The concentration of
calcium (1.2 mmol/L) in clinical
St. Thomas' Hospital cardioplegic solution was chosen several years ago after dose-response studies in the normothermic isolated heart. However, recent studies with
creatine phosphate in St. Thomas' Hospital
solution demonstrated that additional myocardial protection during
hypothermia resulted principally from its
calcium-lowering effect in the
solution. The isolated working rat heart model was therefore used to establish the optimal
calcium concentration in St. Thomas' Hospital
solution during lengthy hypothermic
ischemia (20 degrees C, 300 minutes). The
calcium content of standard St. Thomas' Hospital
solution was varied from 0.0 to 1.5 mmol/L in eight treatment groups (n = 6 for each group). During
ischemia, hearts were exposed to multidose
cardioplegia (3 minutes every 30 minutes). Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of
creatine kinase and the time to return of sinus rhythm during the reperfusion period were also measured. These dose-response studies during hypothermic
ischemia revealed a broad range of acceptable
calcium concentrations (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital
solution at 0.6 mmol/L. This concentration improved the postischemic recovery of aortic flow from 22.0% +/- 5.9% with control St. Thomas' Hospital
solution (
calcium concentration 1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional recovery showed similar dramatic results.
Creatine kinase release was reduced 84% (p less than 0.01) in the optimal
calcium group. Postischemic reperfusion arrhythmias were diminished with the loser
calcium concentration, with a significant decrease in the time between initial reperfusion until the return of sinus rhythm. In contrast, acalcemic St. Thomas' Hospital
solution precipitated the
calcium paradox with massive
enzyme release and no functional recovery. Unlike prior published
calcium dose-response studies at normothermia, these results demonstrate that the optimal
calcium concentration during clinically relevant hypothermic
ischemia is considerably lower than that of normal serum ionized
calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital
solution.