pituitrin and Cerebral-Hemorrhage

A 66-year-old hypertensive male with acute intracerebral hemorrhage developed acute hyponatremic coma 3 days after the addition of enalapril and a combination of amiloride and a thiazide diuretic to his hypotensive regimen. The patient recovered consciousness and serum sodium normalized 2 days after fluid restriction and withdrawal of both medications. Three weeks later, upon inadvertent reinstitution of enalapril and indapamide, severe hyponatremic encephalopathy promptly recurred; recovery was again rapid following fluid restriction and withdrawal of both medications. This temporal relationship establishes the thiazide diuretic or the angiotensin converting enzyme inhibitor or both as the cause of the profound symptomatic hyponatremia in this patient. Results of simultaneous serum and urine osmolality assays on several occasions were consistent with a decrease in free water clearance, a result of either increased antidiuretic hormone (ADH) secretion or potentiation of its peripheral action, and thiazide-induced natriuresis. The use of a thiazide diuretic in the presence of either of these aberrations of ADH homeostasis most likely explains the profound and rapid development of hyponatremia. Drug-induced disturbances in serum osmolality are a potentially reversible cause of deterioration of the mental state in a patient with an acute cerebrovascular accident.

Topics: Aged; Amiloride; Benzothiadiazines; Central Nervous System; Cerebral Hemorrhage; Coma; Diuretics; Enalapril; Humans; Hypertension; Hyponatremia; Indapamide; Male; Osmolar Concentration; Sodium; Sodium Chloride Symporter Inhibitors; Vasopressins; Water

We report a 45 y old male patient with severe hypodipsia, but intact vasopressin secretion and maximal renal response to vasopressin. The patient presented during hot summer days, 18 months after a frontal lobe hemorrhage due to a ruptured aneurysm, with severe hypernatremia (171 mmol/L) and a plasma osmolality of 348 mosm/kg. He was awake and had no interest in fluid intake. After initial correction, a thirst test for 36 hours was performed. Plasma osmolality rose from 295 to 320, urine osmolality rose from 220 to 700 mosm/kg, while plasma vasopressin levels increased more than 3-fold. Throughout the test the patient did not exhibit appreciable thirst. The intact osmoregulation of vasopressin as evidenced by the plasma levels and the elicited renal response, indicates that a selective acquired disturbance of thirst is present. Whether the thirst center is destroyed or/and thirst recognition (frontal lobe affection) is disturbed primarily, can not be decided.

Topics: Aneurysm, Ruptured; Brain Mapping; Cerebral Hemorrhage; Frontal Lobe; Humans; Hypernatremia; Intracranial Aneurysm; Magnetic Resonance Imaging; Male; Middle Aged; Perceptual Disorders; Postoperative Complications; Thirst; Vasopressins; Water-Electrolyte Balance

Vasopressin (VP) levels were evaluated by radioimmunoassay (RIA) in the arterial (A), peripheral (Vp) and jugular (Vj) vein blood and in CSF in 102 patients with brain tumors. In 60 cases the patients' state was complicated by brain edema (BE) and hemodynamic disturbances (HDD). The obtained data revealed significantly higher VP levels: 1) in A, Vp and CSF in patients with BE (Group A) in comparison with patients without BE (Group B), 2) in Vj in patients with HDD only (Group Bc) and 3) in Vp in patients with HDD and BE (Group Ac) in comparison with Group Bc (p < 0.05). There were marked extremely high VP levels in Vj in patients with severe haemorrhage, tachycardia and high blood pressure (BP) and in CSF in patients with tachycardia, high BP and cardiac arrest (p < 0.05 correspondingly in each of the cases). Our results on a clinical basis confirmed CSF VP influence on BE development. We also confirmed the neurohumoral (through blood) and neurotransmitter (possibly through CSF and/or vasopressinergic pathways) VP influences on cardiovascular regulation mechanisms. We content that this is a pathogenetic basis for application of VP direct or indirect antagonists for preventing and treating brain edema in neurosurgical patients.

Topics: Adolescent; Adult; Aged; Blood-Brain Barrier; Brain Edema; Brain Neoplasms; Cerebral Hemorrhage; Child; Child, Preschool; Female; Heart Arrest; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Postoperative Complications; Radioimmunoassay; Synaptic Transmission; Tachycardia; Vasopressins

The study of renin-angiotensin-aldosterone (RAA) and vasopressin (VP) systems in neurosurgical patients with brain tumors and brain edema (BE) had revealed an excessive activity of these systems with secondary hyperaldosteronism especially with BE that proves the pathogenetic role of these systems. Measurement of Aldosterone (Ald) in CSF may serve as a diagnostic test to help manage the patient's clinical condition. Mechanisms of Ald penetration in CSF assumed to be the result of blood-brain-barrier (BBB) destruction (especially in astrocytomas) and/or the mediation by neuropeptides (for example increasing activity of VP V1-receptors). Results serve as a basis for application of the neuropeptide and hormone antagonists and inhibitors on all stages of cascade reactions taking part in the water and sodium retention.

Topics: Adolescent; Adult; Aged; Aldosterone; Astrocytoma; Blood-Brain Barrier; Brain Edema; Brain Neoplasms; Cerebral Hemorrhage; Child; Child, Preschool; Female; Heart Arrest; Hemodynamics; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Postoperative Complications; Prognosis; Radioimmunoassay; Renin-Angiotensin System; Tachycardia; Vasopressins

Injection of arginine vasopressin into the cerebral ventricles in animals with brain injury increased brain water, whereas injection of atrial natriuretic peptide reduced water content. Therefore, to determine the role of endogenous arginine vasopressin in brain edema, we attempted to inhibit edema from a hemorrhagic lesion with an arginine vasopressin V1 receptor antagonist or atrial natriuretic peptide.. Adult Sprague-Dawley rats with hemorrhages induced by 0.4 IU bacterial collagenase were treated with 75 ng (n = 9) or 8 micrograms (n = 9) of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)Arg, 3.2 micrograms (n = 4) atrial natriuretic peptide injected intracerebrally, or 5 micrograms/kg per hour (n = 7) atrial natriuretic peptide intraperitoneally. They were compared with control groups injected with 0.4 IU collagenase only. Brain water and electrolytes were measured 24 hours later. Brain uptake of [14C]sucrose was measured 30 minutes after lesions were induced by 0.4 IU collagenase alone (n = 5) or after collagenase injection and 50 micrograms/kg per hour (n = 5) atrial natriuretic peptide injected intravenously.. The arginine vasopressin V1 receptor antagonist and atrial natriuretic peptide significantly (p < 0.05) reduced water and sodium contents in the posterior edematous regions. Brain uptake of [14C]sucrose was significantly reduced by intravenous atrial natriuretic peptide.. Antagonists to arginine vasopressin V1 receptors and atrial natriuretic peptide both significantly reduce hemorrhagic brain edema, and atrial natriuretic peptide appears to protect the blood-brain barrier.

Topics: Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood-Brain Barrier; Body Water; Brain Edema; Cerebral Hemorrhage; Collagenases; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Sucrose; Vasopressins

Topics: Blood Pressure; Cerebral Hemorrhage; Cerebral Ventricles; Humans; Inappropriate ADH Syndrome; Infant, Newborn; Infant, Premature, Diseases; Vasopressins

There is considerable evidence to suggest that there is a cholinergic link in the neural control of vasopressin release, but the precise role for this link has not been adequately demonstrated in the intact animal. We have, therefore, examined in conscious unrestrained rats the effects of central cholinergic blockade on the stimulation of vasopressin release by increased plasma osmotality (iv infusion of 2.5 M NaCl at 0.1 mg/kg body weight.min for 30 min) and by decreased blood volume (2 successive hemorrhages of 10% of blood volume each). The vasopressin responses to these stimuli were unaffected by either intracerebroventricular (icv) atropine (10 micrograms; muscarinic blockade) or icv hexamethonium (10 micrograms; nicotinic blockade) in doses which block the vasopressin responses to icv cholinergic agonists. The implications of these findings are discussed.

Topics: Acetylcholine; Animals; Atropine; Cerebral Hemorrhage; Cholinergic Fibers; Hexamethonium; Hexamethonium Compounds; Male; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Sodium Chloride; Vasopressins

We investigated whether a reflex increase in plasma vasopressin level due to hemorrhagic hypotension affects brain blood flow. In 60 lightly anesthetized, artificially ventilated rats, the flow was determined with radiolabeled microspheres. We found excellent maintenance of blood flow throughout all brain regions during the hypotensive state (71 mmHg on average), and such maintenance of flow was not modulated at all by a supramaximal intravenous dose of the selective vasopressin V1-receptor antagonist [d(CH2)5 Tyr-(Me)]AVP. The latter finding also implies that the V1 antagonist failed to unmask the vasodilator type actions of V2 receptors on the maintenance of flow during hemorrhagic hypotension. These were true also when the cervical sympathetic bundles were severed bilaterally. The plasma level of endogenous vasopressin was increased during hypotension, ranging from 118 to 973 pg/ml. Despite this increase, the brain blood flow was entirely independent of the plasma vasopressin level in all the brain regions studied. We conclude that the brain circulation of rats can maintain its blood flow during hemorrhagic hypotension without any apparent contribution from a concomitant reflex increase in plasma vasopressin. Despite our negative results for the brain blood flow, the possible segmental effects of circulating vasopressin on the brain arterial caliber remain to be clarified under conditions of hemorrhagic hypotension.

Topics: Animals; Cerebral Hemorrhage; Cerebrovascular Circulation; Hypotension; Male; Microspheres; Osmolar Concentration; Rats; Rats, Inbred Strains; Reference Values; Vasopressins

Intracerebroventricular (i.c.v.) administration of somatostatin-28 (SS-28) (30 ng-1 micrograms) resulted in a dose-dependent elevation of plasma concentrations of vasopressin. Continuous i.c.v. infusion of SS-28 produced a depletion of vasopressin-like immunoactivity within the paraventricular and supraoptic of the hypothalamus as determined by immunocytochemistry. To evaluate the role of endogenous brain somatostatin in the regulation of vasopressin secretion, animals were treated with cysteamine. Cysteamine (90 mg/kg) treatment given s.c. produced a 50% depletion of endogenous brain somatostatin-like peptide concentrations. Pretreatment of animals with cysteamine attenuated hemorrhage-induced elevation of plasma vasopressin levels. The elevation of plasma vasopressin concentrations following the i.v. administration of hypertonic saline or the i.c.v. administration of angiotensin-II were not altered by cysteamine treatment. These results are consistent with the conclusion that an endogenous brain somatostatin may be involved in the physiologic regulation of vasopressin secretion following hemorrhage.

Topics: Animals; Cerebral Hemorrhage; Cysteamine; Dose-Response Relationship, Drug; Hypothalamus; Injections, Intraventricular; Male; Rats; Rats, Inbred Strains; Somatostatin; Somatostatin-28; Vasopressins

The effect of centrally administered indomethacin on hemorrhage-induced vasopressin release was studied in the morphine-sedated, urethan/chloralose-anesthetized dog. Ventriculocisternal perfusion of indomethacin 1) significantly reduced the amount of prostaglandin E2 in the effluent from the cisterna magna, 2) significantly enhanced the vasopressin response to volume depletion, and led to a greater fall in mean arterial blood pressure during severe hemorrhage. The results suggest that central prostaglandins may have an inhibitory effect on vasopressin secretion during volume depletion.

Topics: Animals; Blood Pressure; Cerebral Hemorrhage; Cisterna Magna; Dogs; Heart Rate; Indomethacin; Injections, Intraventricular; Male; Osmolar Concentration; Prostaglandins E; Renin; Vasopressins

Cerebrospinal fluid and plasma vasopressin were measured in patients with cerebral disorders associated with varying levels of elevated intracranial pressure. The mean cerebrospinal fluid vasopressin concentration was significantly increased in patients with pseudotumor cerebri (2.0 +/- 0.2 [SEM] pg/ml), intracranial tumor (2.3 +/- 0.4 pg/ml), and intracranial hemorrhage (1.9 +/- 0.3 pg/ml) compared with control patients (1.2 +/- 0.1 pg/ml). A significant relationship was found between intracranial pressure and the cerebrospinal fluid vasopressin concentration within all groups of patients and in the whole sample as well (r = 0.79; p less than 0.001). In the groups of patients with intracranial tumor, hydrocephalus, and intracranial hemorrhage, some individuals showed plasma vasopressin concentrations inappropriate to the corresponding plasma osmolality, but no relationship was found between intracranial pressure and plasma vasopressin concentration. It is suggested that increased intracranial pressure is a stimulus to centrally released vasopressin. The clinical importance of increased cerebrospinal fluid vasopressin concentrations is still not known.

Topics: Adolescent; Adult; Aged; Brain Diseases; Brain Neoplasms; Cerebral Hemorrhage; Female; Humans; Hydrocephalus; Intracranial Pressure; Male; Middle Aged; Osmolar Concentration; Pseudotumor Cerebri; Vasopressins

In 100 patients with different forms of cerebral strokes the author studied the general water content. Its distribution in the organism. Na and K concentration in the plasma and erythrocytes and the general electrolyte content in spaces of the body. It was established that the most frequent syndromes of water-electrolyte disorders in the acute period of strokes is intracellular or general hydratation (81%). In parenchymatous-subarachnoidal hemorrhages the general dehydratation was combined with a hyperhydratation of the extracellular space, while in sichemic strokes there was an anhydridemia up to 10-18 days. A disturbance of the electrolyte metabolism was also expressed in a transmineralization with a drop of the general Na and K content due to intracellular losses. The K deficit was averagely 29% and the Na--15.5% and should be taken into consideration in a substitutive hydro-electrolyte therapy. Solutions with an increased K content should be used in order to compensate its deficit.

Topics: Acute Disease; Adrenal Cortex; Body Water; Cerebral Hemorrhage; Cerebrovascular Disorders; Extracellular Space; Humans; Hypothalamus; Mineralocorticoids; Plasma Volume; Potassium; Sodium; Time Factors; Vasopressins; Water-Electrolyte Imbalance

Topics: Cerebral Hemorrhage; Diabetes Insipidus; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Parenteral Nutrition; Vasopressins

Schwartz-Bartter-syndrome as a consequence of severe cerebral alterations like bacterial and tuberculous meningitis, encephalitis, hydrocephalus and brain haemorrhage has been observed in 7 cases. Massive natriuresis is followed by marked hyponatremia and hypochloremia which may lead to an intracellular brain edema. Sodium administered even in high dosage is lost rapidly through the kidney, and does not normalize the serum level of sodium. The Schwartz-Bartter-syndrome is caused by inadequatly elevated ADH-secretion with consecutive water retention and an increase in plasma volume. Consecutively an increased excretion of sodium takes place causing a substantial loss of bound water. An analogous situation was seen in a child with neurohormonal diabetes insipidus after an overdosage of ADH, which resulted in a hypervolemia, marked hyponatremia and massive natriuresis. The increased excretion of sodium may be the result of reduced reabsorption of sodium in the proximal tubuli of the kidney, caused by a humeral natriuretic factor (the socalled "third factor"). In the serum of one of our patients an increased natriuretic activity could be shown; this is the first time in a child with Schwartz-Bartter-syndrome.

Topics: Blood Volume; Brain Diseases; Brain Edema; Cerebral Hemorrhage; Child; Chlorides; Encephalitis; Female; Humans; Hydrocephalus; Hyponatremia; Infant; Infant, Newborn; Male; Meningitis; Natriuresis; Osmolar Concentration; Syndrome; Tuberculosis, Meningeal; Vasopressins