Molecular weight interactions in experimental vasospasm.
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Animals↗
Biomedical subjects
B Weir
Publications and source records attributed to B Weir.
Complimentary deoxyribonucleic acid array analysis of cerebral arteries after experimental subarachnoid hemorrhage.
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Animals↗
Delayed clot removal and experimental vasospasm.
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Adaptation, Physiological↗
Vasospasm in monkeys resolves because of loss of and encasement of subarachnoid blood clot.
BACKGROUND AND PURPOSE: We studied in monkeys why vasospasm resolves after subarachnoid hemorrhage (SAH). METHODS: Monkeys underwent angiography and right (n=17) or bilateral (n=8) 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 (n=5), removed and replaced with fresh clot (n=7), or removed and not replaced (n=5). At the same time on day 7, the removed clot (n=12) or fresh clot (n=5) 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.
Analysis of Variance↗
Intraoperative variables and early outcome after aneurysm surgery.
BACKGROUND: The purpose of this study was to investigate the effects of blood pressure, temperature, and anesthetic agents on outcome in patients undergoing craniotomy for cerebral aneurysms. METHODS: All ruptured and unruptured intracranial aneurysms operated on from 1992 to 1998 were reviewed retrospectively. The data included 297 aneurysms (190 ruptured and 107 unruptured). Data were collected on variables known to influence outcome after aneurysmal subarachnoid hemorrhage as well as on intraoperative factors that might influence outcome (intraoperative blood pressure, temperature, temporary clipping, anesthetic agents). Outcome was assessed at discharge using the Glasgow Outcome Scale. RESULTS: In univariate analysis of patients with ruptured aneurysms, younger age, better clinical grade, lower Fisher grade, lower intraoperative blood pressure (maximum systolic and mean blood pressure), smaller decrease in intraoperative compared to preoperative systolic blood pressure, shorter duration of surgery, and use of propofol, pancuronium, or N(2)O were associated with significantly better outcome. In patients with unruptured aneurysms, increased intraoperative minimum diastolic and mean blood pressure, a decrease in the difference between multiple measures of preoperative and intraoperative blood pressure, and a shorter duration of surgery were associated with significantly better outcome. Intraoperative temperature did not affect outcome in either group. In multivariate analysis of patients with ruptured aneurysms, younger age, better clinical grade, lower maximum systolic intraoperative blood pressure, shorter duration of surgery, and use of propofol were independently associated with better outcome. CONCLUSIONS: Multivariate analysis of intraoperative factors affecting outcome in patients undergoing craniotomy for ruptured aneurysms shows that decreased intraoperative blood pressure and use of propofol are associated with improved outcome. Univariate analysis suggests that decreasing the magnitude of drop in blood pressure intraoperatively from preoperative values in patients with ruptured or unruptured aneurysms is associated with better outcome. Intraoperative hypothermia did not affect outcome.
Anesthetics↗
Thrombin reduces cerebral arterial contractions caused by cerebrospinal fluid from patients with subarachnoid hemorrhage.
BACKGROUND AND PURPOSE: We observed that the second application of cerebrospinal fluid (CSF) from subarachnoid hemorrhage (SAH) patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application. It was hypothesized that the difference between the first and second applications of SAH CSF was due to the activity of thrombin. METHODS: Canine vertebrobasilar artery was removed under general anesthesia, cut into rings, and suspended in tissue culture baths so as to measure isometric tension. CSF was taken from patients 1 to 3 days after SAH via ventricular drains. CSF was administered in 10(-5) to 10(-1) dilutions. The thrombin antagonist hirudin (5 U) was administered before CSF in some experiments. The arterial tension response to pure oxyhemoglobin (10(-4) to 3.2 g/dL) and thrombin (10(-4) to 3.2 U/mL), administered alone or in combination, was also examined. RESULTS: Hirudin increased arterial tension generated on the initial application of SAH CSF but had no effect on the tension generated by the second application of the SAH CSF, suggesting that thrombin limits the tension generated by vasoconstrictive agents in the CSF. Thrombin and pure oxyhemoglobin administered together produced less tension than that generated in response to oxyhemoglobin administered alone; no additive response was observed by coadministering the 2 vasoconstrictive agents. CONCLUSIONS: In the presence of oxyhemoglobin, thrombin acts to reduce cerebral arterial tension. This interaction between thrombin and hemoglobin may account for the observation that the second application of CSF from SAH patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application.
Animals↗
Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries.
OBJECT: It is not known whether the factors responsible for vasospasm after subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed independent of the subarachnoid blood clot or whether the continued presence of clot is required for the entire time of vasospasm. The authors undertook the present study to investigate this issue. METHODS: To distinguish between these possibilities, bilateral SAH was induced in monkeys. The diameters of the monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed surgically on Day 1, 3, or 5 or, in control animals, was not removed until the animals were killed on Day 7 or 9. The concentrations of hemoglobins and adenosine triphosphate (ATP), substances believed to cause vasospasm, were measured in the removed clots and the contractile activity of the clots was measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days after placement, vasospasm was significantly diminished 4 days after clot removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a significant decrease over time in hemoglobin and ATP concentrations and in the contractile activity of the clots, although substantial hemoglobin and contractile activity was still present on Day 7. CONCLUSIONS: The authors infer from these results that vasospasm requires the presence of subarachnoid blood for at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid blood clot. Because the clot still contains substantial amounts of hemoglobin and contractile activity after 5 days, there may be an adaptive response in the cerebral arteries that allows them to relax in the presence of the stimulus that earlier caused contraction.
Adaptation, Physiological↗
Extradural posterior inferior cerebellar artery aneurysm.
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Adult↗
Contents of chronic subdural hematoma.
Analysis of chronic subdural hematoma membranes and contents has revealed a complex process of blood breakdown forming a milieu that stimulates neovascularization and repeated hemorrhage.
Blood Proteins↗
Etiology of cerebral vasospasm.
Cerebral vasospasm is a gradual onset and prolonged constriction of the cerebral arteries in the subarachnoid space after subarachnoid hemorrhage. The principal cause is the surrounding blood clot. The significance of vasospasm is that flow through the constricted arteries may be reduced sufficiently to cause cerebral infarction. Subarachnoid blood clot is sufficient to cause vasospasm; it does not require additional arterial injury, intracranial hypertension or brain infarction, although these elements are often coexistent. The blood released at the time of aneurysmal rupture into the alien subarachnoid environment is an extraordinarily complex mix of cellular and extracellular elements that evolves as clotting occurs; cells disintegrate; local inflammation, phagocytosis and repair take place; severe constriction alters the metabolism and structure of the arterial wall as well as the balance of vasoconstrictor and dilator substances produced by its endothelium, neurogenic network and perhaps smooth muscle cells.
Brain↗
Treatment of unruptured cerebral aneurysms.
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Humans↗
Understanding HIV risks of chronic drug-using men who have sex with men.
Focus groups and individual structured interviews were conducted in six cities with 98 predominantly street-recruited men who had a recent history of smoking crack or injecting drugs and who reported having had sex with other men (MSM) in the past year. Twenty-six focus groups explored the cultural and social context of participant's drug use and sexual activity and addressed outreach and HIV prevention issues pertinent to this population. Narrative summaries developed from verbatim focus group transcripts identified seven themes: (a) sexual orientation and gender identity; (b) interactions within and between MSM networks; (c) drug use, sexual activity and personal relationships; (d) HIV transmission bridges; (e) preferred HIV information sources; (f) HIV knowledge, prevention practices and risk behaviours; and (g) availability of HIV and drug-related services. Of the 98 MSM drug users, 42% identified publicly as gay or homosexual; 35% identified publicly, but only 21% privately, as heterosexual. A total of 51% had one or more female sex partners in the past year. There was a high frequency of unprotected sex in conjunction with drug use and a distinct preference for having sex when high. For most participants, drug use rather than sexual orientation formed the core of personal identity. Participants reported associating primarily with other drug users, usually MSM, and had limited contact with people who did not use drugs and the mainstream gay community. Participants' sexual and drug-injecting activities were judged to be a bridge for transmission of HIV to both people who used drugs and those who did not.
Adolescent↗
Effects of cell-permeant calcium chelators on contractility in monkey basilar artery.
Vasospasm after traumatic or aneurysmal subarachnoid hemorrhage is associated with smooth muscle contraction, a process that results in part from increased intracellular calcium in smooth muscle cells. These experiments tested the hypothesis that chelation of intracellular calcium with the cell-permeant calcium chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetoxymethyl ester (BAPTA-AM), decreases smooth muscle contraction in response to agents that cause contraction by increasing intracellular calcium. Effects of BAPTA-AM on vasoconstriction induced by KCl, prostaglandin F2alpha (PGF2alpha), caffeine, and erythrocyte hemolysate were tested on monkey basilar artery under isometric tension. BAPTA-AM, 30 and 100 micromol/L, caused a significant decrease in resting tension in rings with and without endothelium (30 micromol/L; 8+/-6% [n.s.] and 14+/-5%, 100 micromol/L; 19+/-3% and 32+/-6%,p < 0.05, paired t test). Contractions to caffeine were significantly decreased by 30 micromol/L BAPTA-AM and were abolished at 100 micromol/L in rings with and without endothelium (p < 0.05). BAPTA-AM, 100 micromol/L, competitively inhibited contractions to PGF2alpha. BAPTA-AM, 100 micromol/L, significantly decreased the maximum contractions to KCI in rings with and without endothelium (p < 0.05). There were no significant effects of BAPTA-AM on contractions induced by hemolysate in rings with endothelium but in rings without endothelium, BAPTA-AM, 100 micromol/L, significantly inhibited contractions. In rings with endothelium contractions to hemolysate could be significantly reduced by BAPTA-AM plus indomethacin or indomethacin alone, suggesting that hemolysate releases an eicosanoid from the endothelium by a pathway that is not inhibited by BAPTA. These results suggest that the ability of BAPTA-AM to inhibit smooth muscle contractions will depend on the agonists mediating the contraction. In response to erythrocyte hemolysate, loading of endothelial cells with BAPTA-AM increases the release of a vasoconstricting eicosanoid from these cells that counteracts the decreased contraction caused by loading of smooth muscle cells with BAPTA-AM.
Animals↗
Adenosine triphosphate causes vasospasm of the rat femoral artery.
OBJECTIVE: Adenosine 5'-triphosphate (ATP) causes vasoconstriction by activation of P2-purinoceptors on vascular smooth muscle cells. Erythrocytes contain ATP at a concentration (1.6 mmol/L) that contracts smooth muscle. Previous studies of hemoglobin solutions did not assess whether the vasoactivity was caused by ATP rather than or in addition to hemoglobin. It was hypothesized that the hemolysis of erythrocytes that occurs after subarachnoid hemorrhage releases ATP in concentrations that cause vasospasm. METHODS: Thirty-eight rats were randomly assigned to undergo placement of one of the following compounds in a silastic elastomer cuff around each femoral artery: 1) agarose gel (n = 8); 2) dog erythrocyte hemolysate (n = 8); 3) purified human hemoglobin (Hemolink; Hemosol, Inc., Toronto, Canada; n = 8); 4) ATP (n = 8); or 5) clotted autologous blood (n = 6). The amounts of hemoglobins and adenine nucleotides in the compounds were measured by spectrophotometry and high pressure liquid chromatography. Hemolysate, purified hemoglobin, and ATP were mixed with agarose gel to create an artificial clot. Rats were killed and fixed by perfusion at physiological blood pressure 7 days after perivascular cuff and spasmogen placement. Vasospasm was assessed by image analysis of cross sections of fixed femoral arteries. Arteries were assessed for histopathological changes on 3-point scales. RESULTS: There was significant variance in arterial diameters among groups (mean diameter +/- standard deviation: agarose gel, 0.29 +/- 0.06; purified hemoglobin, 0.28 +/- 0.04; hemolysate, 0.24 +/- 0.05; ATP, 0.25 +/- 0.05; clotted blood, 0.24 +/- 0.01; P < 0.05, analysis of variance, n = 11-20). Animals exposed to clotted blood, hemolysate that contained ATP, or ATP, developed vasospasm, whereas purified hemoglobin and agarose did not cause vasospasm. Endothelial proliferation and perivascular inflammation were more severe (P < 0.05) in arteries exposed to clotted blood, purified hemoglobin, and hemolysate. CONCLUSION: These results suggest that ATP may be a vasospastic substance released by erythrocyte hemolysis. The concentration of ATP in impure solutions of hemoglobin is too low to account for the vasoactivity of these solutions. The discrepancy between arterial narrowing and histopathological changes suggests that either histopathological changes may not be an important correlate of arterial vasospasm or that other substances are important in vasospasm.
Adenine Nucleotides↗
Reduced expression of calponin in canine basilar artery after subarachnoid haemorrhage.
Calponin, an actin- and tropomyosin-binding protein, has been characterized as an inhibitory factor in the smooth-muscle actomyosin activity. The level of calponin was determined in canine basilar arteries in a double-haemorrhage model. Thirty dogs were assigned to three groups: day 0 group, control; day 2 group, dogs sacrificed 2 days after cisternal injection of blood; and day 7 group, dogs given double cisternal injections of blood and sacrificed 7 days after the first injection. Constriction of the basilar artery was confirmed by arterial angiography. Portions of the affected arteries or the corresponding region in control animals were solubilized for sodium dodecylsulphate-polyacrylamide gel electrophoresis and Western blotting. A major band corresponding to calponin was seen at 34 kD in the basilar artery extracts using chicken gizzard polyclonal antibodies. The densitometer values of the band on Coomassie blue-stained gels were expressed as percentages of day 0 control values. The signals of day 2 and day 7 samples were 47% +/- 20% and 23% +/- 12%, respectively (mean +/- standard deviation). The proportions of calponin to actin/tropomyosin in the day 0, day 2, and day 7 groups were 13% +/- 6%, 6% +/- 2%, and 4% +/- 2%, respectively. The reduced expression of calponin may be related to sustained contraction during cerebral vasospasm.
Animals↗
Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys.
These studies tested the hypothesis that the cerebral vasospasm that follows subarachnoid hemorrhage (SAH) is due to alterations in endothelin (ET) and ET receptor expression. Eight monkeys underwent cerebral angiography and induction of SAH. Angiography was repeated 7 days later to confirm the presence of cerebral vasospasm, and animals were killed. RNA was isolated from right (vasospastic) and left (control) side middle cerebral arteries and surrounding cerebral cortex. The levels of prepro (PP) ET-1 (ppET-1) and ppET-3 and ETA and ETB receptor MRNAs were determined using a quantitative reverse transcriptase polymerase chain reaction-based assay. ET-1 peptide was also measured in CSF at baseline and after 7 days. Specific agonist binding to ETA and ETB receptors in both middle cerebral arteries and in surrounding brain cortex was measured in three animals by autoradiographic binding assays. Levels of ETB receptor mRNA were 3.4 +/- 2.2-fold higher in the right than in the left cerebral arteries (p < 0.01). There were no significant differences in the levels of ppET-1, ppET-3, or ETA receptor mRNA in cerebral arteries. ET-1 peptide was not elevated in CSF. Levels of ETA and ETB receptor mRNAs were 2.6 +/ 1.1- and 2.1 +/ 1.3-fold higher, respectively, in the right than in the left cerebral cortex, while the level of ppET-3 mRNA was 2.1 +/- 1.0-fold lower. There were no differences in ppET-1 mRNA levels between right and left cerebral cortex. Binding to ETA and ETB receptors in cerebral arteries and cortex did not differ significantly between right and left sides. These results do not support the hypothesis that overexpression of ET-1 is principal cause of vasospasm, but rather they suggest that SAH causes complex changes in the ET system that together are responsible for the cellular response to SAH.
Animals↗
Intraoperative angiography in cerebral aneurysm surgery: a prospective study of 100 craniotomies.
OBJECTIVE: To determine the frequency of unexpected major arterial occlusion and incomplete aneurysm clipping on intraoperative angiography after cerebral aneurysm clipping and to determine factors that predict these unexpected findings. METHODS: Data was collected prospectively on 100 consecutive craniotomies for the clipping of 107 aneurysms in 92 patients. Patient age and sex, aneurysm location and size, how the aneurysm presented, day of surgery after hemorrhage, intraoperative rupture, and postoperative course were recorded. After clipping, the surgeon recorded whether he thought the aneurysm was obliterated and whether he thought the clip occluded a major artery. Intraoperative angiography was then performed. The incidence of unexpectedly finding a major arterial occlusion or residual aneurysm was determined. Factors predicting these unexpected findings revealed by intraoperative angiography were identified by logistic regression. RESULTS: There were 11 giant (10%), 13 posterior circulation (12%), and 68 (64%) ruptured aneurysms. Unexpected angiographic findings necessitating at least one clip adjustment occurred in 12 cases (11%). Clip readjustments restored flow through six major arterial occlusions (6%) and completely obliterated 10 persistently filling aneurysms (10%). Logistic regression showed that factors predicting an unexpected arterial occlusion were giant aneurysm and basilar apex location (P < 0.05). Unexpected residual aneurysm was predicted by giant aneurysm and posterior communicating artery location (P < 0.05). CONCLUSION: Intraoperative angiography detects unexpected arterial occlusions and residual aneurysms in 12% of cases and can decrease complications of aneurysm surgery, although the yield in unselected patients is low. The subgroup of patients with giant, basilar apex, and posterior communicating artery aneurysms has a significantly higher incidence of untoward findings and may benefit from increased usage of intraoperative angiography.
Adolescent↗