REGIONAL BLOOD-FLOW ALTERATIONS AFTER BOVINE FUMARYL BETA-BETA-CROSS-LINKED HEMOGLOBIN TRANSFUSION AND NITRIC-OXIDE SYNTHASE INHIBITION

Objectives: a) To determine whether isovolemic exchange transfusion wi th cell-free, bovine fumaryl beta beta-crosslinked hemoglobin results in a different pattern of regional blood flow distribution than transf usion with a poor oxygen-carrying, colloidal solution, b) Because of p otential nitric oxide scavenging by plasma-based hemoglobin, to determ ine whether blood flow differences are reduced after nitric oxide synt hase inhibition. Design: A prospective, randomized design with repeate d blood flow measurements within groups. Setting: Experimental physiol ogy laboratory in a university medical center. Subjects: Pentobarbital -anesthetized female cats. Interventions: Three groups of eight cats w ere studied: a) a control group with no transfusion (hematocrit of 32% ); b) an anemia group in which exchange transfusion with an albumin co ntaining solution reduced hematocrit to 18% over a 40- to 50-min perio d; and c) a group in which cell-free hemoglobin was exchanged transfus ed to reduce hematocrit to 18%, without a proportional reduction in ox ygen-carrying capacity. Bovine hemoglobin was covalently crosslinked i ntramolecularly between the 81-lysine residues on the beta-subunits to stabilize the tetramer. Regional blood flow was measured by the radio labeled microsphere technique before transfusion and at 10, 100, and 1 80 mins from the start of transfusion. At 190 mins, N-omega-nitro-L-ar ginine methyl ester (L-NAME; 10 mg/kg) was infused to inhibit nitric o xide synthase and blood flow was measured 30 mins later. Measurements and Main Results: Mean arterial pressure was unchanged in the control and albumin transfused groups, However, mean arterial pressure increas ed rapidly in the mean arterial pressure increased rapidly in the hemo globin-transfused group. With hemoglobin transfusion, there were marke d reductions in blood flow to the intestines, kidneys, acid adrenal gl ands. Administration of L-NAME after hemoglobin transfusion failed to increase arterial pressure or cause further reductions in intestinal, renal, or adrenal blood flow. Administration of L-NAME to the control and albumin-transfused groups increased arterial pressure and reduced intestinal, renal, and adrenal blood flows to values attained with hem oglobin transfusion. In contrast, in skeletal muscle and left ventricl e, blood flow rates increased in the albumin-transfused group and were greater than those values found in the control group and the hemoglob in-transfused group. The greater flow in the albumin-transfused group persisted after L-NAME administration. There was no difference in rena l sodium, potassium, or osmolar excretion, or in urine flow between gr oups. Conclusions: Transfusion with cell-free, bovine crosslinked hemo globin in cats can cause selective reductions in blood Row in the inte stines, kidneys, and adrenal glands without evidence of renal dysfunct ion by a mechanism consistent with nitric oxide scavenging. In skeleta l and cardiac muscle, the increase in blood flow persisted after nitri c oxide inhibition in the albumin group relative to the hemoglobin-tra nsfused group at equivalent hematocrit values. This finding is consist ent with compensatory vasoconstriction with hemoglobin transfusion due to improved oxygenation by this oxygen carrier. hemoglobin-transfused group. With hemoglobin transfusion, there were marked reductions in b lood flow to the intestines, kidneys, acid adrenal glands. Administrat ion of L-NAME after hemoglobin transfusion failed to increase arterial pressure or cause further reductions in intestinal, renal, or adrenal blood flow. Administration of L-NAME to the control and albumin-trans fused groups increased arterial pressure and reduced intestinal, renal , and adrenal blood flows to values attained with hemoglobin transfusi on. In contrast, in skeletal muscle and left ventricle, blood flow rat es increased in the albumin-transfused group and were greater than tho se values found in the control group and the hemoglobin-transfused gro up. The greater flow in the albumin-transfused group persisted after L -NAME administration. There was no difference in renal sodium, potassi um, or osmolar excretion, or in urine flow between groups. Conclusions : Transfusion with cell-free, bovine crosslinked hemoglobin in cats ca n cause selective reductions in blood Row in the intestines, kidneys, and adrenal glands without evidence of renal dysfunction by a mechanis m consistent with nitric oxide scavenging. In skeletal and cardiac mus cle, the increase in blood flow persisted after nitric oxide inhibitio n in the albumin group relative to the hemoglobin-transfused group at equivalent hematocrit values. This finding is consistent with compensa tory vasoconstriction with hemoglobin transfusion due to improved oxyg enation by this oxygen carrier.