Calcium channel blocker enhances lung preservation.
BACKGROUND
The standard program for lung transplantation employs PGE1 pretreatment for donor lungs, but its efficacy remains controversial. Calcium channel blocker has been reported more effective for reducing potassium-induced vasoconstriction. We investigate the efficacy of calcium channel blocker in the initial lung flush using rat lung transplant model.


METHODS
The excised rat lungs (n = 30) were flushed with either University of Wisconsin solution (UWS) with a prior injection of 50 microg/kg PGE1 into the pulmonary artery (UWS + PGE1; n = 7), UWS only (UWS; n = 7), or UWS containing 10(-6) M nifedipine (UWS + Nif; n = 8). After storage (4 degrees C) for 24 hours, all lungs were reperfused for 2 hours using an isolated, pulsatile blood perfused lung model. Control lungs (n = 8) were reperfused immediately after harvest. Blood gas analysis and shunt fraction, lung airway resistance, dynamic lung compliance, and pulmonary vascular resistance were assessed.


RESULTS
The pO2 at 30 minutes after reperfusion in the control, UWS, UWS + PGE1, and UWS + Nif group were 88.0 +/- 3.2, 49.6 +/- 2.2, 52.0 +/- 2.4, 85.1 +/- 2.1 (mmHg), respectively. Until 30 minutes after reperfusion, the pO2 in UWS and UWS + PGE1 group were significantly lower than those in UWS + Nif group (p < .001). Shunt fraction, lung airway resistance, and dynamic lung compliance also demonstrated the superiority of UWS + Nif group.


CONCLUSIONS
The early graft function after storage was significantly enhanced in lungs flushed with UWS containing nifedipine. Calcium channel blocker is more effective than PGE1 in reducing the potassium-induced vasoconstriction. Optimal composition of the flush may require both calcium channel blocker for pulmonary vasodilation and PGE1 for pulmonary protection by non-vasodilatory mechanisms.
Sasaki
S
S
Department of Cardiovascular Surgery, Hokkaido University, Sapporo, Japan.
Yasuda
K
K
McCully
J D
JD
LoCicero
J
J
D000241:Adenosine; D000403:Airway Resistance / Q000187:drug effects; D000493:Allopurinol; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005978:Glutathione; D007328:Insulin; D008170:Lung Compliance / Q000187:drug effects; D016040:Lung Transplantation; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000097:blood; D011188:Potassium / Q000494:pharmacology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011887:Raffinose; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D014665:Vasodilator Agents; D000493:Allopurinol; D000527:Alprostadil; D005978:Glutathione; D009543:Nifedipine; D000241:Adenosine; D011887:Raffinose; D011188:Potassium; D010100:Oxygen