Pulsed perfusion in a venous human organ culture model with a Windkessel function (pulsed perfusion venous HOC-model).

BACKGROUND: The effectiveness of human saphenous vein grafting is limited by hyperplasia of the vessel wall. The current paper reports on a pulsed perfused venous human organ culture model (pp-venous HOC-model) with a Windkessel function. MATERIAL/METHODS: Saphenous vein grafts from 21 patients undergoing coronary bypass grafting were cultured either in venous or arterial hemodynamic conditions. Up to four vein segments were fixed in parallel connection and attached to a closed loop pulsed perfusion system consisting of large and small elastic tubes, mimicking the Windkessel function. RESULTS: First, after exposure to arterial blood pressure first signs of reactive cell proliferation (n.s.) were detected at day 4. Second, media thickness of the venous segments in the pulsed pressure group was decreased at day 4 (n.s.) and day 7 (n.s.). Third, staining against smooth muscle alpha actin and v. Willebrand factor was always positive at day 1, 4, and 7. CONCLUSIONS: Pulsed perfusion in a human venous organ culture model with a Windkessel function is an approach to better understand the events taking place during early arterial-vein grafting. First signs of reactive cell proliferation were detected at day four. A period of seven days as described in the current model is probably too short to detect reactive cell proliferation and medial thickening. If the device might be activated for a longer period of time, it should be a suitable model to characterize the effects of intra- and extravascular drug administration as treatment strategies of vein graft disease.

Intimal hyperplasia and expression of transforming growth factor-beta1 in saphenous veins and internal mammary arteries before coronary artery surgery.

BACKGROUND: The development of fibromuscular intimal hyperplasia and subsequent graft failure remains an urgent problem in cardiac surgery. Transforming growth factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis through induction of extracellular matrix proteins. We tested the hypothesis that intimal hyperplasia is already present in human saphenous veins and left internal mammary arteries before coronary artery bypass surgery and is associated with an increased expression of TGF-beta1. METHODS: Forty-six segments of saphenous veins and 27 of left internal mammary arteries were collected from 50 patients undergoing coronary artery bypass surgery. Morphometric analysis was performed by microscopic computer analysis. Immunohistochemistry was performed with antibodies directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2 receptor (RII). RESULTS: The incidence of intimal hyperplasia was significantly higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05). Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF-beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers) when compared with corresponding vessels without hyperplasia (both groups p < 0.05). Endothelial and intimal RII expression was significantly higher in saphenous veins with intimal hyperplasia as compared with saphenous veins without hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima correlated with the presence of an intimal hyperplasia in saphenous veins (rho = 0.317) and mammary arteries (rho = 0.428). CONCLUSIONS: Local TGF-beta1 expression is associated with the presence of intimal hyperplasia in the examined vessels. Preexisting intimal hyperplasia is more prevalent and serious in saphenous veins than in left internal mammary arteries, giving further explanation to the superior long-term results of left internal mammary grafts.

Overexpression of heat shock protein 60/10 in myocardium of patients with chronic atrial fibrillation.

BACKGROUND: Cardiomyocytes respond to chronic atrial fibrillation with increased expression of heat shock protein 60 (HSP60). The aim of this study was to investigate whether expression of the coprotein HSP10 is also increased. METHODS: Right atrial samples from 16 patients undergoing elective cardiac operation were excised and immediately frozen in liquid nitrogen. Eight patients had chronic atrial fibrillation and 8 patients were in sinus rhythm. The HSP60 and HSP10 protein levels were determined by SDS-PAGE, Western blot, and quantified by optical densitometry according to the immunoreactive bands of actin. RESULTS: In myocardial samples from patients with chronic atrial fibrillation we found simultaneous upregulation of both stress proteins. HSP60 expression was more than 2.3-fold and HSP10 expression was more than 2.4-fold increased in atrial myocardium of patients with chronic atrial fibrillation. CONCLUSIONS: These results indicate functional upregulation of mitochondrial HSP60 and HSP10 in response to chronic atrial fibrillation.

The expression of heat shock protein 60 in myocardium of patients with chronic atrial fibrillation.

OBJECTIVE: Cardiomyocytes respond to stress with the expression of different heat shock proteins (HSP). HSP60 is induced by various stress factors. The aim of this study was to investigate the expression of HSP60 in human atrial fibrillation (AF). METHOD: Right atrial samples from 14 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen. Eight patients had chronic AF and six patients were in sinus rhythm. The HSP60 protein level was determined by SDS-PAGE, Western blot and quantified by optical densitometry according to the immunoreactive bands of actin. RESULTS: In myocardial samples from patients with chronic AF, we found a more than 2.5-fold increase in HSP60 expression compared to atrial myocardium of patients in sinus rhythm. CONCLUSION: This result indicates an up regulation of HSP60 in response to chronic atrial fibrillation.