Increasing glutamate promotes ischemia-reperfusion-induced ventricular arrhythmias in rats in vivo.

BACKGROUND

Glutamate mediates cerebral ischemia injury via N-methyl-D-aspartate (NMDA) receptor-coupled ion channels, but the activities of glutamate in the heart remain unclear.

AIMS: To investigate whether or not glutamate contributes to ischemia- and reperfusion (IR)-induced arrhythmias.

METHODS

Myocardial IR was induced by occlusion of the left anterior descending coronary artery for 30 min and reperfusion for another 30 min. A score system was used to quantify arrhythmias. MK801 (a noncompetitive NMDA receptor antagonist), dihydrokainate (DHK, a glutamate transporter inhibitor) and gabapentin (GBP, a glutamate release inhibitor) were used before ischemia. Serum glutamate levels, Ca(2+)-ATPase activity, SERCA2a protein expression and myocardial mitochondrial Ca(2+) content were assayed.

RESULTS

Myocardial IR caused a significant increase in serum glutamate and high incidences of ventricular arrhythmias. GBP and MK801 significantly ameliorated ventricular arrhythmias, improved SERCA2a expression and sarcoplasmic reticulum Ca(2+)-ATPase activity and reduced Ca(2+) accumulated in mitochondria. By contrast, DHK significantly exacerbated reperfusion-related arrhythmias and mitochondrial Ca(2+) overload while it decreased SERCA2a expression and activity.

CONCLUSION

This study showed that glutamate mediates reperfusion arrhythmias, and the corresponding mechanism may be associated with Ca(2+) overload via the NMDA receptor. Reperfusion arrhythmias may be prevented by inhibiting the release of glutamate or by antagonizing NMDA receptors.