The imbalance between proliferation and apoptosis contributes to degeneration of aortic valves and bioprostheses.

BACKGROUND: The pathomechanisms underlying aortic valve degeneration are incompletely understood. Therefore, the aim of our work was to assess the quantitative changes of proliferation and apoptosis accompanied by cellular phenotype alternations and matrix secretionin aortic sclerotic and stenotic valves and degenerative bioprostheses, as well as to detect the expression pattern of the rapamycin receptor FKBP12 across these three valve types. METHODS: Mild-to-moderate sclerotic and stenotic valves and degenerative bioprostheses from 30 patients (n = 10 per group) were collected at autopsy or by surgery. Ki67+, FKBP12+, alpha-actin+, HSP47+ and TUNEL+ apoptotic cells were analyzed by immunohistochemistry. RESULTS: The main finding was the reduced proliferation and increased apoptosis in stenotic valves (ST) compared to the sclerotic ones (SC) (proliferation: ST: 20.8 ± 2.0% vs. SC: 30.1 ±2.2%, apoptosis: ST: 40.7 ± 5.0% vs. SC: 28.0 ± 5.1%, p < 0.05, respectively). Analogical alternations were found in degenerative bioprostheses (BP) (proliferation: 4.8 ± 2.3%; apoptosis: 13.1 ± 6.8%). Corresponding changes were observed in the valve cellularity (ST: 893 ± 168, SC: 1034 ± 284, BP: 385 ± 179 cells/mm2, p < 0.05, respectively). The FKBP12 signaling was reduced in diseased valves and bioprostheses (ST: 28.1 ± 3.6%, SC: 42.2 ± 3.8%, BP: 5.8 ± 1.9%, p < 0.05, respectively). Further, the augmented alpha-actin expressionwas observed as the degenerative process progressed (ST: 30.3 ± 5.0%, SC: 22.6 ± 2.7%, BP:8.7 ± 4.0%, p < 0.05, respectively), followed by the upregulation of HSP47 (ST: 22.6 ± 2.8%,SC: 15.4 ± 2.1%, BP: 3.4 ± 1.0%, p < 0.05, respectively) and consecutive matrix accumulation. CONCLUSIONS: The imbalance between proliferation and apoptosis with cellular phenotypical shift and subsequent matrix secretion may contribute to aortic valve stenosis and bioprosthesis degeneration. The identification of FKBP12 expression may implicate potential therapeutic strategies.

Transit time flow measurement in on-pump and off-pump coronary artery surgery.

OBJECTIVE: Transit time flow measurement is frequently used during coronary artery bypass with and without cardiopulmonary bypass to detect graft dysfunction resulting from technical errors. METHODS: Intraoperative transit time flow measurement measurements of 896 patients requiring surgery for double- or triple-vessel disease were reviewed retrospectively. Six-hundred and ninety-five patients were operated on-pump (Group A: coronary artery bypass with cardiopulmonary bypass), and 201 patients off-pump (Group B: coronary artery bypass without cardiopulmonary bypass). Transit time flow measurement measurements were analyzed for mean flow (mL/min). In total, measurements of 2247 grafts were analyzed. RESULTS: Transit time flow measurement flows were lower in coronary artery bypass without cardiopulmonary bypass patients (left internal thoracic artery to left anterior descending artery: Group A, 37 [31, 40] mL/min vs Group B, 24 [20, 26] mL/min; saphenous vein graft to left anterior descending artery: Group A, 46.5 [40, 56] mL/min vs Group B, 21 [14, 57] mL/min. Troponin I release was reduced in the coronary artery bypass without cardiopulmonary bypass patients, with median values of 7.8 [7.0, 8.3] microg/L in Group A and 1.2 [0.9, 2.3] microg/L in Group B. CONCLUSION: Evaluation of transit time flow measurement is valuable in determining coronary graft patency after coronary artery bypass with cardiopulmonary bypass and coronary artery bypass without cardiopulmonary bypass. Decreased troponin I release suggests a myocardial benefit of coronary artery bypass without cardiopulmonary bypass compared to coronary artery bypass with cardiopulmonary bypass, although the intraoperative transit time flow measurement flow measurements are markedly lower.