Cerebral effects of hypocapnia plus nitroglycerin-induced hypotension in dogs

1986 ◽  
Vol 64 (6) ◽  
pp. 924-931 ◽  
Author(s):  
Alan A. Artru ◽  
Kim Wright ◽  
Peter S. Colley
Keyword(s):  
Sodium Nitroprusside ◽  
Brain Tissue ◽  
Cerebral Metabolism ◽  
Energy Charge ◽  
Metabolic Disturbances ◽  
Induced Hypotension ◽  
Content Type ◽  
Arterial Blood ◽  
Cerebral Metabolites ◽  
Fine Print

✓ This study examined the effect of hypocapnia (PaCO2 20 mm Hg) on cerebral metabolism and the electroencephalogram (EEG) findings in 12 dogs during nitroglycerin (NTG)-induced hypotension. Previous studies suggest that NTG is a more potent cerebral vasodilator than sodium nitroprusside or trimethaphan. It was speculated that combining hypocapnia with NTG-induced hypotension would cause less disturbance of cerebral metabolism and the EEG than the disturbances previously reported when hypocapnia was combined with hypotension induced by sodium nitroprusside or trimethaphan. All 12 dogs were examined at 1) normocapnia with normotension; 2) hypocapnia with normotension; and 3) hypocapnia combined with NTG-induced hypotension to mean arterial blood pressure (MABP) levels of 60, 50, and 40 mm Hg. In six dogs the cerebral metabolic rate of oxygen was determined, and the EEG was evaluated using compressed spectral analysis. Brain tissue metabolites were calculated in the other six dogs. During normotension, hypocapnia caused no deterioration of cerebral metabolism or of the EEG. Hypocapnia combined with NTG-induced hypotension caused a decrease of the power of the α and β2 spectra of the EEG at MABP's of 60 mm Hg or less. At an MABP of 40 mm Hg, brain tissue phosphocreatine and the cerebral energy charge decreased, while the brain tissue lactate:pyruvate ratio increased. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites returned to initial values, but the power of the EEG α and β2 spectra was decreased compared to baseline values. The cerebral metabolic disturbances and EEG alterations seen here with hypocapnia plus NTG-induced hypotension were similar to those previously reported with hypocapnia plus sodium nitroprusside-induced hypotension, and less than those previously reported with hypocapnia plus trimethaphan-induced hypotension. For hyperventilated patients, administration of NTG may be a better hypotensive treatment than trimethaphan, but similar in effect to sodium nitroprusside.

Relative importance of hypertension compared with hypervolemia for increasing cerebral oxygenation in patients with cerebral vasospasm after subarachnoid hemorrhage

2005 ◽  
Vol 103 (6) ◽  
pp. 974-981 ◽  
Author(s):  
Andreas Raabe ◽  
Jügen Beck ◽  
Mike Keller ◽  
Hartmuth Vatter ◽  
Michael Zimmermann ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Tissue ◽  
Cerebral Vasospasm ◽  
Moderate Hypertension ◽  
Cerebral Oxygenation ◽  
Brain Oxygenation ◽  
Content Type ◽  
Arterial Blood ◽  
Hypertension Therapy ◽  
Fine Print

Object. Hypervolemia and hypertension therapy is routinely used for prophylaxis and treatment of symptomatic cerebral vasospasm at many institutions. Nevertheless, there is an ongoing debate about the preferred modality (hypervolemia, hypertension, or both), the degree of therapy (moderate or aggressive), and the risk or benefit of hypervolemia, moderate hypertension, and aggressive hypertension in patients following subarachnoid hemorrhage. Methods. Monitoring data and patient charts for 45 patients were retrospectively searched to identify periods of hypervolemia, moderate hypertension, or aggressive hypertension. Measurements of central venous pressure, fluid input, urine output, arterial blood pressure, intracranial pressure, and oxygen partial pressure (PO2) in the brain tissue were extracted from periods ranging from 1 hour to 24 hours. For these periods, the change in brain tissue PO2 and the incidence of complications were analyzed. During the 55 periods of moderate hypertension, an increase in brain tissue PO2 was found in 50 cases (90%), with complications occurring in three patients (8%). During the 25 periods of hypervolemia, an increase in brain oxygenation was found during three intervals (12%), with complications occurring in nine patients (53%). During the 10 periods of aggressive hypervolemic hypertension, an increase in brain oxygenation was found during six of the intervals (60%), with complications in five patients (50%). Conclusions. When hypervolemia treatment is applied as in this study, it may be associated with increased risks. Note, however, that further studies are needed to determine the role of this therapeutic modality in the care of patients with cerebral vasospasm. In poor-grade patients, moderate hypertension (cerebral perfusion pressure 80–120 mm Hg) in a normovolemic, hemodiluted patient is an effective method of improving cerebral oxygenation and is associated with a lower complication rate compared with hypervolemia or aggressive hypertension therapy.

Resection of a large, high-flow arteriovenous malformation during hypotension and hypothermia induced by a percutaneous cardiopulmonary support system

1997 ◽  
Vol 87 (3) ◽  
pp. 440-444 ◽  
Author(s):  
Toru Iwama ◽  
Nobuo Hashimoto ◽  
Tatemi Todaka ◽  
Yoshikado Sasako ◽  
Syuji Inamori ◽  
...  
Keyword(s):  
Support System ◽  
High Flow ◽  
Percutaneous Cardiopulmonary Support ◽  
Induced Hypotension ◽  
Content Type ◽  
Cardiopulmonary Support ◽  
Arterial Blood ◽  
Percutaneous Cardiopulmonary Support System ◽  
Cardiopulmonary Support System ◽  
Fine Print

✓ The key to successful surgical resection of cerebral arteriovenous malformations (AVMs) is control of bleeding and cerebral swelling. Induced hypotension is one of the most valuable means of achieving this control. The authors introduced induced hypotension with mild hypothermia by using a percutaneous cardiopulmonary support system (PCPS) to resect a large, high-flow AVM. The efficacy and technical points of this method are discussed. The PCPS, whose entire intraluminal surface was coated with heparin, was established through a transfemoral route. During resection of the AVM, a mean arterial blood pressure of 60 mm Hg and a mean body temperature of 30°C were easily maintained by regulating the flow rate of the PCPS and by blood cooling. The activated coagulation time was maintained at approximately 250 seconds with a minimum systemic administration of heparin. The authors report the case of a 30-year-old woman who presented with intraventricular hemorrhage and was diagnosed as having a large, high-flow AVM located in the left sylvian fissure. The AVM was fed by the left middle, posterior, and anterior cerebral arteries and drained by the many cortical ascending veins and the basal vein. The patient underwent surgery after hypotension and hypothermia had been induced via the PCPS method. Induced hypotension decreased the tension of the nidus and made its dissection easier. The AVM was totally resected and no hemostatic difficulties were encountered. On the basis of the authors' experience, they suggest that hypotension and hypothermia induced by using the PCPS is a powerful tool for the successful resection of large, high-flow AVMs.

Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study

2003 ◽  
Vol 98 (5) ◽  
pp. 952-958 ◽  
Author(s):  
Sandra Magnoni ◽  
Laura Ghisoni ◽  
Marco Locatelli ◽  
Mariangela Caimi ◽  
Angelo Colombo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brain Tissue ◽  
Cerebral Metabolism ◽  
Extracellular Fluid ◽  
Redox Status ◽  
Content Type ◽  
Lactate Levels ◽  
Microdialysis Study ◽  
Fine Print ◽  
Pyruvate Ratio

Object. The authors investigated the effects of hyperoxia on brain tissue PO2 and on glucose metabolism in cerebral and adipose tissue after traumatic brain injury (TBI). Methods. After 3 hours of ventilation with pure O2, 18 tests were performed on different days in eight comatose patients with TBI. Lactate, pyruvate, glucose, glutamate, and brain tissue PO2 were measured in the cerebral extracellular fluid (ECF) by using microdialysis. Analytes were also measured in the ECF of abdominal adipose tissue. After 3 hours of increase in the fraction of inspired O2, brain tissue PO2 rose from the baseline value of 32.7 ± 18 to 122.6 ± 45.2 mm Hg (p < 0.0001), whereas brain lactate dropped from its baseline (3.21 ± 2.77 mmol/L), reaching its lowest value (2.90 ± 2.58 mmol/L) after 3 hours of hyperoxia (p < 0.01). Pyruvate dropped as well, from 153 ± 56 to 141 ± 56 µmol/L (p < 0.05), so the lactate/pyruvate ratio did not change. No significant changes were observed in glucose and glutamate. The arteriovenous difference in O2 content dropped, although not significantly, from a baseline of 4.52 ± 1.22 to 4.15 ± 0.76 ml/100 ml. The mean concentration of lactate in adipose tissue fell significantly as well (p < 0.01), but the lactate/pyruvate ratio did not change. Conclusions. Hyperoxia slightly reduced lactate levels in brain tissue after TBI. The estimated redox status of the cells, however, did not change and cerebral O2 extraction seemed to be reduced. These data indicate that oxidation of glucose was not improved by hyperoxia in cerebral and adipose tissue, and might even be impaired.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage

2004 ◽  
Vol 101 (4) ◽  
pp. 594-599 ◽  
Author(s):  
Michael F. Stiefel ◽  
Gregory G. Heuer ◽  
John M. Abrahams ◽  
Stephanie Bloom ◽  
Michelle J. Smith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Subarachnoid Hemorrhage ◽  
Brain Tissue ◽  
Cerebral Oxygenation ◽  
Content Type ◽  
Poor Grade ◽  
Physiological Variables ◽  
Arterial Blood ◽  
End Tidal ◽  
Fine Print

Object. Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Methods. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4 ± 10.9 mm Hg. The baseline MABP and CPP were 90 ± 20 and 84 ± 19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9 ± 7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5 ± 7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7 ± 11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Conclusions. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Cerebral metabolism after fluid-percussion injury and hypoxia in a feline model

2002 ◽  
Vol 97 (3) ◽  
pp. 643-649 ◽  
Author(s):  
Alois Zauner ◽  
Tobias Clausen ◽  
Oscar L. Alves ◽  
Ann Rice ◽  
Joseph Levasseur ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Tissue ◽  
Cerebral Metabolism ◽  
Acid Base ◽  
Content Type ◽  
Hypoxic Injury ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Feline Model ◽  
Fine Print

Object. Currently, there are no good clinical tools to identify the onset of secondary brain injury and/or hypoxia after traumatic brain injury (TBI). The aim of this study was to evaluate simultaneously early changes of cerebral metabolism, acid—base homeostasis, and oxygenation, as well as their interrelationship after TBI and arterial hypoxia. Methods. Cerebral biochemistry and O2 supply were measured simultaneously in a feline model of fluid-percussion injury (FPI) and secondary hypoxic injury. After FPI, brain tissue PO2 decreased from 33 ± 5 mm Hg to 10 ± 4 mm Hg and brain tissue PCO2 increased from 55 ± 2 mm Hg to 81 ± 9 mm Hg, whereas cerebral pH fell from 7.1 ± 0.06 to 6.84 ± 0.14 (p < 0.05 for all three measures). After 40 minutes of hypoxia, brain tissue PO2 and pH decreased further to 0 mm Hg and 6.48 ± 0.28, respectively (p < 0.05), whereas brain tissue PCO2 remained high at 83 ± 13 mm Hg. Secondary hypoxic injury caused a drastic increase in cerebral lactate from 513 ± 69 µM/L to 3219 ± 490 µM/L (p < 0.05). The lactate/glucose ratio increased from 0.7 ± 0.1 to 9.1 ± 2 after hypoxia was introduced. The O2 consumption decreased significantly from 18.5 ± 1.1 µl/mg/hr to 13.2 ± 2.1 µl/mg/hr after hypoxia was induced. Conclusions. Cerebral metabolism, O2 supply, and acid—base balance were severely compromised ultra-early after TBI, and they declined further if arterial hypoxia was present. The complexity of pathophysiological changes and their interactions after TBI might explain why specific therapeutic attempts that are aimed at the normalization of only one component have failed to improve outcome in severely head injured patients.

No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury

2000 ◽  
Vol 92 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Michael N. Diringer ◽  
Kent Yundt ◽  
Tom O. Videen ◽  
Robert E. Adams ◽  
Allyson R. Zazulia ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxygen Content ◽  
Cerebral Metabolism ◽  
Oxygen Extraction Fraction ◽  
Content Type ◽  
Arterial Blood ◽  
Venous Oxygen Content ◽  
Severe Tbi ◽  
Fine Print

Object. Hyperventilation has been used for many years in the management of patients with traumatic brain injury (TBI). Concern has been raised that hyperventilation could lead to cerebral ischemia; these concerns have been magnified by reports of reduced cerebral blood flow (CBF) early after severe TBI. The authors tested the hypothesis that moderate hyperventilation induced early after TBI would not produce a reduction in CBF severe enough to cause cerebral energy failure (CBF that is insufficient to meet metabolic needs).Methods. Nine patients were studied a mean of 11.2 ± 1.6 hours (range 8–14 hours) after TBI occurred. The patients' mean Glasgow Coma Scale score was 5.6 ± 1.8 and their mean age 27 ± 9 years; eight of the patients were male. Intracranial pressure (ICP), mean arterial blood pressure, and jugular venous oxygen content were monitored and cerebral perfusion pressure was maintained at a level higher than 70 mm Hg by using vasopressors when needed. Measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral venous oxygen content (CvO2) were made before and after 30 minutes of hyperventilation to a PaCO2 of 30 ± 2 mm Hg. Ten age-matched healthy volunteers were used as normocapnic controls.Global CBF, CBV, and CvO2 did not differ between the two groups, but in the TBI patients CMRO2 and OEF were reduced (1.59 ± 0.44 ml/100 g/minute [p < 0.01] and 0.31 ± 0.06 [p < 0.0001], respectively). During hyperventilation, global CBF decreased to 25.5 ± 8.7 ml/100 g/minute (p < 0.0009), CBV fell to 2.8 ± 0.56 ml/100 g (p < 0.001), OEF rose to 0.45 ± 0.13 (p < 0.02), and CvO2 fell to 8.3 ± 3 vol% (p < 0.02); CMRO2 remained unchanged.Conclusions. The authors conclude that early, brief, moderate hyperventilation does not impair global cerebral metabolism in patients with severe TBI and, thus, is unlikely to cause further neurological injury. Additional studies are needed to assess focal changes, the effects of more severe hyperventilation, and the effects of hyperventilation in the setting of increased ICP.

Tissue resonance analysis: a novel method for noninvasive monitoring of intracranial pressure

2002 ◽  
Vol 96 (6) ◽  
pp. 1132-1137 ◽  
Author(s):  
David Michaeli ◽  
Z. Harry Rappaport
Keyword(s):  
Intracranial Pressure ◽  
Brain Tissue ◽  
Noninvasive Monitoring ◽  
The Body ◽  
Mechanical Resonance ◽  
Content Type ◽  
Resonance Analysis ◽  
Arterial Blood ◽  
Significant Difference ◽  
Fine Print

✓ A number of noninvasive methods used to measure intracranial pressure (ICP) have been proposed in the literature. For a variety of reasons, however, none of these have displayed significant practical applicability. The authors describe their development of a new, computerized, portable device based on tissue resonance analysis (TRA) technology for the noninvasive monitoring and measurement of ICP. In response to the heart beat, the soft tissue and fluid compartments of the brain each exhibit characteristic vibration and mechanical resonant responses that radiate through the organs and tissues of the body. Patterns of vibration and mechanical resonance of various body organs and tissues are different and provide the possibility of extracting new and specific information in a noninvasive fashion. According to the TRA approach, ICP is dependent on the value of the dominant secondary (mechanical) resonance level of brain tissue. By digitally processing a reflected ultrasound signal (by using a concave ultrasonography probe with a carrier frequency of 1 MHz) from the third ventricle, the authors obtained a digital high-resolution echopulsogram, which visually is equivalent to ICP waves that are obtained invasively. The fast Fourier relationship of electrocardiogram and echopulsogram waves allowed the derivation of the secondary mechanical resonance levels. The authors developed a formula for a quantitative, noninvasive measurement of ICP, which uses information regarding multiple components of the intracranial space—both mechanical (secondary resonance) and physiological (time required for transfer of arterial blood to venous blood through brain tissue)—and the relationship between these components. A comparison of invasive and noninvasive ICP measurements was made during blinded trials in 40 patients with various diseases of the central nervous system, and ranges of ICP were measured from 1 to 66 mm Hg. The ICP values obtained using the two methods were highly correlated (r = 0.99), without a statistically significant difference between simultaneously obtained readings (p = 1). By using an integrative approach that reflects all components of the intracranial compartment, TRA allows for accurate noninvasive recordings of ICP. This method has significant advantages over other noninvasive technologies reported to date.

Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure

2000 ◽  
Vol 92 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Helene Benveniste ◽  
Katie R. Kim ◽  
Laurence W. Hedlund ◽  
John W. Kim ◽  
Allan H. Friedman
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Neurosurgical Procedures ◽  
Shr Rats ◽  
Mr Microscopy ◽  
Content Type ◽  
Wky Rats ◽  
Arterial Blood ◽  
Fine Print

Object. It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model.Methods. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons.There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups.Conclusions. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.

Cerebral oxygen and microdialysis monitoring during aneurysm surgery: effects of blood pressure, cerebrospinal fluid drainage, and temporary clipping on infarction

2002 ◽  
Vol 96 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
Rupert Kett-White ◽  
Peter J. Hutchinson ◽  
Pippa G. Al-Rawi ◽  
Marek Czosnyka ◽  
Arun K. Gupta ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cerebrospinal Fluid ◽  
Brain Tissue ◽  
Total Duration ◽  
Wilcoxon Test ◽  
Fisher Exact Test ◽  
Content Type ◽  
The Impact ◽  
Temporary Clipping ◽  
Fine Print

Object. The aim of this study was to investigate potential episodes of cerebral ischemia during surgery for large and complicated aneurysms, by examining the effects of arterial temporary clipping and the impact of confounding variables such as blood pressure and cerebrospinal fluid (CSF) drainage. Methods. Brain tissue PO2, PCO2, and pH, as well as temperature and extracellular glucose, lactate, pyruvate, and glutamate were monitored in 46 patients by using multiparameter sensors and microdialysis. Baseline data showed that brain tissue PO2 decreased significantly, below a mean arterial pressure (MAP) threshold of 70 mm Hg. Further evidence of its relationship with cerebral perfusion pressure was shown by an increase in mean brain tissue PO2 after drainage of CSF from the basal cisterns (Wilcoxon test, p < 0.01). Temporary clipping was required in 31 patients, with a mean total duration of 14 minutes (range 3–52 minutes), causing brain tissue PO2 to decrease and brain tissue PCO2 to increase (Wilcoxon test, p < 0.01). In patients in whom no subsequent infarction developed in the monitored region, brain tissue PO2 fell to 11 mm Hg (95% confidence interval 8–14 mm Hg). A brain tissue PO2 level below 8 mm Hg for 30 minutes was associated with infarction in any region (p < 0.05 according to the Fisher exact test); other parameters were not predictive of infarction. Intermittent occlusions of less than 30 minutes in total had little effect on extracellular chemistry. Large glutamate increases were only seen in two patients, in both of whom brain tissue PO2 during occlusion was continuously lower than 8 mm Hg for longer than 38 minutes. Conclusions. The brain tissue PO2 decreases with hypotension, and, when it is below 8 mm Hg for longer than 30 minutes during temporary clipping, it is associated with increasing extracellular glutamate levels and cerebral infarction.

Posttreatment with adenovirus-mediated gene transfer of calcitonin gene—related peptide to reverse cerebral vasospasm in dogs

2002 ◽  
Vol 97 (1) ◽  
pp. 136-142 ◽  
Author(s):  
Motoyoshi Satoh ◽  
Eddie Perkins ◽  
Hitoshi Kimura ◽  
Jiping Tang ◽  
Yi Chun ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Cerebral Vasospasm ◽  
Treated Group ◽  
Positive Staining ◽  
Cmv Promoter ◽  
Content Type ◽  
Related Peptide ◽  
Arterial Blood ◽  
Blood Injection ◽  
Fine Print

Object. Gene transfer to cerebral vessels is a promising new therapeutic approach for cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was undertaken to explore whether a delayed treatment with adenovirus encoding the prepro-calcitonin gene—related peptide (CGRP), 2 days after initial blood injection, reduces cerebral vasospasm in a double-hemorrhage model of severe vasospasm in dogs. Methods. In 20 dogs, arterial blood was injected into the cisterna magna on Days 0 and 2. Thirty minutes after the second blood injection, the animals received either adenovirus encoding the prepro-CGRP gene (AdCMVCGRP—treated group, eight dogs) or adenovirus encoding the β-galactosidase gene (AdCMVβgal—treated group, six dogs) under the cytomegalovirus (CMV) promoter. One group of dogs did not receive treatment and served as controls (control SAH group, six dogs). Angiography was performed on Days 0 and 7 to assess cerebral vasospasm. On Day 7 following angiography, the animals were killed and their brains were stained with X-gal to detect the distribution of gene expression. Cerebrospinal fluid (CSF) was also tested for CGRP immunoreactivity. Severe vasospasm was observed in control SAH dogs on Day 7, and the mean basilar artery (BA) diameter was 53.4 ± 5.5% of the value measured on Day 0. Treatment with AdCMVβgal did not alter vasospasm (the BA diameter was 55 ± 3.9% of that measured on Day 0). The leptomeninges and adventitia of the BAs of dogs treated using AdCMVβgal demonstrated positive staining with X-gal. High levels of CGRP were measured in CSF from dogs that received AdCMVCGRP. In the group treated with AdCMVCGRP, vasospasm was significantly reduced (the BA diameter was 78.2 ± 5.3% of that measured on Day 0, p < 0.05 compared with the control SAH group and the AdCMVβgal group). Conclusions. In a model of severe vasospasm in dogs, gene transfer of CGRP after injection of blood attenuated cerebral vasospasm after SAH.

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