Intravenous Hydrogen Sulfide Does Not Induce Hypothermia or Improve Survival from Hemorrhagic Shock in Pigs

Abstract

Several laboratory studies suggested that induced hypothermia during hemorrhagic shock improves survival. Inhaled hydrogen sulfide (H2S) induced hypothermia and decreased metabolism in mice and rats but not in piglets. We tested the hypothesis that i.v. H2S will induce hypothermia, reduce oxygen consumption (VO2), and improve outcome in prolonged hemorrhagic shock in pigs. We also assessed markers of organ injury (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, creatinine, and troponin) and level of protein thiols to monitor H2S metabolism. In a prospective randomized study, pigs were subjected to volume-controlled hemorrhagic shock with limited fluid resuscitation to maintain MAP 30 mmHg or greater. The study group received infusion of H2S at 5 mg·kg·h; the control group received vehicle (n = 8 per group). Dose was based on the highest tolerated dose in pilot studies. Full resuscitation was initiated after 3 h. There were no differences in survival at 24 h between groups (2/8 in H2S vs. 3/8 in control group). Heart rate increased similarly during hemorrhagic shock in both groups. Cardiac output was better preserved in the delayed phase of hemorrhagic shock in the control group. Temperature and VO2 were similar in both groups during hemorrhagic shock and resuscitation. Markers of organ injury and protein thiols markedly increased in both groups with no differences between groups. In conclusion, we were not able to demonstrate the hypothermia-inducing effect or a reduction in VO2 from H2S infusion in our model of hemorrhagic shock in pigs. Our data mirror those seen in piglets and provide additional evidence of difficulty in translating the hypothermia effect of H2S to large animals in a clinically relevant postinsult paradigm.

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

“…Although most of the published studies have reported that H 2 S is able to reduce a variety of organs damage in animal models of disease, Drabek et al have argued that intravenous administration of hydrogen sulfide does not induce hypothermia or improve survival from hemorrhagic shock in pigs [8] ; this result was not in accordance with the results reported by Blackstone [6] . Similarly, whether H 2 S has anti-or pro-inflammatory effects remains controversial.…”

“…onstrated that H 2 S administration may induce a "suspended animation-like state" in small mammals such as mice and rats [6,7] but not in larger mammals such as pigs [8] . There have recently been a number of large studies that were designed to investigate the beneficial effects of H 2 S on important organs.…”

Effects of environmental hypothermia on hemodynamics and oxygen dynamics in a conscious swine model of hemorrhagic shock

“…Because swine models of HS have similar cardiovascular and hemodynamic responses to HS as humans, they are often used to investigate the effects of HS on hemodynamics and prognosis. [12][13][14] At present, anesthetized swine models of hemorrhagic shock were used in many studies. However, HS and anesthesia can not only interfere with the cardiovascular system and body temperature regulation, but also interact each other.…”

An Exogenous Hydrogen Sulphide Donor, NaHS, Inhibits the Nuclear Factor κB Inhibitor Kinase/Nuclear Factor κB Inhibitor/Nuclear Factor-κB Signaling Pathway and Exerts Cardioprotective Effects in a Rat Hemorrhagic Shock Model

“…18) In a recent study on H 2 S, Drabek and colleagues found that H 2 S did not induce hypothermia or improve survival after HS was induced in pigs. 19) The discrepancy in the results may result from the different animal models used and interference, and may indicate the limitations of the effects of H 2 S in different animal models.…”