The Journal of surgical research
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Antibody against tumor necrosis factor-alpha (TNF-alpha) has improved survival in certain models of sepsis, but it remains unproven in clinical studies. In most of the successful animal studies, efficacy has been shown in previously healthy animals subjected to a septic challenge. Patients at risk for sepsis, however, may be ill for some time before the sepsis supervenes. ⋯ High doses of antibody (3.2 x 10(5) n.u.kg-1) were not beneficial and may have been detrimental. These results show that neutralizing antibody against TNF-alpha may reduce the susceptibility to infection seen after thermal injury, but the timing of administration of the antibody and the dose of antibody used are critical to the outcome. This should be considered when neutralizing antibody against TNF is used in the clinical setting.
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Protein kinase C (PKC) is an ubiquitous regulatory enzyme with dense myocardial distribution and activity; however, its physiologic relevance to myocardial function remains poorly understood. Although endogenous Ca2+ is a potent stimulus of PKC isoforms alpha and beta (cPKCs) it remains unknown whether exogenous Ca2+ activates these PKC isoforms, and if so, whether PKC plays any role in Ca2+-induced myocardial inotropy. To study this, ventricular sections from isolated rat hearts, with and without Ca2+-induced inotropy (CaCl2, 0.5 mM coronary concentration x 2 min), were probed for cPKC isoform translocation using immunofluorescence in order to determine if exogenous Ca2+ indeed activates cPKCs. ⋯ This dose of exogenous Ca2+ resulted in myocardial inotropy as determined by DP, dP/dt, and CF. Furthermore, myocardial inotropy was attenuated with concurrent inhibition of PKC activity. These findings link the physiologic effects of exogenous Ca2+ to PKC, providing a better understanding of the physiologic mechanism of Ca2+-induced inotropy.
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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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While it is well known that prolonged preservation of the intestinal graft causes severe mucosal damage after transplantation, little is known about the effect on neuromuscular function. The entire small intestine of adult hound dogs was flushed and preserved with cold lactated Ringer's solution and autotransplanted either immediately (n = 6) or after 24 hr (n = 6). Animals undergoing sham operation (n = 4) were used as a control. ⋯ The results of our study indicate that intestinal dysmotility is augmented in prolonged-preservation grafts compared to those with brief preservation. The dysmotility was transient and normalized 3 to 4 weeks after surgery. Preservation and reperfusion injury to the neuromuscular system of intestinal grafts are reversible and are attenuated by simple hypothermia.