LEFT-VENTRICULAR REMODELING AND DISPARATE CHANGES IN CONTRACTILITY AND RELAXATION DURING THE DEVELOPMENT OF AND RECOVERY FROM EXPERIMENTAL HEART-FAILURE

Objectives: Canine pacing induced heart failure is characterised by im paired left ventricular contractility and relaxation, and clinical rec overy after cessation of pacing. It is unclear whether the impairment is responsive to adrenergic stimulation. The aim of this study- was to assess left ventricular contractility and relaxation and their respon se to beta adrenergic stimulation during heart failure and after recov ery. Methods: Eight dogs were paced (250 beats.min-1) for 3 weeks to s evere heart failure and recovered for 4 weeks after cessation of pacin g. During these periods, haemodynamic and echocardiographic measuremen ts were made with and without beta adrenergic stimulation. Results: At heart failure, impaired left ventricular contractility was evidenced by reduced dP/dt [1412(SD 156) mm Hg.s-1 from 2437(382) mm Hg.s-1 at c ontrol, p<0.01] and a downward displacement of the velocity of circumf erential fibre shortening-end systolic wall stress relation. Impaired left ventricular relaxation was evidenced by raised end diastolic pres sure [35(6) mm Hg from 7(4) mm Hg at control, p < 0.01] and prolonged relaxation time constant tau [28(4) ms from 17(6) ms, p<0.01]. The abi lity of beta adrenergic stimulation to augment contractility was reduc ed: there was blunted dP/dt response to dobutamine. The ability of bet a adrenergic stimulation to shorten relaxation was maintained: there w as a similar degree of shortening of tau by dobutamine. At recovery, d P/dt returned to control and the shortening-stress relation moved upwa rd, suggesting return of contractility. The response of dP/dt to dobut amine was restored. However, tau remained prolonged indicating persist ent abnormal relaxation. Conclusion: In pacing induced heart failure, there is a dissociation between the normal ability of beta adrenergic stimulation to augment contractility and shorten relaxation, and a dif ferential capacity for recovery of contractility and relaxation.