Pulmonary responses to 5-hydroxytryptamine and endothelin-1 in a rabbit model of left ventricular dysfunction

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-1 (ET-1) on pulmonary arterial pressure (PAP).

Eight weeks after experimental coronary artery ligation or sham operation, ejection fractions were assessed by echocardiography. The rabbits were later anaesthetised and pulmonary arterial pressure was measured via a catheter inserted into the pulmonary artery via the right external jugular vein. 5-HT (1-400 micrograms/kg) and ET-1 (0.001-4 nmol/kg) were administered i.v.

Ejection fraction was significantly decreased from 76.6 +/- 1.4% in sham-operated to 42.2 +/- 1.3% in coronary artery-ligated rabbits (n = 9 in each group; P < 0.001), consistent with LVD. Baseline mean pulmonary arterial pressure was significantly increased 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 right ventricular hypertrophy was found in the coronary artery-ligated rabbits (0.70 +/- 0.04 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). There was a significant increase in the percentage of muscularised pulmonary vessels adjacent to alveolar ducts and alveoli < 60 microns 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 mmHg in mean pulmonary artery pressure vs. 4.6 +/- 1.5 mmHg for sham-operated controls; P < 0.05). ET-1 did not have any effect on pulmonary arterial pressure in either group.

In the rabbit, LVD secondary 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 to i.v. 5-HT in the PHT group supports the hypothesis that this substance 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 administered in either group.