Endothelial injury following experimental subarachnoid hemorrhage in rats: effects on brain blood flow

BACKGROUND: The leading cause of death and disability in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is cerebral vasospasm, a persistent, progressive, and often irreversible constriction of cerebral arteries. A wide array of pathological changes occur in cerebral arteries following SAH, with endothelial injury being the earliest and most consistent one. Since intact endothelium modulates many reflexes that influence vascular tone, damage to them may represent a significant contributor to cerebral vasospasm. METHODS: Changes in local cerebellar blood flow (LCBF) and pathological alterations in major cerebral arteries were studied and compared in rats at various time intervals following SAH. SAH induced by the subarachnoid injection of 0.3 ml of whole blood. Sham rats received a subarachnoid injection of 0.3 ml of isotonic saline. RESULTS: Except for an immediate but transient decrease, LCBF remained unchanged over a 3 day period following saline injection. Likewise, there were no pathological alterations in cerebral arteries of saline-injected rats. In contrast, the subarachnoid injection of whole blood produced significant changes in both LCBF and cerebral arteries. Within 30 minutes post-blood injection, LCBF became significantly decreased and remained so for 4 hours. However, within 24 hours, LCBF had returned to control levels where it remained for 3 days. Endothelial injury was observed in the basilar and middle cerebral arteries from 30 minutes through 4 hours, the same periods in which LCBF was significantly reduced. Within 24 hours, the time period in which LCBF had rebounded to control ranges, cerebral arteries showed no evidence of endothelial damage and resembled control cells. CONCLUSION: The results indicate a direct correlation between changes in LCBF and the structural integrity of endothelial cells in the early stages following SAH. The lack of chronically depressed LCBF (after 1 day) may be related to the quick structural repair of endothelium.     

Concurrent subarachnoid hemorrhage due to ruptured aneurysm and hypertensive intracerebral hemorrhage--case report

A 64-year-old female presented with hypertensive thalamic hemorrhage concurrent with subarachnoid hemorrhage (SAH) due to a ruptured aneurysm manifesting as sudden onset of right hemiparesis followed by severe headache. The aneurysm was located in the basilar artery at the origin of the superior cerebellar artery, remote from the thalamic hematoma. The aneurysm was clipped 3 weeks after SAH. She was discharged with slight right hemiparesis. The method and timing of surgery for such patients depend on hematoma size, location of the aneurysm and hematoma, and neurological status. The intracerebral hemorrhage remote from the ruptured aneurysm should be treated initially if necessary, and the aneurysm clipped after the brain swelling has reduced.     

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage

Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.     

Impairment in biochemical level of arterial dilative capability of a cyclic nucleotides-dependent pathway by induced vasospasm in the canine basilar artery

The authors investigated the changes and the potential of cyclic nucleotide-dependent signal transduction, which induces smooth muscle relaxation, in the basilar artery with severe vasospasm in dogs with double experimental subarachnoid hemorrhage (SAH) to explore at which biochemical level the arterial dilative capability was impaired. The amount of cyclic adenosine and guanosine monophosphates (cAMP and cGMP) decreased significantly in the basilar artery after SAH. The activities of adenylate and guanylate cyclases also were decreased significantly in the smooth muscle cells of the basilar artery 4 days after SAH. In addition to the failure of the pathways to produce cyclic nucleotides, the activities of cAMP- and cGMP-dependent protein kinases, which are representative actual enzymes that amplify the signal for vascular dilation, also significantly decreased together with the almost total loss of activation by cyclic nucleotides in the same basilar artery after SAH. It was revealed that the system for smooth muscle relaxation was impaired severely in the cerebral arteries with severe vasospasm after SAH, on the biochemical basis of significantly less vasodilative capability and in several of the steps to produce the cyclic nucleotides of intracellular signal transduction.     

Does subarachnoid blood extravasation per se induce long-term neuropsychological and cognitive alterations?

Although recent advances in medical and management strategies have reduced the mortality and morbidity rates related to subarachnoid haemorrhage (SAH), patients who survive a SAH may remain nevertheless affected by persistent cognitive and neuropsychological disturbances. The presence of these deficits has been attributed to the neurotoxic effects of the widespread subarachnoid blood. To assess the long-term neuropsychological and cognitive outcome related to subarachnoid blood extravasation per se we evaluated 20 patients affected by an unknown origin subarachnoid haemorrhage, and having SAH characteristics generally considered predictive of a favourable outcome. Patients were enrolled after a one-year interval from the initial insult, and were selected accordingly to a pre-designed protocol. We employed a complete battery of tests, assessing general cognitive and language functions, memory and construction ability, attention and vigilance, anxiety and depression. The results were compared with normal reference values and with performances of a socio-demographically homogenous sample of control volunteers. This study did not evidence any significant long-term cognitive and neuropsychological alteration after subarachnoid blood extravasation. These results indicate that the presence of subarachnoid blood initiate a number of secondary mechanisms of pathology.     

Spontaneous subarachnoid hemorrhage first from an intracranial and then from a spinal arteriovenous malformation. Case report

A patient presented with spontaneous subarachnoid hemorrhage (SAH) from a cerebral arteriovenous malformation (AVM) which was later totally removed at surgery. The patient presented again with a new SAH from a spinal AVM that was also totally removed at surgery. Coexistence of spinal and cerebral arteriovenous malformations are exceedingly rare and hemorrhage from each is not previously reported. This case emphasizes the importance of investigating the spinal canal in otherwise unexplained spontaneous SAH.     

The false-positive rate of thoracic outlet syndrome shoulder maneuvers in healthy subjects

Cytokines are considered as mediators of immune and inflammatory responses. Cisternal CSF levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and of the soluble adhesion molecule E-selectin were evaluated in patients operated on for intracranial aneurysms. Cisternal CSF samples were obtained at surgery in 41 selected patients (31 with diagnosis of subarachnoid hemorrhage (SAH) and 10 control patients operated on for incidental unruptured aneurysms); 14 patients were operated within 72 h after SAH (early surgery) and 17 were operated after day 10 after the hemorrhage (delayed surgery). The CSF levels of cytokines were evaluated using radioimmunoassay and their concentrations were related to the timing of surgery, the amount of cisternal subarachnoid blood clots and the onset of clinical and angiographical evidence of arterial vasospasm. Mean cisternal CSF levels of IL-6, IL-8 and AMCP-1 are significantly higher in samples obtained from patients early operated after SAH, while levels of E-selectin were below the threshold value of the method in all 41 cases. In the early operated group 7 patients presented symptomatic vasospasm: levels of IL-8 and MCP-1 were not significantly different were compared to those of uncomplicated cases; on the other hand, significantly higher levels of IL-6 were shown in the subgroup of patients operated within 72 h after SAH and developing vasospasm. Among the patients undergoing delayed surgery 5 presented symptomatic vasospasm, but no significant difference was shown in cisternal CSF levels of cytokines measured. The results of the present study show that in patients with unruptured aneurysms cytokines are present in cisternal CSF in scarce quantities and that in subarachnoid spaces after SAH there is an impressive increase of IL-6, IL-8 and MCP-1. Moreover, the higher cisternal CSF levels of IL-6 found in the early stage after SAH might have a predictive value regarding the occurrence of symptomatic vasospasm.     

Modulatory role of endothelial and nonendothelial nitric oxide in 5-hydroxytryptamine-induced contraction in cerebral arteries after subarachnoid hemorrhage

OBJECTIVE: Endothelial dysfunction is claimed to play a role in the pathogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). We have examined the effect of experimental SAH on the modulatory action of endothelial and nonendothelial nitric oxide (NO) in the contractile response of goat middle cerebral artery to 5-hydroxytryptamine (5-HT). METHODS: We compared the 5-HT-induced contractile responses of cerebral arteries from control goats and from goats with SAH that had been experimentally induced 3 days earlier by delivery of autologous arterial blood into the subarachnoid space. Contractile responses were examined by recording the isometric tension in isolated cerebral arteries. To assess the influence of endothelium, this cell layer was mechanically removed in some of the arteria, segments (rubbed arteries) from both control goats and goats with SAH. RESULTS: In arteries from control goats, contractile responses to 5-HT were significantly higher in rubbed arteries than in arteries with intact endothelium; 5-HT-induced contractions were significantly enhanced by a competitive inhibitor of NO synthesis, NG-nitro-l-arginine, in arteries both with and without endothelium. In arteries from goats with SAH, 5-HT contracted cerebral arteries without showing significant differences between segments with endothelium and those that had been rubbed; in both cases, 5-HT-induced contractions were significantly higher than those obtained in arteries from control goats. NG-Nitro-l-arginine significantly enhanced the contractile response to 5-HT of cerebral arteries from goats with SAH. CONCLUSION: These results suggest that cerebral arteries after SAH exhibit hyperreactivity to 5-HT via a mechanism that involves the absence of the modulatory role of endothelial NO, that SAH does not modify the modulatory role of nonendothelial NO, and that impairment of the modulatory action of endothelial NO on vascular responses to 5-HT could contribute to the pathogenesis of cerebral vasospasm after SAH.     

Amount of subarachnoid blood and vasospasm: current aspects. A transcranial Doppler study

Subsequent to admission after aneurysmal subarachnoid haemorrhage (SAH), 120 patients (74 women and 46 men) underwent microsurgical clipping of a total of 158 cerebral aneurysms within 96 hours after the bleed. Their mean age was 46 (20-91) years. Computed tomography (CT) findings were graded according to the modified Fisher scale and all patients had daily transcranial doppler (TCD) recordings of their basal cerebral arteries. In 19% of SAH was grade I on CT, in 44% grade II and in 37% grade III. The rate of patients who developed severe vasospasm as documented by TCD (mean blood flow velocities exceeding 160 cm/s on 2 or more consecutive days) was 39% for grade I patients, 26% for grade II patients and 34% for patients with SAH grade III on the initial CT. There was no difference in the rate of occurrence of severe vasospasm, when the patients were split into 2 groups according to the time of performance of the initial CT scan-within 24 hours, and 48-80 hours after SAH, respectively. It is concluded that the amount of subarachnoid blood on the initial CT scan should no longer be used as the indicator for occurrence and severity of the multifactorial entity vasospasm.     

CO2 reactivity in patients after subarachnoid haemorrhage

CO2 reactivity was tested in patients with transcranial Doppler sonography (TCD) and endtidal CO2 measurements after an average time interval of ten months after subarachnoid haemorrhage (SAH). After deliberately changing breathing there was a significant change in endtidal CO2 and in flow velocities in all three examination groups. Comparing 27 patients with SAH and 5 patients treated for incidental aneurysms and 20 patients without cerebrovascular disease there were no significant differences in CO2 reactivity. Furthermore, there were no right to left differences. In 12 patients with vasospasm, two of them treated by percutaneous transluminal angioplasty for delayed ischaemic deficits, CO2 reactivity was normal at the time of investigation. Furthermore, normal CO2 reactivity was found in patients after SAH and surgery for ruptured aneurysms regardless of the severity of the SAH.     

Risk of recurrent subarachnoid hemorrhage after complete obliteration of cerebral aneurysms

BACKGROUND and PURPOSE: The neck clipping of cerebral aneurysms is a well-established treatment for subarachnoid hemorrhage (SAH) caused by aneurysmal rupture. However, it is still unclear how great a risk of recurrence patients with a successfully treated aneurysm carry over a long-term period. METHODS: Of 425 patients with SAH surgically treated in Aizu Chuou Hospital from 1976 to 1994, 220 cases meeting the following criteria were studied: (1) all aneurysms detected by 3- or 4-vessel cerebral angiography were clipped, (2) complete obliteration of aneurysm(s) was confirmed by postoperative angiography, and (3) the patient survived >3 years. All patients were traced until January 1998 for recurrent SAH or death. The mean follow-up period was 9.9 (range, 3 to 21) years. RESULTS: Six patients (2.7%) had recurrent SAH, each with an interval ranging from 3 to 17 years (mean, 11 years) since the original treatment. In addition, 2 patients were found to have regrowth of the originally operated aneurysms. The cumulative recurrence rate of SAH, calculated using the Kaplan-Meier method, was 2.2% at 10 years and 9. 0% at 20 years after the original treatment. CONCLUSIONS: The recurrence rate was considerably higher than the previously reported risk of SAH in the normal population, and the rate increased with time. These data indicate that patients with ruptured cerebral aneurysms still carry higher risks for SAH in a long-term period, even after complete obliteration of the aneurysm, and that periodic examination to detect recurrent aneurysms may be indicated for such patients.     

Protein synthesis and immunoreactivities of contraction-related proteins in smooth muscle cells of canine basilar artery after experimental subarachnoid hemorrhage

We examined time-dependent changes in protein synthesis and in the immunoreactivities of representative contraction-related structural proteins in smooth muscle cells of canine basilar arteries after experimental subarachnoid hemorrhage (SAH). Protein synthesis was assessed by the percentage of polyribosome-forming ribosomes to total ribosomes (aggregation rate), a morphological index of the activity of protein synthesis. The aggregation rates in prostaglandin F2 alpha-(PGF 2 alpha) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced contracted basilar arteries were 70.0 +/- 7.0% and 71.4 +/- 8.7%, respectively, quite similar to the value in normal basilar artery (73.0 +/- 8.0%). In the single-SAH group with little delayed histological changes in the basilar arteries, the aggregation rate was significantly decreased to 30.5 +/- 6.4% by 24 h after the SAH, and recovered to 52.3 +/- 9.0% and 70.2 +/- 7.6% at 7 and 14 days postSAH, respectively, when the vasospasm was moderately and completely ameliorated. In contrast, in the double-SAH group in which the basilar arteries developed delayed smooth muscle cell death and long-lasting arterial contraction, a significant decrease in the aggregation rate (25.0 +/- 5.0% on day 4) persisted for 14 days. The in vitro incorporation of [3H]-leucine in the basilar arterial cells was also significantly suppressed 4 and 7 days after the initial SAH (1.2 +/- 0.4 and 1.4 +/- 0.3 x 10(3) dpm/mg protein) in the double-SAH group, as opposed to no significant decrease in the basilar artery at 7 days postSAH in the single-SAH group (1.9 +/- 0.6 x 10(3) dpm/mg protein). The immunoreactivity of alpha-smooth muscle actin, a contractile protein, demonstrated by immunohistochemistry and immunoblots, was not altered for up to 14 days even in the double-SAH group, but that of calponin and of h-caldesmon, contraction-inhibiting proteins, was markedly reduced 4-14 days after the initial SAH. Persistent impairment of protein synthesis and relative reduction of immunoreactivities of the contraction-inhibiting proteins were observed in arteries with severe vasospasm and loss of smooth muscle cells, as noted in the double-SAH subjects. These abnormalities may cooperate to cause cerebral arterial narrowing accompanied by degeneration of smooth muscle cells after SAH.     

The protective effects of ipratropium bromide and terbutaline on distilled water-induced bronchoconstriction

Subarachnoid hemorrhage (SAH) was produced in rabbits by four subarachnoid injections of blood (n = 7) or saline (n = 6); a control group (n = 6) had no injections. Basilar artery vasospasm was assessed by serial angiograms. Resting CBF (microspheres) and CBF reactivity to hypercapnia (65 and 85 mm Hg) and hypoxia (fractions of inspired oxygen of 0.15 and 0.10) were determined. Basilar artery vasospasm was seen with SAH. Resting CBF was reduced by 31% (SAH 43 +/- 12, saline 65 +/- 17, control 60 +/- 21 ml 100 g-1 min-1), and resting cerebrovascular resistance was increased (SAH 1.84 +/- 0.30, saline 1.31 +/- 0.49, control 1.39 +/- 0.25 mm Hg ml-1 100 g-1 min-1) after SAH. CBF rose to a similar degree in all three groups in response to hypercarbia and hypoxia. We conclude that resting CBF is reduced in this model of SAH, but vascular reactivity remains intact.     

Extralobar pulmonary sequestration presenting as a mediastinal malignancy

OBJECTIVE: We intended to characterize the CT patterns of hemorrhage associated with ruptured posterior inferior cerebellar artery (PICA) aneurysms. MATERIALS AND METHODS: CT scans of 44 cases of angiographically confirmed ruptured saccular PICA aneurysms (4) aneurysms at the junction of the vertebral artery and the PICA and three distal PICA aneurysms) were retrospectively reviewed. All scans had been obtained within 2 days of the subarachnoid hemorrhage (SAH) (day 0 [less than 24 hr], 35 patients; day 1, eight patients; day 2, one patient). Presence or absence of hemorrhage in specific subarachnoid, intraventricular, and intraparenchymal locations was noted, as were the presence and degree of hydrocephalus. RESULTS: Posterior fossa SAH was present in 95% of cases. Isolated posterior fossa SAH was present in 30% of cases, but in no case was isolated supratentorial SAH present. Supratentorial SAH was present in 70% of cases. SAH involving the sylvian fissure or the interhemispheric region was present in 25% and 23% of cases, respectively. SAH along the convexity was present in 2% of cases. Intraventricular hemorrhage (IVH) with or without associated SAH was seen in 95% of cases, whereas isolated IVH was seen in 5% of cases. Hydrocephalus was present in 95% of cases and was moderate to marked in 70%. Both IVH and hydrocephalus were present in 93% of cases. CONCLUSION: Ruptured PICA aneurysms almost always coexist with hydrocephalus and IVH, as seen in 93% of cases, and almost never coexist with SAH along the convexity. The most common pattern of hemorrhage associated with such aneurysms includes IVH and posterior fossa hemorrhage. Extensive supratentorial SAH, in conjunction with posterior fossa SAH, is a common finding in patients with ruptured PICA aneurysms. SAH isolated to the posterior fossa is present in a sizeable minority of cases.     

Dysfunction of nitric oxide induces protein kinase C activation resulting in vasospasm after subarachnoid hemorrhage

We hypothesize that the interaction between protein kinase C (PKC) and nitric oxide (NO) plays a role in the modulation of cerebral vascular tone, and the disturbance of this interaction following subarachnoid hemorrhage (SAH) results in vasospasm. To prove this hypothesis with direct evidence, PKC activities of smooth muscle cells of canine basilar arteries in the control and in the SAH groups were measured by an enzyme immunoassay method. N omega-nitro-L arginine (L-NA), an inhibitor of NO production, enhanced PKC activity. This enhancement was inhibited neither by 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) nor SIN-1, a NO releasing agent. PKC activity in the SAH was significantly higher than in the control; however, no further enhancement was produced with L-NA. In the SAH, PKC activity was not inhibited either by 8-bromo-cGMP or SIN-1. We conclude that NO maintains an appropriate vascular tone through inactivation of PKC, and that this effect is disturbed following SAH, resulting in PKC-dependent vascular contraction, such as vasospasm. On the other hand, once PKC has been activated, NO precursors do not inhibit PKC. These facts indicate NO inactivates PKC through the inhibition of phosphatidylinositol breakdown.     

A case of Sj?gren syndrome associated with multiple mononeuritis and dysautonomia including bilateral tonic pupils

In the present study, the feasibility of intrathecal indwelling catheters in the preparation of a repeated subarachnoid hemorrhage (SAH) model in dogs, as well as chronic intrathecal administration of therapeutic agents against the ensuing cerebral vasospasm was examined. Briefly, through a small suboccipital incision, two catheters were introduced into the subarachnoid space so that their tips were positioned in the prepontine cistern. One was used to induce SAH by infusing autologous blood, and the other to administer pharmacological agents (saline and/or saline containing a dye in this study) by means of an osmotic pump. The occurrence of cerebral vasospasm was followed by angiography via the catheter placed in the vertebral artery. The obtained results show: i) the injected blood effectively formed a subarachnoid clot in the prepontine cistern, invariably leading to the occurrence of severe cerebral vasospasm of the basilar artery; ii) the fluid injected by the osmotic pump was evenly distributed in the cisterns around the brain stem; iii) on post mortem pathological examination, no injury of the brain or the major arteries ascribable to the placement of catheters was found. Therefore, the present model is considered to be useful for both the investigation of pathophysiology and therapy of cerebral vasospasm following SAH, to be more favorable from the standpoint of animal protection, and more convenient and reliable than those used until now.     

Prenatal diagnosis of 22q11 microdeletion

It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm. A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically. Mean cisternal CSF level of SOD in 12 control cases (12.99 +/- 2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44 +/- 0.7 U/ml) and in 40 patients treated by delayed surgery (7.64 +/- 0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23 +/- 1.86 U/ml; in 27 cases without vasospasm mean level was 5.43 +/- 0.7 U/ml (p < 001). The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.     

Expression and function of recombinant endothelial nitric oxide synthase gene in canine basilar artery after experimental subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Gene transfer with recombinant viral vectors encoding vasodilator proteins may be useful in therapy of cerebral vasospasm after subarachnoid hemorrhage (SAH). Relaxations mediated by nitric oxide are impaired in cerebral arteries affected by SAH. The present study was designed to determine the effect of SAH on the efficiency of ex vivo adenovirus-mediated gene transfer to canine basilar arteries and to examine whether expression of recombinant endothelial nitric oxide synthase (eNOS) gene may have functional effects on vasomotor reactivity of spastic arteries affected by SAH. METHODS: Replication-deficient recombinant adenovirus vectors encoding bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVbeta-Gal) genes were used for ex vivo gene transfer. Rings of basilar arteries obtained from control dogs and dogs exposed to SAH were incubated with the vectors in minimum essential medium. Twenty-four hours after gene transfer, expression and function of the recombinant genes were evaluated by (1) histochemical or immunohistochemical staining, (2) beta-galactosidase protein measurement, and (3) isometric tension recording. RESULTS: Transduction with AdCMVbeta-Gal and AdCMVeNOS resulted in the expression of recombinant beta-galactosidase and eNOS proteins mostly in the vascular adventitia. The expression of beta-galactosidase protein was approximately 2-fold higher in SAH arteries than in normal arteries. Endothelium-dependent relaxations caused by bradykinin and substance P were suppressed in SAH arteries. The relaxations to bradykinin were significantly augmented in both normal and SAH arteries after AdCMVeNOS transduction but not after AdCMVbeta-Gal transduction. The relaxations to substance P were augmented by AdCMVeNOS transduction only in normal arteries. Bradykinin and substance P caused relaxations even in endothelium-denuded arteries, when the vessels were transduced with AdCMVeNOS. These endothelium-independent (adventitia-dependent) relaxations to bradykinin observed after AdCMVeNOS transduction were similar between normal and SAH arteries, whereas those to substance P were significantly reduced in SAH arteries compared with normal arteries. CONCLUSIONS: These results suggest that expression of recombinant proteins after adenovirus-mediated gene transfer may be enhanced in cerebral arteries affected by SAH and that successful eNOS gene transfer to spastic arteries can at least partly restore the impaired nitric oxide-mediated relaxations through local (adventitial) production of nitric oxide.     

Use of postoperative information to predict mortality rates for patients who have long stays in the intensive care unit after coronary artery bypass grafting

A series of 45 patients after subarachnoid hemorrhage (SAH) with no or only marginal neurologic impairment and 36 patients with chronic obstructive pulmonary disease (COPD) were examined with the German Freiburger Personality Inventory-Revised. Both groups showed a comparable frequency of psychologic impairments, except that the patients with COPD had significantly higher scores in the FPI-R bodily complaints and bodily concern subscales (p < 0.05). In the patients after SAH, loss of motivation (42%), abnormal introversion (40%), increased emotional lability (38%), and strain (31%) were found predominantly. The patients after SAH of unknown origin exhibited psychologic disturbances comparable with patients after aneurysmal SAH. A ruptured aneurysm of the anterior communicating artery did not lead to more psychologic disorders than aneurysms at other locations. Right frontal and right parietal infarctions were associated with significantly less emotional sensitivity (p = 0.013) and bodily concern (p < 0.001). The results demonstrate a substantial discrepancy between the prevalence of psychologic maladjustment and the moderate degree of functional impairment in patients after SAH, which remains to be explained by future research.