INITIATION OF VENTRICULAR EXTRASYSTOLES BY MYOCARDIAL STRETCH IN CHRONICALLY DILATED AND FAILING CANINE LEFT-VENTRICLE

Background Stretch-induced arrhythmias (SIAs) can be elicited in norma l canine left ventricles by transient diastolic dilatation. Since clin ically important ventricular arrhythmias arise most commonly in failin g and dilated ventricles, we hypothesized that the arrhythmogenic effe ct of transient diastolic stretch would be enhanced in chronically dil ated failing canine hearts. Methods and Results Heart failure was indu ced in seven dogs by right ventricular pacing at 250 min(-1) for 20.2/-1.6 days. Left ventricular (LV) mechanical properties were measured in vivo with serial echocardiograms in these seven dogs with the dogs awake and tranquilized to confirm the development of LV dilation and f ailure. By the third week of pacing, average short-axis area ejection fraction decreased by 64.3% (P<.001) as end-diastolic and end-systolic diameters increased by 25.9% and 50.7% respectively (P<.001). After h eart failure was established, the hearts were harvested and in vitro d ata were obtained as an isolated, blood-perfused ventricle preparation . A computerized servo pump system connected to an LV intracavitary ba lloon was used to measure and control LV volume. Results were compared with in vitro data obtained from eight ventricles not subjected to pa cing (controls). LV contractility, quantitated in vitro as the slope o f the peak isovolumic pressure-volume relation (E(max)) normalized to LV cavity size, was much lower in the heart failure group than in cont rols (182+/-18 versus 365+/-38 mm Hg, P<.001). In all isolated hearts, SLAs were induced using an electromechanical stimulation protocol in which eight paced beats at 2 Hz were followed by a transient increase in LV volume during early diastole. Prestretch volume (Vi) was selecte d to yield end-diastolic pressures of 4 to 8 mm Hg in all hearts. The fractional increase in LV volume (Delta V) that produced SIAs 50% of t he time (Delta V-50/V-i) was smaller in failing hearts than in control s (0.78+/-0.04 versus 1.18+/-0.17, P=.009), indicating an increased se nsitivity to SIAs in the failing hearts. Although ventricular pairs we re occasionally induced in both groups, the great majority of the arrh ythmias induced in both groups were single extrasystoles, and nonsusta ined runs of ventricular tachycardia were never elicited in either gro up. LV end-diastolic and peak stretch pressures were similar in the tw o groups, but LV end-diastolic wall stress was higher by 35.7% (P=.029 ) in the dilated failing ventricles because LV hypertrophy, which tend s to normalize wall stress as the heart dilates, did not occur during the 3 weeks of pacing. For stretch stimuli of comparable arrhythmogeni c effectiveness, peak LV wall stress during stretch was similar in the two groups, whereas the fractional increase in volume was significant ly smaller in the heart failure group, indicating impaired viscoelasti c properties in the failing ventricles. In five control ventricles, ac ute exposure to 0.5 mu mol/L dobutamine increased ventricular sensitiv ity to the induction of SIAs, as shown by a decrease in Delta V-50/V-i from 1.27+/-0.16 to 1.06+/-0.11 (P=.04). Conclusions Altered mechanic al properties and/or neurohumoral adaptations associated with chronic dilation and failure predispose the ventricle to induction of ventricu lar extrasystoles by transient LV diastolic stretch.