Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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S-ethylisothiourea (3936W92) is a nonamino acid antagonist of nitric oxide synthase. Its selectivity for the inducible form of nitric oxide synthase is twice as high as for the constitutive form of the enzyme. We tested 3936W92 in 20 sheep, which were surgically prepared for chronic study. ⋯ After 24 h of sepsis, nine sheep received a continuous infusion of 3936W92 over the next 24 h, whereas the control group (n = 9) received saline instead. Two sheep died within the first 24 h of sepsis. 3936W92 caused a complete reversal of the hyperdynamic circulation, while sheep in the control group remained hyperdynamic. Although the cardiac index decreased significantly during treatment with 3936W92 (7.9 +/- .8 vs. 6.0 +/- .7 l/min/m2), a simultaneous increase in oxygen extraction prevented oxygen consumption from falling.
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To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. ⋯ LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.
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A number of clinical studies have shown that multiple and severe trauma causes immunosuppression and increases the susceptibility to sepsis. However, because there is a close temporal relationship between trauma and hemorrhage in humans, it is difficult to dissociate the effects of tissue trauma versus hemorrhage on immunity in the clinical setting. Studies in mice have shown that simple hemorrhage per se as well as laparotomy alone produces a marked depression in cellular immunity and no difference was seen in the extent of depression at 2 h if these two insults were combined. ⋯ The proliferative capacity of the splenocytes, as well as their ability to release IL-2 and IL-3, was markedly decreased in the trauma-hemorrhage animals but was normal in the other groups. Furthermore, the release of IL-6 by peritoneal macrophages from animals that underwent trauma-hemorrhage was also significantly depressed. These results support the concept that traumatic injury in the form of a midline laparotomy combined with hemorrhage produces a more protracted impairment in cell-mediated immunity than laparotomy or hemorrhage alone.
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A Physiologic State Severity Classification (PSSC) derived from clustering of 17 cardiorespiratory variables was used to predict cytokine response in critically ill posttrauma patients. The PSSC defined physiologic states: A-State (A), normal stress response; B-State (B), metabolic insufficiency; C2-State (C), respiratory insufficiency. ⋯ Of 25 deaths (88% s, 60% s-ARDS, mean Pdeath = .64) 0% were A, 44% B, and 56% C. PSSC States were correlated with incidence and mean plasma levels (pl) in picograms/mL of cytokines. 23 samples from recovering nonseptic trauma patients were used as controls.
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Hypertonic sodium acetate has recently been suggested for treatment of hemorrhagic shock. In the present study, the effectiveness of hypertonic sodium acetate (HA) was studied. In controlled hemorrhagic shock, arterial bleeding was followed by a fall in mean arterial pressure (MAP) to 60 +/- 8 mmHg (p < .001). ⋯ The mortality rate after 4 h was 50% in the HA-treated (p < .05) and 75% in the HTS-treated (p < .01) groups. It is concluded that, in awake rats in CHS, both HTS and HA led to a rise in MAP but the response to HTS is significantly higher. In UCHS both HTS and HA led to increased bleeding from injured blood vessels, a fall in MAP, and increased mortality.