Attenuated renal and intestinal injury after use of a mini-cardiopulmonary bypass system

Background. Transient, subclinical myocardial, renal, intestinal, and hepatic tissue injury and impaired homeostasis is detectable even in low-risk patients undergoing conventional cardiopulmonary bypass (CPB). Small extracorporeal closed circuits with low priming volumes and optimized perfusion have been developed to reduce deleterious effects of CPB. Methods. A prospective, randomized trial was conducted in 49 patients undergoing elective coronary artery bypass graft surgery either with the use of a standard or mini-CPB system (Synergy). We determined early postoperative inflammatory response (leukocytosis, C-reactive protein, urine interleukin-6), platelet consumption and activation (urine thromboxane B2), proximal renal tubular injury (urine N-acetyl-glucosaminidase), and intestinal injury (intestinal fatty acid binding protein). Results. In patients undergoing coronary artery bypass grafting with a mini-CPB system, we observed decreased priming volumes with subsequent attenuation of on-pump hemodilution, improved hemostatic status with reduced platelet consumption and platelet activation, decreased postoperative bleeding and minimized transfusion requirements. We also found reduced leukocytosis and decreased urinary interleukin-6. Levels of urine N-acetyl-glucosaminidase were on average threefold lower, and urinary intestinal fatty acid binding protein was 40% decreased in the patients on the mini-CPB system, as compared with standard CPB. Conclusions. The use of the mini-CPB system during myocardial revascularization represents a viable non-pharmacologic strategy that can attenuate the alterations in the hemostatic system, reduce bleeding and transfusion requirements, decrease systemic inflammatory response, and reduce immediate postoperative renal and intestinal tissue injury

Acute isovolemic hemodilution triggers proinflammatory and procoagulatory endothelial activation in vital organs: Role of erythrocyte aggregation

Objectives: The essential role of erythrocytes as oxygen carriers is historically well established, but their function to aggregate and the consequences on the microcirculation is under debate. The pathogenic potential of low erythrocyte aggregation could be important for patients undergoing on-pump cardipopulmonary bypass. These patients are severely hemodiluted due to preoperative isovolemic hemodilution (IHD), circuit priming, and large fluid infusions perioperatively. Considering the vascular endothelium sensitivity to variations in blood rheology, the authors hypothesize that low erythrocyte aggregation will be responsible for activation of vascular endothelium during acute IHD. Methods: Acute IHD (30 mL/kg exchange transfusion with colloid solutions) was induced in an "aggregating species(pigs, n = 15). The hypoxic oxidative stress (plasma malondialdehyde, ex vivo oxygen radicals production in heart, lung, kidney, liver, and ileum tissue biopsies), erythrocyte aggregation (LORCA), and endothelial activation (real-time quantitative RT-PCR on von Willebrand factor (vWF), E- and P-selectins, endothelial nitric oxide synthase gene-expression in tissue biopsies) were investigated. Results: The production of superoxide and hydroxyl radicals, measured as H2O2 generation, was similar at all times in sham-operated and hemodiluted animals, proving a maintained oxygen delivery to tissues. Acute IHD was followed by a dramatic drop in erythrocyte aggregation and immediate prothrombotic (significant vWF mRNA upregulation in heart, lungs, kidney, liver, ileum) and proinflammatory (significant E- and P-selectins mRNA upregulation in lungs and ileum) endothelial activation. Low erythrocyte aggregation was significantly correlated with increased mRNA-expression of vWF (heart, liver, ileum) and P-selectin (lungs, ileum, and heart). Conclusions: These results suggest that low erythrocyte aggregation might trigger endothelium-dependent thrombogenic and proinflammatory response during acute isovolemic hemodilution

Does hepatitis C increase the accumulation of advanced glycation end products in haemodialysis patients?

Methods. AGE accumulation was measured by means of skin autofluorescence (AF) in 92 haemodialysis (HD) patients and 93 age-matched healthy controls. In the HD patients, CVD-related biochemical variables were also measured. The HD patients were tested for hepatitis C virus (HCV) antibodies and allocated to a HCV+ or HCV- group. Results. Skin AF of the healthy subjects was lower than skin AF in the HD patients (3.13 +/- 0.95 vs 2.2 +/- 0.47; P <0.001). We calculated the average increase of skin AF in the healthy subjects to be 0.017 arbitrary units per year, being 14 times lower than in HD patients with CVD only and 20 times lower than in HD patients suffering from combined CVD and diabetes mellitus (DM). Multivariate regression analysis showed that AGE accumulation in HD patients can be described by the independent effects of age, DM, CVD and HD vintage. Although inter-cellular adhesion molecule 1 and liver enzymes were elevated in HCV+ HD patients, levels of oxidative stress markers and skin AF were not significantly different between HCV+ and HCV- HD patients. Conclusions. AGE accumulation was higher in the HD patients than in the healthy controls. AGE accumulation did not differ in HCV+ and HCV- HD patients. This might be due to the fact that hepatitis C did not cause oxidative stress in our HD population. Independent markers of AGE accumulation were age, HD vintage, DM and CVD, but not hepatitis C