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Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic hemodynamics and regional circulation in
1Department of Pharmaceutics and Pharmacodynamics, University of Illinois, Chicago Health Sciences Center 60612-7231.
Insights
Diaspirin cross-linked hemoglobin (DCLHb) matched norepinephrine's (NE) pressor effect without reducing blood flow to organs. Unlike NE, DCLHb increased or maintained blood flow to vital organs, indicating a safer hemodynamic profile.
Area of Science:
- Cardiovascular Physiology
- Hemoglobin-based Oxygen Carriers
- Pharmacology
Background:
- Hemoglobin-based oxygen carriers (HBOCs) are investigated as blood substitutes.
- Diaspirin cross-linked hemoglobin (DCLHb) is a modified HBOC.
- Understanding the hemodynamic effects of DCLHb is crucial for its clinical application.
Purpose of the Study:
- To compare the hemodynamic effects of diaspirin cross-linked hemoglobin (DCLHb) with norepinephrine (NE).
- To evaluate the impact of DCLHb and NE on organ-specific blood flow and vascular resistance.
- To assess the safety profile of DCLHb regarding circulatory function.
Main Methods:
- Intravenous administration of DCLHb (400 mg/kg) and norepinephrine (NE) (25 micrograms/kg/min) in a preclinical model.
- Measurement of systemic hemodynamic parameters: blood pressure, heart rate, cardiac output, and total peripheral resistance.
- Assessment of regional blood flow and vascular resistance in various organs (heart, kidneys, brain, gastrointestinal tract, spleen, skin, musculo-skeletal system).
Main Results:
- DCLHb and NE produced equivalent pressor effects.
- DCLHb increased total peripheral resistance, while NE increased it more significantly.
- DCLHb did not decrease blood flow to any organ; NE significantly reduced blood flow to several organs, including kidneys and spleen.
Conclusions:
- DCLHb demonstrates a favorable hemodynamic profile compared to NE, maintaining organ perfusion.
- DCLHb represents a potentially safer alternative to vasopressors like NE for managing blood pressure.
- Further research into DCLHb's therapeutic potential in conditions requiring circulatory support is warranted.
Abstract:
Diaspirin cross-linked hemoglobin (DCLHb) (400 mg/kg, i.v.) produced a pressor effect that was equal to that produced by norepinephrine (NE) (25 micrograms/kg/min i.v. infusion). Total peripheral resistance was increased by DCLHb and more significantly by NE. Heart rate was not affected by DCLHb but was significantly increased by NE. The cardiac output and stroke volume were insignificantly increased by DCLHb but were significantly decreased by NE. DCLHb and NE produced a significant increase in blood flow to the heart. The vascular resistance in the heart was not affected by DCLHb but was decreased by NE. DCLHb did not affect the renal and brain circulation, but NE in kidneys decreased the blood flow and increased the vascular resistance, whereas in the brain it increased the blood flow and decreased the vascular resistance. DCLHb increased the blood flow to the stomach and small intestine. The vascular resistance was not affected by DCLHb in the gastrointestinal tract. NE did not affect the blood circulation in the gastrointestinal tract. Blood flow to the spleen was increased by DCLHb, and there was no change in the vascular resistance. NE insignificantly decreased the blood flow to the spleen and significantly increased the vascular resistance. The blood circulation to the mesentery and pancreas was not affected by DCLHb, whereas NE increased the blood flow without affecting the vascular resistance. DCLHb produced a significant increase in the blood flow to the skin without affecting the vascular resistance, whereas NE did not affect the blood flow but increased the vascular resistance. DCLHb did not affect the blood flow to the musculo-skeletal system but increased the vascular resistance, whereas NE decreased the blood flow and increased the vascular resistance. In summary, although the pressor effect of DCLHb and NE at the doses studied is equal, DCLHb did not decrease the blood flow to any organ, whereas NE produced significant decreases in blood flow to several organs. It is concluded that the blood flow to most of the organs is either increased or not affected by DCLHb.