Hydrogen Clearance Technique Research Articles

Effect of a calcium channel blocker on posttraumatic spinal cord blood flow.

The normal rat spinal cord blood flow (SCBF) has been shown to increase after administration of nimodipine, a calcium channel blocker. The present study investigates the capability of nimodipine to improve SCBF, as measured by the hydrogen clearance technique, after a 53.0-gm clip compression injury to the T-1 segment of the rat spinal cord. The profound drop in mean systemic arterial blood pressure (MSAP) after cervical cord injury precluded any improvement in posttraumatic SCBF by nimodipine alone. Hence, in a randomized controlled study with five rats per group, pressor agents (whole blood, angiotensin, or adrenaline) were infused to maintain MSAP between 100 and 120 mm Hg after injury. Control animals received only a saline infusion. Nimodipine at the optimal dose found in normal animals (1.5 microgram/kg/min) was added to the pressor agents. The MSAP and other physiological parameters were measured in rats receiving the pressor agents only and in those receiving pressor agents combined with nimodipine. In rats receiving whole blood, angiotensin, or adrenaline the posttraumatic MSAP improved to between 100 and 120 mm Hg, but there was no improvement in SCBF compared to the saline group. The addition of nimodipine decreased MSAP and SCBF in all groups except those animals also receiving adrenaline, where the MSAP was maintained at 109 +/- 5 mm Hg. In these animals a significant increase in posttraumatic SCBF from 16.5 +/- 2.1 to 20.2 +/- 2.3 ml/100 gm/min (mean +/- standard error of the mean) occurred at the site of injury with the addition of nimodipine. The maintenance of an adequate MSAP by a pressor agent was crucial for nimodipine to improve posttraumatic SCBF by its ability to dilate the spinal vascular bed. Adrenaline was the only pressor agent that could fulfill the above criteria, although other pressor agents need to be investigated. Experiments are underway with the combination of adrenaline and nimodipine to further verify these encouraging results demonstrating an improvement in posttraumatic ischemia of the spinal cord.

Experimental carbon dioxide laser brain lesions and intracranial dynamics: Part 3. Effect on cerebral blood flow.

Experimental carbon dioxide brain lesions were created over the intact dura mater of the left parietooccipital region of the anesthetized albino rabbit (40-watt impacts of 0.5-second duration, for a total of 4 seconds, with 0.5-second intervals between impacts), and cerebral blood flow (CBF) studies were performed with the hydrogen clearance technique. The animals were mechanically ventilated to maintain a constant PaCO2. Blood pressure, central venous pressure, electroencephalogram, and intracranial pressure were continuously monitored. The control CBF before lesion was 64.1 +/- 15.8 and 70.9 +/- 13.4 ml/100 g/minute for the left and the right hemispheres, respectively. CBF studies at 2, 4, 6, 8, and 24 hours after the lesion did not significantly change from the control values, save for a trend to increase over the right hemisphere only at 2 hours (range 106.0 +/- 55.4 to 41.6 +/- 9.3). It is concluded that in this model the changes in intracranial pressure and brain edema that are seen and have been previously reported are not due to change in cerebral circulation. The brain edema that results probably has characteristics similar to those seen in the cryogenic lesion (vasogenic) model, and this could account for the rise in intracranial pressure.

Acute gastric ulceration in rats with obstructive jaundice with special reference to gastric mucosal blood flow.

The mechanism of acute gastric ulceration in rats with obstructive jaundice was investigated in terms of the changes in the gastric mucosal blood flow, and the effect of vagotomy on ulceration was examined. 188 Sprague-Dawley rats weighing about 250 g were prepared and divided into 4 groups as follows; control group (sham operation), jaundiced group (ligation of the bile duct), vagotomized group (vagotomy with pyloroplasty), jaundiced and vagotomized group (simultaneous ligation of the bile duct and vagotomy with pyloroplasty). Two weeks after the operation, water immersion and restraint stress procedures were performed in these 4 groups. The gravity of acute gastric ulcerations was calculated by ulcer index. The gastric mucosal blood flow was measured by hydrogen clearance technique. The following results were obtained: In control group, ulcer index was increased and gastric mucosal blood flow was decreased after the stress procedures. The jaundiced group showed significantly higher ulcer index and early significant decrease of gastric mucosal blood flow after the stress procedures compared to the control group. The vagotomized group showed significantly decreased ulcer index after the stress procedures compared to the control group, however, the gastric mucosal blood flow showed almost the same values as the control group. The jaundiced and vagotomized group showed significant decrease of ulcer index and improvement of decrease of gastric mucosal blood flow compared to the jaundiced group. These results indicated that the gastric mucosal blood flow plays an important role in the occurrence of acute gastric ulceration in rats with obstructive jaundice, and vagotomy might be useful to prevent them by maintaining gastric blood flow in obstructive jaundice.

Cerebral and cerebellar blood flow autoregulations in acutely induced cerebral ischemia in spontaneously hypertensive rats--transtentorial remote effect.

Autoregulation of cerebral (CBF) and cerebellar blood flow (CeBF) was studied before, during and after acutely induced cerebral ischemia in spontaneously hypertensive rats. Cerebral ischemia of the supratentorial portion was induced for one hour by bilateral carotid artery ligation (BCL). The animals were artificially ventilated and the blood flow was measured with a hydrogen clearance technique. To test the autoregulation, the blood pressure was stepwise lowered by bleeding and maintained at a new level, i.e. 15% or 30% lower than the baseline values before, during and after cerebral ischemia. At the preischemic state, CBF and CeBF were 52.1 +/- 6.2 and 58.9 +/- 4.6 ml/100 g/min (mean +/- SEM), of which autoregulations were normally preserved. Following BCL, CBF was markedly decreased to about 10% of control value while CeBF was minimally reduced to 46.9 +/- 8.6 ml/100 g/min (80%). At the ischemic state, CBF became almost zero flow during hypotension. CeBF was also reduced to 74% and further to 58% of the resting value by 15% and 30% decrease in the blood pressure, respectively, indicating impaired CeBF autoregulation. At the 30 min post-ischemic state, CBF was recovered to 48.0 +/- 4.9 and CeBF to 53.9 +/- 5.4 ml/100 g/min. Autoregulation of CBF was still abolished, whereas CeBF was kept constant by 15% fall of blood pressure and slightly reduced to 84% by 30% hypotension, indicating almost recovery of CeBF autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Discrepancies among CT, histological, and blood-brain barrier findings in early cerebral ischemia.

The development of ischemic edema and blood-brain barrier (BBB) disruption during the 1st day of experimental cerebral infarction induced by transorbital occlusion of the middle cerebral artery (MCA) in cats was evaluated by computerized tomography (CT) scanning and compared to gravimetric and pathological studies. Regional cerebral blood flow was measured using the hydrogen clearance technique or stable xenon-enhanced CT scanning. Edema was observed gravimetrically and microscopically as early as 1 hour after the onset of ischemia in the cortex and at 3 hours or later in both the cortex and white matter. However, a significant decrease of Hounsfield numbers on the CT scans was not detectable at 1 or 3 hours and was scarcely visible at 9 hours after occlusion. Disruption of the BBB was detected by leakage of Evans blue dye at 3 hours after the occlusion in two of six animals and at 9 hours in five of five animals. However, CT scanning after infusion of contrast material showed no significant increase in Hounsfield number even 24 hours after MCA occlusion. These discrepancies should be emphasized when the dynamics of ischemic edema and BBB disruption are evaluated for clinical therapy by CT scanning.

Effects of long-term antihypertensive treatment on cerebral, thalamic and cerebellar blood flow in spontaneously hypertensive rats (SHR).

Cerebral blood flows (CBF) were measured in the parietal cortex, the thalamus and the cerebellum by the hydrogen clearance technique in anesthetized spontaneously hypertensive rats, of which hypertension was treated for 16 weeks (long-term) or 8 weeks (short-term) with antihypertensive agents of hydralazine and guanethidine. As compared to non-treated control animals, CBF in the three regions were significantly increased while the calculated cerebrovascular resistances (CVR) were decreased in hypertension-treated animals. Such CBF and CVR changes were greater in SHR with long-term than short-term therapy. Both an increase in CBF and a decrease in CVR were closely related to a fall in the blood pressure. From the present results, it was concluded that earlier and longer treatment of hypertension could lessen or even prevent the increased CVR due to the hypertensive vascular changes, and increase CBF as a result.

An experimental study on the effects of DMSO and indomethacin on cerebral circulation and intracranial pressure

Albino rabbits with a cryogenic lesion to the left parieto-occipital cortex had cerebral blood flow studies (CBF) with the hydrogen clearance technique 24 hours after the insult. Similar subgroups were treated with DMSO (1 g/kg) bolus, DMSO (2 g/kg) infusion, indomethacin (20 mg/kg) bolus, and indomethacin followed by DMSO. Following DMSO bolus administration there was an immediate rise in CBF over both hemispheres, with a significant paradoxical decrease at 30 minutes, followed by a second smaller rise at 60 minutes. With DMSO infusion, the rise in CBF was sustained throughout the infusion period with no paradoxical decrease. With indomethacin there was an initial decrease immediately following the drug, and at 60 minutes there was a rise in the insulted left hemisphere, more than the right one. Indomethacin administration 15 minutes prior to DMSO failed to halt the immediate increase in CBF noted following DMSO bolus injection. These results, together with the changes that occurred in intracranial pressure and brain water content, are analyzed.

A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia

A pharmacological analysis was carried out to determine the possible role of aberrant calcium fluxes, vasoactive arachidonic acid metabolites, and microvascular lipid peroxidation in the development of posttraumatic spinal cord white matter ischemia. Pentobarbital-anesthetized cats were treated intravenously 30 minutes before a 500-gm-cm contusion injury to the lumbar spinal cord with one of the following test drugs: the Ca++ channel antagonists verapamil, diltiazem, or nifedipine; the cyclo-oxygenase inhibitors ibuprofen or meclofenamate; the thromboxane A2 (TXA2) synthetase inhibitor furegrelate sodium; or the stable epoprostenol (prostacyclin, or PGI2) analogue ciprostene calcium alone or in combination with furegrelate sodium. Another group of animals was pretreated for 5 days before spinal injury with a combination of the antioxidants vitamin E and selenium in high doses. The hydrogen clearance technique was used to make repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus of the injured segment before and for 4 hours after injury. In 11 untreated uninjured cats, the mean preinjury SCBF was 12.7 +/- 1.5 ml/100 gm/min. Following contusion, there was a progressive decline in SCBF to 6.8 +/- 0.4 ml/100 gm/min, or 53.5% of the preinjury level at 4 hours. In comparison, the Ca++ antagonists diltiazem and nifedipine (but not verapamil) prevented a significant posttraumatic decrease in SCBF. Similarly, both cyclo-oxygenase inhibitors (ibuprofen and meclofenamate) maintained SCBF within normal limits (10 ml/100 gm/min or greater). However, neither TXA2 synthetase inhibition nor the stable PGI2 analogue alone had a significant effect in preventing ischemia, whereas a combination of the two agents did serve to support SCBF. The most impressive preservation of posttraumatic SCBF, however, was observed in the antioxidant-treated animals. Based upon these results, a hypothesis is presented concerning the pathogenesis of posttraumatic central nervous system ischemia which integrates an injury-induced rise in intracellular Ca++, the increased synthesis of vasoactive prostanoids (such as prostaglandin F2 alpha and TXA2), and progressive microvascular lipid peroxidation.

Quantitative measurement of cerebral blood flow and cerebral blood volume after cerebral ischaemia.

CBF obtained by the hydrogen clearance technique and cerebral blood volume (CBV) calculated from the [14C]dextran space were measured in three groups of rats subjected to temporary four-vessel occlusion to produce 15 min of ischaemia, followed by 60 min of reperfusion. In the control animals, mean CBF was 93 +/- 6 ml 100 g-1 min-1, which fell to 5.5 +/- 0.5 ml 100 g-1 min-1 during ischaemia. There was a marked early postischaemic hyperaemia (262 +/- 18 ml 100 g-1 min-1), but 1 h after the onset of ischaemia, there was a significant hypoperfusion (51 +/- 3 ml 100 g-1 min-1). Mean cortical dextran space was 1.58 +/- 0.09 ml 100 g-1 prior to ischaemia. Early in reperfusion there was a significant increase in CBV (1.85 +/- 0.24 ml 100 g-1) with a decrease during the period of hypoperfusion (1.33 +/- 0.03 ml 100 g-1). Therefore, following a period of temporary ischaemia, there are commensurate changes in CBF and CBV, and alterations in the permeability-surface area product at this time may be due to variations in surface area and not necessarily permeability.

Differences in Cerebral Blood Flow with Pulsatile and Nonpulsatile Flow in Normal and Ischemic Brain

The effect of pulsatile versus non pulsatile perfusion on regional cerebral blood flow (CBF) was tested in a canine model with and without focal ischemia. Nine dogs were placed on total cardiopulmonary bypass with a flow rate of 100 cc/kg/min. at normothermia. Control cerebral blood flow measurements were made in both cerebral hemispheres using the hydrogen clearance technique during pulsatile and nonpulsatile perfusion. The cerebral blood flow measurements were repeated after lateralized ischemia was induced by occluding one middle cerebral artery and the ipsilateral carotid artery. Ischemia was confirmed by cerebral blood flow measurements and electroencephalograph changes in these anesthetized animals. In non-ischemic brain, pulsatile perfusion increased cerebral blood flow 19% over that measured during nonpulsatile perfusion. The reduced flow seen with nonpulsatile perfusion never fell into ischemic ranges (i.e., below 25 cc/100 g/min.) in normal brain tissue. However, in brain rendered ischemic by occlusion of conductance vessels, pulsatile perfusion increased cerebral blood flow 55% over nonpulsatile perfusion, presumably by recruiting collaterals more effectively. This study suggests important physiologic benefits from pulsatile perfusion, especially to patients on cardiopulmonary bypass with cerebrovascular insufficiency.

Pial vascular behavior during bilateral and contralateral cervical sympathetic stimulation.

The present study in cats investigates the effect of cervical sympathetic stimulation on changes of diameter of pial arteries and veins, CBF, and intracranial pressure (ICP) using the cranial window and hydrogen clearance techniques. During 20 min of bilateral stimulation, pial arteries maximally constricted by 12%, veins by 13-15%. While the constriction of the large arteries remained stable during the whole 20-min period of bilateral stimulation, small arteries escaped after some 2 min. A similar though weaker trend was noted for the veins. CBF was reduced at 2 min by 31%, and was not different from resting at 18 min. Contralateral stimulation for 20 min induced early constriction only in small arteries, while all other vessels remained more or less unreactive. This phenomenon is explained by interhemispheric arterial collaterals that bring sympathetic fibers mainly to small arteries contralaterally. ICP was lowered initially by 47 +/- 12% during bilateral and by 23 +/- 5% during contralateral stimulation. ICP escaped after 2 and 5 min during bilateral and contralateral stimulation, respectively, and even started to rise after some 10 min. From these data, it is concluded that the sympathoadrenergic system exerts a short-lasting protective effect upon cerebral vascular volume. Small arteries escape from constriction as a consequence of primarily myogenic counteraction of pial and intraparenchymal vessels, and probably additional metabolic dilatation of intraparenchymal vessels.

Isoflurane, halothane, and regional cerebral blood flow at various levels of PaCO2 in rabbits.

The effects of halothane and isoflurane on regional cerebral blood flow (CBF) were studied in 18 New Zealand White rabbits anesthetized with nitrous oxide (N2O) and morphine sulfate (MS) at three different levels of PaCO2. CBF was measured using the hydrogen clearance technique. Monitored variables were intracranial pressure (ICP), central venous pressure, heart rate, mean arterial pressure, electroencephalogram, arterial blood gases, end-tidal (ET) volatile anesthetic, and ET CO2. Addition of 1 MAC halothane to the N2O/MS background anesthetic caused flow to increase significantly in all three regions studied (cortex, dorsal hippocampus, white matter) at all three levels of PaCO2 (low: 20-25 mmHg; normal: 35-40 mmHg; high: 50-55 mmHg). Addition of 1 MAC isoflurane to the background anesthetic caused CBF to decrease significantly in all regions during hypocapnia. During normocapnia, CBF was unchanged with the addition of 1 MAC isoflurane in all regions and during hypercapnia, CBF increased significantly only in the dorsal hippocampus following addition of 1 MAC isoflurane to the MS/N2O background anesthetic. Volatile anesthetic administration was associated with significant, although small, increases in ICP at all PaCO2 levels. We conclude that 1 MAC concentrations of halothane and isoflurane have opposite effects on CBF when added to a N2O/MS anesthetic during hypocapnia and that the effects of isoflurane on regional CBF are dependent on PaCO2 in rabbits under the anesthetic conditions of this experiment.

Effect of topical nimodipine versus its ethanol-containing vehicle on cat pial arteries.

Nimodipine and its solvent containing ethanol were tested in a randomized in vivo study by local administration to the outer vessel wall surface of pial arteries and veins in 15 anesthetized cats. Reactions were studied through a cranial window. Diameter variations of 90 arterial and 78 venous vessel segments were continuously analyzed using a multichannel videoangiometer. The solvent alone caused minor though statistically significant (p less than 0.001) 7.6% dilatation, 8% in small and 7% in large arteries, which returned to their resting state after stopping treatment. 2.4 X 10(-5) M nimodipine plus solvent induced a 21% pial arterial dilatation (p less than 0.001), 26% in small and 17% in large arteries; dilatation induced by nimodipine plus solvent was significantly greater than dilatation by the solvent alone (p less than 0.001). After ceasing topical administration, arteries remained dilated by some 5%. Pial veins exhibited only minor reaction, i.e. a 6% (statistical n.s.) dilatation of large veins during nimodipine, and an 8% dilatation of small veins 20 minutes after stopping nimodipine. During solvent-administration rCBF, as estimated with the hydrogen clearance technique, remained unchanged. It is concluded that the dilatatory effect of the investigated compound on pial arteries is predominantly due to nimodipine.

Cerebral blood flow and tissue metabolism in experimental cerebral ischemia of spontaneously hypertensive rats with hyper-, normo-, and hypoglycemia.

The present study was designed to clarify the effect of blood glucose level on cerebral blood flow and metabolism during and after acute cerebral ischemia induced by bilateral carotid ligation (BCL) in spontaneously hypertensive rats (SHR). Blood glucose levels were varied by intraperitoneal infusion of 50% of glucose (hyperglycemia), insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). Cerebral blood flow (CBF) in the parietal cortex and thalamus was measured by hydrogen clearance technique, and the supratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. In non-ischemic animals, blood glucose levels had no influence on the supratentorial lactate, pyruvate or adenosine triphosphate (ATP) concentrations. In ischemic animals, however, cortical CBF was reduced to less than 1% of the resting value at 3 hours after BCL. However, there were no substantial differences of CBF during and after ischemia among 3 glycemic groups. Cerebral lactate in the ischemic brain greatly increased in hyperglycemia (34.97 +/- 1.29 mmol/kg), moderately in normoglycemia (23.43 +/- 3.13 mmol/kg) and less in hypoglycemia (7.20 +/- 1.54 mmol/kg). In contrast, cerebral ATP decreased in hyperglycemia (0.93 +/- 0.19 mmol/kg) as much as it did in normoglycemia (1.04 +/- 0.25 mmol/kg), while ATP reduction was much greater in hypoglycemia (0.45 +/- 0.05 mmol/kg). At 1-hour recirculation after 3-hour ischemia, ATP tended to increase in all groups of animals, indicating the recovery of energy metabolism. Such metabolic recovery after recirculation was good in hypo- and normoglycemia, and was also evident in hyperglycemia. Our results suggest that hyperglycemia is not necessarily an unfavorable condition in acute incomplete cerebral ischemia.

Effects of intravenous glycerol on cerebral blood flow and tissue metabolism in acute cerebral ischemia in spontaneously hypertensive rats.

The effects of antiedematous agent with intravenous 10% glycerol on cerebral blood flow (CBF) and metabolism were studied in acute cerebral ischemia experimentally induced by bilateral carotid artery occlusion in spontaneously hypertensive rats (SHR). CBF was measured by the hydrogen clearance technique and brain tissue metabolites such as lactate, pyruvate and ATP in the ischemic brain frozen in situ were determined by the enzymatic method. In comparison with saline-infused SHR, the reduction of CBF in the thalamus following carotid occlusion was significantly small in the glycerol treated SHR. Supratentorial ATP concentration in the 3 hr-ischemic brain was reduced in both groups of rats, but its reduction was significantly smaller in the glycerol-infused group than the other. Lactate and lactate/pyruvate ratio tended to be less increased in the glycerol rats, indicating that ischemic metabolism was restrained by the treatment. The present results strongly suggest that intravenous glycerol is effective against acute cerebral ischemia from the view point of cerebral hemodynamic and metabolism.

Development of cyclooxygenase and lipoxygenase metabolites of arachidonic acid after transient cerebral ischemia.

Vasoactive arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to characterize the local generation of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in transient ischemia with reperfusion, Mongolian gerbils were studied for regional cerebral blood flow (CBF), using the hydrogen clearance technique, and for cerebral levels of the thromboxane metabolite TXB2, and prostaglandins 6-keto-PGF1 alpha and PGE2, as well as the leukotriene LTB4. The gerbils were anesthetized with pentobarbital, and half of the animals were pretreated with the cyclooxygenase inhibitor indomethacin. All received 10 or 20 minutes of dense forebrain ischemia followed by reperfusion of 10 minutes, 50 minutes, or 100 minutes. A separate control group received no ischemic lesion. Regional CBF decreased significantly from 23.7 +/- 2.6 to 4.3 +/- 1.7 cc/100 gm/min during ischemia (p less than 0.01). Reperfusion resulted in initially normal flows (22.5 +/- 5.1 cc/100 gm/min) followed by a progressive hypoperfusion (11.3 +/- 2.7 cc/100 gm/min). All metabolites showed parallel significant (p less than 0.05) increases after transient ischemia and reperfusion compared to baseline levels (values (in pg/mg protein) were: TXB2 45.5 +/- 7.1 vs 23.3 +/- 3.6; 6-keto-PGF1 alpha 262.8 +/- 47.9 vs 175.8 +/- 26.8; PGE2 256.5 +/- 35.6 vs 112.5 +/- 11.2; and LTB4 37.8 +/- 4.6 vs 24.6 +/- 6). These levels were all significantly decreased (p less than 0.05) by pretreatment with indomethacin except for the leukotriene LTB4, which was increased. Transient cerebral ischemia results in a reperfusion abnormality and the local generation of cyclooxygenase products, which are reduced by pretreatment with indomethacin; however, cyclooxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction may lead to new understandings of the pharmacological modification of detrimental vascular changes after transient cerebral ischemia.

Selective functional vulnerability of cortical neurons following transient MCA-occlusion in the cat.

Simultaneous recordings of several cortical neurons were obtained before, during and after transient 15 min occlusion of the middle cerebral artery in cats. With the use of a multiple electrode array consisting of 4-7 platinum/iridium microelectrodes, the cortical pericellular blood flow was concurrently measured by means of the hydrogen clearance technique. Hydrogen clearance measurements revealed a homogeneous blood flow distribution throughout all phases of the experiment in the area covered by the different microelectrodes. Considering only the results of experiments with low residual blood flow during ischemia (less than 0.1 ml/g/min), single unit activity ceased immediately after occlusion and remained so during the ischemic period. The recovery time of action potentials after reperfusion ranged from 10 min to 3 hours depending on the examined neuron. Lower values for discharge rates of the individual cells were generally observed after reoccurrence, although some units exhibited temporarily an even higher spike frequency. Furthermore, the spike form usually changed in that the hyperpolarizing afterpotentials were enlarged after recirculation. However, some cells with a nearly unchanged spike form were found as well. The results indicate that the recovery of cell function largely depends on the individual neuron which supports the idea of a selective functional vulnerability of cortical neurons in response to ischemia.

Failure of the somatosensory evoked potential following middle cerebral artery occlusion and high-grade ischemia in the cat--effects of hemodilution.

Acute focal ischemia was created in 10 cats by unilateral retro-orbital middle cerebral artery (MCA) occlusion. Regional cerebral blood flow (CBF) was determined utilizing the hydrogen clearance technique from electrode recordings within the gray matter and white matter of the ectosylvian gyrus of both hemispheres. The somatosensory evoked potential (SSEP) was obtained during contralateral median nerve stimulation. When the MCA was clipped the white and gray matter blood flows in the ipsilateral ectosylvian gyrus were reduced to 14.8 +/- 19.6% and 19.3 +/- 23.7% of control, and the cortical component of the SSEP was abolished. In the contralateral hemisphere an average increase of 3.5% above the control latency and a 10% mean depression in the amplitude of the cortical component of the SSEP were observed following occlusion. CBF in the contralateral hemisphere was unaffected by the MCA clip. Infusion of saline or dextran to lower the hematocrit by approximately 45% did not significantly improve blood flow or restore the SSEP in the hemisphere ipsilateral to the MCA clip. However, significant increases in the contralateral hemisphere gray matter CBF occurred following hemodilution while the latency of the cortical component of the SSEP in this same hemisphere was significantly extended. Elevations in gray and white matter blood flows were achieved in the experimental hemisphere of 3 of 10 cats suggesting a wide range of variation in the collateral circulation.

The influence of induced hypotension and spine distraction on canine spinal cord blood flow.

Deliberate hypotension is used in scoliosis surgery to reduce the need for blood transfusion and to improve operating conditions. There are concerns, however, that hypotension may decrease spinal cord blood flow (SCBF) and thereby predispose the spinal cord to ischemic injury, particularly when it is distracted during Harrington instrumentation. In a canine model, the mean arterial pressure (MAP) was reduced to 50% of the normotensive value with sodium nitroprusside and halothane to study its effects, with and without spinal distraction, on spinal cord blood flow measured by the hydrogen clearance technique. The induction of systemic hypotension resulted in a significant decrease in spinal cord blood flow from 15.7 +/- 1.1 ml/min/100 g (control) to 10.7 +/- 4.7 ml/min/100 g. This initial decrease in spinal cord blood flow returned to normotensive values by 35 minutes following the induction of hypotension, suggesting an autoregulatory effect. This indicates that the induction of deliberate hypotension to half its normotensive mean arterial pressure is associated with a significant decrease in spinal cord blood flow that returns to normotensive levels by 35 minutes. One and two centimeters of longitudinal distraction applied during systemic hypotension did not reduce spinal cord blood flow when it was applied at least 45 minutes after the hypotension was induced. Thus, when longitudinal stretch of a magnitude approximating that used clinically during Harrington instrumentation is applied in the presence of systemic hypotension, the normal SCBF is not reduced when the autoregulating system is functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible non-involvement of lipoxygenase pathway in the cerebral blood flow decrease due to indomethacin

Indomethacin (10n mg/kg i.p.) induced a marked decrease in local cerebral blood flow (1.CBF), which was measured in the frontal cortex of unanesthetized rats by the hydrogen clearance technique. Brain prostaglandins (PGD 2, PGE 2, PGF 2α,) and 6kPGF 1α the stable metabolite of prostacyclin, were significantly decreased. Treatments with inhibitors of lipoxygenase (BW 755C and nordihydroguaiaretic acid) and with FPL 55712, a leukotriene receptor antagonist, did not influence the effect of indomethacin on 1.CBF. The results suggest that the release of vasoconstrictory leukotrienes does not play a major role in the lowering of 1.CBF by indomethacin.