Post-ischemic hypermetabolism in cat brain.

Abstract

SUMMARY Delayed postischemk brain hypoperfusion and hypennetabolism are likely detrimental factors to neurologic recovery after transient global brain ischemia and may be mediated by catecholaraines acting via adrenergic receptors. We evaluated the effects of alpha and beta receptor blockade on cerebral blood flow (CBF) and metabolism after 16 min transient global brain ischemia.Ischemia was induced by arterial hypotension and a high pressure neck tourniquet in 13 anesthetized cats. Six cats were untreated, 4 received propranoloi 1 mg/kg, IV and 3 a combination of propranolol and phentolamine, one mg/kg injected one min before recircnlation. Total CBF was measured by continuous monitoring of cerebral venous "*Xe clearance after bolus intra-arterial injection. Arterial and cerebral venous oxygen, glucose and lactate were measured. Cerebral cortex glucose and lactate were measured 3 hours post-ischemia after in situ freezing with liquid N,. The cerebral cortex of 3 cats anesthetized, but not subjected to ischemia, was similarly frozen and analyzed for glucose and lactate.Total CBF was relatively constant for up to 3 h post-ischemia in all groups, but significant changes in fast and slow-flow rates and compartment sizes were observed. In untreated cats, the normal 60/40 percent relative weight of the fast and slow-flow compartments was reversed to 30/70 percent by 1 hr post-ischemia. Propranolol attenuated the size of the fast-flow compartment in the first 30 min post-ischemia which was partially restored by phentolamine. Brain oxygen consumption Increased 2 to 3-fold by 1 h post-lscbemia in all groups. Propranolol compromised CBF and impaired glucose and lactate oxidation which was partly reversed by phentolamine.We concluded that within the first 30 min post-ischemia, beta, and to a lesser extent, alpha receptors predominate in the modulation of cerebrovascular tone. By 1 h post-ischemia, however, adrenergic modulation of cerebrovascular tone is lost. Delayed post-ischemic hypermetabolism unlike stress-induced, but like hypoxia-induced hypermetabolism is only partially affected by beta blockade. Propranolol apparently compromises brain oxygen consumption secondary to a reduction in brain O, supply while phentolamine improves perfusion and oxygen consumption. Methods and MaterialsSixteen cats of either sex, 3 to 4 kg body weight, were anesthetized with halothane, 4 percent in oxygen, and glass cannulae were tied into the tracheas. The cats were immobilized with pancuronium bromide (0.4 mg) and mechanically ventilated on halothane 1 percent, oxygen 33 percent, and nitrogen 66 percent. Respiratory rates and tidal volumes were adjusted to maintain continuously monitored end-tidal CO, between 4 and 5 percent. Rectal temperature and electrocardiogram were continuously monitored.Polyethylene catheters inserted in femoral veins and arteries were used for drug infusion, intravenous fluid replacement (5 percent dextrose/0.45 percent NaCl, 3 to 5 ml/kg hour), arterial pressure monitoring, blood sampling and reinfusion of c...

Postischemic Hyperglycemia Is Not Protective to the Neonatal Rat Brain

“…In postischemic cerebral tissue, a persistent hypermetabolism that uses anaerobic over oxidative metabolism has been seen during reperfusion in adult animals (25), with damage to mitochondria in the regions of ischemia (26). It is possible then that glucose supplementation may provide the necessary substrate for generation of EAA receptor activation in the presence of injured neurons, thus augmenting cerebral damage, as was seen in our glucose-treated animals.…”

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with ¹⁸F-FDG

“…Therefore, no quantitative changes were observed in glucose uptake between the contralateral and ipsilateral hemispheres (Figure 3, blue and green bars). This could be due to hyper-uptake of glucose by the peri-ischemic region or increased glucose metabolism at this time point to compensate for loss of cellular ATP 10,11 . However, significant decrease in glucose uptake in specific regions of the ipsilateral hemisphere was observed across multiple animals (n = 5) at 24 hr post-reperfusion (Figure 3, red bars).…”

Global cerebral ischemia and intracellular pH during hyperglycemia and hypoglycemia in cats.

“…A tourniquet, constructed similar to a miniature blood pressure cuff, was wrapped around the cat's neck and inflated to 35 psi to induce 16 minutes of transient global cerebral ischemia. 13 Trimethaphan camsylate (Arfonad, Roche Laboratories, Nutley, New Jersey),pressure maintained systemic arterial hypotension (<50 mm Hg) during cuff inflation. Immediately before cuff deflation, the blood pressure was elevated and maintained, when necessary, during recirculation by infusion of 0.1 mg/ml norepinephrine (Levophed, Winthrop-Breon Laboratories, New York, New York).…”

“…A tourniquet, constructed similar to a miniature blood pressure cuff, was wrapped around the cat's neck and inflated to 35 psi to induce 16 minutes of transient global cerebral ischemia. 13 Trimethaphan camsylate (Arfonad, Roche Laboratories, Nutley, New Jersey), 4 mg /ml i.v., was given and titrated to induce rapid systemic arterial hypotension (40-50 mm Hg) immediately before cuff inflation; positive end-expiratory by guest on …”