Use of Insulin to Decrease Septic Shock-Induced Myocardial Depression in a Porcine Model

Abstract

Insulin is known to attenuate septic shock-induced myocardial depression. Possible mechanisms include an anti-inflammatory or inotropic effect of insulin. The objective of this study was to determine whether the mechanism of action of insulin in attenuating septic shock-induced myocardial depression is through an immunomodulatory effect. Fourteen pigs were assigned to one of two groups. Both groups received a 4-h infusion of lipopolysaccharide endotoxin from Escherichia coli 0111:B4. Group 2 additionally received insulin at 1.5 U/kg/h with infusions of D50 normal saline and KCl to maintain normal serum glucose and potassium levels. Cardiac function was measured with shortening fraction using transthoracic echocardiogram. Plasma TNF-α, IL-1β, and IL-6 levels were obtained every 30 min. Postmortem cytokine analysis and histomorphology were performed on the heart tissue. Although insulin attenuated septic shock-induced myocardial depression, this was not due to an anti-inflammatory effect and, therefore, likely resulted from an inotropic effect of insulin.

In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs

“…This might explain why Levenbrown et al (2013) observed a delayed TNF-␣ peak concentration only at 2.5 h p.a. of LPS, as the i.v.…”

“…With the exception of Warren et al (1997) and Levenbrown et al (2013), who surprisingly determined a maximal plasma concentration of TNF-␣ only at 1.5 and 2.5 h post administration (p.a.) of LPS, respectively, the peak concentration of TNF-␣ is unarguably established at 1 h p.a.…”

The effect of positive end-expiratory pressure on cardiac output and oxygen delivery during cardiopulmonary resuscitation

“…Intramuscular anesthesia (choice of medications and dosing) was based on a protocol used in our laboratory for prior studies. Intravenous anesthetic medications and dosing were based on published recommendations [7,8]. The pigs were then given a 30-min stabilization period.…”

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction

“…Experimental studies have been performed to support the use of GIK in septic shock, although the primary mechanism through insulin improves cardiac performance in septic shock is inconsistent among studies (36,37). Several clinical studies have addressed the use of GIK in patients with septic myocardial depression (11)(12)(13).…”