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

Septic shock in young children is often characterized by clinical findings consistent with a reduction in cardiac index (CI) and elevation of systemic vascular resistance index (SVRI). In this context, infusion of inotropic agents, alone or in combination with vasodilators, has been recommended. We have utilized group B streptococcal (GBS) infusion in piglets to develop a model of low-CI/high-SVRI septic shock, and report here the effects of the combination of epinephrine (EPI) plus either nitroglycerin (NG) or nitroprusside (NP) in this model of infant sepsis. Piglets were anesthetized, intubated, and ventilated. All piglets received GBS continuously for 90 minutes and were further divided into three experimental groups. Group 1 received NG 16 micrograms/kg.min plus EPI 2 micrograms/kg.min; group 2 received NP 10 micrograms/kg.min plus EPI 2 micrograms/kg.min, and group 3 received 0.9% sodium chloride (saline) only. CI, which fell for all three groups at the onset of GBS infusion, rose significantly in group 2 animals (but not in groups 1 and 3). This effect was mediated entirely by an increase in myocardial stroke volume. Aortic blood pressure, initially unaffected by GBS infusion, rose significantly in both group 1 and 2 compared with group 3. SVRI, which rose for all three groups at the onset of GBS infusion, was further markedly elevated in group 1 (but not in groups 2 and 3). Pulmonary artery pressure and pulmonary vascular resistance index, both significantly increased after GBS infusion, were reduced in group 2 but not groups 1 and 3. These observations illustrate the potential for unexpected, and possibly detrimental, hemodynamic consequences when vasoactive agents are combined in young septic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic effects of combining epinephrine with nitroglycerin or nitroprusside during group B streptococcal sepsis in piglets. 141 51

Perioperative circulatory disorders in patients may take the form of a transitory reduction in oxygen transport to the peripheral tissues (pre-shock), manifest circulatory insufficiency in the presence or absence of concomitant heart insufficiency or general congestive heart failure due to the destabilization of an preexisting heart disease. The least problematical stage in this programme of therapy is the treatment of transitory perioperative circulatory insufficiency by manipulation of the oxygen transport system using the following means: comparative volume optimization [according to the central venous pressure (CVP)], positive inotropic support with dobutamine (5-10 micrograms.kg-1.min-1), monitoring of the blood pressure, heart rate and oxygen consumption and, in severe cases, insertion of a Swan-Ganz catheter. In manifest circulatory insufficiency, sepsis or acute congestive heart failure, the Swan-Ganz catheter seems to be obligatory. In such cases, the positive inotropic therapy is based on catecholamines of medium (dobutamine) or high (epinephrine) positive inotropic efficacy, as a normal pattern and functioning of beta-adrenoceptors can be assumed in such cases if there is no history of cardiac insufficiency. The systemic vascular resistance (SVR) is adjusted to 800-1200 n.s.cm-5 to relieve the working capacity of the heart and to maintain sufficient perfusion pressure by means of constrictors (phenylephrine, norepinephrine) or dilators [nifedipine, nitroglycerin or, if necessary, angiotensin-converting-enzyme (ACE) inhibitors].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapeutic concepts in treatment of circulatory and heart failure in surgery]. 181 8

No therapeutic agent consistently decreases pulmonary arterial pressure (PAP) more than aortic pressure in neonates with persistent pulmonary hypertension of the newborn. We have investigated whether nitroglycerin (NG) or nitroprusside (NP) selectively decreases PAP in an animal model of sepsis-induced pulmonary hypertension. Piglets were anesthetized, intubated, and ventilated. Pulmonary hypertension was induced by an iv infusion of group B Streptococci. Piglets were then divided into three groups with group B Streptococci infusion ongoing. Neither PAP nor the pulmonary vascular resistance index was decreased significantly by either NP or NG. NP decreased significantly both mean aortic pressure and the systemic vascular resistance index. Cardiac index decreased significantly during both NG and placebo infusion. These data suggest that neither NP nor NG is likely to be beneficial in sepsis-induced pulmonary hypertension in newborns.
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PMID:Neither nitroglycerin nor nitroprusside selectively reduces sepsis-induced pulmonary hypertension in piglets. 311 93

In spite of all the scientific and technical advances in recent years, shock that is not rapidly correctable with fluid can have a morbidity rate exceeding 80%. Consequently awareness of such precipitating factors as sepsis and early diagnosis and treatment are essential. Treatment should be rapid and should follow a previously outlined protocol. Such protocols should include correction of the precipitating problem and aggressive resuscitation to assure adequate ventilation and oxygenation of the blood and optimal oxygen delivery to the tissues. Fluid and blood should be given as needed until filling pressures begin to rise rapidly with further fluid infusion. With hemorrhagic shock in previously healthy individuals, a hemoglobin level of 10.0 g/dL is usually adequate. In older, septic, or cardiogenic shock patients, a hemoglobin level of 12.5 to 14.0 may be preferable. If an optimal preload does not increase cardiac output to normal or higher levels, inotropic agents should be used. If shock still persists, one must be sure that the arterial pH is not excessively high or low. Glucocorticoids may then be given in low dose (200 mg hydrocortisone) in case some degree of adrenal insufficiency is present. They can also be given in high doses (equivalent to 150 mg/kg hydrocortisone) early in septic shock primarily to prevent excess complement activation and to preserve membrane integrity. Vasopressors may occasionally be required if there is excessive vasodilation, especially if there is persistent hypotension in the presence of high-grade coronary or cerebral artery stenosis. Vasodilators may be used to try to correct myocardial ischemia (nitroglycerin), excessive preload (nitroglycerin), or excessive afterload (nitroprusside or hydralazine). Combinations of vasodilators and inotropic agents may be required in some patients with high systemic vascular resistance and persistently low cardiac outputs. Mechanical assist with IABP can be of great value in persistent cardiogenic shock. Diuretics may occasionally help prevent renal failure in patients who are persistently oliguric after blood flow and pressure are restored. Heparin is occasionally of value if DIC develops with no concomitant fibrinolysis. Antibiotics are important in septic shock and may also be important if persistent shock has reduced gastrointestinal mucosal integrity so that bacteria and bacterial products can enter the portal system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Science and shock: a clinical perspective. 389 56

The objective of this study was to determine whether endothelium-derived nitric oxide (NO) production is reduced at the macrocirculatory and microcirculatory levels during sepsis. To examine this, rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h after CLP (i.e., midpoint of hyperdynamic sepsis) or sham operation, the aorta and superior mesenteric artery were isolated. Responses to an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, nitroglycerin (NTG), were determined. In additional studies, the small intestine was isolated 5 or 20 h (hypodynamic sepsis) after CLP. Responses to ACh and NTG were determined in the isolated intestine. The results indicate that endothelium-dependent relaxation in both the aorta and superior mesenteric artery was depressed at 5 h after CLP. In contrast, there was no significant difference in the relaxation induced by NTG. Moreover, ACh-induced vascular relaxation in the isolated small intestine decreased at 5 and 20 h post-CLP without any significant alterations in NTG-induced relaxation. Since studies have shown that ACh-induced relaxation in the aorta is reduced at 20 h after CLP, it could be concluded that endothelium-derived NO release is depressed during hyperdynamic and hypodynamic stages of sepsis, not only in large arteries, but also at the microcirculatory level.
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PMID:Endothelium-dependent relaxation is depressed at the macro- and microcirculatory levels during sepsis. 750 27

We examined vascular reactivity to vasoconstrictors [phenylephrine (PE), serotonin (5-HT), and high K+] and vasodilators [acetylcholine (ACh), A23187, L-arginine, and nitroglycerin (NTG)] in isolated mesenteric arterial rings from control and septic rats. Sepsis was induced by cecal ligation and puncture (CLP). A possible mechanism underlying CLP-induced alteration in vascular reactivity was also investigated with N omega-nitro-L-arginine (L-NNA 50 microM), methylene blue (MB 10 microM), and indomethacin (5 microM). In vivo, septic rats manifested two distinct hemodynamic phases, a hyperdynamic state during early (9 h after CLP) phase, followed by a hypodynamic state during late (18 h after CLP) phase. Therefore, we examined ex vivo vascular reactivity in these two phases. Results demonstrated that CLP operation caused hyporesponsiveness to contractile agents and hyperresponsiveness to vasodilator agents. After endothelium removal, most of the contractile responses were enhanced in both CLP-operated (9 and 18 h after operation) and sham-operated rats, whereas enhancement of high-K(+)-induced contraction was observed only in denuded rings from CLP 18-h rats. In addition, augmentation of relaxation induced by ACh at 9 or 18 h after CLP was abolished by N omega-nitro-L-arginine or MB but not by indomethacin. A possible mechanism responsible for alterations of vascular reactivity may be overproduction of nitric oxide (NO) which is blocked by L-NNA or MB.
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PMID:Alterations of ex vivo vascular reactivity in intraperitoneal sepsis. 753 57

Torsade de pointes is an unusual life-threatening ventricular arrhythmia that has been associated with vasopressin, neuroleptic drugs, and electrolyte imbalances, including hypokalemia and hypomagnesemia. Over a 9-month period, we observed torsade de pointes in three patients with cirrhosis and bleeding esophageal varices who did not have prior cardiac disease. All had received endoscopic sclerotherapy and continuous infusions of vasopressin and nitroglycerin. For sedation, two patients received haloperidol and one droperidol. In addition, two patients had either hypokalemia or hypomagnesemia. In all three patients, there was prolongation of the electrocardiographic QT interval and a "long-short" initiating sequence followed by ventricular tachycardia with torsade de pointes morphology. All were successfully cardioverted; there was one late death due to aspiration and septicemia. We conclude that cirrhotics with variceal hemorrhage may be at increased risk of developing this arrhythmia in the setting of treatment with vasopressin, sedation with neuroleptic drugs, and electrolyte abnormalities. We urge close monitoring of these patients for cardiac arrhythmia and recommend that neuroleptics be used cautiously, if at all.
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PMID:Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. 773 96

Hypotension caused by hypovolemic, hemorrhagic shock induces disturbances in the immune system that may contribute to an increased susceptibility to sepsis. The effect of chemically induced hypotension on circulating cytokines and adhesion molecules has not been investigated yet. In 21 patients scheduled for resection of malignant choroidal melanoma of the eye the perioperative serum levels of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha, and the adhesion molecules sE-Selectin and sICAM-1 were investigated. Moderate hypothermia of 32 degrees C was induced in all patients. In 14 patients profound hypotension (mean arterial blood pressure 35-40 mmHg, hypotension group) was induced by enalapril and nitroglycerin for a mean duration of 71 min. In 7 patients the tumor was not resectable, and hypotension was not induced (controls). We did not detect significant differences in serum levels of cytokines or sE-Selectin perioperatively in patients with profound hypotension compared with controls. In both groups IL-6 serum levels increased significantly and reached a maximum after rewarming (17 +/- 6 and 16 +/- 5 pg/dL, respectively, P < 0.001). IL-1beta, IL-10, and TNF-alpha did not change perioperatively in both groups. On the first postoperative day sICAM-1 serum levels were significantly increased in both groups (mean increase of 96 and 54 ng/mL, respectively, P < 0.01 and P < 0.05). We conclude from this study that profound normovolemic arterial hypotension does not seem to have effects on serum levels of circulating IL-1beta, IL-6, IL-10, TNF-alpha, and sE-Selectin. Perioperative moderate hypothermia may be the reason for the postoperative increase in sICAM-1 levels independent of the blood pressure.
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PMID:Effect of profound normovolemic hypotension and moderate hypothermia on circulating cytokines and adhesion molecules. 1056 7

The purpose of this study was to determine whether short-term exposure to clinically relevant concentrations of Pseudomonas aeruginosa lipopolysaccharide (LPS) impairs vasoreactivity of resistance arterioles in the intact spinotrapezius muscle microcirculation and, if so, to determine the mechanisms mediating this response. Using intravital microscopy, we found that 60-min suffusion of P. aeruginosa LPS (0.03-3.0 microg/ml) on the in situ hamster spinotrapezius muscle elicited an immediate, profound, and prolonged concentration-dependent vasodilation (P < 0.05). This response was reversible once suffusion of P. aeruginosa LPS was stopped. Pretreatment with N(G)-nitro-L-arginine methyl ester (10.0 microM), a nonselective nitric oxide (NO) synthase inhibitor, but not N(G)-nitro-D-arginine methyl ester, abrogated P. aeruginosa LPS-induced vasodilation and elicited a small, albeit significant, vasoconstriction. Indomethacin had no significant effects on P. aeruginosa LPS-induced responses. P. aeruginosa LPS had no significant effects on acetylcholine- and nitroglycerin-induced vasodilation in the spinotrapezius muscle. Collectively, these data indicate that short-term exposure to clinically relevant concentrations of P. aeruginosa LPS evokes an immediate, potent, prolonged, and reversible NO-dependent, prostaglandin-independent vasodilation in skeletal muscles in vivo. We suggest this response could play an important role in the pathophysiology of the profound vasomotor dysfunction observed in the peripheral circulation of patients with P. aeruginosa sepsis syndrome.
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PMID:Effects of Pseudomonas aeruginosa endotoxin on vasodilation in the intact spinotrapezius muscle. 1140 51

In vascular smooth muscle, cyclic nucleotide-dependent phosphorylation of heat shock protein 20 (HSP20) on serine-16 (Ser16) has been suggested to cause force suppression, i.e., reduced force with only minimal myosin regulatory light chain (MRLC) dephosphorylation. We hypothesized that heat pretreatment also suppresses force by increasing HSP20 phosphorylation. After heat pretreatment of swine carotid artery at 44.5 degrees C for 4 h and reduction to 37 degrees C for 1 h, Ser16-HSP20 phosphorylation was increased and histamine-induced increases in contractile force were suppressed. Subsequent addition of nitroglycerin induced additive force suppression. Heat and nitroglycerin induced a similar relation between Ser16-HSP20 phosphorylation and force. Heat pretreatment induced a small, but significant, increase in total HSP20 immunostaining. These results demonstrate that vascular smooth muscle responds to thermal stress by increasing Ser16-HSP20 phosphorylation in addition to a possible small increase in total HSP20 concentration. The resulting heat-induced reduction in force should be considered "force suppression" because histamine-induced increases in MRLC phosphorylation were not significantly altered by heat pretreatment. These processes may bring about a resistance to contractile agonists, which could have clinical significance in conditions such as hyperthermia and/or sepsis with vasodilatory shock.
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PMID:Heat-induced force suppression and HSP20 phosphorylation in swine carotid media. 1213 54


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