Direct cardiac effects in isolated perfused rat hearts measured at increasing concentrations of morphine, alfentanil, fentanyl, ketamine, etomidate, thiopentone, midazolam and propofol

Abstract

The direct cardiac effects of morphine, alfentanil, ketamine, etomidate, thiopentone, midazolam and propofol were measured in isolated Wistar rat hearts. Experiments were performed using a multiple conlumnar Langendorff apparatus and the hearts were perfused with a modified Tyrode solution under constant pressure. Each drug was applied from a different column in rising concentrations at 5-min intervals. Dose ranges were chosen to compare effects at sub-clinical, clinically relevant and more than clinical concentrations. Six rat hearts were chosen at random for each drug. Only thiopentone reduced contractile force at a clinically relevant concentration: measured as g contractility per g heart weight⁻¹ (mean±standard deviation), base-line contractility was 8.8±2.4, and contractility at 10⁻⁴ mol litre⁻¹ thiopentone was 7.1±1.5 (P<0.01). Alfentanil was the only drug to have no significant effect on the isolated heart at any concentration. Propofol was not cardiodepressant at clinically relevant concentrations, but had a lower therapeutic range than the other drugs.