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Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition.
Blood 1997; 89(12):4591-9Blood

Abstract

The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

Authors+Show Affiliations

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9192784

Citation

French, J A., et al. "Mechanisms of Stroke in Sickle Cell Disease: Sickle Erythrocytes Decrease Cerebral Blood Flow in Rats After Nitric Oxide Synthase Inhibition." Blood, vol. 89, no. 12, 1997, pp. 4591-9.
French JA, Kenny D, Scott JP, et al. Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition. Blood. 1997;89(12):4591-9.
French, J. A., Kenny, D., Scott, J. P., Hoffmann, R. G., Wood, J. D., Hudetz, A. G., & Hillery, C. A. (1997). Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition. Blood, 89(12), pp. 4591-9.
French JA, et al. Mechanisms of Stroke in Sickle Cell Disease: Sickle Erythrocytes Decrease Cerebral Blood Flow in Rats After Nitric Oxide Synthase Inhibition. Blood. 1997 Jun 15;89(12):4591-9. PubMed PMID: 9192784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease cerebral blood flow in rats after nitric oxide synthase inhibition. AU - French,J A,2nd AU - Kenny,D, AU - Scott,J P, AU - Hoffmann,R G, AU - Wood,J D, AU - Hudetz,A G, AU - Hillery,C A, PY - 1997/6/15/pubmed PY - 2001/3/28/medline PY - 1997/6/15/entrez SP - 4591 EP - 9 JF - Blood JO - Blood VL - 89 IS - 12 N2 - The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9192784/Mechanisms_of_stroke_in_sickle_cell_disease:_sickle_erythrocytes_decrease_cerebral_blood_flow_in_rats_after_nitric_oxide_synthase_inhibition_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9192784 DB - PRIME DP - Unbound Medicine ER -