Pulmonary and systemic haemodynamic effects of cromakalim in conditions of normoxia and hypoxia in dogs.
1. In anaesthetized-closed chest dogs, exposure to hypoxia (60 min) caused a sustained increase in arterial pulmonary pressures (diastolic: DPP, mean: MPP and effective capillary: EPCP by 132, 66 and 104% respectively) and increased total pulmonary vascular resistance (TPVR, 143%) with minimal changes in systemic haemodynamics. 2. Under normoxia, cromakalim infusion (2 micrograms kg-1 min-1 for 30 min) progressively decreased diastolic systemic arterial pressure (DBP, 30%) and total systemic vascular resistance (TSVR, 54%). In contrast, DPP was increased by 45%, due to an increase in cardiac output (CO: 55%), while TPVR was essentially unchanged. 3. Under hypoxic conditions, cromakalim (2 micrograms kg-1 min-1 for 30 min) induced changes in systemic haemodynamics comparable to those seen under normoxia. However, DPP was decreased by 37% at the end of infusion. The compound progressively decreased TPVR in a dose-related manner and PaO2 (55.9 mmHg) was maintained since cardiac output was increased. 4. Thus, under normoxia, cromakalim induced haemodynamic effects on the pulmonary circulation which were directly related to an increase in CO, but were clearly different from those observed under hypoxia. In the hypoxia-induced constricted pulmonary vascular bed, cromakalim effectively reduced the elevated pulmonary vascular resistance at low doses but showed comparable vasodilator effects on the systemic circulation under both conditions. The findings suggest that a vasodilator agent like cromakalim may be useful in patients with respiratory conditions associated with elevated pulmonary vascular resistance.
Martin
D J
DJ
Department of Pharmacology, Recherche Syntex France, Leuville sur Orge.
Gellotte
M
M
Armstrong
J M
JM
Hicks
P E
PE
D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D019806:Cromakalim; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008168:Lung / Q000098:blood supply; D011652:Pulmonary Circulation / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim