Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism.
BACKGROUND
We assess whether remote ischemic preconditioning (rIPC) of the recipient can modify ischemia-reperfusion (IR) injury in the donor heart following orthotopic heart transplantation from brain dead donors and to examine potential mechanisms of protection.


METHODS
Sixteen pigs weighing from 26 to 34.2 (mean 29.2) kg, randomized to control group (n=5), ischemic preconditioning (rIPC) group (n=6), and to receive rIPC with prior glibenclamide administration (Glib + rIPC) group (n=5) underwent orthotopic heart transplantation with the support of hypothermic (32 degrees C) cardiopulmonary bypass (CPB). The hearts were harvested from donor animal rendered brain dead by balloon compression via a craniotomy. Preconditioning of the recipients was induced by four 5-min cycles of lower limb ischemia. Myocardial infarction (MI) was induced following heart transplantation by 30 min of left anterior descending (LAD) artery occlusion following by 2 hr of regional reperfusion. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining.


RESULTS
Preconditioning of the recipient reduced the mass of MI (6.75+/-6.3 g in rIPC vs. 18.1+/-5.8 g in control, P=0.01), MI to area at risk (ARR) mass ratio by 57% (15.6%+/-15.2% vs. 36.3%+/-13.4%, P=0.04). The protective effect of preconditioning was abolished by pretreatment with glibenclamide.


CONCLUSIONS
Remote ischemic preconditioning of the recipient, decreases ischemia-reperfusion injury in the brain dead donor heart following orthotopic heart transplantation via a Katp channel-dependent mechanism. This study suggests that a circulating effector persists after the rIPC stimulus is applied, and excludes an ongoing afferent neurogenic mechanism of cardioprotection.
Konstantinov
Igor E
IE
Division of Cardiovascular Surgery, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
Li
Jia
J
Cheung
Michael M
MM
Shimizu
Mikiko
M
Stokoe
Jacqueline
J
Kharbanda
Rajesh K
RK
Redington
Andrew N
AN
D000818:Animals; D001794:Blood Pressure; D001926:Brain Death; D002395:Catecholamines / Q000097:blood; D003714:Denervation; D006339:Heart Rate; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D015221:Potassium Channels / Q000502:physiology*; D013552:Swine; D014184:Transplantation, Homologous / Q000473:pathology / Q000502:physiology
D002395:Catecholamines; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel