Left ventricular remodelling and disparate changes in contractility and relaxation during the development of and recovery from experimental heart failure.

Abstract

Canine pacing induced heart failure is characterised by impaired left ventricular contractility and relaxation, and clinical recovery 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 response to beta adrenergic stimulation during heart failure and after recovery. Eight dogs were paced (250 beats.min-1) for 3 weeks to severe heart failure and recovered for 4 weeks after cessation of pacing. During these periods, haemodynamic and echocardiographic measurements were made with and without beta adrenergic stimulation. 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 control, p < 0.01] and a downward displacement of the velocity of circumferential fibre shortening-end systolic wall stress relation. Impaired left ventricular relaxation was evidenced by raised end diastolic pressure [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 ability of beta adrenergic stimulation to augment contractility was reduced: there was blunted dP/dt response to dobutamine. The ability of beta adrenergic stimulation to shorten relaxation was maintained: there was a similar degree of shortening of tau by dobutamine. At recovery, dP/dt returned to control and the shortening-stress relation moved upward, suggesting return of contractility. The response of dP/dt to dobutamine was restored. However, tau remained prolonged indicating persistent abnormal relaxation. 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 differential capacity for recovery of contractility and relaxation.