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Biomedical subjects

P Mares

Publications and source records attributed to P Mares.

At least 145 records · Page 8Linked to original sources
PubMed1994

Clonidine, but not ritanserin, suppresses kainic acid-induced automatisms in developing rats.

In young rats, systemic or local administration of kainic acid (KA) elicits scratching as the prevailing automatism whereas in adult rats, wet dog shakes (WDS) are usually recorded. We tested the effects of the alpha 2-adrenergic agonist clonidine (0.25 mg/kg, IP; also acting, however, on imidazoline receptors), which has been reported to block KA-induced WDS in adult rats and the 5-HT2 antagonist ritanserin (20 mg/kg, IP) in rats aged 7, 12, 18, 25, and 90 days treated IP with doses of KA that induce maximum number of automatisms with minimal early lethal effects (i.e., 4, 6, 8, 10, and 14 mg/kg, respectively). Both WDS and scratching were frequently recorded together in one animal. Neither ritanserin nor its solvent had significant effects on the total number of automatisms or on their distribution between WDS and scratching. In contrast, clonidine suppressed automatisms throughout the development studied. In 90-day-old (adult) rats clonidine decreased the incidence of both WDS and scratching, whereas it usually attenuated scratching at younger ages. Kainic acid-induced seizures were also recorded because of reported incompatibility between tonic-clonic seizures and WDS in adult rats. In 18-90-day-old rats, tonic-clonic seizures and WDS were found incompatible. In 7-18-day-old pups, scratching and KA-induced tonic-clonic seizures occurred together. Moreover, in 7-day-old rats, clonidine was anticonvulsant. We have demonstrated that KA-induced automatisms develop from scratching in pups to prevailing WDS in adult rats, whereas the incidence of scratching rather decreases during development.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

Thoracoabdominal aneurysm repair: spinal cord protection using profound hypothermia and circulatory arrest.

Between January 1991 and February 1993, 14 patients (11 male, 3 female) between 21 and 79 years of age (median 50 years) underwent reconstruction of the thoracic (n = 7) and thoracoabdominal aorta (n = 7). Four patients had previously undergone operation of the ascending aorta, and in three patients coronary artery bypass grafting had previously been performed. All patients were operated on a via a posterolateral thoracotomy using cardiopulmonary bypass with continuous blood cardioplegia and hypothermic circulatory arrest (11 degrees C nasopharyngeal temperature, flat-EEG). All patent lower intercostal and lumbar arteries (T3 to L5) were reimplanted. The 30-day mortality after repair of the thoracic aorta was 0%; after replacement of the thoracoabdominal aorta, mortality was 28.5% (n = 2). One patient died 70 days after replacement of the thoracic aorta as a consequence of a perioperative stroke. None of the surviving 11 patients developed a permanent neurological deficit or renal or cardiac dysfunction. The average intensive care stay was 6 days for patients after replacement of the thoracic aorta and 18 days for patients after replacement of the thoracoabdominal aorta. Our results suggest that use of elective hypothermia and circulatory arrest for spinal cord protection is highly effective. We, therefore, recommend this method for complex reconstructions of the thoracoabdominal aorta.

Adult↗
PubMed1994

Effects of MK-801 (dizocilpine) and ketamine on strychnine-induced convulsions in rats: comparison with benzodiazepines and standard anticonvulsants.

The effects of two non-competitive NMDA antagonists--MK-801 and ketamine--were studied in a model of generalized seizures elicited by s.c. injection of strychnine (2 or 3 mg/kg) in adult rats. The animals were observed in isolation for 30 min after strychnine administration. Pretreatment with MK-801 (0.5 or 2 mg/kg i.p.) suppressed the tonic, but not the clonic phase of generalized seizures following both doses of strychnine. A similar action of ketamine (20 or 40 mg/kg i.p.) was indicated but it did not attain statistical significance. Strychnine-induced lethality was not changed significantly. A comparison with antiepileptic drugs demonstrated that only phenobarbital (10-80 mg/kg i.p.) was clearly effective against strychnine-induced seizures; carbamazepine (25 or 50 mg/kg i.p.) and partly phenytoin (30 or 60 mg/kg i.p.) were able to suppress the incidence of the tonic phase. Primidone (40 or 80 mg/kg i.p.) as well as the benzodiazpines bretazenil (0.1 or 1 mg/kg i.p.) and midazolam (two lower doses of 0.5 and 1 mg/kg i.p.) were without significant effect. The 2 mg/kg dose of midazolam was partly effective. Only phenobarbital, carbamazepine and the highest dose of midazolam prevented strychnine-induced lethality.

Animals↗
PubMed1994

Influence of carbamazepine and phenytoin on spontaneous activity of cerebellar neurons.

Action of carbamazepine (50 mg/kg i.p.) and phenytoin (60 mg/kg i.p.) on the activity of cerebellar neurones was studied in rats under urethane anaesthesia. Carbamazepine markedly decreased the firing frequency of all ten neurones recorded continually before and after drug administration. The same conclusion was reached when a group of 53 cells recorded before drug administration was compared with 48 neurones recorded after carbamazepine administration only. The effects of phenytoin were ambiguous--a decrease as well as an increase in frequency was recorded. The solvent used did not change cerebellar unit activity. Cerebellum cannot be considered as a possible target structure for phenytoin but it might be a target for carbamazepine action.

Animals↗
PubMed1994

Effect of phenytoin on cortical epileptic foci in cerveau isolé rats.

The action of phenytoin was studied in acute experiments in rats with brainstem transection at the midcollicular level. Symmetrical epileptogenic foci were elicited in sensorimotor cortical areas of both hemispheres by local application of penicillin. Seven rats formed a control group, ten animals were pretreated with phenytoin (60 mg/kg i.p., 10 min before penicillin application). Synchronization of interictal discharges in control rats was delayed in comparison to animals with an intact brainstem; phenytoin did not influence this synchronization. Spontaneous transition of interictal into ictal activity was not abolished by phenytoin, i.e. in cerveau isolé preparations phenytoin lost this activity. The loss of anticonvulsant activity was not complete. Ictal episodes were modified; they started as very short ones and their duration progressively increased. Structures localized below the level of transection represent a site of at least one of the mechanisms of phenytoin anticonvulsant action.

Animals↗
PubMed1994

Is the site of action of ethosuximide in the hindbrain?

The action of ethosuximide, valproate and clonazepam against pentylenetetrazol-induced epileptic EEG phenomena was studied in acute experiments in rats with intercollicular brainstem transection. Ethosuximide lost its action against both rhythmic metrazol activity (model of human absences) and EEG seizures. On the contrary, the action of valproate and clonazepam in cerveau isolé rats was the same as in intact animals. The site of anticonvulsant action of ethosuximide may be localized in hindbrain structures, whereas the actions of both valproate and clonazepam may be demonstrated even if hindbrain structures had been eliminated.

Animals↗
PubMed1994

Influence of flunarizine on hippocampal epileptic afterdischarges in the rat.

Epileptic afterdischarges elicited by electrical stimulation of the dorsal hippocampus in freely moving rats were not significantly changed by flunarizine administration in comparison with control sessions in which the animals received the solvent only. On the other hand, flunarizine significantly reduced the number of wet dog shakes, the main automatisms accompanying limbic afterdischarges.

Animals↗
PubMed1993

Differential action of phenytoin and carbamazepine on cortical interhemispheric responses in young but not in adult rats.

Single as well as paired responses to stimulation of the contralateral sensorimotor cortex were recorded in adult and 12-day-old rats under urethane anesthesia. Carbamazepine (50 mg/kg i.p.) prolonged the peak latencies of single responses in both adult and young rats, while phenytoin (60 mg/kg i.p.) prolonged the latencies in adult animals but shortened them in the young ones. Excitability cycles of the amplitude of the initial positive-negative complex remained uninfluenced by either drug in both age groups. Since solvent alone did not induce any effects in either test, our results demonstrate a qualitative change in the action of phenytoin during development.

Aging↗
PubMed1993

Successful lung transplantation in a long-term ventilator-dependent patient.

Ventilator dependence has been postulated to be a major contraindication for successful lung transplantation. We describe the case of a 44-year-old female patient mechanically ventilated for 10 months after adult respiratory distress syndrome. After a program of physical training the patient underwent successful bilateral sequential lung transplantation. Six months postoperatively she is in good physical condition and is able to carry out the activities of normal daily living. We conclude that in selected patients long-term mechanical ventilatory support is not a contraindication for lung transplantation.

Activities of Daily Living↗
PubMed1993

Ethosuximide suppresses seizures and lethality induced by picrotoxin in developing rats.

The action of ethosuximide (125 or 250 mg/kg, IP) against picrotoxin-induced seizures (3-6 mg/kg, IP) was assessed in rats 12, 18, 25, and 90 days old. In 18-day-old and older controls, picrotoxin regularly elicited clonic seizures; tonic-clonic seizures were induced in all age categories with high consequent mortality. Only the higher dose of ethosuximide (250 mg/kg) increased the latency of clonic seizures in 18- and 25-day-old pups. Tonic-clonic seizures were delayed by ethosuximide in 12-, 18-, and 90-day-old rats. Picrotoxin-induced lethality was suppressed only in 18- and 90-day-old rats by the 250-mg/kg dose of ethosuximide. In contrast, ethosuximide pretreatment increased the incidence of clonic seizures in 12-day-old rats. The results suggest that only high doses of ethosuximide can suppress clonic seizures, and this action is not consistent. Tonic-clonic seizures probably have model-specific sensitivity to ethosuximide because in previous studies ethosuximide completely suppressed pentylenetetrazol-induced tonic-clonic seizures but had no effect on kainic acid-induced tonic-clonic seizures. The suppression of mortality rates is probably due to nonspecific effects of high doses of ethosuximide.

Animals↗
PubMed1993

Models of simple partial and absence seizures in freely moving rats: action of ketamine.

The action of ketamine was studied in two models of seizures: a) bilateral neocortical discharges produced by topical application of pentylenetetrazol (model of simple partial seizures); and b) rhythmic spike-and-wave activity induced by systemic administration of pentylenetetrazol (model of absence seizures). Ketamine exerted biphasic effects. In the first model, the dose of 20 mg/kg ketamine significantly suppressed the ictal neocortical discharges (i.e., continuous spiking or ictal activity) accompanied by clonic motor seizures. However, at the dose of 40 mg/kg ketamine significantly accentuated the onset and increased the number of individual discharges (interictal spikes) in bilateral neocortical foci. In the model of rhythmic spike-and-wave activity, the lower dose of ketamine (20 mg/kg) decreased the number of rhythmic spike-and-wave episodes when compared to the higher dose (40 mg/kg) of ketamine, which increased the number of episodes. However, neither result differed significantly from control values. The present results suggest a dose-dependent action of ketamine: Lower doses (10 and 20 mg/kg in the rat) are able to suppress seizure activity, whereas a higher dose (40 mg/kg) potentiates the seizures. Moreover, the action of ketamine may be dependent upon the seizure model used. The study presents a new model of acute epileptic focus in freely moving rats.

Animals↗
PubMed1993

Anticonvulsant activity of flumazenil in rats during ontogenetic development.

The influence of flumazenil on seizures induced by pentylenetetrazol (PTZ) was studied in rats aged 7, 12, 18, 25, and 90 days. Flumazenil in doses of 25, 37.5, and 50 mg/kg IP injected 10 min before PTZ exhibited a dose-dependent anticonvulsant action in all age groups studied. It was more effective against generalized tonic-clonic than against minimal clonic seizures at all developmental stages studied. In the two youngest groups, minimal seizures were elicited only rarely under control conditions. Pretreatment with the two lower doses of flumazenil resulted in an increased incidence of this type of seizure for these two groups. The anticonvulsant activity found in all age groups is in agreement with data from other benzodiazepines and speaks against a pure benzodiazepine-antagonistic action of flumazenil.

Aging↗
PubMed1993

Paired-pulse and frequency potentiation of cortical responses in developing rats.

The postnatal development of paired-pulse and frequency potentiations of the first positive and negative components (P1N1) of the cortical interhemispheric response (IHR) was studied in urethane anesthetized rats aged from 7 to 90 days. The paired-pulse potentiation appeared in the rat sensorimotor cortex starting from the age of 15 days. The magnitude of potentiation increased with age. The interpulse interval inducing maximum potentiation shortened from 125 ms in 15-day-old rats to 70 ms in adult rats. Similar results concerning the paired-pulse responses were found for visual cortex but the maturation was somewhat delayed--potentiation first appeared at postnatal day (PND) 18. The frequency potentiation reached adult properties in the sensorimotor cortex by PND 25. There is no time coincidence in the development of the two potentiation phenomena studied, paired pulse potentiation appeared earlier than frequency potentiation.

Animals↗
PubMed1993

New model of cortical epileptic foci in freely moving developing rats.

Electrocorticographic and motor phenomena produced by epileptogenic foci were studied in freely moving rats with implanted electrodes in five age groups (7, 12, 18, 25 days and adults). Foci were induced by local application of a 1 or 2 mM solution of bicuculline methiodide to the sensorimotor cortical area by means of an implanted cannula in 106 rats. Interictal focal discharges formed by mono- to triphasic spikes (in rats aged 18 days and more) or sharp waves (in 7-day-old rats) were recorded in all animals. Spontaneous transition into an ictal phase was common in all age groups, there was no clear dependence on the age. Ictal EEG was formed by spike-and-wave rhythm in rats 18 days old and older, by huge delta waves in the youngest rats. Electroclinical correlation was poor in the youngest rats and ameliorated with age. The most frequent motor counterpart of focal discharges was represented by a jerk of the contralateral limbs or of the whole body. EEG seizures were mostly accompanied by clonus of facial and forelimb muscles, but EEG ictal phases without any motor correlate were also common.

Aging↗
PubMed1993

Motor and electrocorticographic epileptic activity induced by 3-mercaptopropionic acid in immature rats.

The convulsant action of 3-mercaptopropionic acid (3-MPA), a known inhibitor of glutamate decarboxylase activity, was studied in 7-, 12-, 18- and 25-day-old rats and in adult animals. 3-MPA elicited predominantly clonic, minimal seizures as well as generalized tonic-clonic (major) seizures at all developmental stages studied. The CD50 for major seizures did not change during development; CD50 for minimal seizures was significantly lower in 18-day-old rats than in older animals. Latency to the onset of seizures was shortest in 18-day-old rats and extremely long in 12- and, especially, in 7-day-old rats. This long latency might signify either changing molecular properties of glutamate decarboxylase during development or slow turnover of GABA at early postnatal stages. Electrocorticographic recordings demonstrated sharp EEG components in the frontal region as a first sign of 3-MPA action, and seizure patterns exhibited similar developmental changes as found with other seizure models (a decrease in duration of individual graphoelements and an increase in synchronization among various cortical regions). This indicates the primary importance of brain maturation in the expression of epileptic EEG phenomena. The correlation between EEG and motor phenomena was poor in the youngest animals and it ameliorated with age, but it never became perfectly coincidental.

3-Mercaptopropionic Acid↗
PubMed1993

Improved cardiac performance and reduced pulmonary vascular constriction by epinephrine administration via a left atrial catheter in cardiac surgical patients.

Diminished left ventricular contractility and increased right ventricular afterload are issues in cardiac surgery. The usual administration of catecholamines (epinephrine) via the central venous (CV) catheter increases cardiac output, but also may increase pulmonary vascular constriction. Epinephrine was, therefore, administered via the left atrial (LA) catheter or the CV catheter in 8 cardiac surgery patients, each serving as his or her own control. The LA administration of epinephrine has an advantage with its immediate effect on the coronary circulation, while avoiding associated pulmonary vasoconstriction by passing through the systemic capillary bed before reaching the lung. It was found in this study that administration of epinephrine via an LA catheter increased the average cardiac output by 1.05 L/min, which was significantly (P < 0.05) greater than with administration via the CV catheter. With LA administration of epinephrine, systemic arterial pressure (systolic arterial pressure and diastolic arterial pressure) (SAP, DAP) were also elevated to a greater extent than by CV administration. On the other hand, pulmonary arterial pressures (systolic pulmonary arterial pressure and diastolic pulmonary arterial pressure) (SPAP, DPAP) were less elevated than by administration via the CV catheter. This produced increased coronary perfusion and a smaller increase in pulmonary vascular tone by LA administration in contrast to CV administration of epinephrine. It is concluded that epinephrine administration via an LA catheter improved myocardial performance and pulmonary perfusion due to direct entry of the agent into the coronary circulation and partial metabolism while passing through the systemic capillary bed before reaching the lung.

Blood Pressure↗
PubMed1993

Stable anticonvulsant action of benzodiazepines during development in rats.

The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg-1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0.1 and 0.02 mg kg-1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.

Aging↗