title: Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during hypothermic ischemia.
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.
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha 68198-2315.
authors.forename: L A
authors.initials: LA
authors.lastname: Robinson
authors.forename: D L
authors.initials: DL
authors.lastname: Harwood
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D001639:Bicarbonates / Q000032:analysis; D001783:Blood Flow Velocity; D002118:Calcium / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D002122:Calcium Chloride / Q000032:analysis; D002302:Cardiac Output; D003326:Coronary Circulation; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008274:Magnesium / Q000032:analysis; D008297:Male; D015425:Myocardial Reperfusion; D011189:Potassium Chloride / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000032:analysis; D014655:Vascular Resistance
chemical_list: D001639:Bicarbonates; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride; D002118:Calcium