Intravenous hydrogen sulfide does not induce hypothermia or improve survival from hemorrhagic shock in pigs.
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.
Safar Center for Resuscitation Research, University of Pittsburgh, 3434 Fifth Ave, Pittsburgh, PA 15260, USA. drabekt@anes.upmc.edu
Tomas
T
Drabek
Patrick M
PM
Kochanek
Jason
J
Stezoski
Xianren
X
Wu
Hülya
H
Bayir
Ryan C
RC
Morhard
S William
SW
Stezoski
Samuel A
SA
Tisherman
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000627:therapeutic use*; D007035:Hypothermia / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D011897:Random Allocation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013552:Swine
D006862:Hydrogen Sulfide