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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic alcoholism causes a cardiac contractile dysfunction which, in rats, may occur after 6 mo to 1 yr of alcohol consumption. Sepsis, on a more acute basis, can also induce intrinsic cardiac dysfunction. We tested the hypothesis that 2 mo of chronic alcohol feeding, while not directly causing overt depression of the myocardium, might sensitize the heart to a known cardiac stress, i.e., sepsis. We proposed that sepsis, induced in an alcoholic animal, would cause a more severe myocardial depression than in a nonalcoholic rat. Thus rats were fed a liquid diet with 36% of the total calories as alcohol for 8-10 wk and were then anesthetized and received an injection of live Escherichia coli (approximately 10(10) E. coli) through a dorsal subcutaneous catheter followed by a second dose approximately 5 h later. The following day, hearts were removed and, using the isolated working heart preparation, intrinsic contractile performance was assessed by generating ventricular function curves. Four groups of animals were studied. Hearts from the nonalcoholic-nonseptic group and the alcoholic-nonseptic group showed identical cardiac work (cardiac output x peak systolic pressure at the highest preload was 6,113 +/- 324 and 5,955 +/- 406 ml.min-1.mmHg-1, respectively). Work in the nonalcoholic-septic and the alcoholic-septic groups was decreased by 30 and 50%, respectively (4,806 +/- 478 vs. 2,917 +/- 435 ml.min-1.mmHg-1 at the highest preload). Thus 2 mo chronic alcohol consumption caused no overt cardiac dysfunction by itself but did exacerbate the myocardial injury induced by sepsis.
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PMID:Chronic alcohol consumption enhances sepsis-induced cardiac dysfunction. 205 23

Experiments were conducted to test the hypothesis that the previously demonstrated depression in ventricular function of rats with hyperdynamic sepsis was a result of depressed high energy phosphate levels or altered myocardial substrate utilization. Rats were inoculated with a pooled fecal homogenate, and 48 hr later their hearts were removed and studied using the Langendorff preparation. The coronaries were perfused with a hydrostatic pressure of 90 mmHg, and hearts were paced at 310-320 beats/min. Substrate oxidation was determined by supplying 14C-labeled glucose, lactate, or palmitate in physiologic concentrations, ie, 5.5, 1, and 0.6 mM, respectively. Hearts were frozen either in situ or after 40-50 min of perfusion for the determination of tissue metabolite levels. Myocardial content of high energy phosphates, total adenine nucleotides, and creatine were similar in septic animals and time-matched controls both in situ and after perfusion. Oxidation of exogenous substrates accounted for the total myocardial O2 consumption in both groups of perfused hearts. Palmitate oxidation was responsible for approximately 50% of the total O2 consumption of the heart, with glucose accounting for approximately 20% and lactate for the remainder. The percentage contribution of the three substrates to oxidative metabolism was similar in hearts from septic and time-matched controls; therefore, myocardial substrate preference was not altered by sustained sepsis. These studies also indicate that ischemia and the concomitant fall in high energy phosphates do not contribute to the myocardial dysfunction of hyperdynamic sepsis.
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PMID:Substrate utilization and high energy phosphate levels of hearts from hyperdynamic septic rats. 369 11

Experimental studies have documented that myocardial dysfunction is precipitated between 3 and 6 hr after endotoxin or E. coli. This finding has now been confirmed in human septic shock. A "Hinshaw-modified" isolated working left ventricle preparation has been used to document and assess the degree of failure. It was found that the failure is often severe and reversible only temporarily by adrenergic agents but reversible by digoxin or insulin. The cause of the failure has not been identified, but evidence is presented against a myocardial depressant factor (MDF) being the causative factor. Hearts subjected to a 2-4 hr period of hypotension on the threshold of failure show no signs of failure when subjected to blood circulating from an animal in splanchnic arterial occlusion shock. Hearts from pancreatectomized animals subjected to endotoxin shock with their source of MDF removed demonstrate the typical failure in 4-6 hr. Other factors are suggested that contribute to myocardial dysfunction: hypotension or nonuniform perfusion of subendocardial regions of the heart, depressed responsiveness to inotropic and chronotropic stimuli, intracardiac ionic and fluid disturbances, and increases in heart chamber and muscle stiffness. Since steroid/antibiotic therapy increases the probability (p less than 0.05) that an animal will survive lethal sepsis, investigating the effect of this therapy on myocardial function may aid in determining whether or not this degree of heart failure contributes in the animal to irreversible shock and death.
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PMID:Myocardial dysfunction in endotoxin- and E. coli-induced shock: pathophysiological mechanisms. 388 34

The reviewed studies support the contention that during the high flow or hyperdynamic phase of gram-negative septicemia, cardiac reserve is compromised because of intrinsic myocardial dysfunction. The latter is not referable to coronary hypoperfusion or peripheral pooling or decreased venous return. Although, under resting, nonstressed conditions, indices of myocardial function may appear normal or even elevated, a decreased reserve is evident when additional stress is imposed on the myocardium. Hearts removed from septic rats during the hyperdynamic stage and perfused in vitro (using the isolated perfused working heart preparation) showed a rightward and downward shift in work function curves, indicating a severe depression in cardiac function. Possible mechanisms for the observed dysfunction are discussed. No significant alterations in high energy phosphate production or substrate utilization were observed, indicating that altered myocardial metabolism is not likely to be a significant contributor to the dysfunction. Our results suggest that cardiac dysfunction is partially due to an elevation in the cytosolic calcium concentration which may slow the rate of ventricular relaxation. These studies emphasize that intrinsic cardiac function is depressed early during the course of the septic episode at a time that precedes the onset of circulatory shock.
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PMID:The effect of hyperdynamic sepsis on myocardial performance. 399 94

Gram-negative sepsis causes a depression of the myocardium such that ventricular function curves generated on isolated perfused hearts removed from septic rats are displaced downward and to the right of control. Alcohol consumption can also cause a depression of the myocardium, especially if the period of alcohol feeding is prolonged. However, even before overt changes in the myocardium can be measured as a result of alcohol consumption, chronic alcoholism can result in a potentiation of sepsis-induced cardiac depression (Am. J. Physiol. 250:H1857-H1863, 1991). The purpose of the present study was to determine if 1 week of withdrawal of alcohol from the diet after 8 weeks of alcohol consumption would reverse the potentiation by alcohol of sepsis-induced cardiac depression. Animals were fed an ethanol-containing diet in which ethanol contributed 36% of the total calories. Rats were fed this diet or a control liquid diet for 8 weeks, and then some animals were taken off the alcohol diet and placed on the control diet for 1 week. Sepsis was induced in control-fed, alcohol-fed or withdrawal animals by the administration of Escherichia coli into the dorsal subcutaneous space. Nonseptic animals received sterile saline in this space. The following day animals were anesthetized, and the hearts were removed and studied as isolated working hearts. Hearts removed from septic and alcohol septic animals showed severe depression of cardiac contractile performance. Hearts from the withdrawal group, however, were less compromised by sepsis and showed only a few signs of cardiac dysfunction. Withdrawal from alcohol for 1 week thus resulted in protection of the heart from sepsis-induced cardiac depression.
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PMID:1-week withdrawal from 8 weeks alcohol consumption protects the heart from sepsis-induced dysfunction. 748 27

Ischemia causes significant damage to the heart as manifested by decreases in ventricular performance. Several different methods have been shown to protect the heart from ischemic injury--one is operative over a short period (an hour) and the other over longer periods (a day). The latter form of protection has been demonstrated in rats after induction of Gram-negative sepsis or administration of endotoxin or cytokines. In the present study we determined whether guinea pigs would also show induction of cardiac protection subsequent to a dose of endotoxin. Male guinea pigs were injected with 1 mg of endotoxin and studied the following day. Hearts were perfused at a constant perfusion pressure and studied in an isovolumic mode. Left ventricular developed pressure was significantly lower in the endotoxin-treated group than in the control group. After 35 min of total ischemia and 25 min of reperfusion, recovery of left ventricular developed pressure was complete in the endotoxin group but significantly decreased in the control group such that after ischemia and reperfusion, there was no significant difference in left ventricular performance between the two groups. Coronary flow was significantly greater in the endotoxin group than in the control group both prior to and after ischemia. Hearts from endotoxin-treated guinea pigs resumed spontaneous contractile activity sooner and released less lactate upon reperfusion than did the control group. Thus prior treatment of guinea pigs with endotoxin resulted in depression of the isolated heart but also resulted in protection of the isolated heart from further damage due to ischemia/reperfusion injury.
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PMID:Effects of endotoxin on the guinea pig heart response to ischemia reperfusion injury. 749 99

We have previously shown that administration of Escherichia coli to a rat induces cardiac dysfunction, but also prevents the myocardium from being further damaged by total ischemia. We have also previously shown that induction of sepsis in a rat that has consumed alcohol as 36% of its caloric intake for 8-10 weeks, results in a potentiation of the cardiac depression resulting from sepsis. In this study, we determined if administration of Gram-negative bacteria to a chronically alcoholic rat would still protect the heart from ischemia-reperfusion injury. We tested the protective effect of sepsis using an in vitro, isovolumically contracting heart preparation. Global ischemia was maintained for 35 min, followed by 25-min reperfusion. In the present experiments, sepsis produced a 40% decrease in cardiac performance, but was also protective of hearts made ischemic the next day. Hearts from septic and alcoholic septic rats recovered 100% of preischemic ventricular function after 35-min ischemia, whereas hearts from the control and alcohol groups recovered only 80% of preischemic left ventricular performance. Whereas preischemic function was significantly decreased in the septic groups compared with the two nonseptic groups, postischemic function was no longer significantly different in the four groups. Thus, sepsis resulted in development of protection of the hearts from ischemia-reperfusion injury, even in hearts that were severely compromised by the combination of chronic alcoholism and Gram-negative sepsis.
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PMID:Sepsis protects the heart of alcoholic rats from ischemia-reperfusion injury. 769 39

Alcohol, consumed as 36% of the caloric intake for 8-10 wk, causes a potentiation of cardiac dysfunction induced by a second insult, sepsis. Because chronic alcoholism may attenuate the responsiveness of the myocardium to catecholamine stimulation, and because catecholamine support seems to be essential for the myocardium to generate an adequate cardiac output in sepsis, we hypothesized that the heart from the alcoholic septic rat would show a compromised inotropic responsiveness to catecholamines compared with the heart from the nonalcoholic septic rat. To test this hypothesis, rats were fed an ethanol-containing or control liquid diet for 8-10 wk and were then made septic with live Escherichia coli (10(10) E. coli) through a dorsal subcutaneous catheter. The next day, hearts were removed and perfused at a constant hydrostatic pressure, and a compliant balloon was placed in the left ventricule for measurement of pressure (LVP). Hearts were paced at 350-360 beats/min. Hearts were allowed to stabilize for 15 min, and then the response to a submaximal dose of isoproterenol (Iso) was measured. Hearts recovered for 30 min, at which time the response to a maximum dose of Iso was recorded. Basal (pre-Iso) LVP was lower in the control septic and alcoholic septic groups than in the control and alcohol groups. However, the maximum increase in LVP in response to Iso was greater in the two septic groups than in the two nonseptic groups. The peak LVP in response to Iso was similar in the control, septic, and alcoholic septic groups, and was significantly greater than in the alcohol group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial responses to isoproterenol are altered by chronic alcoholism and infection. 844 52

We have previously demonstrated that chronic alcohol consumption (8 to 10 weeks with ethanol as 36% of the caloric intake) does not exacerbate the effects of ischemia reperfusion injury on the heart. In those same studies, however, Gram-negative sepsis caused myocardial depression in both control and alcoholic rats, but also protected hearts from further damage due to ischemia-reperfusion. In the present study, we determined if preconditioning, a very short ischemia-reperfusion episode that protects the heart from more prolonged ischemia, would have similar effects on hearts from alcoholic and control rats with or without sepsis. Thus, rats were fed a liquid diet supplemented with ethanol or dextrin for 8 to 10 weeks. Some alcoholic and control rats were made septic with Escherichia coli injected into the subcutaneous space, whereas others received an injection of sterile saline. Isolated, isovolumically beating hearts were studied the following day. Hearts were made ischemic for 5 min, reperfused for 5 min, and then made ischemic for 35 min and reperfused for 25 min. Data from similar groups of hearts receiving only 35 min ischemia, and studied at the same time as the present groups, have been previously reported. The 5-min preconditioning episode was more effective in protecting hearts in the alcohol group than in the control group. Postischemic left ventricular developed pressure and +dP/dtmax were not significantly decreased from the preischemic values in the alcohol group, but were significantly decreased in the control group. The time to recovery of spontaneous contractions was decreased by preconditioning in the alcohol group but not in the control group, and the recovery of coronary flow was enhanced in the alcohol group, but not in the control group by pre-conditioning. Thus a single 5-min ischemic procedure was effective in protecting the heart from prolonged ischemia in the alcohol group, whereas it was not sufficient to elicit protection in the control group. Sepsis depressed preischemic function in both groups, but recovery from ischemia was complete.
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PMID:Chronic alcohol consumption causes accelerated myocardial preconditioning to ischemia-reperfusion injury. 926 37

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.
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PMID:Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. 1038 Nov 49


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