Effects of Trimetazidine on Rat Heart Muscle during Hypoxia and Reperfusion
Effects of trimetazidine on contractile and recovery contractile properties of isolated papillary rat heart muscle during hypoxia and reperfusion.Effects of trimetazidine on contractile and recovery contractile properties of isolated papillary rat heart muscle during hypoxia and reperfusion.
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Abstract
Abstract
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.
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