The protection of ischemic lung with verapamil and hydralazine.
The optimum method for lung preservation in preparation for transplantation remains unresolved. In this study, we evaluated the effectiveness of two pharmacologic agents for prolonging the preservation time of the ischemic lung. We compared hydralazine, a vasodilator, and verapamil, which is both a vasodilator and a calcium channel blocker, in regard to their effectiveness in promoting functional recovery of the ischemic dog lung in a new experimental model. The model consists of exposing the left lung of each dog to normothermic ischemia after clamping the pulmonary artery, vein, and bronchus. After ischemic periods of 1 to 5 hours, pulmonary circulation was reestablished. The functional integrity of the left lung was then evaluated by ligating the right bronchus, so that the dog was completely dependent on the previously ischemic lung. The left lung of eight dogs was perfused with 200 ml of Collins-Sachs solution alone in group A, with Collins-Sachs solution containing 20 mg of hydralazine in group B (n = 8), and with Collins-Sachs solution containing 5 mg of verapamil in group C (n = 8). The mean ischemic time was 2.3 hours in group A, 3.0 hours in group B, and 3.1 hours in group C. One dog in group A survived after 1 hour of ischemia, two dogs in group B survived after 1 and 3 hours of ischemia, and six dogs in group C survived 2 to 4 hours of ischemia. Oxygen tension in room air after bronchial ligation was 39.9 +/- 10.2 mm Hg in group A, 59.4 +/- 35.3 in group B, and 76.1 +/- 32.9 in group C. Statistical significance existed between groups A and C (p less than 0.05). Pulmonary vascular resistance after bronchial ligation was 428.9 +/- 158.8 dynes.sec.cm-5 in group A, 219.9 +/- 51.9 in group B, and 208.3 +/- 84.5 in group C. Thus tissue damage caused by ischemia was significantly less with verapamil than with the vasodilating drug hydralazine.
Hachida
M
M
Division of Surgical Oncology, School of Medicine, University of California, Los Angeles 90024.
Morton
D L
DL
D000818:Animals; D001706:Biopsy; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D016040:Lung Transplantation; D009926:Organ Preservation / Q000379:methods; D013997:Time Factors; D014700:Verapamil / Q000627:therapeutic use*
D006830:Hydralazine; D014700:Verapamil