Pathophysiological aspects of predominant preload lowering on pulmonary circulation, gas exchange, and the biventricular function in patients with chronic obstructive lung disease

Abstract

Summary:A group of 21 patients with various degrees of chronic obstructive pulmonary disease underwent radionuclide ventriculography with hemodynamic monitoring to assess the extent to which pulmonary artery pressures and pulmonary vascular resistance can be lowered by the vasodilator molsidomine. Molsidomine (N-carboxy-3-morpholino-sydnonimin-ethylester) is similar to nitroglycerin in its mode of action. After hemodynamic and radionuclide data acquisition, at rest and during submaximal exercise in the steady state, 2 mg molsidomine was injected intravenously. Rest and exercise measurements were repeated 45 min after molsidomine injection. In patients with mild to moderate disease (group l), pulmonary artery resting pressures decreased by 12% (~~0 . 0 5 ) at rest and by 22% (p<O.Ol) during exercise after the administration of the drug. Total pulmonary resistance during exercise decreased significantly (p <0.01) as a result of a marked decrease of pulmonary artery pressure (PAP) compared with a minimal decrease in cardiac index (CI). In patients with severe disease (group 2), only the resting values of PAP decreased while the relationship between pressure and flow was unchanged. During the exercise period, the preload parameters of the right and left ventricles decreased by an average of 30%. With regard to gas exchange, only the arterial PO2 at rest decreased slightly but significantly (p <0.05) after molsidomine, while the coefficient of oxygen delivery was not affected by the drug. However, in four patients arterial PO2 was markedly reduced by the drug. Right ventricular ejection fraction increased significantly (p<O.Ol) both at rest and during exercise in group 1 and during exercise in group 2 after administration of molsidomine. The left ventricular ejection fraction increased at rest (p < 0.05) and during exercise (p < 0.01) only in group 1. In conclusion, our results show that only a few patients with advanced lung disease and hypoxia benefit from this vasodilator with predominant preload lowering effect. The lowering of total pulmonary vascular resistance in the exercise state and the marked lowering of preload and afterload of the right ventricle in patients with mild to moderate lung disease after administration of molsidomine might be relevant to patients during surgical stress. In these patients, the net effect of the drug may be beneficial despite a slight reduction of cardiac output in most patients.

Right Heart Catheterization During Exercise in Patients with COPD—An Overview of Clinical Results and Methodological Aspects

“…Although RVEF correlated with PaO 2 (r ¼ 0.56; p < 0.01), it did not correlate with lung function and did not predict RV contractility under exercise. These findings were substantiated by a further study (60). In an earlier study, the majority of patients with COPD did not show an adequate increase in RVEF during submaximal exercise (61).…”

“…The acute effects of a vasodilator on hemodynamics at rest and during exercise were investigated in 21 patients with COPD following administration of intravenous molsidomine (60). Molsidomine lowered PAPm, cardiac index and PAOP at rest and during exercise, but this effect was not observed in all patients.…”