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A Kader

Publications and source records attributed to A Kader.

32 records · Page 2Linked to original sources

Effect of mild hypothermia on nitric oxide synthesis during focal cerebral ischemia.

The cerebroprotective effects of mild hypothermia have been extensively studied in various animal models of ischemia, but the mechanism by which mild hypothermia diminishes ischemic injury is not well understood. Nitric oxide (NO) has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures, and its synthesis is acutely increased during focal ischemia in vivo. To evaluate possible mechanisms of hypothermic neuroprotection, we measured markers of NO synthesis--nitrite and cyclic guanosine monophosphate (cGMP) levels and NO synthase activity--during right middle cerebral artery occlusion (MCAO) in the rat under normothermic (36.5 degrees C) and mild hypothermic (33 degrees C) conditions. There was a significant increase in nitrite concentration in the right hemisphere versus the left under normothermic conditions at 10 and 20 minutes after MCAO (P < 0.01), with a return to baseline levels by 60 minutes. The increase in cortical nitrite levels in the right hemisphere versus the left was not observed with mild hypothermia. There was a threefold increase in cGMP synthesis in the normothermic right cortex 10 minutes after MCAO (P < 0.05). This rise in cGMP did not occur in hypothermic animals, and the right to left cortical disparity in cGMP production was abolished. Finally, the significant increase in NO synthase activity seen in the normothermic ischemic cortex was absent in hypothermic rats (P < 0.05). These results suggest that mild hypothermia (33 degrees C) modulates the burst of nitric oxide synthesis during cerebral ischemia and may account, at least partially, for its cerebroprotective effects.

Amino Acid Oxidoreductases↗

Arteriovenous malformation draining vein physiology and determinants of transnidal pressure gradients. The Columbia University AVM Study Project.

Arteriovenous malformation (AVM) draining vein pressure (DVP) may have an influence on both the natural history of the disease and treatment outcome. The purposes of this study were to assess the relationship between DVP and other clinical and physiological variables and to characterize the transmission of arterial pressure across the AVM nidus. DVP measurements were carried out during elective AVM resection with isoflurane/nitrous oxide anesthesia with arterial carbon dioxide pressure of approximately 30 mm Hg. The gradient between the right atrium and operative measurement site was noted. Pre-excision feeding mean arterial pressure and DVP were measured with a 26-gauge needle simultaneously with systemic mean arterial pressure and central venous pressure (CVP). DVP was tested with systemic mean arterial pressure increased to approximately 20 mm Hg with phenylephrine or CVP increased with a Valsalva maneuver. Finally, preresection and postresection DVP values were compared. Relative to the site of measurement, DVP was 7 +/- 5 mm Hg at a CVP of -4 +/- 5 mm Hg (n = 45). There was no influence of presentation, presence of deep venous drainage, size, location, or prior embolization on DVP. In 19 patients, DVP decreased (8 +/- 4 to 5 +/- 3; P < 0.05) whereas CVP increased from pre- to postresection (-4 +/- 5 to -2 +/- 5; P < 0.05). For the phenylephrine challenge (n = 11), there was no difference (P = 0.84) between the delta DVP (2 +/- 1 mm Hg) and the delta CVP (2 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriovenous Malformations↗

Characterization of arteriovenous malformation feeding vessels by carbon dioxide reactivity.

PURPOSE: To characterize cerebral hemodynamics in patients immediately before microsurgical resection of moderate to large arteriovenous malformations during isoflurane anesthesia. METHODS: In angiographically defined arteriovenous malformation feeding and nonfeeding arteries, transcranial Doppler studies were performed in 25 surgeries on 22 patients. The mean blood flow velocity and pulsatility index were recorded in the middle, anterior, and posterior cerebral arteries. Transcranial Doppler velocities were measured at end-tidal carbon dioxide tensions (PetCO2) of about 25 and 35 mm Hg. Carbon dioxide reactivity was calculated as percentage mean blood flow velocity change per mm Hg PetCO2 change. RESULTS: Patient demographic and clinical data for the arteriovenous malformation group followed the expected strata of a large arteriovenous malformation population. All patients were neurologically stable before surgery. A total of 43 feeding arteries and 55 nonfeeding arteries were studied. Compared with nonfeeders, feeders exhibited higher mean blood flow velocity (68 +/- 5 vs 31 +/- 3 cm/sec, P < 0.0001) and lower pulsatility index (0.64 +/- 0.03 vs 0.88 +/- 0.04, P < 0.001); anterior and middle cerebral artery velocities at normo- and hypocapnia were significantly higher than posterior cerebral arteries for both feeders and nonfeeders (P < 0.001). Carbon dioxide reactivity was 0.2 +/- 0.2%/mm Hg in feeders and 2.1 +/- 0.2%/mm Hg in nonfeeders, with no significant difference between arteries. In four of eight patients with lesions fed by the anterior circulation (middle cerebral artery with or without anterior cerebral artery feeders), posterior cerebral artery nonfeeders exhibited low reactivity. In 2 of 5 patients with ipsilateral posterior cerebral artery feeders, contralateral posterior cerebral artery nonfeeders exhibited impaired reactivity. CONCLUSIONS: Quantitative transcranial Doppler studies are technically feasible in the operating room or interventional suite during anesthesia. Hemodynamic assessment using physiologic challenges of arteriovenous malformation feeders as well as angiographically uninvolved vessels may be useful as criteria in the assessment of malformations and arteriovenous malformation patients may exhibit abnormal vasoreactivity in distant uninvolved perfusion territories, suggesting a deranged neural control mechanism.

Adolescent↗

Transcranial Doppler changes during staged surgical resection of cerebral arteriovenous malformations: a report of three cases.

The removal of large arteriovenous malformations (AVMs) in stages has been advocated to reduce the risk of perioperative hyperemic complications. In three patients who had a two-stage surgical removal of their large (> 6 cm) frontal AVMs, transcranial Doppler (TCD) was performed 1 day before and 1 day after each surgery. Arteries still feeding the AVM after the first procedure had an increase in mean velocity (MV) and a decrease in the pulsatility index (PI) in the period between the two surgeries. MV reactivity to carbon dioxide before each stage was higher in feeding arteries at the second surgery, suggesting that the total magnitude of the shunt through the AVM was lower in spite of flow recruitment. TCD can be used to monitor the hemodynamic changes after embolization or partial surgery and may be of help in better defining the optimal time for final resection.

Adult↗

Nitric oxide production during focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Nitric oxide has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures. METHODS: A number of indicators of brain nitric oxide production (nitric and cyclic guanosine monophosphate [cGMP] concentrations and nitric oxide synthase activity) were examined after bilateral carotid ligation and right middle cerebral artery occlusion in adult rats. RESULTS: Brain nitrite was significantly increased in the right versus left cortex 5, 10, and 20 minutes after middle cerebral artery occlusion (P < .05), with a return to baseline at 60 minutes. There were no significant changes in cerebellar concentrations. Cortical levels of cGMP were increased at 10, 20, and 60 minutes after occlusion, with significant right-to-left differences (P < .05). Cerebellar concentrations of cGMP were also increased but without significant side-to-side differences. Nitric oxide synthase activity increased approximately 10-fold from baseline 10 minutes after occlusion in the right cortex but decreased markedly by 60 minutes from its peak at 10 minutes. The right-to-left difference in nitric oxide synthase activity was significant at 20 minutes (P < .05). Pretreatment of rats with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, abolished the rise in nitrite and cGMP. CONCLUSIONS: These results suggest that a sharp transient increase in the activity of nitric oxide synthase occurs during the first hour of cerebral ischemia, which leads to a burst in nitric oxide production and activation of guanylate cyclase.

Amino Acid Oxidoreductases↗

Relationship of transcranial Doppler flow velocities and arteriovenous malformation feeding artery pressures.

BACKGROUND AND PURPOSE: Feeding mean arterial pressure immediately proximal to the nidus of arteriovenous malformations may influence the frequency of spontaneous intracerebral hemorrhage. This study assessed the usefulness of transcranial Doppler ultrasound velocities as a noninvasive estimate of feeding mean arterial pressure. METHODS: We studied 41 patients undergoing 73 staged treatments of arteriovenous malformations with endovascular embolization, surgery, or both. Before treatment during the awake state, transcranial Doppler mean and peak velocities were recorded in proximal Willisian vessels. During superselective angiography with the patient under conscious sedation or during surgery with the patient under general anesthesia, feeding mean arterial pressure was measured through a 1.5F transfemoral intracranial microcatheter or a 26-g needle by direct puncture. Measurement of insonated artery diameter was possible in 41 embolizations, and a flow velocity index (mL/min) and Reynolds' number were estimated. RESULTS: Mean +/- SEM feeding mean arterial pressure was 38 +/- 2 mm Hg at a systemic mean arterial pressure of 77 +/- 2 mm Hg; mean velocity was 102 +/- 4 cm/s. There was an inverse correlation between feeding mean arterial pressure and parent artery mean velocity (y = -0.74x + 130, r = .35, P = .0025). The best correlation was for the first treatment in each patient (n = 27) using the highest peak velocity obtainable in a Willisian vessel ipsilateral to the arteriovenous malformation (y = -1.61x + 221, r = .62, P = .0005). Flow velocity index (775 +/- 106 mL/min) did not correlate with feeding mean arterial pressure, but there was a weak correlation with Reynolds' number (y = -12x + 1616, r = .27, P = .1283). Mean Reynolds' number was 1257 +/- 119. CONCLUSIONS: Transcranial Doppler mean velocity is correlated with feeding mean arterial pressure but only weakly predictive. Considerations influencing the relation of distal feeding mean arterial pressure to proximal mean velocity might include the influence of other fistulae in the circuit between major inflow and outflow channels as well as turbulent flow at vascular branch points between point of insonation and the nidus, as suggested by Reynolds' number values of more than 400.

Adult↗

Pressure autoregulation is intact after arteriovenous malformation resection.

The loss of autoregulatory control of cerebral perfusion to changes in perfusion pressure in tissue remote from an arteriovenous malformation (AVM) has been proposed as the mechanism underlying "normal perfusion pressure breakthrough." This study is the first direct test of this mechanism. Studies were performed during the resection of moderate to large AVMs in 25 patients undergoing 28 procedures under isoflurane anesthesia. Cerebral blood flow (CBF) was measured (xenon-133 method) in the hemisphere adjacent to the nidus before resection after dural exposure (pre), after AVM removal before dural closure at spontaneous systemic blood pressure (post), and, finally, with the mean arterial pressure increased by 20 mm Hg, using phenylephrine (post-BP). AVM resection resulted in a significant enhancement of perfusion in the adjacent hemisphere (30 +/- 2 vs. 25 +/- 1 ml/100g/min, P < 0.01), but no further increase of CBF occurred during increased perfusion pressure (30 +/- 2 ml/100g/min). One patient suffered a postoperative hemorrhage and another developed intraoperative brain swelling during the course of the resection that necessitated staging the procedure. These two patients had the highest increases in CBF, but intact pressure autoregulation. Preserved autoregulation to increased mean arterial pressure after resection does not support a hemodynamic mechanism for the observed increase in CBF from before the resection to after the resection. Pathological events, however, do appear to be related to increases in hemispheric perfusion.

Adolescent↗

Microsurgery for 67 intracranial arteriovenous malformations less than 3 cm in diameter.

The surgical outcome in a series of small arteriovenous malformations (AVM's) that might have been considered optimal for radiosurgery is reviewed. In a total microsurgical series of 360 patients, 67 (19%) underwent resection of AVM's less than 3 cm in largest diameter, regardless of location. Many of these lesions (45%) were in locations that might be considered surgically inaccessible such as the thalamus, brain stem, medial hemisphere, and paraventricular regions. Complete angiographic obliteration of the AVM by microsurgical technique was accomplished in 63 patients (94%) with a surgical morbidity of 1.5% and no operative mortality. Patients with hemispheric AVM's had a cure rate of 100% and no neurological morbidity. Stereotactically guided craniotomy was used in 14 patients (21%) to locate and resect deep or concealed malformations. The results from five major radiosurgery centers treating similar-sized AVM's are analyzed. The authors' surgical results compare favorably with those from radiosurgery centers which, in their opinion, supports the conclusion that microneurosurgery is superior to radiosurgery, except for a small percentage of lesions that are truly inoperable on the basis of inaccessibility.

Adolescent↗

The effect of mild hypothermia on permanent focal ischemia in the rat.

The effect of mild hypothermia on cerebral injury was evaluated in a rat model of permanent middle cerebral artery (MCA) and ipsilateral carotid artery occlusion. The MCA occlusion was performed in rats at temporalis muscle temperatures of 30 degrees C, 33 degrees C, 34.5 degrees C and 36.5 degrees C (n = 10, 8, 10, and 13, respectively). The animals were kept at the desired temperature for 1 hour and rewarmed to 36.5 degrees C. In a separate group of animals (n = 11), the temperature was decreased to 33 degrees C 1 hour after performing the arterial occlusion at normothermia. These animals were rewarmed to 36.5 degrees C after another hour with side by side controls (n = 9) kept at 36.5 degrees C throughout the experiment. Twenty-four hours after the MCA occlusion, rats were killed and the percentage of infarcted right hemisphere was determined in coronal brain sections with 2,3,5-triphenyltetrazolium chloride. The percentage of infarcted volume at 30 degrees C, 33 degrees C, and 34.5 degrees C (9.3 +/- 2.1%, 8.2 +/- 2.2%, and 8.4 +/- 2.2%) (SEM) was significantly smaller than at 36.5 degrees C (19.6 +/- 1.6%, P < 0.01). There were no significant differences between the hypothermic groups. When rats were cooled to 33 degrees C 1 hour after the arterial occlusion, the percentage of infarcted volume was also significantly smaller than the control group (8.0 +/- 1.8% vs. 17.4 +/- 2.1%) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chronic cerebral blood flow changes following experimental subarachnoid hemorrhage in rats.

Experimental subarachnoid hemorrhage was induced in 52 adult male Wistar rats by microsurgical transclival basilar artery puncture. Telencephalic blood flow measured in 24 rats with subarachnoid hemorrhage was compared with that in 23 sham-operated rats and 10 unoperated control rats using the [14C]butanol indicator fractionation technique. Telencephalic blood flow was significantly less in the rats with subarachnoid hemorrhage than in the sham-operated rats 3 (78.7 +/- 6.9 [n = 7] and 112.0 +/- 8.5 [n = 8] ml/100 g/min, respectively; p less than 0.01), 7 (74.9 +/- 5.1 [n = 9] and 112.6 +/- 4.6 [n = 8] ml/100 g/min, p less than 0.001), and 14 (81.9 +/- 6.0 [n = 8] and 104.1 +/- 5.4 [n = 7] ml/100 g/min, p less than 0.01) days after surgery. Telencephalic blood flow in unoperated controls (114.7 +/- 4.9 ml/100 g/min) did not differ significantly from sham-operated rats. Clinically, the 52 rats with subarachnoid hemorrhage were indistinguishable from 32 sham-operated rats. Postmortem examinations in 10 rats used in a preliminary investigation demonstrated significant blood clot in the basal cisterns 2 hours after basilar artery puncture. Intracranial pressure was slightly elevated (2.3 mm Hg over baseline) 30 minutes after the hemorrhage (n = 7), but when measured 3 (n = 3) or 7 (n = 3) days after surgery it had returned to baseline. Histologic examination of the brains from 10 rats subjected to subarachnoid hemorrhage 7 (n = 5) or 14 (n = 5) days before sacrifice revealed no evidence of cerebral ischemia or vasculopathic changes in the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain.

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

Animals↗