A Randomized Porcine Study in Low Cardiac Output of Vasoactive and Inotropic Drug Effects on the Gastrointestinal Tract.
Animals
Cardiac Output, Low
/ metabolism
Disease Models, Animal
Female
Gastrointestinal Tract
/ drug effects
Male
Milrinone
/ pharmacology
Norepinephrine
/ pharmacology
Random Allocation
Simendan
/ pharmacology
Splanchnic Circulation
/ drug effects
Swine
Vasodilator Agents
/ pharmacology
Vasopressins
/ pharmacology
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
pubmed:
15
1
2021
medline:
14
1
2022
entrez:
14
1
2021
Statut:
ppublish
Résumé
Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO. In anesthetized pigs, CO was lowered to 60% of baseline by partial inferior caval vein balloon inflation. The animals were randomized to placebo (n = 8), levosimendan (24 μg kg-1 bolus, 0.2 μg kg-1 min-1, n = 7), milrinone (50 μg kg-1 bolus, 0.5 μg kg-1 min-1, n = 7), vasopressin (0.001, 0.002 and 0.006 U kg-1 min-1, 1 h each, n = 7) or norepinephrine (0.04, 0.12, and 0.36 μg kg-1 min-1, 1 h each, n = 7). Hemodynamic variables including mesenteric blood flow were collected. Systemic, mixed-venous, mesenteric-venous, and intraperitoneal metabolites were analyzed. Cardiac output was stable at 60% in all groups, which resulted in systemic hypotension, low superior mesenteric artery blood flow, lactic acidosis, and increased intraperitoneal concentrations of lactate. Levosimendan and milrinone did not change any circulatory variables, but levosimendan increased blood lactate concentrations. Vasopressin and norepinephrine increased systemic and mesenteric vascular resistances at the highest dose. Vasopressin increased mesenteric resistance more than systemic, and the intraperitoneal lactate concentration and lactate/pyruvate ratio. Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High-dose vasopressors may have side effects in the splanchnic circulation.
Sections du résumé
BACKGROUND
Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO.
METHODS
In anesthetized pigs, CO was lowered to 60% of baseline by partial inferior caval vein balloon inflation. The animals were randomized to placebo (n = 8), levosimendan (24 μg kg-1 bolus, 0.2 μg kg-1 min-1, n = 7), milrinone (50 μg kg-1 bolus, 0.5 μg kg-1 min-1, n = 7), vasopressin (0.001, 0.002 and 0.006 U kg-1 min-1, 1 h each, n = 7) or norepinephrine (0.04, 0.12, and 0.36 μg kg-1 min-1, 1 h each, n = 7). Hemodynamic variables including mesenteric blood flow were collected. Systemic, mixed-venous, mesenteric-venous, and intraperitoneal metabolites were analyzed.
RESULTS
Cardiac output was stable at 60% in all groups, which resulted in systemic hypotension, low superior mesenteric artery blood flow, lactic acidosis, and increased intraperitoneal concentrations of lactate. Levosimendan and milrinone did not change any circulatory variables, but levosimendan increased blood lactate concentrations. Vasopressin and norepinephrine increased systemic and mesenteric vascular resistances at the highest dose. Vasopressin increased mesenteric resistance more than systemic, and the intraperitoneal lactate concentration and lactate/pyruvate ratio.
CONCLUSION
Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High-dose vasopressors may have side effects in the splanchnic circulation.
Identifiants
pubmed: 33443363
doi: 10.1097/SHK.0000000000001726
pii: 00024382-202108000-00018
pmc: PMC8529897
doi:
Substances chimiques
Vasodilator Agents
0
Vasopressins
11000-17-2
Simendan
349552KRHK
Milrinone
JU9YAX04C7
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
308-317Informations de copyright
Copyright © 2021 by the Shock Society.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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