Cerebral Ischemia In Cats Research Articles

Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.

Selective platelet deposition during focal cerebral ischemia in cats.

Platelet deposition in the microcirculation may play a role in focal cerebral ischemia. We investigated platelet deposition in selected parts of the cat brain after temporary middle cerebral artery occlusion. Ten anesthesized cats were given autologous indium-111-labeled platelets and chromium-51-labeled erythrocytes. The right middle cerebral artery was occluded with miniature aneurysm clips for 3 hours via a transorbital approach; blood pressure was reduced concomitantly to decrease the collateral circulation. Removal of the clips initiated a 45-minute period of normotensive reperfusion. After sacrifice, the brain was removed and sectioned for comparison of right- versus left-hemisphere platelet deposition. Platelets were selectively deposited in the territory of the occluded right middle cerebral artery. Significant deposition was found in the caudate nucleus, internal capsule, parietal cortex, and the centrum semiovale. Our findings support the evidence that platelets are deposited in the microvasculature during temporary severe focal cerebral ischemia.

Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats.

We investigated the effect of mild whole-body hyperthermia before and after 16 minutes of global cerebral ischemia on metabolic recovery during recirculation in cats using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Hyperthermia (temperature 40.6 +/- 0.2 degrees C) was induced greater than or equal to 1 hour before ischemia and was maintained during 1.5-2 hours of recirculation in nine cats; four cats were subjected to hyperthermia without cerebral ischemia, six to hyperthermia during recirculation (after return of intracellular pH to preischemic values), and 14 to normothermic ischemia and recirculation. Our data indicate that preischemic hyperthermia results in an intracellular cerebral pH during recirculation significantly lower than that in normothermic cats. In hyperthermic cats beta-ATP and phosphocreatine (PCr) concentrations and the ratio of PCr to inorganic phosphate failed to return to preischemic levels during recirculation in contrast to normothermic cats. Hyperthermia without ischemia and hyperthermia during recirculation had no significant effect on intracellular pH. Thus, preischemic hyperthermia has a detrimental effect on metabolic recovery after transient global cerebral ischemia.

Effects of a new Ca 2+ antagonist, KB-2796, on the regional cerebral blood flow and somatosensory evoked potentials in the ischemic brain in cats

Effects of a new Ca 2+ antagonist, 1-[bis(4-fluorophenyl) methyl]-4-(2,3,4-trimethoxybenzyl) piperazine dihydro-chloride (KB-2796), on the regional cerebral blood flow (rCBF) and somatosensory evoked potentials (SEPs) were investigated using a model of focal cerebral ischemia in cats. In experiment 1, an occlusion of the middle cerebral artery for 4 hours persistently reduced the ipsilateral rCBF in both the control and the KB-2796-treated groups. However, the flow reduction was much milder in the treatment group than in the control group. Amplitudes of the SEPs diminished in both groups but the rate of deterioration was much slower in the treatment group than in the control group. In experiment 2, an occlusion of the middle cerebral artery for 1 hour was followed by reperfusion for 3 hours. The ipsilateral rCBF decreased during occlusion in both the control and the treatment groups. In the control group, postischemic hyperper-fusion was seen in the ectosylvian gyrus after reperfusion, whereas the ipsilateral rCBF recovered rapidly to the control values without showing a phase of hyperperfusion in the treatment group. The rate of recovery of the SEPs was also much more rapid in the treatment group.

Evolving focal cerebral ischemia in cats: spatial correlation of nuclear magnetic resonance imaging, cerebral blood flow, tetrazolium staining, and histopathology.

The spatial correlation of nuclear magnetic resonance imaging (NMRI) and cerebral blood flow (CBF) may improve our ability to identify ischemic brain lesions and may provide further insight into the pathophysiology of early cerebral ischemia. Eleven pentobarbital-anesthetized adult cats underwent exposure of the common carotid arteries bilaterally and the right middle cerebral artery through a transorbital approach. Baseline NMRI images were obtained with a single spin-echo, multislice technique using a 0.6-T field, 0.4-cm slice thickness, and a surface coil. Focal ischemia was produced with right middle cerebral artery occlusion and potentiated with bilateral common carotid artery ligation. Sequential NMRI studies were then performed at 1, 2, 4, 6, and 12 hours or until CBF was determined in the same cats using [14C]iodoantipyrine at either 2 (n = 2), 4 (n = 2), 6 (n = 2), or 12 (n = 1) hours after the time of occlusion. This protocol allowed temporal and spatial correlation of NMRI and CBF. Alternate 5-mm brain slices were incubated with 1% 2,3,5-triphenyltetrazolium chloride (TTC) for 45 minutes at 37-41 degrees C and frozen in liquid Freon for later autoradiographic CBF determination. Four cats were studied only with NMRI and TTC (not CBF). The correlation between areas of increased NMRI signal intensity observed in T2-weighted images (repetition time 2,000 msec, echo time 120 msec), vital staining with TTC, low CBF, and routine histology was evaluated. During the early phase (less than 6 hours), T2-weighted NMRI changes were localized to the central ischemic gray matter areas, as defined in the later CBF images, with no involvement of the white matter. By the twelfth hour the NMRI changes involved the entire ischemic area including gray and white matter. The initial visible changes seen on T2-weighted NMRI are suggestive of cellular edema, and the later changes are characteristic of vasogenic edema. The spread of NMRI changes compared with the ischemic area determined from autoradiographic CBF is consistent with the previously described biphasic evolution of ischemic injury. These data suggest that T2-weighted NMRI could be used clinically to delineate areas of acute ischemic stroke.

The Protective Effect of Mannitol and Methylprednisolone in the Acute Focal Cerebral Ischemia in Cats

The Protective Effect of Mannitol and Methylprednisolone in the Acute Focal Cerebral Ischemia in Cats

Extracellular K+, microflow and NAD/NADH changes in focal cerebral ischemia in cats.

The interrelationship of electrical function of the brain, the extra-cellular K+, NADH fluorescence and microflow was studied in acute focal cerebral ischemia in cats. The electrical activity, extracellular potassium (K+ e) changes and fluororeflectometry (NAD/NADH redox state and microflow) were measured in the middle ectosylvian gyrus in closed skull animals. The middle cerebral artery was clamped for two hours, and the observation was followed four additional hours after the release of the occlusion. The animals were classified into three distinct groups based on electrophysiological criteria. The severe stroked animals showed more than 80% reduction in the ratio of the electrical activity of the occluded territory to that on the contralateral side. In the moderate group the ECoG ratio was between 0.2–0.7 and if the ratio was over 0.7, the animals were classified as mild.

Effect of Naloxone on Neurologic Deficit and Cortical Blood Flow During Focal Cerebral Ischemia in Cats

Using middle cerebral artery occlusion in the cat as a model of focal cerebral ischemia, we investigated the effect of naloxone on both neurologic deficit and regional cortical blood flow during cerebral ischemia. In all animals with major strokes, 2 mg/ml naloxone administered intravenously produced a dramatic reversal of neurologic symptoms four hours after the ischemic lesion. Animals were then anesthetized and cortical blood flow was measured by the hydrogen clearance method. Blood flow in the ischemic cortex was noted to be approximately 55% that of the control side. Naloxone produced a significant decrease of approximately 20% in cortical blood flow in the ischemic hemisphere while no effect on blood flow on the control side was noted. Thus, naloxone appears to reverse the neurologic deficits following middle cerebral artery occlusion in the cat. This effect appears to be accompanied by a decrease in local blood flow to the ischemic cortex.

Effect of naloxone on neurologic deficit and cortical blood flow during focal cerebral ischemia in cats

Using middle cerebral artery occlusion in the cat as a model of focal cerebral ischemia, we investigated the effect of naloxone on both neurologic deficit and regional cortical blood flow during cerebral ischemia. In all animals with major strokes, 2 mg/ml naloxone administered intravenously produced a dramatic reversal of neurologic symptoms four hours after the ischemic lesion. Animals were then anesthetized and cortical blood flow was measured by the hydrogen clearance method. Blood flow in the ischemic cortex was noted to be approximately 55% that of the control side. Naloxone produced a significant decrease of approximately 20% in cortical blood flow in the ischemic hemisphere while no effect on blood flow on the control side was noted. Thus, naloxone appears to reverse the neurologic deficits following middle cerebral artery occlusion in the cat. This effect appears to be accompanied by a decrease in local blood flow to the ischemic cortex.

Pentoxifylline in regional cerebral ischemia in cats.

The effect of pentoxifylline on regional cerebral ischemia was evaluated in 22 cats. In one group of 10 cats the middle cerebral artery (MCA) was occluded by a transorbital approach, and the cats were maintained on an intensive care protocol for 48 h. Pentoxifylline 10 mg.kg-1 initiated intravenously 30 min post-occlusion and followed by 6.3 mg.kg-1.h-1 for 48 h failed improve the neurologic outcome or infarct size when compared to controls. In another group of 12 cats with the same ischemic lesion, regional cerebral blood flow in the anterior (ischemic) area and an ipsilateral parieto-occipital region was measured by 133Xe wash-out after intra-arterial injection. MCA occlusion reduced the anterior flow by 50% from a mean control value of 62.7 ml.100 g-1.min-1 to 31.9 ml.100 g-1.min-1. The parieto-occipital flow was reduced by 20-30%, probably due to diaschisis. Pentoxifylline produced only a brief, although approximately 50%, increase in flow detected over both brain regions and failed to improve the cerebral energy stores as measured 150 min following MCA occlusion. From the neurologic, blood flow and metabolic data, it is concluded that pentoxifylline failed to affect cerebral ischemia favorably in cats.

3 - Effect of a novel imidazole derivative (Y-9179) on cerebral function after cerebral ischemia in cats

3 - Effect of a novel imidazole derivative (Y-9179) on cerebral function after cerebral ischemia in cats

Action of cytidine diphosphocholine on functional and hemodynamic effects of cerebral ischemia in cats.

The depression of evoked cortical potentials caused by brief periods of cerebral ischemia is attenuated by prior intracarotid injection of cytidoline (2, 4 or 8 mg/kg). Studies performed in hypercapnic cats suggest that the protection afforded by cytidoline is of metabolic rather than hemodynamic origin. The participation of the central dopaminergic structures by the drug is suggested according to the previous data.