High-dose hydroxocobalamin administered after H₂S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep

Abstract

Context. Severe H₂S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. Objectives. To determine the time course and the nature of H₂S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure. Materials and methods. NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H₂S in the blood, which was previously found to lead to cardiac arrest within minutes following the cessation of H₂S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion. Results. All animals were still alive at the cessation of H₂S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H₂S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H₂S trapping. Conclusion. In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H₂S exposure. Very high dose of hydroxocobalamin (5 g), injected very early after the cessation of H₂S exposure, improved cardiac contractility and prevented PEA.

Keywords:

• H₂S
• Cardiac contractility
• antidotes

Acknowledgements

The authors are grateful to Ms. Nicole Tubbs for her skillful technical assistance.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This work has been supported in part by the CounterACT Program, National Institutes of Health, Office of the Director (NIH OD), and the National Institute of Neurological Disorders and Stroke (NINDS), Grant Number 5R21NS080788-02.

Dr. Sonobe was supported in part by a Grant-in-Aid for scientific research (N11J10987) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.