pituitrin and Subarachnoid-Hemorrhage

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

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

In this case report, we present a 28-year-old woman who was admitted to a neuro-intensive care unit with sub-arachnoid haemorrhage. She was intubated and haemodynamically unstable. Over five days the need for norepinephrine reached the level of 1.2 µg/kg/min to insure a sufficient cerebral perfusion pressure. Epinephrine and vasopressin were without effect in raising the blood pressure. On suspicion of tachyphylaxis the norepinephrine infusion was stopped, and no decline in blood pressure was observed. After two days without use of any vasopressor agents, the efficacy of norepinephrine returned to normal.

Topics: Adult; Blood Pressure; Cerebrovascular Circulation; Epinephrine; Female; Humans; Norepinephrine; Subarachnoid Hemorrhage; Tachyphylaxis; Vasoconstrictor Agents; Vasopressins

Vasopressin is one of the vasopressors used to augment blood pressure in subarachnoid hemorrhage (SAH) patients with clinically significant vasospasm. The purpose of the present study was to determine whether the administration of vasopressin to a population of SAH patients was an independent predictor of developing hyponatremia.. A retrospective review on the health records of 106 patients admitted to the University of Alberta Hospital Neurosciences ICU, Edmonton AB, Canada, with SAH from June 2013 to December 2015 was conducted. Serum sodium changes in patients receiving vasoactive drugs were compared. In addition, independent predictors for hyponatremia (Na < 135 mmol/L) were determined using a multivariate logistic regression model.. Patients treated with vasopressin in addition to other vasoactive drugs had significantly higher sodium changes compared to those treated with other vasoactive drugs (-4.7 ± 6 vs -0.1 ± 2.4 mmol/L, respectively, p value 0.001). Hyponatremia occurred in 14 patients (70 %) treated with vasopressin, 10 patients (44 %) treated with vasoactive drugs other than vasopressin (p value 0.081), and 24 patients (38 %) who did not receive any vasoactive drug (p value 0.013). In multivariate logistic regression analysis, when adjusting for disease severity, age, sex, aneurysm location, and treatment, vasopressin was associated with hyponatremia (OR 3.58, 95 % CI, 1.02-12.5, p value 0.046).. The results of the present study suggest that hyponatremia may be more common in SAH patients treated with exogenous vasopressin compared to those who did not receive it. Serum sodium should be monitored closely when vasopressin is being used in the SAH population. Further studies are needed to confirm the effect of exogenous vasopressin on serum sodium levels in SAH populations.

Topics: Adult; Female; Humans; Hyponatremia; Male; Middle Aged; Retrospective Studies; Subarachnoid Hemorrhage; Vasoconstrictor Agents; Vasopressins

To investigate the dynamic expression of vasopressin and its potential role in rat brain tissue after experimental subarachnoid hemorrhage (SAH).. Male Sprague-Dawley rats were divided into 10min, 1h, 6h, 24h, 48h and 72h groups. The SAH model was established by endovascular puncture. ELISA and immunohistochemistry were performed to evaluate dynamic expression of vasopressin. Immunohistochemistry of GPIIb/IIIa integrin was used to assess platelet aggregation. Double immunofluorescence labeling was carried out to observe the reaction between vasopressin and platelet. Early brain injury was evaluated by apoptotic cells counting. Neurobehavioral score was performed to assess neuroprotective role of SR 49059 (a selective antagonists of vasopressin receptor).. In peripheral blood and hypothalamus, vasopressin increased rapidly at 6h and 24h. Expression of GPIIb/IIIa integrin peaked at 24h in cortex and hippocampus. Immunofluorescence showed that vasopressin and GPIIb/IIIa integrin located at the same site. Administration of SR 49059 significantly decreased platelet aggregation and number of apoptotic cells. The neurobehavioral score was promoted significantly after the intervention.. The results indicate that rapidly increased vasopressin could induce platelet aggregation and contribute to early brain injury after SAH.

Topics: Animals; Apoptosis; Brain; Disease Models, Animal; Disease Progression; Enzyme-Linked Immunosorbent Assay; Hormone Antagonists; Immunohistochemistry; Indoles; Male; Neuroprotective Agents; Platelet Aggregation; Pyrrolidines; Random Allocation; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Time Factors; Vasopressins

Hemodynamic augmentation is utilized as a treatment in the setting of symptomatic cerebral vasospasm. This approach includes the use of vasopressors to induce hypertension with the aim of improved cerebral blood flow. Agents with potent alpha-1 antagonism properties, including clozapine, can inhibit or blunt the response of several vasopressor agents.. Case report.. A 54-year-old schizophrenic male with an aneurysmal subarachnoid hemorrhage required hemodynamic augmentation in which several vasopressor trials resulted in no or poor response. The addition of epinephrine resulted in a decrease of mean arterial pressure. Vasopressin initiation demonstrated an immediate vasopressor effect.. Vasopressors are an important treatment modality in symptomatic cerebral vasospasm. This case highlights the potential for clozapine to blunt the effects of vasopressors; or in the case of epinephrine, it causes a reversal effect. Vasopressin may be considered an agent of choice in patients who have recently taken clozapine and require hemodynamic augmentation.

Topics: Clozapine; Drug Interactions; Epinephrine; GABA Antagonists; Humans; Hypertension; Intracranial Aneurysm; Male; Middle Aged; Schizophrenia; Subarachnoid Hemorrhage; Vasoconstrictor Agents; Vasopressins; Vasospasm, Intracranial

Clinicopathological studies on patients succumbing to subarachnoid haemorrhage (SAH) demonstrated hypothalamic lesions. The implication of the hypothalamic neuropeptides arginine-vasopressin (AVP) and oxytocin (OXT) has not been linked to aneurysmal SAH yet. This study investigates AVP and OXT in CSF and plasma of patients with spontaneous aneurysmal SAH and their association with outcome.. CSF and plasma samples of 12 patients with aneurysmal SAH were prospectively studied for 2weeks. AVP and OXT were measured by radioimmunoassay. Outcome was assessed on Glasgow-Outcome-Scale. Twenty-nine patients without neuropsychiatric disturbances served as controls. Differences in neuropeptide concentration time courses were assessed by regression models. Group comparisons were performed by Kruskal-Wallis and correlations by Spearman tests.. Regression of CSF levels between patients with poor and good outcome revealed significantly lower levels of AVP in patients with poor outcome (p=0.012) while OXT showed a trend towards lower levels (p=0.063). In plasma, no significant differences between outcome groups were found. Group comparisons between poor outcome patients and controls revealed significant differences in CSF for AVP (p=0.001) and OXT (p=0.015). In plasma, AVP yielded significantly different results while OXT did not. No differences were found between the good outcome group and controls. Plasma and CSF concentrations showed no significant correlation.. Patients with poor outcome after aneurysmal SAH have lower AVP and OXT levels in CSF than patients with good outcome while neuropeptide levels in plasma failed to reflect differences in outcome. The data indicate hypothalamic damage as an aetiologic factor for outcome after aneurysmal SAH.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Glasgow Outcome Scale; Humans; Hypothalamus; Male; Middle Aged; Oxytocin; Prognosis; Regression Analysis; Subarachnoid Hemorrhage; Vasopressins; Young Adult

Symptoms of hyponatremia and diuresis due to cerebral salt wasting syndrome (CSWS) are often observed after aneurysmal subarachnoid hemorrhage (SAH). Inadequately treated CSWS is known to work as a trigger of symptomatic vasospasm in SAH patients. Therefore, it is indispensable to detect and treat CSWS as early as possible in ICU. A 36-year-old man with SAH was admitted to our ICU. His urine volume increased excessively 3 days after ICU admission, and it reached a peak (39,250 ml x day(-1)) on the 6th day in ICU. Since infusion volume was controlled with regard to daily urinary output, hyponatremia was not noticeable and excessive urine volume stood out conspicuously. Though vasopressin and desmopressin were administered, the symptoms of natriuresis and hyponatremia were aggravated, associated with hyper secretion of natriuretic peptides (ANP 160 pg x dl(-1), BNP 172 pg x dl(-1)). Recent studies revealed that hyponatremia and hypovolemia following SAH might be caused by exaggerated secretion of natriuretic peptides. Experimental studies showed that the administration of vasopressin and desmopressin cause excessive secretion of natriuretic peptides under the circumstance of volume expansion in rats. We infer that the administration of vasopressin and desmopressin to our patient deterionated natriuresis in CSWS as in the previous experimental findings.

Topics: Adult; Animals; Atrial Natriuretic Factor; Brain Diseases; Contraindications; Humans; Hyponatremia; Hypovolemia; Male; Natriuresis; Rats; Subarachnoid Hemorrhage; Syndrome; Urination Disorders; Vasopressins

Labetalol is an effective antihypertensive medication frequently used to treat systemic hypertension in acute care settings, including the management of hypertension associated with a subarachnoid hemorrhage. We present a case of profound hypotension, refractory to inotropic and vasopressor therapy following an iv infusion of labetalol.. Initiation of an iv labetalol infusion resulted in good blood pressure control in a patient suffering from a Fisher grade 3 subarachnoid hemorrhage with an initial Glascow coma scale of 14/15 and mild hydrocephalus. Progressive deterioration of neurological symptoms and evidence of worsening hydrocephalus preceded the sudden development of profound hypotension (60/35 mmHg) and bradycardia with a minimum heart rate of 40 beats.min(-1). Initial resuscitative efforts included administration of intravascular fluid, hypertonic saline, atropine, adrenalin (more than 10 mg in divided doses) and noradrenalin. These measures restored the blood pressure to 80/45 with a HR of 98 beats.min(-1). Intraoperative placement of an intraventricular drain released cerebrospinal fluid under pressure with an initial intracranial pressure of 15 cm H(2)O. A combination of adrenalin, noradrenalin, dopamine and vasopressin infusions were required to restore the blood pressure to 130/65 mmHg after an additional two hours. All inotropic and vasopressor support was weaned off after the 14th hr (about two drug half-lives). The patient was awake and responsive the following day, with no obvious neurological consequences. No evidence of neurological injury, drug administration error or myocardial dysfunction was documented.. The episode of profound hypotension which occurred after initiating a labetolol infusion required maximal combined vasopressor therapy to restore the blood pressure suggesting that this patient demonstrated an extreme sensitivity to labetalol. Combination therapy with adrenergic and nonadrenergic agonists may be required for optimal treatment of profound hypotension associated with labetalol-induced vasoplegia.

Topics: Antihypertensive Agents; Bradycardia; Cardiotonic Agents; Dopamine; Epinephrine; Female; Humans; Hypotension; Intracranial Aneurysm; Labetalol; Middle Aged; Norepinephrine; Subarachnoid Hemorrhage; Time Factors; Vasoconstrictor Agents; Vasopressins

Subarachnoid hemorrhage increases the plasma level of vasopressin, a well-known vasoconstrictor. We examined the sensitivity to vasopressin in rat basilar artery after subarachnoid hemorrhage using a rat subarachnoid hemorrhage model. Vasospasm was observed 1-2 days after subarachnoid hemorrhage induction, and the contractile response to vasopressin in rat basilar arteries was assessed. The concentration-response curve for vasopressin in subarachnoid hemorrhage (1 day) rats shifted leftward compared with that of control rats. The concentration-response curve for vasopressin V(1) receptor agonist also shifted leftward and upward compared with that of control rats. The concentration-response curve for vasopressin was inhibited not by vasopressin V(2) receptor antagonist but by vasopressin V(1) receptor antagonist. Thus, it was demonstrated that the vasoconstricting effect of vasopressin was significantly enhanced in the vasospasm phase after subarachnoid hemorrhage.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Basilar Artery; Dose-Response Relationship, Drug; Endothelium, Vascular; In Vitro Techniques; Male; Morpholines; Oxytocin; Potassium Chloride; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Spiro Compounds; Subarachnoid Hemorrhage; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasopressins; Vasospasm, Intracranial

We retrospectively studied 133 patients with subarachnoid hemorrhage (SAH) to assess whether there was any gender disparity in serum electrolytes levels throughout the clinical course. Serum concentrations of sodium and potassium were measured in all patients, while catecholamines or antidiuretic hormone were assessed in a number of cases. Female SAH-patients had lower potassium level (3.29 +/- 0.47 mEq/L) than did male patients (3.68 +/-0.38) on the first day of SAH. This gender disparity continued to the beginning of the chronic phase and disappeared several months later. Mean serum sodium level was lower in the male group than in the female group throughout the clinical course. Mean serum levels of adrenaline and antidiuretic hormone were characterized by their prominent high value on the first day. Serum potassium levels were inversely related to serum levels of catecholamines, especially adrenaline, during the acute and subacute phases, particularly on the first day.

Topics: Adult; Aged; Aged, 80 and over; Catecholamines; Electrolytes; Female; Humans; Male; Middle Aged; Neurophysins; Potassium; Protein Precursors; Retrospective Studies; Sex Characteristics; Sodium; Statistics, Nonparametric; Subarachnoid Hemorrhage; Vasopressins

Central salt wasting syndrome may be caused by pathological increases in serum natriuretic peptides after subarachnoid hemorrhage (SAH). However, it is unclear as to why the serum concentration of atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) increases in the subacute phase of SAH. The present study was designed to assess the correlation between focal brain edema and serum concentration of ANP or BNP in patients with SAH. Focal brain edema was found in 8 SAH-patients and peaked between days 4 and 7 of SAH. The mean serum ANP and BNP levels in patients with focal brain edema were significantly higher than those in patients without focal brain edema between days 4 and 14 of SAH. These results suggest that focal brain edema might correlate with increased levels of ANP and BNP in the subacute phase of SAH.

Topics: Atrial Natriuretic Factor; Brain Edema; Humans; Natriuretic Peptide, Brain; Retrospective Studies; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Vasopressins

The effects of the non-peptide vasopressin V2 receptor antagonist, 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrah ydro-1 H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced significant water retention after water loading, increased the brain content of water and Na+ and increased plasma vasopressin levels. The water retention and brain water and Na+ accumulation were prevented by OPC-31260 administration, but the plasma vasopressin levels were further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of antidiuresis and disturbances in brain water and electrolyte balance in response to subarachnoid haemorrhage. The subarachnoid haemorrhage-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on renal tubular function: it blocks the renal vasopressin V2 receptors. These observations might suggest a new, effective approach to the treatment of subarachnoid haemorrhage-induced cerebral oedema in humans.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Body Water; Brain; Brain Edema; Diuresis; Dose-Response Relationship, Drug; Drinking; Male; Osmolar Concentration; Potassium; Rats; Rats, Wistar; Sodium; Subarachnoid Hemorrhage; Urination; Urine; Vasopressins

Hyponatremia after subarachnoid hemorrhage (SAH) is commonly associated with diuresis and natriuresis, but the causes are still controversial. We investigated whether brain natriuretic peptide (BNP) was related to such hyponatremia.. Plasma BNP concentrations were measured by immunoradiometric assay in 18 patients at 0 to 2 days (period 1), 7 to 9 days (period 2), and > 14 days (period 3) after SAH. Plasma concentrations of antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and noradrenaline were also measured during period 2.. The 11 patients with hyponatremia (serum sodium concentration of < 135 mEq/L) had much higher plasma BNP concentrations during each period than did healthy controls (P < 0.05), whereas the 7 patients with normonatremia did not show statistically higher values. In the patients with hyponatremia, the plasma BNP concentration during period 2 was statistically higher than that during periods 1 and 3 (P < 0.05). The plasma noradrenaline concentration during period 2 was higher in patients with hyponatremia than in those with normonatremia (P < 0.05), whereas the plasma concentrations of ADH and ANP during period 2 were not statistically different between the hyponatremic and normonatremic patients.. We conclude that BNP may be related to hyponatremia associated with natriuresis following SAH. The increase of noradrenaline may promote the secretion of BNP.

Topics: Acute Disease; Aged; Female; Humans; Hyponatremia; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norepinephrine; Radioimmunoassay; Sodium; Subarachnoid Hemorrhage; Vasopressins

To investigate the influence of inducible nitric oxide synthase on cerebral arteries after subarachnoid haemorrhage (SAH) in vivo, lipopolysaccharide (LPS), a major inducer of inducible nitric oxide synthase, was injected intracisternally into control and SAH model dogs. Intracisternal injection of LPS (0.5 mg) produced a long-lasting, submaximal vasodilation of the basilar artery of control dogs on angiography. This effect became significant at 4 hours after LPS injection and plateaued after 6 hours. This vasodilation was reduced by N(G)-monomethyl-L-arginine. Vasopressin slightly suppressed the vasodilation, while bradykinin increased it. The concentration of L-arginine in CSF decreased after LPS injection, while that of L-citrulline increased. In cytokines, the concentration of tumour necrosis factor-alpha; (TNF-alpha;) in CSF increased transiently at 4 hours after LPS injection, while interleukin-1 beta, interleukin-6, interferon-gamma, did not change. These data suggest that vasodilation by LPS is mainly due to nitric oxide predominantly synthesized by an inducible nitric oxide synthase, proximally induced by TNF-alpha. Our data make it unlikely that SAH itself induces the inducible nitric oxide synthase in vascular tissue, since isolated endothelium-denuded basilar artery from SAH model dogs did not respond to L-arginine. In SAH model dogs, the degree of vasodilation by LPS differed with the severity of vasospasm. Vasodilation was much greater in mild than in severe vasospasm in dogs, and was increased by superoxide dismutase. These findings suggest that the induction of inducible nitric oxide synthase or its activity may be less effective in severe vasospasm.

Topics: Analysis of Variance; Angiography; Animals; Arginine; Basilar Artery; Bradykinin; Citrulline; Cytokines; Dogs; Enzyme Inhibitors; Female; Injections, Spinal; Lipopolysaccharides; Male; Microscopy, Electron; Nitric Oxide Synthase; omega-N-Methylarginine; Subarachnoid Hemorrhage; Vasoconstrictor Agents; Vasodilation; Vasopressins

Hyponatremia following subarachnoid hemorrhage (SAH) occurs due to the inappropriate secretion of antidiuretic hormone (SIADH). However, this condition is also sometimes associated with certain dehydration states.. To clarify the pathogenesis, daily values of urine volume, water balance, and sodium balance (Na Bal) were correlated with plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in 31 cases of SAH.. Na Bal was markedly negative on days 2 and 3. Cumulative Na Bal showed continuous negative values until day 10 following SAH. ANP values showed a consistent elevation, while ADH showed only an initial surge. PRA, as the gross indicator of circulatory volume, showed a lack of suppression, indicating no increase in the circulatory volume.. Hyponatremia following SAH therefore appears to be the result of increased natriuresis, due to the inappropriate elevation of ANP rather than SIADH. In this situation, water restriction should not be recommended, since the circulatory volume is decreased.

Topics: Adult; Aged; Aneurysm, Ruptured; Atrial Natriuretic Factor; Body Water; Dehydration; Female; Humans; Hyponatremia; Intracranial Aneurysm; Male; Middle Aged; Natriuresis; Renin; Subarachnoid Hemorrhage; Vasopressins

A causal or supportive relationship between 1,2-diacylglycerol (DAG) content and the maintenance of tonic vasoconstriction was sought in canine basilar arteries treated in vitro with various agents reported to increase DAG levels in other tissues (platelet-derived growth factor, vasopressin, angiotensin II, and endothelin-1) and, conversely, with agents known to activate sustained constriction (high K+, phorbol ester, hemolysate, and endothelin-1). Multiple segments from individual isolated arteries were prepared. Some segments were immediately frozen as controls and others incubated in physiological saline solution at 37 degrees C for either 5 minutes or 30 minutes in the presence or absence of different concentrations of the test materials. Segments were then quickly frozen until homogenized for lipid extraction and DAG assay. The DAG content of samples incubated up to 2 hours in physiological saline solution alone did not significantly differ from that of immediately frozen control samples. Resting DAG content expressed relative to total protein measured in each sample averaged 3.82 +/- 0.26 (standard error of the mean) pmol DAG/microgram of protein (74 samples from 37 arteries). Endothelin at 2 x 10(-7) mol/L led to a statistically significant increase in DAG content of approximately 40% of basal content at 5 and 30 minutes. A smaller increase in DAG attributable to hemolysate (approximately 25%) was statistically significant at 30 minutes, whereas vasopressin provoked a notable decrease in DAG content. The other agents had no effect. No differences in these results were noted between normal canine basilar arteries and arteries constricted in vivo by subarachnoid blood clot before isolation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Basilar Artery; Culture Techniques; Diglycerides; Dogs; Dose-Response Relationship, Drug; Endothelins; Female; Ischemic Attack, Transient; Isometric Contraction; Male; Phorbol 12,13-Dibutyrate; Platelet-Derived Growth Factor; Subarachnoid Hemorrhage; Vasoconstrictor Agents; Vasopressins

The function of nitric oxide in spastic cerebral arteries after subarachnoid hemorrhage (SAH) was angiographically investigated in dogs. On days 4 and 7, after two intracisternal injections of autologous blood, higher concentrations of L-arginine than those of endogenous L-arginine in the cerebrospinal fluid produced a transient vasodilation of the spastic basilar artery, whereas NG-monomethyl-L-arginine (L-NMMA) produced no significant vasoconstriction. The vasodilator effect of L-arginine after SAH was stronger on day 4 than day 7, but less than that in intact dogs. Vasopressin, which is known to activate the endothelial L-arginine pathway, could induce a vasodilation only after the treatment with L-arginine. Intracisternal injection of superoxide dismutase (SOD), which caused no effect by itself, enhanced the duration of the vasodilator effect of L-arginine on the basilar artery on day 4 and both the magnitude and duration of that effect on day 7. Thus, the basal release of nitric oxide was impaired after SAH, but the ability to synthesize nitric oxide in the vascular wall was not abolished. Enhancement of L-arginine's effect by SOD suggested that the inactivation of nitric oxide by superoxide anion contributed to the development of vasospasm.

Topics: Animals; Arginine; Basilar Artery; Blood Pressure; Cerebral Angiography; Cisterna Magna; Dogs; Injections; Ischemic Attack, Transient; Nitric Oxide; omega-N-Methylarginine; Subarachnoid Hemorrhage; Superoxide Dismutase; Vasodilation; Vasopressins

Hyponatremia is a common complication after subarachnoid hemorrhage. In this study we investigated the relations among hyponatremia, plasma natriuretic peptides, and antidiuretic hormone concentrations after subarachnoid hemorrhage.. Blood samples for radioimmunoassay measurement of plasma brain natriuretic peptide-like immunoreactivity, atrial natriuretic peptide-like immunoreactivity, and antidiuretic hormone were obtained every 2 to 4 days until day 14 after subarachnoid hemorrhage.. Eleven of 20 patients with verified subarachnoid hemorrhage demonstrated mild hyponatremia (126 mEq/L < serum sodium < 135 mEq/L) during their clinical course. Atrial natriuretic peptide and antidiuretic hormone concentrations were significantly elevated on days 0 to 2 after onset of subarachnoid hemorrhage. Atrial natriuretic peptide concentrations remained high in patients who developed mild hyponatremia on days 6 to 14 after onset of subarachnoid hemorrhage. In contrast, antidiuretic hormone concentrations became significantly lower during the second week in these patients.. Mild hyponatremia after subarachnoid hemorrhage may be attributable not to the syndrome of inappropriate secretion of antidiuretic hormone but to cerebral salt-wasting syndrome. Atrial natriuretic peptide may be a causal natriuretic factor in cerebral salt-wasting syndrome.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Water; Female; Humans; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Osmolar Concentration; Sodium; Subarachnoid Hemorrhage; Vasopressins

The relationship between plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) both of which show high values after subarachnoid hemorrhage and cerebral vasospasm was studied. The subjects were 23 patients who were admitted because of aneurysmal subarachnoid hemorrhage during three years from March, 1989 to March, 1992 and in whom plasma ANP and ADH levels could be determined over time. Cerebral vasospasm was evaluated by the finding of cerebral angiography, clinical symptoms, and presence or not of low density areas on CT. Hyponatremia was defined as the serum sodium level of 130 mEq/l or less for two days or more. Angiographical vasospasm was found in 17 patients (85%), symptomatic vasospasm in 15 patients (65.2%), low density areas on CT in 9 patients (40.9%) and hyponatremia in 8 patients (34.8%). Symptomatic vasospasm was noted in 7 of the 8 patients (87.5%) with hyponatremia, low density areas on CT in 4 patients (50%), the detection rate being high. The plasma ANP and ADH levels were 76.7 +/- 32.1 pg/ml and 2.2 +/- 0.7 pg/ml respectively in the patients with symptomatic vasospasm against 38.3 +/- 21.3 pg/ml and 2.4 +/- 0.6 pg/ml respectively without symptomatic vasospasm, the plasma ANP level being significantly high in the patients with symptomatic vasospasm (p < 0.01). The plasma ANP and ADH were 71.2 +/- 33.8 pg/ml and 2.0 +/- 1.1 pg/ml respectively in the patients with low density areas on CT against 51.2 +/- 31.3 pg/ml and 1.8 +/- 0.5 pg/ml respectively without low density areas on CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Humans; Hyponatremia; Intracranial Aneurysm; Ischemic Attack, Transient; Rupture, Spontaneous; Subarachnoid Hemorrhage; Vasopressins

Topics: Animals; Arginine Vasopressin; Body Water; Brain; Brain Edema; Electrolytes; Inappropriate ADH Syndrome; Male; Rats; Rats, Wistar; Subarachnoid Hemorrhage; Vasopressins

Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A "double-hemorrhage" canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography.. Secondary branches of both untreated basilar arteries (inner diameter, 324 +/- 11 microns; n = 12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328 +/- 12 microns; n = 12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer.. In untreated arteries, 10(-11) to 10(-7) M vasopressin, 10(-10) to 10(-6) M bradykinin, and 10(-9) to 10(-6) M calcium ionophore A23187 caused endothelium-dependent relaxations. At 10(-6) and 3 x 10(-4) M the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced small but significant rightward shifts of the concentration-response curves to bradykinin and A23187. At 10(-3) M L-arginine prevented the inhibitory effect of L-NAME. Subarachnoid hemorrhage abolished relaxations to vasopressin but did not affect relaxations to bradykinin or A23187.. These studies suggest that in small arteries of the brain stem vasopressin causes relaxations by activation of the endothelial L-arginine pathway. This mechanism of relaxation is selectively inhibited by subarachnoid hemorrhage. Preservation of endothelium-dependent relaxations to bradykinin and A23187 is consistent with the concept that small arteries are resistant to vasospasm after subarachnoid hemorrhage.

Topics: Animals; Arginine; Arterioles; Bradykinin; Brain Stem; Calcimycin; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Male; NG-Nitroarginine Methyl Ester; Subarachnoid Hemorrhage; Vasodilation; Vasopressins

In vivo experiments on the vasoactive effects of vasopressin and oxytocin on cerebral circulation were carried out in anesthetized dogs, using an electromagnetic flowmeter to measure vertebral blood flow and angiography to measure the internal diameter of the basilar artery. Direct bolus infusion of 1 pmol to 1 nmol of vasopressin or 10 pmol to 10 nmol of oxytocin into a femoral-vertebral artery shunt produced a dose-dependent decrease in vertebral artery blood flow without significantly affecting mean arterial blood pressure. Vasopressin was more potent than endothelin and neuropeptide Y, which have also been demonstrated to induce long-lasting decreases in vertebral artery blood flow. However, direct bolus infusion of vasopressin (100 pmol and 1 nmol) or oxytocin (1 nmol and 10 nmol) into the vertebral artery dilated major vessels including the vertebral, anterior spinal, and basilar arteries, as well as the circle of Willis and its main branches, while endothelin (1 nmol) and neuropeptide Y (5 nmol) caused no change in the diameters of major cerebral arteries. The V1 antagonist d(CH2)5tyrosine(methyl) arginine vasopressin suppressed the effects of both vasopressin and oxytocin. Vasopressin was over 10 times as potent as oxytocin in both assays. The vasodilatory effect of vasopressin, which may be mediated by an endothelium-dependent mechanism, was functionally damaged in dogs after experimental subarachnoid hemorrhage. These data suggest regional differences in the sensitivity and responsiveness of vasculature to vasopressin and oxytocin, and specifically that both peptides act through V1 receptors to decrease the resistance of large vessels and increase the resistance of small vessels.

Topics: Animals; Basilar Artery; Cerebral Angiography; Cerebrovascular Circulation; Dogs; Dose-Response Relationship, Drug; Oxytocin; Subarachnoid Hemorrhage; Vasoconstriction; Vasodilation; Vasopressins; Vertebral Artery

We determined serum atrial natriuretic peptide (ANP) and anti-diuretic hormone (ADH) on a time course basis in cases of subarachnoid hemorrhage and studied their influence on the development of hyponatremia. Twenty six cases of subarachnoid hemorrhage were admitted to our hospital in the past 1 year, and by the site of ruptured aneurysms, there were Acom 6 cases, ICA 6 cases, MCA 5 cases and VA BA 4 cases. Serum ANP and ADH levels were determined in the acute phase on Day 1-4, in the hyponatremia phase on Day 5-14 and in the chronic phase on Day 15 downward. Levels of not more than 130 mEq/l were regarded as hyponatremia. Cases showing other evident causes such as heart failure and renal insufficiency were excluded. In the normal control group (n = 20) which was admitted to this hospital for a close check-up, serum ANP was 26.5 +/- 11.6 pg/ml (10-50); levels of more than 50 pg/ml were regarded as being abnormally high. 1) Hyponatremia was observed in 7 cases (26-9%); the day of onset was 11.9 hospital day. The duration was 5.0 days and the minimum serum Na level was 126.4 mEq/l. 2) The serum ADH level was high regardless of whether or not there was the development of hyponatremia in the acute phase but tended to decrease gradually and became normal in the hyponatremia phase. 3) The serum ANP level in the cases of hyponatremia was 40.7 +/- 9.1 pg/ml in the acute phase, 69.0 +/- 25.7 pg/ml in the hyponatremia phase and 40.2 +/- 21.5 pg/ml in the chronic phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Humans; Hyponatremia; Subarachnoid Hemorrhage; Vasopressins

One hundred patients affected by S.A.H. have been studied, evaluating the possible correlations between clinical findings and hyponatremia. For a better understanding of hyponatremia during S.A.H., the hematic concentration of A.D.H. and A.N.P. have been determined and correlated with hyponatremia.

Topics: Atrial Natriuretic Factor; Cerebral Arterial Diseases; Female; Humans; Hyponatremia; Male; Prognosis; Spasm; Subarachnoid Hemorrhage; Vasopressins

Topics: Blood Proteins; Cardenolides; Digoxin; Humans; Hyponatremia; Intracranial Aneurysm; Plasma Volume; Renin; Saponins; Sodium-Potassium-Exchanging ATPase; Subarachnoid Hemorrhage; Vasopressins

Vascular endothelial cells of the basilar artery and secretory axons of the neurohypophysis from rabbits after experimental subarachnoid haemorrhage were investigated by postembedding peroxidase--anti-peroxidase technique for electron microscopy to detection of vasopressin (VP). The results indicate an lack of VP-positive endothelial cells in basilar artery, while VP-positive secretory granules were commonly present in the neurohypophysis. The results are discussed in terms of pathophysiological aspect of subarachnoid haemorrhage.

Topics: Animals; Basilar Artery; Cytoplasmic Granules; Endothelium, Vascular; Microscopy, Immunoelectron; Muscle, Smooth, Vascular; Rabbits; Reference Values; Subarachnoid Hemorrhage; Vasopressins

The authors describe a case of subarachnoid hemorrhage with hyponatremia accompanied by elevation of plasma atrial natriuretic peptide (ANP). The early phase of hyponatremia was classified as the syndrome of inappropriate secretion of antidiuretic hormone (ADH) due to subarachnoid hemorrhage. However, in the later phase, hyponatremia and natriuresis were accompanied by suppression of ADH while plasma ANP remained elevated. The patient was effectively treated with demeclocycline and hypertonic saline. The significance of ANP in the pathophysiology of increased natriuresis is discussed.

Topics: Aged; Atrial Natriuretic Factor; Demeclocycline; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Intracranial Aneurysm; Natriuresis; Saline Solution, Hypertonic; Subarachnoid Hemorrhage; Vasopressins

Measurement of plasma alpha-humanANP (ANP) and antidiuretic hormone (ADH) in 28 cases with aneurysmal subarachnoid haemorrhage (SAH) was carried out, and then compared with control subjects who were infused with hypertonic saline. In cases with hyponatremia (HN), statistical correlation between control subjects and cases without HN was not evident with regards to ANP and plasma osmolality (Posm), excreted fraction of filtrated sodium (FENa) and urinary Na/K. Furthermore, they secreted supernumerarilly in spite of HN. Cases with HN were further subdivided into two groups, they were those cases with negative total sodium balance at the time of appearance of HN, and those cases without total negative sodium balance. In the former, central venous pressure had a tendency to decrease, however, secretion of ANP and ADH was statistically not different in either groups. It appears that ANP regulated urinary sodium excretion against an osmotic or sodium load acts as a maintenance of homeostasis as an osmotic regulator. Cases with HN in which secretion of ADH was physiological, ANP secreted supernumerarilly in spite of hypoosmonaemia and hypovolaemia. Our findings may contribute to a better understanding of the pathophysiological processes leading to hyponatremia in cases with cerebral disorders, and may help to improve the treatment possibilities.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Hyponatremia; Intracranial Aneurysm; Male; Middle Aged; Peptide Fragments; Rupture, Spontaneous; Subarachnoid Hemorrhage; Vasopressins

We examined the relation between plasma atrial natriuretic peptide (ANP) and the changes of the regulating hormones ADH and renin aldosterone in 20 neurosurgical intensive care patients. All patients suffered from elevated intracranial pressure due to severe head trauma or severe subarachnoidal hemorrhage of the anterior circulation. Under controlled mechanical hyperventilation (CMV) with PEEP, 15 patients without evidence of central dysregulation showed no change in plasma ANP, ADH and aldosterone. In five patients with severe central dysregulation of either electrolytes or blood pressure, increases of plasma ANP of various degrees could be observed together with a decline in serum aldosterone.

Topics: Aldosterone; Atrial Natriuretic Factor; Brain Diseases; Craniocerebral Trauma; Critical Care; Humans; Intracranial Pressure; Reference Values; Renin; Subarachnoid Hemorrhage; Vasopressins; Water-Electrolyte Balance

Centrally released arginine vasopressin (AVP) has been implicated in the regulation of intracranial pressure (ICP) and brain water, and is elevated in the cerebrospinal fluid (CSF) of some patients with pseudotumor cerebri or subarachnoid hemorrhage. The authors have examined the relationship of AVP levels in CSF to ICP and brain water content in three experimental groups of cats with and without cold-induced vasogenic edema. With the cats under general anesthesia, a cold lesion was made and cannulas were placed in the cisterna magna, lateral ventricle, and aorta. Subsequent central and systemic measurements were made while the animals were awake and free-roaming. In Experiment 1, endogenous AVP levels in CSF were measured every 12 hours over a 48-hour period by radioimmunoassay in cats with sham craniotomy, mild edema, or moderate edema; no significant difference was found between groups although a diurnal variation was seen (range 2 to 18 pg/ml). In Experiment 2, either carrier solution or AVP, in doses of 1.5 or 30 ng, was administered via a lateral ventricle every 2 hours over 24 hours in unlesioned cats. In Experiment 3, cats received 2 or 35 ng of carrier solution or AVP in a similar manner, but coupled with a cold lesion. The CSF AVP levels ranged from an average of 100 to 681 pg/ml and 1.4 to 11.9 ng/ml in the two dose groups in both experiments. Neither the low nor the high dose had an effect on brain water content in normal white matter (Experiment 2), but both doses increased brain water content in edematous white matter (p less than 0.05 in Experiment 3), as determined by wet and dry weight measurements of standardized pieces of white matter. The ICP was decreased by high-dose AVP in normal cats (p less than 0.01 at 24 hours), but in lesioned cats was unchanged by low-dose and increased by high-dose AVP (p less than 0.05 at 18 hours). The authors conclude that pharmacological doses of central AVP facilitate the production of vasogenic edema.

Topics: Animals; Brain Edema; Cats; Cerebrospinal Fluid; Cold Temperature; Intracranial Pressure; Subarachnoid Hemorrhage; Vasopressins

Topics: Female; Humans; Inappropriate ADH Syndrome; Male; Subarachnoid Hemorrhage; Vasopressins

Topics: Humans; Inappropriate ADH Syndrome; Subarachnoid Hemorrhage; Vasopressins

A monkey model of subarachnoid hemorrhage (SAH) was used to study both the incidence of hyponatremia and natriuresis and the associated changes in antidiuretic hormone (ADH) secretion and salt and water balance. Following SAH, seven of nine monkeys became natriuretic and hyponatremic. The natriuretic period lasted an average of 4.4 +/- 0.4 days. The mean nadir of serum sodium content was 125.7 +/- 1.6 mEq/liter, and occurred on the average on the 5th day following SAH. The sodium balance after SAH was negative as compared to the preoperative positive sodium balance (p less than 0.001). The plasma vasopressin level was usually elevated for a day following surgery, but there was no significant difference in the levels during the preoperative period and during the period of natriuresis following SAH. The daily urine output and aldosterone levels were not significantly different, and the plasma volume was slightly, but not significantly, decreased after SAH. Four of the animals that had a hyponatremic and natriuretic response following SAH showed a normal regulation of vasopressin in response to both a water challenge and hypertonic saline challenge. The three monkeys that underwent sham procedures did not become hyponatremic and natriuretic postoperatively. The sham-operated monkeys did not show significant differences in their plasma vasopressin levels, urine volume, plasma volume, and aldosterone levels following surgery. These observations are more consistent with primary natriuresis as the cause of hyponatremia rather than the syndrome of inappropriate secretion of ADH. The cause of the renal loss of sodium is not known, but the possibility of a brain natriuretic factor or an alteration in the neural control of the kidney should be considered.

Topics: Animals; Hyponatremia; Inappropriate ADH Syndrome; Macaca fascicularis; Male; Models, Biological; Natriuresis; Subarachnoid Hemorrhage; Vasopressins

Brain water accumulation (1.2%) with an accompanying increase in the sodium content was observed in Wistar rats as early as 1 hour after experimental subarachnoid hemorrhage (SAH). After 6 and 24 hours, the water content was 1.3 and 1.4%, respectively, higher than that of control animals. In contrast, in Brattleboro diabetes insipidus rats the content of brain water and electrolytes had not changed significantly 1 hour after the administration of blood into the subarachnoid space. Increased brain water and sodium and a normal potassium content, indicative of a vasogenic type of brain edema, were seen at 6 hours after SAH. In these animals, known to be devoid of vasopressin, the increase in brain water 24 hours after SAH was 2.6%, compared with 1.4% for Wistar rats with SAH. It is suggested that the lack of vasopressin could alter the course of brain edema formation after experimental SAH in Brattleboro diabetes insipidus rats. It is hypothesized that vasopressin, by regulating the water permeability of the brain capillaries, the choroid plexus, and the cerebrospinal fluid absorption structures, plays an important role in controlling the brain fluid and electrolyte balance during the course of SAH.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Diabetes Insipidus; Female; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Subarachnoid Hemorrhage; Vasopressins; Water-Electrolyte Balance

A young male presented within hours after closed head injury with hypotension, tachycardia, and polyuria. A diagnosis of post-traumatic diabetes insipidus was made. Although a rare entity, the rapid diagnosis of diabetes insipidus and early treatment with vasopressin may have been life-saving in this case. A detailed approach for treatment with continuous intravenous vasopressin may be the most accurate and efficient method of managing acute onset diabetes insipidus, especially in the hemodynamically compromised patient. This will allow for a controlled fluid management in order to achieve hemodynamic stability and prevent aggravation of cerebral edema.

Topics: Acute Disease; Adult; Brain Edema; Diabetes Insipidus; Facial Bones; Humans; Male; Skull Fractures; Subarachnoid Hemorrhage; Vasopressins

Serum osmolality and antidiuretic hormone (ADH) levels were determined for 17 patients with cerebral infarction, 4 with subarachnoid hemorrhage, and 12 controls. The ADH levels were elevated significantly in the stroke patients. Hyponatremia was not observed. Stroke patients are at risk for developing electrolyte disturbances; thus, fluid intake and electrolyte levels should be closely observed.

Topics: Cerebral Infarction; Humans; Inappropriate ADH Syndrome; Subarachnoid Hemorrhage; Vasopressins; Water-Electrolyte Imbalance

Topics: Blood Volume; Erythrocyte Volume; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Plasma Volume; Postoperative Period; Subarachnoid Hemorrhage; Vasopressins

Topics: Animals; Brain Diseases; Cats; Cytoplasmic Granules; Intracranial Pressure; Microscopy, Electron; Pituitary Gland, Posterior; Subarachnoid Hemorrhage; Vasopressins

Topics: Female; Humans; Middle Aged; Subarachnoid Hemorrhage; Syndrome; Vasopressins

Topics: Female; Humans; Hyponatremia; Middle Aged; Subarachnoid Hemorrhage; Vasopressins

Topics: Adult; Female; Humans; Hyponatremia; Hypothalamo-Hypophyseal System; Intracranial Aneurysm; Male; Middle Aged; Rupture, Spontaneous; Subarachnoid Hemorrhage; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Animals; Female; Humans; Hyponatremia; Male; Middle Aged; Subarachnoid Hemorrhage; Vasopressins