title: The effects of cross-linked hemoglobin on regional vascular conductance in dogs.
abstract: Hemoglobin (Hgb) solutions cause systemic vasoconstriction, which might limit their use as intraoperative blood substitutes. This constriction is thought to be caused by interaction between Hgb and nitric oxide (NO). To determine whether alpha-alpha cross-linked hemoglobin (XL-Hgb) interferes with NO-mediated vasodilation caused by acetylcholine (ACh) and sodium nitroprusside (NTP), we infused these compounds into the femoral, superior mesenteric, and circumflex coronary arteries of anesthetized dogs (n = 6) before and after partial exchange transfusion with XL-Hgb. Additional animals (n = 6) were studied after treatment with 5% albumin. XL-Hgb administration increased mean arterial pressure (MAP) from 81 +/- 5 to 112 +/- 8 (P < 0.05). Albumin reduced MAP from 84 +/- 4 mm Hg to 76 +/- 4 mm Hg (P < 0.05). Vascular conductance after XL-Hgb decreased in the femoral artery, was not changed in the mesenteric bed, and increased modestly in the coronary artery (from 0.19 +/- 0.03 to 0.26 +/- 0.02 mL x mm Hg(-1) x min(-1), P < 0.05). After albumin, conductance was unchanged in the femoral artery and increased in the mesenteric artery. Conductance also increased in the coronary bed (from 0.25 +/- 0.02 to 0.49 +/- 0.03 mL x mm Hg(-1) x min(-1), P < 0.05). The vasodilator response to ACh in the femoral or mesenteric beds was either unaffected or augmented by either XL-Hgb or albumin. In the coronary bed, XL-Hgb blunted the dilator responses to ACh and NTP, while albumin augmented the coronary dilator responses to ACh. In five additional dogs, the NO synthase inhibitor N(G)-monomethyl L-arginine caused MAP to increase from 85 +/- 4 to 90 +/- 8 mm Hg and blunted the coronary dilator responses to ACh by approximately 25%. Subsequent XL-Hgb administration caused a further increase in MAP to 112 +/- 19 mm Hg (P < 0.05) and also further blunted ACh-mediated vasodilator responses in the coronary circulation. XL-Hgb has complex effects on the circulatory system, including a reduction in the vasodilator responses to ACh and NTP in canine coronary arteries in vivo. The potential impact of these events on patients with significant coexisting disease is unclear.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Dietz
authors.forename: C M
authors.initials: CM
authors.lastname: Martin
authors.forename: A G
authors.initials: AG
authors.lastname: Beltran-del-Rio
authors.forename: M J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005078:Exchange Transfusion, Whole Blood; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007430:Intraoperative Care; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012709:Serum Albumin / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects; D018924:Vascular Capacitance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001802:Blood Substitutes; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D012709:Serum Albumin; D014665:Vasodilator Agents; C053936:hemoglobin XL99alpha; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester