Pablo M. Lawner

Ischemic brain edema: comparative effects of barbiturates and hypothermia.

The effect of pentobarbital and hypothermia on the development of ischemic brain edema was studied in 23 rhesus monkeys undergoing transorbital middle cerebral artery occlusion. Fifteen additional animals served as undipped controls. Regional cortical cerebral blood flow (rCBF), arteriovenous oxygen content difference (AVDOa), and regional cortical metabolic rate of O2 (rCMROa) were measured hourly until sacrifice 11 hours postocclusion, at which time ischemic cerebral edema was measured. In 8 animals no treatment followed the occlusion, and these developed significant edema. In 7 animals pentobarbital 14 mg/kg was administered intravenously 30 min after occlusion and 7 mg/kg every 2 hours thereafter. In this group ischemic brain edema was negligible. In 8 animals, hypothermia to 25.9 ± 0.5°C was started 30 min after occlusion and maintained until sacrifice; ischemic brain edema was not significantly altered from untreated-clipped animals. On the basis that both pentobarbital and hypothermia produced similar changes in rCBF, AVDOj, and rCMRO2, but only pentobarbital prevented edema, it is postulated that the mode of action of barbiturates in preventing ischemic brain edema is not entirely related to their known effect on blood flow and metabolism.

Attenuation of ischemic brain edema by pentobarbital after carotid ligation in the gerbil.

The efficacy of pentobarbital in the treatment of ischemic cerebral edema was evaluated in 160 gerbils. Animals underwent carotid ligation under ether or pentobarbital (50 mg/kg) anesthesia. The pentobarbital anesthetized group received an additional dose of 30 mg/kg 4 h after ligation. Animals were evaluated for neurologic deficit at 4 and 8 h post-ligation, then sacrificed. Water content of each hemisphere and swelling percentage were calculated from the wet and dry weights of the hemispheres. Swelling percentage in animals anesthetized with ether was 6.374 ± 0.89 SE, whereas gerbils who underwent sham carotid ligation showed a negligible (0.491 ± 0.15) swelling percentage (p < 0.01). Pentobarbital animals had a swelling percentage of 3.359 ± 0.68. This represents a significant edema reduction compared to ether-anesthetized animals (p < 0.01). Neurologic deficit was decreased by 56.7< (17/60 vs 30/60) in pentobarbital animals compared with ether animals (p ± 0.025). Mortality at 8 hours was reduced by 75< (2/60 vs 8/60) in pentobarbital animals (p < 0.05).

Method for continuous conjunctival oxygen monitoring during carotid artery surgery.

A new device for measuring conjunctival oxygen tension (PcjO2) was used for intraoperative monitoring during carotid endarterectomy. The PcjO2 measures local tissue oxygenation and, thus, reflects the oxygen delivery to the areas supplied by the internal carotid artery. PcjO2 was found to be sensitive to manipulation, clamping, and obstruction of the carotid artery; it provided a useful monitoring system for assessment of the cerebral circulation during carotid surgery.

Hemodynamic and clinicopathologic verification of a stroke model in the dog.

Twenty-fire mongrel dogs bad Intracranial internal carotid and proximal middle cerebral artery occlusions. The animals were followed for one week and subsequently sacrificed. This method of clipping produced a mean drop in cortical cerebral blood flow of 48.4% as measured by the MKr washout technique. Cerebral blood flow was not affected by the brain retraction necessary for clip placements. Mortality in the first week was 16% and neurological deficits were obserred In 73% of the animals. Infarction was present in 80% of the animals, and the mean percent infarction of the affected hemisphere was 17.00 ± 3.98SE. This is a useful stroke model in an animal which is easily available, inexpensive, and suitable for microvascular intracranial surgery research.

Rapid, transient drop in brain glucose after intravenous phloretin or 3-0-methyl-D-glucose.

Rats were injected intravenously with either phloretin (100 mg/kg) or 3-0-methyl glucose (2 g/kg) to reduce the carrier-mediated flux of glucose into brain. Plasma glucose and brain free glucose (BFG), lactate, and glycogen were measured over a 16 min time course. Injection of these substances caused a rapid drop in BFG to 60% of control at one minute and a minimum (50% of control values) at 4 min., followed by a gradual rise to control levels at 16 min. While plasma glucose fell, and then increased after injection, brain lactate and glycogen content was unaffected. Repeated injections of phloretin eventually caused a drop in brain glycogen; but with either competitor, BFG never fell below 50% of normal values. The i.v. injection of the glucose analog, 3-0-methyl glucose (the less toxic of the two drugs) is proposed as a possible means of cutting off the potentially hazardous supply of blood glucose to the postischemic brain.

Qualitative measurement of cerebral infarction using ultraviolet fluorescence

A reliable method of macroscopically determining the volume of cerebral infarction using ultraviolet fluorescence was developed in an animal model. Cerebral infarction was induced in 40 dogs by occluding the distal internal carotid and middle cerebral arteries. No barbiturates were administered. Intravenous sodium fluorescein was given before the animal was killed. Following fixation, 1 cm coronal sections were evaluated with ultraviolet light of 366 nm wavelength. The area of induced fluorescence for each section was determined using a grid overlay. Microscopic examination revealed that the areas of ischemic cell necrosis corresponded to areas of maximal fluorescence. This is an easily reproducible method to determine the volume of cerebral infarction.

Measurement of cerebral blood flow by washout of microwave induced heating.

A method is described for measurement of cerebral blood flow utilizing the washout of microwave delivered heating. Using a microwave source attenuated to achieve a brain temperature elevation of 0.5-0.75 degrees C after a 2 second exposure in the rat, cerebral blood flow was calculated from the temperature washout curve monitored by a small thermistor implanted in the brain. The results obtained with this method were comparable to those obtained using the [14C] butanol method. To our knowledge this represents the first description of a method to deliver a blood flow “indicator” atraumatically directly into brain tissue.

Effects of vasoconstriction and distal dilation on carotid stenoses in the dog.

Traditionally, arterial stenoses have been assumed to be inflexible, static obstructive lesions that could not acutely change their configuration or cross-sectional area. However, recent clinical and experimental observations have shown that coronary arterial stenoses can respond to vasoconstriction and intraluminal pressure changes. This experimental study evaluated whether similar dynamic changes could occur in a carotid artery stenosis. The effects of dilation distal to a circumferential snare were examined in 6 mongrel dogs. To eliminate collateral flow, the distal carotid artery was occluded and blood flow diverted through a 16 or 20 gauge needle. With no stenosis, distal dilation increased flow from 29.0 +/− 2.0 to 90.1 +/− 3.8 ml/min, (p less than 0.01). With moderate stenosis, the flow increase (25.5 +/− 1.3 to 56.4 +/− 3.7 ml/min, p less than 0.01 following dilation was attenuated. With severe stenosis, flow paradoxically decreased (20.4 +/− 1.0 to 11.4 +/− 1.0 ml/min, (p less than 0.01). This flow decrease was associated with a large stenotic resistance increase (2.13 +/− 0.51 to 18.93 +/− 5.58 mm Hg/ml · min-1, (p less than 0.01). In eight additional experiments, an in vitro preparation was used to examine the effects of vasoconstriction on stenotic severity. Vasoconstriction, induced by ergonovine, methoxamine, angiotensin, or vasopressin, resulted in a significant flow decrease and stenotic resistance increase. Thus, both vasoconstriction and intraluminal pressure were shown to affect stenotic severity, and thereby influence blood flow. These data illustrate hemodynamic factors which may be important in patients with severe carotid artery stenosis.