Comparison of pulmonary and systemic effects of adenosine triphosphate in chronic obstructive pulmonary disease--ATP: a pulmonary controlled vasoregulator?

Abstract

During stepwise incremental intravenous adenosine triphosphate (ATP) infusion, systemic and pulmonary vascular effects were compared in 10 patients with stable chronic obstructive pulmonary disease (COPD). Pulmonary vasodilation was: 1) predominant and maximal as early as the lowest dose infusion (0.1 mumol.kg-1.min-1) with pulmonary arterial mean pressure (Ppa) (-16%; p less than 0.01) and pulmonary vascular resistance (PVR) decreases (-28%; p less than 0.005) and simultaneous increasing delta PVR/delta SVR ratio; 2) associated with worsening hypoxaemia (-14%; p less than 0.001), but also with increasing alveolar-arterial oxygen pressure difference (P(A-a)O2) and venous admixture (Qs/Qt) suggesting some inhibition of hypoxic pulmonary vasoconstriction. Systemic vasodilation was: 1) clearly dose-dependent, but only reached significant level at 0.2 mumol.kg-1.min-1 with systemic arterial mean pressure (Psa) (-12.5%; p less than 0.05) and systemic vascular resistance (SVR) decreases (-30%; p less than 0.01); 2) associated with arterial carbon dioxide tension (PaCO2) decrease (-12.5%; p less than 0.005) and recurring uncontrollable hyperpnoea, suggesting a ventilatory stimulatory effect of ATP in man. In patients with stable COPD, ATP infusion has dual acute haemodynamic effects depending on the dose-level. The predominant pulmonary vasodilating effect occurs as early as the lowest dose-levels without any further increase of pulmonary vasodilation. This contrasts with the dose-related systemic vasodilation effect. Such a dual haemodynamic effect is an indirect indication of in vivo lung metabolism of ATP.