Pedro Cabrales1, Amy G Tsai, Marcos Intaglietta. 1. La Jolla Bioengineering Institute, 505 Coast Boulevard South Suite #405, La Jolla, CA 92037, United States. pcabrales@ucsd.edu
Abstract
INTRODUCTION: 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. MATERIALS AND 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. DISCUSSION: 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.
INTRODUCTION: 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. MATERIALS AND 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. DISCUSSION: 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.
Authors: Pedro Cabrales; Scott Caroen; Arnold Oronsky; Corey Carter; Jane Trepel; Thomas Summers; Tony Reid; Neil Oronsky; Michelle Lybeck; Bryan Oronsky Journal: Expert Rev Hematol Date: 2017-05-22 Impact factor: 2.929
Authors: James D Reynolds; Kyla M Bennett; Anthony J Cina; Diana L Diesen; Matthew B Henderson; Faisal Matto; Andrew Plante; Rachel A Williamson; Keivan Zandinejad; Ivan T Demchenko; Douglas T Hess; Claude A Piantadosi; Jonathan S Stamler Journal: Proc Natl Acad Sci U S A Date: 2013-06-24 Impact factor: 11.205