Monocrotaline-induced pulmonary vascular disease after contralateral lung transplantation in the rat.
To test a hypothesis that reduction in pulmonary perfusion pressure and flow affect underlying vascular disease, pulmonary pathology was studied in monocrotaline-treated rats undergoing single lung transplantation. Inbred rats were treated with 40 mg/kg (group T1, n = 6) and 80 mg/kg of monocrotaline (group T2, n = 9), received a left lung isograft 2 and 4 weeks after medication, and were killed 4 and 6 weeks after single lung transplantation, respectively. For each group, rats receiving the same amount of monocrotaline (M1, M2) or vehicle (N1, N2) served as controls. Monocrotaline-treated rats developed pulmonary vascular disease and right heart failure, resulting in severe exercise intolerance in M1 or death in M2 unless single lung transplantation had been carried out. At death, pulmonary blood flow was directed toward the left lung isograft, and the retained right lung received a significantly reduced fraction of cardiac output. Right to left ventricular weight ratio was significantly reduced in both groups as compared to the respective control rats, suggesting reduced perfusion pressure. Although thickness of media in small pulmonary arteries (media/radius) was normal (34% +/- 4%) in the lung isografts, it was significantly increased in the contralateral lung (group T1, 45% +/- 5%; group T2, 48% +/- 3%), which was not significantly different from that of monocrotaline-treated control rats, respectively (group M1, 47% +/- 7%; group M2, 49% +/- 6%). Although single lung transplantation reduced perfusion pressure and flow toward the monocrotaline-treated native lung, it failed to affect vascular morphology significantly.
Kawaguchi
A T
AT
National Cardiovascular Center, Osaka, Japan.
Kawashima
Y
Y
Ishibashi-Ueda
H
H
Mizuta
T
T
Kitoh
Y
Y
Kunieda
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016040:Lung Transplantation; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D016686:Monocrotaline