MECHANISMS OF VOLUME-INDUCED INCREASE IN LEFT-VENTRICULAR CONTRACTILITY

Volume-induced increases in left ventricular (LV) contractility were s tudied in 18 anesthetized dogs. Denervation eliminated cardiac reflexe s, and hearts were paced at 100 +/- 9 (SD) beats/min. Acute volume loa ding increased LV end-diastolic pressure from approximately 4 to 14 mm Hg within 1 min. Contractility increased over 10 min as measured by a decrease in end-systolic length (ESL) (sonomicrometer) at matched LV e nd-systolic pressure (ESP) or increase in LVESP measured at matched ES L. Volume-dependent increase in contractility was not attenuated by ve rapamil (0.3 +/- 0.2 mug/kg iv, n = 6) or myocardial stunning (15 min ischemia, 30 min reperfusion, n = 6) but was attenuated by ryanodine ( 1-16 mug/kg iv, n = 6), which alters calcium release from the sarcopla smic reticulum. From 1 to 10 min after volume loading, LV anterior ESL (measured at LVESP 132 +/- 12 mmHg) decreased by 6.7 +/- 0.5% before, but only by 4.0 +/- 1.7% after 1 mug/kg ryanodine (P < 0.05). The LVE SP (measured at anterior ESL 11.6 mm) increased 32 +/- 4 mmHg before, but only by 17 +/- 12 mmHg after 1 mug/kg ryanodine. In conclusion, ac ute volume loading produces a time-dependent increase in LV contractil ity, which is mediated in part by an increase in calcium release from the sarcoplasmic reticulum.