Warm ischemia lung protection with pinacidil: an ATP regulated potassium channel opener.
BACKGROUND
Ischemia/reperfusion injury remains a limiting factor in lung transplantation. Traditional hyperkalemic preservation solutions are associated with a host of metabolic derangements. ATP-regulated potassium channel openers (PCOs) may provide an attractive alternative to traditional solutions by utilizing inherent mechanisms of ischemic preconditioning. The purpose of this study was to assess warm ischemia graft protection with pinacidil, a nonspecific PCO.


METHODS
An isolated recirculating blood perfused ventilated rabbit lung model was used (n = 15). No ischemia control lungs underwent immediate reperfusion (n = 5). Warm ischemia control lungs were flushed with lactated Ringers (LR), stored at 37 degrees C for 2.5 hours and then reperfused for 2 hours (n = 5). PCO protected lungs were flushed with LR + 100 micromol/L pinacidil, stored, and then reperfused (n = 5). Intermittent blood gases were taken from the pulmonary artery and left atria. Every 30 minutes, graft function was assessed with a 10-minute 100% fractional inspired oxygen concentration challenge to measure maximal gas exchange. Lung samples were graded for histologic injury and assayed for myeloperoxidase activity.


RESULTS
A mixed-models repeated measures ANOVA demonstrated a significant difference between groups. Tukey's honestly significant difference multiple comparison test demonstrated significantly improved graft function and reduced histologic injury with pinacidil protection compared with the warm ischemia controls. There was no significant difference in graft function or pathology grade between the pinacidil protected lungs and the no ischemia controls. A similar trend, although not significant, was seen in myeloperoxdiase activity.


CONCLUSIONS
Potassium channel openers with pinacidil can provide pulmonary protection against warm ischemia reperfusion injury.
Tang
Daniel G
DG
Division of Cardiothoracic Surgery, Department of Surgery, Medical College of Virginia Hospitals & Physicians of Virginia Commonwealth University Health System, Richmond, VA 23298, USA.
Pavot
Dawn R
DR
Mouria
Michelle M
MM
Holwitt
Dana M
DM
Cohen
Neri M
NM
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D016040:Lung Transplantation / Q000009:adverse effects* / Q000379:methods / Q000473:pathology*; D008297:Male; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011322:Primary Prevention / Q000379:methods; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D013696:Temperature; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil