Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition.
OBJECTIVE
Hemoglobin-based oxygen carriers (HBOC) of several types scavenge nitric oxide from the vasculature resulting in vasoconstriction and hypertension, both systemic and pulmonary. Phosphodiesterase-5 (PDE5) inhibitors promote nitric oxide activity and enhance vasodilation. The purpose of this study was to determine whether combined therapy of glutaraldehyde-polymerized bovine hemoglobin (HBOC) with a PDE5 inhibitor would counter the negative hemodynamic consequences of HBOC therapy alone, resulting in improved hemodynamics and oxygen delivery.


METHODS
A controlled, experimental study.


METHODS
A research laboratory at a university.


METHODS
Conscious male Sprague-Dawley rats.


METHODS
Glutaraldehyde-polymerized bovine hemoglobin (HBOC), sildenafil (PDE5 inhibitor), and lactated Ringer's solution (control).


RESULTS
Infusion of the HBOC resulted in significant (p < 0.05) systemic and pulmonary vasoconstriction, with reduced cardiac output and reduced oxygen delivery to the periphery. Infusion of lactated Ringer's demonstrated no changes in the measured variables. Infusion of sildenafil alone reduced systemic and pulmonary artery blood pressure, while maintaining cardiac output and oxygen delivery. Combined HBOC and sildenafil infusion resulted in stable systemic blood pressure, cardiac output, and oxygen delivery. However, the addition of sildenafil to HBOC did not fully ameliorate the pulmonary vasoconstriction caused by HBOC.


CONCLUSIONS
The HBOC used in this study resulted in pulmonary and systemic hypertension, reduced cardiac output, and oxygen delivery. These negative consequences of HBOC treatment can be largely overcome by combing HBOC treatment with a PDE5 inhibitor (sildenafil). Thus, these data support the continued investigation of combined HBOC and PDE5 inhibitor treatment in circumstances in which HBOC therapy is being considered.
Gotshall
Robert W
RW
Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA. robert.gotshall@colostate.edu
Hamilton
Karyn L
KL
Foreman
Benjamin
B
van Patot
Martha C Tissot
MC
Irwin
David C
DC
D000818:Animals; D001802:Blood Substitutes / Q000009:adverse effects*; D005976:Glutaral; D006454:Hemoglobins / Q000627:therapeutic use*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011108:Polymers / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D001802:Blood Substitutes; D006454:Hemoglobins; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011108:Polymers; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; C080663:polymerized bovine hemoglobin; D000068677:Sildenafil Citrate; D005976:Glutaral