LEFT-VENTRICULAR AND MYOCYTE STRUCTURE AND FUNCTION FOLLOWING CHRONICVENTRICULAR-TACHYCARDIA IN RABBITS

Recent studies have shown that chronic pacing induced tachycardia in l arge animals such as dogs and pigs causes congestive heart failure acc ompanied by myocyte contractile abnormalities, neurohormonal activatio n, alterations in sarcolemmal receptor systems, and changes in myocard ial structure. However, fundamental studies directed at identifying ba sic contributory mechanisms responsible for the development of this fo rm of heart failure are problematic in these large animals. Accordingl y, the present study examined the direct effects of pacing induced tac hycardia upon LV and myocyte structure and function in the adult rabbi t. Twelve adult rabbits (New Zealand White; 3.5-4.5 Kg) underwent 30 d ays of pacing induced ventricular tachycardia (VT; right ventricular p aced, 400 bpm) and 12 additional age and weight matched rabbits served as controls. Echocardiography revealed increased LV end-diastolic dim ension (1.92 +/- 0.04 vs 1.10 +/- 0.20 cm; p < 0.05) and decreased fra ctional shortening (41.5 +/- 3 vs 22.3 +/- 4 %; p < 0.05) in the VT gr oup compared to controls with no change in LV mass. Steady-state isola ted myocyte contractile function was significantly reduced in the VT g roup compared to control. For example, isolated myocyte velocity of sh ortening was 41 +/- 2 mu m/s in the VT group compared to 84 +/- 5 mu m /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 compar ed to controls. Finally, myocyte contractile responsiveness with beta- adrenergic receptor stimulation was reduced by 52 % in the VT group co mpared to controls. Isolated myocyte length significantly increased in the VT group compared to control (157 +/- 3 vs 128 +/- 2 mu m; p < 0. 05) with a concomitant decrease in cross-sectional area (274 +/- 6 vs 400 +/- 31 mu m(2); p < 0.05). Myocyte myofibril volume fell by 27 % i n the VT group compared to control with no change in mitochondrial per cent volume. In summary, this study demonstrated that chronic pacing i nduced tachycardia in rabbits caused: 1) LV dilation and dysfunction, 2) depressed isolated myocyte contractile function and inotropic respo nsiveness, and 3) alterations in myocyte structure and composition. Th e changes in LV and myocyte function and structure following chronic t achycardia in rabbits are similar to that reported previously with tac hycardia induced heart failure in larger animals. These findings sugge st that this rabbit model of chronic tachycardia may provide a useful and practical means by which to examine basic mechanisms responsible f or the development of congestive heart failure.