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B Weir

Publications and source records attributed to B Weir.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

The University of Chicago Neurosurgical Program.

The current members of the faculty at the University of Chicago are acutely aware of the great historic tradition they have inherited. Like all academic medical centers, they are challenged by the current socioeconomic climate, but with the vast intellectual resources of the University of Chicago and its secure place in the community, both locally and nationally, we are confident of our ability to make a continuing contribution to the development of neurosurgery.

Chicago↗
PubMed1996

Changes in endothelial nitric oxide synthase mRNA during vasospasm after subarachnoid hemorrhage in monkeys.

OBJECTIVE: We attempt to determine whether changes in messenger ribonucleic acid (mRNA) for nitric oxide synthase (NOS) and soluble guanylate cyclase, enzymes that mediate endothelium-dependent vasodilation in cerebral arteries, occur after subarachnoid hemorrhage (SAH) in monkeys. METHODS: Baseline cerebral angiograms were obtained, and right-sided SAH was induced by microsurgically placing autologous blood clot against the right anterior circle of Willis in seven monkeys. Seven days later, angiographic studies were repeated and the animals were killed. Right (vasospastic) and left (control) middle cerebral arteries and underlying cortex were removed. The competitive reverse transcriptase polymerase chain reaction was used to quantify mRNA for soluble guanylate cyclase and two isoforms of constitutive NOS in these tissues. RESULTS: Comparison of angiograms at baseline and after 7 days showed a 41 +/- 7% (mean +/- standard error of the mean, P < 0.05, Wilcoxon test) decrease in diameter of the right middle cerebral artery. After the animals were killed, comparison of right and left middle cerebral arteries showed a 56 +/- 11% decrease (P < 0.005, paired t test) in endothelial NOS mRNA. There was a 142 +/- 39% (P < 0.05) increase in right cortex endothelial NOS mRNA compared to the left cortex. There were no significant differences between right and left sides in mRNAs for soluble guanylate cyclase or brain NOS. CONCLUSION: Decreased endothelial NOS mRNA in cerebral arteries 7 days after SAH may be caused by endothelial cell damage and could contribute to vasospasm after SAH. Increased endothelial NOS in brain tissue may reflect a compensatory vasodilator mechanism of the brain against the cerebral ischemia associated with vasospasm and SAH.

Animals↗
PubMed1996

Effect of P2-purinoceptor antagonists on hemolysate-induced and adenosine 5'-triphosphate-induced contractions of dog basilar artery in vitro.

OBJECTIVE: To test the hypothesis that the vasoactive effects of hemolysate of dog erythrocytes on dog basilar artery in vitro are caused by adenosine 5'-triphosphate (ATP). METHODS: Dog erythrocyte hemolysate was assayed for ATP by high-pressure liquid chromatography. Dog basilar arteries were cut into rings and studied under isometric tension to determine the effects of the P2-purinoceptor antagonists suramin, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, and reactive blue 2 on contractions induced by hemolysate, prostaglandin F2 alpha (PGF2 alpha), KCl, uridine 5'-triphosphate, and ATP. RESULTS: Dog erythrocyte hemolysate contained 34 mumol/L of ATP. Hemolysate produced concentration-dependent contractions of dog basilar artery. Suramin (100 mumol/L) significantly inhibited contractions to hemolysate, ATP, and uridine 5'-triphosphate but not to PGF2 alpha and KCl (P < 0.05). Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (100 mumol/L) caused a small but significant reduction of the contractions to hemolysate and did not affect contractions to PGF2 alpha and KCl. Reactive blue 2 (30 mumol/L) produced significant inhibition of contractions to hemolysate and PGF2 alpha but did not affect contractions to KCl. CONCLUSION: These findings suggest that ATP mediates a smooth muscle contractile response of hemolysate on dog basilar artery. Because erythrocyte cytosol is known to be important in the pathogenesis of vasospasm, these results suggest that ATP may contribute to the vasoconstriction that occurs in vasospasm.

Adenosine Triphosphate↗
PubMed1996

Effect of BQ-123 and tissue plasminogen activator on vasospasm after subarachnoid hemorrhage in monkeys.

BACKGROUND AND PURPOSE: We aimed to determine the effect of intracisternal administration of an endothelin-A receptor antagonist (BQ-123) against vasospasm in a monkey model and to determine whether this drug would have adverse interactions with intracisternal tissue plasminogen activator (TPA). METHODS: Thirty-three monkeys were randomly allocated to undergo baseline cerebral angiography, creation of right subarachnoid hemorrhage (SAH), and intracisternal delivery of (1) placebo (n = 10); (2) low-dose BQ-123 (5 mg/kg per day, n = 7); (3) high-dose BQ-123 (10 mg/kg per day, n = 9); or (4) BQ-123 10 mg/kg per day plus TPA 1 mg every 12 hours for three doses (n = 7). Angiography was repeated after 7 days, and animals were killed. Vasospasm was assessed by comparisons of angiograms within groups across time by paired t test and by comparisons across groups at each time by ANOVA. RESULTS: Significant clot remained in the basal cisterns in all groups except those receiving TPA, in whom complete clot clearance was noted. Comparisons of angiograms at baseline and after 7 days showed significant vasospasm of the right middle cerebral artery in animals receiving placebo (mean +/- SEM reduction in diameter, 36 +/- 7%; P < .05) and low- and high-dose BQ-123 (16 +/- 4% and 18 +/- 7%, respectively). Animals that received TPA did not develop significant right cerebral artery vasospasm. Comparisons of arterial diameters at day 7 revealed significant variance in right middle cerebral artery diameter, with animals in the placebo group having significantly more and animals in the TPA group having significantly less vasospasm than the BQ-123 groups. Histopathological examination of the brains did not show inflammation or pathological change in animals that received BQ-123 or BQ-123 plus TPA. CONCLUSIONS: Intracisternal TPA was efficacious against vasospasm in monkeys. Combination therapy with TPA and BQ-123 was not associated with reduction in efficacy of either drug or with evidence of toxicity.

Animals↗
PubMed1996

Vertebrobasilar junction aneurysms associated with fenestration: treatment with Guglielmi detachable coils.

Three patients with vertebrobasilar junction aneurysms and associated fenestration were treated with Guglielmi detachable coils. The structure and hemodynamics of fenestrations may account for their frequent association with aneurysms. The complex hemodynamics of these aneurysms requires evaluation of both vertebral arteries. One treatment complication occurred but resulted in no deficit. All patients have returned to normal activity and remain healthy at 14 to 46 months.

Aged↗
PubMed1995

Protection of the brain after aneurysmal rupture.

The majority of patients survive the first dangerous hours after an aneurysmal rupture. However, many subsequently succumb as a result of a variety of lethal complications. The most important of these develop as sequelae of the initial ischemia, rebleeding and the delayed onset of vasospasm. Some of these deleterious cascades can be aborted. Since the delayed complications such as vasospastic infarction can be accurately predicted, this is one of rare "strokes" that can have pharmacological pre-treatment. The natural history of rebleeding and vasospasm are described as well as their effects on blood flow, oxygen delivery and metabolism. Strategies to ameliorate acute and delayed ischemia and hypoxia are discussed. Finally, potential pharmacotherapies are detailed.

Aneurysm, Ruptured↗
PubMed1995

Mechanisms of hemolysate-induced [Ca2+]i elevation in cerebral smooth muscle cells.

The effects of hemolysate on free cytosolic [Ca2+] ([Ca2+]i) homeostasis were studied in freshly isolated rat basilar artery smooth muscle cells using fura 2 and dual excitation wavelength microfluorimetry. Hemolysate reversibly produced a transient [Ca2+]i peak followed by a slowly decaying plateau which was absent in Ca(2+)-free solution. This effect of hemolysate was attenuated by 1) the sarcoplasmic reticulum Ca2+ pump inhibitors thapsigargin and cyclopiazonic acid, 2) the Ca2+ release-blocking agents ryanodine and dantrolene, 3) the cytochrome P-450 inhibitor econazole, and 4) the inorganic Ca2+ channel blocker lanthanum but was not significantly attenuated by 1) the receptor-regulated Ca2+ channel blocker SKF-96365 or 2) the voltage-dependent Ca2+ channel blocker nimodipine. Fractionation of hemolysate using membranes with specific pore sizes (0.5, 1, and 12-14 kDa) indicated that a component(s) > 0.5 but < 1 kDa could produce a similar [Ca2+]i peak and plateau while fractions > 1 and > 12-14 kDa produced a small and slow [Ca2+]i rise without a significant peak. ATP, which was found in hemolysate, produced a [Ca2+]i response similar to that of hemolysate. P2-purinoceptor antagonists significantly attenuated the effect of ATP, hemolysate, and the fractions < 1 and < 12-14 kDa. We conclude that hemolysate elevates [Ca2+]i by both releasing Ca2+ from internal stores and triggering Ca2+ entry, possibly from a voltage-independent Ca2+ influx pathway, an effect apparently identical to that of ATP.

2,3-Diphosphoglycerate↗
PubMed1995

Activation of protein kinase C inhibits potassium currents in cultured endothelial cells.

The effect of protein kinase C on potassium channels in cultured endothelial cells was investigated by using whole-cell patch-clamp techniques. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), but not phorbol 12-monomyristate (PMM), an inactive analogue of phorbol esters, depressed an outward calcium-dependent potassium current. The inhibitory actions of PMA and PDBu could be reversed by the kinase inhibitor H-7. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum calcium pump, and LP-805, a novel vasodilator which also releases endothelium-derived relaxing factors, activated the outward calcium-dependent potassium conductance. PMA and PDBu, but not PMM, reduced the outward conductance induced by cyclopiazonic acid and LP-805. These effects of PMA and PDBu on potassium currents may be mediated either by phosphorylation of ion channels, or by decreasing intracellular calcium concentration.

Animals↗
PubMed1994

Cyclopiazonic acid stimulates Ca2+ influx through non-specific cation channels in endothelial cells.

A non-specific cation channel in cultured human umbilical vein endothelial cells was obtained by cell-attached patch-clamp study. This channel showed a conductance of 28 pS when both pipette and bath contained 140 mM potassium chloride. when pipette solution was changed into 140 sodium chloride with 5 mM calcium chloride, the conductance was 26 pS. when 120 mM calcium chloride was used as the only cation in the pipette, a conductance of 6 pS was obtained. Bath application of cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca2+ pump in smooth muscle and other tissues, dose dependently activates this non-specific cation channel. It is assumed that cyclopiazonic acid by blockade of the refilling of Ca2+ stores depletes the rapidly exchanging intracellular Ca2+ stores and this action stimulates Ca2+ influx through the non-specific cation channels in human umbilical vein endothelial cells.

Calcium↗