Influence of temperature on the positive inotropic effect of levosimendan, dobutamine and milrinone.

BACKGROUND AND OBJECTIVE: Patients in cardiac surgery and critically ill patients often demonstrate either hypothermia or fever. In addition, owing to heart failure, they frequently require inotropic support. The relative effectiveness of modern inotropic agents at various temperatures has not yet been evaluated. Therefore, we investigated the influence of levosimendan, dobutamine and milrinone on the contractile response of myocardial trabeculae at various temperatures. METHODS: A total of 120 guinea pig ventricular trabeculae were placed in oxygenated 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES) buffer, stimulated at a frequency of 1.3 Hz and randomly assigned to a temperature of 31 degrees C, 34 degrees C, 37 degrees C or 40 degrees C. Concentrations of all substances were increased stepwise from 10(-9) to 10(-5) mol l(-1) (milrinone up to 10(-4) mol l(-1)). Maximum developed force, time to peak tension, Tsystolic(50%) and Tdiastolic(50%) were continuously recorded. RESULTS: All agents showed a dose-dependent positive inotropic effect (P < 0.0001 for all). Levosimendan acted at every temperature as a positive inotrope (P = 0.0643). Dobutamine-related inotropy showed a clear trend towards temperature dependence, although statistical evaluation did not prove this (P = 0.0624). Milrinone-related inotropy was abolished at 31 degrees C and 34 degrees C, and temperature dependence was significant (P < 0.0001). Hypothermia induced a positive inotropic effect. CONCLUSION: Our results suggest no modulation of levosimendan-induced inotropy under the experimental temperatures tested. This observation is possibly due to its Ca2+-sensitizing mechanism, which might not be influenced by temperature-related changes in intracellular Ca2+ levels. In contrast, the inotropic effect of cyclic AMP-coupled dobutamine and milrinone is suppressed under hypothermia-related interaction with intracellular Ca2+ homeostasis. Hence, levosimendan might prove to be the preferred inotropic drug in hypothermic patients.

Xenon does not impair the responsiveness of cardiac muscle bundles to positive inotropic and chronotropic stimulation.

BACKGROUND: Most volatile anesthetics exhibit a direct myocardial depressant effect. This side effect often limits their applicability in patients with impaired cardiac function. Xenon is a new gaseous anesthetic that did not show any adverse cardiovascular effects in clinical and experimental studies. The authors tested the hypothesis that xenon does not affect myocardial contractility or the positive inotropic effect of isoproterenol, calcium, and increase in pacing rate in isolated guinea pig ventricular muscle bundles. METHODS: Thin ventricular muscle bundles from guinea pig hearts with a mean diameter of 0.4-0.45 mm were prepared under stereomicroscopic control. Force of contraction and contraction times were studied in muscles superfused with medium equilibrated with either 65% xenon and 35% oxygen (xenon group), 1.2% isoflurane in oxygen (isoflurane group), or 65% nitrogen and 35% oxygen (control group). In addition, the positive inotropic effects of calcium, isoproterenol (10(-10)-3 x 10(-8) M) and increasing frequency (0.5-2 Hz) were studied during xenon and isoflurane exposure. RESULTS: In contrast to isoflurane, xenon did not alter myocardial force of contraction or contraction times. The positive inotropic effect of isoproterenol, calcium, and increasing pacing frequencies did not differ between the muscles exposed to xenon and the control group. Isoflurane elicited the expected negative inotropic effect (30% reduction of force of contraction) but did not impair the response to inotropic stimuli. CONCLUSIONS: Xenon does not alter myocardial contractility and the response to inotropic stimuli such as calcium, isoproterenol, or increase in pacing frequency in isolated guinea pig ventricular muscle bundles.