Myocardial substrate extraction, coronary sinus flow, cardiac output, and left ventricular pressure were measured at increasing pacing rates before and after propranolol (0.2 mg/kg) in 13 patients with hypertrophic obstructive cardiomyopathy (HOCM) during diagnostic cardiac catheterisation. At the lowest pacing rate myocardial oxygen consumption varied considerably between patients and very high values were found in several individuals (range 10.1 to 57.5 ml/min). These large differences between patients were not explicable by differences in cardiac work; consequently, cardiac efficiency, estimated from the oxygen cost of external work, varied between patients and was lower than normal in all but two. The pattern of substrate extraction at the lowest pacing rate was similar to results reported for the normal heart, and measured oxygen consumption could be accounted for by complete oxidation of the substrates extracted; thus there was no evidence of a gross abnormality of oxidative metabolism, suggesting that low efficiency lay in the utilisation rather than in the production of energy. Each of the four patients with the highest myocardial oxygen consumption and lowest values of efficiency sustained progressive reductions in lactate and pyruvate extraction as heart rate increased, and at the highest pacing rate had low (< 3%) or negative lactate extraction ratios. In three of these four, coronary sinus flow did not increase progressively with each increment in heart rate. One patient with low oxygen consumption and normal efficiency also failed to increase coronary flow with the final increment in heart rate, and produced lactate at the highest pacing rate. Thus the five patients in whom pacing provoked biochemical evidence of ischaemia all had excessive myocardial oxygen demand and/or limited capacity to increase coronary flow. Propranolol did not change lactate extraction significantly at any pacing rate in either the ischaemic or non-ischaemic groups. In only one patient was ischaemia at the highest pacing rate abolished after propranolol, and this was associated with a 30 per cent reduction in oxygen consumption. These results do not demonstrate a direct effect of propranolol upon myocardial metabolism in patients with HOCM, but emphasise the potential value of beta-blockade in protecting these patients from excessive increases in heart rate.

SUMMARY When a decrease in left ventricular isovolumic pressure is considered as an exponential, the rate of relaxation can be defined by a time constant (T). Previously, T has been calculated from the slope of In (pressure) against time, but this method is valid only when the asymptote of the exponential is zero. In this study two estimates of T were made: Tin from the slope of In (pressure) against time, and TEXP by a method of exponential analysis that also estimated the asymptote. These techniques were applied to measurements of left ventricular pressure made at increasing pacing rates in three groups of patients catheterized for chest pain: group 1 (n = 9) normal coronary arteriograms; group 2 (n = 9) -coronary artery disease (CAD) but no angina or lactate production during pacing; and group 3 (n = 9) CAD and angina during pacing. Tjn was always shorter than TEXP, and in groups 1 and 2 TEXP was dependent on heart rate, whereas Tin was not. The asymptote was negative, and increased toward zero during pacing in groups 1 and 2. The difference between TEXP and Tin could be related to the value of the asymptote. In 18 of 20 beats tested, pressures calculated from TEXP and the asymptote were in closer agreement with measured pressures than were the pressures predicted by T1n. Despite their different values, TEXP and Tin each distinguished between the three groups. Although the choice of an exponential model is arbitrary, isovolumic pressure decrease approximates to a single expontial; but this study suggests that both T and the asymptote are variable.THE STUDY of the decrease in left ventricular pressure during isovolumic relaxation is hindered by the lack of a method of quantifying pressure decrease that can be used to compare individual subjects. The maximal rate of pressure decrease (dP/dt min) can decrease during ischemia,l but dependence on endsystolic pressure and fiber length limits its value.2' More recently, a pressure decrease from the point of dP/dt min has been treated as a single exponential, which allows derivation of a time constant that describes relaxation.4 6 The time constant is calculated as the negative reciprocal of the slope of ln (pressure) against time, and the correlation coefficient is used to test the validity of the monoexponential model.4-6 The time constant so derived is relatively insensitive to heart rate, ventricular volume and the level from which pressure decreases,4 7 8 but is prolonged during ischemia.6' This semilogarithmic method of estimating the time constant of an exponential is valid only when the asymptote of the exponential is zero. The zero reference for pressure measurement is an external point; one cannot assume that it corresponds to the asymptote of ventricular pressure decrease or that the asymptote remains constant under different conditions. In this study, we estimated the time constant of isovolumic pressure decrease both from the plot of In (pressure) against time and by a method of exponential analysis that also estimates the asymptote. We used these techn...

SUMMARY Myocardial substrate extraction, coronary sinus flow, left ventricular pressure, and cardiac output were measured in 11 patients with angina pectoris at three pacing rates before and after atenolol (0.2 mg/kg). Left ventricular pressures, and the product of systolic pressure time index and heart rate did not change, but max dP/dt and KV max fell after atenolol. Only at the lowest pacing rate did the drug reduce cardiac output. Coronary sinus blood flow and myocardial oxygen uptake did not change after atenolol. At the highest pacing rate before atenolol four patients developed angina, accompanied by a rise in end-diastolic pressure. After atenolol angina was abolished in three, but the end-diastolic pressure still rose at the highest pacing rate. Myocardial lactate extraction ratio fell as heart rate increased, and was lower in the patients who developed angina. After atenolol, lactate extraction ratio increased significantly at the highest and lowest pacing rates. Myocardial pyruvate extraction rose after the drug. Arterial concentrations ofhydroxybutyrate and acetoacetate fell after atenoldl, but the decrease in their extraction was not significant. Myocardial extraction of free fatty acids was related to arterial concentration, which fell after atenolol. The changes in lactate and pyruvate extraction after atenolol were related inversely to changes in arterial free fatty acid concentration suggesting that the improvement in myocardial metabolism could have been secondary to reduced peripheral lipolysis. The increase in lactate extraction was associated with reliefofangina, but did not abolish the rise in end-diastolic pressure induced by pacing.The beneficial effect of beta-adrenergic blocking drugs in angina has been attributed to a reduction in myocardial oxygen demand secondary to their haemodynamic actions.1-3 When heart rate is controlled by atrial pacing, beta blockade has little effect upon myocardial oxygen consumption.45 Studies in which patients with angina have been paced before and after beta-blocking drugs have yielded conflicting results; some have shown no beneficial effect,3 6 while others have shown an improvement in anginal threshold or lactate extraction,4 suggesting that beta blockade may modify myocardial metabolism independently of its haemodynamic actions. The possible direct effects of beta-blocking drugs upon the human myocardium are poorly understood, and though their actions upon peripheral metabolism are well documented8 the relevance of these to the heart has not been established.Atenolol is a cardioselective beta-adrenergic antagonist without intrinsic sympathomimetic acReceived for publication 12 November 1979 tivity,9 and is effective in the treatment of angina.'0 When heart rate is controlled, atenolol does not change myocardial oxygen consumption or coronary blood flow.5 This study describes the effects of atenolol upon myocardial substrate extraction, coronary sinus blood flow, and systemic haemodynamics during pacing in 11 patients with angina, and attempts to id...

SUMMARY Disopyramide phosphate was administered intravenously in a dose of 1-2 mg/kg body weight over one minute to nine patients after open-heart surgery and coronary artery bypass grafting. The haemodynamic changes were studied during and for 30 minutes after drug administration. Heart rate was unchanged throughout the study. During infusion the only significant changes were an increase in systemic blood pressure and systolic impedance signifying a direct increase in peripheral arterial resistance. Systemic blood pressure remained significantly higher for 10 minutes and systolic impedance for 30 minutes. Immediately after infusion max. dPower/dT, a measure of ventricular contractility, was significantly depressed for 15 minutes. Both cardiac output and aortic flow were significantly depressed for 30 minutes. DPTI/TTI, an estimate of subendocardial supply/demand ratio, showed an insignificant increase throughout the study.This study shows that intravenous disopyramide starts acting within 45 seconds of the start of infusion, directly increases peripheral arterial resistance, has a brief negative inotropic action, and does not reduce subendocardial blood flow.

We describe the case of an asymptomatic 24-year-old man with hypertension who was investigated for aortic coarctation but found on MR scanning to have narrowing of the distal thoracic aorta. Stenosis of the thoracolumbar aorta--the Middle Aorta Syndrome--is rare and is usually found below the diaphragm. The MRI and angiographic findings are presented.