Alterations of vasoconstrictor and sodium-regulating hormone systems in vascularly decompensated liver cirrhosis

Plasma levels of atrial natriuretic peptide (ANP), aldosterone (PA), vasopressin (AVP), and the plasma renin activity (PRA) were examined in 15 vascularly decompensated patients suffering from liver cirrhosis, before and after administration of albumin and after a subsequent administration of furosemide. The initial ANP level was lower in 9 patients (group "A") and higher in 6 patients (group "B") than in healthy controls (Group "A": 19.5 +/- 3.0 fmol/ml; group "B": 36.7 +/- 3.9 fmol/ml; control: 25.8 +/- 2.4 fmol/ml). The initial PRA (4.4 +/- 1.0 ng AngI/ml/h) and AVP (8.5 +/- 1.5 pg/ml) activity in group "A" increased significantly compared to group "B" (PRA: 0.44 +/- 0.09; AVP: 4.1 +/- 0.5), indicating an intravascular volume depletion in group "A". Albumin infusion raised the urine and sodium excretion and the plasma concentration of ANP in group "A" but lowered in plasma levels of renin and vasopressin. The same parameters were not changed by albumin in group "B". Furosemide equally raised the urine flow rate and sodium excretion in both groups. Plasma ANP level depends on the intravascular volume, and the secondary change in its plasma concentration plays a considerable role in the retention of fluid and electrolytes in patients with cirrhosis. The increased intravascular volume in these patients depletes the fluid and electrolyte retention via the increase in ANP level.     

Effects of oral salt load on arginine-vasopressin secretion in normal subjects

Arginine-vasopressin (AVP) plays an important role in regulating water balance in humans. Its secretion is under control of several mechanisms, some of which are not completely understood. The purpose of the present study was to evaluate the effects of an acute oral salt load on AVP secretion in normal subjects. Six normal volunteers received 350 mEq of NaCl per os. Pulmonary capillary wedge pressure and right atrial pressure, plasma AVP, plasma sodium and potassium concentration, plasma osmolality, hematocrit, urinary sodium and potassium excretion, and urinary flow were measured at baseline and every 30 minutes for two hours after the salt load. Hemodynamics as well as urinary sodium and potassium excretion did not change over the study. Ninety minutes after the salt load, plasma AVP increased from the basal value of 6.0 +/- 0.9 pg per ml to 10.1 +/- 1.2 pg per ml (mean +/- SE, p less than 0.005) and a significant reduction in diuresis of about 50% was observed. However, plasma osmolality and plasma sodium concentration increased significantly only 120 min after the salt load, from the initial value of 277.7 +/- 2.2 mOsm per kg and 145.3 +/- 1.4 mEq per 1 (mean +/- SE) to 284.8 +/- 2.5 mOsm per kg and 148.7 +/- 1.5 mEq per 1, respectively (p less than 0.01). Ninety minutes after the salt load, no correlation was found between plasma osmolality and plasma AVP concentration, indicating that AVP secretion was independent of changes in systemic blood osmolality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inappropriate drinking and secretion of vasopressin after caval constriction in dogs

The object of this study was to determine if chronic thoracic vena caval constriction affected mechanisms regulating water balance, independent of known changes in sodium metabolism in the dog. Fluid and electrolyte balances were determined for 5 days before and 14 days after constriction of the vena cava (n = 5) and in a separate population of time controls (n = 4). Cardiac output was reduced and heart rate was increased in response to chronic caval constriction although blood pressure was maintained at control levels. Water intake and plasma arginine vasopressin (AVP) increased from 31 +/- 4 ml/kg and 1.3 +/- 0.2 pg/ml during the control period to 81 +/- 6 ml/kg and 3.4 +/- 0.6 pg/ml during the period of caval constriction. The caval dogs developed a positive water balance, which preceded the development of a positive sodium balance. This led to a significant fall in plasma osmolality from a control mean of 296 +/- 1 to 284 +/- 4 mosmol/kg during caval constriction and dilutional hyponatremia. Plasma and blood volume increased significantly in response to constriction and were accompanied by formation of 123 +/- 10 ml/kg of ascitic fluid. These results show that water intake and plasma levels of AVP were increased in spite of a fall in plasma osmolality and an increase in vascular volume. These responses cannot be secondary to sodium retention because water was retained in excess of sodium hence hyponatremia. Therefore, chronic caval constriction causes a profound primary disturbance in mechanisms regulating water balance, which may contribute to the formation of edema fluid.     

Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism.

The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.     

Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in rats

We investigated the effects of chronic administration of sertraline (SERT; approximately 20 mg kg(-1) day(-1) in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 +/- 0.5 versus 20.0 +/- 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT-treated rats (1.6 +/- 0.5 versus 10.2 +/- 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 +/- 1.3 versus 1.2 +/- 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 +/- 0.36 versus 1.31 +/- 0.16 pg ml(-1), P < 0.005; OT, 17.16 +/- 1.06 versus 11.3 +/- 1.03 pg ml(-1), P < 0.0009, at the third week post-treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT.     

Mannitol-induced hyperosmolality and cerebrospinal fluid vasopressin in anesthetized cats

Arginine-vasopressin (AVP) has been found to influence brain water. Since AVP is released by hyperosmolality into plasma we determined the role of AVP in controlling cerebrospinal fluid (CSF) pressure. Adult cats were anesthetized with pentobarbital and samples of plasma and cisternal CSF were collected 1 or 2 h before i.v. infusion of 2 g/kg of mannitol and for 2 h afterwards. We found a significant increase in plasma osmolality from 320.0 +/- 1.6 to 331.6 +/- -3.4 mOsm/l (mean +/- S.E.M.), while CSF osmolality was unchanged. Prior to mannitol infusion, AVP was elevated to 105 +/- 19 pg/ml in plasma and to 136 +/- 19 pg/ml (mean +/- S.E.M.) in CSF. After infusion of mannitol AVP levels were unchanged in either plasma or CSF. The reduction of CSF pressure by mannitol is independent of AVP in the anesthetized cat.     

Renal prostaglandin E2 secretion and excretion in conscious dogs.

Renal prostaglandin E2 (PGE2) secretion and excretion rates were determined in nine conscious dogs. Renal venous (RV) and urine PGE2 concentrations were measured by radioimmunoassay. In 21 controls tests RV PGE2 ranged from 37 to 215 pg/ml, with a mean concentration of 97 +/- 11 pg/ml. Basal left kidney PGE2 secretion was 317 +/- 42 pg.g-1.mm-1. Urine PGE2 concentration averaged 8,320 +/- 1,510 pg/ml with a PGE2 excretion rate of 3,260 +/- 480 pg/min from both kidneys. Indomethacin (2 mg/kg) reduced RV and urine PGE2 concentrations by 60 and 77%, respectively. Meclofenamate (2 mg/kg) decreased RV and urine PGE2 concentrations by 36 and 48%, respectively. PG inhibition had no significant influence on blood pressure or renal blood flow (RBF). PG inhibition reduced urine flow rate and increased urine osmolality. Indomethacin had no effect on urine sodium concentration or sodium excretion; meclofenamate increased urine sodium concentration and slightly diminished sodium excretion. These data demonstrate that PGE2 is released from the kidney in a conscious animal and that both indomethacin and meclofenamate significantly reduce the renal secretion and excretion of PGE2. In a normal, conscious animal prostaglandins do not control blood pressure or RBF but are involved in the excretion of water.     

Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion in septic patients with trauma

We investigated whether microalbuminuria/urinary creatinine ratio (MACR) is increased in septic patients with trauma and whether polymyxin B immobilized fiber (PMX-F) treatment decreases MACR. Twelve trauma patients without sepsis, 18 trauma patients with sepsis, and 10 healthy controls were included in this study. The 18 trauma patients with sepsis were randomly assigned to one of two groups, PMX-F treatment or conventional treatment. Urinary microalbumin and creatinine were measured before and after treatment. Plasma endotoxin levels were determined by endospecy test. Hemoperfusion with PMX-F was carried out twice, for 2 hours, at a flow rate of 100 ml/min. MACR increased in the 30 trauma patients (5.2+/-2.2 mg/mmol) in comparison to that in the healthy controls (1.0+/-0.6 mg/mmol, p < 0.01). In the 18 trauma patients with sepsis, MACR after sepsis (16.6+/-4.8 mg/mmol) was significantly greater than that before sepsis (5.5+/-2.3 mg/mmol, p < 0.01). There was a significant correlation between plasma endotoxin levels and MACR in septic trauma patients (p < 0.001). MACR was reduced from 17.0+/-5.0 mg/mmol to 4.2+/-1.5 mg/mmol (p < 0.01) with PMX-F, and plasma endotoxin levels were also reduced from 34.5+/-18.5 pg/ml to 10.8+/-6.6 pg/ml (p < 0.01). Neither MACR nor plasma endotoxin levels were affected by conventional treatment, however. In summary, trauma patients with sepsis appear to show increased MACR, and PMX-F therapy may be effective for attenuating the increase in MACR.     

Effect of chronic acamprosate treatment on voluntary alcohol intake and beta-endorphin plasma levels in rats selectively bred for high alcohol preference

Our previous studies have shown that repeated acamprosate administration to ethanol-naive Warsaw high preferring (WHP) rats resulted in increased plasma beta-endorphin levels and at least partially prevents increases in levels of this peptide after a single administration of ethanol compared with untreated control rats. The objective of the present study, which included 45 WHP rats, was to continue the past research and investigate the effect of 10-day acamprosate treatment (200 mg/kg p.o.) on alcohol intake using a free-choice procedure and on changes in plasma beta-endorphin levels while alcohol is available, and 10 days after alcohol withdrawal. Voluntary alcohol consumption increases plasma levels of beta-endorphin from 440+/-25 pg/ml to 711+/-57 pg/ml (p=0.0002). After a 10-day of alcohol withdrawal, the levels of this peptide were significantly reduced compared with levels in rats with free access to ethanol (711+/-57 pg/ml vs. 294+/-38 pg/ml, p=0.000001) and in control naive rats (440+/-25pg/ml vs. 294+/-38pg/ml, p=0.044). Chronic treatment with acamprosate increased plasma beta-endorphin levels both in WHP rats with free access to ethanol (440+/-25 pg/ml vs. 616+/-49 pg/ml, p=0.008) and in rats after ethanol withdrawal (440+/-25 pg/ml vs. 620+/-56 pg/ml, p=0.007). In the group with free access to ethanol, there was a significant reduction in mean ethanol intake, from 6.75+/-0.20 g/kg body weight/day to 4.68+/-0.25 g/kg/day. Our results indicate that chronic acamprosate treatment may have beneficial effects, as it increases the beta-endorphin concentration thereby compensating for beta-endorphin deficiency during ethanol withdrawal. As the endogenous opioid system has an important role in the development of craving for alcohol, restoring the alcohol-induced deficits in beta-endorphin levels may be an important factor to prevent craving and maintaining abstinence. We suppose that the anti-craving mechanism of acamprosate that has been reported to abolish excessive glutamate release during alcohol withdrawal may be accompanied by compensation for the beta-endorphin deficiency.     

Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women

Elevated plasma prolactin and mild hypocortisolemia have been observed in patients with rheumatic disorders. This study was designed to assess the potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary-adrenocortical function. Hypoglycemia was induced by intravenous insulin injection (0.1 IU/kg) in 10 female volunteers of fertile age during their follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo administration. Blood samples were collected from an indwelling catheter inserted into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine and glucose were measured in plasma. Domperidone administration significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14 +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol, norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and 139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/- 62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at 30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine responses to hypoglycemia was similar in both groups. We observed mild norepinephrine response to hypoglycemia but this was irrespective of the medication. In conclusion, pharmacologically-induced hyperprolactinemia did not induce significant changes of hypothalamic-pituitary-adrenocortical function and did not influence sympathoadrenal activity in healthy young women.     

Synergistic interaction of corticotropin releasing factor and arginine vasopressin on adrenocorticotropin and cortisol secretion in Macaca fuscata

Plasma immunoreactive CRF measured by radioimmunoassay decreased rapidly after intravenous injection of synthetic ovine corticotropin releasing factor (CRF) and showed a bi-exponential decay curve in five macaca fuscatas. Half lives of plasma immunoreactive CRF were 5.8 +/- 1.4 (Mean +/- SEM) min for the fast component and 38.3 +/- 2.4 min for the slow component. A bolus injection of 5 micrograms/kg CRF significantly increased the plasma cortisol level. CRF at 5 micrograms/kg induced a delayed response of ACTH and cortisol. Arginine vasopressin (AVP) at 0.5 micrograms/kg induced a slight increase in plasma ACTH and cortisol, but AVP at 0.1 micrograms/kg evoked no significant increase. When 0.5 micrograms/kg CRF and 0.1 micrograms/kg AVP were administered simultaneously, significant ACTH and cortisol responses occurred. The results indicate that CRF and AVP act synergistically to stimulate ACTH secretion in vivo.     

Renal response to captopril in conscious dogs pretreated with indomethacin

This study was designed to determine whether the prostaglandins mediate the renal effects of captopril in the conscious sodium-replete dog. In a group of control animals (n = 9), effective renal plasma flow (ERPF) increased from 185 +/- 15 to 230 +/- 12 ml/min and plasma renin activity (PRA) increased from 0.64 +/- 0.15 to 12.9 +/- 1.1 ng ANG I . ml-1 . h-1 after captopril (10 mg/kg bolus plus 10 micrograms . kg-1 . min-1 i.v.) administration. Glomerular filtration rate (GRF) and sodium excretion (UnaV) were also increased significantly following captopril treatment, whereas urine volume (V), potassium excretion (UkV), mean arterial pressure (MAP), and heart rate (HR) remained unchanged throughout the experiment. When the same dose of captopril was given to indomethacin-pretreated dogs (5 mg/kg bolus plus 2 micrograms . kg-1 . min-1 i.v.), ERPF increased from 170 +/- 8 to 265 +/- 18 ml/min and PRA increased from 1.2 +/- 0.4 to 14.6 +/- 3.0 ng ANG I . ml-1 . h-1 after the captopril, while UnaV, UkV, and V remained unchanged. These data demonstrate that the prostaglandins do not mediate the ability of captopril to increase PRA or effective renal plasma flow in this experimental model.     

Renal response to central volume expansion induced by water immersion (WI) in heart transplant patients

This work was aimed to assess the secretion of volume related hormones in heart transplant patients (HTP) and their relationship to excretory renal function studied under bed rest and water immersion conditions. Fractional sodium (FENa%) and potassium (FEK%) clearance, plasma renin activity (PRA), plasma aldosterone (Ald), vasopressin (AVP) and atrial natriuretic peptide (ANP) were estimated in six HTP with moderate renal failure (C creat = 69 +/- 6.9 ml/min) and in 10 healthy subjects (N) (C creat = 110 +/- 2.0 ml/min). All HTP were treated with cyclosporine A and azathioprine. In HTP basal AVP (6.18 +/- 0.92 pg/ml) and ANP (138.17 +/- 14.69 pg/ml) levels were significantly higher than in normals (2.07 +/- 0.11 pg/ml and 74.10 +/- 7.10 pg/ml, respectively). HTP were also characterized by increased FENa% and FEK% both under bed rest (DI) and water immersion (WI) conditions. As abnormalities of excretory renal function in HTP were not significantly related to the plasma endocrine profiles factors other than PRA, Ald, AVP and ANP seemed to be also involved in their pathogenesis.     

Vasopressin in cerebrospinal fluid and plasma of man, dog, and rat

Arginine-8-vasopressin (AVP) levels were measured by a sensitive and specific radioimmunoassay (RIA) in plasma and cerebrospinal fluid (CSF) of three species man, dog, and rat (Wistar and the Brattleboro strain). Basal plasma values were 1.7 pg/ml in Wistar rat, and 2.4 pg/ml in dog. Pentobarbitone, used as anesthetic during collection of CSF from dog and rat, caused a significant rise of plasma AVP values in Wistar rats, but not in dogs. After withdrawal of CSF, the plasma AVP levels of Wistar rats were increased to 29.5 +/- 9.5 pg/ml, whereas the CSF levels from the same animals were 11.5 +/- 3.9 pg/ml. The response to the various stimuli was similar in Brattleboro rats, heterozygous for hereditary hypothalamic diabetes insipidus, and in Wistar rats. In Brattleboro rats, homozygous for hereditary hypothalamic diabetes insipidus, AVP was neither detectable in plasma nor in CSF. In dog and man, AVP levels in CSF samples were higher than in simultaneously obtained plasma samples. The possibility that AVP present in CSF, might be released directly from the synthetizing hypothalamic nuclei into the ventricular system is discussed.     

The effect of trimetazidine on C-reactive protein, cytokines and adhesion molecules in the course of acute myocardial infarction

The aim of this randomised, double-blind, placebo controlled, parallel group study was to assess the effect of trimetazidine (TMZ), a potent antiischaemic drug, on plasma C-reactive protein (C-RP), cytokine and adhesion molecule levels. The study population consists of 18 patients (16 males, 2 females, average age 56.45 +/- 10.97 years) with acute myocardial infarction admitted within 6 hours after onset of symptoms and treated with streptokinase. Blood samples were taken at 3-hour intervals during the time of treatment. All patients were randomised blindly using a centralised randomisation process, between trimetazidine (40 mg bolus i.v. then 60 mg per day for 48 hours intravenously in glucose infusion) or placebo group. Plasma C-RP level was significantly lower in TMZ group (39.5 mg/ml +/- 9.7 mg/ml) as compared to placebo (75.7 +/- 29.4 mg/ml, p < or = 0.001) and peaked 28 hours later in TMZ group. Plasma interleukin 6 (IL 6) level showed a sharp peak 9 hours after the onset of the symptoms in TMZ group (116.9 +/- 180.2 pg/ml vs. 45.4 +/- 37.9 pg/ml) and was increased up to 30 hours after the onset of the symptoms. Plasma interleukin 1 beta (IL 1 beta) was also higher in TMZ group notably 21 hours after the onset of symptoms (26.4 +/- 9.3 pg/ml vs. 16.2 +/- 2.4 pg/ml). TMZ group showed lower plasma E-selectin levels. Plasma IL 8, TNF alpha and ICAM 1 levels were without statistical significant differences. The present study demonstrates a significant reduction of plasma C-reactive protein level in the course of acute myocardial infarction treated with streptokinase and intravenous trimetazidine infusion compared with the group of patients without trimetazidine treatment.     

Moderate hypothermia with low flow rate cardiopulmonary bypass used in surgeries for congenital heart defects

Low flow rate perfusion has been recommended in profound hypothermic cardiopulmonary bypass (CPB) in recent years. However, most patients with congenital heart defects are still operated on under moderate hypothermic CPB, where high flow rate perfusion has been adopted by most perfusionists. Fifty patients with congenital heart defects, ranging from 1 to 11 yr of age and 6.5 to 25 kg of weight, were included in the trial. Once on CPB, a high flow rate of 2.37 +/- 0.39 L/min/m was used to cool the patient to 27.3 degrees C +/- 0.84 degrees C rectal temperature, followed by a low flow rate of 1.31 +/- 0.09 L/min/m until the main intracardiac repair was completed and rewarming started. High flow rate was still used in rewarming the patients to a rectal temperature of 35 degrees C-36 degrees C. The total CPB, cross-clamp, and low flow rate perfusion time were 86.4 +/- 26.6, 46.4 +/- 22.3, and 40.7 +/- 22.4 min, respectively. After 24-99 min low flow rate perfusion, venous oxygen saturation remained above 80% for all the patients, and lactate concentration did not increase. Only three patients showed slight metabolic acidosis during CPB and required an extra 6-12 mEq sodium bicarbonate. Average urine output was 199 +/- 155 (50-600) ml during CPB. All patients recovered well after operation. No surgical death or neurologic complications occurred. Low flow rate perfusion might be safely used in moderate hypothermic CPB as long as the oxygen saturation of returned venous blood was kept above 80%.     

Effects of water deprivation and hyperhydration in pregnant and lactating goats

The response to 30 h water deprivation was studied in 7 goats during the last month of pregnancy and during lactation with anestrus as the control period. Plasma osmolality and plasma Na concentration increased by about 4% in pregnant and lactating goats and by about 2% in anestral goats. Plasma AVP concentration rose by about 7 pg/ml in pregnant and lactating goats, but only by about 3 pg/ml during anestrus. PRA was elevated in pregnant animals, but dehydration caused only a minor further rise. Total plasma protein concentration was low in pregnant goats and did not increase during water deprivation, but it did so in lactating animals. Neither the hematocrit nor the plasma K concentration changed in response to dehydration. GFR fell by about 24% in pregnant goats and by 22% in lactating animals, but remained unchanged during anestrus. ERPF fell by 20% in lactating animals, but no consistent effect of the dehydration was seen during pregnancy and anestrus. Urine flow decreased by about 75% during pregnancy, 55% during lactation and 65% during anestrus with the highest urine osmolality observed during anestrus. Milk production was only slightly reduced, but the milk osmolality increased in parallel with that of the blood plasma. When allowed to drink at the end of the water deprivation period, pregnant goats immediately drank 2.5 +/- 0.5 litres, lactating goats 3.3 +/- 0.9 litres and anestral goats 1.1 +/- 0.3 litres. When hyperhydrated, pregnant goats excreted the excessive water more readily and showed less response to exogenous AVP than lactating and anestral animals. In conclusion, pregnant and lactating goats are obviously more susceptible to a shortage of water supply than anestral animals but can easily excrete an excess of water.     

Ontogeny of endocrine (ACTH, vasopressin, cortisol) responses to hypotension in lamb fetuses

We studied the ACTH, vasopressin (AVP), and cortisol responses to nitroprusside-induced hypotension in 27 chronically cannulated lamb fetuses between 0.53 and 0.98 gestation. Age-related differences in the hormonal responses to hypotension were found. Hypotension was associated with peak AVP levels of 7.8 +/- 2.7 pg/ml (mean +/- SE) in animals less than 0.68 gestation and 63.5 +/- 20 pg/ml in animals 0.89-0.98 gestation (P less than 0.05). The peak ACTH response was 95 +/- 20 pg/ml in the youngest animals and 380 +/- 111 pg/ml in animals 0.83-0.88 gestation (P less than 0.05). These observations suggest that maturation of the systems (possibly neuroendocrine) subserving the hormonal responses occurs in utero. Fetal plasma cortisol levels did not increase in response to the increase in ACTH except in animals 0.89-0.98 gestation. At this time, the basal plasma cortisol levels were high (58.8 +/- 16.8 pg/ml) and the ACTH response to hypotension was attenuated. Taken together, these findings suggest functional negative feedback regulation of ACTH by cortisol in the late gestation fetus.     

Influence of surgical procedures on interleukin-6 and monocyte chemotactic and activating factor responses: CABG vs. valvular surgery.

Interleukin-6 (IL-6) and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1) play pivotal roles in systemic inflammation, immune response, and tissue damage after cardiopulmonary bypass (CPB). Previous reports have described transient rises in IL-6 and MCAF after CPB, but the data seem to vary according to the different surgical procedures used. To evaluate the influence of the different surgical procedures on the proinflammatory cytokine responses, we compared perioperative serum IL-6 and MCAF release in coronary artery bypass grafting (CABG) and valvular surgery cases. Eighteen CABG (CABG group) and 7 single valvular cardiac surgery patients (valve group) were included in this study. Blood samples were taken to measure the serum concentrations of IL-6 at the induction of anesthesia, at the removal of the aortic cross-clamp, at the end of CPB, at the end of surgery, and 24 h after the termination of surgery. Serum IL-6 and MCAF were assayed by ELISA. Serum IL-6 increased immediately after aortic declamping and reached its peak at the end of surgery in both groups. Serum IL-6 concentrations at the end of surgery and 24 h after surgery were significantly higher in the valve group than in the CABG group (123.9 +/- 21.7 pg/ml vs. 79.7 +/- 10.4 pg/ml, p = 0.049; 113.6 +/- 25.0 pg/ml vs. 39.9 +/- 11.5 pg/ml, p = 0.006, respectively). Serum MCAF increased immediately after aortic declamping, and the MCAF level at the end of surgery was significantly higher in the valve group than in the CABG group (1118.4 +/- 353.9 pg/ml vs. 241.0 +/- 71.2 pg/ml, p = 0.002, respectively). IL-6 and MCAF may play important roles in the pathophysiology of surgical damage with CPB, and the different surgical procedures appear to affect the proinflammatory cytokine release after cardiac surgery differently.     

Neurovascular and hemodynamic responses to hyperinsulinemia in healthy postmenopausal women

Acute hyperinsulinemia produces sympathetic activation, vasodilation, and cardiovascular changes in healthy young men. Postmenopausal period is accompanied by sympathetic, vascular and cardiovascular changes. Nevertheless, the effects of acute insulin infusion were not known in postmenopausal women. To study this aspect, 26 postmenopausal healthy women were submitted to an euglycemic hyperinsulinemic clamp performed during 120 min. Heart rate (HR: ECG), blood pressure (BP: oscillometric method), forearm blood flow (FBF: plethysmography), plasma norepinephrine (NE), plasma epinephrine (EP), and cardiovascular autonomic modulation (spectral analysis of R-R interval and BP variabilities) were measured before and during the clamp. Glycemia was kept similar to baseline during the clamp (84.6+/-1.2mg/dl versus 87.1+/-1.6 mg/dl), while plasma insulin increased significantly to a level of 89.3+/-5.6 microU/ml. Insulin infusion significantly increased plasma NE (+45+/-17 pg/ml), EP (+20+/-9 pg/ml), and low to high frequency ratio of R-R interval variability (LH/HF: 1.2+/-0.4), but did not change low frequency component of BP variability. FBF (+0.7+/-0.2 ml min(-1)100ml(-1)) was also significantly enhanced by hyperinsulinemia. HR and systolic BP increased with insulin infusion (+4+/-1 bat/min and +6+/-2 mmHg, respectively, P<0.05), while diastolic BP did not change. In conclusion, in healthy postmenopausal women, acute hyperinsulinemia produces sympathetic activation, and vasodilation, which results in HR and systolic BP enhancements, with no change in diastolic BP. This pattern of response is similar to the one usually observed in healthy young men.