Single lung transplantation in rats with chemically induced pulmonary hypertension.
Physiologic effects of single lung transplantation on pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred rats treated with monocrotaline (40 mg/kg) received a left lung isograft from a normal donor 2 weeks later, when pulmonary hypertension became significant (transplant group; n = 6). These rats and control rats treated with monocrotaline (mediated control group; n = 11) or vehicle alone (normal control group; n = 9) were followed up weekly by metabolic treadmill testing for exercise tolerance and oxygen consumption up to 6 weeks after monocrotaline (4 weeks after transplantation), when all rats underwent hemodynamic and histologic examinations. Whereas maximal oxygen consumption and exercise tolerance consistently deteriorated in the medicated control group of rats, indices in the transplant group stopped deteriorating 2 weeks after lung transplantation and remained at levels similar to those of normal control rats. Severe pulmonary hypertension (68 +/- 19 mm Hg) and right ventricular hypertrophy (right ventricular/left ventricular weight ratio, 0.95 +/- 0.19) were confirmed in medicated control rats in contrast to transplant animals, in which these two indices remained at normal control levels. Whereas left-to-right lung perfusion ratio was constant among rats not receiving transplants (0.69 +/- 0.16), it was significantly elevated (2.27 +/- 0.65; p less than 0.001) in those receiving transplants, suggesting preferential flow through the lung isograft. The results suggest that, in the early phase of pulmonary hypertension, single lung transplantation shifts pulmonary perfusion to the grafted lung, avoiding right ventricular pressure overload and thereby preserving exercise tolerance at a nearly normal level in rats with monocrotaline-induced pulmonary hypertension.
Kawaguchi
A T
AT
First Department of Surgery Osaka University School of Medicine, Japan.
Mizuta
T
T
Matsuda
H
H
Shirakura
R
R
Nakahara
K
K
Tanaka
H
H
Kawashima
Y
Y
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005080:Exercise Test; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D016686:Monocrotaline; D010101:Oxygen Consumption; D051381:Rats; D011917:Rats, Inbred Lew
D016686:Monocrotaline