Glutamate release predicts ongoing myocardial ischemia of rat hearts

Abstract

Background. Glutamate metabolism is associated with myocardial ischemia-reperfusion, but it is not clear whether glutamate reveals ongoing ischemia (OI). We evaluated whether microdialysis would detect OI induced by coronary artery ligation in a rat cardiac transplantation model. Material and methods. A total of 24 Fischer 344 rats underwent syngeneic heterotopic cardiac transplantation. Of these, 16 rats underwent ligation of the left anterior coronary artery (LAD) of the heart to induce ongoing ischemia (OI), of which eight grafts received intra-aortally Gabapentin (12 mg/graft), a glutamaterelease inhibitor and eight grafts with transplantation only served as the control. With a microdialysis catheter samples for glucose, lactate, pyruvate, glutamate, and glycerol were analysed spectrophotometrically. Histology and aquaporin 7 evaluations were performed after graft harvesting. Results. Glutamate was elevated after 15 min of reperfusion in OI as compared with Control (14.31 ± 5.03 μM vs 6.75 ± 2.21 μM, p = 0.05), respectively. Glycerol remained high in OI (61.89 ± 46.13 μM to 15.84 ± 0.85 μM, p = ns) and low in Control (12.33 ± 3.36 μM to 5.52 ± 0.25 μM, p = ns). Gabapentin decreased glutamate release from 7.32 ± 1.57 μM to 2.71 ± 0.64 μM, (p < 0.05) and resulted in decrease of glycerol levels from 24.64 ± 4.03 μM to 10.43 ± 2.49 μM, (p < 0.05) in OI. The expression of aquaporin 7 and histology confirmed OI. Conclusions. We suggest that glutamate release may be used as an early indicator of OI after cardiac arrest.

Key Words::

• Microdialysis
• Gabapentin
• glycerol
• aquaporin 7 protein
• rat
• cardiac transplantation

Acknowledgements

We thankfully acknowledge the support offered by The Research Foundation of Tampere University Hospital, Tampere Tuberculosis Foundation, The Finnish Heart Association, The China Scholarship Council and Guangdong International Cooperation Fund (#2007B050200024). We thank Maarit Patrikainen for technical assistance with evaluation of aquaporin 7.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.