The effect of nifedipine alone or combined with low dose acetylsalicyclic acid on endotoxin-induced pulmonary hypertension in the piglet.
Cardiovascular responses to the calcium antagonist nifedipine, alone and combined with low dose acetylsalicyclic acid (ASA), were evaluated in a piglet model of endotoxin-induced pulmonary hypertension. All animals were anesthetized, paralyzed and mechanically ventilated. Cardiac output (CO), pulmonary artery pressure (PAP), aortic blood pressure (SAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAPM) and arterial blood gases were measured before and after induction of pulmonary hypertension by E. coli endotoxin and after treatment. Results of treated groups were compared to a control group of piglets subjected to the same dose (0.15 micrograms/kg i.v.) of endotoxin. Control animals responded to a bolus injection of endotoxin within 15 min with an increase in mean PAP by 110%. Pulmonary vascular resistance (PVR) increased by 144%. Mean arterial pressure did not change significantly from baseline values. In animals treated with a single dose of 1 mg/kg ASA prior to endotoxin, the initial pulmonary response was not quantitatively different from control values, whereas ASA 20 mg/kg abolished the pulmonary vascular reaction. The increase of systemic vascular resistance (SVR) produced by endotoxin was aggravated by high dose ASA. In piglets treated with nifedipine (4 micrograms/kg/min) over 30 min after the application of endotoxin with and without additional infusion of nifedipine 60 min prior to endotoxin the PVR could be attenuated. The combination of nifedipine and low dose ASA showed synergistic effects compared to control. The increase of mean PAP was significantly reduced, the PVR remained in baseline range due to a marked elevation of cardiac output.
D000818:Animals; D000831:Animals, Newborn; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004731:Endotoxins / Q000008:administration & dosage / Q000009:adverse effects*; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D004338:Drug Combinations; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D009543:Nifedipine; D001241:Aspirin