Effects of Trimetazidine on Rat Heart Muscle during Hypoxia and Reperfusion

Objective: Trimetazidine (TMZ) is a cardioprotective drug with anti-ischemic and anti-hypoxic metabolic actions. This study aims to investigate the impact of TMZ on the contractile and recovery properties of isolated papillary heart muscle under normoxic and hypoxic conditions. Methods: Left ventricular papillary muscles were harvested from 40 Wistar rats. After a 10-minute equilibration period in a normoxic bath, contractile and relaxation responses were recorded in normoxic and hypoxic baths with varying concentrations of TMZ (0 M, 5 x 10–6 M, and 5 x 10-5 M). The specimens were then re-perfused with oxygenated Krebs-Henseleit solution (95% O2 and 5% CO2) and equilibrated for 10 minutes in a normoxic bath. Recovery contractile and relaxation responses were measured. Results: Both doses of TMZ had a negative inotropic effect on muscle (p < 0.001), resulting in a limited decline in biomechanical performance in the hypoxic bath (p < 0.001). However, both doses of TMZ also increased the recovery biomechanical performance compared to the control group (p < 0.001). Conclusions: Under normoxic conditions, TMZ pretreatment alone did not show any cardioprotective effect. However, adding TMZ at a concentration of 5 x 10-6 M, a therapeutic level in humans, reduced ischemic contracture and improved postischemic recovery of contraction forces in both pretreated and control groups. Despite trimetazidine's negative inotropic effect under normoxic conditions, near-therapeutic doses of the drug have significant protective effects on isolated papillary heart muscle contractility, leading to improved contractile function under hypoxic conditions.