The Effects And Mechanisms Of N-methyl-d-aspartate Receptor On Acute Myocardial Infarction In Rats

Objective1. Aim to investigate the Effects and mechanisms of N-methyl-d-aspartate Receptor on Myocardial Infarction in Rats.2. To investigate the effect of NMD A on intracellular calcium operations.Methods1. A total of 60 Sprague-Dawley rats were randomly assigned to a Sham group, an AMI group, AMI plus NMD A group (NMD A group) and an AMI plus MK801 group (MK-801 group).The ligation of the left anterior descending coronary artery was performed to induce AMI, we record the occurrence of VAs within 30 minutes period during the early infarction. 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 area; and the expression of Cx43 and NMDAR protein was measured with western-blot.2. The aim to investigate the effect of NMDAR activation on the calcium operation of ventricular myocytes in rats. After incubating ventricular myocytes with NMDA,NMDA+MK801, the confocal microscopy was using to measure the calcium concentration, sarcoplasmic reticulum calcium concentration, the amplitude of calcium transients, the incidence of spontaneous calcium release events in rat ventricular myocytes.Results1. Compared with the sham group, the level of 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, the MK-801 group displayed a marked decrease in the incidence of VAs during both of 30 minutes and 24 hour periods(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 area (36.58±2.57% vs 43.72±3.11%,P<0.01) and fewer NMDAR expression (1.12±0.09 vs 0.81±0.07, P<0.01) were showed in the treatment group than those of MI group. Compared with the MI group, the NMDA group displayed a marked increase in the incidence of VAs during both of 30 minutes and 24 hour periods(P<0.01).In addition, the less Cx43 expression (0.32±0.08% vs 0.74±0.15%,P<0.01), more apoptotic bodies (36.26±2.58% vs 13.49±2.25%,P<0.01), lager infarction area(54.3±1.60% vs 48.62±1.51%,P<0.01). The Cx43 expression down-regulation and the NMDAR expression up-regulation were showed in the NDMA group (P<0.01).2. Compared with the control group, the NMDA group showed a significant increase in the cytoplasmic calcium concentration (239.3±7.5 nmol/L vs 128.9± 9.3 nmol/L, P<0.01), high calcium transient amplitude both under 0.5Hz (0.78± 0.06 vs 0.63±0.04, P<0.01) and 1Hz (2.94±0.13 vs 0.74±0.03, P<0.01), and increased spontaneous calcium release events under 1Hz pacing (P<0.01). Furthermore, compared with the control group, the sarcoplasmic reticulum calcium concentration was significantly increased (0.5Hz:3.52±0.09 vs 1.41±0.08, P<0.01; 1Hz:3.76± 0.11 vs 1.74±0.04, P<0.01), sarcoplasmic reticulum release of calcium scores were also significantly higher (0.5Hz:0.68±0.07 vs 0.42±0.05, P<0.01; 1Hz:0.78±0.08 vs 0.43±0.06, P<0.01) in the NMDA group.Conclusion1. Chronic NMDAR activation significant increases the incidence of ventricular arrhythmias and infarct size in rats with acute myocardial infarction, by down Cx43 and increased apoptosis. The inhibition of NMDAR can prevent the occurrence of ventricular arrhythmias and reduce infarct size in rats with acute myocardial infarction.2. NMDAR activation significant increase cytosolic calcium load, lead to calcium operation disorder, and significantly increase the sarcoplasmic reticulum calcium release events ultimately.