Canine nonresponders to alveolar hypoxic vasoconstriction and quantitative restoration of the response by aspirin I-3.
Hypoxic pulmonary vasoconstriction is characterized by considerable variability in rate of response (pulmonary vascular resistance [PVR] as a function of time under hypoxia). To further define this response, forty-five closed chest dogs were anaesthetized (pentobarbitone sodium), intubated, and mechanically ventilated. Constant left lower lobar pulmonary artery flow was maintained through a balloon tipped 14F catheter via an extracorporeal pump at a rate to achieve lobar pulmonary artery pressure (Plobar) equal to main pulmonary artery pressure (PPA) and thereafter held constant. Left ventricular end diastolic pressure (PLVED) was measured by left ventricular catheter and lobar pulmonary artery flow rate (Q) by flow meter. Lobar PVR (mmHg/min per 1) was calculated every 15 min. Ventilation with 10% oxygen (O2) separated two groups based on the increase in PVR over time: twenty-two rapid hypoxic responders [HR] (slope= delta PVR/delta min greater than 0.3) and twenty-three slow or nonresponders [NR] (slope less than 0.1). The twenty-three NR were divided into two groups. Ten NR dogs (NR control) had no change in mean PVR (23.9, s.d. = 8.2, to 24.1, s.d. = 9.6) over a mean of 78 min and were used as controls. Thirteen NR dogs (NR ASA) had no change in mean PVR (32.9, s.d. = 9.5, to 32.3, s.d. = 9.8) over 75 min and were given aspirin (ASA), 10-15 mg/kg intra-arterially. The NR ASA group mean PVR then increased from 32.3 (s.d. = 9.8) to 59.1 (s.d. = 23.9, 82.9% increase, P less than 0.01) over a mean of 54 min. The mean PVR for the twenty-two HR rose from 39.8 (s.d. = 34.0) to 64.5 (s.d. = 36.6, 62.1% increase, P less than 0.01) over a mean of 72 min. The slopes of rate of response for HR (0.66) and for NR ASA (0.88) were not significantly different. The absolute values of PVR reached after plateau for HR and for NR ASA (after ASA) were also not different. Aspirin restored the NR capability to develop pulmonary vasoconstriction in response to alveolar hypoxia. The rate of response and the absolute level of response reached were also restored by aspirin.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D001241:Aspirin