The Journal of surgical research
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Early fluid resuscitation in hypotensive trauma patients is controversial due to the risk of increasing blood loss and mortality. We determined the effects of infusion rate and time of resuscitation on blood loss and mortality and compared the outcome to nonresuscitated animals in severe, uncontrolled hemorrhagic shock in a rat model. In anesthetized rats, piercing of the infrarenal aorta with a 25-G needle caused a fall of mean arterial pressure to <20 mm Hg and blood loss of about 20 ml/kg in 90% of the animals. Animals were assigned to the following treatment groups (n = 6): 60 ml/kg of lactated Ringer's solution (LR) infused at a rate of 1.5 ml/min and given at 2.5 min (Group I), 5 min (Group II), or 10 min (Group III) postinjury, or LR infused at a rate of 3.0 ml/min and given at 5 min (Group IV) or 10 min (Group V) postinjury. Another group (n = 9) was not resuscitated. The animals were followed for 3 hr. Total blood loss in Group I (30.5 +/- 2.6 ml/kg) was significantly (P < 0.05) higher when compared to nonresuscitated animals (22.1 +/- 0.8 ml/ kg) or Group III (22.7 +/- 1.0 ml/kg), and also significantly higher in Group IV (35.8 +/- 4.1 ml/kg) when compared to nonresuscitated animals or Group V (23.0 +/- 1.2 ml/kg). The mortality rate was 7/9 in nonresuscitated animals and 5/6 in Group IV, both were significantly higher than in Groups II, III, and V (0 or 1/6) and markedly higher than in Group I (2/6). ⋯ In this model of uncontrolled hemorrhage, initially uncorrected severe shock resulted in a high mortality rate. The risk of increased blood loss and mortality associated with early fluid resuscitation could be diminished by avoiding too fast of infusion rates early after the injury.
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Comparative Study
A [+18RGD] protamine variant for nontoxic and effective reversal of conventional heparin and low-molecular-weight heparin anticoagulation.
Protamine sulfate reversal of heparin anticoagulation causes adverse side effects. Additionally, protamine sulfate is relatively ineffective at reversing factor Xa inhibition caused by low-molecular weight heparin (LMWH, Enoxaparin). Previously, a +18 compound partially reversed heparin and LMWH with minimal toxicity. ⋯ Maximum hemodynamic perturbations paralleled the TTS pattern. [+18RGD] provided equal reversal efficacy to [Prot +21] for Hep, with a statistically significant (P < 0.05) lessening of platelet count declines (Plt 27, -46, and -55%, respectively). [+18RGD] improved reversal efficacy for LMWH, at 3, 10, and 30 min following its administration. At 3 min, antifactor Xa reversal was 72, 40, and 30%, respectively, for [+18RGD], [+18BE], and [Prot +21]; [+18RGD] effects were significantly better (P < 0.01). [+18RGD] reversed both Hep and LMWH anticoagulation with minimal toxicity. Such a compound should decrease clinical complications attending the use of standard protamine for reversal of conventional heparin or LMWH anticoagulation.
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Although burn wound excision and grafting have been shown to improve patient survival, the effects on immune function, especially humoral immunity, are not completely understood. The purpose of this study was to investigate the effect of immediate and early wound excision on antibody synthesis and B-cell proliferation, specifically, antibody response to PGPS, a ubiquitous bacterial cell wall antigen. Thirty-six male BALB/c mice were divided into four groups. ⋯ Early excision and grafting (BE&G72), however, failed to significantly improve any B-cell functions. Immediate but not early BE&G restored antibody synthesis to the bacterial cell wall antigen (PGPS). Immediate BE&G may therefore lead to a decrease in bacterial infection after burn injury.
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The pineal hormone melatonin has been used in clinical trials in patients suffering from AIDS and also as an adjuvant for cancer therapy. Although melatonin has been reported to have beneficial effects in some animal models of immune dysfunction, it remains unknown whether this hormone has any salutary effects on immunity following soft-tissue trauma and/or major blood loss. To study this, soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (arterial BP 35 +/- 5 mm Hg) were induced in C3H/HeN mice. ⋯ The results indicate that melatonin administration after trauma-hemorrhage significantly improved the depressed immune functions, as evidenced by the restoration of Mphi IL-1 and IL-6 release, as well as significantly improved splenocyte IL-2 and IL-3 release and splenocyte proliferative capacity. No differences in circulating corticosterone levels between vehicle- and melatonin-treated animals were observed. This is the first study to show that melatonin, which is reported to be free of adverse side effects, can be considered a safe and effective therapeutic agent for restoring the depressed immunological function after soft-tissue trauma and hemorrhagic shock.
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To characterize the mesenteric alpha1- and alpha2-adrenoceptor populations in newborn piglets, an extracorporeal circuit was established to control intestinal blood flow in 0- to 2-day old and 10- to 14-day old animals. In both groups, alpha-adrenoceptor activation was first documented by observing dose-dependent increases in mesenteric perfusion pressure after intramesenteric arterial injection of alpha-adrenoceptor agonists. ⋯ In addition, mesenteric vasoconstrictor responses to other known vasoconstrictor agents--angiotensin II, neuropeptide Y, and a thromboxane A2 mimic (U-46619)--were not effected in either age group by prazosin or yohimbine, implying these agents act independently of alpha-adrenoceptor mechanisms. These data suggest that (1) there exists functional mesenteric alpha1- and alpha2-adrenoceptor-like activity in 10- to 14-day old piglets that, in 0- to 2-day old animals, is not specifically expressed; and (2) mesenteric alpha-adrenoceptor function becomes more selective as newborn piglets mature.