A Randomized Porcine Study in Low Cardiac Output of Vasoactive and Inotropic Drug Effects on the Gastrointestinal Tract

Abstract

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.

Vasopressors and Risk of Acute Mesenteric Ischemia: A Worldwide Pharmacovigilance Analysis and Comprehensive Literature Review

“…First, high-dose of norepinephrine may induce oxidative stress and myocardial cells insult but also alter sepsis-associated immunomodulation ( 90 ). Furthermore, high-dose of norepinephrine may impair the splanchnic circulation with an increase in systemic and mesenteric vascular resistances ( 91 ). Nevertheless, a large randomized trial, the SEPSISPAM study, assessed the effects of two levels of mean arterial pressure in 776 patients with septic shock ( 92 ).…”

Alternatives to norepinephrine in septic shock: Which agents and when?

“…[ 14 ] In particular, the use of high doses of norepinephrine is associated with more frequent atrial fibrillation, [ 14 ] possible induction of oxidative stress and insult to myocardial cells, [ 13 ] and possible alterations in the splanchnic circulation. [ 15 ] Second, the use of high doses of catecholamines, known as “vasopressor load,” is directly related to mortality in patients with septic shock regardless of the targeted mean arterial pressure (MAP), because of catecholamine-induced cardiac toxicity. [ 16 ] Third, norepinephrine (but not vasopressin) may alter sepsis-associated immunomodulation by dysregulating the immune response through anti-inflammatory effects, thus contributing to sepsis-induced immunoparalysis with persistent adrenergic stimulation.…”

What's New in Shock, August 2021?

“…Potent vasodilators and constrictors have been used clinically to combat the cardiovascular and metabolic effects of low flow in this condition, to mixed affects. Seilitz et al (17) have developed a swine mode of cardiac dysfunction to test two inodilators (Levosimendan and milrinone) and two vasoconstrictors (vasopressin and norepinephrine) commonly used in this condition. The authors found that inodilators had negligible vasodilatory effects on the gastrointestinal circulation.…”