No abstract

When the fall in left ventricular pressure during isovolumic relaxation is treated as a monoexponential the rate of relaxation can be measured by a time constant. Though an empirical measurement, the time constant has been used extensively to study relaxation. It can be accepted, however, as a valid measurement only if isovolumic pressure fall approximates very closely to a monoexponential in a wide range of circumstances.We analysed 60 beats recorded at different heart rates in 20 patients with a variety of left ventricular disease. In the first part of the study a powerful non-linear regression program was used off-line to test three exponential models: (1) a monoexponential, the asymptote of which is zero, (2) a monoexponential with a variable asymptote, and (3) a biexponential. The pressures predicted by models 2 and 3 were in very close agreement with measured pressure, whereas the predictions of model 1 were consistently less accurate. Model 3 had no advantage over model 2. Thus, in all the beats tested isovolumic pressure fall approximated very closely to a monoexponential of which both the time constant and asymptote are variable. A second exponential term does not increase precision, and is an unnecessary complication.In the second part of the study the same 60 beats were analysed by a small program on the catheter laboratory computer. The time constant was estimated by two methods, corresponding to models 1 and 2 described above: (1) from the slope of In (pressure) against time, and (2) by a method of exponential analysis. The first method underestimated the time constant of model 1, particularly in beats where pressure fell to low levels. The second method accurately estimated the time constant of model 2.It is concluded that isovolumic pressure fall approximates closely to a monoexponential in a wide variety of circumstances, and it is legitimate, therefore, to describe the rate of relaxation by a time constant. But the time constant must be estimated by a method based upon an exponential model of which both the time constant and asymptote are variable. We have shown that such a time constant can be estimated reliably by a small program suitable for use on-line. The usual method of estimating the time constant, from the slope of In (pressure) against time, provides an unreliable estimate of the time constant of an unsatisfactory model.During isovolumic relaxation the fall in left ventricu-must decay exponentially during relaxation. Its use lar pressure from the point of its maximum rate of can be justified only if isovolumic pressure fall change until it reaches the level of end-diastolic pres-approximates closely to a monoexponential in a wide sure of the preceding beat approximates to a monoex-range of circumstances. In addition, the estimate of ponential and can be characterised by a time con-the time constant is highly dependent upon its stant. 14 Though it has been used widely to study method of calculation.89 The purpose of this study relaxation of the intact ventricle' -7 the time constant was ...

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 The effects of intravenous amrinone and sodium nitroprusside on haemodynamic indices, left ventricular contractility, and myocardial metabolism were compared in patients with cardiac failure. All patients received one dose of each drug and some received serial doses. Eight patients had dilated cardiomyopathy and six coronary artery disease, but the responses to the two drugs were independent of the aetiology of cardiac failure. Both drugs lowered left ventricular end diastolic pressure and aortocoronary sinus oxygen difference and increased cardiac index and left ventricular efficiency; these effects were dose related. Although the effects of the drugs on peripheral blood substrate concentrations were different, those on myocardial substrate metabolism were identical. Pressure derived indices of contractility in each group of patients were unaltered by either drug. After amrinone administration increases in cardiac index were related to plasma amrinone concentration, but alterations in contractility were not. In four individual patients increases in contractility were associated with alterations in plasma metabolite concentrations, which suggested that catecholamine release had occurred. For the groups of patients as a whole, however, amrinone had effects which did not differ significantly from those of the pure vasodilator, nitroprusside. There was no evidence that amrinone had a direct positive inotropic effect since no dose related changes in indices of contractile function could be established.Amrinone (Inocor, Sterling-Winthrop) has been reported to produce considerable improvements in ventricular filling pressures and cardiac index in patients with cardiac failure during intravenous' and oral administration.2 An increase in maximum rate of rise in left ventricular pressure (max dP/dt) after intravenous administration of amrinone in some small series3-5 has largely been attributed to a direct positive inotropic effect of the drug, although no dose response relation has been found, and a larger series6 has failed to confirm these changes in max dP/dt and other contractility indices. In isolated myocardiumRequests for reprints to Dr P T Wiimshurst, Department of Cardiology, St Thomas's Hospital, London SEI 7EH.