Lowering of blood pressure by increasing hematocrit with non nitric oxide scavenging red blood cells.
Isovolemic exchange transfusion of 40% of the blood volume in awake hamsters was used to replace native red blood cells (RBCs) with RBCs whose hemoglobin (Hb) was oxidized to methemoglobin (MetHb), MetRBCs. The exchange maintained constant blood volume and produced different final hematocrits (Hcts), varying from 48 to 62% Hct. Mean arterial pressure (MAP) did not change after exchange transfusion, in which 40% of the native RBCs were replaced with MetRBCs, without increasing Hct. Increasing Hct with MetRBCs lowered MAP by 12 mm Hg when Hct was increased 12% above baseline. Further increases of Hct with MetRBCs progressively returned MAP to baseline, which occurred at 62% Hct, a 30% increase in Hct from baseline. These observations show a parabolic "U" shaped distribution of MAP against the change in Hct. Cardiac index, cardiac output divided by body weight, increased between 2 and 17% above baseline for the range of Hcts tested. Peripheral vascular resistance (VR) was decreased 18% from baseline when Hct was increased 12% from baseline. VR and MAP were above baseline for increases in Hct higher than 30%. However, vascular hindrance, VR normalized by blood viscosity (which reflects the contribution of vascular geometry), was lower than baseline for all the increases in Hct tested with MetRBC, indicating prevalence of vasodilation. These suggest that acute increases in Hct with MetRBCs increase endothelium shear stress and stimulate the production of vasoactive factors (e.g., nitric oxide [NO]). When MetRBCs were compared with functional RBCs, vasodilation was augmented for MetRBCs probably due to the lower NO scavenging of MetHb. Consequently, MetRBCs increased the viscosity related hypotension range compared with functional RBCs as NO shear stress vasodilation mediated responses are greater.
Salazar Vázquez
Beatriz Y
BY
Department of Bioengineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92037-0412, USA.
Cabrales
Pedro
P
Tsai
Amy G
AG
Johnson
Paul C
PC
Intaglietta
Marcos
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006224:Cricetinae; D017707:Erythrocyte Transfusion; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006400:Hematocrit; D008297:Male; D008647:Mesocricetus; D009569:Nitric Oxide / Q000097:blood* / Q000737:chemistry
D016166:Free Radical Scavengers; D009569:Nitric Oxide
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