Abraham Kader

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 (nitrite 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 7VG-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. (Stroke. 1993;24:1709-1716.)

The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations.

The physiological and anatomical aberrations that result in hemorrhage from cerebral arteriovenous malformations (AVMs) remain unclear. In an attempt to clarify which conditions may predispose to hemorrhage, we examined clinical and physiological indices on presentation groups of either hemorrhage or nonhemorrhage in a large cohort of patients (n = 449). Variables examined included AVM size, type of venous drainage, transcranial Doppler (TCD) velocities, feeding mean arterial pressure (FMAP), and draining vein pressure. TCD and pressure data were obtained before any treatment. Age (mean +/- standard deviation) at the time of presentation was 33 +/- 13 years and did not differ between groups. Patients with small (< or = 2.5 cm) AVMs presented more frequently with hemorrhage (90%) than did patients with medium (> 2.5 and < or = 5.0 cm; 52%) or large (> 5.0 cm; 50%) AVMs (P = 0.0001). The 48 of 94 AVMs (51%) with deep venous drainage were more likely to have hemorrhage (P = 0.0219) than were those with superficial drainage (24 of 73 [33%]). Deep drainage was a predictor of hemorrhage even in the subgroup of medium and large supratentorial AVMs (P = 0.005). There was no difference in draining vein pressure (n = 18) between groups (21 +/- 10 and 19 +/- 11 mm Hg, respectively; P = 0.7812). FMAP (n = 52) was higher in the hemorrhage than in the nonhemorrhage group (44 +/- 13 versus 34 +/- 10 mm Hg; P = 0.0007) but was only weakly related to the size of the lesion (largest dimension) (y = -0.74x + 40; r = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

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)

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.

Deliberate mild intraoperative hypothermia for craniotomy.

BackgroundDespite enthusiasm for the use of mild hypothermia during neurosurgical procedures, this therapy has not been evaluated systematically. This study examined the feasibility and safety of deliberate mild hypothermia and rewarming. MethodsThirty patients scheduled for craniotomy were assigned to either a normothermic or mildly hypothermic group. Tympanic membrane temperature was monitored at anesthetic induction, throughout the isoflurane-fentanyl-N2O-O2 anesthetic, and for 18 h postoperatively. Normothermic patients were warmed to 36.5–37.0°C after an initial temperature decrease, and hypothermic patients were cooled to 35°C. In the hypothermic group temperatures were allowed to drift to 34.5°C before rewarming was initiated. Water blankets and convective heating devices were used to cool and rewarm. ResultsThe minimum temperature achieved by the hypothermic group was 34.3 ± 0.4°C. Cooling occurred at a rate of 1.0 ± 0.4°C/h. Rewarming took place at a rate of 0.7 ± 0.6°C/h (range 0.1–1.8) in the hypothermic group. Hypothermia did not delay emergence from anesthesia (20 ± 15 min) compared with normothermia (15 ± 15 min, P = .45). Mean temperature upon intensive care unit admission was 35.8 ± 1.0°C for the hypothermic group and 37.1 ± 0.5°C for the normothermic group (P < 0.0001). The hypothermic patients had more postoperative shivering. From 8 to 18 h postoperatively the temperatures of the two groups were similar except for a slightly greater temperature in the hypothermic patients at 12 h (37.6 ± 0.5 vs. 37.3 ± 0.4°C, P = .029). ConclusionsAlthough deliberate mild hypothermia is easily achieved intraoperatively, complete rewarming may be difficult to attain during craniotomy with current methods. In addition to the need for determining whether deliberate mild hypothermia confers cerebral protection in humans, the potential risks of the therapy need to be further characterized.

Cerebral Hyperemia after Arteriovenous Malformation Resection Is Related to “Breakthrough” Complications but Not to Feeding Artery Pressure

To study the pathophysiology of idiopathic postoperative brain swelling or hemorrhage after arteriovenous malformation resection, termed normal perfusion pressure breakthrough (NPPB), we performed cerebral blood flow (CBF) studies during 152 operations in 143 patients, using the xenon-133 intravenous injection method. In the first part of the study, CBF was intraoperatively measured (isoflurane/N2O anesthesia) during relative hypocapnia in 95 patients before and after resection. The NPPB group had a greater increase (P < 0.0001) in mean +/- standard deviation global CBF (28 +/- 6 to 47 +/- 16 ml/100 g/min, n = 5) than did the non-NPPB group (25 +/- 7 to 29 +/- 10 ml/100 g/min, n = 90); both arteriovenous malformation groups showed greater increase (P < 0.05) than did controls undergoing craniotomy for tumor (23 +/- 6 to 23 +/- 6 ml/100 g/min, n = 22). Ipsilateral and contralateral CBF changes were similar. In a second cohort of patients with arteriovenous malformations, CBF was measured at relative normocapnia and it increased (P < 0.002) from pre- to postresection (40 +/- 13 to 49 +/- 15 ml/100 g/min, n = 57). There were no NPPB patients in this latter cohort. The feeding mean arterial pressure was measured intraoperatively before resection or at the last embolization before surgery (n = 64). The feeding mean arterial pressure (44 +/- 16 mm Hg) was 56% of the systemic arterial pressure (78 +/- 12 mm Hg, P < 0.0001) and was not related to changes in CBF from pre- to postresection. There was an association between increases in global CBF from pre- to postresection and NPPB-type complications, but there was no relationship of these CBF changes to preoperative regional arterial hypotension. These data do not support a uniquely hemodynamic mechanism that explains cerebral hyperemia as a consequence of repressurization in hypotensive vascular beds.

The safety of intraoperative lumbar subarachnoid drainage for acutely ruptured intracranial aneurysm: Technical note

Recently, some concern has arisen regarding the safety of intraoperative spinal drainage for brain relaxation in aneurysm surgery, due to anecdotal association with both aneurysmal rebleeding and increases in symptomatic vasospasm. To address these concerns, we reviewed our experience with frequent spinal drainage and early surgery in 432 consecutive cases of surgically treated aneurysmal subarachnoid hemorrhage. Unless contraindicated by mass effect or associated pathology, all grade I-III patients referred within 14 days were treated with spinal drainage at surgery. In this cohort (n = 314), there were no cases of meningitis or nerve root injury. Only one case of intraoperative rebleeding could be associated with spinal drain placement (0.3%). In grade IV-V patients, 47% required preoperative ventriculostomy, and 11% were ineligible for spinal drainage due to mass effect. There were, however, no complications related to spinal drainage in the remaining 23 patients. Permanently-shunted hydrocephalus (8%) and symptomatic vasospasm (19%) were infrequent overall. When analyzed by grade, spinal drains were generally associated with equal or reduced incidence of these developments when compared to patients without spinal drainage. We conclude that brain relaxation can be safely and effectively obtained using intraoperative spinal drains during early aneurysm surgery.

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.