Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation☆☆☆

Received 1 September 2009; received in revised form 24 November 2009; accepted 17 December 2009. published online 18 January 2010.

Abstract

Background

Vasoconstriction, an inherent property of Hemoglobin Based Oxygen Carriers (HBOC) potentially due to nitric oxide (NO) scavenging, may increase cardiovascular complications in HBOC resuscitated trauma patients. The purpose of this study was to determine if co-administration of a weak NO donor, intravenous nitroglycerin (NTG), with HBOC-201 during resuscitation from hemorrhagic shock could safely attenuate HBOC-201 vasoconstriction.

Methods and results

Hemorrhagic shock was induced in 44 swine randomized to receive fluid resuscitation with HBOC, HBOC+NTG10mcg/kg/min, HBOC+NTG20mcg/kg/min, HBOC+NTG40mcg/kg/min, Hetastarch (HES), HES+NTG20mcg/kg/min, NTG20mcg/kg/min and Lactated Ringers (LR). HBOC resuscitation from hemorrhagic shock increased mean arterial pressure (MAP=94±33mmHg), mean pulmonary artery pressure (MPAP=29±11mmHg) and systemic vascular resistance (SVR=2684±871dyns/cm5) in comparison to HES. Co-administration of NTG during HBOC resuscitation attenuated vasoconstriction with HBOC+40mcg/kg/min demonstrating the most robust reduction in vasoconstriction (MAP=59±23mmHg, MPAP=18±7mmHg, and SVR=1827±511dyns/cm5), although the effects were transient. Co-administration of NTG with HBOC did not alter base deficit, lactate, methemoglobin levels, nor cause profound hypotension during resuscitation.

Conclusion

Nitroglycerin attenuates vasoconstrictive properties of HBOC when co-administered during resuscitation in this swine model of hemorrhagic shock. Translational survival studies are required to determine if this strategy of attenuation of the vasoconstriction of HBOC-201 reduces cardiovascular complications and improves outcome with HBOC fluid resuscitation for hemorrhagic shock.

Keywords: Hemorrhage, Hemoglobin Based Oxygen Carrier, Nitroglycerin, Vasoconstriction

a Department of Emergency Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States

b Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL, United States

c Combat Casualty Directorate, Naval Medical Research Center, Silver Springs, MD, United States

d Infectious Diseases, National Naval Medical Center, Silver Springs, MD, United States

e Medicine and Surgery Departments, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

Corresponding author at: Campus Box 7594, Physician Office Building 1st Floor Room p1114, 170 Manning Drive, Chapel Hill, NC 27599, United States. Tel.: +1 919 843 1966; fax: +1 919 966 3049.

☆ A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2009.12.015.

☆☆ The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.

PII: S0300-9572(09)00669-8

doi:10.1016/j.resuscitation.2009.12.015

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