Effect of N-Methyl-D-Aspartate receptor inhibition on acute myocardial infarction in rats

Abstract

Objective To investigate the effects of N-Methyl-D-Aspartate receptor (NMDAR) inhibition on acute myocardial infarction (AMI) in respect of reduction in the incidence of ventricular arrhythmias (VAs) and infarct size in a rat model in order to provide experimental evidence for the prevention and treatment of AMI. Methods A total of 45 Sprague-Dawley rats were randomly (random number) divided into Sham group, AMI group and AMI plus MK801 (a specific inhibitor of NMDAR) group (treatment group). The ligation of the left anterior descending coronary artery was performed to induce AMI, and the occurrence of VAs within 30 minutes period during the early stage of infarction was recorded. Then the telemetry ECG was implanted to record the incidence of VAs during the later 24-hour period. The histology staining was performed to measure the level of Cx43, apoptotic body and infarction size; and the expression of NMDAR protein was measured with western-blot. Results Compared with the sham group, the NMDAR expression was markedly increased in the MI group [(1.12±0.09) vs. (0.54±0.06) , P < 0.01]; Compared with the MI group, there was marked decrease in the incidences of VAs in treatment group during both 30 min period and 24 hour period (P <0.01) .In addition, the higher Cx43 expression [(1.68±0.27)% vs. (0.74±0.15)%, P <0.01], fewer apoptotic bodies [(13.49±3.25)% vs. (32.53±7.21)%, P <0.01], smaller infarction size [(36.58±2.57)% vs. (43.72±3.11)%, P < 0.01]and lower NMDAR expression [(1.12±0.09) vs. (0.81±0.07) , P <0.01]were found in the treatment group than those in MI group. Conclusions The NMDAR inhibition would protect against VAs and reduce infarct size in AMI rats, and the inhibition of Cx43 degradation and apoptosis may be the potential mechanism. Key words: N-Methyl-D-Aspartate receptor; Acute myocardial infarction; Ventricular arrhythmias; Apoptosis