Left ventricular and myocyte structure and function following chronic ventricular tachycardia in rabbits

Recent studies have shown that chronic pacing induced tachycardia in large animals such as dogs and pigs causes congestive heart failure accompanied by myocyte contractile abnormalities, neurohormonal activation, alterations in sarcolemmal receptor systems, and changes in myocardial structure. However, fundamental studies directed at identifying basic contributory mechanisms responsible for the development of this form of heart failure are problematic in these large animals. Accordingly, the present study examined the direct effects of pacing induced tachycardia upon LV and myocyte structure and function in the adult rabbit. Twelve adult rabbits (New Zealand White; 3.5-4.5 Kg) underwent 30 days of pacing induced ventricular tachycardia (VT; right ventricular paced, 400 bpm) and 12 additional age and weight matched rabbits served as controls. Echocardiography revealed increased LV end-diastolic dimension (1.92 +/- 0.04 vs 1.10 +/- 0.20 cm; p < 0.05) and decreased fractional shortening (41.5 +/- 3 vs 22.3 +/- 4%; p < 0.05) in the VT group compared to controls with no change in LV mass. Steady-state isolated myocyte contractile function was significantly reduced in the VT group compared to control. For example, isolated myocyte velocity of shortening was 41 +/- 2 microns/s in the VT group compared to 84 +/- 5 microns/s for controls (p < 0.05). In the presence of 8 mM extracellular Ca2+, myocyte velocity of shortening was 40% lower in the VT group compared to controls. Finally, myocyte contractile responsiveness with beta-adrenergic receptor stimulation was reduced by 52% in the VT group compared to controls. Isolated myocyte length significantly increased in the VT group compared to control (157 +/- 3 vs 128 +/- 2 microns; p < 0.05) with a concomitant decrease in cross-sectional area (274 +/- 6 vs 400 +/- 31 microns 2; p < 0.05). Myocyte myofibril volume fell by 27% in the VT group compared to control with no change in mitochondrial percent volume. In summary, this study demonstrated that chronic pacing induced tachycardia in rabbits caused: 1) LV dilation and dysfunction, 2) depressed isolated myocyte contractile function and inotropic responsiveness, and 3) alterations in myocyte structure and composition. The changes in LV and myocyte function and structure following chronic tachycardia in rabbits are similar to that reported previously with tachycardia induced heart failure in larger animals. These findings suggest that this rabbit model of chronic tachycardia may provide a useful and practical means by which to examine basic mechanisms responsible for the development of congestive heart failure.