pituitrin and Brain-Ischemia

Hyponatremia is a water-electrolyte balance disorder diagnosed in about 30% of patients after subarachnoid hemorrhage (SAH). The main factors responsible for hyponatremia in these patients are increased plasma concentrations of either vasopressin (leading to water retention and dilutional hyponatremia) or natriuretic peptides (leading to plasma sodium ions deficiency). Data demonstrates that the leading causes of post-SAH disability - delayed cerebrovascular spasm (CVS) and delayed cerebral ischemia (DCI) - are more often diagnosed in patients who develop hyponatremia than in normonatremic patients with SAH. Data also indicates that reducing sodium ion concentration in the blood/perfusate affects the tone and regulation of cerebral blood vessels in a manner that depends on the vessel's location in a vascular tree (intraparenchymal arterioles vs. large vessels on the brain surface) and environmental conditions. In the present article, we review possible mechanisms underlying the effects of hyponatremia on cerebral blood vessels and discuss the potential role of hyponatremia in the development of large vessels and microvascular spasm, taking into consideration the presence of vasopressin and natriuretic peptides.

Topics: Brain Ischemia; Humans; Hyponatremia; Natriuretic Peptides; Risk Factors; Sodium; Spasm; Subarachnoid Hemorrhage; Vasopressins; Vasospasm, Intracranial

Brain edema formation is a major cause of brain damages and the high mortality of ischemic stroke. The aim of this review is to explore the relationship between ischemic brain edema formation and vasopressin (VP) hypersecretion in addition to the oxygen and glucose deprivation and the ensuing reperfusion injury.. Pertinent studies involving ischemic stroke, brain edema formation, astrocytes, and VP were identified by a search of the PubMed and the Web of Science databases in January 2016. Based on clinical findings and reports of animal experiments using ischemic stroke models, this systematic review reanalyzes the implication of individual reports in the edema formation and then establishes the inherent links among them.. This systematic review reveals that cytotoxic edema and vasogenic brain edema in classical view are mainly under the influence of a continuous malfunction of astrocytic plasticity. Adaptive VP secretion can modulate membrane ion transport, water permeability, and blood-brain barrier integrity, which are largely via changing astrocytic plasticity. Maladaptive VP hypersecretion leads to disruptions of ion and water balance across cell membranes as well as the integrity of the blood-brain barrier. This review highlights our current understandings of the cellular mechanisms underlying ischemic brain edema formation and its association with VP hypersecretion.. VP hypersecretion promotes brain edema formation in ischemic stroke by disrupting hydromineral balance in the neurovascular unit; suppressing VP hypersecretion has the potential to alleviate ischemic brain edema.

Topics: Animals; Astrocytes; Brain; Brain Edema; Brain Ischemia; Humans; Phenotype; Prognosis; Risk Factors; Signal Transduction; Stroke; Up-Regulation; Vasopressins

Is a vasopressin, steroid, and epinephrine (VSE) protocol for in-hospital cardiac arrest resuscitation associated with better survival to hospital discharge with favourable neurologic outcome compared to epinephrine alone? Article chosen Mentzelopoulos S, Malachias S, Konstantopoulos D, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA 2013;310:270-9.. To determine if a VSE protocol during cardiopulmonary resuscitation with hydrocortisone administration in patients with postresuscitative shock at 4 hours after return of spontaneous circulation would improve survival to hospital discharge with favourable neurologic outcome.

Topics: Brain Ischemia; Cardiopulmonary Resuscitation; Drug Therapy, Combination; Epinephrine; Glucocorticoids; Heart Arrest; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vasopressins

The primary goal of cardiopulmonary resuscitation is to reestablish blood flow to vital organs until spontaneous circulation is restored. Adrenergic vasopressor agents produce systemic vasoconstriction. This increases aortic diastolic pressure, and consequently, coronary and cerebral perfusion pressures. The pharmacologic responses to the adrenergic agents are mediated by a group of receptors that are classified as alpha (alpha), including alpha1 and alpha2, and beta (beta), including beta1 and beta2. Epinephrine, which has each of these adrenergic actions, has been the preferred adrenergic agent for the management of cardiac arrest for almost 40 years. Its primary efficacy is due to its alpha-adrenergic vasopressor effects. This contrasts with its beta-adrenergic actions, which are inotropic, chronotropic, and vasodilator. Accordingly, beta-adrenergic actions prompt increases in myocardial oxygen consumption, ectopic ventricular arrhythmias, and transient hypoxemia due to pulmonary arteriovenous shunting. This may account for the failure to demonstrate that epinephrine improves ultimate outcomes in human victims of cardiac arrest. Major interest has more recently been focused on selective alpha-adrenergic agonists. Both alpha1-agonists and alpha2-agonists are peripheral vasopressors. However, rapid desensitization of alpha1-adrenergic receptors occurs during cardiopulmonary resuscitation. Moreover, alpha1-adrenergic receptors are present in the myocardium, and beta1-agonists, like beta-adrenergic agonists, increase myocardial oxygen consumption. If they cross the blood-brain barrier, alpha2-adrenoceptor agonists also have centrally acting vasodilator effects. In the absence of central nervous system access, alpha2-adrenergic agonists have selective peripheral vasoconstrictor effects. Under experimental conditions of cardiopulmonary resuscitation, selective alpha2-agonists, which do not gain entrance into the brain, produce only systemic vasoconstriction. Experimentally, these selective alpha2-agonists are as effective as epinephrine for initial cardiac resuscitation and have the additional advantage of minimizing myocardial oxygen consumption during the global myocardial ischemia of cardiac arrest. Accordingly, myocardial ischemic injury during cardiopulmonary resuscitation is minimized, and postresuscitation myocardial function is preserved with improved survival.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Animals; Brain Ischemia; Cardiopulmonary Resuscitation; Epinephrine; Heart Arrest; Humans; Vasoconstrictor Agents; Vasopressins

Aneurysmal subarachnoid hemorrhage (aSAH) is an important indication for intensive care unit admission and may lead to significant morbidity and mortality. We assessed the ability of C-terminal proarginine vasopressin (CT-proAVP) to predict disease outcome, mortality, and delayed cerebral ischemia (DCI) in critically ill patients with aSAH compared with the World Federation of Neurological Surgeons (WFNS) score and Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model.. C-terminal proarginine vasopressin was collected on admission in this single-center, prospective, observational cohort study. The primary aim was to investigate the relationship between CT-proAVP and poor functional outcome at 1 year (Glasgow Outcome Scale score 1-3) in a multivariable logistic regression model adjusted for WFNS and APACHE IV scores. Secondary aims were mortality and DCI. The multivariable logistic regression model for DCI was also adjusted for the modified Fisher scale.. In 100 patients, the median CT-proAVP level was 24.9 pmol/L (interquartile range 11.5-53.8); 45 patients had a poor 1-year functional outcome, 19 patients died within 30 days, 25 patients died within 1 year, and DCI occurred in 28 patients. Receiver operating characteristics curves revealed high accuracy for CT-proAVP to identify patients with poor 1-year functional outcome (area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.77-0.92, p < 0.001), 30-day mortality (AUC 0.84, 95% CI 0.76-0.93, p < 0.001), and 1-year mortality (AUC 0.79, 95% CI 0.69-0.89, p < 0.001). CT-proAVP had a low AUC for identifying patients with DCI (AUC 0.67, 95% CI 0.55-0.79, p 0.008). CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for poor 1-year functional outcome (odds ratio [OR] 8.04, 95% CI 2.97-21.75, p < 0.001), and CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and 1-year mortality (OR 9.31, 95% CI 1.55-56.07, p 0.015 and OR 5.15, 95% CI 1.48-17.93, p 0.010) in multivariable models with WFNS and APACHE IV scores. CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI in a multivariable model adjusted for the modified Fisher scale (p = 0.061).. C-terminal proarginine vasopressin was able to predict poor functional outcome and mortality in critically ill patients with aSAH. Its prognostic ability to predict DCI was low.. Nederlands Trial Register: NTR4118.

Topics: Brain Ischemia; Cerebral Infarction; Cohort Studies; Critical Illness; Humans; Prospective Studies; Subarachnoid Hemorrhage; Vasopressins

To investigate the feasibility of a refined aortic flush catheter and pump system to induce emergency preservation and resuscitation before extracorporeal cardiopulmonary resuscitation in a normovolemic cardiac arrest swine model simulating near real size/weight conditions of adults.. In this feasibility study, 8 female Large White breed pigs weighing 70 to 80 kg underwent ventricular fibrillation cardiac arrest for 15 minutes, followed by 4°C aortic flush (150 mL/kg for the brain; 50 mL/kg for the spine) via a new hardware ensued by resuscitation with extracorporeal cardiopulmonary resuscitation.. Brain temperature was lowered from 39.9°C (interquartile range [IQR] 39.6-40.3) to 24.0°C (IQR 20.8-28.9) in 12 minutes (IQR 11-16) with a median cooling rate of 1.3°C (IQR 0.7-1.6) per minute. A median of 776 mL (IQR 673-840) per minute with a median pump pressure of 1487 mm Hg (IQR 1324-1545) were pumped to the brain.. With the new hardware, we were able to cool the brain within a few minutes in a large pig cardiac arrest model. The exact position; the design, diameter, and length of the flush catheter; and the brain perfusion pressure seem to be critical to effectively reduce brain temperature. Redistribution of peripheral blood could lead to sterile inflammation again and might be avoided.

Topics: Animals; Aorta; Body Temperature; Brain Ischemia; Catheters; Epinephrine; Equipment Design; Extracorporeal Membrane Oxygenation; Feasibility Studies; Heart Arrest; Heparin; Hypothermia, Induced; Infusions, Intra-Arterial; Models, Animal; Resuscitation; Sodium Chloride; Swine; Vasopressins

The effects of the non-peptide vasopressin V(2) receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma vasopressin level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma vasopressin level was further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Body Water; Brain; Brain Edema; Brain Ischemia; Disease Models, Animal; Kidney; Male; Microscopy, Electron, Transmission; Rats; Receptors, Vasopressin; Sodium; Survival Rate; Treatment Outcome; Vasopressins; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Blood Pressure; Brain Ischemia; Calcium Channels; Hemostatics; Humans; Hypotension; Muscle, Smooth, Vascular; Shock; Shock, Cardiogenic; Shock, Septic; Vasoconstrictor Agents; Vasodilation; Vasopressins

Microdialysis is an established tool to analyse tissue biochemistry, but the value of this technique to monitor cardiopulmonary resuscitation (CPR) effects on cerebral metabolism is unknown. The purpose of this study was to assess the effects of active-compression-decompression (ACD) CPR in combination with an inspiratory threshold valve (ITV) (=experimental CPR) vs. standard CPR on cerebral metabolism measured with microdialysis.. Fourteen domestic pigs were surfaced-cooled to a body core temperature of 26 degrees C and ventricular fibrillation was induced, followed by 10 min of untreated cardiac arrest; and subsequently, standard (n=7) CPR vs. experimental (n=7) CPR. After 8 min of CPR, all animals received 0.4 U/kg vasopressin IV, and CPR was maintained for an additional 10 min in each group; defibrillation was attempted after a total of 28 min of cardiac arrest, including 18 min of CPR.. In the standard CPR group, microdialysis measurements showed a 13-fold increase of the lactate-pyruvate ratio from 7.2+/-1.3 to 95.5+/-15.4 until the end of CPR (P<0.01), followed by a further increase up to 138+/-32 during the postresuscitation period. The experimental group developed a sixfold increase of the lactate-pyruvate ratio from 7.1+/-2.0 to 51.1+/-8.7 (P<0.05), and a continuous decrease after vasopressin. In the standard resuscitated group, but not during experimental CPR, a significant increase of cerebral glucose levels from 0.6+/-0.1 to 2.6+/-0.5 mM was measured (P<0.01).. Using the technique of microdialysis we were able to measure changes of brain biochemistry during and after the very special situation of hypothermic cardiopulmonary arrest. Experimental CPR improved the lactate-pyruvate ratio, and glucose metabolism.

Topics: Analysis of Variance; Animals; Brain; Brain Ischemia; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Disease Models, Animal; Female; Heart Arrest; Male; Microdialysis; Probability; Random Allocation; Risk Assessment; Statistics, Nonparametric; Survival Rate; Sus scrofa; Vasopressins

NC-1900, an arginine-vasopressin derivative, has been reported to enhance memory for avoidance behavior. Specifically, NC-1900 ameliorated cycloheximide-induced learning impairments in a passive avoidance test in rats. In the present study, we investigated that effects of NC-1900 on place learning in rats with selective lesions in the CA1 subfield of the hippocampal formation produced by transient forebrain ischemia. NC-1900 was administered daily (1 microg/kg, p.o.) 1 h before the place learning task. A rat was required to alternate between 2 small circular areas located diametrically opposite each other on the circumference of an open field in order to obtain intracranial electrical stimulation reward (the spatial navigation task). Rats with hippocampal lesions showed severe place learning impairments both in task performance (indicated by number of rewards obtained per a session) and in navigation performance (forming efficient trails) over the 30-day test period. Treatment with NC-1900 ameliorated deficits in the place learning exhibited by rats with the same hippocampal lesions, such that their performance reached normal levels. There were no significant differences in the ischemic hippocampal lesions, spontaneous locomotor activity, and stimulation current intensity between the treated and untreated rats. The results demonstrated that NC-1900 reduced place learning impairments produced by hippocampal lesions.

Topics: Amnesia; Animals; Brain Ischemia; Disease Models, Animal; Hippocampus; Learning; Male; Memory Disorders; Oligopeptides; Prosencephalon; Pyrrolidonecarboxylic Acid; Rats; Rats, Wistar; Vasopressins

Pial artery dilation in response to activators of the ATP-sensitive K(+) (K(ATP)) and calcium-sensitive K(+) (K(Ca)) channels is impaired after fluid percussion brain injury (FPI). Vasopressin, when coadministered with the K(ATP) and K(Ca) channel agonists cromakalim and NS1619 in a concentration approximating that observed in cerebrospinal fluid (CSF) after FPI, blunted K(ATP) and K(Ca) channel-mediated vasodilation. Vasopressin also contributes to impaired K(ATP) and K(Ca) channel vasodilation after FPI. In addition, protein kinase C (PKC) activation generates superoxide anion (O(2)(-)), which in turn contributes to K(ATP) channel impairment after FPI. We tested whether vasopressin generates O(2)(-) in a protein kinase C (PKC)-dependent manner, which could link vasopressin release to impaired K(ATP) and K(Ca) channel-induced pial artery dilation after FPI.. Injury of moderate severity (1.9 to 2.1 atm) was produced with the lateral FPI technique in anesthetized newborn pigs equipped with a closed cranial window. Superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O(2)(-) generation.. Under sham injury conditions, topical vasopressin (40 pg/mL, the concentration present in CSF after FPI) increased superoxide dismutase-inhibitable NBT reduction from 1+/-1 to 23+/-4 pmol/mm(2). Chelerythrine (10(-7) mol/L, a PKC inhibitor) blunted such NBT reduction (1+/-1 to 9+/-2 pmol/mm(2)), whereas the vasopressin antagonist l-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)2-(o-methyl)-Tyr-arginine vasopressin (MEAVP) blocked NBT reduction. Chelerythrine and MEAVP also blunted the NBT reduction observed after FPI (1+/-1 to 15+/-1, 1+/-1 to 4+/-1, and 1+/-1 to 5+/-1 pmol/mm(2) for sham-, chelerythrine-, and MEAVP-treated animals, respectively). Under sham injury conditions, vasopressin (40 pg/mL) coadministered with cromakalim or NS1619 blunted dilation in response to these K(+) channel agonists, whereas chelerythrine partially restored such impaired vasodilation for cromakalim but not NS1619. Cromakalim- and NS1619-induced pial artery dilation also was blunted after FPI. MEAVP partially protected dilation to both K(+) channel agonists after FPI, whereas chelerythrine did so for only cromakalim responses (for cromakalim at 10(-8) and 10(-6) mol/L, 13+/-1% and 23+/-1%, 2+/-1% and 5+/-1%, 9+/-1% and 15+/-2%, and 9+/-1% and 16+/-2% for sham-, FPI-, FPI-MEAVP-, and FPI-chelerythrine-pretreated animals, respectively).. These data show that vasopressin, in concentrations present in CSF after FPI, increased O(2)(-) production in a PKC-dependent manner and contributes to such production after FPI. These data show that vasopressin contributes to K(ATP) but not K(Ca) channel function impairment in a PKC-dependent manner after FPI and suggest that vasopressin contributes to K(Ca) channel function impairment after FPI via a mechanism independent of PKC activation.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Arteries; Benzimidazoles; Brain Injuries; Brain Ischemia; Calcitonin Gene-Related Peptide; Cromakalim; Disease Models, Animal; Enzyme Activation; Enzyme Activators; Enzyme Inhibitors; Female; Male; Pia Mater; Potassium Channels; Protein Kinase C; Superoxides; Swine; Vasodilation; Vasopressins; Wounds, Nonpenetrating; Xanthine Oxidase

This study determined if vasopressin generates superoxide anion (O2(-)) in a cyclooxygenase dependent manner and if such production contributes to impairment of dilation to activators of ATP sensitive K(+) (K(ATP)) and calcium sensitive K(+) (K(ca)) channels following fluid percussion brain injury (FPI) in newborn pigs equipped with closed cranial windows. Superoxide dismutase (SOD) inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O2(-) generation. Under non-brain injury conditions, topical vasopressin (40 pg/ml, the concentration present in CSF following FPI) increased SOD inhibitable NBT reduction from 1+/-1 to 25+/-4 pmol/mm(2). Indomethacin, a cyclooxygenase inhibitor, blunted such NBT reduction (1+/-1 to 5+/-1 pmol/mm(2)), while the vasopressin antagonist, l-(beta-mercapto-beta beta-cyclopentamethylene propionic acid) 2-(o-methyl)-Tyr-AVP (MEAVP) blocked NBT reduction. MEAVP and indomethacin also blunted the NBT reduction observed after FPI. Under non-brain injury conditions, vasopressin (40 pg/ml) coadministered with the K(ATP) and K(ca) channel agonists, cromakalim and NS1619 (10(-8), 10(-6) M) diminished dilation to these K(+) channel agonists while indomethacin partially prevented such impairment (13+/-1 and 23+/-1 vs. 4+/-1 and 10+/-2 vs. 8+/-1 and 19+/-1% for cromakalim in untreated, vasopressin, and vasopressin plus indomethacin treated piglets, respectively). Cromakalim and NS1619 induced pial artery dilation was attenuated following FPI, while indomethacin or MEAVP preadministration partially prevented such impairment (13+/-1 and 23+/-1, sham control; 1+/-1 and 4+/-1, FPI; 8+/-1 and 16+/-3%, FPI-indomethacin pretreated for responses to cromakalim 10(-8), 10(-6) M, respectively). These data show that vasopressin increased O2(-) production in a cyclooxygenase dependent manner and contributed to this production after FPI. These data also show that vasopressin blunted K(ATP) and K(ca) channel mediated cerebrovasodilation in a cyclooxygenase dependent manner. These data suggest that vasopressin induced cyclooxygenase dependent O2(-) generation contributes to K(ATP) and K(ca) channel function impairment after FPI.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Arginine Vasopressin; Benzimidazoles; Blood; Brain Injuries; Brain Ischemia; Calcitonin Gene-Related Peptide; Cerebral Arteries; Cerebrovascular Circulation; Cromakalim; Female; Indomethacin; Male; Potassium Channels; Prostaglandin-Endoperoxide Synthases; Superoxides; Swine; Vasodilation; Vasodilator Agents; Vasopressins

For better understanding of glial participation in cerebral ischemia, spectrofluorimetric analysis using the calcium indicator Fura-2AM was applied to examine the role of intracellular free Ca2+ ([Ca2+])i elevation induced by different neuroactive substances in cultured rat brain astrocytes. The activation by the general receptor agonist glutamate resulted in a biphasic cell response in [Ca2+]i. We couldn't observe N-methyl-D-aspartate-evoked [Ca2+]i response at all. Quisqualate triggered a complex [Ca2+]i response in astrocytes consisting of mobilization of Ca2+ from the intracellular stores and also Ca2+ influx from the extracellular space. Kainate elicited a markedly different Ca2+ signal an external Ca(2+)-dependent sustained [Ca2+]i rise resulting from the activation of the ionotropic glutamate receptor. According to our results two types of glutamate receptors, the quisqualate-specific metabotropic and kainate-specific ionotropic receptor, are involved in [Ca2+]i elevation in these cultures. We could monitor agonist-specific cell response to noradrenaline, serotonin, vasopressin and ATP as well in these cultured rat astrocytes.

Topics: Adenosine Triphosphate; Adrenergic alpha-Agonists; Animals; Animals, Newborn; Astrocytes; Brain Ischemia; Calcium; Cells, Cultured; Cytoplasm; Excitatory Amino Acid Agonists; Extracellular Space; Fluorescent Dyes; Fura-2; Glutamic Acid; Kainic Acid; N-Methylaspartate; Neurotransmitter Agents; Norepinephrine; Quisqualic Acid; Rats; Receptors, Glutamate; Serotonin; Spectrometry, Fluorescence; Vasoconstrictor Agents; Vasopressins

Vasopressin in cerebrospinal fluid has been measured in 27 fullterm newborns with hypoxic-ischemic encephalopathy. These newborns were divided into three groups according to the degree of neurological involvement, and they have been compared with a control group of 10 newborns. Determinations of vasopressin in cerebrospinal fluid and plasma were done by RIA. The cerebrospinal fluid vasopressin in asphyxiated newborns was higher than in the control group (p < 0.001); the mean concentration in the group of newborns classified as moderate or severe hypoxic-ischemic encephalopathy was higher than in the control group (18.7 pg/ml vs 4.66 pg/ml), and also higher than in the group classified as mild (14.2 pg/ml). Cerebrospinal fluid vasopressin values have a direct relationship to the plasmatic values at 12 hours of life (r = 0.76; p < 0.001). We concluded that vasopressin values in cerebrospinal fluid at 12 hours increase according to the clinical severity of the neonatal hypoxic-ischemic encephalopathy and that they have a strong relationship with plasmatic vasopressin.

Topics: Asphyxia Neonatorum; Brain Diseases; Brain Ischemia; Gestational Age; Humans; Hypoxia; Infant, Newborn; Vasopressins

The object of this study was to investigate the role of the ventrolateral medullary pressor area in mediating the cardiovascular responses to experimentally induced global cerebral ischemia, and to test if excitatory amino acids or acetylcholine are the transmitters released in this brain region during these responses. The cerebral ischemic response was elicited in pentobarbital-anesthetized, artificially ventilated male Wistar rats by bilateral ligation of vertebral arteries followed by temporary clamping of the common carotid arteries. The pressor area was identified by microinjections of L-glutamate. Inhibition of neurons in this area by microinjections of muscimol, a gamma-aminobutyric acid receptor agonist, abolished the ischemic response, which demonstrated that this area is important in mediating these responses. Microinjections of a broad-spectrum excitatory amino acid receptor blocker (kynurenate), of specific antagonists for N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors (injected alone or in combination), and of atropine failed to block the ischemic responses. These results indicate that: 1) the ventrolateral medullary pressor area mediates pressor responses to cerebral ischemia, and 2) excitatory amino acids or acetylcholine in this area do not mediate the cardiovascular responses to cerebral ischemia.

Topics: Acetylcholine; Amino Acids; Animals; Antidiuretic Hormone Receptor Antagonists; Atropine; Blood Pressure; Brain Ischemia; Dose-Response Relationship, Drug; Glutamates; Heart Rate; Kainic Acid; Kynurenic Acid; Male; Medulla Oblongata; Muscimol; N-Methylaspartate; Quinoxalines; Quisqualic Acid; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Receptors, Vasopressin; Vasopressins

Brain edema formation was investigated in the vasopressin-deficient Brattleboro rat using a middle cerebral artery occlusion model of early ischemic injury. Water and sodium accumulation after 4 h of ischemia were attenuated 36 and 20%, respectively, in the Brattleboro strain as compared to the control Long-Evans strain. This effect was independent of differences in animal size and state of hydration. In addition, measurements of cerebral blood flow indicated that Brattleboro and Long-Evans rats had equal levels of ischemia following middle cerebral artery occlusion. Systemic treatment of Brattleboro rats with vasopressin normalized their serum electrolyte concentrations and osmolarity but did not alter sodium or water accumulation in the ischemic brain. In contrast, intraventricular administration of vasopressin in Brattleboro rats increased edema formation to that seen in control rats. The reduced water and sodium accumulation in Brattleboro rats subjected to middle cerebral artery occlusion may be related to alterations in blood-brain barrier permeability since the blood-to-brain sodium flux was 36% less in the ischemic tissue of the Brattleboro as compared to the Long-Evans strain. These results support the hypothesis that central vasopressin is a regulator of brain volume and electrolyte homeostasis. Furthermore, our findings suggest a role for central vasopressin in the development of ischemic brain edema.

Topics: Aminoisobutyric Acids; Animals; Blood-Brain Barrier; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Electrolytes; Osmolar Concentration; Permeability; Rats; Rats, Brattleboro; Rats, Inbred Strains; Sodium; Vasopressins

The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia-reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells.

Topics: Animals; Basilar Artery; Bradykinin; Brain Ischemia; Cerebrovascular Circulation; Dogs; Endothelium; Potassium Chloride; Reperfusion; Serotonin; Uridine Triphosphate; Vasoconstriction; Vasopressins

Water diuresis was produced in rats after s.c. injections of d(CH2)5,D-Ile2,Ile4-AVP (compound 1) and d(CH2)5,Tyr(OEt)2Val4-AVP (compound 2). Compound 1 is known to be a more potent antagonist against the antidiuretic effect, while Compound 2 is a more potent antagonist against the vasopressor effect of vasopressin. Compound 1 (but not compound 2) also increased plasma osmolality significantly at the diuretic doses. In rats rendered ischemic of the forebrain by 4-hour occlusion of both common carotid arteries, the resulting increases in brain water were significantly reversed by the injection of compound 1. Compound 2 did not reduce the edema. The results suggests a novel approach to the treatment of cerebral edema.

Topics: Animals; Arginine Vasopressin; Blood; Brain Edema; Brain Ischemia; Diuresis; Male; Rats; Rats, Inbred F344; Vasopressins; Water-Electrolyte Balance

U-50488 is a specific kappa opioid agonist which produces in rats water diuresis resulting in an elevation of plasma osmolarity. Pretreatment with U-50488H (the methanesulfonate salt) in Fisher rats prior to 4 h of bilateral carotid occlusion prevented the development of edema in the forebrain, and the effect was greater than that from pentobarbital anesthesia. An additional injection of an antidiuretic hormone which prevented the plasma hyperosmolarity also significantly reduced the anticerebral edemic effects of U-50488H. The plasma osmotic effect, however, may not completely account for the ischemic protection produced by U-50488H.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Body Water; Brain Chemistry; Brain Edema; Brain Ischemia; Diuresis; Male; Osmolar Concentration; Potassium; Pyrrolidines; Rats; Rats, Inbred F344; Receptors, Opioid; Sodium; Vasopressins

Results of using vasopressin and pituitrin in 20 patients with memory disturbances of various genesis (due to circulatory disturbances in the vertebrobasilar system, cerebral atherosclerosis, neurasthenia, brain concussion, epilepsy) are reviewed. The therapeutic efficacy of the hormones was evaluated with the use of a complex of psychophysiological methods. Objective changes in the patients' neurological status and subjective state were taken into account. A high therapeutic efficacy of the hormones in the treatment of amnestic syndromes is demonstrated.

Topics: Adult; Amnesia, Retrograde; Basilar Artery; Brain Concussion; Brain Ischemia; Epilepsy, Temporal Lobe; Female; Humans; Intracranial Arteriosclerosis; Male; Memory Disorders; Middle Aged; Neurasthenia; Pituitary Hormones, Posterior; Vasopressins; Vertebral Artery