Alveolar type II (ATII) cells are exposed to mechanical stretch during breathing and mechanical ventilation. Increased stretch may contribute to lung injury. The influence of three stretching patterns (characterized by frequency [min(-1)] - increase in surface area [%]: S40-13, S60-13, S40-30) on parameters of apoptosis, necrosis, and membrane integrity of rat ATII cells was compared with that in static cultures. The S40-13 stretching pattern simulated normal breathing. The other patterns were chosen to study increased amplitude and frequency. There were no significant differences between the S40-13 group and static cultures. Lactic acid dehydrogenase (LDH) release and early apoptotic cells were significantly increased in S60-13 and S40-30 in comparison with static cultures (LDH: 0.089 +/- 0.014 microg/ml and 0.177 +/- 0.050 microg/ml versus 0.050 +/- 0.011 microg/ml; early apoptosis: 17 +/- 3.5% and 23 +/- 3.1% versus 9.7 +/- 1.4%) at 24 h. Necrosis was significantly increased only in the S40-30 group (13 +/- 2.4% versus 6.1 +/- 0.9% in static culture at 24 h). Captopril as well as L-Arginine prevented apoptosis and reduced apoptotic cells to static culture levels in the S40-30 group, but did not influence necrosis and LDH release. Increased mechanical stretch may contribute to lung injury by induction of apoptosis and necrosis in ATII cells. Apoptosis induced by high-amplitude mechanical stretch is prevented by captopril and L-Arginine.
] ± Oberflä-chenzunahme [%]: S40 ± 13, S60 ± 13, S40 ± 30) auf Parameter von Apoptose, Nekrose und Zellmembranintegrität im Vergleich zu statischen Kontrollen. Das Dehnungsmuster S40 ± 13 simuliert physiologische Atmung, die anderen sollen den Einfluss gesteigerter Frequenz und Amplitude demonstrieren. Ergebnisse: Zwischen der Gruppe S40 ± 13 und statischen Kulturen bestanden keine Unterschiede. LDH-Freisetzung und frühapoptotische Zellen waren in den Gruppen S60 ± 13 und S40 ± 30 im Vergleich zu statischen Kulturen nach 24 h signifikant erhöht (LDH: 0,089 0,014 ìg/ml und 0,177 0,050 ìg/ml gegenüber 0,050 0,011 ìg/ ml; frühapoptotische Zellen: 17 3,5 % und 23 3,1 % gegenüber 9,7 1,4 %). Nekrotische Zellen fanden sich nur in der Gruppe S40 ± 30 signifikant erhöht (13 2,4 % gegenüber 6,1 0,9 % in statischer Kultur nach 24 h). Captopril und L-Arginin reduzierten das Ausmaû der Apoptose in der Gruppe S40 ± 30 nahezu auf das Niveau statischer Kulturen, ohne das Ausmaû an Nekrose und Abstract Background: Alveolar type-II(ATII)-cells are exposed to mechanical stretch during breathing and mechanical ventilation. Increased stretch may contribute to lung injury. Methods: The influence of three stretching patterns (characterized by frequency [min ± 1 ] ±
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