, a specific inhibitor of sarcoplasmic reticulum calcium release, the metabolic changes did not occur, and the excess oxygen consumption in zero sodium was substantially reduced. Thus, the effect of lowered perfusate sodium in beating hearts, i.e., to dissociate oxygen consumption and systolic function, and to increase diastolic pressure and its effect in arrested hearts to increase oxygen consumption, are calcium dependent, energy consuming, and modulated by sarcoplasmic reticulum calcium cycling.

Adenosine Triphosphate↗
PubMed1984

'Calcium paradox' in the heart is modulated by cell sodium during the calcium-free period.

We hypothesized that after a Ca2+-free period the magnitude of the Na+ gradient at the onset of Ca2+ reperfusion would grade the ensuing cell Ca2+ gain. Rabbit interventricular septa perfused with Hepes buffered solution (pH 7.4, [Ca2+] = 1.0 mM) and stimulated to contract isometrically at 60 min-1 at 30 degrees C were exposed to a 30-min Ca2+-free period followed by 30-min of Ca2+ re-introduction. Cell Na without Ca2+-free perfusion was 137 +/- 5 mumol/g dry wt. During the Ca2+-free period, the perfusate was manipulated to result in three groups of septa in which cell Na just prior to Ca2+ re-introduction was 64 +/- 9 (perfusate [Na+] reduced to 47 mM), 170 +/- 12 (perfusate unaltered), and 293 +/- 16 mumol/g dry wt (addition of 5 X 10(-5) M ouabain). Following Ca2+ re-introduction, cell Ca2+ content was 3.4 +/- 0.5, 6.5 +/- 1.0, and 10.6 +/- 0.7 mumol/g dry wt in the low, intermediate, and high cell Na+ groups, respectively. Similar marked and highly significant gradations among the three groups were observed in the extent of cell K+ loss and recovery of contractile function during Ca2+ reintroduction. These results indicate that (1) myocardial cell Na+ increases during Ca2+ free perfusion and (2) the magnitude of the Na+ gradient at the end of the Ca2+ free period is an important determinant of the extent of cell Ca2+ gain, cell K+ loss, and reduction of contractile function with Ca2+ re-introduction, which collectively have been referred to as the 'calcium paradox' in the heart.

Animals↗
PubMed1984

Perfusate sodium during ischemia modifies post-ischemic functional and metabolic recovery in the rabbit heart.

Metabolic and functional recovery following 60 minutes of low flow (0.1 ml/min) ischemia were compared in rabbit hearts perfused with normal sodium and potassium, low sodium (120 mM NaCl replaced by 120 mM LiCl), or zero potassium perfusate during ischemia. During the control, pre-ischemic, and reperfusion periods, all hearts were perfused identically with normal sodium and potassium. 31P NMR was used to monitor intracellular pH (pHi), ATP, and phosphocreatine (PGr). Developed pressure, end diastolic pressure, pHi, and the integrated areas of ATP and PCr were equivalent in the three groups in the pre-ischemic period. The fall in pHi, PCr, ATP, and developed pressure and the rise in end diastolic pressure during 60 min ischemia also did not differ among the three groups. In contrast to the lack of an effect of perfusate sodium and potassium on the decline in parameters of metabolism and function during ischemia, there was a marked difference in the recovery of these indices during reperfusion. Hearts perfused with low sodium during ischemia exhibited the best recovery (expressed as percent of control) of developed pressure (95 +/- 4%), PCr (106 +/- 6%), and ATP (51 +/- 2%) and the smallest rise in end diastolic pressure (229 +/- 50%); hearts perfused with normal sodium and potassium during ischemia had intermediate recovery values for developed pressure (53 +/- 10%), PCr (78 +/- 9%), ATP (45 +/- 4%) and end diastolic pressure (487 +/- 73%) and the hearts perfused with zero potassium solution during ischemia exhibited the poorest recovery of developed pressure (23 +/- 6%), PCr (49 +/- 6%), ATP (39 +/- 5%) and end diastolic pressure (968 +/- 185%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

Acute nifedipine withdrawal: consequences of preoperative and late cessation of therapy in patients with prior unstable angina.

Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias. An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing. Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Effect of sodium on calcium-dependent force in unstimulated rat cardiac muscle.

It has previously been demonstrated that 1) changes in superfusate calcium concentration [Ca2+]o within the low millimolar range result in changes in "resting" force and in the light-scattering properties of unstimulated rat cardiac muscle, and 2) if [Ca2+]o is increased from zero to millimolar concentrations, i.e., reperfusion with Ca2+ after a Ca2+-free period, a large influx of Ca2+ occurs and is associated with a substantial increase in resting force. The present study determined whether the Ca2+ influx in either case was influenced by intracellular sodium (Na+i). In unstimulated isometric rat right ventricular papillary muscles equilibrated at 29 degrees C, [Ca2+]o was increased from 1 to 4 mM or from 0 to 2 mM under conditions that vary Na+i, and the resulting change in intracellular calcium concentration [( Ca2+]i) was monitored by changes in both resting force and the frequency of intensity fluctuations in laser light scattered by the muscle. In each case, lowering Na+i by equilibration in lowered extracellular sodium concentration [( Na+]o) or enhancing [Na+]i by equilibration in the absence of extracellular potassium or in the presence of ouabain markedly lowered and enhanced respectively the apparent Ca2+ influx in response to the step increase in [Ca2+]o. Thus, in unstimulated rat cardiac muscle, Na+i modulates the Ca2+ influx resulting from a step increase in [Ca2+]o both under physiological conditions and following a period of Ca2+-free superfusion, i.e., the "Ca2+ paradox." A passive influx of Ca2+ down its electrochemical gradient would not depend on Na+i, and the voltage-time dependent slow Ca2+o channel is inactivated under the experimental conditions employed. The results are best explained by a sarcolemmal Na+-Ca2+ exchange mechanism and suggest that the reversal potential of this electrogenic exchanger is exceeded during a step increase in [Ca2+]o even at the transmembrane potential of resting muscle.

Animals↗
PubMed1984

Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate.

To assess the effect of age on cardiac volumes and function in the absence of overt or occult coronary disease, we performed serial gated blood pool scans at rest and during progressive upright bicycle exercise to exhaustion in 61 participants in the Baltimore Longitudinal Study of Aging. The subjects ranged in age from 25 to 79 years and were free of cardiac disease according to their histories and results of physical, resting and stress electrocardiographic, and stress thallium scintigraphic examinations. Absolute left ventricular volumes were obtained at each workload. There were no age-related changes in cardiac output, end-diastolic or end-systolic volumes, or ejection fraction at rest. During vigorous exercise (125 W), cardiac output was not related to age (cardiac output [1/min] = 16.02 + 0.03 [age]; r = .12, p = .46). However, there was an age-related increase in end-diastolic volume (end-diastolic volume [ml] = 86.30 + 1.48 [age]; r = .47, p = .003) and stroke volume (stroke volume [ml] = 85.52 + 0.80 [age]; r = .37, p = .02), and an age-related decrease in heart rate (heart rate [beats/min] = 184.66 - 0.70 [age]; r = -.50, p = .002). The dependence of the age-related increase in stroke volume on diastolic filling was emphasized by the fact that at this high workload end-systolic volume was higher (end-systolic volume [ml] = 3.09 + 0.65 [age]; r = .45, p = .003) and ejection fraction lower (ejection fraction = 88.48 - 0.18 [age]; r = -.33, p = .04) with increasing age. These findings indicate that although aging does not limit cardiac output per se in healthy community-dwelling subjects, the hemodynamic profile accompanying exercise is altered by age and can be explained by an age-related diminution in the cardiovascular response to beta-adrenergic stimulation.

Adult↗
PubMed1984

Variables predictive of successful medical therapy in patients with unstable angina: selection by multivariate analysis from clinical, electrocardiographic, and angiographic evaluations.

Although unstable angina can be initially controlled with medical therapy in most patients, there is a high incidence of subsequent death, myocardial infarction, or need for coronary bypass surgery to control symptoms. Identification at the time of presentation of the patient likely to do poorly on continued medical therapy would be useful in advising consideration of surgical therapy. Since coronary arterial spasm may have a significant role in the pathophysiology of unstable angina in some patients, the recently developed calcium channel antagonists may therefore be of particular benefit in the medical therapy of unstable angina. One hundred thirty-eight patients were entered into a randomized double-blind study of the efficacy of adding nifedipine to conventional treatment of unstable angina (nitrates and beta-blockers) and were followed for 18 months. Of these patients, 104 underwent coronary arteriography. A multivariate Cox's hazard function analysis was applied to variables selected from the history, electrocardiographic (ECG) changes during chest pain, and from scintigraphic and coronary arteriographic data to determine those variables most predictive of response to medical therapy. The percentage of the left ventricular myocardium supplied by vessels with 70% or greater luminal stenosis was the most significant variable in influencing failure of medical therapy defined as sudden death, myocardial infarction, or need for bypass surgery. Whether or not the patient received nifedipine was the second most powerful variable, with the use of nifedipine reducing by half the relative risk of failing medical therapy. These were followed by cigarette smoking and presence of global ST segment changes during ischemia. After 18 months the nifedipine group had fewer patients failing medical therapy (p = .02), with fewer patients undergoing coronary bypass surgery (p less than .01). However, nifedipine did not appear to have a preventive effect against myocardial infarction or death. Kaplan-Meier actuarial curves confirmed that medical therapy was significantly less successful in the presence of increasing numbers of significantly stenotic vessels (p = .03). However, nifedipine provided a significant beneficial effect in patients with two or more stenotic vessels (p less than .01) and in whom 50% or more of the myocardium was supplied by vessels with 70% or greater stenosis (p = .01). Thus, although patients with advanced obstructive coronary disease have the greatest likelihood of unfavorable outcomes, the addition of nifedipine is of significant benefit.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗
PubMed1983

A randomized clinical trial of intravenous nitroglycerin in patients with acute myocardial infarction: benefits of early treatment.

A prospective randomized clinical trial of intravenous nitroglycerin administered for 48 hours following acute infarction was undertaken to determine whether clinical improvement and/or preservation of ischemic myocardium could be demonstrated. One hundred four patients were randomized to receive either nitroglycerin or placebo infusion. Nitroglycerin infusion was titrated to lower mean arterial pressure 10% using non-invasive monitoring. Early nitroglycerin treatment, defined as treatment initiated less than 10 hours after symptom onset, resulted in a lower incidence of new congestive heart failure, myocardial infarct extension, and/or early death from pump failure (15%) compared to late nitroglycerin treatment (50%, p = 0.008) or early placebo treatment (48%, p = 0.01). Improvement in ejection fraction of greater than or equal to 10% was demonstrated in 7 of 20 (35%) early nitroglycerin treated patients compared to 6, 11 and 0% of patients in the three other subgroups, respectively (p = 0.004). Similarly, thallium-201 perfusion scintigrams showed a greater than 75% improvement in defect score in 23 (48%) patients receiving nitroglycerin within 10 hours compared to 14%, 33% and 0% respectively, in the remaining subgroups (p = 0.035). However, before routine administration of nitroglycerin can be recommended for all patients with acute infarction, larger clinical trials will be required.

Clinical Trials as Topic↗
PubMed1982

Nifedipine in unstable angina: a double-blind, randomized trial.

We assessed the efficacy of adding nifedipine to the conventional treatment of unstable angina in 138 patients in a prospective, double-blind, randomized, placebo-controlled trial. There was no difference between the two groups in the dose of conventional antianginal medication or in age, prior myocardial infarction, ejection fraction, or other risk factors. Failure of medical treatment (defined as sudden death, myocardial infarction, or bypass surgery within four months) occurred in 43 of 70 patients given placebo and in 30 of 68 given nifedipine. Kaplan-Meier survival-curve analysis of the number and time dependence of treatment failures demonstrated a benefit of nifedipine over placebo (P = 0.03). The benefit was particularly marked in patients with ST-segment elevation during angina (P = 0.02). Side effects (transient hypotension or diarrhea) required withdrawal of the drug from four patients given nifedipine and from one given placebo. We conclude that the addition of nifedipine to conventional therapy is safe and effective in unstable angina.

Adult↗
PubMed1981

The predictive value of a strongly positive stress test in patients with minimal symptoms.

The ability of a strongly positive stress test to predict left main coronary artery disease in people with suspected coronary artery disease but with minimal or no angina was investigated in 40 such patients. Nine had a history of myocardial infarction but no angina. Thirty-one had mild angina or a history of mild angina. The stress electrocardiograms were analyzed according to criteria known to be associated with left main coronary artery disease in moderately or severely symptomatic patients; (1) early S-T segment changes (stage I or II of exercise), (2) 2 mm or more S-T segment depression, (3) downsloping S-T segments, (4) associated exercise-induced hypotension, (5) prolonged S-T segment changes after the test (greater than or equal to 8 minutes) and (6) anterior and inferior S-T segment depression. The prevalence of left main coronary artery disease was 35 percent and that of any severe coronary artery disease 75 percent. The criterion of anterior and inferior electrocardiographic changes with exercise was most predictive of left main coronary artery disease (P less than 0.01 by chi 2). Exercise electrocardiography is useful in the prediction of left main or other severe coronary artery disease even when performed in patients who have minimal angina or in those who are asymptomatic after myocardial infarction.

Adult↗