Abstract Oxygenation of a bicarbonate-containing crystalloid cardioplegic solution alters the partial pressure of both oxygen (O 2) and carbon dioxide (CO 2). Therefore, oxygenating St. Thomas' Hospital II plus glucose (11 mmol/L) cardioplegic solution with 95% O 2 + 5% CO 2 induces a pH shift to 7.0 (10 °C) as opposed to pH 9.3 with 100% O 2. In an isolated working rat heart model, we show that pH 7.0 (10 °C) improves mechanical postischemic recovery in the absence or presence of O 2. However, in the absence of O 2, pH 7.0 appears to inhibit glycolysis and diminish the stability of cellular membranes. The provision of O 2 independently improved mechanical recovery and at pH 7.0, improved the preservation of the sarcolemma. Increasing the O 2 content by including a perfluorocarbon (FC-43) in the oxygenated St. Thomas' plus glucose cardioplegia is not additionally beneficial. St. Thomas' Hospital plus glucose cardioplegic solution should be oxygenated, but with 95% O 2 + 5% CO 2 and not 100% O 2.