Transition From Compensated Hypertrophy to Intrinsic Myocardial Dysfunction During Development of Left Ventricular

Background. Patients with aortic stenosis have a period of compensated left ventricular hypertrophy but may eventually develop congestive heart failure. Previous experimental studies showed either normal myocardial contractility in mild short-term pressure overload or myocardial dysfunction with severe pressure overload. Transition from compensated left ventricular hypertrophy to myocardial dysfunction has not been experimentally demonstrated in an adult large animal. Controversial issues in pressure-overload hypertrophy include whether the left ventricular dysfunction is due to insufficient hypertrophy (afterload mismatch) or to intrinsic myocardial dysfunction and whether diastolic dysfunction precedes systolic dysfunction. Methods and Results. We induced left ventricular hypertrophy (41 % increase in left ventricular to body weight ratio) by gradually tightening a hydraulic constrictor around the ascending aorta in 9 chronically instrumented conscious sheep. Afterload (end-systolic stress) elevation remained constant (approximately 33 % greater than baseline) by adjustment of the aortic constrictor over 6 weeks, gradually increasing left ventricular pressure (from 117±6 to 163±5 mm Hg) as hypertrophy developed. Four sets (baseline, 2 weeks, 4 weeks, and 6 weeks) of serial hemodynamic studies were performed in each animal with «8-blockade, first with and then without aortic constriction to mechanically match loading conditions