Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a chronic hypercholesterolemic porcine model.

OBJECTIVE: The value of prophylactic brachytherapy on vein graft disease is unknown. METHODS AND RESULTS: Vein bypass grafts in 23 hypercholesterolemic pigs after ex vivo gamma irradiation of the vein grafts (10, 20, and 40Gy) and 16 control veins were analyzed regarding: (1) expression of platelet-derived growth factor (PDGF-AA and -BB, ELISA); (2) smooth muscle cell (SMC) proliferation/cell death (double-immunohistochemistry Mib-1/TUNEL/SMC alpha-actin); and (3) vessel wall dimensions. Planimetric data on vessel wall dimensions revealed no positive effect of gamma radiation on neointima formation and inner lumen diameter. On the contrary, vein grafts subjected to 40Gy were significantly more likely to be occluded and to have reduced inner lumen and increased neointima formation. Radiation therapy had no effect on PDGF expression and SMC proliferation/cell death. The mean inner lumen diameter decreased as PDGF-AA expression increased. CONCLUSIONS: Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a hypercholesterolemic porcine model. High-dose radiation (40Gy) resulted in more frequent graft occlusion and vein sclerosis.     

Safety of low-dose aprotinin in coronary artery bypass graft surgery: a single-centre investigation in 2,436 patients in Germany

BACKGROUND: The antifibrinolytic agent aprotinin is used to limit blood loss in cardiac surgery. In a recently performed multicentre observational study, the use of aprotinin was dose-dependently associated with a higher risk of renal failure and cardiovascular events. OBJECTIVE: Therefore, the aim of this study was to evaluate the impact of low-dose aprotinin (2 million kallikrein-inhibitor units) on safety variables in a large single-centre investigation in patients who underwent coronary artery bypass graft (CABG) surgery. METHODS: Clinical outcome variables such as renal failure, myocardial infarction, gastrointestinal failure, neurological complications and in-hospital mortality were assessed in 2,436 CABG surgery patients, whereof 1,162 patients received low-dose aprotinin perioperatively and 1,274 patients did not receive aprotinin. Statistical analysis was performed using multivariable logistic regression. RESULTS: In patients receiving aprotinin, the odds ratios of experiencing one of the aforementioned adverse events were not significantly different from the patients who did not receive aprotinin (p = 0.136-0.288). Moreover, the need for rethoracotomy did not differ between the two groups (p = 0.129). However, the use of low-dose aprotinin reduced the risk of peri- and postoperative use of packed red blood cells by 39% and was associated with a mean reduction in postoperative blood loss of 201 mL compared with patients who did not receive aprotinin (p < 0.001). Mean total blood loss in the aprotinin group and the control group was 875 mL (standard deviation [SD]: 757 mL) and 1,105 mL (SD: 867 mL), respectively (p < 0.001). In a sub-analysis in 2,049 patients undergoing their first cardiac surgery and undergoing CABG using the internal mammary artery, efficacy and safety data of aprotinin were similar to the results of the entire study cohort of 2,436 patients. CONCLUSIONS: Our data indicate that low-dose aprotinin efficiently reduces blood loss and does not adversely affect relevant safety variables in CABG surgery.     

Plasma N-terminal pro-brain natriuretic peptide as a marker of right ventricular dysfunction in patients with tetralogy of Fallot after surgical repair

OBJECTIVE: Chronic heart failure is associated with neurohormonal activation that is not only related to outcome but is also a therapeutic target. We have attempted to demonstrate whether a similar pattern of neurohormonal activation exists in adult congenital heart disease (ACHD) and, if so, whether it relates to disease severity determined by cardiopulmonary exercise testing. METHODS AND RESULTS: Concentrations of N-terminal pro-atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin (ET)-1, renin, aldosterone, adrenalin, and noradrenalin were determined in 50 adults (mean age, 27.8 +/- 1.7 years [+/- SEM]; 26 women) with tetralogy of Fallot (TOF) after surgical repair (New York Heart Association functional class 1.1 +/- 0.1). One hundred age- and sex-matched healthy blood donors served as a control group for NT-proBNP determination. Dimensions of ventricles, left ventricular pump function, and estimated right ventricular (RV) systolic pressure were determined by echocardiography. Maximum oxygen uptake (V(O2max) was measured in all patients using spiroergometry. TOF patients had elevated levels of NT-proBNP compared with healthy individuals: NT-proBNP (women: 180 pg/mL vs 43 pg/mL, and men: 147 pg/mL vs 32 pg/mL; p < 0.0001) and ET-1 (2.5 fmol/L vs 0.7 fmol/L). There was a significant correlation of NT-proBNP to dimension and estimated peak systolic pressure of the RV as well as impairment of V(O2max). CONCLUSIONS: RV dysfunction detected by echocardiography and plasma NT-proBNP determination in asymptomatic or minimally symptomatic TOF patients correlates well with their cardiopulmonary exercise capacity. Thus, these simple and noninvasive screening methods can be used additionally to stratify ACHD patients with impaired cardiac function before they become clinically symptomatic.     

Expression of the gene for hematopoietic cell specific protein is not restricted to cells of hematopoietic origin

Hematopoietic cell line specific protein (HS1) is an intracellular signaling protein that has been reported as specifically expressed in hematopoietic cells. HS1 is known as a major substrate of protein-tyrosine kinases following activation by B-cell or T-cell receptor complexes. We report the first evidence that HS1 is also expressed in a variety of tissues different from hematopoietic tissues by using sensitive expression analysis including real-time quantitative RT-PCR. While former studies on HS1-expression were mostly limited to cells of hematopoietic origin, we screened a larger number of human tissues including tumor samples. Normal lung tissue showed a high degree of HS1 expression, second to the expression of hematopoietic cells. Expression of HS1 in tumor tissues was also clearly detectable. Our findings suggest that the signaling protein HS1 is involved in pathways different from the ones that have a specific role in the intracellular processes of hematopoietic cells.