Myocardial protection with pinacidil induced hyperpolarized arrest during cardiopulmonary bypass.
OBJECTIVE
To investigate the myocardial protective effects of pinacidil-induced hyperpolarized arrest and compare with those afforded by conventional depolarized hyperkalemic arrest.


METHODS
Eighteen dogs were equally divided into three groups: normothermic hyperpolarized group (Group A), hypothermic hyperpolarized group (Group B), and hyperkalemic group (Group C). Pinacidil (50 mumol/L) containing 37 degrees C St. Thomas solution (K+ 5 mmol/L, 10 ml/kg), pinacidil (50 mumol/L, Sigma, USA) containing 4 degrees C St. Thomas solution (K+ 5 mmol/L, 10 ml/kg) and 4 degrees C standard St. Thomas solution (K+ 16 mmol/L, 10 ml/kg) were infused respectively through the aortic root after aortic-clamping. Heart arrest and its recovery, ultrastructure of the myocardium, the level of serum myocardial enzymes, and lipid peroxide and adenine nucleotide of the myocardium were measured. Hemodynamics during ischemia and after reperfusion were observed.


RESULTS
The percentages of normal mitochondria and glycogen did not change much during ischemia (except at 60 min) and after reperfusion in B Group, but declined markedly in Group C 30 min and 60 min after ischemia and 20 min after reperfusion (P < 0.01). In Group A, they were lower than those of Group B before ischemia, but higher than those of Group C. The recoveries of CO, SV, CI, LVSW, RVSW and MAP in Group B were significantly better than those in other two groups 15 min and 30 min after reperfusion (P < 0.05 and 0.01, respectively). However, they were still better in Group A than those in Group C (P < 0.05 and 0.01, respectively). The onset of heart arrest was faster in Groups C and B than that in Group A. Highly elevated serum myocardial enzymes were observed 60 min after ischemia and 20 min after reperfusion in Group C, while they were only mild in the hyperpolarized groups, especially in Group B, and their recoveries were rapid. Adenine nucleotides of the myocardium were better preserved in Group B than in other two groups 30 min, 60 min after ischemia, and 20 min after reperfusion (P < 0.05 and 0.01, respectively). They were also much better in Group A than in Group C (P < 0.05 and 0.01, respectively). Lipid peroxide of the myocardium were significantly lower in Group B than in other groups 20 min after reperfusion (P < 0.01), and they were lower in Group A than in Group C (P < 0.05).


CONCLUSIONS
Myocardial protection for global ischemia during cardiopulmonary bypass (CPB) could be achieved with hyperpolarized heart arrest induced by pinacidil, an ATP-sensitive potassium channel opener, especially in the hypothermic state. The protection is weaker in normothermia but is still superior to that with traditional depolarized hyperkalemic arrest.
Yu
T
T
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Guizhou 563003, China.
Yu
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Z
Liu
X
X
Yang
S
S
Ye
Y
Y
D000227:Adenine Nucleotides / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects; D006947:Hyperkalemia / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology*; D013997:Time Factors
D000227:Adenine Nucleotides; D000959:Antihypertensive Agents; D008054:Lipid Peroxides; D010725:Phosphocreatine; D020110:Pinacidil; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D000469:Alkaline Phosphatase