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This study compared the cardioprotective effects of three oxygenated "extracellular" crystalloid cardioplegic solutions. These were MBS (containing glucose, aspartate, and lactobionate [GAL]), St. Thomas' Hospital No. 2 (STH), and modified STH (added glucose, aspartate, and lactobionate) (STHGAL). Isolated working rat hearts (45) were initially injured with 10 min of global normothermic ischaemia and then arrested for 4 hr at (30 degrees C) with multidose cardioplegia (2 min every 30 min). The hearts (n = 9 per group) were then reperfused for 7 min in the non-working mode and for a further 23 min in the working mode. MBS-treated hearts rapidly resumed spontaneous sinus rhythm (0.69 +/- 0.06 minutes) with nearly complete recovery of function (aortic flow 93.3 +/- 5.4%, cardiac output 95.7 +/- 3.6%, stroke volume 95.3 +/- 3.7%, heart rate 102.2 +/- 3.7%, and aortic pressure 88.3 +/- 3.2% of pre-ischaemic control values). With either STH or STHGAL these indices were significantly (p < 0.01) lower (aortic flow 25.5 +/- 10.4% or 69.5 +/- 6.5%, cardiac output 30.1 +/- 11.1% or 67.6 +/- 6.6%, aortic pressure 36.5 +/- 7.7% or 63.9 +/- 8.0%, respectively). Total lactate efflux (indicating glycolysis) during cardioplegia was increased (p < 0.01) by inclusion of GAL (MBS 63.7 +/- 1.8, STHGAL 68.7 +/- 2.2, STH 28.5 +/- 1.3 mumol/heart). Progressive increase in coronary vascular resistance was observed during STH-based cardioplegia but not during MBS-based. The improved recovery of function was associated with reduced depletion of adenosine triphosphate (MBS 9.44 +/- 0.79, STHGAL 8.21 +/- 1.00, STH 1.02 +/- 0.10 mumol/g dry wt), total adenine nucleotide pool (14.61 +/- 0.83, 16.81 +/- 0.85, 7.33 +/- 0.52 mumol/g dry wt) and energy charge (0.767 +/- 0.019, 0.620 +/- 0.037, 0.248 +/- 0.012) during arrest, and significantly (p < 0.01) better resynthesis during reperfusion (ATP: 66%, 16%, 40%; TAN: 64%, 22%, 43% of control respectively). These findings indicate that the novel cardioplegic solution MBS (US Pat. No. 5,290,766) provides better myocardial protection than STH in hearts with pre-arrest ischaemic injury not only by providing metabolic substrates but also because of its more appropriate balance of cations.

The isolated working rat heart model was use to define the cardioprotective effects (function, metabolic and ultrastructure) of the oxygenated St. Thomas' Hospital No. 2 cardioplegic solution (STH) during lengthy, hypothermic ischaemia (20 degrees C, 4 hours and 5 hours). Hearts (n = 9 for each group) were arrested with and exposed to multidose reinfusion (2 min every 40 min interval) throughout the ischaemic period with the cold (4 degrees C) STH or oxygenated (95% O2:5% CO2) STH. Oxygenated STH significantly (p < 0.01) improved the postischaemic recovery of cardiac output from 49.5 +/- 11.1% to 96.8 +/- 1.5% (in 4 hours) and from 20.3 +/- 7.2% to 72.2 +/- 5% (in 5 hours). Other indices of functional recovery showed similar improved performance with the significant decrease in time from the onset of reperfusion to the return of regular sinus rhythm (57 +/- 8 v 495 +/- 150 s). The efflux of lactate during 5 hr ischaemic arrest was decreased (20.62 +/- 1.3 v 26.18 +/- 1.73 mumol/heart for oxygenated STH and STH, respectively, p < 0.05) and the progressive increase in the coronary vascular resistance was abolished in the oxygenated STH treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (14.49 +/- 2 v 3.3 +/- 0.19 mumol/g dry wt), creatine phosphate (24.61 +/- 3.47 v 7.48 +/- 1.34 mumol/g dry wt) and guanosine triphosphate (1.69 +/- 0.2 v 0.84 +/- 0.08 mumol/g dry wt) during ischaemia, total resynthesis after reperfusion (ATP: 103% v 36%, CP: 105% v 69% and GTP: 203% v 61% of control) and the total absence of myocardial cells and microvasculature injuries in ischaemic (non-reperfused) hearts. These results confirm that the provision of additional oxygen to the St. Thomas' Hospital solution (with 95% O2:5% CO2) can meet the metabolic demand of the ischaemic myocardium and thus increase the safe duration of cardiac arrest.