PROLONGED EJECTION DURATION HELPS TO MAINTAIN PUMP PERFORMANCE OF THERENAL-HYPERTENSIVE-DIABETIC RAT-HEART - CORRELATIONS BETWEEN ISOLATEDPAPILLARY-MUSCLE FUNCTION AND VENTRICULAR PERFORMANCE IN-SITU

Objective: The purpose of this study was to examine the degree to whic h mechanical alterations in left ventricular papillary muscles of rena l hypertensive-diabetic rat hearts correlate with functional measureme nts made on the same hearts in situ. Methods: Female Wistar rats weigh ing 170-200 g were made hypertensive by placing a 0.24 mm clip on the left renal artery, and made diabetic 1 week later by a single intraven ous injection of streptozotocin (60 mg/kg), Approximately 3-5 months l ater hemodynamic measurements including left ventricular pressure and dP/dt(max) arterial pressure and aortic flow were made on control and hypertensive-diabetic hearts in situ and correlated with mechanical me asurements in left ventricular papillary muscles isolated from the sam e hearts. Body and tissue weights and biochemical and histological mea surements were made at the time of sacrifice. Results: Hypertensive-di abetic rats which survived to the time of study had decreased body wei ghts, increased left ventricular weight?, and increased right ventricu lar weight to body weight and lung weight to body weight ratios. Those rats which died before the scheduled in-situ measurements had signifi cantly more severe hypertension, greater left ventricular hypertrophy, increased right ventricular and lung weights, and mon interstitial fi brosis than either surviving hypertensive-diabetics or controls. Rates of isometric tension development (normalized) and relaxation as well as shortening and relaxation velocities were significantly depressed i n papillary muscles from hypertensive-diabetic rat hearts despite unch anged developed tension and peak shortening. Time to peak tension and time to peak shortening were markedly prolonged. Mean aortic flow was maintained in the hypertensive-diabetic group despite significant depr ession of left ventricular dP/dt(max) (normalized), peak aortic flow, peak aortic flow acceleration and heart rate. There was also significa nt depression of left ventricular - dP/dt(max). Ejection duration was markedly prolonged and correlated with both time to peak shortening in vitro and with stroke volume in vivo, Conclusions: Surviving hyperten sive-diabetic rats were not in overt congestive heart failure; neverth eless, their hearts showed abnormal contractile performance which was qualitatively and quantitatively similar to that of left ventricular p apillary muscles obtained from them. Depression of peak aortic flow, p eak aortic flow acceleration and heart rate in the hypertensive-diabet ic group was offset by increased ejection duration, resulting in norma l mean aortic flow. The close correlation of ejection duration with ti me to peak shortening of the isolated papillary muscles suggests that it is a manifestation of an intrinsic change in the myocardium. To the extent that this prolongation is already maximized, further decreases in contractile speed would be expected eventually to cause depressed pump function and congestive heart failure. The possibility that this sequence of events occurred in the dying animals needs to be examined by evaluating in-vitro and in-vivo myocardial function at various stag es of this disease model.