Showing papers by "Eugene Braunwald published in 1972"

Precordial S-T segment elevation mapping: An atraumatic method for assessing alterations in the extent of myocardial ischemic injury

Abstract: A noninvasive technique for evaluating the extent of myocardial ischemic injury after experimental coronary artery occlusion was devised and applied to study alterations in the extent of injury produced by hemodynamic and pharmacologic interventions. The technique was then extended to the assessment of myocardial ischemic injury in patients with acute myocardial infarction. In 7 closed chest dogs, electrocardiograms were recorded from 15 sites on the chest wall before and after intermittent occlusions of the left anterior descending coronary artery. There was no S-T segment elevation before the occlusion; 15 minutes after occlusion the sum of S-T segment elevations (ΣS-T) averaged 15.0 ± 3.0 mm (SEM, 1 mm deflection = 0.1 mv), and an average of 4.2 ± 0.6 sites exhibited elevations exceeding 0.1 mv (NS-T). Occlusions occurring during administration of isoproterenol (0.25 μg/kg per min) increased ΣS-T to 51.0 ± 9.0 mm and NS-T to 10.6 ± 0.9, whereas occlusions occurring after administration of propranolol (1 mg/kg) decreased ΣS-T to 3.0 ± 1.5 mm and NS-T to 0.2 ± 0.2. In 8 dogs the extent of ischemic injury, manifested by S-T segment changes, was decreased by propranolol and norepinephrine and increased by hemorrhagic hypotension and isoproterenol, applied up to 6 hours after occlusion. Reproducible S-T segment maps, using 35 surface electrodes, were obtained in 19 patients with acute myocardial infarction. In 15 patients studied serially, ΣS-T decreased from 54.25 ± 7.00 to 38.50 ± 6.30 mm and NS-T from 18.7 ± 2.5 to 12.3 ± 2.8, respectively, during a 24 hour period. However, in 3 patients in whom ventricular fibrillation, arterial hypotension and further ischemic pain occurred, ΣS-T and NS-T increased whereas in another patient propranolol decreased ΣS-T and NS-T. Thus, precordial mapping, both in dogs and patients, shows changes parallel to those measured by the epicardial technique and should provide a useful clinical tool for determining acute changes in the extent of ischemic injury.

Effect of Glucose-Insulin-Potassium Infusion on Myocardial Infarction following Experimental Coronary Artery Occlusion

Abstract: The effects of glucose-insulin-potassium (GIK) infusion and glucose (G) infusion started 30 min after experimental coronary occlusion and the combination of GIK and propranolol (P) started 3 hours after coronary occlusion on the development of myocardial infarction were studied in 37 dogs. Fifteen minutes after the coronary occlusion, epicardial electrocardiograms were recorded at 10-15 sites; 24 hours later transmural specimens were obtained from the same sites for determination of myocardial creatine phosphokinase (CPK) activity and the evaluation of morphologic changes. In the control group (normal saline infusion) the relationship between S-T-segment elevation (mv) 15 min after occlusion and CPK activity (IU/mg of protein) 24 hours later was: log CPK = –0.064 S-T + 1.24; r = 0.81. In the GIK group, the infusion was begun 15 min following epicardial mapping, and sites with the same S-T-segment elevations showed less CPK depression than did the control group: log CPK = –0.022 S-T + 1.25. The G group als...

Alterations in the Baroreceptor Reflex in Conscious Dogs with Heart Failure

Abstract: The effectiveness of the baroreceptor reflex in conscious dogs with experimental cardiac hypertrophy and heart failure was compared with that in a group of normal conscious dogs. Cardiac hypertrophy and heart failure were produced by tricuspid avulsion and progressive pulmonary stenosis. The sensitivity of the baroreceptor reflex to transient hypertension was assessed by determining the slope of the regression line relating the prolongation of the R-R interval to the rise in systolic arterial pressure during the transient elevation of arterial pressure induced by an intravenous injection of 1-phenylephrine. The mean slope averaged 22.4+/-2.3 msec/nm Hg in 16 normal animals. 23.1 +/-1.5 in five sham-operated animals, and was significantly reduced to 8.3 +/-0.8 in 10 dogs with hypertrophy alone (P < 0.001), and to 3.3+/-0.5 in nine dogs with heart failure (P < 0.001). The response to baroreceptor hypotension was compared during bilateral carotid artery occlusion (BCO) in six normal and six heart failure dogs previously instrumented with Doppler flow transducers on the superior mesenteric and renal arteries. During BCO, in normal dogs arterial pressure increased 52+/-4 mm Hg, heart rate 33+/-2 beats/min, mesenteric resistance 0.17+/-0.03 mm Hg/ml per min, and renal resistance 0.37+/-0.10 mm Hg/ml per min. In the heart failure group all of these variables increased significantly less (P < 0.01); arterial pressure rose 25 +/-3 mm Hg, heart rate 13 +/-4 beats/min, mesenteric resistance 0.04+/-0.007 mm Hg/ml per min, and renal resistance 0.18+/-0.09 mm Hg/ml per min.Thus, in heart failure, all measured systemic and regional circulatory adjustments consequent to baroreceptor hypo- and hypertension are markedly attenuated. This study demonstrates a profound derangement of a major cardiovascular control mechanism in experimental heart failure.

Effects of Intraaortic Balloon Counterpulsation on the Severity of Myocardial Ischemic Injury following Acute Coronary Occlusion Counterpulsation and Myocardial Injury

Abstract: The effects of intraaortic balloon counterpulsation (IABC) on the magnitude and severity of myocardial ischemic injury were studied in 19 dogs following acute coronary occlusion and in two patients with cardiogenic shock. In the experimental group, epicardial electrocardiograms were taken from 10-14 sites on the anterior surface of the left ventricle following occlusion of the left anterior descending coronary artery or its apical branch. The average S-T-segment elevation ([see Equation in PDF File]) was used as an index of the magnitude of myocardial ischemic injury. In six dogs, two successive 20-min occlusions were performed, and IABC was started prior to the second occlusion. [see Equation in PDF File] 15 min following occlusion decreased from 3.3 ± 0.9 mv after the control occlusion to 1.4 ± 0.4 mv (P < 0.01) after the occlusion with IABC. In three dogs in which the occlusion was maintained and IABC initiated 30 min later, [see Equation in PDF File] decreased from 1.2 to 0.6 mv. In six dogs in which ...

Reduction by Hyaluronidase of Myocardial Necrosis following Coronary Artery Occlusion

Abstract: Electrocardiographic, enzymatic, and morphologic signs of myocardial ischemic injury following coronary occlusion have previously been shown to be ameliorated by reducing myocardial oxygen requirements, and/or by increasing the availability of oxygen as well as of substrates for anaerobic ATP production. Since hyaluronidase increases diffusion through the extracellular space and may facilitate delivery of substrates to ischemic cells, the influence of its administration on the size of experimentally produced infarcts was studied. In 14 control dogs epicardial electrocardiograms were taken in 10-15 sites on the anterior surface of the left ventricle before and after occlusion of the left anterior descending coronary artery. Twenty-four hours later, transmural specimens were obtained from the same sites from which electrocardiograms had been recorded, and were analyzed for creatine phophokinase (CPK) activity, for histologic changes, and glycogen content. In control dogs, sites exhibiting S-T-segment elevation 15 min after occlusion showed early structural signs of necrosis and glycogen depletion in 97% of specimens taken after 24 hours. The relationship between S-T-segment elevation at 15 min (mv) and CPK activity 24 hours later (IU/mg protein) was log CPK = –0.061 S-T + 1.26. Hyaluronidase (225 u/kg) was given to 15 dogs; no hemodynamic changes occurred but the depression of CPK activity was reduced following occlusion; log CPK = –0.024 S-T + 1.28. Similarly, only 55% of sites that showed S-T-segment elevation prior to hyaluronidase administration exhibited histologic signs of early infarcts and glycogen depletion 24 hours later. It is concluded that hyaluronidase diminished myocardial necrosis following acute coronary occlusion.

Left Ventricular Response to Severe Exertion in Untethered Dogs

Abstract: The left ventricular response to severe exercise was studied by telemetering direct measurements of left ventricular diameter (D) and pressure (P) and aortic blood flow from healthy dogs running at speeds up to 30 mph in the field. Severe exercise increased cardiac output from 101 to 478 ml/kg per min, heart rate from 95 to 297 beats/min, stroke volume from 31 to 44 ml, left ventricular isolength (iso) systolic pressure from 120 to 186 mm Hg, left ventricular end diastolic pressure from 6 to 18 mm Hg, and left ventricular end diastolic diameter from 58.9 to 60.1 mm, while end systolic diameter decreased from 53.0 to 52.2 mm. Two indices of myocardial contractility, (dP/dt)/P increased from 37 to 92 sec−1, while dD/dt, the velocity of myocardial fiber shortening at isolength, rose from 54 to 119 mm/sec. All of these changes were statistically significant. When, in resting dogs, heart rate was first raised to exercise levels by electrical stimulation, severe exercise subsequently increased left ventricular end diastolic diameter more profoundly, from 55.7 to 59.7 mm, while end systolic diameter remained constant and the increases in left ventricular pressure, (dP/dt)/P and velocityiso were roughly comparable to those occurring during exercise in spontaneous rhythm. After propranolol, 1.0 mg/kg, severe exercise resulted in significantly smaller increases in cardiac output (from 82 to 240 ml/kg), in heart rate (from 87 to 186 beats/min), in left ventricular pressureiso (from 122 to 150 mm Hg), in (dP/dt)/P (from 32 to 44 sec−1), in velocityiso (from 47 to 59 mm/sec), and in slightly greater increases in end diastolic diameter, from 59.8 to 62.0 mm and pressure from 8 to 22 mm Hg, while end systolic diameter did not change significantly. Thus, the left ventricle responds to severe exercise with near maximal increases in heart rate and contractility, while significant increases in end diastolic diameter (Frank-Starling mechanism) and stroke volume occur as well. When heart rate was held constant severe exercise produced similar increases in contractility but end systolic size failed to diminish and the increases in end diastolic size were greater. Beta adrenergic receptor blockade interfered with the chronotropic and particularly the inotropic response to severe exercise and while the participation of the Frank-Starling mechanism was somewhat greater, the latter was not sufficient to increase cardiac output normally.

Effects of increased arterial pressure and positive inotropic agents on the severity of myocardial ischemia in the acutely depressed heart.

Abstract: Recently it has been established that factors that affect myocardial oxygen consumption also influence the magnitude and extent of ischemic injury. In the nonfailing heart when mean arterial pressure was increased, the extent of ischemic injury decreased and, after isoproterenol or digitalis administration, ischemic injury increased. However, agents such as digitalis and catecholamines can have differing effects on myocardial oxygen consumption, depending on the initial contractile state and heart size. Moreover, since many patients with acute myocardial infarction have an associated depression of left ventricular function, the relevance of the earlier findings to the failing heart must be considered. The present study was undertaken to examine the effects of systemic arterial hypertension, digitalis and isoproterenol on the extent of myocardial ischemic injury after acute pharmacologic depression of the dog heart. Following cardiac depression in 22 experiments, when mean arterial pressure was increased from 110 to 145 mm Hg, mean S-T segment elevation increased from 3.6 to 4.7 mv ( P P

Extent of carotid sinus regulation of the myocardial contractile state in conscious dogs.

Abstract: The effects of bilateral carotid artery occlusion (BCO) and carotid sinus nerve stimulation (CSNS) on left ventricular (LV) pressure (P), diameter (D), velocity of contraction (V), rate of change of pressure (dP/dt), and cardiac output were studied in conscious dogs instrumented with ultrasonic diameter gauges, miniature pressure gauges, and aortic electromagnetic flow transducers. The effects of BCO and CSNS were also studied after automatic blockade and were compared to similar alterations in pressure produced by norepinephrine, methoxamine, and nitroglycerin. When heart rate was maintained constant with atrial stimulation, BCO had little effect on ventricular contractility, increasing isolength systolic pressure (LV P(iso)) by 36% while isolength velocity of myocardial shortening (V(iso)) decreased by 12% and (dP/dt)/P fell by 8%. These effects could be explained largely by vasoconstriction, since elevating systolic pressure with methoxamine produced similar results, while norepinephrine increased V(iso) by 36% and (dP/dt)/P by 56%. CSNS produced directionally opposite results from BCO; it decreased P(iso) by 15%, V(iso) increased by 11%, while (dP/dt)/P remained almost constant. These effects may be explained largely by vasodilatation since reducing systolic pressure to the same level with nitroglycerin produced similar results. When peripheral vasoconstriction was minimized by phenoxybenzamine pretreatment. BCO produced a slight positive inotropic effect (P(iso) increased by 8%, V(iso) by 4%, and (dp/dt)/P by 10%), while CSNS produced a slight negative inotropic effect (P(iso) decreased by 3%, V(iso) decreased by 5%, and (dP/dt)/P by 7%).Thus, in the normal, healthy, conscious dog, the carotid sinuses exert relatively little control of the inotropic state of the left ventricle; moreover, this small inotropic action is masked by the more powerful effects on peripheral resistance.

Mechanism of Prolongation of the R-R Interval with Electrical Stimulation of the Carotid Sinus Nerves in Man

Abstract: To elucidate the mechanism by which stimulation of the carotid sinus nerves prolongs the R-R interval, the effects of activating an implanted carotid sinus nerve stimulator were studied in eight patients at varying levels of background autonomic activity and with varying types of efferent autonomic blockade. Beta-receptor blockade was induced with intravenous propranolol, 0.20 mg/kg, and parasympathetic blockade with intravenous atropine, 0.04 mg/kg. In the supine position, average prolongation of the R-R interval due to stimulation of the carotid sinus nerves was 269 ± 56 msec prior to autonomic blocking drugs, 442 ± 214 msec after propranolol (NS), and 44 ± 13 msec after propranolol and atropine (P < 0.025). Comparable changes were produced in the standing position. With moderate treadmill exercise, stimulation of the carotid sinus nerves prolonged the R-R interval by only 40 ± 30 msec prior to blocking drugs, 62 ± 19 msec after propranolol, and 40 ± 30 msec after propranolol and atropine. It is conclud...

Effects of Experimentally Produced Heart Failure on the Peripheral Vascular Response to Severe Exercise in Conscious Dogs

Abstract: The peripheral vascular response to severe exercise in eight dogs with heart failure produced by tricuspid avulsion and progressive pulmonary stenosis was compared to the response determined in eight control dogs. After full recovery from implantation of Doppler flow probes and miniature pressure gauges, measurements of arterial blood pressure and blood flow were telemetered from untethered dogs running behind a mobile recording vehicle at speeds of 10-25 mph over distances averaging 1 mile. Severe exercise in control dogs increased heart rate from 78 to 281 beats/min and mean arterial blood pressure from 93 to 134 mm Hg. Iliac blood flow rose from 151 to 897 ml/min, but mesenteric and renal blood flows did not change significantly. Iliac vascular resistance decreased from 0.64 to 0.15 mm Hg/ml min-1, but mesenteric vascular resistance increased from 0.31 to 0.47 mm Hg/ml min-1 and renal vascular resistance increased from 0.49 to 0.75 mm Hg/ml min-1. Severe exercise in dogs with heart failure increased heart rate from 102 to 274 beats/min, but mean arterial blood pressure only increased from 100 to 107 mm Hg. Iliac blood flow rose from 96 to 360 ml/min, whereas mesenteric blood flow decreased from 237 to 89 ml/min and renal blood flow decreased from 226 to 79 ml/min. Iliac vascular resistance decreased from 1.09 to 0.34 mm Hg/ml min-1, but mesenteric vascular resistance increased from 0.49 to 1.31 mm Hg/ml min-1 and renal vascular resistance increased from 0.47 to 1.81 mm Hg/ml min-1. Thus, in heart failure a distinctly abnormal peripheral vascular response to severe exercise occurs, characterized by a very small elevation in mean arterial blood pressure and intense visceral vasoconstriction resulting in diversion of visceral blood flows.

Natural history of mild congenital aortic stenosis elucidated by serial hemodynamic studies.

Abstract: There is a paucity of information on the natural history of congenital aortic stenosis. This report analyzes serial clinical and hemodynamic data obtained prospectively from 15 initially asymptomatic children with congenital aortic stenosis. The first hemodynamic study was performed at an average age of 8.5, and the follow-up study at an average age of 15.1 years. The cardiac index was consistently normal in all patients. The peak pressure difference across the left ventricular outflow tract increased between initial and final studies in 12 of the 15 patients. The gradient ranged from 5 to 45 mm Hg (mean 26) during the first study, and from 15 to 81 mm Hg (mean 44) at follow-up examination. Severe obstruction (gradient > 50 mm Hg, normal cardiac output; or calculated aortic valve orifice

Present Status of Digitalis Treatment of Acute Myocardial Infarction

Abstract: The available experimental and clinical data still leave many unanswered questions concerning the role of digitalis therapy after acute myocardial infarction. It seems clear that little is to be gained by glycoside administration to patients with uncomplicated infarctions who do not have cardiomegaly. The precise role of digitalis therapy in the treatment of cardiogenic shock remains undefined on the basis of the available data. However, until evidence to the contrary appears, its use should be continued on the basis of experience with experimental cardiogenic shock and the presumption that this state, when observed clinically, is a form of extreme left ventricular failure. Digitalis appears to be indicated in the treatment of atrial fibrillation with rapid ventricular rate complicating acute myocardial infarction. Other supraventricular arrhythmias, such as atrial flutter and ectopic atrial tachycardia, frequently require larger doses of the glycoside, and other means of therapy, such as antiarrhythmic a...

Regional Hemodynamic Effects of a Digitalis Glycoside in the Conscious Dog with and without Experimental Heart Failure

Abstract: The effects of intravenous ouabain (G-strophanthin), 20 µg/kg, on the superior mesenteric, renal, and external iliac beds were studied over a 30-minute period in eight normal conscious dogs before, and in five of them after, cholinergic blockade and in six conscious dogs with heart failure produced by tricuspid avulsion and progressive pulmonary stenosis. Blood flows were measured with Doppler ultrasonic and electromagnetic flowmeters. In normal dogs, prior to cholinergic blockade, ouabain caused early increases in mesenteric, renal, and external iliac resistances but later, between 15 and 30 minutes, mesenteric resistance decreased below the control level while renal and external iliac resistances remained elevated. After cholinergic blockade, the ouabain-induced alterations in renal and iliac resistance were unaltered, but the later decline in resistance in the mesenteric bed was reversed, resulting in sustained constriction. The late decline in mesenteric resistance also was not observed in the conscious animal after the injection of ouabain, 5 µg/kg, directly into the mesenteric artery or in the majority of dogs given ouabain intravenously after having been anesthetized with pentobarbital sodium. In the conscious dogs with heart failure, ouabain resulted in increased renal and iliac resistances initially, and in vasodilatation later while mesenteric resistance fell initially and remained below control for the entire 30 minutes. Thus, in the normal conscious dog, ouabain causes vasoconstriction in the regional vascular beds, apparently by its direct vascular action, and, in addition, a cholinergically mediated vasodilatation in the mesenteric bed. In the conscious dog with heart failure, ouabain increases blood flow to all beds, reducing the compensatory vasoconstriction of the low output state.

Fatal familial cardiac arrhythmias: Histologic observations on the cardiac conduction system☆

Abstract: Alternating bidirectional tachycardia leading to death during attempted suppressive therapy was observed in a 16 year old girl without prior clinical evidence of cardiac disease. At autopsy, there was fatty and mononuclear cell infiltration in the atrioventricular conduction system and the main left bundle branch. A similar arrhythmia has been documented in an 18 year old sister who died suddenly 9 months after discovery of her arrhythmia; autopsy revealed no gross cardiac abnormality although the conduction system was not studied. A brother, 21 years old, and the mother of the propositus, aged 45 years, also exhibited ventricular bigeminal rhythm, and a maternal uncle and grandmother had died suddenly, the latter with knowledge of an irregular heart beat. Q-T interval prolongation and auditory defects were not found. Histopathologic changes in the heart and in the conduction system in the propositus support the concept of the origin of the arrhythmia in degenerative change of the conduction system having a genetic base in this kindred.

Future shock in academic medicine.

Abstract: The current social revolution clearly influences patterns of academic medicine. The increasingly rapid turnover of academic physicians results largely from rapidly changing government-sponsored programs in goal-oriented research, in education and in clinical services carried out by medical schools. This increased transience of faculty inhibits personal pride in and loyalty to institutions, diminishes opportunities for professional identification and reduces the importance of academie tenure. The reorganization of clinical departments into divisions of primary and of specialty care is likely. The impact of an increased fraction of women in academic medicine is yet to be felt. The viability of monthly scientific journals as the backbone of communication among bio-medical investigations is questionable. A variety of steps may, however, be designed to maximize the potential benefits and to minimize the deleterious consequences resulting from these changes.

Intra-aortic balloon counterpulsation: an assessment.

Abstract: Excerpt It has been recognized for a number of years that the definitive therapy of cardiac insufficiency not responsive to currently available forms of medical or surgical treatment will consist o...