Regional blood flow alterations after bovine fumaryl beta beta-crosslinked hemoglobin transfusion and nitric oxide synthase inhibition.
OBJECTIVE
a) To determine whether isovolemic exchange transfusion with cell-free, bovine fumaryl beta beta-crosslinked hemoglobin results in a different pattern of regional blood flow distribution than transfusion with a poor oxygen-carrying, colloidal solution. b) Because of potential nitric oxide scavenging by plasma-based hemoglobin, to determine whether blood flow differences are reduced after nitric oxide synthase inhibition.


METHODS
A prospective, randomized design with repeated blood flow measurements within groups.


METHODS
Experimental physiology laboratory in a university medical center.


METHODS
Pentobarbital-anesthetized female cats.


METHODS
Three groups of eight cats were studied: a) a control group with no transfusion (hematocrit of 32%); b) an anemia group in which exchange transfusion with an albumin-containing solution reduced hematocrit to 18% over a 40- to 50-min period; and c) a group in which cell-free hemoglobin was exchanged transfused to reduce hematocrit to 18%, without a proportional reduction in oxygen-carrying capacity. Bovine hemoglobin was covalently crosslinked intramolecularly between the 81-lysine residues on the beta-subunits to stabilize the tetramer. Regional blood flow was measured by the radiolabeled microsphere technique before transfusion and at 10, 100, and 180 mins from the start of transfusion. At 190 mins, N omega-nitro-L-arginine methyl ester (L-NAME; 10mg/kg) was infused to inhibit nitric oxide synthase and blood flow was measured 30 mins later.


RESULTS
Mean arterial pressure was unchanged in the control and albumin-transfused groups. However, mean arterial pressure increased rapidly in the hemoglobin-transfused group. With hemoglobin transfusion, there were marked reductions in blood flow to the intestines, kidneys and adrenal glands. 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 hemoglobin transfusion. In contrast, in skeletal muscle and left ventricle, blood flow rates increased in the albumin-transfused group and were greater than those values found in the control group and hemoglobin-transfused group. The greater flow in the albumin-transfused group persisted after L-NAME administration. There was no difference in renal sodium, potassium, or osmolar excretion, or in urine flow between groups.


CONCLUSIONS
Transfusion with cell-free, bovine crosslinked hemoglobin in cats can selective reductions in blood flow in the intestines, kidneys, and adrenal glands without evidence of renal dysfunction by a mechanism consistent with nitric oxide scavenging. In skeletal and cardiac muscle, the increase in blood flow persisted after nitric oxide inhibition in the albumin group relative to the hemoglobin-transfused group at equivalent hematocrit values. This finding is consistent with compensatory vasoconstriction with hemoglobin transfusion due to improved oxygenation by this oxygen carrier.
Ulatowski
J A
JA
Department of Anesthesiology/Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Nishikawa
T
T
Matheson-Urbaitis
B
B
Bucci
E
E
Traystman
R J
RJ
Koehler
R C
RC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D002415:Cats; D002417:Cattle; D003432:Cross-Linking Reagents / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005078:Exchange Transfusion, Whole Blood / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D006454:Hemoglobins / Q000302:isolation & purification / Q000627:therapeutic use*; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D011446:Prospective Studies; D011868:Radioisotopes; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D011868:Radioisotopes; C099148:fumaryl beta,beta-crosslinked hemoglobin; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester