Showing papers by "Eugene Braunwald published in 1970"
TL;DR: Blood pressure and velocity waveforms were recorded in a series of patients at cardiac catheterization and the changes in shape of the waveforms are interpreted in terms of reflections and are related to computations of vascular input impedance.
Abstract: Blood pressure and velocity waveforms were recorded in a series of patients at cardiac catheterization. The changes in shape of the waveforms are interpreted in terms of reflections and are related to computations of vascular input impedance.
344 citations
TL;DR: A fixed abnormality in diastolic LV pressure-volume characteristics, determined from preoperative and postoperative measurements of pressure and radius during diastole, had occurred in patients with depressed myocardial function, suggesting reversal of stress relaxation, or creep, following relief of volume overload.
Abstract: Left ventricular (LV) myocardial contractility, or inotropic state, was characterized in terms of the instantaneous relations between velocity of circumferential fiber shortening (VCF), determined cineangiographically, and LV wall tension (hoop stress), calculated from LV dimensions and pressure, in five patients before and 7 to 10 mo after aortic valve replacement for free aortic regurgitation. Preoperatively the cardiac index was reduced or the LV end-diastolic pressure was markedly increased (or both occurred) in four patients, in each of whom depression of inotropic state was documented by a reduced VCF at maximum wall tension, ranging from 0.13 to 1.07 circumferences (circ)/sec (normal, > 1.40 circ/sec) at wall tensions of 318 to 464 g/cm2 (normal, 178 to 417 g/cm2). In one patient in whom LV end-diastolic pressure and cardiac index were normal preoperatively, VCF was 1.66 circ/sec at a maximum tension of 440 g/cm2. Following operation, LV end-diastolic pressure fell in the four patients with depress...
200 citations
TL;DR: Patients with type III HLP are particularly susceptible to the development of PVD and objective improvement ofPVD can occur with medical treatment of this lipid transport disorder.
Abstract: The purpose of this study was to determine the effect of familial hyperlipoproteinemia (HLP) on peripheral vascular disease (PVD) and the extent to which the vascular disease (PVD) and the extent to which the vascular disease is modified by treatment of the lipoprotein disorder. PVD was detected plethysmographically by observing a diminished peak reactive hyperemia blood (PRHBF) following ischemia. The value for PRHBF in the extremity demonstrating the lowest response in 32 normal subjects (age 19-50 yr) was 39.6±1.5 SEM, ml/min per 100 g. Patients with untreated HLP. who had PRHBF below the lower limit of normal, were 2 of 11 type II, 9 of 12 type III, 1 of 10 type IV. As a group, patients with type III HLP showed diminished PRHBF (26.6 ±3.0 ml/min per 100 g, P <0.01). In view of the high incidence of PVD and the striking reduction in serum lipids and complete resorption of xanthomas observed in type III HLP with therapy, six patients were studied before and after 3-6 months of treatment with a therapeutic diet and clofibrate. PRHBF in the most severely affected extremity increased markedly, from 20.4 ±1.6 to 31.9 ±1.8 ml/min per 100 g (P<0.01), indicating a dramatic increase in maximum blood flow to this extremity. In two type III patients with PVD not treated, no change in PRHBF occurred over 5 months. In two other type III patients the PRHBF increased 17% during the first 25 days of therapy concomitant with a 30% reduction in whole blood viscosity. Over the next 120 days, blood viscosity decreased only an additional 4.6% whereas the PRHBF increased 57%, indicating that the observed changes seen in the PRHBF with therapy of type III patients can be only minimally accounted for by changes in the viscosity of the blood. Thus, patients with type III HLP are particularly susceptible to the development of PVD and objective improvement of PVD can occur with medical treatment of this lipid transport disorder.
128 citations
TL;DR: Electrical stimulation of the carotid sinus nerves in the conscious dog produced a differential pattern of peripheral vasodilatation, the most profound dilatation being observed in the hind-limb circulation.
Abstract: The effects of stimulating the carotid sinus nerves on the distribution of cardiac output and peripheral vasoactivity was studied in intact, unanesthetized dogs instrumented with ultrasonic or electromagnetic flow probes on the ascending aorta, mesenteric, renal, and iliac arteries, and miniature pressure gauges in the aorta. A radiofrequency pacemaker was used to stimulate the nerves in dogs at rest, during treadmill exercise, and after autonomic blockade. Thirty-second periods of stimulation in the resting dog resulted in an average decrease in aortic pressure of 28%, cardiac output remained unchanged, total peripheral resistance fell 29%, mesenteric flow 12%, mesenteric vascular resistance 18%, renal flow 8%, and renal vascular resistance 22%. In the iliac bed flow increased by 90% while resistance declined by 62%. Heart rate decreased initially by 13%, and returned to control during stimulation. The bradycardia was determined to be predominantly due to vagal stimulation. During treadmill exercise carotid sinus nerve stimulation resulted in similar decreases in arterial pressure, mesenteric and renal resistance, and a further decrease in iliac resistance from exercise control values. Thus, electrical stimulation of the carotid sinus nerves in the conscious dog produced a differential pattern of peripheral vasodilatation, the most profound dilatation being observed in the hind-limb circulation. This release of sympathetic tone also occurred during stimulation in exercising animals when the muscular bed was already dilated on a metabolic basis.
123 citations
TL;DR: It is demonstrated that both the skin and muscle resistance vessels participate in reflex changes initiated by alterations in baroreceptor activity, as well as the ratio of mean arterial pressure to the blood flow of each vascular bed.
Abstract: The role of skin and muscle vascular beds in baroreceptor-mediated alterations of peripheral vascular resistance was evaluated in six normal subjects in whom the skin circulation in one forearm was temporarily suppressed by epinephrine iontophoresis. Baroreceptor activity was enhanced by application of negative pressure to the neck (neck suction) and inhibited by application of lower body negative pressure. Forearm blood flow was measured simultaneously in both arms with strain gauge plethysmographs. Since blood flow in the treated arm consisted entirely of muscle flow, skin flow was calculated from the difference between total forearm flow in the intact arm and muscle flow in the treated arm. Vascular resistances were calculated as the ratio of mean arterial pressure to the blood flow of each vascular bed. During neck suction, mean arterial pressure decreased from an average of 89 to 75 mm of Hg (P < 0.005), heart rate decreased from an average of 60 to 55 beats/min (P < 0.005), and total skin and muscle flows remained essentially unchanged. Cutaneous vascular resistance decreased from an average of 75 to 49 mm of Hg/ml per 100 g per min (P < 0.05), muscle vascular resistance from 68 to 51 (P < 0.005), and total forearm vascular resistance from 36 to 24 (P < 0.025). During lower body negative pressure, heart rate increased from an average of 59 to 69 beats/min (P < 0.005), mean arterial pressure did not change significantly, and significant decreases occurred in forearm blood flow from 5.4 to 2.7 ml/100 g per min, in skin blood flow from 3.1 to 1.4, and in muscle blood flow from 2.3 to 1.3. Cutaneous vascular resistance increased from an average of 47 to 110 mm of Hg/ml per 100 g per min (P < 0.05), muscle vascular resistance from 43 to 72 (P < 0.005), and total forearm vascular resistance from 20 to 38 (P < 0.001). These results demonstrate that both the skin and muscle resistance vessels participate in reflex changes initiated by alterations in baroreceptor activity.
110 citations
TL;DR: It is concluded that the predominance of the parasympathetic nervous system on the sinoatrial frequency is a result of the interaction of the neurotransmitters, norepinephrine and acetylcholine on the mesthetized rabbits.
Abstract: The sinoatrial node is under the control of both parasympathetic and sympathetic influences. To study the interaction between these opposing influences, the response of the frequency of contraction of a spontaneously contracting rat right atrium to combinations of the neurotransmitters, norepinephrine and acetylcholine was observed. Norepinephrine in concentrations of 1 x 10-7M, 1 x 10-6M, and 1 x 10-5M, which by themselves increased atrial frequency by averages of 30%, 51% and 82%, respectively, and acetylcholine in concentrations of 1 x 10-5M, 1 x l0-4M, and 1 x 10-3M, which by themselves decreased atrial frequency by averages of 17%, 52%, and 97%, respectively, were added in all combinations to the atrial preparations. The response was not an algebraic sum of the effects of each of the agents; rather, the bradycrotic influence of acetylcholine predominated in all cases. This action of acetylcholine was blocked by atropine. To evaluate this interaction under more physiologic circumstances, the response of heart rate of anesthetized rabbits to isoproterenol, a potent beta-receptor stimulant, and to asphyxia, a stimulus which produces a marked parasympathetic discharge, was studied. Asphyxia alone induced a marked bradycardia that could be abolished by vagotomy. However, this bradycardia was not prevented by isoproterenol. It is concluded that the predominance of the parasympathetic nervous system on the sinoatrial frequency is a result of the interaction of the neurotransmitters, norepinephrine and acetylcholine on the sinoatrial node. In this interaction the presence of acetylcholine appears to prevent the action of norepinephrine.
55 citations
TL;DR: While tension in HT muscles is maintained in vitro at a stimulus frequency of 100 stimuli/sec, the reduction in duration of active state may lower tension in vivo by preventing complete fusion of contractile events.
Abstract: Contractile properties of soleus muscles isolated from 31 euthyroid (EU), 20 hyperthyroid (HT), and 18 myxedematous (MY) rats were studied in a myograph. At 100 stimuli/sec maximum isometric tension was essentially identical in EU (17.2 +/-0.5 g/mm(2)) and HT (17.7 +/-0.5 g/mm(2)) muscles, but was significantly depressed in MY muscles (11.5 +/-0.7 g/mm(2)). The rate of tension development was increased in HT (103 +/-4.5 g/sec per mm(2)) as compared to both EU (86.2 +/-4.6 g/sec per mm(2)) and MY (38.4 +/-2.2 g/sec per mm(2)) muscles, while the duration of the active state was shortened in HT (77.1 +/-2.3 msec) as compared to EU (105.1 +/-1.1 msec) muscles and was prolonged in MY muscles (153.3 +/-6.0 msec). The mean rate of isometric relaxation was 26.5 +/-4.9 g/mm(2) per sec in EU muscles, more rapid in HT muscles (33.1 +/-1.3 g/sec per mm(2)), and slower in MY muscles (16.0 +/- g/mm(2) per sec). The fusion frequency was greater in HT muscles, averaging 68.5 +/-3.6 stimuli/sec compared to EU muscles (38.1 +/-1.2 stimuli/sec) and to MY muscles (33.3 +/-4.0 stimuli/sec). At 40 stimuli/sec tension averaged 16.4 +/-0.8 g/mm(2) in EU muscles while at the same frequency tension was reduced in HT muscle, averaging 14.2 +/-0.5 g/mm(2). All differences were significant (P < 0.01). In conclusion, HT and MY result in profound alterations in the intrinsic contractile properties of skeletal muscle. While tension in HT muscles is maintained in vitro at a stimulus frequency of 100 stimuli/sec, the reduction in duration of active state may lower tension in vivo by preventing complete fusion of contractile events. In MY tension is reduced as a consequence of the lowered intensity of the active state. These changes explain, at least in part, the weakness of muscle activity in both HT and MY.
55 citations
TL;DR: Experimental hyperthyroidism augments myocardial VO2 whether measured in resting or contracting cardiac muscle, which can be attributed, at least in part, to altered contractile function of the heart in hyperthyoidism.
Abstract: To clarify the effects of hyperthyroidism on myocardial oxygen consumption (VO2), a polarographic method was employed to compare the VO2 of isolated papillary muscles from 13 normal euthyroid cats with that of 11 hyperthyroid cats. Basal VO2 was greater in the hyperthyroid group (3.03±0.20 vs. 2.36±0.19 SE filter-ing dry wrr1 · hour1, P < 0.05). In muscles studied under afterloaded isotonic conditions, hyperthyroidism shifted the forcevelocity curve upward and to the right, with an increase in both extent and velocity of shortening at equivalent loads. These changes in myocardial behavior in hyperthyroidism were associated with an increase in myocardial VO2. Isometrically contracting muscles from hyperthyroid animals demonstrated significant increases in both developed tension (6.3±0.7 vs. 4.7±0.4 g/mm2, P < 0.05) and rate of tension development (32.6±3.5 vs. 19.4±1.5 g/mm2 · second-1, P < 0.01), as compared to the euthyroid group. Myocardial VO2, expressed per g/mm2 isometric developed tension, was signi...
39 citations
TL;DR: It is concluded that maximal doses of isoproterenol produce significantly greater increases in myocardial contractility and cardiac output compared to ouabain, even when the toxicity produced by the latter is suppressed by electrical stimulation.
Abstract: The relative peak effects of isoproterenol and ouabain on myocardial contractility and cardiac output were compared by infusing increasing amounts of these two drugs into seven open-chest anesthetized dogs until toxicity developed. Just prior to the development of toxicity isoproterenol increased contractile force an average of 149% and the peak rate of force development (df/dt) an average of 278% of control values, compared to an increase of only 49% and 35%, respectively, with the administration of ouabain. Cardiac output and stroke volume were also significantly greater with the catecholamine than the glycoside. The combination of isoproterenol and ouabain produced essentially the same contractile force and stroke volume achieved by isoproterenol alone. Suppression of ouabain-induced arrhythmias by ventricular pacing allowed additional glycoside to be infused until ventricular fibrillation terminated the study. With pacing and ouabain, contractile force increased 131% above control, a level similar to that achieved by isoproterenol; peak df/dt increased to 200% above control, a value significantly lower than that obtained with isoproterenol. However, stroke volume decreased despite a substantial increase in left ventricular end-diastolic pressure. It is concluded that maximal doses of isoproterenol produce significantly greater increases in myocardial contractility and cardiac output compared to ouabain, even when the toxicity produced by the latter is suppressed by electrical stimulation.
35 citations
TL;DR: Findings point to competition for space by the ventricles in the distended pericardial sac as being the major factor in the production of pulsus paradoxus.
Abstract: Measurements have been made of pressure and blood velocity in venae cavae and aorta in a patient with severe cardiac tamponade in whom there was pulsus paradoxus. The characteristic pressure changes of pulsus paradoxus were associated with variations in peak blood velocity in the ascending aorta and stroke output. Maximum filling of the right side of the heart occurred during inspiration, and was associated in time with minimum left ventricular stroke volume.
These findings point to competition for space by the ventricles in the distended pericardial sac as being the major factor in the production of pulsus paradoxus.
31 citations
TL;DR: It is concluded that ventricular pacing with a single electrical stimulus will effectively overcome serious digitalis-induced arrhythmias and that it should be considered for trial in patients with refractory digitalis toxicity.
Abstract: Paired electrical ventricular pacing has been shown to be an effective means of overcoming digitalis-induced arrhythmias, but it has not been used clinically because of the danger of inducing ventricular fibrillation and because the second contraction interferes with ventricular filling. For these reasons, the possibility that ventricular pacing with a single electrical stimulus might accomplish the same effect was examined. A pacing catheter was passed by way of the jugular vein into the right ventricle of 16 dogs, and ouabain was infused at the rate of 1 μg/kg per min. In 9 control animals serious ventricular arrhythmias occurred at 51.0 ± 3.6 (SEM) min and death at 94.9 ± 5.9 min. In 7 dogs arrhythmias occurred at 51.6 ± 3.7 min but were completely abolished by pacing at a frequency 20 percent above the intrinsic rate. However, the total cumulative dose of ouabain that caused death remained unchanged, and the animals with pacing died of ventricular fibrillation at 94.6 ± 8.2 min. In other studies in 23 dogs infusion of potassium was started at the time of initial toxicity, but it had no effect on the cumulative dose of ouabain considered lethal. Neither pacing nor infusion of potassium altered the maximal tolerated dose of ouabain. We found that arrhythmias can be completely suppressed by ventricular pacing, but that they recur during administration of potassium. We conclude that ventricular pacing with a single electrical stimulus will effectively overcome serious digitalis-induced arrhythmias and that it should be considered for trial in patients with refractory digitalis toxicity.
TL;DR: This flowmeter catheter allows accurate, rapid and safe measurement of instantaneous linear blood flow and pressures in great vessels of intact patients in the assessment of cardiovascular function.
31 Dec 1970
TL;DR: The application of a catheter tip oximeter incorporating a lumen, which allows simultaneous recordings of intracardiac oxygen saturation and pressure, to the diagnosis of patients with congenital heart disease is described and results were in close agreement with the results of the 85 krypton inhalation test.
Abstract: The application of a catheter tip oximeter incorporating a lumen, which allows simultaneous recordings of intracardiac oxygen saturation and pressure, to the diagnosis of patients with congenital heart disease is described. When combined with the cinetrace system, intracardiac oxygen saturation and pressure could be correlated precisely with the anatomic position of the catheter tip. Fifty patients with congenital heart disease and intracardiac and great vessel shunts were studied. The detection, localization and quantification of left to right shunts required no withdrawal of blood, and the findings were in close agreement with the results of the 85 krypton inhalation test. The fiberoptic catheter incorporating a lumen for pressure recording allows beat to beat display of the relations among intracardiac and intravascular oxygen saturation, shunt flow, pressure and the electrocardiogram. The simultaneous visual display of catheter position, hemodynamic data, blood oxygen saturation, and electrocardiogram on cine film permits rapid, complete and accurate assessment of the condition of children and adults with congenital cardiac defects.