ASYNCHRONY AND RYANODINE MODULATE LOAD-DEPENDENT RELAXATION IN THE CANINE LEFT-VENTRICLE

Load-dependent relaxation was studied in six anesthetized dogs by infl ating an intra-aortic balloon to increase peak left ventricular (LV) p ressure by 1-20 mmHg within a single cardiac cycle. A series of timed and graded pressure loads was produced by inflating the balloon either during diastole (early loads) or midsystole (midsystolic pressure loa ds). The rate of LV pressure fall was measured with the time constant (tau). There was a significant increase in tau with 63 midsystolic pre ssure loads [tau increased 1.4 +/- 0.1% (SE)/mmHg increase in peak LV pressure] but not with 67 early pressure loads (-0.5 +/- 0.1%/ mmHg). This difference remained with LV pacing-induced asynchrony (tau increa sed 1.8 +/- 0.1%/mmHg with 54 midsystolic pressure loads compared with -0.2 +/- 0.1%/mmHg with 56 early pressure loads) and after 5 mu g/kg of intravenous ryanodine (tau increased 1.0 +/- 0.2%/mmHg with 58 mids ystolic pressure loads compared with -0.7 +/- 0.1%/mmHg with 59 early pressure loads). When compared with control, asynchrony significantly augmented and ryanodine significantly attenuated the effects of midsys tolic pressure loads. In conclusion, asynchrony and ryanodine modulate the extent of load-dependent relaxation in the intact left ventricle.