Biomedical subjects
Kalle Korhonen
Publications and source records attributed to Kalle Korhonen.
Pentoxifylline reduces regional inflammatory and ventilatory disturbances in meconium-exposed piglet lungs.
Neonatal meconium aspiration frequently produces severe respiratory distress, which is associated with patchy pulmonary neutrophil influx and inflammatory injury. To examine the effects of pentoxifylline (PTX), a potent anti-inflammatory agent, on regional pulmonary inflammation and ventilation after meconium aspiration, we studied 17 anesthetized and ventilated neonatal piglets (age <2 d) for 12 h. After unilateral intrapulmonary instillation of meconium, PTX treatment was started in nine animals, and eight untreated animals served as controls. Bronchoalveolar lavage (BAL) fluid and lung tissue were studied for inflammatory variables at the end of the study, and changes in regional ventilation were serially analyzed with a dynamic pulmonary x-ray imaging method. Meconium insufflation increased BAL fluid total cell, neutrophil, and macrophage counts and tumor necrosis factor-alpha (TNF-alpha) and protein concentrations as well as lung tissue myeloperoxidase activity in the instilled lungs, compared with the noninstilled side. PTX treatment prevented the increase of BAL fluid alveolar macrophage count and TNF-alpha and protein concentrations in the meconium-instilled lungs but had no significant effect on the pulmonary neutrophil accumulation. Ventilation of the meconium-insulted lung was initially disturbed similarly in both study groups, but PTX administration prevented the sustained local ventilatory perturbation at 4, 6, and 12 h after meconium instillation. The results thus indicate that PTX treatment may attenuate meconium-induced regional ventilation derangements, mainly through its effects on local alveolar macrophages and TNF-alpha production as well as alveolocapillary permeability rather than via significant prevention of accumulation of active neutrophils in the insulted lungs.
Meconium induces only localized inflammatory lung injury in piglets.
Neonatal meconium aspiration often produces severe respiratory distress due to an inflammatory pulmonary injury, but the extension of this damaging reaction to the noncontaminated lung regions is still uncertain. To investigate the presence of generalized pulmonary inflammatory response, 31 anesthetized and ventilated neonatal piglets (1-3 d) were studied. Meconium (n = 16) or saline (n = 15) was instilled unilaterally into the right lung, and analysis of the lung tissue or bronchoalveolar lavage (BAL) fluid from both lungs was performed after 12 h. Meconium increased the wet/dry weight ratio, histologic tissue injury score and tissue myeloperoxidase activity as well as BAL fluid total cell count in the contaminated lung. Tumor necrosis factor-alfa concentrations in BAL fluid did not however differ significantly. Furthermore, in the meconium-instilled lungs the tissue and lavage fluid catalytic activity of phospholipase A2 (PLA2) and tissue PLA2 group-I and group-II concentrations were significantly elevated. Although BAL fluid catalytic activity of PLA2 was moderately increased also in the meconium noninstilled lung, significant inflammatory injury in this lung was absent. The results thus indicate that meconium aspiration induces severe local inflammation and lung injury, but significant generalized pulmonary inflammatory damage in the pathogenesis of meconium aspiration syndrome is unlikely.