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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Septic shock is characterized by an increase in cardiac output and a fall in systemic vascular resistance index and mean arterial pressure. Endotoxin alters the smooth muscle function of blood vessels, probably by means of an increased production of the potent vasodilator nitric oxide (NO). The present study was accomplished to determine how the inhibition of NO synthesis influences cardiovascular performance in an ovine model of hyperdynamic endotoxemia. Endotoxemia was induced in five range ewes (41 +/- 2 kg) by continuous infusion of Escherichia coli endotoxin (LPS, 10 ng.kg-1.min-1) over the entire study period. After 24 h of LPS infusion, cardiac output increased from 5.2 +/- 0.3 to 7.9 +/- 0.6 (SE) 1/min (P less than 0.05) and mean arterial pressure and systemic vascular resistance index fell from 92 +/- 5 to 79 +/- 6 mmHg (P = 0.08) and from 1,473 +/- 173 to 824 +/- 108 dyn.s.cm-5.m2 (P less than 0.05), respectively. The pulmonary shunt fraction increased from 0.23 +/- 0.03 to 0.32 +/- 0.03 (P less than 0.05). The intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (25 mg/kg) 24 h after the start of the LPS infusion changed these values to approximately baseline levels over the subsequent 4 h. Although N omega-nitro-L-arginine methyl ester increased pulmonary arterial pressure and pulmonary vascular resistance (P less than 0.05), right and left ventricular stroke volume index showed no significant changes. It is concluded that NO has a major function in cardiovascular performance in endotoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. 150 87

Monophosphoryl lipid A (MPL) is a nontoxic lipid A derivative that maintains many of the beneficial immunomodulatory activities of the parent lipopolysaccharide molecule, including the induction of tolerance to endotoxin. The hemodynamic effects of Salmonella minnesota MPL (300 mg/kg) and S. minnesota lipopolysaccharide (300 micrograms/kg) were compared in 20 minipigs. Decreases in cardiac output and arterial pressure and increases in pulmonary artery pressure and lactic acidosis were significantly greater in animals treated with lipopolysaccharide. These changes were associated with peak tumor necrosis factor (TNF) levels of 1373 +/- 79 U/ml in animals treated with LPS and 157 +/- 31 U/ml in animals treated with MPL. Ten minipigs were subsequently randomized to receive S. minnesota MPL (30 micrograms/kg) or diluent intravenously 48 hours before receiving S. minnesota lipopolysaccharide (300 micrograms/kg IV). MPL significantly attenuated lipopolysaccharide-induced decreases in mean arterial pressure, cardiac index, stroke volume index, and mixed venous oxygen saturation. At baseline, no significant difference could be seen in TNF levels between diluent and MPL pigs. TNF levels peaked 2 hours after LPS infusion at 1190 +/- 156 U/ml in diluent pigs and at 539 +/- 126 U/ml in MPL pigs (p less than 0.05). Each of the pigs pretreated with MPL survived endotoxic shock, whereas only one of the five diluent pigs survived. These observations are consistent with the induction of endotoxin tolerance by pretreatment with MPL.
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PMID:Monophosphoryl lipid A attenuates the effects of endotoxic shock in pigs. 158 79

Eight awake sheep were monitored with ultrasonic crystals, positioned at the anterior and posterior left ventricular wall. A left-sided intraventricular pressure transducer and a right ventricular ejection fraction catheter were positioned in the right and left hearts, respectively. After administration of endotoxin (Escherichia coli, LPS 1.5 micrograms/kg in 30 min), the hemodynamic variables showed a triphasic course. Phase I, (0-1 hr post LPS) was characterized by an increased pulmonary artery pressure and a decreased right ventricular ejection fraction. The inability of the right ventricle to compensate for the increased preload resulted in a fall of the left ventricular preload, stroke volume, and cardiac output. Three hours after LPS administration a second drop of the cardiac output was noted (phase II). This occurred as a result of a fall in preload. Eight hours post LPS a hyperdynamic phase (phase III) was distinguished, with a high cardiac output and a low systemic vascular resistance. During this time there was evidence of probable reduced myocardial contractility.
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PMID:Cardiac function in an ovine model of endotoxemia. 174 59

We compared the cardiopulmonary responses to a single bolus (1.5 microgram/kg) vs. continuous infusion of endotoxin (LPS) (24 ng/kg/hr) in unanesthetized sheep. A single bolus produced an initial marked increase in pulmonary arterial pressure and plasma thromboxane levels and an elevated flow rate of lung lymph low in protein. Concomitantly, the cardiac output dropped and systemic vascular resistance rose. In the animals that received a continuous infusion of LPS, only very small changes in these variables were noted during this early period. Later, lung lymph flow rate and protein flux were elevated in both groups with a greater response in the bolus group. At 6 hr after LPS, the systemic vascular resistance fell in both groups, but to a greater extent in the bolus group, whereas the cardiac output rose to the same extent. Plasma levels of neutrophils, lymphocytes, and plasma prekallikrein levels decreased in both groups; neutropenia was more pronounced in the bolus group. The most important difference between both endotoxemia models during this phase was the reduction of the stroke work index in the bolus model, which was not observed with the continuous infusion. The apparent myocardial depression, the early reduction in cardiac output, and eicosanoid mediated pulmonary hypertension are the major differences between the two responses.
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PMID:Comparison of the cardiopulmonary responses to single bolus and continuous infusion of endotoxin in an ovine model. 265 Sep 14

The presence of myocardial depression is difficult to assess in most animal models of septic shock caused by hypovolemia. We studied endotoxemia in fluid-resuscitated conscious sheep. They underwent chronic instrumentation with pulmonary artery, arterial, and left atrial catheters. After 1 week of recovery, 1.5 micrograms/kg of endotoxin (LPS) was administered intravenously over a period of 30 min. One group of nine sheep stayed on baseline fluids (2 ml/kg/h of Ringer's lactate), while a second group (n = 6) was resuscitated with 7 ml/kg/h Ringer's lactate solution over the 24-h study period. Both groups were compared with controls. Eight hours after LPS, left ventricular stroke work index was depressed in both groups. In the group resuscitated with 7 ml/kg Ringer's lactate this depression associated with a normal left atrial pressure and a constant peripheral resistance indicated a shift in the Starling work curve downward and to the right evidencing myocardial depression.
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PMID:Myocardial depression in hyperdynamic endotoxemia. 319 61

Heat stress causes a marked reduction in splanchnic blood flow in order to compensate for the increased flow to the skin. Splanchnic ischemia causes a leakage of endotoxins from the gut lumen into the portal circulation and, especially in the presence of a compromised reticuloendothelial system, may cause severe systemic endotoxemia. Since many of the pathological features of heat stroke are similar to the shock state produced by LPS, we examined whether heat-stress causes endotoxemia. Five anesthetized monkeys were subjected to an environmental temperature of 41 degrees +/- 0.3 degrees C and relative humidity of 100%, until death. Rectal temperatures were recorded continuously, blood pressure and ECG were recorded at 5-min intervals, and arterial blood samples were taken at 15-30 min intervals. A decline in mean arterial pressure and rapid rise in heart rate occurred at about 42 degrees C. Plasma LPS remained at 0.071 +/- 0.006 ng.ml-1 until a rectal temperature of +/- 42 degrees C. Thereafter, it increased slowly until beyond 43 degrees C when it rose rapidly to 0.347 +/- 0.024 prior to death. Endotoxemia may have been a contributing factor in the pathogenesis of heat stroke. If so, then the use of anti-LPS antibodies may be expected to be beneficial.
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PMID:Time course of endotoxemia and cardiovascular changes in heat-stressed primates. 368 71

We tested the influence of in vivo volume resuscitation on intrinsic contractile properties of left ventricular (LV) preparations of endotoxemic guinea pigs. Escherichia coli endotoxin (LPS)-injected animals were divided into nonresuscitated and resuscitated groups. Volume resuscitation improved cardiac output and stroke volume, increased arterial pH and body temperature, and decreased mortality. In isovolumetric LV preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) of LPS with (42 +/- 3) and without (42 +/- 2) fluid resuscitation were consistently less than control values (70 +/- 3). LV end-diastolic pressure-volume (compliance) decreased in LPS-nonresuscitated hearts, while LV compliance of LPS-resuscitated hearts was similar to control. Thus, intravascular volume expansion selectively improved LV diastolic compliance of LPS hearts without affecting LV systolic function. These findings suggest that LV systolic and diastolic dysfunctions associated with endotoxemia and Gram-negative sepsis may involve separate pathogenic mechanisms.
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PMID:Cardiodynamic response to Escherichia coli endotoxemia: effects of fluid resuscitation. 774 51

Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 microgram.kg-1 x min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1 x min-1 of NPY (equipotent to 0.1 microgram.kg-1 x min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
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PMID:Neuropeptide Y infusion improves hemodynamics and survival in rat endotoxic shock. 790 7

Calcitonin gene-related peptide (CGRP) is a potent vasodilatory neuropeptide, which may play a role in vascular dysfunction during septic shock. Sixteen pigs (25-50 kg) were anesthetized with ketamine and isoflurane in O2, and administered 100 micrograms/kg Escherichia coli lipopolysaccharide i.v. (LPS; n = 8) or saline vehicle (n = 8). Pigs were instrumented for hemodynamic determinations and blood sampling for CGRP assay (pg/ml) from the portal vein (PV) and the pulmonary (PA) and carotid (CA) arteries. Blood samples were collected into EDTA and aprotinin before (baseline) and at 60, 120, and 180 min after LPS administration. LPS caused significant deterioration in indices of hemodynamic function and a significant increase in plasma CGRP concentration at all sampling sites by 120 min (P < 0.01). No significant difference between sampling sites was recorded at any time. Plasma CGRP concentrations displayed significant negative correlations with mean arterial pressure, cardiac index, and left ventricular stroke work. These data confirm our previous findings of CGRP elevations in endotoxemic rats, and indicate that 1) LPS is a potent stimulus for the systemic release of CGRP, 2) increasing plasma CGRP concentrations temporally correlates with cardiovascular deterioration during LPS shock, and 3) there is little evidence that the portal circulation is a major source of circulating CGRP levels during LPS shock. Vasoactive neuropeptides, such as CGRP, may interact with other documented mediators of vascular dysfunction in the pathogenesis of septic shock.
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PMID:Elevations in circulating calcitonin gene-related peptide correlate with hemodynamic deterioration during endotoxic shock in pigs. 802 80

We sought to determine if a recombinant amino terminal fragment of bactericidal/permeability increasing protein (rBPI23) alters the hemodynamic responses to endotoxin. Experiments were performed on Sprague Dawley rats anesthetized with Ketamine and xylazine. In rats challenged with a 30 min infusion of 0.25 mg/kg lipopolysaccharide (LPS; Escherichia coli 0111:B4), there were early (30-90 min), significant increases in cardiac index, heart rate, and stroke volume, accompanied by significant decreases in blood pressure and total peripheral resistance. For the remainder of the 210 min observation period, cardiac index, and stroke volume progressively declined to levels significantly below those of control rats receiving only vehicles. At the same time, blood pressure and total peripheral resistance steadily increased above the vehicle control group. Infusion of 3 mg/kg of rBPI23 abolished these LPS-induced hemodynamic responses. A dose of 1.0 mg/kg of rBPI23 was associated with a modest, significant inhibition of changes evoked by LPS, whereas 0.3 mg/kg was without significant effect. Thaumatin, a control cationic protein with molecular weight and isoelectric point similar to those of rBPI23, failed to alter any responses to LPS. These results indicate that rBPI23 produces a dose-dependent inhibition of hemodynamic changes, associated with endotoxemia, and provides further support for the potential utility of rBPI23 as a therapeutic agent in the treatment of gram-negative sepsis and infection.
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PMID:Recombinant amino terminal fragment of bactericidal/permeability-increasing protein prevents hemodynamic responses to endotoxin. 826 47


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