Effects of L-arginine on cerebral blood flow, microvascular permeability, number of perfused capillaries, and brain water content in the traumatized mouse brain.
It is has been suggested that decreased production of the vasodilatory and anti-aggregative substance NO (nitric oxide) may result in lower cerebral blood flow (CBF) in injured areas of the traumatized brain. The NO-precursor L-arginine has been shown to counteract CBF decreases early after trauma, but microcirculatory and more long-term effects on CBF of L-arginine have not been investigated. In an attempt to analyze effects of L-arginine on the microcirculation in the traumatized brain, the present study was designed to evaluate the effects of L-arginine compared to vehicle (0.9% saline) following a standardized controlled cortical-impact brain trauma in mice. Cerebral blood flow (autoradiography [(14)C]-iodoantipyrine), number of perfused capillaries (FITC-dextran fluorescence technique), brain water content (wet vs. dry weight) and the blood to brain transfer constant K(i) for [(51)Cr]-EDTA were analyzed in the injured and the contralateral cortex. Cortical blood flow in the injured cortex was 0.43+/-0.3 mL/g/min and 0.81+/-0.3 mL/g/min 3 h after trauma in the vehicle and L-arginine groups, respectively (p<0.05), and no treatment effect was seen 24 h after trauma. The number of perfused capillaries decreased following trauma and was unaffected by L-arginine. K(i) increased following trauma and was unaffected by L-arginine. Brain water content was lower in the L-arginine group than in the vehicle group 3 h after trauma and there was no difference between the groups 24 h after trauma. We conclude that L-arginine reduces brain edema formation and improves cortical blood flow in the early phase after a brain trauma, whereas no circulatory effects can be seen after prolonged treatment.
Lundblad
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C
Department of Anesthesia and Intensive Care, University of Lund and Lund University Hospital, SE-224 81 Lund, Sweden.
Bentzer
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P
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects*; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002860:Chromium Radioisotopes; D004195:Disease Models, Animal; D004492:Edetic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D002860:Chromium Radioisotopes; D001120:Arginine; D004492:Edetic Acid