Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model

Introduction: Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15°C. Methods: Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15°C (60. min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30. min at 37°C and during cooling. Results: In normothermic controls continuous milrinone infusion for 90min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15°C were found: Compared to saline treated animals throughout cooling from 33 to 15°CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24°C. Likewise, during cooling between 33 and 28°C also LVdP/dt_max was significantly higher in the milrinone group. Conclusions: Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15°C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15°C.