The Effect of Diazepam on the Function of Hypertrophied Rats’ Hearts in Ischemia-Reperfusion Conditions

Abstract

: Background: Hypertrophied hearts are susceptible to ischemic injury. Besides, cardiac vulnerability could be changed in the presence of diazepam. Objectives: The current study aimed to investigate the effect of diazepam on hypertrophied rats’ hearts in ischemia-reperfusion conditions. Materials and Methods: Male Wistar rats (body weight 210 - 270 gr) were administered with isoproterenol (4 mg/kg body weight, intraperitoneally for 7 days) alone or along with diazepam (1 and 5 mg/kg body weight, intraperitoneally for 5 days). The control rats received normal saline intraperitoneally. The animal s’ hearts were isolated according to langendorff setup and were passed through baseline, ischemia, and reperfusion stages. Then, cardiac mass index (ratio of heart weight to body weight) was measured. Cardiac functional parameters, including left ventricular developed pressure and rate pressure product, were also assessed at baseline and following ischemia. The data were analyzed using ANOVA and P < 0.05 was considered to be statistically significant. Results: Isoproterenol-induced cardiac hypertrophy was significantly reduced by both doses of diazepam compared to the group only treated with isoproterenol (P < 0.05) although it did not reach the control level. However, diazepam administration (1 and 5 mg/kg) did not change isoproterenol-induced exacerbated ischemia-reperfusion injury compared to the control group (P = 0.001 and P = 0.013, respectively). Conclusions: Diazepam relatively prevented the isoproterenol–induced cardiac hypertrophy in the animal model. This effect could be probably explained by the modification of oxidative stress and preservation of intracellular calcium concentration. Considering the common clinical usage of diazepam, as a peripheral benzodiazepine ligand, antihypertrophic effects of diazepam are recommended to be investigated in clinical trials.