Modulation of nitric oxide expression with methylene blue does not improve outcome after hypovolemic cardiac arrest

Aim of the study

We recently reported that female sex protects against cerebral and cardiac injury after hypovolemic cardiac arrest (CA), independent of sex hormone effects. As female sex was also associated with a smaller increase in inducible and neuronal nitric oxide synthase (NOS), we hypothesised that nitric oxide inhibition with methylene blue (MB) improves the outcome, primarily in male animals.

Methods

Twenty sexually immature piglets (10 males and 10 females) were bled to mean arterial blood pressure of 35 mmHg, and were subjected to 2 min of untreated CA followed by 8 min of open chest cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3 ml kg⁻¹ hypertonic saline-dextran. Methylene blue was then administered as bolus of 2.5 mg kg⁻¹ over 20 min, followed by 1.5 mg kg⁻¹ infusion over 40 min. Historical data from 21 animals were used as control (no MB). Hemodynamic parameters, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. Histopathological evaluation of heart specimens was performed.

Results

There were no differences between male and female animals in survival or resuscitation rate. After CA female piglets had significantly greater systolic and mean arterial pressures, and had lower troponin I plasma concentrations compared to male piglets, with or without MB. No difference was observed in histopathological analysis of heart specimens between sexes.

Conclusions

After resuscitation from hypovolemic CA, female sex protects against cardiac injury, independent of sex hormones. Modulation of NO expression with MB does not improve survival or myocardial histological injury in either sex.