The effects of intravenous anesthetics and lidocaine on proliferation of cultured type II pneumocytes and lung fibroblasts.
Type II pneumocytes synthesize surfactant and differentiate into type I pneumocytes to maintain the epithelium (1). Alveolar type II cell proliferation is required for reepithelization after acute lung injury (ALI) and is thought to minimize the subsequent fibrotic response (1). Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are among the most potent mitogen for type II epithelial cells, but not for fibroblasts in the lung (1). These growth factors attenuate several experimental ALI models by promoting epithelial repair (2,3). Thus, KGF and HGF may be a promising therapeutic approach to ALI. Critically ill patients with ALI often receive IV anesthetics or sedatives to facilitate mechanical ventilation. Furthermore, these patients sometimes undergo bronchoscopy under local anesthesia to obtain bronchoalveolar lavage fluid or to remove respiratory secretions. Several IV and local anesthetics inhibit proliferation of various cells including epithelium (4,5). If these anesthetics impede proliferation of type II pneumocytes, this suppressive effect may be a disadvantage for alveolar reepithelization in the course of recovery from ALI. In this study, we examined the effects of midazolam, propofol, ketamine, thiopental, and lidocaine on proliferation of type II alveolar epithelial cells using in vitro culture system. Because fibroblast proliferation is a key event in late phase of ALI, inhibition of this fibroproliferation is probably beneficial. Thus, we further determined whether these anesthetics could regulate proliferation of lung fibroblasts. In the current study, rolipram was used as a positive control. In our previous preliminary experiment, we found that rolipram, a phosphodiesterase inhibitor type IV, augments spontaneous or KGF-/HGF-promoted type II cell proliferation (6).


CONCLUSIONS
Midazolam, ketamine, thiopental, propofol, or lidocaine did not inhibit proliferation of cultured rat type II pneumocytes. Our findings suggest that these anesthetics do not impede alveolar reepithelization after acute lung injury.
Nishina
Kahoru
K
Department of Anesthesia and Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
Mikawa
Katsuya
K
Morikawa
Osamu
O
Obara
Hidefumi
H
Mason
R J
RJ
D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology*; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology; D013874:Thiopental / Q000494:pharmacology
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; C496455:Fgf7 protein, rat; D010726:Phosphodiesterase Inhibitors; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor; D007649:Ketamine; D008012:Lidocaine; D013874:Thiopental; D020889:Rolipram; D008874:Midazolam; D004121:Dimethyl Sulfoxide