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Biomedical subjects

E Braunwald

Publications and source records attributed to E Braunwald.

At least 289 records · Page 16Linked to original sources
PubMed1984

Ventricular performance in rats with myocardial infarction and failure.

Ventricular performance was assessed in rats three weeks following coronary artery ligation and the subsequent production of a wide range of infarct sizes. The entire spectrum of ventricular dysfunction was observed, from minimal impairment to overt congestive heart failure. Rats with small infarcts ejected normal baseline and volume-stressed forward outputs from a modestly dilated ventricular chamber. Rats with moderate infarcts exhibited normal baseline hemodynamics but had a reduced reserve flow capacity when challenged with a volume load despite considerable ventricular dilatation. Rats with large infarcts demonstrated frank congestive heart failure with elevations in both left and right ventricular filling pressures and consequent right ventricular hypertrophy; marked reductions in both baseline and volume-stressed forward outputs; and ventricular volumes that were twice those of rats without infarcts. Thus, a progressive impairment in ventricular performance and an increase in chamber volume occurred in relation to infarct size in rats with healed myocardial infarction.

Animals↗
PubMed1984

Heparin inhibits bovine testicular hyaluronidase activity in myocardium of dogs with coronary artery occlusion.

Bovine testicular hyaluronidase (BTH) reduces experimental myocardial infarct size and ameliorates electrocardiographic signs of ischemia. This study was done to determine if heparin, an in vitro inhibitor of hyaluronidase activity, blocks the action of BTH in the myocardium of dogs after coronary artery occlusion. BTH was administered intravenously as 5,000 NF units/kg at 0.5 and 2.5 hours after coronary occlusion. Heparin was administered intravenously as a 150-unit/kg loading dose, followed by 10 units/kg per hour i.v., beginning 15 minutes before coronary occlusion. The area of myocardial ischemia at risk was assessed by a radiolabeled microsphere technique; the area that developed necrosis was assessed by a histochemical technique. In vivo activity of BTH was assessed by a colorimetric analysis of the BTH substrate, i.e., hyaluronic acid (HA), extracted from myocardial tissue. For biochemical analysis of HA, the heart was divided into anterior myocardium, which included ischemic tissue and posterior nonischemic myocardium. The myocardial HA content of dogs treated with BTH plus heparin (anterior, 3.44 +/- 0.40 micrograms HA/mg protein; posterior, 3.69 +/- 0.33 micrograms HA/mg protein) was not significantly different from control (anterior, 3.61 +/- 0.29 micrograms HA/mg protein; posterior, 3.55 +/- 0.23 micrograms HA/mg protein). In contrast, BTH lowered myocardial HA content (anterior, 2.16 +/- 0.21 micrograms HA/mg protein; posterior, 2.08 +/- 0.14 micrograms HA/mg protein) compared with either BTH plus heparin or control groups in both anterior myocardium (p = 0.006) and posterior myocardium (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Response of reperfusion-salvaged, stunned myocardium to inotropic stimulation.

The purpose of this study was to determine whether myocardium salvaged by reperfusion following coronary occlusion could respond to inotropic stimulation by dopamine. Mongrel dogs underwent a 2-hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for 5 or 28 hours. Dopamine (5 to 10 micrograms/kg/min) or dextrose was administered 1 hour or 24 hours after the onset of reperfusion. Serial, computer-assisted, two-dimensional echocardiographic determination of percentage of systolic wall thickening (%SWT) and cross-sectional ejection fraction (% delta area) were used to evaluate the response to treatment. Myocardium in the region of central ischemia contracted poorly after 1 hour of reperfusion (mean %SWT = 1.3 +/- 13.3% [mean +/- SD] compared to preocclusion value of 43.6 +/- 18.5%, p less than 0.001) and tended to thin at 24 hours of reperfusion (mean %SWT = -6.0 +/- 12.3%, p less than 0.001). After 1 hour of reperfusion, dopamine produced a greater than fourfold improvement in %SWT within the reperfused zone (to 15.3 +/- 7.3%, p less than 0.05). After 24 hours of reperfusion, dopamine again produced an improvement in %SWT (to 5.8 +/- 12.5%, p less than 0.05). There were no significant changes in %SWT with dextrose infusion. Thus, dopamine stimulates the reperfusion-salvaged but noncontracting (stunned) myocardium to contract as early as 1 hour after reperfusion.

Animals↗
PubMed1984

Enhancement of salvage of reperfused myocardium by early beta-adrenergic blockade (timolol).

Although reperfusion of severely ischemic myocardium with thrombolytic agents or surgery has shown reduction in infarct size, the time after coronary occlusion during which reperfusion can salvage ischemic myocardium is limited. To determine whether beta-adrenergic blockade could enhance the salvage of ischemic myocardium by reperfusion, the left anterior descending coronary artery was occluded in 18 anesthetized dogs. An in vivo area at risk was determined by injecting technetium-99m-labeled albumin microspheres into the left atrium 5 minutes after occlusion and carrying out radioautography to define the poorly perfused tissue. Fifteen minutes after coronary occlusion, the dogs were randomized either to a control (saline-treated) group (n = 8) or to a timolol-treated group (n = 10). Timolol was administered until a decrease of 20% in heart rate or blood pressure occurred (mean total dose = 0.85 +/- 0.22 mg/kg +/- standard error of the mean). Coronary occlusion was maintained for 3 hours and was followed by 3 hours of reperfusion in both groups. At the end of 6 hours, infarct size was defined by triphenyltetrazolium chloride staining and masses of infarct and risk were calculated. Percent left ventricular mass at risk was similar for both groups (control = 20.9 +/- 2.4%, timolol-treated = 23.7 +/- 2.1%, p = not significant). Mass of necrosis/mass at risk was significantly smaller in the timolol-treated reperfusion group (27.3 +/- 2.7%) versus saline reperfusion alone (46.5 +/- 5.6%) (p less than 0.005). Thus, beta-adrenergic blockade administered early after coronary occlusion results in substantial enhancement of the salvage achieved by reperfusion alone.

Animals↗
PubMed1984

Drug-induced expansion of infarct: morphologic and functional correlations.

It has been established that glucocorticoids and several nonsteroidal antiinflammatory drugs, when administered early after coronary occlusion, interfere with myocardial scar formation. To determine whether this action is associated with expansion of myocardial infarct during the first week of coronary occlusion and whether expansion affects ventricular function, the effects of indomethacin on the left ventricle in the early phase of infarction were studied. In a blinded randomized study, experimental myocardial infarction was produced in 17 open-chest dogs by ligation of the proximal left anterior descending coronary artery; the treated group (n = 8) received 10 mg/kg iv indomethacin at 15 min and 3 hr after occlusion, and the control group (n = 9) received saline. After 7 days, regional function expressed as percent change of area (% delta A) of the left ventricular cavity was calculated from short-axis two-dimensional echocardiograms at the level of the infarct, the animals were killed, and their hearts were examined. The ratio of infarct thickness to noninfarcted wall thickness was 1.20 +/- 0.08 (mean +/- SEM) in the control group, and the ratio was lower in the indomethacin group, 0.96 +/- 0.04 (p less than .025). An expansion index of myocardial infarction was calculated as previously described and was 1.02 +/- 0.04 in the control group vs 1.29 +/- 0.06 in the indomethacin group (p less than .005). In eight dogs (six control and two treated) without expansion (expansion index less than 1.09), regional function expressed as % delta A was 46.8 +/- 2.6% (SEM), and in nine dogs (six treated and three control) with expansion, % delta A was significantly lower, 28.7 +/- 4.0% (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Instantaneous measurement of left and right ventricular stroke volume and pressure-volume relationships with an impedance catheter.

The feasibility of using continuous on-line recording of intraventricular electrical impedance to measure ventricular stroke volume was assessed in 12 patients at cardiac catheterization with a multielectrode impedance catheter and a 1.3 kHz measuring current of 4 microA. Stroke volumes determined by electrical impedance were compared with stroke volumes determined by the thermodilution technique in 10 patients and correlated with an r value of .95. Directional changes in impedance recordings throughout the cardiac cycle were also compared with volume curves obtained from six patients by radionuclide ventriculography, and in all instances the agreement between the two volume recordings was excellent. For all patients, on-line measurements of impedance showed a beat-by-beat decrease in stroke volume with the Valsalva maneuver and the administration of amyl nitrite, as well as an immediate increase in stroke volume in the contraction following an extra-systolic beat. Similar directional changes in stroke volume were recorded in both left and right ventricles. Left ventricular pressure-volume relationships were assessed with simultaneous left ventricular pressure recordings and volume signals recorded from the impedance catheter to determine if impedance measurements of volume can be used clinically. Pressure-volume diagrams were subsequently plotted, and for all patients these diagrams showed characteristic isovolumetric contraction and relaxation phases as well as typical ejection and filling periods. Moreover, beat-by-beat sequential pressure-volume diagrams constructed for patients during the administration of amyl nitrite revealed a linear end-systolic pressure-volume relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1984

Preservation of high-energy phosphates by verapamil in reperfused myocardium.

To determine whether verapamil prevents depletion of adenine nucleotides during and after severe myocardial ischemia, dogs were subjected to 15 min occlusions of the left anterior descending coronary artery followed by 240 min of reperfusion. One hour before occlusion, dogs were randomly assigned to a treatment group (n = 10) to which an infusion of intravenous verapamil was given until the onset of reperfusion or to an untreated saline group (n = 9). Verapamil reduced mean aortic pressure and heart rate. After 15 min of ischemia, endocardial adenosine triphosphate (ATP) level, determined by needle biopsy, decreased in the untreated group from 34.7 +/- 2.0 to 24.4 +/- 2.7 nmol X mg protein-1 (p less than .005 vs preocclusion) and in the verapamil group from 32.8 +/- 1.5 to 30.3 +/- 1.5 nmol X mg protein-1 (NS vs preocclusion). Dogs receiving verapamil had significantly higher ATP levels than untreated animals after 90 and 240 min of reperfusion. In untreated animals the sum of inosine and hypoxanthine levels increased during occlusion from very low levels to 4.6 +/- 1.1 nmol X mg protein-1 in the epicardium and to 6.8 +/- 1.5 nmol X mg protein-1 in the endocardium (p less than .05 compared with preocclusion values). In verapamil-treated dogs inosine and hypoxanthine levels increased to only 1.2 +/- 0.3 (epicardium) and 1.9 +/- 0.6 nmol X mg protein-1 (endocardium) (both NS compared with preocclusion values). After 90 min of reperfusion the sum of ATP, adenosine diphosphate, adenosine monophosphate, inosine, and hypoxanthine levels was decreased in the endocardium by 10.2 nmol X mg protein-1 in the untreated group, but no change was observed in verapamil-treated animals. We conclude that breakdown of ATP to inosine and hypoxanthine during severe ischemia is reduced by verapamil, resulting in higher ATP concentrations during occlusion and reperfusion and decreased washout of the diffusible purines inosine and hypoxanthine during reperfusion.

Adenosine Diphosphate↗
PubMed1984

Thirty-five years of progress in cardiovascular research.

In this overview of the achievements of the National Heart, Lung, and Blood Institute (NHLBI), the major developments in each major form of heart disease since the birth of the Institute 35 years ago are reviewed. In the case of congenital heart disease, it has become possible to establish an accurate diagnosis, often by noninvasive methods, and to correct by surgical treatment almost all congenital cardiac malformations. The major challenge now is to eliminate these disorders; this will require an understanding of the fundamental molecular basis of these lesions. Acquired valvular heart disease can also now be characterized by hemodynamic, angiographic, as well as noninvasive techniques, principally echocardiography. Surgical treatment is usually successful, but improvement in the durability of valves without thromboembolic potential remains an important challenge. While essential hypertension can now be managed pharmacologically in almost every patient and while such management reduces the excess mortality resulting from this condition, current research focuses on elucidating the underlying basis of this disorder. Atherosclerosis remains the most common cause of cardiac and vascular disease. Although its cause has not been defined, several abnormalities in lipid metabolism that play an etiologic role in many patients with atherosclerosis have been identified. The treatment of these disorders with cholesterol-binding resins, which increase the number of cellular receptors for low-density lipoprotein, and with inhibitors of the enzyme required for cholesterol biosynthesis holds considerable promise. Noninvasive techniques will be used increasingly for detection of atherosclerosis in asymptomatic persons and for determining the efficacy of therapy. The mortality resulting from acute myocardial infarction has been reduced in half by the development of coronary care units and the prompt treatment of potentially fatal ventricular tachyarrhythmias. Current research is focused on preventing pump failure by limiting infarct size; lysis of coronary thrombi now appears to be the most promising method of accomplishing this. Chronic angina pectoris can be relieved by the judicious use of three classes of drugs--organic nitrates, beta-adrenergic blockers, and calcium antagonists, and two mechanical approaches--percutaneous transluminal coronary angioplasty and coronary artery bypass grafting--are usually successful in relieving angina in patients who do not respond adequately to medical management. Whether or not any of these approaches prolong life is not yet settled.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗