Cardioprotective effects of tetrahydrobiopterin in cold heart preservation after cardiac arrest.
BACKGROUND
It has recently been shown that tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase (NOS), reduces ischemia-reperfusion myocardial injury. The aim of this study was to determine if supplementation with BH4 after cardiac arrest followed by cold heart preservation would exert a cardioprotective effect against ischemia-reperfusion injury.


METHODS
Isolated perfused rat hearts were subjected to 4 degrees C cold ischemia and reperfusion. Hearts were treated with cold cardioplegic solution with or without BH4 just before ischemia and during the first 5 min of reperfusion period. Effects of BH4 on left ventricular function, myocardial contents of high-energy phosphates, and nitrite plus nitrate were measured in the perfusate, before ischemia and after reperfusion. Moreover, the effect of BH4 on the cold-heart preservation followed by normothermic (37 degrees C) ischemia was determined.


RESULTS
BH4 improved the contractile and metabolic abnormalities in reperfused cold preserved hearts that were subjected to normothermic ischemia. Furthermore, BH4 significantly alleviated ischemic contracture during ischemia, and restored the diminished perfusate levels of nitrite plus nitrate after reperfusion.


CONCLUSIONS
These results demonstrated that BH4 reduces ischemia-reperfusion injury in cold heart preservation. The cardioprotective effect of BH4 implies that BH4 could be a novel and effective therapeutic option in the preservation treatment of donor heart after cardiac arrest.
Yamashiro
Satoshi
S
Second Department of Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Kuniyoshi
Yukio
Y
Arakaki
Katsuya
K
Uezu
Toru
T
Miyagi
Kazufumi
K
Koja
Kageharu
K
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology*; D050377:Cold Ischemia; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000188:drug therapy / Q000201:enzymology; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000187:drug effects*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D001708:Biopterins; D019001:Nitric Oxide Synthase; C003402:sapropterin