Showing papers by "Eugene Braunwald published in 1971"

Factors Influencing Infarct Size Following Experimental Coronary Artery Occlusions

Abstract: The purpose of this study was the determination of whether hemodynamic and pharmacologic factors influence the extent and severity of myocardial necrosis produced by coronary occlusion. In 48 dogs, 10 to 14 epicardial leads were recorded on the anterior surface of the left ventricle in the distribution and vicinity of the site of occlusion of a branch of the left anterior descending coronary artery. The average S-T segment elevation for each animal was determined at 5-min intervals after occlusion. This elevation was used as an index of the presence and severity of myocardial ischemic injury. The number of sites showing this elevation provided an additional measure of the size of the injured area. Occlusion alone raised the average S-T segment elevation from 0.22 ± 0.04 to 3.32 ± 0.37 mv (SEM). Isoproterenol, ouabain, glucagon, bretylium, and tachycardia given prior to a repeated occlusion increased the severity and extent of ischemic injury, while propranolol decreased it. Elevation of arterial pressure ...

Defective cardiac parasympathetic control in patients with heart disease.

Abstract: To define the state of the parasympathetic nervous system in heart failure, parasympathetic blockade with atropine was induced after adrenergic blockade with propranolol in 12 normal subjects and in nine patients with heart disease. Atropine elevated heart rate by 55 ± 9 per cent in normal subjects, but by only 23 ± 8 per cent in patients with heart disease (p less than 0.05). In 23 control subjects and 22 patients, transient elevations in arterial pressure were produced by intravenous injections of phenylephrine, and successive R-R intervals were plotted as a function of systolic pressure. The slowing of heart rate per unit rise in systolic arterial pressure averaged 16.0 ±1.8 msec per millimeter of mercury in normal subjects but only 3.70 ± 0.8 msec per millimeter of mercury in the patients (p less than 0.001). Baroreceptor-induced slowing of heart rate in normal subjects was shown to be mediated by the parasympathetic nervous system since it could be abolished with atropine. These findings poi...

Control of myocardial oxygen consumption: physiologic and clinical considerations.

Abstract: The basal oxygen consumption of the heart is small, approximately 20 percent of that of the contracting organ. Oxygen cost of depolarization is approximately 0.5 percent of the total oxygen consumed by the normally working heart. There is a far greater oxygen cost of “pressure work” as opposed to “flow work,” and a close relation between the area beneath the left ventricular pressure curve, that is, the tension-time index, and myocardial oxygen consumption. Also, the contractile state of the heart, as reflected in the maximal velocity of isotonic shortening, is a major determinant of myocardial oxygen consumption. Thus, velocity of contraction shares the role of important determinant of myocardial oxygen consumption with developed tension and heart rate. Although the precise costs of activation and maintenance of the active state of the myocardium have not yet been clearly defined, it is likely that they are relatively low. In studies on isolated papillary muscles, oxygen consumption was found to be a function of the tension that is developed and the velocity of shortening of the unloaded muscle. Shortening against a load requires oxygen above and beyond that required for the development of tension. Almost the entire increase in myocardial oxygen consumption produced by the administration of catecholamines results from the increased contractile activity produced rather than from a direct stimulating effect of the catecholamines on myocardial metabolism. Severe valvular regurgitation does not increase myocardial consumption significantly when myocardial tension is held constant. Congestive heart failure is associated with depression of myocardial contractility, but this cannot be attributed to any reduction of high energy phosphate stores in muscles that are utilized normally. A technique for reducing myocardial oxygen requirements by stimulating the carotid sinus nerves is described and its application to the treatment of angina pectoris demonstrated. It is also shown that following coronary occlusion, interventions that increase myocardial oxygen consumption appear to increase the size of the infarction, whereas those that decrease myocardial oxygen consumption reduce the size of the infarction.

Assessment of cardiac contractility. The relation between the rate of pressure rise and ventricular pressure during isovolumic systole.

Abstract: It was considered that the relationship between dp/dt and simultaneously developed pressure during the course of isovolumic contraction might afford a more accurate measure of contractility than the maximum rate of intraventricular pressure rise (peak dp/dt). In six cat papillary muscles contracting isometrically from any given preload, the ratio of the rate of tension development (dT/dt) to simultaneously occurring isometric tension always varied directly with the contractile state. This ratio rose slightly as preload was increased, but it was not affected by changes in afterload. In 17 experiments in an intact canine heart preparation in which left ventricular end-diastolic pressure was constant, dp/dt at any given pressure during isovolumetric contraction again was observed to be a function of the contractile state when the latter was enhanced by norepinephrine and acetylstrophanthidin. High-fidelity left ventricular pressures and dp/dt were recorded throughout isovolumic contraction in eight patients....

Effects of a Digitalis Glycoside on Coronary and Systemic Dynamics in Conscious Dogs

Abstract: The effects of ouabain (G-strophanthin), 20 µg/kg were compared in 12 conscious dogs with Doppler flow transducers on the ascending aorta and left circumflex coronary artery and pressure gauges in the aorta, and in 9 of these dogs after general anesthesia with Na pentobarbital. In conscious dogs ouabain caused an initial bradycardia, but heart rate returned almost to control at 15 to 30 minutes, while arterial pressure rose and remained elevated. Cardiac output and coronary blood flow decreased initially, returned to control by 5 minutes and then remained constant. Systemic, mean, and late diastolic coronary resistances were elevated within 1 minute and remained elevated for 30 minutes. After anesthesia, ouabain caused similar increases in arterial pressure and slightly greater increases in systemic resistance, but the bradycardia and reduction of cardiac output were more profound and sustained. In the anesthetized state, coronary resistance rose when heart rate was allowed to slow after ouabain but was not elevated when heart rate was returned to control. Thus, in the conscious state, ouabain caused a distinct elevation in coronary and systemic resistances with no change in cardiac output, while in the anesthetized state ouabain reduced cardiac output and when heart rate was controlled, did not alter coronary resistance.

Effects of anesthesia and sleep on circulatory response to carotid sinus nerve stimulation.

Abstract: VATNER, STEPHEN F., DEAN FRANKLIN, AND EUGENE BRAUNWALD. Effects of anesthesia and sleep on circulatory response to carotid sinus nerve stimulation. Am. J. Physiol. 220(5) : 12491255. 197 l.The effects of electrical stimulation of the carotid sinus nerves on arterial pressure, heart rate, and peripheral blood flows were studied in healthy dogs while conscious, asleep, after general anesthesia with Na pentobarbital, and after autonomic blockade. In the resting conscious dog, 30-set periods of carotid sinus nerve stimulation resulted in average decreases in heart rate of 12 %, arterial pressure 27 %, coronary flow 5 %, mesenteric flow 9 %, and renal flow 8 %, while iliac flow increased by 112 %. In sleeping dogs, the decrease in heart rate (22 %) was greater than when awake. In anesthetized dogs, the decreases in resistance in all beds with stimulation were not as great as in conscious dogs and the periods necessary for arterial pressure and heart rate to return to control following stimulation were prolonged. The bradycardia was mediated predominantly by the vagus nerves in conscious dogs and by the sympathetic nerves in anesthetized dogs. Thus, when compared to conscious dogs, baroreceptor stimulation in anesthetized dogs resulted in less peripheral vasodilatation, slower recovery of arterial pressure and heart rate, and a different pattern of autonomic control of heart rate.

Myocardial Perfusion Imaging with Radioactive-Labeled Particles Injected Directly into the Coronary Circulation of Patients with Coronary Artery Disease

Abstract: Macroaggregated serum albumin (MAA) particles labeled with 131iodine (131I) or similar particles-labeled with 99mtechnetium (99mTc) or both types were injected directly into the coronary circulation of 29 patients at the time of conventional coronary arteriography. Radionuclide images of the distribution of these small (10-60 µ) biodegradable particles in the small vessels of the heart wall were made with a commercial Anger-type scintillation camera in much the same way as routine pulmonary perfusion scans are made. The resulting images depicted the relative regional distribution of blood flow to the myocardium in these patients suspected of having coronary artery disease. The myocardial perfusion images were of good quality and allowed gross assessment of perfusion by way of each major coronary artery. This was done by injecting 99mTc-labeled particles into the left coronary artery and 131I-MAA into the right coronary artery through the coronary artery catheter. Separate or composite images of the relati...

On the difference between the heart's output and its contractile state.

Abstract: T HE HEART'S prime function is to deliver sufficient oxygenated blood to meet the metabolic requirements of the tissues, and heart failure is said to exist when the heart is unable to pump blood at a rate commensurate with these requirements. Accordingly, an accurate measure of the heart's ability to perform this task, i.e., the determination of the cardiac output, has properly been considered a key test of cardiac function. The development of cardiac catheterization techniques in the early 1940's provided the clinical physiologist, for the first time, with the ability to sample mixed venous blood and, thereby, to apply the Fick principle to the measurement of the cardiac output. This approach, and the theoretically closely related indicator-dilution method, have remained cornerstones on which much of the structure of modern cardiology is built. It is, therefore, understandable that the clinician tends to view the cardiac output, at rest and during various levels of activity, as a prime index of the heart's ability to carry out its major function, and that therapeutic interventions in patients with heart disease are frequently evaluated in terms of their effects

Detection of left-ventricular-wall motion disorders in coronary-artery disease by radarkymography.

Abstract: Radarkymography, a new, noninvasive technic that records horizontal movements of the cardiac silhouette as projected on a television screen, was used to detect and sequentially to follow left-ventricular-wall motion disorders in patients with acute myocardial infarction and chronic coronary-artery disease. Asynergistic motion of the left ventricular wall was recorded in 44 of the 56 patients studied. Over a follow-up period extending up to 18 months, 36 of the 54 patients surviving the acute episode retained the asynergism of contraction. Ten of the 44 patients with wall motion abnormalities expired. Wall motion abnormalities were also recorded in 28 of 42 patients with chronic coronary-artery disease. Radarkymography was compared with left ventricular cineangiography in 18 patients, and in 16 of these the results were identical in detection of asynergy of contraction. Radarkymography was found to be more accurate than fluoroscopy since wall motion disorders could not be detected in 16 of 32 pati...

Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside

Abstract: The effects of ouabain (G-strophanthin) 20 μg/kg, on left ventricular (LV) pressure (P), diameter (D), velocity of contraction (dD/dt), and dP/dt were studied in conscious dogs instrumented with ultrasonic diameter gauges and miniature pressure gauges. The effects of ouabain were compared on separate occasions in the same dogs after cardiac depression with propranolol, 3.0 mg/kg, and also after general anesthesia with Na pentobarbital, 30 mg/kg. Maximal pressor effects were observed in the first 10 min, but maximal effects on the contractile state occurred at 30 min after ouabain. At this time, in conscious dogs, ouabain had increased LV isolength systolic pressure by 5%, LV isolength velocity by only 9%, and LV (dP/dt)/P by 21%, while end systolic diameter (ESD) decreased slightly and end diastolic diameter (EDD) and heart rate (HR) were unchanged. After anesthesia, ouabain increased LV systolic pressure by 8%, velocity 32%, (dP/dt)/P by 47%, and ESD decreased by 1.2 mm while EDD rose slightly and HR fell by 26 beats/min. Returning HR to control with atrial pacing decreased EDD 0.9 mm below control. After cardiac depression with propranolol, ouabain caused responses similar to those observed in the anesthetized dogs. Thus, the cardiac glycoside was found to exert only minor inotropic effects on the nonfailing heart of conscious dogs but far more striking inotropic responses in the anesthetized state.

Effects of altering ventricular rate on blood flow distribution in conscious dogs

Abstract: WHITE, SAXON, THOMAS PATRICK, CHARLES B. HIGGINS, STEPHEN F. VATNER,DEAN FRANKLIN, AND EUGENE BRAUNWALD. Effects of altering ventricular rate on blood Jlow distribution in conscious dogs. Am. J. Physiol. 221(5): 1402-1407. 1971.-The peripheral vascular response to stepwise changes in ventricular rate was studied in eight conscious dogs with chronic atrioventricular block. Systemic arterial pressure, cardiac output, and flows in the left circumflex coronary, mesenteric, renal, and external iliac arteries were measured using chronically implanted pressure gauges and Doppler ultrasonic or electromagnetic flow transducers. Between 110 and 180 beats/min, arterial pressure and cardiac output were independent of ventricular rate, but fell as rate was further raised or lowered. Total systemic vascular resistance rose at the lowest rates. In the peripheral circulation, coronary flow rose continuously and renal flow remained unchanged as rate was elevated from 40 to 220 beats/min, while mesenteric and hindlimb flows fell at lower rates. Sudden cessation of pacing at 100 beats/min was followed by asystole from 6 to 12 set, a fall in arterial pressure to 20 mm Hg, and flow in all beds ceased. On resumption of ventricular contraction, to spontaneous rates averaging 52 beats/min, the hemodynamic pattern resembled that seen at the lowest pacing rates with flow resistance rising to the greatest extent in the hindlimb (132 =t 4.7 y0 of control) and less so in the coronary circulation (119 rt 7.5 y0 of control). There was little change in the mesenteric circulation, and renal resistance decreased (81 =t 5.4% of control).

Mechanochemistry of cardiac muscle: V.Influence of thyroid state on energy utilization

Abstract: The possibility that alterations in the rate or efficiency of energy utilization could be involved in the control of cellular oxygen consumption by thyroid hormone was examined in right ventricular papillary muscles isolated from normal euthyroid cats and cats with experimentally induced hyperthyroidism and hypothyroidism. Energy production in the muscles was inhibited and isolated from the process of energy utilization by exposure to iodoacetic acid and nitrogen. After resting or performing variable amounts of contractile element work under isometric conditions, muscles were frozen, and the total amount of chemical energy ( approximately P = creatine phosphate + ATP) used was determined. The resting rate of energy utilization in muscles from euthyroid animals was 0.78+/-0.07 mumoles/g per min of approximately P. This rate was elevated in muscles from hyperthyroid cats to 1.00+/-0.09 mumoles/g per min and decreased in muscles from hypothyroid cats to 0.23+/-0.14 mumoles/g per min. Isometrically contracting muscles from cats with hypothyroidism utilized only 64% as much energy as muscles from euthyroid cats while performing 81% as much contractile element work at a moderately decreased level of contractile state. Muscles from hyperthyroid cats utilized an average of 41% more energy than did muscles from euthyroid cats while contracting an identical number of times and performing an equal amount of contractile element work at a slightly increased level of contractile state. These results suggest that thyroid hormone directly influences the rate of cellular energy utilization. Furthermore, the increase in energy utilization in muscles from hyperthyroid cats could not be attributed entirely to observed alterations in contractile behavior, which indicates that excess thyroid hormone may decrease the efficiency of the conversion of cellular energy to work. However, the opposite effect, an increased efficiency of energy utilization, was not observed in muscles from hypothyroid cats. Thus, it is concluded that the calorigenic effects of thyroid hormone may be explained, at least in part, by alterations in the process of energy utilization.

Effects of Prostaglandin A1 on the Systemic and Coronary Circulations in the Conscious Dog

Abstract: The effects of intravenous prostaglandin A1 (PGA1) on systemic and coronary hemodynamics were studied in 13 intact, conscious dogs after recovery from operation for implantation of Doppler ultrasonic flow probes on the ascending aorta and left circumflex coronary artery. Graded doses of PGA1 (0.01 to 1.0 µg/kg) caused arterial pressure and total systemic resistance to decrease progressively and heart rate and cardiac output to increase progressively. At the maximum dose administered (1.0 µg/kg), arterial pressure and systemic resistance decreased by averages of 30% and 51% below control, respectively, and heart rate and cardiac output rose 64% and 47%, respectively. After beta-receptor blockade with propranolol, PGA1 still caused a similar increase in cardiac output. In spite of arterial hypotension, PGA1 produced a progressive increase in coronary flow, with a peak increase of 74% above control with 1.0 µg/kg and a corresponding graded decrease in coronary resistance, with a decrease of 61% below control...

Structure and function of the normal myocardium

Abstract: The myocardium is composed of individual striated muscle cells (fibres), io to i5 ,um. in diameter and 30 to 6o ,um. in length. Under the light microscope each fibre contains multiple cross-banded strands (myofibrils), which run the length of the fibre and are composed of a serially repeating structure, the sarcomere. The remainder of the cytoplasm, lying between the myofibrils, contains other cell constituents such as the single centrally located nucleus, numerous mitochondria, and intracellular membrane systems. The sarcomere, the fundamental structural and functional unit of contraction, is delimited by two adjacent dark lines, the Z lines (Fig. I). The distance between Z lines varies with the degree of contraction or stretch of the muscle and ranges between I-5 and 2-2 ,tm. Within the confines of the sarcomere alternating light and dark bands are seen, giving the myocardial fibres their striated appearance under the light microscope. At the centre of the sarcomere is a broad dark band of constant width (i5 ,um.), the A band, which is flanked by two lighter bands, the I bands, which are of variable width. The sarcomere of heart muscle, like that of skeletal muscle, is made up of two sets of myofilaments. Thicker myofilaments, composed of the protein myosin, traverse and are limited to the A band. The myosin filaments are about iooA in diameter, with tapered ends, and they measure i 5 to i -6 ,tm. in length. Thinner myofilaments, composed primarily of actin, course from the Z line through the I band into the A band. The thin filaments are approximately 5o A in diameter and i o ,um. in length. Thus there is overlapping of thick and thin filaments only within the A band, while the I band contains only thin filaments (Fig. I). Bridges extend between the myosin and actin filaments within the A band. The 'sliding' model for muscle rests on the fundamental observation that both the thick and thin contractile filaments are constant in