During open-heart surgery, the period between cross-clamping and maintenance of homogeneous diastolic arrest is often accompanied by significant ischaemic-hypoxic injury. The topical application of glutamate-aspartate or pentoxifylline may reduce energy demands during this period and thus prevent myocardial damage. Fifty rats were divided into five groups. In group A (control) the pericardial cavity was opened, all inlet and outlet vasculature cross-clamped, and the heart excised after 60 s. In groups B-E, the pericardial cavity was opened, all inlet and outlet vasculature cross-clamped for 60 s (groups B and D) or 90 s (groups C and E), and the pericardial cavity filled with glutamate-aspartate solution (groups B and C) or pentoxifylline solution (groups D and E) for 2 min. Following clamping, blood was withdrawn from the right atrium for biochemical analysis, and the heart excised for histological analysis. Histopathological and biochemical analysis showed a significant reduction in ischaemic-hypoxic cardiac injury in rats treated with topically applied glutamate-aspartate or pentoxifylline.