PULMONARY RESPONSES TO 5-HYDROXYTRYPTAMINE AND ENDOTHELIN-1 IN A RABBIT MODEL OF LEFT-VENTRICULAR DYSFUNCTION

Objective: To determine whether pulmonary hypertension developed in a coronary artery-ligated rabbit model of left ventricular dysfunction ( LVD) and to examine the effects of i.v. 5-hydroxytryptamine (5-HT) and endothelin-l (ET-1) on pulmonnry arterial pressure (PAP). Methods: Ei ght weeks after experimental coronary artery ligation or sham operatio n, ejection fractions were assessed by echocardiography. The rabbits w ere later anaesthetised and pulmonary arterial pressure was measured v ia a catheter inserted into the pulmonnry artery via the right externa l jugular vein. 5-HT (1-400 mu g/kg) and ET-I (0.001-4 nmol/kg) were a dministered i.v. Results: Ejection fraction was significantly decrease d from 76.6 +/- 1.4% in sham-operated to 42.2 +/- 1.3% in coronary art ery-ligated rabbits (n = 9 in each group, P < 0.001), consistent with LVD. Baseline mean pulmonary arterial pressure was significantly incre ased in the coronary artery-ligated group compared to the shams, (16.5 +/- 0.5 vs. 11.5 +/- 0.8 mmHg; P < 0.001), A significant degree of ri ght ventricular hypertrophy was found in the coronary artery-ligated r abbits (0.70 +/- 0.03 g/kg final body weight (f.b.wt.),n = 8 cf. 0.48 +/- 0.02 g/kg f.b.wt. in sham-operated controls, n = 8; P < 0.001). Th ere was a significant increase in the percentage of muscularised pulmo nary vessels adjacent to alveolar ducts and alveoli < 60 mu m i.d. in the LVD rabbits compared with their sham-operated controls (8.5 +/- 0. 4 cf. 20 +/- 0.5; P < 0.0005). 5-HT produced a greater response in the coronary artery-ligated rabbits (a maximum increase of 8.7 +/- 1.0 mm Hg in mean pulmonary artery pressure vs. 4.6 +/- 1.5 mmHg for sham-ope rated controls: P < 0.05). ET-I did not have any effect on pulmonary a rterial pressure in either group. Conclusion: In the rabbit, LVD secon dary to coronary artery ligation, causes right ventricular hypertrophy , pulmonary vascular remodelling, and an increased PAP consistent with the onset of pulmonary hypertension (PHT). The greater PAP response t o i.v. 5-HT in the PHT group supports the hypothesis that this substan ce could be involved in the development of PHT. A role for ET-1 cannot be excluded, despite its lack of effect on PAP when intravenously adm inistered in either group. (C) 1998 Elsevier Science B.V. All rights r eserved.