Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities.

Multiple common cardiovascular comorbidities produce coronary microvascular dysfunction. We previously observed in swine that a combination of diabetes mellitus (DM), high fat diet (HFD) and chronic kidney disease (CKD) induced systemic inflammation, increased oxidative stress and produced coronary endothelial dysfunction, altering control of coronary microvascular tone via loss of NO bioavailability, which was associated with an increase in circulating endothelin (ET). In the present study, we tested the hypotheses that (1) ROS scavenging and (2) ETA+B-receptor blockade improve myocardial oxygen delivery in the same female swine model. Healthy female swine on normal pig chow served as controls (Normal). Five months after induction of DM (streptozotocin, 3 × 50 mg kg-1 i.v.), hypercholesterolemia (HFD) and CKD (renal embolization), swine were chronically instrumented and studied at rest and during exercise. Sustained hyperglycemia, hypercholesterolemia and renal dysfunction were accompanied by systemic inflammation and oxidative stress. In vivo ROS scavenging (TEMPOL + MPG) reduced myocardial oxygen delivery in DM + HFD + CKD swine, suggestive of a vasodilator influence of endogenous ROS, while it had no effect in Normal swine. In vitro wire myography revealed a vasodilator role for hydrogen peroxide (H2O2) in isolated small coronary artery segments from DM + HFD + CKD, but not Normal swine. Increased catalase activity and ceramide production in left ventricular myocardial tissue of DM + HFD + CKD swine further suggest that increased H2O2 acts as vasodilator ROS in the coronary microvasculature. Despite elevated ET-1 plasma levels in DM + HFD + CKD swine, ETA+B blockade did not affect myocardial oxygen delivery in Normal or DM + HFD + CKD swine. In conclusion, loss of NO bioavailability due to 5 months exposure to multiple comorbidities is partially compensated by increased H2O2-mediated coronary vasodilation.

Risk factors in hepatitis C virus-infected blood donors.

Risk factors of parenteral and nonparenteral exposure to hepatitis C virus (HCV) infection were studied in 125 blood donors in The Netherlands who were positive for anti-HCV on enzyme-linked immunosorbent assay (ELISA). Risk factors were related to confirmatory test results of four-antigen recombinant immunoblot assay (4-RIBA) and polymerase chain reaction (PCR) of the HCV 5' untranslated region. Twelve (10%) of the 125 anti-HCV C100 ELISA-positive blood donors were 4-RIBA positive. Eleven (92%) of 12 4-RIBA-positive blood donors were PCR positive, and all 113 remaining 4-RIBA-negative or -indeterminate donors were PCR negative. Eleven (92%) of 12 4-RIBA-positive blood donors had a risk factor of parenteral exposure, as compared to 17 (15%) of 113 4-RIBA-negative or -indeterminate donors. The prevalence of confirmed HCV infection among Amsterdam blood donors is calculated at 0.04 percent; parenteral exposure appears to be the major risk factor for HCV infection.