The Combined Effect of Desflurane and Milrinone on the Function of the Isolated Rat Heart

Yoon, Joon Ro; Kong, Myoung Hoon; Kim, Ki Nam; Lee, Il Ok; Lee, Mi Kyoung; Lim, Sang Ho; Choi, Young Seok; Kim, Nan Suk

Abstract

BACKGROUND: Desflurane depresses the contractile function of the myocardium. It also causes direct coronary vasodilation. Milrinone, a phosphodiesterase III inhibitor, usually increases myocardial contractility and also has vasodilatory activity. Some inhalation anesthetic agents, such as isoflurane, are safely combined with phosphodiesterase III inhibitors clinically, but milrinone sometimes causes significant hypotension by reducing systemic vascular resistance. The purpose of this study was to evaluate the effect of the combined use of desflurane and milrinone on the function of the isolated rat heart. METHOD: Thirty isolated rat hearts were divided into two groups. [Group 1 (n = 15): desflurane, Group 2 (n = 15): desflurane and milrinone] They were perfused continuously with modified Krebs' solution in a Langendorff retrograde perfusion apparatus. After measuring the control values of the hemodynamic and oxygenation parameters in each group, we administered 6.6 vol% of desflurane to both groups and added sequential perfusion of modified Krebs' solution containing 0.5, 1.0, and 1.5mug/ml of milrinone in Group 2 and then measured the parameters and analyzed them statistically.
RESULTS
Baseline measurements in both groups were not statistically different. In Group 1, desflurane significantly decreased LVP (55+/-5 mmHg), dp/dt (557+/-65 mmHg/sec) and MVO2 (71.2+/-16.3 ml/g/min) after 15 minutes. CF (13.9+/-3.1 ml/g/min) and DO2 (176.7+/-43.4 ml/g/min) were increased after 15 minutes. There was no further change after this. In Group 2, desflurane decreased LVP (53+/-18 mmHg), dp/dt (558 90 mmHg/sec) and MVO2 (72.0+/-11.0 ml/g/min) and increased CF (14.2+/-1.9 ml/g/min) and DO2 (175.3+/-29.1 ml/g/min). But, there was no significant difference in the effects of desflurane between the two groups. Milrinone restored LVP, dp/dt and MVO2 to the baseline level, but not with dose-dependency. Desflurane-induced elevated CF and DO2 did not show further changes.
CONCLUSIONS
These findings suggest that milrinone increased myocardial contractility and restored the desflurane-induced myocardial depression of the isolated rat heart without further increase of oxygen consumption from the baseline control value. In addition, no additive effects was observed on coronary blood flow when these two agents were used in combination.