Myocardial protection during prolonged ischaemic cardiac arrest: experimental evaluation of three crystalloid...

The aim of this study is to define the cardioprotective effects (functional and metabolic) of our modified "extracellular" cardioplegic solution (MBS: containing glucose, aspartate and lactobionate), St. Thomas' Hospital No. 2 (STH) and Bretschneider's No. 3 (Bret) solutions during prolonged hypothermic ischaemia (20 degrees C, 6 hours) in the isolated working rat heart. hearts (n = 9-10 in each group) were arrested with, and exposed to, multidose reinfusion (2 minutes every 40 minutes interval) throughout the ischaemic period with cold (4 degrees C) MBS, STH or oxygenated (95% O2: 5% CO2) Bret. All MBS treated hearts resumed spontaneous regular sinus rhythm (0.51 +/- 0.01 minutes) of contraction during post-ischaemic reperfusion for 30 minutes at 37 degrees C with the complete recovery of all the functional indices (aortic flow: 87.4 +/- 3.4%, cardiac output: 94.1% +/- 3.3%, coronary flow: 101.8 +/- 4.1%, heart rate: 99.8 +/- 2.8% and aortic pressure: 105.7 +/- 4.6% of prearrest control values). In contrast, hearts protected with either STH or Bret showed the poor or no post-ischaemic recovery of cardiac pump function (aortic flow: 7.2 +/- 4.8% and 0%, respectively). Recovery of all other left ventricular function indices were also significantly (p < 0.001) decreased with increasing more hearts failing to regain function (MBS: 0/10, STH: 7/9 and Bret: 9/9). The efflux of lactate during 6 hours ischaemic arrest was increased [52.40 +/- 1.50 v 36.8 +/- 1.70 (STH) or 14.45 +/- 0.70 (Bret) mumol/heart, p < 0.001] and the progressive increase in the coronary vascular resistance was completely abolished in MBS treated hearts. These improvements were associated with the reduction in the decline of the myocardial adenosine triphosphate (23.44 +/- 1.08 v 3.79 +/- 1.08 or 4.51 +/- 0.71 mumol/g dry wt), creatine phosphate (30.23 +/- 1.52 v 8.01 +/- 2.21 or 5.41 +/- 0.03 mumol/g dry wt) and guanosine triphosphate (2.26 +/- 0.23 v 0.24 +/- 0.11 or 0.59 +/- 0.07 mumol/g dry wt) during ischaemia, and total resynthesis after reperfusion (ATP: 92% v 36% or 25% and CP: 126% v 92% or 59% of control). These results indicate that the new cardioplegic solution, MBS can meet the metabolic demand of the ischaemic myocardium because of the greater synthesis of intramyocardial ATP and CP during cardioplegic arrest, provide substantially improved protection of hearts from injury and thus increase (double) the safe duration of cardiac arrest.