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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Vagotomy alters regional blood flow distribution by interrupting the tonic central inhibitory effect of cardiopulmonary vagal afferent nerves on sympathetic outflow predominantly to the renal, splanchnic, and cutaneous circulations. We hypothesized that the alteration of blood flow distribution by vagotomy would lead to disruption of the oxygen consumption-oxygen delivery relationship (VO2/DO2), increase critical DO2 (DO2Crit), and decrease whole-body oxygen extraction ratio (O2ER). Nineteen chloralose-anesthetized, paralyzed, splenectomized dogs were submitted to either bilateral vagosympathectomy (n = 7), bilateral vagotomy (n = 6), or sham denervation (n = 6) following baseline cardiorespiratory parameter measurement. ⋯ After hemorrhage had been performed to a point that decreased mean arterial pressure to approximately 70 mmHg from baseline values, carotid blood flow in the vagosympathectomy group was significantly greater than the control group. We conclude that vagotomy disrupts the VO2/DO2 relationship. Vagosympathectomy causes a severe disruption of the VO2/DO2 relationship, probably by the combined effect of vagotomy and interruption of sympathetic nervous system control of blood flow to the head and neck.
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Hemorrhagic shock appears to predispose patients to subsequent sepsis. This study examined the effect of different resuscitation fluids on macrophage function following hemorrhagic shock. Male Sprague-Dawley rats were bled to a blood pressure of 50 mmHg for 60 min and then resuscitated with 6% hydroxyethyl starch (HES) or Lactated Ringers (LR). ⋯ A final group had shock with either LR or HES resuscitation and then CLPE as above. Splenocytes were harvested 48 h after shock for mixed lymphocyte culture (MLC). Animals undergoing shock with subsequent septic challenge (Shock/CLPE) showed significantly increased mortality 40 vs. 0% (chi square, p < .05) and immunosuppression on MLC 2,088(LR)/3,300 (HES) vs. 18,570 (LR)/17,705 (HES) compared to CLPE alone (Student's t test, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Pentoxifylline (PTX), a xanthine derivative used in the treatment of circulatory insufficiency, has been found to have protective effects in different models of sepsis. We hypothesized that this drug might improve the cellular oxygen availability following endotoxin challenge by increasing oxygen delivery (DO2) and/or tissue oxygen extraction. The oxygen extraction capabilities were studied during a reduction in blood flow induced by cardiac tamponade. ⋯ PTX also improved ventilation/perfusion matching in the lungs as indicated by a higher PaO2 and PvO2 and a lower venous admixture than in the untreated group during cardiac tamponade (both p < .05). In addition, the critical DO2 (DO2 crit) was lower and the critical oxygen extraction ratio was higher in the PTX treated than in the control group (9.1 +/- 1.8 vs. 11.6 +/- 2.4 ml/kg.min, and 70.6 +/- 14.0 vs. 49.3 +/- 14.6%, both p < .05). The VO2/DO2 dependency slope was also steeper in the PTX-treated than in the control group (.80 +/- .28 vs. .43 +/- .19, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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The free radical nitric oxide (NO) is synthesized from the guanidino group of L-arginine by a family of enzymes termed NO synthase (NOS). Hemorrhagic shock leads to an inhibition of NO production by the calcium-dependent, endothelial NOS (ecNOS), which may lead to maldistribution of blood flow leading to, e.g., coronary, renal, and cerebral ischemia and may enhance the adhesion of neutrophil granulocytes and platelets to the endothelial surface. ⋯ An impairment of NO formation by the ecNOS has been demonstrated in various models of traumatic shock, whereas there is good experimental evidence supporting the hypothesis that an enhanced formation of NO contributes to the pathophysiology of experimental thermal injury and anaphylactic shock. We speculate that a pharmacological modulation of NO biosynthesis which either enhances NO concentration in the vicinity of endothelium (i.e., NO donors) or inhibits NO overproduction following iNOS expression (i.e., iNOS-selective NOS inhibitors) may become novel therapies to improve the outcome of patients with circulatory shock of various etiologies.
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Our previous work suggests that Caco-2 cells play an active role in bacterial translocation (BT). Since bacterial enterocyte interactions may be receptor-mediated, the current study was performed to investigate the role of beta 1 integrin and mannose receptors as well as the general protective effect of the mucous layer in this process. Caco-2 cells grown to confluence on semipermeable membranes contained in the upper compartment of a two compartment system were utilized. ⋯ Pretreatment of the Caco-2 cells with the beta 1 integrin receptor competitive inhibitors fibronectin or RGD did not inhibit BT; while pretreatment of Caco-2 cells with the LFA-1 (lectin) receptor competitive inhibitor mannose (12 mg/ml) or purified mucin (8 mg/ml) decreased BT compared to control membranes (p < .001). Transepithelial resistance was similar among all the groups indicating maintenance of tight junction integrity. These studies suggest that E. coli BT in the Caco-2 system can be reduced by mannose and that intestinal mucin contributes to the barrier function of the monolayer.