EFFECTS OF CHOLINERGIC BLOCKADE ON HEMODYNAMIC DISTURBANCES AND INTESTINAL LESIONS IN ENDOTOXIC-SHOCK IN NEWBORN PIGLETS

The parasympathetic nervous system actively participates in the regula tion of pathophysiologic responses in circulatory shock. To determine the effects of cholinergic blockade in endotoxic shock in newborn pigl ets, 16 chronically instrumented newborn piglets were infused with 10 mg/kg of endotoxin over 10 min. Eight animals were injected intravenou sly with 10 mg/kg of anisodamine, an anticholinergic drug, 10 min befo re endotoxin and then with escalating doses of 2, 5, 10, and 20 mg/kg every 10 min, beginning 60 min after endotoxin. The other eight animal s were given saline as a control. Endotoxin infusion caused elevations in mean pulmonary artery pressure and vascular resistance index and a n initial increase in systemic artery pressure followed by hypotension . Heart rate was stable for 45 min and then increased. Cardiac index f ell from a baseline of 173 +/- 20 (mean +/- S.E.) to 136 +/- 23 mL.min (-1).kg(-1) 60 min after endotoxin. Pretreatment with anisodamine incr eased heart rate from 163 +/- 15 to 289 +/- 10 beats.min(-1) and cardi ac index from 195 +/- 15 to 238 +/- 14 mL.min(-1).kg(-1) before endoto xin infusion. These variables remained at higher levels than in the co ntrol group until 60 min after endotoxin infusion; thereafter, the two groups were similar. The changes in pulmonary and systemic artery pre ssures were not significantly altered by anisodamine. After 60 min, ad ditional doses of anisodamine caused no significant hemodynamic respon ses, and the differences between the two groups were not significant. Arterial plasma thromboxane B-2 levels rose immediately and tumor necr osis factor-alpha levels increased 60 min after endotoxin infusion; no significant differences were noted between groups at any time. Intest inal histopathologic examination showed massive hemorrhage and/or necr osis in the lamina propria, submucosa, and/or serosa in five of seven control piglets, while six of seven anisodamine-treated animals develo ped only edema and/or congestion in the submucosa (p < .01). Mean surv ival times were 9.2 +/- 2.8 h and 16.6 +/- 2.6 h for the control and a nisodamine groups, respectively (p = .06). The markedly reduced intest inal lesions observed in the anisodamine group suggest that cholinergi c blockade may be helpful in treatment of septic shock. The phase-depe ndent effects of anisodamine on endotoxin-induced hemodynamic disturba nces suggest that parasympathetic tone to the heart is elevated in the early phase of shock in newborn piglets and gradually decreases in th e later phases and indicate that any therapeutic benefits resulting fr om cholinergic blockade in newborns with septic shock would likely be maximized by early use.