Plasmolemmal potassium gradient does not affect lung protection by an ATP-regulated potassium channel opener.
BACKGROUND
We have previously shown that metabolic arrest induced with ATP-regulated potassium channel openers (PCOs) can improve lung preservation by adding Aprikalim (a PCO, Rhone-Poulene Roher) to modified Euro-Collins solution for pulmonary artery flush. Because the membrane hyperpolarizing effects of a PCO potentially competes with the depolarizing effects of a hyperkalemic solution, this study evaluated the effects of the potassium gradient on PCO-mediated lung protection.


METHODS
Twenty rabbits underwent lung protection in four groups. Group 1 underwent harvest and reperfusion as a "no ischemia" control. Groups 2, 3, and 4 underwent harvest followed by 18 hours of cold ischemic storage before reperfusion. Groups 1 and 4 received Euro Collins as the pulmonary flush at induction of ischemia. Group 2 received Euro Collins plus Aprikalim (100 microM); and group 3 received lactated Ringer's plus Aprikalim. After ischemic storage, the lungs were reperfused with autologous blood for 2 hours. Every 30 minutes, the lungs were given a 10-minute 100% fractional inspired oxygen (F(i)O(2)) challenge to measure maximal gas exchange as an indication of graft function.


RESULTS
Repeated measures ANOVA showed Aprikalim improved graft function after 18 hours of cold ischemia (p < 0.0001). No significant differences were found when Aprikalim was used in either Euro-Collins (group 2) or lactated Ringer's (group 3) solution.


CONCLUSIONS
The ability of the PCO Aprikalim to preserve gas exchange in a model of hypothermic pulmonary ischemia-reperfusion injury was not affected by the plasmolemmal potassium gradient. This is consistent with recent findings in myocardial protection studies that the protective effects of PCOs may be intracellular.
Tang
Daniel G
DG
Laboratory of Cardiovascular and Thoracic Surgery Research, Division of Cardiothoracic Surgery, Department of Surgery, Medical College of Virginia Hospitals & Physicians of Virginia Commonwealth University Health System, Richmond, VA, USA.
Vaida
Alexandru M
AM
Wise
Robert
R
Higgins
Robert S D
RS
Cohen
Neri M
NM
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D005260:Female; D006982:Hypertonic Solutions / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation; D008297:Male; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000494:pharmacology*; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011659:Pulmonary Gas Exchange; D011714:Pyrans / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*; D000077325:Ringer's Lactate
C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D007552:Isotonic Solutions; D019188:Organ Preservation Solutions; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D000077325:Ringer's Lactate; C061043:aprikalim; D000255:Adenosine Triphosphate