Inhibition of Poly(Adenosine Diphosphate-Ribose) Polymerase Attenuates Ventilator-induced Lung Injury |
| |
Authors: | Vaschetto, Rosanna M.D. Kuiper, Jan W. M.D. Chiang, Shyh Ren M.D. Haitsma, Jack J. M.D., Ph.D.
Juco, Jonathan W. M.D. Uhlig, Stefan Ph.D.# Pl tz, Frans B. M.D., Ph.D. Corte, Francesco Della M.D. Zhang, Haibo M.D., Ph.D. Slutsky, Arthur S. M.D.
|
| |
Affiliation: | Vaschetto, Rosanna M.D.*; Kuiper, Jan W. M.D.†; Chiang, Shyh Ren M.D.‡; Haitsma, Jack J. M.D., Ph.D.§; Juco, Jonathan W. M.D.∥; Uhlig, Stefan Ph.D.#; Plötz, Frans B. M.D., Ph.D.**; Corte, Francesco Della M.D.††; Zhang, Haibo M.D., Ph.D.‡‡; Slutsky, Arthur S. M.D.§§ |
| |
Abstract: | Background: Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury. Methods: Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34. Results: The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor [alpha] and interleukin 6, and attenuated the degree of apoptosis in the kidney. |
| |
Keywords: | |
|
| 点击此处可从《Anesthesiology》浏览原始摘要信息 |
|