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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because sepsis is characterized by a depression in vascular reactivity, we hypothesized that changes in organ blood flows (Q) would differ between the nonseptic and septic state during the infusion of sympathomimetics. Therefore we examined the (sepsis x organ Q) interaction during the infusion of five sympathomimetics in 36 mature, awake sheep before and after cecal ligation and perforation produced hyperdynamic sepsis. A 3-hour infusion of dobutamine, norepinephrine, dopamine, dopexamine, or salbutamol was compared with that of placebo during both nonseptic and septic studies; drug infusion was titrated to an increase in cardiac index of greater than 20%. Increased plateau infusion doses of norepinephrine (+305%), salbutamol (+275%), dopamine (+70%), and dobutamine (+49%) were required to achieve predefined treatment guidelines during the septic versus nonseptic study. Few differences in the regional effects of individual sympathomimetics were found in the nonseptic study, although infusion of sympathomimetics was accompanied by a redistribution of systemic Q toward the heart and away from the brain, kidney, small intestine, liver, and pancreas. In the septic study, however, the sympathomimetic infusions were not accompanied by the redistribution of Q away from small intestine and liver that was demonstrated in the nonseptic study. Therefore (1) the depressed vascular reactivity in hyperdynamic sepsis altered the dose profile of exogenous sympathomimetics required to augment systemic Q, and (2) the (sepsis x sympathomimetic) interaction was characterized by a depression in the anticipated redistribution of organ Q from "nonvital" to "vital" circulations.
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PMID:The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis. 151 72

Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR). For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased. In survivors, these abnormalities reverse to normal within 7 to 10 days. The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia. In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high-energy stores, or abnormal myocardial oxygen utilization. However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury. The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time. The pathophysiology of this disease is complex. Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock. Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate. Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease.
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PMID:Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock. 151 2

Although hepatocellular dysfunction occurs early in sepsis despite fluid resuscitation, it is unknown if an increased volume of resuscitation protects hepatocellular function. To study this, rats were subjected to sepsis by cecal ligation and puncture (CLP). These and sham-treated rats then received either 3 or 6 mL/100 g BW normal saline subcutaneously. Studies were performed at 5 hours (i.e., early sepsis) or 20 hours (late sepsis) after CLP. Hepatic blood flow was determined by radioactive microspheres, 3H-galactose clearance technique, and laser Doppler flowmetry in both groups. Active hepatocellular function (i.e., Vmax and Km) was assessed by an in vivo indocyanine green clearance technique. The results indicate that: (1) hepatic blood flow increased markedly in early sepsis; (2) Vmax and Km decreased significantly at 5 hours and 20 hours after CLP; and (3) the increased volume of fluid resuscitation did not improve the depressed active hepatocellular function 5 hours following CLP. Cardiac output and hepatic microcirculation, however, were significantly increased in early sepsis. These results confirm the notion that the depression in hepatocellular function in early sepsis is not the result of any reduction of hepatic perfusion. The dissociation of increased hepatic blood flow from depressed hepatocellular function remains despite the larger volume of resuscitation. The hepatocellular dysfunction that occurs even in early sepsis cannot be corrected simply by increasing the volume of crystalloid resuscitation.
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PMID:Hepatocellular dysfunction persists during early sepsis despite increased volume of crystalloid resuscitation. 154 29

Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.
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PMID:Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism. 156 25

Tumor necrosis factor-alpha (TNF alpha) has been implicated as an endogenous mediator of the cardiovascular manifestations of sepsis and septic shock. We studied the acute effects of a single dose (50 or 200 micrograms/kg) of intravenous recombinant human TNF alpha (rhTNF alpha) on myocardial function in halothane-anesthetized dogs. Regional cardiac dimensions were measured by using sonomicrometry. Intracavitary left ventricular, ascending aortic, and pulmonary artery pressures were measured by use of micromanometers. Cardiac index was determined by means of thermodilution. Myocardial performance was analyzed by assessing changes in the slope of the left ventricular end-diastolic length-stroke work relationship obtained by performing transient vena caval occlusions. Animals were resuscitated by means of normal saline solutions to maintain baseline regional end-diastolic length. Over a 3-hour period of observation, rhTNF alpha decreased systemic vascular resistance index, but the cytokine did not compromise intrinsic myocardial performance. The circulatory response to rhTNF alpha was a hyperdynamic state characterized by tachycardia, augmented cardiac index, and increased intrinsic myocardial contractility (leftward shift of the left ventricular end-diastolic length-stroke work relationship). In addition, rhTNF alpha caused systemic acidosis and increased plasma levels of prostacyclin metabolite (6-keto-prostaglandin F1 alpha). After the dose of rhTNF alpha large volumes of fluid were required to maintain baseline end-diastolic length. We conclude that in the acute setting, rhTNF alpha elicits abnormalities in peripheral vascular tone that are not accompanied by depression of myocardial function.
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PMID:Load-insensitive assessment of myocardial performance after tumor necrosis factor-alpha in dogs. 159 65

Hypovolemic hyponatremia attributable to severe fluid and electrolyte alterations was diagnosed in a foal with diarrhea. Subsequent consumption of water resulted in rapid reduction of serum sodium concentration and serum osmolar depression. Clinical signs of neurologic disease developed including blindness, loss of menace response, and seizures. Treatment of this condition with IV administered fluids included hypertonic saline solution (7.2%; 2 ml/kg of body weight), and frequent monitoring of serum electrolyte concentrations and osmolality resulted in gradual correction of the fluid and electrolyte imbalance and resolution of the neurologic signs. Hyponatremia has been recognized in foals with renal failure, ruptured urinary bladder, and iatrogenic water overload. The key to diagnosis and management of profound hyponatremia is accurate diagnosis of the status of plasma volume and association of the electrolyte imbalance with clinical signs of neurologic disease. This report describes an unusual complication of a commonly encountered problem in equine practice and documents that the severe metabolic and electrolyte abnormalities associated with diarrhea can result in clinical neurologic disease. The differential diagnosis also should include bacterial sepsis, parasitism, thoracic mass, acute renal failure, congenital neurologic deficit, or seizure syndrome. Serum electrolyte disorders should be considered as a potential cause of signs of neurologic disease in foals with diarrhea.
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PMID:Hypovolemic hyponatremia and signs of neurologic disease associated with diarrhea in a foal. 160 18

Ventilatory depression and apnea are well-known early pulmonary responses of sepsis in infants, yet their underlying mechanisms are not understood. To further elucidate the pathophysiology, we induced Escherichia coli septicemia in piglets and studied the sequential changes in intrapulmonary shunt (QS/QT), physiological dead space (VD/VT), minute ventilation (VE), and blood gases for up to 6 hours of lethal sepsis. Lung lymph was also collected and extravascular lung water (EVLW) was measured. Histology confirmed that interstitial edema developed 1 hour after E. coli infusion. These data suggest that high permeability pulmonary edema and hypoxemia following early intrapulmonary shunt increase may be the causes of septic ventilatory depression.
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PMID:[An experimental study on the pathophysiology of septic ventilatory depression]. 165 Jun 39

Although often not considered, the heart is one of the targets of multiple organ failure in sepsis and septic shock, with myocardial depression being a prominent component of this "acute septic cardiomyopathy". Hypotheses concerning the etiology of this depression are increasingly elucidated on a cellular level, including dysfunction of the beta-adrenoceptor/G protein/adenylate cyclase system, calcium channel blockade by cardiodepressant factor, contractile impairment by activated leucocytes, as well as inhibition of protein synthesis by Pseudomonas exotoxin A. In the search for "mechanisms of myocardial depression in sepsis", isolated cardiomyocytes may play a role as research tools with respect to: a) discrimination between direct and indirect cardiodepressant effects; b) identifying not only the acute, but also chronic toxin- and mediator-induced cardiodepression; c) clarification of the mechanism of action of cardiodepressant bacterial toxins and sepsis mediators; d) establishment of in vitro models of leucocyte-mediated cardiodepression in sepsis.
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PMID:Mechanisms in acute septic cardiomyopathy: evidence from isolated myocytes. 166 46

Hyperbilirubinaemia in newborn infants is generally regarded as a problem, and bilirubin itself as toxic metabolic waste, but the high frequency in newborn infants suggests that the excess of neonatal bilirubin may have a positive function. To investigate the hypothesis that bilirubin has a role as a free-radical scavenger, the rate of rise in serum bilirubin in the first few days of life was measured in 44 infants with five illnesses thought to enhance free-radical production and in 58 control infants. The infants were selected from 2700 consecutive births by exclusion of those with factors known to affect bilirubin metabolism, including enteral feeding. The control infants were those who seemed to be ill and received treatment, including restriction of enteral feeds, but in whom no illness, or disorders not related to free-radical production, were found. The mean serum bilirubin rise was significantly lower in the combined illness group than in the control group (36.1 [95% Cl 26.9-45.3] vs 66.7 [55.9-77.5] mumol.l-1.day-1; p less than 0.0001). In subgroup analyses the mean rises in infants with circulatory failure, neonatal depression/asphyxia, aspiration syndromes, and proven sepsis were significantly lower than in controls matched for gestational age and birthweight, but rises in infants with respiratory distress and their matched controls did not differ. These findings are consistent with the hypothesis that bilirubin is consumed in vivo as an antioxidant. Such consumption may operate in vivo in addition to the standard pathways for bilirubin metabolism (production, isomerisation, and excretion).
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PMID:Variation of initial serum bilirubin rise in newborn infants with type of illness. 167 69

Complement components C3, C1q, factor B and breakdown products of C3, i.e. C3c and C3d, were evaluated in the diagnosis and prognosis of sepsis in 24 neonates with proven sepsis. The complement components were measured by electroimmunodiffusion and breakdown products by counterimmunoelectrophoresis (CIEP). The babies with sepsis were found to have decreased levels of C1q and factor B as compared with suitably matched healthy controls. No statistically significant depression was observed in C3 levels of infected babies. However, breakdown products of C3, i.e. C3c and C3d, were detected in 58.3% of these babies. The breakdown products of C3 were not present in any of the healthy controls. The degree of depression of complement components was of no prognostic significance in neonatal sepsis.
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PMID:Complement components in neonatal sepsis. 169 42


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