OBJECTIVES: Depolarizing cardioplegia is the most common method for myocardial preservation in cardiac operations. However, depolarizing cardioplegia causes depolarization of the membrane potential by extracellular hyperkalemia, resulting in depletion of energy stores and calcium overload. This study examined the hypothesis that non-depolarizing cardioplegia would provide superior protection compared with depolarizing cardioplegia. METHODS: In an isolated rat heart Langendorff model, hearts were perfused for 10 min with St. Thomas' Hospital cardioplegic solution (Group I: n=20), St. Thomas' Hospital cardioplegic solution+Lidocaine 1 mM (Group II: n=20) or non-depolarizing cardioplegia (Group III: n=20). The hearts then were subjected to 60 min of normothermic global ischemia, after which they were perfused with Krebs-Henseleit buffer at 37 degrees C for 30 min. The percent recovery of functional data, myocardial cyclic AMP contents, and myocardial cyclic GMP contents were recorded at each time point (base, after the administration of cardioplegia, after global ischemia, and after 30 min of reperfusion). Ca(2+)-ATPase in sarcoplasmic reticulum was measured at pre-ischemia and 30 min of reperfusion. RESULTS: The percent recovery of developed pressure and +/-dp/dt were significantly higher in Group III than in other groups. Myocardial cyclic AMP and GMP contents were elevated after reperfusion in all groups. However, in Group III, myocardial cyclic AMP contents after 30 min of reperfusion were significantly higher than in other groups (Group III: 14.7+/-1.6 vs. Group I: 8.7+/-1.0, Group II: 8.3+/-0.2 pmol/mg dry weight, P=0.05) but not cGMP. The sarcoplasmic reticulum Ca(2+)-ATPase activities at 30 min of reperfusion significantly increased in Group III compared with Groups II and I (Group III: 70.3+/-3.6 vs. Group I: 46.8+/-3.4, Group II: 53.9+/-6.1 micromol Pi/mg per h, P=0.025 and P=0.030). CONCLUSIONS: Non-depolarizing cardioplegia induced the activity of Ca(2+)-ATPase in sarcoplasmic reticulum after reperfusion. The activity would be increased by the cyclic AMP pathway. These findings suggested that non-depolarizing cardioplegia prevented calcium overload after reperfusion, especially decreased cytosolic calcium during the diastolic phase.
OBJECTIVES: Depolarizing cardioplegia is the most common method for myocardial preservation in cardiac operations. However, depolarizing cardioplegia causes depolarization of the membrane potential by extracellular hyperkalemia, resulting in depletion of energy stores and calcium overload. This study examined the hypothesis that non-depolarizing cardioplegia would provide superior protection compared with depolarizing cardioplegia. METHODS: In an isolated rat heart Langendorff model, hearts were perfused for 10 min with St. Thomas' Hospital cardioplegic solution (Group I: n=20), St. Thomas' Hospital cardioplegic solution+Lidocaine 1 mM (Group II: n=20) or non-depolarizing cardioplegia (Group III: n=20). The hearts then were subjected to 60 min of normothermic global ischemia, after which they were perfused with Krebs-Henseleit buffer at 37 degrees C for 30 min. The percent recovery of functional data, myocardial cyclic AMP contents, and myocardial cyclic GMP contents were recorded at each time point (base, after the administration of cardioplegia, after global ischemia, and after 30 min of reperfusion). Ca(2+)-ATPase in sarcoplasmic reticulum was measured at pre-ischemia and 30 min of reperfusion. RESULTS: The percent recovery of developed pressure and +/-dp/dt were significantly higher in Group III than in other groups. Myocardial cyclic AMP and GMP contents were elevated after reperfusion in all groups. However, in Group III, myocardial cyclic AMP contents after 30 min of reperfusion were significantly higher than in other groups (Group III: 14.7+/-1.6 vs. Group I: 8.7+/-1.0, Group II: 8.3+/-0.2 pmol/mg dry weight, P=0.05) but not cGMP. The sarcoplasmic reticulum Ca(2+)-ATPase activities at 30 min of reperfusion significantly increased in Group III compared with Groups II and I (Group III: 70.3+/-3.6 vs. Group I: 46.8+/-3.4, Group II: 53.9+/-6.1 micromol Pi/mg per h, P=0.025 and P=0.030). CONCLUSIONS: Non-depolarizing cardioplegia induced the activity of Ca(2+)-ATPase in sarcoplasmic reticulum after reperfusion. The activity would be increased by the cyclic AMP pathway. These findings suggested that non-depolarizing cardioplegia prevented calcium overload after reperfusion, especially decreased cytosolic calcium during the diastolic phase.
Authors: Mohammed Aldakkak; David F Stowe; Edward J Lesnefsky; James S Heisner; Qun Chen; Amadou K S Camara Journal: J Cardiovasc Pharmacol Date: 2009-10 Impact factor: 3.105