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Biomedical subjects

E Braunwald

Publications and source records attributed to E Braunwald.

At least 433 records · Page 24Linked to original sources
PubMed1976

Role of arterial baroreceptors in mediating cardiovascular response to exercise.

The role played by the major arterial baroreceptor reflexes in the cardiovascular response to exercise was examined by comparing the responses of untethered conscious dogs instrumented for the measurement of aortic pressure and cardiac output with those of dogs with total arterial barorecptor denervation (TABD). Moderately severe levels of exercise (12 mph) in intact dogs increased cardiac output from 111 +/- 17 ml/kg per min, increased heart rate from 101 +/- 5 to 265 +/- 8 beats/min, and reduced total peripheral resistance from 0.039 +/- 0.003 to 0.015 +/- 0.002 mmHg/ml per min. Dogs with TABD responded in a very similar fashion; exercise increased cardiac output from 119 +/- 8 to 356 /+- 23 ml/kg per min, increased heart rate from 122 +/- 7 to 256 +/- 5 beats/min, and decreased total peripheral resistance from 0.042 +/- 0.005 to +/- 0.015 +/- 0.001 mmHg/ml per min. The reflex heart rate responses to intravenous bolus doses of methoxamine were also examined in intact animals, both at rest and during exercise. Methoxamine caused striking bradycardia at rest, but little bradycardia during exercise. These results suggest that the arterial baroreceptor reflex is normally turned off during severe exercise and thus does not modify significantly the cardiovascular response to exercise.

Animals↗
PubMed1976

Use of changes in the epicardial QRS complex to assess interventions which modify the extent of myocardial necrosis following coronary artery occlusion.

The goal of this study was to determine if changes in the epicardial QRS complex after coronary artery occlusion (CAO) can be used to evaluate the efficacy of interventions designed to limit infarct size. Forty-one open-chest dogs with CAO were studied: 15 were controls, 18 received hyaluronidase and eight received propranolol starting 20 minutes after CAO. Epicardial ECGs were recorded at specific time intervals to analyze ST-segment elevation and changes in Q and R waves. Transmural specimens were obtained 24 hours after CAO from the same sites at which ECGs were recorded. Q wave development (deltaQ), R wave fall (deltaR), and their combination (deltaR + deltaQ) at 24 hours correlated with the extent of necrosis, as determined by myocardial creatine phosphokinase activity depression and histologic appearance. In the control group ST-segment elevation 15 minutes after CAO (ST15M) predicted changes in Q and R waves 24 hours later; in the treated groups, the same ST15M prior to drug administration resulted in significantly less QRS changes. Thus, 1) Q wave development and R wave fall 24 hours after CAO accurately reflect myocardial necrosis. 2) ST15M predicts subsequent changes in Q and R waves. 3) The efficacy of hyaluronidase and propranolol, agents previously shown to reduce myocardial necrosis, can be detected by less Q wave development and a smaller fall in R wave voltage.

Animals↗
PubMed1976

The role of arterial baroreceptors in the regulation of arterial pressure in conscious dogs.

To elucidate the role of arterial baroreceptors in the acute regulation of arterial pressure in the conscious animal, arterial pressure was lowered and raised in intact, conscious dogs, and in dogs after bilateral section of both carotid sinus and aortic nerves (total arterial baroreceptor denervation, TABD). Pressure was altered by intravenous bolus injections and continuous infusions of nitroglycerin and methoxamine and also by hemorrhage. TABD resulted in a change in peak mean arterial pressure 2-4 times as great as that seen in intact dogs following injection of nitroglycerin or methoxamine. However, when the time taken for the arterial pressure disturbance to return to control levels, as well as the absolute change in arterial pressure, was considered (the pressure-time product), responses of dogs with TABD were far greater for nitroglycerin (7-9 times that seen in intact dogs) and methoxamine (11-15 times). Arterial pressure responses of dogs with selective section of the carotid sinus nerves were intermediate but closer to those of intact dogs than to dogs with TABD. With infusion of drugs or following hemorrhage, responses of mean arterial pressure were 3- to 5-fold greater in dogs with TABD than in intact dogs, indicating that the static open loop gain of the arterial baroreceptor system ranged from 2 to 4.

Animals↗
PubMed1976

Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion.

A number of hemodynamic, pharmacologic, and metabolic interventions were found to change the extent of acute ischemic injury of the myocardium and subsequent necrosis following experimental coronary artery occlusion. Reduction in myocardial damage occurred by decreasing myocardial oxygen demands (beta-adrenergic blocking agents, intra-aortic balloon counterpulsation, nitroglycerin, decreasing afterload in hypertensive patients, inhibition of lipolysis, and digitalis in the failing heart); by increasing myocardial oxygen supply either directly (coronary artery reperfusion or elevating arterial pO2), or through collateral vessels (evevation of coronary perfusion pressure by alpha adrenergic agonists, intra-aortic balloon counterpulsation); or by increasing plasma osmolality (manitol, hypertonic glucose); presumably by augmenting anaerobi metabolism (glucose-insulin-potassium, hypertonic glucoxe insulin potassium, hypertonic glucose); by enhancing transport to the ischemic zone of substrates utilized in energy production (hyaluronidase); by protecting against autolytic and heterolytic damage (hydrocortisone, cobra venom factor, aprotinin). Augmentation of myocardial ischemic damage occurred as a consequence of increasing myocardial oxygen requirements (isoproterenol, glucagon, ouabain, bretylium tosylate, tachycardia); by decreasing myocardial oxygen supply either directly (hypoxia, anemia), through reduction of collateral flow (hemorrhagic hypotension, minoxidil), or by decreasing substrate availability (hypoglycemia). Pilot studies have been carried out in patients with hyaluronidase, nitroglycerin intra-aortic balloon counterpulsation, beta-blocking agents and Arfonad and have shown that these interventions may also reduce myocardial damage, which suggests that the concept of reduction in infarct size following coronary occlusion is applicable clinically.

Anaerobiosis↗
PubMed1975

The training of manpower needed for biomedical research.

Increased federal interest in the health of the American people implies federal support not only of biomedical research but also of training the personnel competent to carry out that research. Mechanisms to implement support biomedical research training include institutional training grants, individual fellowships, training grants, training as part of research grants and contracts, and self-support with assistance by federal loans when necessary. Of these, the institutional grants provide the best mechanism since they are most likely to produce stable, high-quality scholarly programs that are continuously under peer review, and since they allow central direction of the mix of disciplines based on monitoring of current and projected requirements.

Academies and Institutes↗
PubMed1975

Effects of hypoxemia on the extent of myocardial necrosis after experimental coronary occlusion.

Arterial oxygen tension is variable in patients with acute myocardial infarction, and the effect of hypoxemia on the extent of myocardial necrosis after coronary occlusion has not been defined. In 11 anesthetized open chest dogs the left anterior descending coronary artery or one of its major branches was occluded for 20 minutes, and 10 to 15 epicardial electrocardiographic leads were recorded in the distribution and vicinity of the site of occlusion. Average S-T segment elevation and the number of sites showing S-T segment elevation greater than 2 mv, 15 minutes after occlusion were used as indexes of the severity and extent of ischemic injury. After occlusion with an inspired oxygen concentration of 20 percent these indexes were, respectively, 2.0 plus or minus 0.5 mv (mean plus or minus standard error) and 3.6 plus or minus 0.8 sites; the respective values increased to 3.3 plus or minus 0.5 mv (P smaller than 0.01) and 6.7 plus or minus 0.7 sites (P smaller than 0.01) after occlusion with an inspired oxygen concentration of 10 percent, and arterial partial pressure of oxygen decreased from 92 plus or minus 5 to 45 plus or minus 3 mm Hg. In 23 dogs the occlusion was maintained for 24 hours and the S-T segment elevation 15 minutes after occlusion was compared with myocardial creatine phosphokinase (CPK) activity and histologic appearance 24 hours later. In control dogs (inspired oxygen concentration of 20 percent) sites with no S-T segment elevation 15 minutes after occlusion showed normal myocardial CPK activity 24 hours later, whereas in sites with S-T segment elevation exceeding 2 mv there was an inverse relation between S-T segment elevation in each site and its myocardial CPK activity 24 hours later. Histologic examination revealed early myocardial necrosis in 98 percent (82 of 84) of sites with S-T segment elevation greater than 2 mv. In experimental dogs (inhaling a 10 percent oxygen concentration for the first 8 of the 24 hours of occlusion) many sites that showed no S-T segment elevation before hypoxemia was induced exhibited S-T segment elevation before hypoxemia was induced exhibited S-T segment elevations 30 minutes later and showed abnormally low CPK activity and histologic evidence of early necrosis. We conclude that after experimental coronary occlusion, hypoxemia is deleterious because it substantially increases myocardial damage.

Animals↗
PubMed1975

The effect of hypoglycemia on myocardial ischemic injury during acute experimental coronary artery occlusion.

To determine the effect of hypoglycemia on myocardial ischemic injury following coronary artery occlusion epicardial electrograms were recorded 15 minutes after two 20-minute coronary artery occlusions in seven anesthetized dogs. The first occlusion was a control (blood glucose 85 plus or minus 5(sd) mg per cent). Before the second occlusion hypoglycemia was induced (blood glucose 40 plus or minus 5 mg per cent) by the intravenous administration of insulin (2 units/kg). The average ST-segment elevation in leads during control was 3.5 plus or minus 1.0 mV which rose to 6.1 plus or minus 1.4 mV during the second occlusion (P smaller than 0.05). The number of sites showing ST-segment elevation exceeding 2 mV increased from 7.6 plus or minus 1.6 during control to 10.6 plus or minus 1.4 (P smaller than 0.05) during the occlusion with hypoglycemia. In other dogs, a coronary artery was occluded for 24 hours. Epicardial ST-segment elevations were compared to creatine phosphokinase (CPK) activity and histological appearance from the same sites. CPK activity in sites with normal ST segments (0-2 mV) was 33.1 plus or minus 6.0 IU/mg protein. Six additional dogs received insulin following the 15 minute epicardial map and blood sugar was maintained at a level of 46 plus or minus 6 mg per cent for the 24 hours. These dogs showed more myocardial necrosis than predicted by the ST-segment elevation prior to insulin administration. Forty-six percent of sites, which in control dogs would have been expected to have normal CPK and histological appearance, showed depressed CPK activity and histological evidence of early myocardial necrosis. Thus, hypoglycemia increases myocardial damage, as reflected by enzymatic and histological analyses.

Animals↗
PubMed1975

Evaluation of precordial electrocardiographic mapping as a means of assessing changes in myocardial ischemic injury.

Precordial electrocardiographic mapping has been proposed as a method for evaluating the extent of myocardial injury in patients with acute myocardial infarction. To assess the relationship between direct measures of myocardial cell damage and findings obtained by precordial mapping, the left anterior descending coronary artery (LAD) was occluded in dogs instrumented for simultaneous recording of epicardial and precordial electrocardiograms. The sum in millivolts of ST-segment elevation recorded from 30 electrodes placed in a Silastic grid sutured to the epicardium (EPIsigmaST) was compared to that recorded from 30 precordial electrodes (PresigmaST). While ischemic injury was: 1) maintained constant with a fixed occlusion; 2) reduced by partial reperfusion; 3) increased by addition of a second occlusion; or 4) increased repeatedly by intermittent infusions of isoproterenol, EPIsigmaST and PresigmaST were always closely correlated in each of the 16 dogs studied: r equal 0.92 plus or minus 0.01 (SEM). In seven control dogs, 30 minutes after coronary occlusion, PresigmaST had fallen to 77.4 plus or minus 6.6% of its value 15 minutes postocclusion. In seven experimental dogs, two branches of the LAD were occluded. Fifteen minutes after double occlusion, one occlusion was released; 30 min after the initial occlusion PresigmaST had fallen significantly more than control, to 43.1 plus or minus 13.1% of its value 15 minutes postocclusion. Simultaneously, epicardial sites in the reperfused area also showed normalization of ST segments and 24 hours later exhibited normal myocardial creatine phosphokinase activity and normal histologic appearance. During the same experiment, the mean precordial R wave voltage of sites with ST-segment elevations exceeding 0.15 mV 15 minutes following occlusion fell significantly (P less than 0.05) more in the control group (from 1.14 plus or minus 0.15 to 0.75 plus or minus 0.06 mV) than in the reperfused group (from 1.06 plus or minus 0.09 to 0.96 plus or minus 0.17 mV) during the ensuing 45 minutes. Thus, more rapid normalization of PresigmaST or preservation of precordial R wave voltage reflected the actual prevention of myocardial necrosis by reperfusion. These findings demonstrate the usefulness of precordial electrocardiographic mapping for evaluation changes in myocardial ischemic injury. Sites at which appearance of epicardial ST segment is not a reliable index of ischemic injury were associated with the development of intraventricular conduction blocks with Q to intrinsic deflection intervals exceeding 40 mesc or QRS durations exceeding 65 msec; these changes were associated with precordial RSR' configurations. Such sites, whether recorded from precordial or epicardial leads, should be excluded from ST-segment measurements used in the assessment of myocardial ischemia.

Acute Disease↗
PubMed1975

Reduction of infarct size by oxygen inhalation following acute coronary occlusion.

This study was carried out in order to determine the effects of the inspiration of O2-enriched air on the size of myocardial infarction. In 15 anesthetized dogs, epicardial electrograms were recorded from 10 to 14 sites on the anterior surface of the left ventricle before and after intermittent occlusion of the left anterior descending coronary artery or one of its major branches. In each dog, one occlusion was carried out while the fraction of inspired oxygen (FIO2) was 0.20 and the other while the FIO2 was 0.40. With an FIO2 of 0.20 the average ST-segment elevation (ST) was 4.0 +/- 0.6 mV (SEM) and the number of sites exhibiting ST-segment elevations exceeding 2 mV (NST) 15 minutes following occlusion was 6.2 +/- 0.7 sites; comparable values following occlusion with an FIO2 of 0.40 were 1.8 +/- 0.4 mV (P less than 0.01) and 2.7 +/- 0.7 sites (P less than 0;01), reflecting reduction in acute myocardial ischemic injury; An FIO2 of 1.0 did not decrease myocardial injury further. In 24 other dogs, occlusion was maintained for 24 hours. In nine dogs in which FIO2 was increased from 0.20 to 0.40 30 minutes after occlusion, myocardial creatine phosphokinase activity (CPK) was less depressed in sites having comparable levels of ST-segment elevation at 15 minutes than in dogs that respired an FIO2 of 0.20 during the entire 24 hours. All (54) sites with ST-segment elevations greater than 3 mV in the 0.20 FIO2 group showed early signs of myocardial infarction, while only 49% of such specimens showed infarction in the 0.40 FIO2 group. Thus it is concluded that 0.40 FIO2 following an experimental coronary artery occusion decreases acute ischemic injury and reduces the eventual development of necrosis, as evaluated by enzymatic and histological techniques.

Acute Disease↗
PubMed1975

Effects of hyaluronidase administration on myocardial ischemic injury in acute infarction. A preliminary study in 24 patients.

The effect of hyaluronidase on myocardial ischemic injury was examined in 13 patients with acute myocardial infarction, and the results were compared with 11 patients who did not receive hyaluronidase. A 35-electrode precordial mapping method was used to assess the rate of resolution of ST segment elevations. In the 11 control patients, the sum of ST segment elevations (sigmaST) fell after 2 hours to an average of 93.5% plus or minus 17.3% (SEM) and after 24 hours to 89.6% plus or minus 7.6% of the initial values, while the number of electrodes exhibiting ST segment elevations exceeding 0.1 mV (NST) fell to 98.0% plus or minus 12.3% and 94.3% plus or minus 10.4% of the initial values respectively. In the hyaluronidase-treated group, at the same time sigmaST fell significantly more (P less than 0.05), to 54.1% plus or minus 5.0% and 51.3% plus or minus 11.8% and NST was also more markedly reduced (P less than 0.05) to 50.7% plus or minus 7.8% and 50.1% plus or minus 12.4%, thus indicating that hyaluronidase can accelerate the reduction of myocardial ischemic injury in patients with acute myocardial infarction.

Acute Disease↗