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Biomedical subjects

J H Milde

Publications and source records attributed to J H Milde.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effects of suxamethonium on the cerebrum following disruption of the blood-brain barrier in dogs.

We have studied the effects of suxamethonium 1.0 mg kg-1 i.v. on cerebral blood flow (CBF), cerebral metabolic rate (CMRO2), and the electroencephalogram (EEG) in dogs anaesthetized with halothane (1.0 MAC) following blood-brain barrier (BBB) disruption with intracarotid (i.c.) mannitol. The combination produced a transient increase in CBF, while CMRO2 did not change. These responses were similar to those produced by i.c. mannitol plus i.v. saline. Suxamethonium produced desynchronization of the EEG that persisted longer than that produced by saline. In only one of the six animals was the desynchronization sustained (90 min) beyond that found in dogs with a normal BBB. We conclude that disruption of the BBB did not enhance the cerebral stimulating effects of i.v. suxamethonium, and did not increase the likelihood of seizure activity following suxamethonium.

Animals↗
PubMed1990

The cerebral functional, metabolic, and hemodynamic effects of desflurane in dogs.

The effects of 0.5-2.0 MAC (3.6-15%) desflurane on cerebral function, metabolism, and hemodynamics and on systemic metabolism and hemodynamics were examined in dogs. Desflurane produced a significant dose-related decrease in cerebral vascular resistance from 1.53 +/- 0.21 mmHg.ml-1.min.100 g at 0.5 MAC to 0.50 +/- 0.03 mmHg.ml-1.min.100 g at 2.0 MAC desflurane. This was accompanied by an increase in cerebral blood flow (CBF) from 61 +/- 7 ml.min-1.100 g-1 at 0.5 MAC to 78 +/- 3 ml.min-1.100 g-1 at 1.5 MAC desflurane. At 2.0 MAC desflurane CBF was 52 +/- 2 ml.min-1.100 g-1 but was associated with a decrease in mean arterial pressure (MAP) to 43 +/- 2 mmHg. When MAP was increased to 73 +/- 3 mmHg with phenylephrine, CBF increased to 87 +/- 3 ml.min-1.100 g-1 at this concentration. At 0.5 MAC desflurane, intracranial pressure (ICP) was 15 +/- 5 mmHg, higher than normal, but did not change significantly with increasing concentrations of desflurane. Increasing concentrations of desflurane initially produced on the EEG the common pattern sequence of increasing depth of anesthesia with decreasing frequency and increasing amplitude progressing to burst suppression and then at 2.0 MAC desflurane to regular attenuation with interruption by periodic polyspiking, a pattern similar to that seen with isoflurane. At both 1.5 and 2.0 MAC the EEG pattern initially observed at that concentration changed to one with faster background activity with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1990

The effects of intravenous succinylcholine on cerebral function and muscle afferent activity following complete ischemia in halothane-anesthetized dogs.

The effects of iv succinylcholine (SCh) on cerebral blood flow (CBF), the electroencephalogram (EEG), muscle afferent activity (MAA), electromyographic activity (EMG), and PaCO2 were tested in six halothane-anesthetized dogs (1.0 MAC) more than 1 h after a 10-min period of complete cerebral ischemia. All dogs received treatments of both iv SCh (1.0 mg.kg-1) and saline placebo in a random sequence. Fasciculations and substantial increases in EMG activity were observed in all dogs following SCh administration. At the onset of fasciculations, there was an increase in MAA to a peak value of 353 +/- 74% of control (mean +/- SE; n = 5 for MAA; n = 6 for all other variables) at the 1-min measurement point. Thereafter, MAA gradually declined toward control values. There were delayed increases in PaCO2 throughout the 45-min study period, achieving values of 106 +/- 1% to 118 +/- 4% of control (an increase in PaCO2 of 2-7 mmHg). Despite the increases in MAA and PaCO2, there were no significant increases in CBF during the study. The control EEG 1-h after complete cerebral ischemia, but immediately before administering the drug treatments, consisted predominantly of a delta rhythm, denoting cerebral dysfunction. In one dog, SCh administration produced transient attenuation of the delta rhythm, a change consistent with cerebral stimulation. In the remaining five dogs, SCh had no effect on the EEG. Treatment with saline placebo did not affect any variable measured. The authors conclude that, in the electrically dysfunctioning brain (e.g., as occurs following resuscitation from complete cerebral ischemia), the cerebral (i.e., CBF and EEG) response to iv SCh is attenuated when compared to the previously reported response in normal brain.

Anesthesia, Inhalation↗
PubMed1990

Effects of sufentanil on cerebral circulation and metabolism in dogs.

The cerebral and peripheral vascular effects of sufentanil (10-200 micrograms/kg) were examined in dogs. The cerebral blood flow (CBF) was measured continuously by an electromagnetic flow probe on the outflow of the posterior sagittal sinus. Sufentanil at all doses significantly increased CBF that lasted for approximately 20 min. The CBF then gradually decreased so that it was significantly below baseline levels by the end of the 60-min study period. The transient increase in CBF was accompanied by an equally transient statistically significant decrease in cerebrovascular resistance. Intracranial pressure did not change. Sufentanil produced an electroencephalographic pattern of deep anesthesia accompanied by a decrease in cerebral oxygen consumption significantly below baseline levels. At the end of the study tissue concentrations of metabolites taken from the cerebral hemispheres were within normal limits, indicative of a normal cerebral energy state. Sufentanil had little effect on systemic hemodynamics. The observation that sufentanil significantly increases CBF in the absence of seizure activity makes it unique among the narcotics. It is hypothesized that in the presence of decreased intracranial compliance, this sudden increase in CBF, although transient, may be detrimental if it is accompanied by an acute increase in intracranial pressure which could produce cerebral ischemia.

Anesthetics↗
PubMed1989

The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia.

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic variables. The absence of systemic effects in Group II dogs suggests that dizocilipine administration in normal dogs results in a centrally mediated activation of the peripheral sympathetic nervous system. The uncoupling of CBF and CMRO2 observed following dizocilipine treatment is similar to that reported for two other known NMDA antagonists, ketamine and phencyclidine. If administration of dizocilipine results in improved histopathological and neurological outcome following an episode of complete cerebral ischemia, this improvement is unrelated to changes in postischemic CBF or hemispheric CMRO2.

Animals↗
PubMed1989

Evaluation of the glutamate antagonist dizocilipine maleate (MK-801) on neurologic outcome in a canine model of complete cerebral ischemia: correlation with hippocampal histopathology.

This study was designed to determine if dizocilipine maleate (MK-801), administered following 11 min of complete ischemia in dogs, could favorably alter neurologic outcome and hippocampal damage. Eighteen dogs were anesthetized and subjected to complete cerebral ischemia by temporary occlusion of the ascending aorta and the venae cavae via a thoracotomy. Five min postischemia, 9 dogs were given dizocilipine 150 micrograms/kg, followed by an infusion of 1.25 microgram/kg/min for 8 h. Control dogs were given equal volumes of placebo. Dogs were evaluated neurologically at 24, 48, and 72 h; thereafter, the brains were perfused, fixed and harvested. There was no significant difference in outcome between dizocilipine- and placebo-treated dogs: 5 of 9 given dizocilipine were normal, 1 was mildly injured and 3 were severely injured or dead. In the control animals given placebo, 3 of 9 were normal, 2 were mildly injured and 4 were moderately to severely injured. Histopathologic examination was limited to the hippocampus. CA1 and CA2,3,4 pyramidal neurons were graded according to degree of injury on a 5-point scale. There were no differences in histopathologic grades between the two groups. However, in both groups combined there was a significant correlation between neurologic outcome grade and histopathologic grade. The only notable systemic effect of dizocilipine appeared to be prolonged sedation which extended beyond 24 h postischemia but was not evident at 48 h postischemia. The authors conclude that more outcome studies in more sensitive models are needed.

Animals↗
PubMed1989

Cerebral effects of fentanyl in dogs.

We have studied the cerebral haemodynamic and metabolic effects of fentanyl 50 micrograms kg-1 and 100 micrograms kg-1 in dogs undergoing ventilation with oxygen and nitrogen at normocapnia. Cerebral blood flow was measured continuously by direct measurement of the outflow of the posterior sagittal sinus. Arterial and sagittal sinus blood-gas tensions were measured intermittently for calculation of cerebral metabolism. Systemic pressures were measured continuously with intermittent measurements of cardiac output. These doses of fentanyl had minimal effect on cerebral blood flow, cerebral oxygen consumption and the energy state of the brain reflected by the normal concentration of cerebral metabolites at the end of the study. There was also little effect on systemic haemodynamics. It is concluded that, in the absence of other anaesthetic agents which might influence cerebral haemodynamics and metabolism, large doses of fentanyl have little effect on the cerebral circulation.

Animals↗
PubMed1989

Cerebral function and muscle afferent activity following intravenous succinylcholine in dogs anesthetized with halothane: the effects of pretreatment with a defasciculating dose of pancuronium.

The effects of iv succinylcholine (SCh) on cerebral blood flow (CBF), muscle afferent activity (MAA), electromyographic activity (EMG), visible fasciculations, and PaCO2 were tested in 12 dogs anesthetized with 0.87% end-expired halothane (1 MAC). Six dogs (group I) received treatments of both SCh 1.0 mg/kg iv and saline placebo 3.0 ml iv. Fasciculations and substantial increases in EMG activity were observed in all six dogs given SCh. At the onset of fasciculations, there were parallel increases in MAA and CBF to peak values of 466% +/- 77% of control (mean +/- SE) and 136% +/- 5% of control, respectively, at the 1-min measurement point. Thereafter, both MAA and CBF declined toward control values. An additional six dogs (group II) were prepared as above; however, they were pretreated with a defasciculating dose of pancuronium 0.01 mg/kg iv 5 min before being given SCh 1.0 mg/kg. These dogs were also given treatments of saline placebo 3.0 ml iv during another portion of the study. None of these six dogs had visible fasciculations following SCh, and only in one was slight EMG activity detected. Following iv SCh, there were parallel increases in both MAA and CBF. The peak MAA value of 255% +/- 56% of control occurred at the 1-min measurement point and was followed by a gradual decline in MAA. CBF increases were greatest during the periods of greatest MAA (i.e., the 1- to 3-min measurement points). The largest increase in CBF (128% +/- 9% of control) occurred at the 3-min measurement point.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1988

Post-ischemic neurologic recovery and cerebral blood flow using a compression model of complete "bloodless" cerebral ischemia in dogs.

Complete "bloodless" cerebral ischemia was produced in 14 dogs by increasing intracranial pressure above systolic blood pressure (compression ischemia) for 10 min after the onset of an isoelectric EEG. Six dogs were observed for 48 h post-ischemia to assess neurologic recovery, and in 6 other dogs, acute post-ischemic cerebral blood flow was determined for 2 h. In 2 additional dogs, pre-ischemic and intra-ischemic cerebral blood volume (CBV) was measured using 111In-labeled red blood cells. Compression ischemia resulted in 2 of 6 dogs that were normal at 48 h post-ischemia, 3 dogs had moderate cerebral injury, and 1 dog died. These results were similar to results from previous studies in our laboratory in which complete "stagnant" cerebral ischemia of a comparable duration was produced in dogs using aortic and caval cross-clamping. Restoration of cerebral perfusion pressure following compression ischemia was accompanied by an initial phase of cerebral hyperemia followed by a delayed period of hypoperfusion similar to that observed following stagnant ischemia. The CBV studies in 2 dogs revealed that compression ischemia decreased CBV to 12% and 14% of pre-ischemic control values, respectively. The authors conclude, contrary to previous reports, that compression ischemia, although producing near bloodless ischemia, does not improve the brain's tolerance to ischemia.

Animals↗
PubMed1988

Cerebral effects of high-dose midazolam and subsequent reversal with Ro 15-1788 in dogs.

The effects of a continuous high-dose infusion of midazolam on cerebral function, metabolism, and hemodynamics were studied in nine dogs receiving a spinal anesthetic and breathing 65% nitrogen/35% oxygen. In five dogs, the effects of 65% nitrous oxide (N2O) inspired and the benzodiazepine antagonist Ro 15-1788 were also examined. Midazolam was infused at a rate of 0.66 mg.kg-1.min-1 for 60 min for a total dose of 40 mg.kg-1. Cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) (measured by venous outflow technique) both decreased until a plateau level was reached at approximately 75% of control values (4.0 +/- 0.2 ml.min-1.100 g-1 and 49 +/- 3 ml.min-1.100 g-1, respectively, mean +/- SEM). This occurred after 6-10 mg.kg-1 of midazolam, corresponding to serum midazolam levels between 18.4 +/- 3.8 and 31.2 +/- 3.3 micrograms.ml-1. Serum midazolam levels increased throughout the midazolam infusion, reaching a mean value of 53 +/- 5.5 micrograms.ml-1 by the end of the midazolam infusion. A similar plateau was seen for changes in the electroencephalogram (EEG), which never developed burst suppression. Five dogs inspired 65% nitrous oxide/35% oxygen during minutes 30-45 of the midazolam infusion, rather than 65% nitrogen/35% oxygen. Nitrous oxide had no effect upon CMRO2, but significantly increased CBF when compared to dogs receiving nitrogen. Ro 15-1788, 1.0 mg.kg-1 caused a return of CMRO2 and EEG activity to control levels. CBF and intracranial pressure (ICP) increased markedly, to greater than control levels immediately following Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The interaction of sodium nitroprusside, hypotension, and isoflurane in determining cerebral vasculature effects.

Eighteen mongrel dogs were anesthetized with isoflurane and prepared for determining cerebral blood flow (CBF, sagittal sinus outflow), cerebral metabolic rate (CMRO2), and ICP. Dogs were divided into three groups of six each. Group 1 dogs were maintained on 1 MAC isoflurane and, following control measurements (step 1), sodium nitroprusside (SNP) was infused to decrease mean arterial pressure (MAP) to 60 mmHg (step 2). After 20 min SNP was discontinued and a second control period of 20 min followed (step 3). Thereafter, SNP was repeated for 20 min as in step 2, but MAP was maintained by inflating a balloon in the descending aorta (step 4). SNP was again discontinued followed by a final 20 min control period (step 5). During SNP with hypotension (step 2) there was a significant 21% decrease in CBF and no change in ICP. During SNP with normotension (step 4) both CBF and ICP increased (16 and 39%, respectively). In group 2 dogs isoflurane was discontinued and a spinal anesthetic was administered. Thereafter, these dogs were studied as in group 1. The only significant change in these dogs was a 35% increase in ICP during SNP with normotension. Group 3 dogs were studied identically to group 2, but hypotension was induced with trimethaphan (TMP). There were no significant changes in these dogs. The authors conclude that SNP, in the absence of isoflurane, dilates capacitance vessels because ICP increased without a concomitant increase in CBF at normotension. In the presence of isoflurane, SNP dilates both capacitance and resistance vessels because ICP and CBF increased concomitantly at normotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparison of the effects of isoflurane and thiopental on neurologic outcome and neuropathology after temporary focal cerebral ischemia in primates.

In an attempt to determine whether one anesthetic might be clearly advantageous over another in clinical situations of temporary focal ischemia, isoflurane or thiopental (in concentrations producing equal suppression of cerebral function as measured by the electroencephalogram) were studied for their effects on neurologic outcome and cerebral infarct size in pigtailed monkeys exposed to temporary focal ischemia produced by 5 h of middle cerebral artery occlusion (MCAo). Burst suppression was produced for 15 min before MCAo and maintained throughout the ischemic period by 2.18 +/- 0.11% (mean +/- SE) end-expired isoflurane or 135 +/- 18 mg.kg-1 thiopental. Mean arterial pressure was supported with phenylephrine and maintained at approximately 90 mmHg in both groups throughout the ischemic period. At the end of the ischemic period, the isoflurane or thiopental was discontinued, allowing the animals to awaken. Intensive care was provided as needed. Neurologic function was scored for 8 days at the end of which surviving animals were killed and the brains were fixed in formalin and then examined for infarct size. There was no significant difference in final neurologic outcome between the animals receiving isoflurane and those receiving thiopental as determined by the Mann-Whitney rank sum test. Neurologic deficit scores ranged from normal (one of eight in the group receiving isoflurane and three of nine in the group receiving thiopental) to death resulting from brain injury (three in the isoflurane group and five in the thiopental-treated group). There also was no significant difference in infarct size between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Superoxide dismutase and catalase failed to improve neurologic outcome after complete cerebral ischemia in the dog.

Superoxide dismutase (SOD) and catalase, natural scavengers of free oxygen radicals, or saline were administered as a continuous systemic infusion to 12 dogs, in a blind randomized fashion, starting 10 min prior to a 10-min episode of complete cerebral ischemia, and continued thereafter for 60 min. Reversible complete cerebral ischemia was achieved by simultaneously occluding the ascending aorta and venae cavae. There were no significant differences in physiological variables (arterial blood gases, hemoglobin, mean arterial blood pressure, heart rate, and temperature) between the two groups, either pre-ischemia or post-ischemia. There was no significant difference in neurologic outcome when evaluated at 48 h post-ischemia. It has previously been reported that the same dose of SOD and catalase as used in the current study could reduce infarct size by 50% when given systemically before reperfusion following coronary ischemia in dogs. The lack of a measurable effect on neurologic outcome in our cerebral ischemic model might be because of the failure of the free oxygen radical scavengers to reach the ischemic cells in sufficient amounts, or because free oxygen radicals do not contribute to brain injury following complete cerebral ischemia.

Animals↗
PubMed1987

Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs.

Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Lidoflazine does not improve neurologic outcome when administered after complete cerebral ischemia in primates.

In order to investigate the effects of the calcium entry blocker lidoflazine on neurologic outcome in primates following an episode of global brain ischemia, 12 pigtail monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia, followed by 48 h of intensive care treatment and daily neurologic evaluations for 96 h. The monkeys were randomly assigned to receive, in a blind fashion, either lidoflazine 1.0 mg/kg (n = 6) or inactive lidoflazine solvent (n = 6) at 5 min, 8 h, and 16 h postischemia. One monkey in the lidoflazine group did not meet preestablished protocol criteria and was excluded from data analysis. The remaining monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome was not significantly different between the lidoflazine- and placebo-treated groups (p greater than 0.5). No monkey in either group achieved a normal neurologic exam by 96 h postischemia. Three lidoflazine-treated monkeys and two placebo-treated monkeys died prior to the 96-h neurologic evaluation. These deaths were judged to be neurologic in origin. The authors concluded that lidoflazine does not improve neurologic outcome in primates when administered after 17 min of complete cerebral ischemia.

Animals↗
PubMed1987

The effects of dextrose infusion and head position on neurologic outcome after complete cerebral ischemia in primates: examination of a model.

The hypothesis that iv dextrose infusion prior to--and head position during--cerebral ischemia would influence the severity and pattern of neurologic injury was tested in primates. Fifteen pigtail monkeys weighing 3.3 +/- 0.2 kg (mean +/- SE) were subjected to 17 min complete cerebral ischemia followed by 24 h intensive care treatment and neurologic assessment for an additional 72 h. Monkeys were given 50 ml iv infusions of either dextrose 5% in 0.45% saline solution (n = 8) or lactated Ringer's solution (n = 7) during the preparatory period. This volume corresponds to approximately 1 1/70 kg individual. These same monkeys were placed in either the lateral (n = 3), prone (n = 5), or supine (n = 7) position during the ischemic period. Two monkeys failed to meet preestablished protocol criteria and were excluded from data analysis. Blood glucose immediately preischemia in the dextrose-treated group (181 +/- 19 mg X dl-1) was not significantly greater than in the group given lactated Ringer's solution (140 +/- 6 mg X dl-1; P = 0.07). Dextrose infusion resulted in significantly greater cerebral injury at 96 h postischemia when comparing both neurologic (P less than 0.05) and histopathology (P less than 0.05) scores. Specifically, dextrose administration resulted in the greatest injury to the insular cortex, thalamus, Purkinje cells, and substantia nigra. Although blood glucose was less than 250 mg X dl-1 in all monkeys at the time of complete cerebral ischemia, there was a high correlation between blood glucose rank and neurologic function rank (rs = 0.76; P less than 0.005). The authors were unable to note any effect of head position on the distribution of histopathologic lesions. Prior to removing the brain for histopathologic studies, four monkeys were given repeat infusions of 50 ml dextrose 5% in 0.45% saline solution over 11 +/- 1 min. These infusions produced increases in blood glucose from 56.7 +/- 7.6 to 244 +/- 24.9 mg X dl-1 (P less than 0.01) and increases in brain glucose from 1.64 +/- 0.22 to 5.11 +/- 0.48 mumol X g-1 (P less than 0.01).

Animals↗
PubMed1987

Effect of lidoflazine on cerebral blood flow and neurologic outcome when administered after complete cerebral ischemia in dogs.

This study tested the hypothesis that lidoflazine, a calcium entry blocking drug, will improve post-ischemic neurologic outcome when administered after a period of complete cerebral ischemia, and that the improvement in outcome is related to an increase in post-ischemic cerebral blood flow (CBF). Complete cerebral ischemia was produced in 31 dogs by temporary ligation of the aorta and venae cavae. In six dogs, 10 min of complete cerebral ischemia was followed by an infusion of lidoflazine 1.0 mg X kg-1 iv over 10 min. CBF and cerebral metabolic rate for oxygen (CMRO2) were measured pre-ischemia, and for 90 min post-ischemia. The results from these six dogs were compared with results previously obtained from eight untreated dogs under similar, but not identical, conditions. The CBF measured post-ischemia in the dogs administered lidoflazine did not differ from the CBF measured post-ischemia in the untreated dogs. Both groups showed an initial hyperemia post-ischemia, followed by significant decreases in CBF from control values by 35 min post-ischemia. The post-ischemic CMRO2 also did not differ between lidoflazine treated and untreated groups. In 25 dogs, 11 min of complete cerebral ischemia was followed by an iv infusion of either lidoflazine 1.0 mg X kg-1 or saline placebo. The same iv infusions were repeated at 8 and 16 h post-ischemia. Seven dogs were excluded from data analysis for failure to meet pre-established protocol criteria. Neurologic injury was evaluated in the remaining dogs at 48 h post-ischemia by an observer blinded to the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗