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Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during
1Department of Surgery, University of Nebraska Medical Center, Omaha 68198-2315.
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Lowering calcium in St. Thomas
Area of Science:
- Cardiovascular Science
- Biochemistry
- Surgical Research
Background:
- The standard calcium concentration in St. Thomas' Hospital cardioplegic solution (1.2 mmol/L) was determined under normothermic conditions.
- Recent findings suggest that reduced calcium levels enhance myocardial protection during hypothermia, primarily due to creatine phosphate's effects.
- Optimal calcium concentration for hypothermic cardioplegia requires re-evaluation.
Purpose of the Study:
- To determine the optimal calcium concentration in St. Thomas' Hospital cardioplegic solution for myocardial protection during prolonged hypothermic ischemia.
- To assess the impact of varying calcium concentrations on post-ischemic cardiac function, enzyme release, and arrhythmias.
Main Methods:
- Utilized an isolated working rat heart model subjected to hypothermic ischemia (20°C for 300 minutes).
- Compared eight treatment groups with calcium concentrations ranging from 0.0 to 1.5 mmol/L in St. Thomas' Hospital solution.
- Administered multidose cardioplegia during ischemia and measured post-ischemic functional recovery, creatine kinase release, and time to sinus rhythm restoration.
Main Results:
- The optimal calcium concentration for hypothermic ischemia was found to be 0.6 mmol/L, within an acceptable range of 0.3–0.9 mmol/L.
- This concentration significantly improved post-ischemic aortic flow recovery (86.0% vs. 22.0% with 1.2 mmol/L calcium).
- Creatine kinase release was reduced by 84%, and post-ischemic arrhythmias were diminished.
Conclusions:
- The optimal calcium concentration for St. Thomas' Hospital cardioplegic solution during hypothermic ischemia is significantly lower (0.6 mmol/L) than previously established for normothermia.
- This lower calcium concentration enhances cardioprotection and reduces arrhythmias, offering superior myocardial preservation.
- Acalcemic solutions can induce calcium paradox, highlighting the critical role of controlled calcium levels.
Abstract:
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.