Systemic and mesenteric vascular effects of platelet-activating factor and cocaine. In vivo effects on a neonatal swine model.
Mesenteric hypoperfusion may be responsible for alterations in gut mucosa leading to necrotizing enterocolitis. Platelet-activating factor (PAF) and cocaine have been implicated in the etiology of necrotizing enterocolitis. We have demonstrated direct toxic effects of these compounds in vitro, but the in vivo mechanism of bowel damage is unknown. Newborn piglets (3.0 +/- 0.3 kg) had physiologic parameters (electrocardiogram, blood pressure, pulse, and central venous pressure) continuously monitored as well as Doppler probe recordings of superior mesenteric artery flow (Qsma). Aortic flow with calculation of cardiac index, and systemic and mesenteric vascular resistances (SVR and MVR) were also determined. Group 1 (N = 8) received PAF (0.5 microgram/kg). Groups 2 (N = 8) and 3 (N = 8) received high (17 mg/kg) and low (9 mg/kg) doses of cocaine, respectively. Each subject served as its own control. Histology demonstrated edema or early mucosal hemorrhage in all groups. PAF caused a third-degree atrioventricular block of short duration and a prolonged decrease of the cardiac index, but only a brief elevation of SVR and MVR. The cocaine groups had a sustained increase of SVR and MVR associated with a decrease of cardiac index. The decrease of Qsma paralleled the changes of MVR in each subject. These data show that both PAF and cocaine induce mesenteric ischemia. The effect of PAF is of short duration and mainly related to its cardiotoxic effects resulting in low Qsma. Cocaine causes an increase in MVR with prolonged depression of mesenteric flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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David Paley Lichtenstein Laboratory of Surgical Metabolism and Nutrition, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104.
Brown
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McGeehin
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O'Niell
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Ross
A J
AJ
D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output / Q000187:drug effects; D003042:Cocaine / Q000009:adverse effects*; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology*; D006327:Heart Block / Q000139:chemically induced; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000139:chemically induced* / Q000150:complications; D010972:Platelet Activating Factor / Q000009:adverse effects*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D010972:Platelet Activating Factor; D003042:Cocaine