No abstract

Carbon monoxide (CO) Is known to increase cerebral blood flow, but the effect of CO on the vascular tone of large cerebral arteries Is uncertain. We tested whether CO affects cerebral artery tone by measuring tension generated by ex vivo segments of dog basilar artery upon exposure to CO. In cerebral artery segments contracted with either KCI or prostaglandin F 2 , CO caused a concentration-related relaxation beginning with a concentration of 57 IJM. Relaxation did not occur if CO was administered In the presence of bubbling carboxygen (95% O 2:5% CO 2) , which reduces greater than 99% of CO from the solution. Furthermore, the CO-Induced relaxation of cerebral artery segments was reduced in the presence of the guanylyl cyclase Inhibitor 1H-[1,2,4joxadlazolo[4,3-a]quinoxalin-1-one (000, 10 IJM)orthe potassium channel blocker tetraethylammonium (TEA, 1 mM). Neither 000 nor TEA completely eliminated the relaxation caused by CO and there was no additive effect if 000 and TEA were administered together. These results suggest that cerebral arteries are directly relaxed by CO and that this relaxation depends upon the activation of guanylyl cyclase and the opening of potassium channels.

Hemoglobin is a key factor in the production of cerebral vasospasm. Metabolism of hemoglobin involves breakdown of heme by heme oxygenase (HO) and sequestration of the released iron in ferritin. We determined whether subarachnoid hemorrhage induces these proteins in cerebral arteries and, if so, in which cells they are produced. Whether the changes correlated with vasospasm also was investigated. Subarachnoid hemorrhage was created in monkeys, and vasospasm was assessed by angiography in cohorts of animals killed 3, 7, or 14 days after the hemorrhage. Ferritin and HO-1 messenger ribonucleic acid (mRNA) and protein were measured by competitive reverse transcription-polymerase chain reaction and Western blotting in hemorrhage-side and control-side cerebral arteries and brain tissue. The location of these proteins was determined by immunohistochemistry. There was significant vasospasm 3 and 7 days but not 14 days after subarachnoid hemorrhage. There were no significant changes in mRNA for HO-1 or ferritin in cerebral arteries or brain tissue at any time. There was a significant increase in HO-1 and ferritin protein in hemorrhage-side compared with control-side cerebral arteries at 3, 7, and 14 days. The increase in HO-1 protein was maximal at 3 days, whereas the increase in ferritin protein was maximal at 7 days. There was no detectable increase in HO-1 or ferritin protein in brain tissue at any time. Immunohistochemistry localized HO-1 protein and ferritin to cells in the adventitia of the arterial wall. We show that subarachnoid hemorrhage is associated with a significant increase in HO-1 and ferritin proteins in cerebral arteries that begins at least as early as 3 days after the hemorrhage and that persists for up to 14 days.

Background and Purpose-We studied in monkeys why vasospasm resolves after subarachnoid hemorrhage (SAH). Methods-Monkeys underwent angiography and right (nϭ17) or bilateral (nϭ8) SAH. Animals with bilateral SAH underwent angiography 1, 3, 5, and 7 days later. Animals with right SAH underwent angiography 7 days later. The clot was then not removed (nϭ5), removed and replaced with fresh clot (nϭ7), or removed and not replaced (nϭ5). At the same time on day 7, the removed clot (nϭ12) or fresh clot (nϭ5) was placed on the left side. Angiography was repeated every 2 days until day 14. Results-SAH caused significant vasospasm on day 7 that resolved by day 14. Removal of clot on day 7 resulted in more rapid resolution of vasospasm. Placement of fresh clot onto arteries that had already been exposed to clot for 7 days produced vasospasm that persisted without resolving for an additional 7 days. Placement of 7-day-old clot from the right onto previously unexposed left arteries or of clot from blood removed from an animal 7 days after SAH caused significantly more rapid onset of vasospasm compared with de novo vasospasm. Microscopic examination of the clots showed they were surrounded by macrophages 7 days after SAH. Arterial compliance and contractility were reduced in relation to duration of the exposure of arteries to clot. Conclusions-Vasospasm resolves because of loss of subarachnoid blood clot. We hypothesize that reduced spasmogen release from the clot contributes to resolution of vasospasm. There was no response in the cerebral arteries that rendered them less responsive to the subarachnoid clot.

The authors review the remodeling response of blood vessels that occurs after various injuries to arteries. The role of this response in vasospasm after subarachnoid hemorrhage (SAH) is reviewed. There is some evidence that cerebral arteries remodel after SAH in that they are less compliant and contractile than normal. Evidence for other features, such as alteration of smooth muscle phenotype, proliferation of cells and synthesis of extracellular matrix, is conflicting and requires a further study. A remodeling response probably contributes to vasospasm but the magnitude of its importance, in relation to smooth muscle contraction, which also occurs, also needs to be further defined.