Metabolic differences have been reported between normal and hypertrophic hearts (Suleiman et al. 1998). Moreover, the expression and activity of the glutamate transporters, EAAT1 and 3 are significantly increased in hypertrophic compared to control heart (King et al. 2004a, b). This suggests that lower concentrations of glutamate will be needed to protect the hypertrophic myocardium against ischaemia and reperfusion injury. Therefore, the effect of supplementation with 0.5mM glutamate during ischaemia and reperfusion was investigated using isolated and perfused hypertrophic hearts from spontaneously hypertensive rats (SHR) and their corresponding control hearts from normotensive Wistar Kyoto (WKY) rats. Male SHR and WKY rats were humanely killed and the hearts dissected. Isolated working rat hearts were perfused with Krebs buffer at 37°C as described previously (Javadov et al. 2000). After 25 min equilibration in the working mode, hearts were exposed to normothermic global ischaemia for 20 min. Hearts were then reperfused and functional recovery and release of lactate dehydrogenase (LDH) determined. Where used, 0.5mM glutamate was present before and during ischaemia, but was washed out after 10 min reperfusion. Data are expressed as means ± S.E.M. of n=6-7 hearts. Hypertrophic hearts from SHR were more susceptible to ischaemia than control hearts from WKY. Recovery (%) in cardiac output (CO, aortic flow + coronary flow) was 76 ± 7 vs. 37 ± 3 for WKY and SHR respectively (p<0.01, unpaired t test). Glutamate significantly improved recovery of CO in SHR hearts (68 ± 7%, p < 0.05 vs. untreated SHR, unpaired t test), but did not affect WKY hearts (82 ± 7%,). Similarly, total release of LDH (IU/g dry weight) during the first ten minutes of reperfusion was higher in untreated SHR (9.9 ± 0.7, p<0.05, unpaired t test) compared to WKY (4.9 ± 0.6) and was significantly reduced with glutamate in the SHR (6.7 ± 0.9, p<0.05 vs. untreated SHR, unpaired t test) but not WKY (6.3 ± 1.8). In conclusion, this work shows that the increased expression and activity of glutamate transporters in hypertrophic hearts is associated with improved recovery of hypertrophic (SHR) rat hearts but not their corresponding control (WKY) hearts following normothermic global ischaemia and reperfusion in the presence of low concentration of glutamate.