Exogenous nitric oxide induces protection during hemorrhagic shock.
BACKGROUND
This study analyzed the systemic and microvascular hemodynamic changes related to increased nitric oxide (NO) availability during the early phase of hemorrhagic shock. Hemodynamic responses to hemorrhagic shock were studied in the hamster window chamber.


METHODS
Exogenous NO was administered in the form of nitrosothiols (nitrosylated glutathione, GSNO) and was given prior the onset of hemorrhage. Moderate hemorrhage was induced by arterial controlled bleeding of 50% of the blood volume, and the hypovolemic shock was followed over 90 min.


RESULTS
Animals pre-treated with GSNO maintained systemic and microvascular conditions during hypovolemic hemorrhagic shock, when compared to animal treated with glutathione (GSH) or the Sham group. Low concentrations of NO released during the early phase of hypovolemic shock from GSNO mitigated arteriolar vasoconstriction, increased capillary perfusion and venous return, and improved cardiac function (recovered of blood pressure and stabilized heart rate). GSNO's effect on resistance vessels influenced intravascular pressure redistribution and blood flow, preventing tissue ischemia.


CONCLUSIONS
Increases in NO availability during the early phase of hypovolemic shock could preserve cardiac function and microvascular perfusion, sustaining organ function. Direct translation into a clinical scenario may be limited, although the pathophysiological importance of NO in the early phase of hypovolemia is clearly highlighted here.
La Jolla Bioengineering Institute, 505 Coast Boulevard South Suite #405, La Jolla, CA 92037, United States. pcabrales@ucsd.edu
Pedro
P
Cabrales
Amy G
AG
Tsai
Marcos
M
Intaglietta
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006224:Cricetinae; D004195:Disease Models, Animal; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
D002317:Cardiovascular Agents; D009569:Nitric Oxide