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Biomedical subjects

W B Hood

Publications and source records attributed to W B Hood.

At least 19 recordsLinked to original sources

Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.

BACKGROUND: It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. METHODS: Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. RESULTS: There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). CONCLUSIONS: The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.

Blood Pressure

Beta-adrenoceptor and adenylate cyclase function in the infarct model of rat heart failure.

In order to determine the possible etiology for diminished inotropic responsiveness to catecholamines in the infarction model of chronic congestive heart failure in rats, we studied beta-adrenoceptor number and site-specific stimulated adenylate cyclase activity in noninfarcted left ventricular tissue of rats at 3 months after ligation of the left coronary artery. Rats were divided into sham, small infarct, and large infarct groups according to infarct size. The large infarct groups showed increased right ventricle to body weight ratio (0.93 +/- 0.07 mg/g for the large infarcts vs 0.52 +/- 0.02 and 0.54 +/- 0.02 mg/g for the shams and small infarcts, respectively). Beta-Adrenoceptor number among the groups was similar (shams, 27 +/- 1 fmol/mg; small infarcts, 26 +/- 1 fmol/mg; and large infarcts, 29 +/- 1 fmol/mg), as was Kd (20 +/- 1 pmol, 18 +/- 2 pmol, and 18 +/- 2 pmol, respectively). Site-specific stimulation of adenylate cyclase using isoproterenol, Gpp(NH)p, forskolin, and MnCl2 revealed no significant differences among the groups. We conclude that this system is not responsible for the altered inotropic responsiveness to catecholamines seen in this model.

Adenylyl Cyclases

Initial blood pressure response to enalapril in hospitalized patients (Studies of Left Ventricular Dysfunction [SOLVD]).

Studies of Left Ventricular Dysfunction (SOLVD) is a randomized trial of enalapril versus placebo in reducing mortality in patients with cardiac dysfunction (defined as left ventricular ejection fraction less than or equal to 35%). Before randomization, patients at risk for hypotension were hospitalized for a test dose of 2.5 mg of enalapril administered orally at baseline and again 12 hours later. As of February 1989, 89 of 7,539 (1.2%) patients had been studied during hospitalization. Baseline systolic and diastolic blood pressures were 115 +/- 18 and 73 +/- 10 mm Hg, respectively. After enalapril, systolic blood pressure decreased slightly but significantly 8 to 20 hours after the initial dose (mean reduction 8 to 11 mm Hg). In this highly selected group of 89 patients, symptoms relating to decrease in blood pressure were noted in 13 (15%). It is emphasized that most patients with cardiac dysfunction readily tolerate enalapril. However, the agent should be administered with caution to patients with advanced congestive failure and diminished baseline blood pressure, owing to a significant incidence of symptomatic hypotension.

Aged

Effects of short-term, diet-induced hypercholesterolemia on systemic hemodynamics, myocardial blood flow, and infarct size in awake dogs with acute myocardial infarction.

BACKGROUND: Short-term cholesterol feeding has been shown to affect vasomotor tone and increase infarct size in anesthetized rabbits. The purpose of the study was to determine whether acute hypercholesterolemia reduced collateral flow to ischemic myocardium and increased infarct size in the awake dog. METHODS AND RESULTS: Acute myocardial infarction was produced in awake dogs by a 4-hour left anterior descending coronary artery occlusion followed by 6-hour reperfusion after either a cholesterol-supplemented diet (n = 14) or a control diet of dog chow (n = 15) for 10 days. Infarct size was determined using nitroblue tetrazolium staining. In two subgroups, a 15-minute transient occlusion of the left anterior descending coronary artery was produced before the diet treatments and was compared with occlusion after diet treatments, so that the effects of hypercholesterolemia of collateral flow could be determined by paired comparisons. Cholesterol feeding increased plasma cholesterol to 288 +/- 52 mg/dl, which was twofold to threefold that in the control group (127 +/- 35 mg/dl), but had no effects on baseline systemic hemodynamics and myocardial blood flow. Coronary artery occlusion produced similar increases in heart rate, mean aortic pressure, left atrial pressure, and plasma norepinephrine in both groups of animals. However, cholesterol feeding reduced collateral flow to ischemic myocardium and increased infarct size, compared with the control group. The infarct size correlated with ischemic myocardial blood flow in both groups, but the slopes of regression lines relating the two variables did not differ between the two groups. CONCLUSIONS: Short-term, diet-induced hypercholesterolemia increased infarct size in awake dogs. This change results, at least in part, from a decrease in collateral blood flow to ischemic myocardium during coronary artery occlusion.

Animals

Controlled and uncontrolled studies of phosphodiesterase III inhibitors in contemporary cardiovascular medicine.

The phosphodiesterase inhibitors are new inotrope vasodilators that have beneficial hemodynamic effects in patients with congestive heart failure (CHF). The most extensively studied agents are milrinone and enoximone. Both drugs have clearly been shown in numerous studies to improve hemodynamics in patients with CHF when given acutely by either the intravenous or oral route. In long-term studies, milrinone has been shown to have sustained beneficial hemodynamic effects during active treatment. Effects on exercise tolerance have been less clear-cut in several uncontrolled trials, but a recent large-scale randomized trial does show sustained improvement in exercise performance. When milrinone is withdrawn after long-term therapy, some studies show worsened cardiac performance; the exact cause remains ill-defined, but could be due to deterioration of baseline ventricular function or to "rebound." Both uncontrolled studies and a large recently reported randomized trial show that the hemodynamic response to readministration of milrinone after withdrawal is well-preserved, i.e., no tolerance is observed. Studies of enoximone show that its acute hemodynamic effects are similar to those of milrinone, but its long-term efficacy, using both hemodynamic and exercise end points, is less clear-cut, and no large-scale randomized trials of enoximone therapy have yet been reported. The studies of both these agents performed thus far indicate that the phosphodiesterase inhibitors have considerable promise for both acute and long-term treatment of patients with CHF.

Clinical Trials as Topic

Effects of pinacidil on myocardial blood flow and infarct size after acute left anterior descending coronary artery occlusion and reperfusion in awake dogs with and without a coexisting left circumflex coronary artery stenosis.

To determine whether partial stenosis of a second major coronary artery promoted vasodilator-induced coronary steal and increased infarct size after acute coronary artery occlusion, we produced acute myocardial infarction by 4-h left anterior descending coronary artery occlusion and 20-h reperfusion in awake dogs with and without a mild to moderate stenosis (33-72%) of the proximal left circumflex coronary artery. Dogs were randomized to receive intravenous (i.v.) normal saline or pinacidil, a new antihypertensive agent with a marked coronary dilator property, beginning 40 min after onset of coronary artery occlusion and continuing throughout the occlusion and the first hour of reperfusion. Pinacidil was titrated to decrease mean aortic pressure 25 mm Hg, which resulted in an increase in heart rate (HR), cardiac output (CO), and left ventricular (LV) dP/dt and LVdP/dt/P. Saline infusion had no effects. Blood flows to ischemic and remote myocardium did not differ between dogs with and without coronary stenosis. Pinacidil increased blood flow threefold in normal myocardium, but had no effect on infarct zone myocardial blood flow or infarct size (58 +/- 4% of region at risk vs. 56 +/- 4% in animals receiving normal saline) in dogs without coronary stenosis. In contrast, similar administration of pinacidil in dogs with coronary stenosis reduced infarct size zone myocardial blood flow and increased infarct size (69 +/- 3% vs. 55 +/- 5% in the saline group, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of milrinone on systemic hemodynamics and regional circulations in dogs with congestive heart failure: comparison with dobutamine.

Milrinone is a new bipyridine inotropic agent with direct vasodilator properties. To determine the role of the vasodilator action in mediating systemic and regional hemodynamic responses to milrinone, we administered two equipotent inotropic doses of either milrinone or dobutamine to dogs with chronic congestive right heart failure produced by tricuspid avulsion and pulmonary artery stenosis. Similar increases in cardiac output, right and left ventricular dP/dt, and left ventricular dP/dt/P were produced by milrinone and dobutamine; however, heart rate increased and mean aortic pressure decreased only with milrinone infusion. In addition, while total peripheral vascular resistance decreased with both agents, the decrease was greater with milrinone. Regional blood flows were measured by a radioactive microsphere method. Milrinone and dobutamine produced similar increases in myocardial blood flow and left ventricular oxygen consumption. Dobutamine infusion decreased quadriceps muscle vascular resistance and had no effect on renal and splanchnic circulations. In contrast, milrinone infusion increased vascular resistance in quadriceps muscle and decreased it in renal and splanchnic beds. Thus, when milrinone was used in inotropic doses similar to those of dobutamine, the responses in systemic and regional hemodynamics in congestive heart failure differed. Milrinone produced a greater decline in total peripheral, renal, and splanchnic vascular resistances, probably resulting from its direct vasodilator action.

Animals

Noninvasive assessment of cardiac motion: comparison of the apexcardiogram and cardiokymorgram.

The apexcardiogram (ACG) and cardiokymogram (CKG) (displacement cardiogram) tracings were compared in 45 patients with a variety of cardiac diseases and in 16 normal subjects. The ACG and CKG were generally comparable in waveform and timing of standard tracing intervals; however, on a case by case comparison frequent discrepancies between the ACG and CKG were observed. In 13 patients where no ACG could be recorded, an interpretable CKG tracing was obtained. However, the CKG produced frequent artifacts, mirror images, was very sensitive to probe position, and was judged to be of limited advantage over the ACG.

Adult

Effects of nitroglycerin on echocardiographic measurements of left ventricular wall thickness and regional myocardial performance during acute coronary ischemia.

The effects of nitroglycerin on regional left ventricular performance, assessed by echocardiographic techniques, were investigated in anesthetized, open-chest dogs during acute myocardial ischemia. During transient occlusion of the left anterior descending coronary artery, there was end-diastolic thinning and marked reduction in systolic thickening in the central ischemic zone. Similar changes of lesser degree were noted in the border zone. The normal zone was unaffected. Infusion of nitroglycerin during ischemia in dosages of 2.5--50 microgram/kg/min reduced left ventricular end-diastolic pressure without changing the abnormalities of systolic wall thickening. Effects of bolus injections of 20 and 50 microgram/kg of nitroglycerin were similar, although this also lowered aortic pressure. In a subgroup of animals in which nitroglycerin infusion was unaccompanied by tachycardia, there was also no evidence that ischemic dysfunction was altered. We conclude that nitroglycerin does not improve regional myocardial performance in acutely ischemic canine myocardium. The decrease in preload is probably entirely due to the peripheral effects of the agent.

Animals

Conditioning effects of chronic infusions of dobutamine. Comparison with exercise training.

We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 mug/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10 degrees incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning. To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups. Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning.

Animals

An assessment of emergency medical technicians' performance as related to seasonal population influx.

The periodic influx of large numbers of people into resort areas substantially increases the use of emergency medical services. This investigation assesses the effects of such a threefold increase in the summer population of the Cape Cod area upon the accuracy of emergency medical technicians' diagnoses and treatments. The technicians' diagnoses for ambulance patients were evaluated against those given by the emergency room physicians during the months of August 1975 and February 1976. The distribution of conditions was similar for both months and the observed frequency of correct diagnoses for common conditions was more than 90% in both months. The overdiagnosis rate of 25% to 50% for common conditions and the correct treatment rate for suspected myocardial infarction of 65% did not vary significantly between summer and winter. Thus, a large influx in population does not seem to affect adversely EMT diagnosis rates. Although misdiagnoses were uncommon, a failure to follow through with a correct treatment for patients with suspected myocardial infarctions, thus indicating the need for better quality control on EMT performance.

Allied Health Personnel

The predictive value of anginal chest pain as an indicator of coronary disease during exercise testing.

To determine the significance of anginal chest pain during exercise testing, a series of 302 patients undergoing coronary arteriography with exercise testing was reviewed. Of the 302 patients, 85 had ischemic ECG changes and chest pain (Group I); 87 patients had ischemic ECG changes but no chest pain (Group II); 25 patients had chest pain but no ischemic ECG changes (Group III); 105 patients had neither chest pain nor ischemic ECG changes (Group IV). Coronary artery disease was present in 95% of Group I, 75% of Group II, 72% of Group III, and 28% of Group IV. Of those patients with coronary disease, multiple vessels were involved in 94% of Group I, 51% of Group II, 67% of Group III, and 21% of Group IV. The predictive value for presence and extent of coronary disease showed Group I greater than Groups II and III greater than Group IV (p less than 0.025). We conclude that (1) anginal chest pain during exercise testing predicts the presence and extent of coronary disease more accurately than its absence; (2) the presence of chest pain even without an ischemic ECG response during exercise testing appears to be as predictive of coronary disease as an ischemic ECG response alone; and (3) the combination of anginal chest pain during exercise testing and an ischemic ECG response is highly predictive of multivessel coronary artery disease.

Angina Pectoris

Experimental myocardial infarction. XVI. The detection of inotropic contractile reserve with postextrasystolic potentiation in acutely ischemic canine myocardium.

Postextrasystolic potentiation after a single closely coupled extrasystole may identify residual ventricular contractile performance in acutely ischemic myocardium without producing sustained secondary ischemic depression of myocardial function. Postextrasystolic potentiation was systematically used in eight open chest dogs to assess the progression of regional contraction abnormalities during a 10 minute occlusion of the left anterior descending coronary artery. Segment function was determined from pressure-length loop areas inscribed during right ventricular pacing at 128 +/- 3 (mean +/- standard error of the mean) beats/min, and after single closely coupled (179 +/- 3 msec) extrasystoles. Despite a 50 percent decrease in border zone segment function, postextrasystolic potentiation consistently augmented mechanical performance to control levels throughout the ischemic period. Central ischemic zone segment function deteriorated more profoundly, with the development of holosystolic aneurysmal bulging within 30 seconds after occlusion. Nonetheless, postextrasystolic potentiation produced marked inotropic augmentation, but not to control levels, for up to 10 minutes of ischemia. These results suggest that latent viability and contractile reserve may exist during brief periods of coronary occlusion.

Animals

Electrocardiographic mapping of the precordium in the coronary care unit.

Precordial electrocardiographic mapping systems comprising a large number of recording sites have been utilized in the Coronary Care Unit for following the natural course of ischemic injury and detecting extension of acute myocardial infarction in patients. These electrocardiographic techniques have also been found useful in evaluating the effects of a number of metabolic, hemodynamic and pharmacologic interventions currently proposed as effective means of reducing the extent of ischemic damage. However, these methods have not been found useful in the study of patients with inferior transmural or nontransmural myocardial infarctions. Bundle branch blocks and pericarditis complicating acute myocardial infarction invalidate the mapping technique. To assess effectiveness of therapeutic interventions, ST-segment changes taken as an index of ischemic injury are correlated with alterations of the QRS complex, used as a parameter of ischemic necrosis.

Coronary Care Units