CLINICAL INVESTIGATION Left ventricular contractility and contractile reserve in humans after cardiac transplantation

Limited data are available concerning left ventricular contractility and contractile reserve in the chronically denervated, transplanted human heart. This is primarily because of the inability of traditional tests of left ventricular performance to distinguish changes in contractility from alterations in ventricular loading conditions. In this study, load-independent end-systolic indexes of left ventricular contractility were measured by echocardiography and calibrated carotid pulse tracings in 10 patients who had undergone orthotopic cardiac transplant (age 48 4 years; interval from operation to study 1.2 0.8 years) and in 10 normal control subjects (age 25 4 years) matched for donor heart age (25 6 years). None of the transplant patients had evidence of rejectidn as determined by endomyocardial biopsy. Baseline left ventricular contractility was assessed over a wide range of afterload generated by infusion of methoxamine. Contractile reserve was measured as the response to an infusion of dobutamine plus methoxamine. Before afterload challenge, baseline left ventricular percent fractional shortening was higher for the transplant patients than for the control subjects (36.5 5.7% vs 32.1 ± 2.1 %; p < .05). These differences occurred at a time that end-systolic wall stress (a measure of afterload) was significantly lower for the transplant patients (38 + 16 vs 50 ± 9 g/cm2; p < .05). When the left ventricular end-systolic pressure-dimension and stress-shortening relationships were determined for the transplant and control subjects, no differences in contractility or contractile reserve were noted. Thus the chronically denervated, transplanted, nonrejecting human left ventricle demonstrates normal contractile characteristics and reserve. Circulation 71, No. 5, 866-872, 1985. OVERALL PERFORMANCE of the denervated transplanted heart has been reported to be adequate under basal conditions in the absence of rejection.' However, no study has determined whether the transplanted human left ventricle has normal contractility and contractile reserve. Previous, investigations performed at rest or during exercise have used hemodynamic measurements at cardiac catheterization,1"6 ejection phase indexes of left ventricular performance determined by echocardiography,7 surgically implanted radiopaque myocardial markers,9 '4 or radionuclide angiography'5 in an attempt to address these issues. These traditional approaches for assessing left ventricular performance are limited by their inability to distinguish abnormalities in contractility from alterations in preload or afterFrom the Division; of Cardiovascular Surgery, Harefield Hospital, Harefield, Middlesex, England, and the Cardiology Division, Department of Medicine, The University of Chicago Hospitals and Clinics, Chicago. Address for correspondence: Kenneth M. Borow, M.D., Director, Cardiac Noninvasive Imaging Laboratory, The University of Chicago Hospitals and Clinics, 950 East 59th St., Box 44, Chicago, IL 60637. Received Nov. 30, 1984; revision accepted Feb. 14, 1985. 866 load."6' 11 This is particularly important since the ejection phase indexes are often used inappropriately as measures of contractility, whereas they truly reflect a complex interaction between contractile state and loading conditions. 16 17 In recent years, several load-independent indexes of left ventricular contractility have been shown to be useful in the identification of preclinical ventricular dysfunction in humans.'8-25 One index is the slope of the relationship between left ventricular end-systolic pressure and dimension, parameters that are related linearly over a wide range of values for a given contractile state.26 27 This slope is independent of preload, incorporates afterload, and is a sensitive measure of contractility. 18-21 The relationship between left ventricular end-systolic wall stress (a measure of afterload) and percent fractional shortening also appears to be a reliable and clinically useful index of contractility in patients with normal intravascular volume.28 29 In this study, these two end-systolic indexes were used to assess left ventricular contractility in.transplanted and normal hearts under baseline and augmented inotropic conditions. CIRCULATION by gest on M ay 8, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-VENTRICULAR PERFORMANCE