Alveolar liquid clearance is increased by endogenous catecholamines in hemorrhagic shock in rats

The primary objective of this study was to test the hypothesis that hemorrhagic shock would stimulate alveolar liquid clearance by a catecholamine-dependent mechanism. Anesthetized rats were hemorrhaged to a mean arterial pressure of 30 mmHg for 90 min, but they were not resuscitated. Alveolar liquid clearance was measured by the concentration of labeled and unlabeled protein over 2 h in an isosmolar physiological solution of 5% albumin that had been instilled into one lung. Hemorrhaged rats developed a severe metabolic acidosis that was associated with a 5- to 10-fold rise in plasma epinephrine levels. There was a 60% increase in alveolar liquid clearance in the hemorrhaged rats compared with control rats (55 +/- 6 vs. 34 +/- 7%; P < 0.05). Amiloride (10(-4) M) or propranolol (10(-4)M) inhibited the increase in alveolar liquid clearance. Thus the endogenous release of catecholamines associated with hemorrhagic shock markedly stimulates alveolar fluid clearance by a beta-adrenergic-mediated stimulation of active sodium transport. These data suggest a new, previously unrecognized mechanism that may protect against alveolar flooding in the acute phase of hemorrhagic shock.     

P-selectin blockade is beneficial after uncontrolled hemorrhagic shock

OBJECTIVE: Increased intra-abdominal pressure (IAP) compromises cardiopulmonary function and visceral perfusion. Our goal was to characterize acute changes in these subsystems associated with operative abdominal decompression. PATIENT POPULATION: A series of 11 consecutive injured patients monitored with a pulmonary artery catheter and nasogastric tonometer in whom operative decompression was performed. Indications for decompression included oliguria or progressive acidosis despite aggressive resuscitation in the presence of elevated IAP (>25 mm Hg). MAIN OUTCOME MEASURES: Studied hemodynamic variables included pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic volume index (RVEDVI), and cardiac index (CI). Pulmonary variables included shunt fraction (Qs/Qt) and dynamic compliance (Cdyn). Visceral perfusion was assessed using hourly urine output 4 hours before and after decompression (UOP) and gastric intramucosal pH (pHi). Mean values before and after decompression were compared using the paired t test. Linear regression and Fisher's z transformation were used to evaluate the relationships between RVEDVI, PAOP, CI, and IAP. IAP was transduced via bladder pressures. Significance was defined as p < 0.05. Data are expressed as means+/-SD. RESULTS: IAP decreased with decompression (49+/-11 to 19+/-6.8 mm Hg; p < 0.0001). RVEDVI improved independent of CI and correlated better (p < 0.01) with CI (r =0.49, p=0.04) than PAOP did (r=-0.36, p=0.09). PAOP correlated significantly with IAP (r=0.45, p=0.04). Decompression resulted in significant improvements in Qs/Qt, Cdyn, UOP, and pHi. CONCLUSION: Abdominal decompression in patients with increased IAP improves preload, pulmonary function, and visceral perfusion. Elevated IAP has important effects on PAOP, which makes the PAOP an unreliable index of preload in these patients.     

Corticosterone is involved in foot shock-induced inactivity in rats

Inescapable shock (IS) exposure induces behavioral inactivity, related to behavioral alterations in subsequent tests (i.e., escape failure, and inactivity during shuttle box task). Metyrapone (150 mg/kg, IP), a corticosterone (CS) synthesis inhibitor, administered 3 h prior to IS reduced inactivity during this aversive experience. Forty-eight hours later, when these rats were submitted to a shuttle box task, a reduction in both escape failure and inactivity was observed. These effects were reversed by CS (20 mg/kg, SC) and dose dependent of the synthetic glucocorticoid dexamethasone, both administered 1 h before IS. When metyrapone was administered 3 h before the shuttle box task to IS-exposed animals, escape failures and inactivity were markedly reduced. This effect was subsequently reversed by CS. The dynamics of changes in serum CS concentrations after both IS and shuttle box task paralleled behavioral changes. Animals injected with metyrapone before IS, which displayed active behavior, showed serum CS levels stable at their basal levels after shock, and their secretion pattern was quite attenuated after the shuttle box task, whereas vehicle-, CS alone-, and metyrapone + CS-injected animals showed higher serum CS concentrations post-IS, which slowly decreased to their corresponding basal levels. CS secretion after the shuttle box task was similar for the three groups: it had the same magnitude as after IS, though the decrease was faster. In all groups, animals displayed passive behavior. These results indicate that glucocorticoids are involved in the onset and expression of passive behaviors induced by uncontrollable stressors. Therefore, it is possible to suggest a functional relationship between CS released by exposure to inescapable stressor and the behavioral strategies adopted by rats under this stressful condition.     

Prolonged severe hemorrhagic shock and resuscitation in rats does not cause subtle brain damage

OBJECTIVE: Some patients who survived severe hemorrhagic shock (HS) seem to exhibit persistent subtle neurobehavioral deficits. This finding is of concern if limited hypotensive fluid resuscitation is applied in hypotensive victims with penetrating trauma. This study was designed to determine whether subtle brain damage would occur in rats after severe prolonged HS. We hypothesized that rats surviving HS with mean arterial pressure (MAP) controlled at 40 mm Hg for 60 minutes would recover with slight permanent brain damage in terms of cognitive function without morphologic loss of neurons and that rats surviving HS with MAP at 30 mm Hg for 45 minutes (60 minutes were not tolerated) would have grossly abnormal brain function and loss of neurons. METHODS: Under light nitrous oxide-halothane anesthesia, spontaneously breathing rats underwent MAP-controlled HS (HS phase I), volume resuscitation to normotension and invasive monitoring to 60 minutes (resuscitation phase II), and observation to 10 days with detailed assessment of cognitive function (observation phase III). Five conscious rats served as normal controls. Three treatment groups were compared: group 1, shams (11 of 12 rats survived to 10 days); group 2, HS at MAP 40 mm Hg for 60 minutes (10 of 17 rats survived); group 3, HS at 30 mm Hg for 45 minutes (10 of 14 rats survived). RESULTS: On post-HS day 10, all normal controls and all survivors of all three groups were functionally normal with overall performance category = 1 (normal) (overall performance category 1 = normal, 5 = death) and neurologic deficit scores < or = 7% (neurologic deficit scores 0-10% = normal, 100% = brain death). Post-HS beam balance, beam walking, and Morris water maze test results in HS groups 2 and 3 showed latencies not significantly different from those in shams and normal controls. Light microscopic scoring of five selectively vulnerable brain regions and other regions in five coronal sections revealed no ischemic (pyknotic, shrunken, eosinophilic) neurons in any of the survivors to 10 days. There was no statistical difference between normal controls, sham animals, and both HS groups in the number of normal neurons counted in the hippocampal CA-1 region in the 10-day survivors. All nonsurvivors died with intestinal necrosis. CONCLUSION: HS at MAP 40 mm Hg for 60 minutes or MAP 30 mm Hg for 45 minutes does not cause subtle functional or histologic brain damage in surviving rats. Controlling MAP at 30 mm Hg carries a risk of sudden cardiac arrest. These data suggest that limited fluid resuscitation, to maintain MAP at about 40 mm Hg, as recommended for victims of penetrating trauma with uncontrolled HS, is safe for the brain.     

Serotonin concentration in the blood of patients with hemorrhagic fever with renal syndrome

Differences in the concentrations of serotonin in whole blood and plasma of patients with hemorrhagic fever with the renal syndrome prompted measurements of serotonin in different components of the blood. The concentration of serotonin in whole blood was found to depend on its hemoconcentration: the higher is the hematocrit, the greater is the difference between serotonin content in the plasma and whole blood. In case of hemoconcentration or hemodilution it is impossible to assess serotoninemia from the level of serotonin in whole blood.     

GABAA receptor activation is involved in noncontingent shock inhibition of instrumental conditioning in spinal rats.

Previous work has demonstrated that the spinal cord, isolated from higher neural structures, can support a simple form of instrumental learning. Furthermore, preexposure to uncontrollable (noncontingent) shock to the leg or tail inhibits this form of learning. The present study explores the role of GABAA receptor modulation on this inhibitory effect in spinal cord-transected rats. Intrathecal administration of the GABAA receptor antagonist bicuculline blocked induction and expression of the inhibition. The GABAA receptor agonist muscimol inhibited learning in a dose-dependent manner. However, this effect was transient and showed no additivity with shock. The findings suggest that GABAA receptor activation may work like a pharmacological switch that is activated by noncontingent shock to inhibit instrumental conditioning within the spinal cord. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Function of the liver reticuloendothelial system in hemorrhagic shock in dogs

The function of hepatic reticulo-endothelial system at normal circulation and during hemorrhagic shock was examined in 13 dogs. The results were as follows:1.198Au-colloid liver scintigraphy demonstrated no essential alterations by shock. A trifling diminution caused by the diminished blood amount in the liver was found at heavy blood loss. The spleen was opcified in no case. 2. The elimination rate, resp. the blood clearance, of 198Au-colloid remained constant during the first 2 hours, proving that the vital clearance function of hepatic reticulo-endothelial system is completely maintained in this phase of hemorrhagic shock. After longer duration of hypovolemic shock (5 hours) elimination rate decreased. 3. It can be concluded that hepatic circulation at first alters according to the blood volume. 4. Consequently, functional testing of hepatic reticulo-endothelial system is not fit for early diagnosis of shock.     

Gastroduodenal resistance and neural mechanisms involved in saline flow decrease elicited by acute blood volume expansion in anesthetized rats

We have previously demonstrated that blood volume (BV) expansion decreases saline flow through the gastroduodenal (GD) segment in anesthetized rats (Xavier-Neto J, dos Santos AA & Rola FH (1990) Gut, 31: 1006-1010). The present study attempts to identify the site(s) of resistance and neural mechanisms involved in this phenomenon. Male Wistar rats (N = 97, 200-300 g) were surgically manipulated to create four gut circuits: GD, gastric, pyloric and duodenal. These circuits were perfused under barostatically controlled pressure (4 cmH2O). Steady-state changes in flow were taken to reflect modifications in circuit resistances during three periods of time: normovolemic control (20 min), expansion (10-15 min), and expanded (30 min). Perfusion flow rates did not change in normovolemic control animals over a period of 60 min. BV expansion (Ringer bicarbonate, 1 ml/min up to 5% body weight) significantly (P < 0.05) reduced perfusion flow in the GD (10.3 +/- 0.5 to 7.6 +/- 0.6 ml/min), pyloric (9.0 +/- 0.6 to 5.6 +/- 1.2 ml/min) and duodenal (10.8 +/- 0.4 to 9.0 +/- 0.6 ml/min) circuits, but not in the gastric circuit (11.9 +/- 0.4 to 10.4 +/- 0.6 ml/min). Prazosin (1 mg/kg) and yohimbine (3 mg/kg) prevented the expansion effect on the duodenal but not on the pyloric circuit. Bilateral cervical vagotomy prevented the expansion effect on the pylorus during the expansion but not during the expanded period and had no effect on the duodenum. Atropine (0.5 mg/kg), hexamethonium (10 mg/kg) and propranolol (2 mg/kg) were ineffective on both circuits. These results indicate that 1) BV expansion increases the GD resistance to liquid flow, 2) pylorus and duodenum are important sites of resistance, and, 3) yohimbine and prazosin prevented the increase in duodenal resistance and vagotomy prevented it partially in the pylorus.     

Central NO is involved in the antinociceptive action of intracisternal antidepressants in freely moving rats

The present study was performed to examine the central effects of antidepressants on nociceptive jaw opening reflex after intracisternal injection. we also investigated the mechanisms of central antinociceptive action of intracisternal antidepressants. We recorded the jaw opening reflex in freely moving rats and chose to administer antidepressants intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the spinal site of action of antidepressants. After intracisternal injection of 15 microg imipramine, digastric electromyogram (dEMG) was decreased to 76+/-6% of the control. Intracisternal administration of 30 microg desipramine, nortriptyline or imipramine suppressed dEMG remarkably to 48+/-2, 27+/-8, or 25+/-5% of the control, respectively. The suppression of dEMG was maintained for 50 min. L-NG-Nitroarginine methyl ester (NAME) blocked the suppression of dEMG from 32+/-2 to 81+/-5% of the control. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. The central NO pathway seems to be involved in the antinociception of intracisternal antidepressants at supraspinal sites.     

A GABAB-receptor mechanism is involved in the prolactin release in both male and female rats

Scintigraphy of the reticuloendothelial system (RES) was performed in 19 patients with polycythemia vera (PCV) and in 18 with secondary or relative polycythemia (PS). Bone marrow extension was found in all patients with PCV and in 11 of 18 patients with PS. The patients with PCV had a higher degree of extension than those with PS. Increased pelvic bone marrow activity was found in 16 of 19 PCV patients, but in none with PS. Splenomegaly was found in 9 patients with PCV, and in none with PS. It is concluded that RES scintigraphy in the majority of patients may differentiate between PCV and PS using the parameters pelvic bone marrow activity, bone marrow extension and splenic size.     

Indomethacin inhibits the natriuretic effects of neuropeptide Y in anesthetized rats

Neuropeptide Y (NPY) is a unique modulator of renal function that enhances urine flow and sodium excretion despite marked reductions in renal blood flow. We investigated whether the cyclooxygenase inhibitor indomethacin alters the renal NPY effects in anesthetized rats. Treatment with 5 mg/kg indomethacin i.p. lowered urinary prostaglandin excretion by approximately 85%. Systemic infusion of NPY elevated mean arterial pressure by approximately 15 mm Hg and renovascular resistance by approximately 8.0 mm Hg/ml/min, whereas the related peptide YY3-36 (PYY3-36) did not. Nevertheless, both peptides enhanced urine flow rate by approximately 250 and approximately 100 microl/15 min, respectively, and sodium excretion by approximately 15 micromol/15 min. Treatment with indomethacin did not affect NPY- and PYY3-36-induced alterations of systemic and renovascular hemodynamics but completely abolished NPY- and PYY3-36-induced diuresis and natriuresis. Endogenous creatinine clearance was not affected by any treatment. We conclude that cyclooxygenase-derived arachidonic acid metabolites are not involved in the systemic or renal hemodynamic effects of NPY and PYY3-36 but mediate NPY- and PYY3-36-induced diuresis and natriuresis.     

The Fas/Fas ligand system is involved in the pathogenesis of autoimmune myocarditis in rats

The mechanisms responsible for myocardial injury and cell death in myocarditis are still unclear. We examined whether myocardial cell death occurs via apoptosis in myosin-induced autoimmune myocarditis in rats and whether the Fas/Fas ligand (FasL) system plays a role in this apoptosis. On days 14, 17, 21, and 35 after immunization with porcine heart myosin, some cardiomyocytes and infiltrating lymphocytes were found to be apoptotic on in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay, but none was on day 60 and in control rats. Apoptotic indices peaked at day 17, and laddering of genomic DNA from the affected myocardium was observed on days 17 and 21 on agarose gel electrophoresis. The expression of Fas mRNA and protein was detected on days 17 and 21 in some cardiomyocytes and infiltrating lymphocytes by Northern blot analysis and immunohistochemistry, respectively. In addition, FasL was detected in some infiltrating lymphocytes on days 14, 17, and 21 by both in situ hybridization and immunostaining, and FasL-positive lymphocytes were mainly CD4+ cells. Some rats were injected with anti-Fas Ab (0.1 mg/kg) or anti-FasL Ab (0.1 mg/kg), and subsequently, inflammatory lesions exhibited less severe than did untreated rats with myocarditis. These findings suggest that cell death via apoptosis of cardiomyocytes and lymphocytes is one of the mechanisms of myocardial injury in autoimmune myocarditis, and that the Fas/FasL system might play a role in the induction of this apoptosis.     

The septohippocampal system is involved in prepulse inhibition of the acoustic startle response in rats.

Prepulse inhibition (PPI) of the acoustic startle response (ASR) can be used as an operational measure for brain mechanisms that prevent disruption of ongoing stimulus processing routines by other stimuli and that thereby avoid behavioral interference. Deficient PPI has been observed in schizophrenics; therefore, much interest has been devoted to the understanding of the neural basis of PPI. This study investigated the role of the septohippocampal system in the modulation of PPI in rats. Stimulation of the medial septum by injection of the glutamate agonist kainate led to a profound disturbance of PPI and reduced the ASR amplitude. The PPI deficit induced by intraseptal kainate was attenuated by systemic or intrahippocampal administration of the acetylcholine antagonist scopolamine. Lesions of the medial septum, made by the neurotoxin AMPA, did not affect PPI. The present data indicate that activation of the septohippocampal system reduces PPI of the ASR, suggesting its role in sensorimotor gating. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunohistochemical study of myoglobin deletion from myocardium in hemorrhagic shock

Myoglobin (MB) deletion from myocardium in the case of hemorrhagic shock was firstly studied by immunohistochemical and morphometry technique. The results showed that there were different degrees of segmental deletion of MB from myocardium in each case of hemorrhagic shock which has continued over an hour. The significance of these changes in forensic medicine are discussed.     

CNS regulation of blood lactate concentration in anesthetized rats

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.     

Role of ischemia in the induction of changes in cell membrane during hemorrhagic shock

Herbal preparations, designed to be smoked or ingested for "health and happiness", are promoted as legal hallucinogens, euphoriants, and marihuana substitutes. A total of 25 psychoactive substances have been identified in these products, and a number of intoxications have resulted from their short- or long-term use. Physicians should be alerted to the nature of these effects when taking drug histories, and their possible role in the causation of medical complaints should be considered.     

Reevaluation of the linkage between acute hemorrhagic shock and bacterial translocation in the rat

The present study was undertaken to determine the conditions under which acute periods of hemorrhagic shock induce bacterial translocation. Rats (at least six per group) were anesthetized intraperitoneally with the barbiturate, pentobarbital (50 or 65 mg/kg), or the inhalation anesthetic methoxyflurane. Following anesthesia, the femoral artery was catheterized, from which blood was withdrawn to maintain a mean arterial blood pressure of 30 mmHg for 30, 60, or 90 min, followed by reinfusion of shed blood. Instrumented, but nonshocked animals served as controls. Rats were sacrificed at 0, 2, or 24 hr postshock, and quantitative bacterial cultures of the mesenteric lymph node complex (MLN), liver, and spleen were made. Within groups, the effects of heparinization were also determined. In pentobarbital-treated animals, regardless of the extent of heparinization, consistent translocation to both MLN and distant organs occurred when shock was prolonged for 90 min, and assessment of translocation was made 24 hr after reinfusion of shed blood. Furthermore, a mortality rate of approximately 30% was found in rats subjected to this protocol. The magnitude of translocation was less consistent, and did not differ from that in sham shock controls, under other conditions of shock and evaluation. In rats anesthetized with methoxyflurane, no mortality occurred, and no statistical significance between the incidence or degree of translocation in shocked animals vs. sham shock controls could be demonstrated, regardless of the shock protocol. In additional studies, effects of these anesthetics on intestinal morphology and superior mesenteric arterial (SMA) flow in the context of hemorrhagic shock were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)