Continuous, low dose of hydralazine, reduces acute hypoxic pulmonary hypertension without a corresponding fall in systemic arterial pressure.
Administration of hydralazine in patients with pulmonary hypertension has been reported to cause excessive systemic vasodilatation, limiting its clinical utility (N Engl J Med 1982; 306: 1326). We studied the effects of hydralazine on hypoxic pulmonary vasoconstriction (HPV) in chronically instrumented sheep and evaluated whether different methods of intravenous administration could prevent severe systemic hypotension. Mean left atrial, pulmonary and systemic arterial pressures (Pla, Ppa and Psa mmHg), cardiac output (CO, l/min, electromagnetic flowmeter) and heart rate were measured continuously. Systemic (SVR) and pulmonary vascular resistances (PVR) were calculated by Psa/CO and (Ppa-Pla)/CO, respectively. Following a 30 min baseline period, we initiated hypoxia with mixture of 10% oxygen in nitrogen. After 20 min of hypoxia we then performed the following two experiments: Group A-Hydralazine (10 micrograms/kg/min) was infused continuously for a further 20 min of hypoxia (n = 6); Group B-Hydralazine (400 micrograms/kg) was administered as a single bolus, followed by an additional 20 min of hypoxia (n = 6). In both Groups A and B, hypoxia produced a prominent pulmonary hypertensive response. Continuous infusion of hydralazine (Group A) significantly decreased the hypoxic values of Ppa and PVR from 25.1 +/- 1.1 to 21.7 +/- 1.6 mmHg (p less than 0.01) and from 4.82 +/- 0.50 to 4.17 +/- 0.40 mmHg/l/min (p less than 0.05), respectively. In Group B, hydralazine as a bolus also significantly decreased HPV, with Ppa dropping from 20.9 +/- 0.9 to 18.3 +/- 1.5 mmHg (p less than 0.05) and PVR falling from 4.98 +/- 0.55 to 4.34 +/- 0.53 mmHg/l/min (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006830:Hydralazine / Q000008:administration & dosage*; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D012756:Sheep
D006830:Hydralazine