Acute effects of alcohol on the human myocardium

The effect of acute alcoholic ingestion after 6 oz. of 84 proof Vodka was studied in 11 patients with a known history of chronic alcoholism. No patient had any evidence of vitamin deficiency nor any clinical evidence of heart or liver disease. The results would indicate no significant changes in pulse rate, blood pressure, cardiac output, stroke volume, arterial venous oxygen extraction or respiratory quotient. Despite the lack of these hemodynamic alterations, electrocardiographic changes as evidenced by flattened and inverted T waves occurred 30 minutes after the ingestion of alcohol in 2 of the patients.

Metabolically the significant findings included a rise in blood lactate, a decline in arterial pyruvate, a marked fall in blood glucose, a decline in free fatty acids and a rise in triglycerides one half hour after the ingestion of alcohol. Phospholipid blood levels remained unchanged. Coronary arterial and venous contents of magnesium, copper and zinc were essentially unchanged 30 minutes after alcohol; three hours postingestion, peripheral venous contents exceeded that of the 30 minute arterial and coronary venous determination. Zinc was liberated by the heart following alcohol in the majority of patients. Serum alcoholic dehydrogenase activity closely followed that of blood zinc. The myocardial extraction of the substrates was consistent with the rise or decline in arterial blood levels with the exception of lactate and glucose; the former fell and the latter rose significantly. Both alcoholic dehydrogenase and isocitric dehydrogenase coronary venous enzyme activities also frequently exceeded that found in arterial blood in several patients.

The implications of these findings were discussed. It is suggested that repeated exposure to acute alcoholism could result in permanent alterations in myocardial metabolism which could lead to the development of irreversible alcoholic cardiomyopathy.     

Effect of nitroglycerin on ventricular fibrillation threshold of nonischemic myocardium

The threshold for ventricular fibrillation induced by a 200 msec train of pulses was measured during a control period and during an intravenous infusion of nitroglycerin in 14 nonischemic open chest dogs. Infusion of nitroglycerin in doses sufficient to reduce mean arterial blood pressure an average of 17 mm Hg was associated with a rise in ventricular fibrillation threshold from a control value of 24 ± 3 (mean ± 1 standard error of the mean) to 41 ± 6 milliamperes (P < 0.001). In a subgroup of six animals simultaneous infusions of nitroglycerin and phenylephrine abolished the hypotensive effect of nitroglycerin but did not significantly alter the rise in ventricular fibrillation threshold observed with nitroglycerin infusion alone. In five other animals mean arterial blood pressure was similarly reduced an average of 17 mm Hg by venous hemorrhage, but was associated with a lowering rather than a rise in ventricular fibrillation threshold from a prehemorrhage value of 28 ± 6 to 15 ± 2 milliamperes, (P < 0.005). Thus, intravenously administered nitroglycerin raises ventricular fibrillation threshold in nonischemic canine myocardium independent of its hypotensive effects.     

Acute effects of ethanol on left ventricular diastolic function

Transmitral flow velocities were measured by Doppler echocardiography in nine healthy men who ingested 1 g/kg of ethanol within one hour. The measurements were made before the first drink and every hour thereafter for three hours. The peak mean (SE) blood ethanol concentration was 21.4 (1.0) mmol/l. Each man was also studied after drinking fruit juice. Ethanol increased the heart rate but did not change the peak transmitral velocities, the normalised peak filling rate, the deceleration of early flow, or the duration of relaxation as measured from the second heart sound to the peak early diastolic velocity. The ratio of the peak atrial to the peak early diastolic velocity rose from 0.41 (0.03) to 0.44 (0.03) after ethanol but remained unchanged after juice. The difference between juice and ethanol was independent of changes in heart rate. The fluid balance was more negative in the ethanol experiment (-727 (114) ml v -107 (70) ml), suggesting a reduction in preload, and the ethanol-induced net loss of fluid correlated with the concomitant change in the velocity ratio. A moderate dose of ethanol causes a small acute increase of the ratio of the peak atrial to the peak early diastolic velocity of mitral flow in healthy subjects. Although this change indicates altered diastolic function of the left ventricle, most of it may result from the diuretic effect of ethanol. Any major impairment of ventricular relaxation seems unlikely.     

Acute effects of His bundle pacing versus left ventricular and right ventricular pacing on left ventricular function

Dual-chamber pacing with His bundle pacing has theoretical advantages over conventional right ventricular (RV) apical pacing. We compared indexes of left ventricular (LV) function during acute dual-chamber pacing from the His bundle and other RV and LV pacing sites. Twelve patients (6 men; 63 +/- 11 years) with a standard indication for electrophysiologic study were included. Average QRS duration was 100 +/- 19 ms. Ejection fraction was 48 +/- 15%. A pressure-volume catheter was positioned in the left ventricle through the femoral arterial access. Pressure-volume loops were collected during atrial (AAI) and dual-chamber overdrive pacing at 82 +/- 15 beats/min after 2 minutes of hemodynamic stabilization. Ventricular pacing catheter position was randomized between the RV apex, RV septal, and free wall portions of the outflow tract, LV free wall, and His bundle. His bundle capture was verified from surface electrocardiographic morphometry using standard criteria. Atrioventricular delay was set to the P wave-His duration -10 ms to minimize the effects of fusion (96 +/- 22 ms). LV only pacing, but not His pacing, resulted in improved stroke work and stroke volume compared with alternate site RV pacing. No changes in +dP/dt, LV end-systolic pressure. LV end-diastolic pressure, or cycle efficiency, were observed between RV pacing sites. In conclusion, acute His bundle pacing did not improve LV function compared with alternate site RV pacing and may be inferior to LV pacing.     

The effects of pretreatment with nitroglycerin on ischemic left ventricular dysfunction during coronary angioplasty

To evaluate the degree to which nitroglycerin reduces myocardial ischemia and dysfunction induced by transient coronary occlusion, 19 patients were studied during coronary angioplasty of the left anterior descending coronary artery. After a control occlusion of 60 seconds, 0.2 mg nitroglycerin was administered intravenously and the occlusion was repeated for 60 seconds. Before and during the occlusion period, pulmonary capillary wedge pressure was measured, the intracoronary ECG was recorded, and ventricular volumes, ejection fraction, and regional systolic shortening were obtained by digital subtraction angiography. Nitroglycerin caused a significant fall in pulmonary capillary wedge pressure before (10 vs. 7 mmHg) and at 60 seconds occlusion (18 vs. 14 mmHg), but did not significantly delay the rise in wedge pressure (37 vs. 44 seconds). End-systolic left ventricular volume at 60 seconds of occlusion was reduced by nitroglycerin (77 vs. 68 ml), whereas regional shortening of the ischemic segments remained unchanged (22 vs. 23%). Nitroglycerin did not delay the onset of ischemic ST-segment elevation (14 vs. 14 seconds) and had no effect on the changes of ST elevation in the intracoronary ECG (1.9 vs. 1.9 mV). These findings suggest that intravenous nitroglycerin reduces filling pressure and slightly improves left ventricular global function during acute coronary occlusion. Nitroglycerin, however, has little effect on ischemia-induced regional dysfunction and on ST-segment elevation in the intracoronary ECG.     

Microvasculature of the dog left ventricular myocardium

One of the main branches of the left main coronary artery of normally beating dog hearts was perfused with a silicone elastomer which solidified within the vasculature. Prolonged immersion in increasingly concentrated ethanol and in methyl salicylate rendered the tissue translucent and the vasculature clearly visible. Surfaces were photographed by reflected or transmitted light microscopy, showing large groups of capillaries running parallel to muscle fibers and extending for up to a few centimeters. The arrangement of arteriolar inflows to the capillary network and venular outflows (two to four times as frequent) suggested that functional capillary lengths were 500–1000 μm. Estimates of capillary diameters, presumably at maximal dilatation, were 5.6 ± 1.3 μm. Capillary densities within muscle groups were 3100–3800/mm², giving intercapillary distances of 19-17.5 μm. With the lesser density value, the capillary surface area is estimated to be 500 cm²/g of myocardium. Inclusion of interfascial spaces lowered the average density to about 2500/mm². Unbranched capillary lengths averaged 100 μm, with a strongly right-skewed distribution. The anatomic arrangement provides a basis mainly for concurrent flow in neighboring capillaries, and also for some diffusional exchange between inflow and outflow regions.     

Acute effects of ethanol on left ventricular diastolic function.

Transmitral flow velocities were measured by Doppler echocardiography in nine healthy men who ingested 1 g/kg of ethanol within one hour. The measurements were made before the first drink and every hour thereafter for three hours. The peak mean (SE) blood ethanol concentration was 21.4 (1.0) mmol/l. Each man was also studied after drinking fruit juice. Ethanol increased the heart rate but did not change the peak transmitral velocities, the normalised peak filling rate, the deceleration of early flow, or the duration of relaxation as measured from the second heart sound to the peak early diastolic velocity. The ratio of the peak atrial to the peak early diastolic velocity rose from 0.41 (0.03) to 0.44 (0.03) after ethanol but remained unchanged after juice. The difference between juice and ethanol was independent of changes in heart rate. The fluid balance was more negative in the ethanol experiment (-727 (114) ml v -107 (70) ml), suggesting a reduction in preload, and the ethanol-induced net loss of fluid correlated with the concomitant change in the velocity ratio. A moderate dose of ethanol causes a small acute increase of the ratio of the peak atrial to the peak early diastolic velocity of mitral flow in healthy subjects. Although this change indicates altered diastolic function of the left ventricle, most of it may result from the diuretic effect of ethanol. Any major impairment of ventricular relaxation seems unlikely.     

Influence of aortic valve disease on systolic stiffness of the human left ventricular myocardium

The new concept of systolic myocardial stiffness was applied to the study of ejection mechanics in aortic valve disease. Frame-by-frame analysis of stress (sigma) and volume (V) was performed for two differently loaded beats in 26 patients who underwent simultaneous cineangiography and micromanometry: nine normal subjects, eight with isolated aortic regurgitation (AR), and nine with aortic stenosis (AS). Maximum myocardial stiffness (maxEav) was defined as the slope of the end-systolic (es) stress-strain relationship. End-systole was defined as the frame where stiffness was maximal, and strain was defined as epsilon = loge (Dm/Dom), where Dm is left ventricular midwall diameter and Dom is the theoretical Dm at zero stress. Expressed in terms of cavity volume, epsilon = gamma X loge (V/Vo), where gamma is the geometric factor relating Dm to V during systole. Vo was obtained by extrapolating to sigma es = 0 the function, sigma es = maxEav X gamma X loge (Ves/Vo), which was fit to the end-systolic data. Vo always had a value greater than zero. MaxEav was preserved in the AR group (1575 +/- 565) and increased in the AS group (1877 +/- 544; p = .02) compared with normal (1320 +/- 268), suggesting maintenance of contractile force per unit of myocardium in these two lesions. However, theoretical "unloaded" shortening fraction (SFo) was depressed in the AS group (0.30 +/- 0.06; p = .01) compared with normal (0.37 +/- 0.04), preserved in the AR group (0.34 +/- 0.07; p = .24), and inversely related to maxEav (r = -.66, p = .01), suggesting a disparity between shortening potential and force potential.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolonged salutary effects of isosorbide dinitrate and nitroglycerin ointment on regional left ventricular function.

To assess the long-term effects of orally and topically administered nitrates on left ventricular function, 11 patients with previous myocardial infarction were studied with use of isosorbide dinitrate, 20 mg orally, nitroglycerin ointment, 12.5 to 40 mg and placebo ointment. Both nitrates produced a sustained decrease in systolic blood pressure and estimated left ventricular wall stress but no change in heart rate during 4 hours of study. The triple product of heart rate, systolic blood pressure and left ventricular ejection time decreased by 21 percent after administration of isosorbide dinitrate (P < 0.001) and 19 percent after administration of nitroglycerin ointment (P < 0.001). The echocardiographic left ventricular end-diastolic dimension decreased significantly after isosorbide dinitrate (from 52.4 to 49.2 mm at 2 hours, P < 0.01) and nitroglycerin ointment (from 52.4 to 50.5 mm, P < 0.01). The end-systolic dimension was similarly reduced. Left ventricular sites showing abnormally small excursion (less than 3 mm) on wall motion videotracking showed improved motion after the administration of each nitrate, and the velocity of systolic inward motion was consistently increased after each. Thus, determinants of myocardial oxygen consumption, such as systolic blood pressure, left ventricular ejection time, left ventricular size and triple product appear to be consistently reduced for at least 4 hours after administration of isosorbide dinitrate and nitroglycerin ointment, and impairment of left ventricular wall motion appears to be significantly decreased.     

Acute effects of cigarette smoking on left ventricular diastolic function.

Cigarette smoking increases coronary resistance in patients with coronary artery disease, causing profound disturbances in myocardial perfusion. The acute effects of smoking a single cigarette on left ventricular diastolic function were studied in 20 smokers with typical angina pectoris and angiographically documented coronary artery disease. Twenty healthy smokers served as a control group. We used simultaneous M-mode echocardiography of the mitral and aortic valves to measure isovolumic relaxation time, and pulsed Doppler echocardiography of transmitral blood flow was recorded to evaluate left ventricular filling before and immediately after smoking. In the patients with coronary artery disease, systemic blood pressure and heart rate significantly increased after smoking. The isovolumic relaxation time, the deceleration time as well as peak A velocity remained unchanged. The peak E velocity decreased by 0.06 m.s-1 (P = 0.02) and the peak E/A velocity ratio by 0.17 m.s-1 (P = 0.01). There were no significant changes in left ventricular diastolic function indexes in the controls. These results indicate that in patients with coronary artery disease, each cigarette provokes disturbances of left ventricular diastolic function.     

Unfavorable effects of ventricular pacing on myocardial energetics

Summary The effects of ventricular pacing (90–330 beats/min) and atrial pacing (120–210 beats/min) on myocardial oxygen consumption and its hemodynamic determinants and on myocardial pumping efficiency were studied systematically on intact dogs. In six closed-chest experiments 158 steady states were analyzed. Myocardial blood flow was measured with a differential pressure sinus catheter, oxygen consumption (5–30 ml/min·100 g) was determined simultaneously by the Fick principle and the additive hemodynamic parameter E_t. Ventricular and atrial pacing were compared with both methods at identical heart rates. Additionally, the coincidence between both methods of determining overproportionally up to 50% in sinus rhythm with sympathetic stimulation (norepinephrine, atropine) within each experiment. Ventricular pacing increased overproportionally up to 50% in relation to the hemodynamic determinants. Consequently, myocardial pumping efficiency markedly decreased with increasing ventricular rate. The close relation between directly measured and E_t, found in previous studies, was maintained under sympathetic stimulation. Atrial pacing, as compared to ventricular pacing at identical rates, resulted in a decrease of up to 25% although the expected according to its hemodynamic determinants rather increased. The hemodynamic and metabolic mechanisms probably responsible for the energetic difference between ventricular and atrial pacing at equal heart rates are discussed.Supported by the Deutsche Forschungsgemeinschaft, SFB 89-Kardiologie Göttingen     

Scintigraphic evidence that the right ventricular myocardium tolerates ischaemia better than the left ventricular myocardium

To study the incidence of right ventricular infarction and theeffect of intracoronary thrombolysis on the ischaemic rightventricular myocardium, we performed intracoronary myocardialthallium scintigraphy in 18 patients with complete occlusionof the right coronary artery who underwent intracoronary thrombolysis.In 15 of these patients, intracoronary thallium-201 and technetium-99m pyrophosphate scintigrams were performed simultaneously. All18 patients had a right ventricular thallium defect before thrombolysis,and all had new thallium uptake after thrombolysis. 17 out of18 patients had a left ventricular thallium defect before thrombolysis,but only 10 of them showed new thallium uptake after thrombolysis.14 out of 15 patients had a left ventricular technetium-99 mpyrophosphate spot after thrombolysis and some diffuse pyrophosphateaccumulation in the area of the right ventricle. In one patientpyrophosphate accumulation was found only in the area of theright ventricle. Thus, right ventricular thallium defects weredetected by intracoronary thallium scintigraphy in the majorityof patients with inferior acute myocardial infarction due toright coronary artery occlusion. Right ventricular thalliumdefects were always reversible in contrast to left ventricularthallium defects in the same patients, suggesting that rightventricular myocardium tolerates ischaemia better than leftventricular myocardium.     

Reduced positive inotropic effects in diseased human ventricular myocardium

In isolated contracting human ventricular myocardium taken from patients undergoing mitral valve replacement the positive inotropic effects of calcium, isoprenaline, dobutamine, dopamine, histamine, milrinone, isobutylmethylxanthine, and theophylline were determined. Calcium (15 mmol X litre-1) produced an increase in force of contraction similar to that of a maximal effective concentration of ouabain (1 X 10(-7) mol X litre-1); significantly lower maximal effects were measured with all the other positive inotropic compounds tested. The addition of these positive inotropic substances after a stable maximum effect with ouabain (1 X 10(-7) mol X litre-1) had been reached increased the incidence of toxicity without producing any further inotropic effects. These results suggest that inotropic substances acting through cyclic adenosine monophosphate give less than the maximum inotropic response in isolated muscle from diseased human hearts, which is not additive to the maximal ouabain induced inotropy.     

Age-related hemodynamic effects of intravenous nitroglycerin for acute myocardial infarction and left ventricular failure

Acute hemodynamic effects of intravenous nitroglycerin (NTG) were assessed in 24 patients with acute myocardial infarction and left ventricular failure, and results were compared between 2 groups of different age (group A--65 years or less, n = 12; group B--75 years or more, n = 12). Overall, hemodynamic effects of NTG consisted of an increase in stroke volume index and left ventricular stroke work index (+21 and +23%), coupled with a 16% reduction in systemic vascular resistance, and of a marked decrease in right atrial and pulmonary artery (PA) pressures. The hemodynamic end-point (5 to 10% reduction in mean systemic arterial pressure) used for NTG titration was achieved with a significantly lower dose in group B, in which a greater percent reduction in mean PA and mean PA wedge pressures was also observed. However, because effects of NTG on systemic vascular resistance were similar in groups A and B, it was concluded that the vasodilating action of NTG is maintained in advanced age, as opposed to what has been demonstrated for beta-adrenergic agents.