Prolonged ejection duration helps to maintain pump performance of the renal-hypertensive-diabetic rat heart: correlations between isolated papillary muscle function and ventricular performance in situ

Objective: The purpose of this study was to examine the degree to which mechanical alterations in left ventricular papillary muscles of renal hypertensive-diabetic rat hearts correlate with functional measurements made on the same hearts in situ. Methods: Female Wistar rats weighing 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 intravenous injection of streptozotocin (60 mg/kg). Approximately 3–5 months later hemodynamic measurements including left ventricular pressure and dP/dtmax, arterial pressure and aortic flow were made on control and hypertensive-diabetic hearts in situ and correlated with mechanical measurements in left ventricular papillary muscles isolated from the same hearts. Body and tissue weights and biochemical and histological measurements were made at the time of sacrifice. Results: Hypertensive-diabetic rats which survived to the time of study had decreased body weights, increased left ventricular weights and increased right ventricular weight to body weight and lung weight to body weight ratios. Those rats which died before the scheduled in-situ measurements had significantly more severe hypertension, greater left ventricular hypertrophy, increased right ventricular and lung weights, and more interstitial fibrosis 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 in papillary muscles from hypertensive-diabetic rat hearts despite unchanged 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 depression of left ventricular dP/dtmax (normalized), peak aortic flow, peak aortic flow acceleration and heart rate. There was also significant depression of left ventricular −dP/dtmax. Ejection duration was markedly prolonged and correlated with both time to peak shortening in vitro and with stroke volume in vivo. Conclusions: Surviving hypertensive-diabetic rats were not in overt congestive heart failure; nevertheless, their hearts showed abnormal contractile performance which was qualitatively and quantitatively similar to that of left ventricular papillary muscles obtained from them. Depression of peak aortic flow, peak aortic flow acceleration and heart rate in the hypertensive-diabetic group was offset by increased ejection duration, resulting in normal mean aortic flow. The close correlation of ejection duration with time 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 stages of this disease model.