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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The ability to clinically assess myocardial contractility in a load-independent fashion facilitates the selection of appropriate inotropes, when needed, during shock resuscitation. Within the framework of the ventricular pressure-volume diagram, the slope of the ventricular end-systolic pressure-volume relationship (expressed as ventricular end-systolic elastance, Ees), has been shown to accurately reflect ventricular inotropic state, and to be insensitive to loading conditions. It has not, however, been widely used at the bedside. ⋯ Left ventricular end-diastolic volume index (mL/m2) improved with fluid administration (54 +/- 8.9 to 62 +/- 9.8, p < .0001) and effective arterial elastance (mmHg/mL/m2) decreased with afterload reduction (3.3 +/- .9 to 2.6 +/- .7, p < .0001). We conclude that Ees is a load-independent measure of contractility, which is measurable at the bedside. The pressure-volume diagram is a useful method of monitoring hemodynamic changes associated with interventions during shock resuscitation.
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In a porcine endotoxin shock model, the mixed nonpeptide endothelin receptor antagonist bosentan was administered 2 h after onset of endotoxemia (n = 8). Cardiopulmonary vascular changes, oxygen-related variables, and plasma levels of endothelin-1-like immunoreactivity were compared with a control group that received only endotoxin (n = 8). Bosentan abolished the progressive increase in mean pulmonary artery pressure and pulmonary vascular resistance seen in controls. ⋯ Endotoxemia resulted in an increase in tumor necrosis factor-alpha and endothelin-1-like immunoreactivity plasma levels, the latter being further increased by bosentan. In conclusion, in porcine endotoxemia, treatment with the endothelin receptor antagonist bosentan, administered during fulminate shock, abolished pulmonary hypertension and restored cardiac index. These findings suggest that bosentan could be an effective treatment for reversing a deteriorated cardiopulmonary state during septic shock.
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Comparative Study
Superoxide radical scavenging prevents cellular calcium dysregulation during intraabdominal sepsis.
The role of superoxide in sepsis-altered hepatocyte Ca2+i regulation was studied by examining the effect of treatment of septic rats with superoxide dismutase-polyethylene glycol (SOD-PEG) on hepatocyte Ca2+ influx and efflux, and cytosolic [Ca2+]. Rats were implanted with sterile or bacteria-laden (Escherichia coli and Bacteroides fragilis) fecal pellets into the abdominal cavity. Eight hours after the implantation, rats were treated with SOD-PEG or its vehicle PEG. ⋯ When challenged with vasopressin, the hepatocytes from septic rats, administered with PEG alone, did not elevate their [Ca2+]i as was characteristic of the hepatocytes from the nonseptic rats. The treatment of septic rats with SOD-PEG was effective in restoring Ca2+ influx, cellular exchangeable Ca2+, [Ca2+]i, and the [Ca2+]i response to vasopressin to levels found in the control and sterile groups. These findings support the concept that the generation of the superoxide free radical leads to Ca2+i-related derangements and related cell/organ dysfunction in sepsis.
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Small-volume resuscitation using hypertonic saline (7.5%) is effective for various types of shock. Recently, hypertonic saline has been proposed for fluid management in patients with impaired cardiovascular function. Whether hypertonic saline is safe in the compromised heart during coronary occlusion is not known. ⋯ Our data demonstrates variant effects of hypertonic saline on either normal or ischemic myocardium. Whereas contractile function and blood flow in the normal myocardium were improved after hypertonic saline infusion, further decreases in blood flow and contractile function in region distal to coronary occlusion could lead to worsening of ischemic injury. These data suggest that hypertonic saline may be deleterious in hearts with impaired contractile function caused by ischemia.
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Review Comparative Study
Beneficial versus detrimental effects of nitric oxide synthase inhibitors in circulatory shock: lessons learned from experimental and clinical studies.
Septic shock is a physiological derangement of the cardiovascular system characterized by pathological vasodilation. Recent studies have established a role for nitric oxide, previously known as endothelium-derived relaxing factor, in the vascular dysfunction of sepsis. ⋯ We provide here an overview of the preclinical studies of NOS inhibitors and an update of the clinical studies. The low toxicity and marked antihypotensive activity of NOS inhibitors in humans highlight some of the drawbacks of certain animal models and provide important insights into the experimental study of septic shock.