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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ibuprofen pretreatment increases arterial pressure and reduces mortality in endotoxic dogs. The increase in arterial pressure may be caused by increases in arterial resistance, arterial sphincter tone, or both. Thus it is not clear if ibuprofen pretreatment prevents the hemodynamic effects of endotoxemia or merely masks such effects by producing concomitant increases in arterial resistance. Accordingly, this study was performed to determine the effects of ibuprofen pretreatment on arterial pressure-flow relations and other measures of cardiovascular function in a canine model of endotoxic shock. In 19 pentobarbital-anesthetized and splenectomized, closed-chest dogs, biventricular stroke volumes were measured with electromagnetic flow probes, and intrathoracic vascular and pleural pressures were measured with catheters. Instantaneous venous return curves (see Pinsky MR, J Appl Physiol 56:765, 1984) were generated during positive-pressure ventilation, and steady-state arterial pressure-flow relations, left ventricular function, peripheral vascular compliance, oxygen consumption/oxygen delivery ratio, and arterial blood lactate levels were measured during two sequential volume loading and removal (20 ml/kg) sequences. All but two dogs received a bolus infusion of Escherichia coli endotoxin (2 mg/kg) between the two fluid challenge runs. Eleven of the 17 endotoxic dogs also received ibuprofen (15 mg/kg) immediately before the initial fluid challenge. Ibuprofen pretreatment abolished all hemodynamic effects of endotoxin, whereas in the untreated group endotoxin caused decreases in calculated arterial outflow pressure and in peripheral vascular capacitance. Oxygen consumption remained constant despite changes in oxygen delivery in the nonendotoxic dogs and in the ibuprofen-pretreated dogs, whereas oxygen consumption covaried with oxygen delivery in the endotoxic dogs not pretreated with ibuprofen. Arterial lactate levels were higher after endotoxin infusion (2.1 +/- 0.5 to 3.1 +/- 0.6 mmol/liter; P less than 0.05 pre- to postvolume) but were not different between treatment groups. These data suggest that ibuprofen alters many, but not all, of the hemodynamic effects of endotoxin infusion in the dog.
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PMID:Cardiovascular response in canine endotoxic shock: effect of ibuprofen pretreatment. 144 91

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

The hemodynamic effect of diprenorphine (M5050) in canine endotoxic shock was studied. Mean arterial pressure, left ventricular pressure, left ventricular contractility (dp/dt max), stroke volume, and cardiac output in the endotoxin-shocked dogs were significantly improved by intravenous injection of naloxone (2 mg/kg) and intraventricular microinjection of diprenorphine (40 micrograms), but not by intravenous injection of diprenorphine. It was suggested that the site of action of diprenorphine might be in the central nervous system, and the endogenous opioid substances in the central nervous system may play a more important role in the pathogenesis of septic shock than does that in the peripheral system.
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PMID:[Hemodynamic effect of an opioid receptor antagonist diprenorphine in canine endotoxic shock]. 183 8

The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution. 189 78

Hypertonic colloid solutions have been found efficacious in the resuscitation from hemorrhagic/traumatic shock. The present study investigated the hemodynamic, gasometric, and metabolic effects of hypertonic colloids in endotoxic shock in the dog. Thirty minutes after administration of 3 mg/kg normal body weight of Escherichia coli endotoxin, dogs were randomly assigned to receive 10 mL/kg hydroxyethylstarch (HES) either in 0.9% NaCl (HES, 10 dogs) or in 7.5% NaCl (HT-HES, 10 dogs) in 30 min. Thereafter, 0.9% NaCl solution was administered in volumes adequate to maintain pulmonary artery balloon-occluded pressure at baseline levels. Total fluid administered averaged 64 +/- 30 mL/kg (mean +/- SD) in the HES group and 73 +/- 34 mL/kg in the HT-HES group. As these differences were not statistically significant, total sodium load was higher in the HT-HES group. The persistent volume effect was associated with persistently lower hematocrit and protein levels in the HT-HES group. Initial fluid resuscitation with HT-HES resulted in arterial pressure, cardiac filling pressures, cardiac output, stroke volume, and rates of oxygen delivery and oxygen consumption that were greater than those with HES. Vascular resistances were similar. Analysis of left ventricular function curves also indicated an improvement in cardiac performance. However, these effects almost completely vanished during the remainder of the study. In the HT-HES group, serum sodium and osmolality levels increased to 167 +/- 4 mEq/L and 344 +/- 4 mOsm/kg H2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertonic saline solution-hetastarch for fluid resuscitation in experimental septic shock. 248 71

In seven anaesthetized dogs the central circulatory effects of changes in Paco2 were studied before and after an intravenous injection of E. coli endotoxin 1.0 mg kg-1. The animals were on controlled ventilation with constant minute volumes, and Paco2 was changed by variations in the inspired gas mixture. Before endotoxin was given, cardiac output, mean aortic pressure, mean pulmonary artery pressure, total peripheral resistance and stroke volume were little affected by the changes in Paco2 from 3.9 +/- 0.4 to 7.2 +/- 0.4 kPa (mean +/- s.e.mean). Only heart rate decreased significantly (P less than 0.05). The intravenous endotoxin injection resulted in a decreased cardiac output (P less than 0.01), a decreased mean aortic pressure (P less than 0.01) and a decreased stroke volume (P less than 0.05). Mean pulmonary artery pressure, total peripheral resistance and heart rate showed only minor changes. In endotoxic shock an increase in Paco2 from 4.4 +/- 0.4 to 7.8 +/- 0.3 kPa (mean +/- s.e.mean) resulted in a significant increase in cardiac output (P less than 0.05), stroke volume (P less than 0.05) and mean pulmonary artery pressure (P less than 0.05), while the other parameters remained unchanged. It can be concluded that the carbon dioxide tension is of importance for the cardiac performance in experimental endotoxic stock in a manner not seen in control animals. The mechanisms behind these findings need further investigation.
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PMID:Circulatory effects of carbon dioxide in experimental endotoxic shock. 308 32

We compared, at constant preload maintained by polygeline (gelatin) infusion, the hemodynamic effects of continuous infusion of norepinephrine (0.5, 1, and 1.5 micrograms/kg X min) in anesthetized dogs with and without hyperdynamic endotoxic shock. In both groups, norepinephrine infusion increased systolic, diastolic and mean aortic BP, cardiac index, stroke index, index of myocardial contractility, and mean pulmonary artery pressure. No significant change in right atrial pressure, left ventricular end-diastolic pressure, heart rate, systemic vascular resistance, or pulmonary vascular resistance was observed. Oxygen consumption index and oxygen extraction ratio remained unchanged. Increases in systolic aortic BP were dose-related, whereas maximal effects on other variables were obtained at 0.5 to 1 microgram/kg X min. The rise in aortic pressure resulted from an increased cardiac index but not from an increased systemic vascular resistance. Stroke index increased as contractility improved. The slight alpha-adrenergic effect of continuous, low-dose norepinephrine infusion did not impede the beneficial effects of the marked beta-adrenergic stimulation on cardiac function. The combination of these two effects improved hemodynamic disturbances of hyperdynamic endotoxic canine shock.
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PMID:Hemodynamic effects of continuous norepinephrine infusion in dogs with and without hyperkinetic endotoxic shock. 329 92

Hypertonic saline has been used in the treatment of hypovolemic or burn shock for its rapid volemic effects. Hypertonic solutions could also improve cardiac performance and protect cellular metabolism in acute circulatory failure. We therefore studied the hemodynamic effects of continuous hypertonic saline infusion in the treatment of severe endotoxic shock in the dog. Thirty minutes after slow injection of 3 mg/kg of Escherichia coli endotoxin, fluid resuscitation with either hypertonic saline containing 1,200 mOsm of NaCl/liter (eight dogs) or normotonic saline solution (eight dogs) was started and titrated to maintain left-sided filling pressures at control level. For the next 210 min, the total amount of fluid administered was 64.5 +/- 7.8 ml/kg in the hypertonic group and 83.6 +/- 10.3 ml/kg in the normotonic group. These differences were not statistically significant. Intravascular pressures were similar in the two groups, but cardiac output, stroke volume, and oxygen consumption were significantly higher in the hypertonic group. These results therefore indicate that hypertonic saline can rapidly restore oxygen transport and tissue oxygen consumption in septic shock. The duration of these hemodynamic effects, however, remains to be determined.
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PMID:Fluid resuscitation with hypertonic saline in endotoxic shock. 379 79

Fasted mongrel dogs were anesthetized with pentobarbital sodium and instrumented for the continuous measurement of blood glucose (BG), a lead II electrocardiogram, and pressures in the left ventricle (LV), pulmonary artery, and aorta. Cardiac output was measured every 15 min using thermodilution and LV stroke work, and pulmonary and systemic resistances were calculated. After a 30-min pretreatment period, glucose clamping was initiated. The desired glucose levels were reached within 45 min (hypoglycemic 20 +/- 1 mg/dl, n = 11; normoglycemic 85 +/- 1, n = 7; hyperglycemic 156 +/- 3, n = 7). At this point dogs were treated with either endotoxin (8 mg/kg to 6 hypoglycemic, 4 normoglycemic, and 4 hyperglycemic) or saline (5 hypoglycemic, 3 normoglycemic, and 3 hyperglycemic). All infusions were terminated after 2 h glucose clamping, and all dogs were monitored either until death or for a maximum of 10 h. Hypoglycemic clamping curtailed survival in endotoxic dogs. Hyperglycemic clamping markedly prolonged survival. Normoglycemic clamping left survival time unchanged compared with untreated dogs. The effects of glucose clamping on cardiovascular function during endotoxic shock paralleled the effects on survival. Cardiovascular function was also depressed in hypoglycemic-clamped saline dogs. It is concluded that glucose dyshomeostasis may be a crucial factor in the development of fatal cardiovascular dysfunction and shock after endotoxin administration.
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PMID:Glucose clamping and cardiovascular function in endotoxic dogs. 390 86

1. Long-lasting haemorrhagic hypotension (4.5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP(9a)), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP(9a) was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days.2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock.3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock.4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period.5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock.6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period.7. BPP(9a) had no measurable effect on the course of endotoxic shock.8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed.
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PMID:On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock. 437 70


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