To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 + 47 vs 130 ± 21 ml/min in the control group, p < .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p < .005), while that of lactate was increased (36% vs 12%, p < .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41 % of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock. These data indicate that myocardial utilization of endogenous substrates may probably account for this discrepancy, suggesting that a "mandatory" utilization of endogenous energy sources might underlie progressive cardiac involvement in septic shock. Circulation 75, No. 3, 533-541, 1987. SEPTIC SHOCK is a frequent and serious disorder with a high mortality. In recent years, increasing attention has been directed to the study of the hemodynamic and metabolic alterations accompanying septic shock.

In order to test the existence of a possible oxidative damage during hemodialysis, plasma conjugated dienes (CD), plasma and red blood cell (RBC) thiobarbituric acid (TBA) reactants were investigated in 25 patients receiving regular dialysis treatment (RDT). The RBC TBA reactant concentration was significantly increased in RDT patients in comparison with healthy subjects. The extracellular antioxidant systems were evaluated by the assay of plasma antioxidant activity, plasma tocopherol, urate, transferrin, haptoglobin and ceruloplasmin levels. Except urate and transferrin, none of these parameters were different between the two groups. On the other hand, in RDT patients, RBC superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were significantly lower than in healthy subjects. There was an inverse correlation between decreased RBC GPX and RBC TBA reactant concentration. These results show in RDT patients the existence of an oxidizing stress, mainly intracellular, which could be due, in part, to a decrease in SOD and GPX activities.

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alpha 1-Acid glycoprotein (alpha 1-AGP), a naturally occurring human plasma protein and acute-phase reactant, was extracted by a two-step procedure from sera collected from four healthy men. Its activity was tested in vitro on human polymorphonuclear (PMN) functions (migration, aggregation, O2- generation). alpha 1-AGP was not chemoattractant but inhibited the PMN response to the chemoattractant formylmethionyl-leucyl-phenylalanine without affecting spontaneous migration (Boyden and agarose methods of assessment). At concentrations between 0.15 and 0.45 mg/ml, alpha 1-AGP exerted an aggregating effect with a maximal effective concentration of 0.3 mg/ml. alpha 1-AGP inhibited superoxide generation by PMNs stimulated either by opsonized zymosan or phorbol myristate acetate. This inhibition varied according to the intensity of the stimulation. At low stimulus concentrations, a dose-dependent inhibition of membrane-associated PMN responsiveness to soluble or particulate stimuli was observed. These findings suggest that alpha 1-AGP may be able to prevent PMN activation in the course of inflammatory processes in vivo.

An in vitro model of Giardia duodenalis and the Caco2 cell line enable the study of parameters that could play a part in trophozoite attachment. We explored the role of membranous lectins of G. duodenalis in attachment-inhibition studies using carbohydrates in solution. Attachment rates were reduced by 14% and 23% in the presence of 100 mmol/l mannose-6-phosphate and glucose, respectively, as compared with control values. No significant modification was observed after trophozoite trypsinization at room temperature or at 37 degrees C. The inhibitory effects of colchicine (35%) and nocodazole (70%) suggest a primordial role of the cytoskeleton; microtubules appear to be the principal effectors of trophozoite fixation. Scanning electron microscopy revealed circular imprints on the Caco2 brush border after trophozoite detachment. The mechanisms of attachment of G. duodenalis to intestinal enterocyte-like cells in culture are thus essentially of the mechanical or hydrodynamic type; surface lectins would appear to intervene in the specificity for duodenal cells.