Effects of cholinergic blockade on hemodynamic disturbances and intestinal lesions in endotoxic shock in newborn piglets.
The parasympathetic nervous system actively participates in the regulation of pathophysiologic responses in circulatory shock. To determine the effects of cholinergic blockade in endotoxic shock in newborn piglets, 16 chronically instrumented newborn piglets were infused with 10 mg/kg of endotoxin over 10 min. Eight animals were injected intravenously with 10 mg/kg of anisodamine, an anticholinergic drug, 10 min before 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 animals were given saline as a control. Endotoxin infusion caused elevations in mean pulmonary artery pressure and vascular resistance index and an initial increase in systemic artery pressure followed by hypotension. Heart rate was stable for 45 min and then increased. Cardiac index fell from a baseline of 173 +/- 20 (mean +/- S.E.) to 136 +/- 23 mL.min-1.kg-1 60 min after endotoxin. Pretreatment with anisodamine increased heart rate from 163 +/- 15 to 289 +/- 10 beats.min-1 and cardiac index from 195 +/- 15 to 238 +/- 14 mL.min-1.kg-1 before endotoxin infusion. These variables remained at higher levels than in the control group until 60 min after endotoxin infusion; thereafter, the two groups were similar. The changes in pulmonary and systemic artery pressures were not significantly altered by anisodamine. After 60 min, additional doses of anisodamine caused no significant hemodynamic responses, and the differences between the two groups were not significant. Arterial plasma thromboxane B2 levels rose immediately and tumor necrosis factor-alpha levels increased 60 min after endotoxin infusion; no significant differences were noted between groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
J X
JX
Department of Pediatrics, University of Alabama at Birmingham 35233-7335, USA.
Kelly
D R
DR
Oliver
J R
JR
Grantham
K D
KD
Philips
J B
JB
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003967:Diarrhea; D004064:Digestive System / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010276:Parasympatholytics / Q000494:pharmacology*; D010313:Partial Pressure; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D012772:Shock, Septic / Q000473:pathology / Q000503:physiopathology*; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014839:Vomiting
D004731:Endotoxins; D010276:Parasympatholytics; D012991:Solanaceous Alkaloids; D014409:Tumor Necrosis Factor-alpha; C003922:anisodamine; D002245:Carbon Dioxide; D013929:Thromboxane B2; D010100:Oxygen