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Biomedical subjects

E Braunwald

Publications and source records attributed to E Braunwald.

At least 325 records · Page 18Linked to original sources
PubMed1983

The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat.

Female spontaneously hypertensive and normotensive rats were studied at 6, 12, 18, and 24 months of age to determine which characteristics of myocardial performance herald the onset of left ventricular dysfunction. Peak ejection fraction index was derived from measurements of peak stroke volume (in vivo volume loading) and passive pressure-volume relations. The myocardial stiffness constant (km, slope of the incremental modulus-stress relation, EINC = km sigma), chamber stiffness constant (kc, slope of the chamber stiffness-pressure relation, dP/dV = kcP), and left ventricular cavitary volume-to-wall volume ratio at 10 mm Hg) were calculated from the pressure-volume data and the contractile state was assessed from the ejection fraction index-afterload relations. In the normotensive rats, the myocardial stiffness constant was not affected by age, whereas, in the spontaneously hypertensive rats, the myocardial stiffness constant remained within normal limits until 18 months, at which time a significant increase in this index of myocardial stiffness occurred. Baseline and maximal cardiac indices and ejection fraction index of spontaneously hypertensive rats were normal from 6 to 18 months, but were markedly reduced at 24 months. This reduction in cardiac performance was associated with a decrease in the left ventricular chamber stiffness constant, i.e., kc. This decreased chamber stiffness, which occurred at a time when myocardial stiffness was increased, was due to a greater increase in cavity size than in myocardial stiffness. The left ventricular cavity-to-wall volume ratio of normotensive rats was not affected by age, whereas, in the spontaneously hypertensive rats, this ratio markedly declined by 18 months. The ejection fraction index-afterload relations i.e., a measure of the contractile state, of the 6- and 12-month-old spontaneously hypertensive rats were similar to those of the normotensive rats of all ages. However, a depression in the contractile state of the spontaneously hypertensive rats occurred at 18 months and was further depressed at 24 months. This abnormality of the contractile state was evident before the deterioration of cardiac performance, as reflected in a decrease in baseline and maximal cardiac indices, and dilation of the left ventricle occurred. The contractile state (ejection fraction index-afterload relation) is thus the most sensitive indicator of left ventricular dysfunction in spontaneously hypertensive rats.

Animals↗
PubMed1983

Studies of experimental coronary artery reperfusion. Effects on infarct size, myocardial function, biochemistry, ultrastructure and microvascular damage.

The present report is a review of recent experimental studies in a canine model of acute coronary occlusion. The questions addressed were: (1) Does coronary reperfusion reduce myocardial infarct size? (2) What is the relationship between microvascular damage and hemorrhage and the development of myocardial necrosis? (3) What are the biochemical, functional and ultrastructural characteristics of reperfused tissue salvaged from necrosis? Coronary occlusion followed by reperfusion in the dog resulted in significant subepicardial salvage of myocardium if reperfusion was instituted before 6 hours of ischemia. Because ultrastructural evidence of microvascular damage was found only after irreversible damage to myocytes, and because gross hemorrhage after coronary reperfusion was confined to zones of myocardium that were already necrotic, it does not appear that hemorrhage should serve as a deterrent to reperfusing reversibly injured myocytes. Severely ischemic myocardium that had been salvaged by coronary reperfusion required several days before it returned to normal from biochemical, functional and ultrastructural standpoints.

Adenosine Triphosphate↗
PubMed1982

Effects of hypertension on cardiac performance in rats with myocardial infarction.

To determine the effects of hypertension and myocardial infarction on cardiac performance, hemodynamic studies were performed on ether-anesthetized, female spontaneously hypertensive rats and on two strains of normotensive rats, Wistar-Kyoto and American Wistar, 26 days after coronary arterial ligation. Baseline measurements of ventricular and arterial pressures and cardiac output (electromagnetic flowmeter) were obtained. Peak cardiac pumping and pressure-generating capacities were determined during a volume load and aortic occlusion, respectively. Infarct size was determined by planimetry. There was a progressive reduction in mean arterial pressure in relation to infarct size in both hypertensive and normotensive rats, but this reduction was twice as great in spontaneously hypertensive rats as in the normotensive rats, such that the arterial pressure of hypertensive rats with a moderate or large infarction decreased to within the "normotensive range." However, spontaneously hypertensive rats still maintained significantly higher arterial pressures than did normotensive rats at comparable infarct sizes. There was also a progressive reduction in the peak pressure developed during an afterload stress, and this reduction was greater in hypertensive rats than in normotensive rats with a large infarct. Maximal flow-generating capacity was similarly altered in rats with infarction: Peak stroke volume index varied inversely with infarct size and the reduction in this index was significantly greater in spontaneously hypertensive rats than in normotensive rats with a large infarct. Moreover, peak stroke work index was reduced to a greater extent in spontaneously hypertensive rats than in both normotensive strains of rats at any infarct size. Thus, after myocardial infarction, greater reductions in both pressure and flow-generating capacities occurred in hypertensive rats than in normotensive rats.

Animals↗
PubMed1982

Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat.

To determine whether chronic antihypertensive therapy prevents the progression of cardiac hypertrophy and the deterioration in cardiac performance observed in spontaneously hypertensive rats (SHR) with long-term hypertension, 14-month-old female SHR and normotensive American Wistar rats (NWR) were treated for 10 months with an inhibitor of angiotensin I-converting enzyme, captopril (2 g/liter of drinking water). Captopril reduced the marked left ventricular hypertrophy of 24-month-old SHR (untreated, 4.37 +/- 0.2 mg/g of body weight; treated, 3.01 +/- 0.1 mg/g; P less than 0.02) to levels observed in 6-month-old SHR. Treatment prevented the reductions in baseline and maximal aortic blood flows that occurred in SHR between ages 12 and 24 months yet had no effect on the blood flows of NWR. The diminished maximal stroke volume of untreated SHR was ejected from a significantly increased left ventricular end-diastolic volume, so that the ejection-fraction index was markedly reduced (24-month-old untreated NWR, 84 +/- 3%; untreated SHR, 56 +/- 5%; P less than 0.001). Therapy restores this index in SHR to normal (77 +/- 4%). The relationship between ejection-fraction index, and afterload was also normal in treated SHR. Thus, chronic therapy with captopril produced a marked regression of cardiac hypertrophy and prevented the deterioration of cardiac performance in SHR with long-standing hypertension.

Age Factors↗
PubMed1982

Extension of myocardial necrosis into normal epicardium followng hypotension during experimental coronary occlusion.

In an effort to determine the manner in which hypotension following experimental coronary occlusion affects myocardial infarct size, the left anterior descending coronary artery was occluded in 22 barbiturate anaesthetised dogs, the chest was closed, and the dogs allowed to recover. Thirty minutes following coronary occlusion, seven dogs were haemorrhaged to a mean arterial pressure of 8.2 +/- 0.3 kPa (62 +/- 2 mmHg) and maintained at this pressure; no intervention was undertaken in control dogs. Twenty-four hours after coronary occlusion infarct size in control and hypotensive animals was determined. The hypotensive group developed larger percentages of necrosis of the left ventricles distal to the site of occlusion than did the control dogs (37.8 +/- 2.3 vs 30.4 +/- 1.4 (P less than 0.01)). Although the percentage of infarcted endocardium did not change significantly, the infarction of epicardium was 45% larger in the hypotensive group (34.4 +/- 3.3% vs 23.7 +/- 1.9%, P less than 0.01). Regional myocardial blood flow (RMBF) was determined by means of radioactive microspheres in 5 dogs following coronary occlusion before and after hypotension. RMBF following haemorrhage fell by an equal proportion, 61.9 +/- 3.3% in normal tissue and 61.2 +/- 2.4% in ischaemic zones. In conclusion, hypotension caused infarct extension into the epicardium, ie, into tissue that does not become necrotic under control conditions.

Animals↗
PubMed1982

Favorable effects of therapy on cardiac performance in spontaneously hypertensive rats.

To determine whether chronic antihypertensive therapy reduces cardiac mass and improves performance in spontaneously hypertensive rats (SHR) with marked left ventricular hypertrophy and evidence of cardiac dysfunction, 12-mo-old male and female SHR and age- and sex-matched normotensive rats (NORM) were treated for 6 mo with either tap water or tap water containing hydralazine or guanethidine. Cardiac performance was assessed by the peak stroke volume and cardiac indices attained during volume loading and by the maximum left ventricular pressure developed during an aortic occlusion. Passive diastolic pressure-volume curves were obtained in the potassium-arrested heart. Treatment prevented the progression of left ventricular hypertrophy in SHR and the marked deterioration in peak pumping ability observed in untreated male SHR and the modest impairment observed in female SHR. The peak developed pressure of both the male and female treated SHR was reduced toward that of NORM and was associated with a reduction in the left ventricular mass-to-volume ratio toward that of NORM. Thus chronic therapy with either hydralazine or guanethidine reduced cardiac mass and prevented the deterioration in cardiac pumping performance observed in SHR with sustained hypertension and marked cardiac hypertrophy.

Aging↗
PubMed1982

Studies of amiodarone during experimental myocardial infarction: beneficial effects on hemodynamics and infarct size.

The effect of amiodarone was investigated in a canine model of myocardial infarction. The left anterior descending coronary artery was occluded in 24 anesthetized dogs. After 15 minutes of coronary artery occlusion, the ischemic myocardium at risk of necrosis was determined by labeling the heart with technetium-99m-labeled human albumin microspheres injected into the systemic circulation through the left atrium, and the dogs were than randomized to either a saline-treated control group (n = 13) or an amiodarone-treated group (n = 11) that received i.v. amiodarone, 10 mg/kg, administered in a single bolus 30 minutes after coronary artery occlusion. Myocardial infarct size was determined directly after 6 hours of coronary occlusion by incubation of sections of myocardium in triphenyltetrazolium chloride, a dehydrogenase stain, and expressed as a percentage of left ventricle below occlusion. Autoradiography of the stained myocardial sections was performed to determine the ischemic myocardium at risk of necrosis, which was similar in the control and amiodarone-treated groups (31.8 +/- 2.8% vs 32.5 +/- 3.3% of the left ventricle, respectively). In the amiodarone-treated group, only 67.1 +/- 8.4% of the myocardium at risk became necrotic; in the control group, 97.5 +/- 7.7% of the myocardium at risk became necrotic (p less than 0.01), representing 21.8 +/- 3.5% vs 31.1 +/- 2.8% of the left ventricle below occlusion, respectively (p less than 0.025). Amiodarone decreased heart rate, contractility and afterload. Its beneficial action on infarct size is related presumably to reduced myocardial oxygen demand.

Amiodarone↗
PubMed1982

The stunned myocardium: prolonged, postischemic ventricular dysfunction.

Myocardial ischemia has, for many decades, been viewed as an all-or-none process that causes myocardial necrosis when prolonged and severe, but whose effects are transient when it is brief or mild. In view of the evidence that the ischemic process may "hit, run and stun," perhaps our thinking about the consequences of myocardial ischemia should be expanded. According to this formulation, an ischemic insult not of sufficient severity of duration to produce myocardial necrosis may acutely affect myocardial repolarization and cause angina (hit); but these changes wane rapidly (run), when the balance between myocardial oxygen supply and demand has been reestablished. However, the ischemia may interfere with normal myocardial function, biochemical processes and ultrastructure for prolonged periods (stun). The severity and duration of these postischemic changes depend on the length and intensity of the ischemia, as well as on the condition of the myocardium at the onset of the ischemic episode. Furthermore, it is likely that when the myocardium is repeatedly stunned, it may exhibit chronic postischemic left ventricular dysfunction, an ill-defined condition. If prolonged, chronic postischemic left ventricular dysfunction can progress to myocardial scarring and ischemic cardiomyopathy, it may be important to determine how often it can be ameliorated by permanent improvement of myocardial perfusion by surgical treatment.

Adenosine Triphosphate↗