Yohimbine modulates diaspirin crosslinked hemoglobin-induced systemic hemodynamics and regional circulatory effects

Diaspirin crosslinked hemoglobin, a hemoglobin-based blood substitute, is proposed to be an effective resuscitative solution. It produces an immediate, but limited increase in blood pressure when administered to conscious or anesthetized rats. This vasoactivity is associated with an increase in blood flow to several major organs. It has been shown that alpha-adrenergic receptors in the peripheral vascular system are sensitized by diaspirin crosslinked hemoglobin in rats. The present study was conducted to determine the effect of yohimbine, an alpha 2-adrenergic receptor antagonist on systemic hemodynamics and regional circulatory effects of diaspirin crosslinked hemoglobin.

Prospective, randomized comparison of cardiovascular effects of diaspirin crosslinked hemoglobin in control and yohimbine-pretreated rats.

Laboratory of experimental medicine.

Male Sprague-Dawley rats weighing 300 to 350 g.

Modified, highly purified, and heat-pasteurized hemoglobin (diaspirin crosslinked hemoglobin) in control and yohimbine-treated (2 mg/kg i.v.) rats.

The systemic hemodynamics and regional circulation were measured using a radioactive microsphere technique. Diaspirin crosslinked hemoglobin (400 mg/kg i.v.) produced an increase in blood pressure and total peripheral resistance, while heart rate, cardiac output, and stroke volume were not significantly altered in control rats. In yohimbine-pretreated (2 mg/kg i.v.) animals, diaspirin crosslinked hemoglobin did not produce any change in heart rate, stroke volume, cardiac output, and total peripheral resistance, but a slight increase in blood pressure was observed compared with baseline values obtained after the administration of yohimbine. The increase in blood pressure induced by diaspirin crosslinked hemoglobin was significantly blocked by pretreatment with yohimbine. Yohimbine (2 mg/kg i.v.) per se decreased blood pressure, while other systemic hemodynamic parameters were not affected. Diaspirin crosslinked hemoglobin increased blood flow to the heart, gastrointestinal tract (stomach, small intestine, cecum, and large intestine), portal (spleen, mesentery, and pancreas) and skin, while blood flow to the brain (cerebral hemispheres, diencephalon, cerebellum, and brain stem), liver, kidneys, and musculoskeletal system was not affected in control rats. In yohimbine-pretreated animals, diaspirin crosslinked hemoglobin produced an increase in blood flow to the heart, brain (cerebellum and brain stem), liver, small intestine, cecum, spleen, mesentery and pancreas, kidneys, skin and musculoskeletal system, while blood flow to the stomach and large intestine was not affected. Yohimbine pretreatment significantly attenuated the diaspirin crosslinked hemoglobin-induced increase in blood flow to the large intestine, mesentery, and pancreas.

The cardiovascular actions of diaspirin crosslinked hemoglobin are partially mediated through alpha 2-adrenergic receptors. Adrenergic receptor antagonists may be useful in attenuating the pressor effect of diaspirin crosslinked hemoglobin while maintaining the regional perfusion.