Gastric and cardiac organoprotection by lidocaine.
The concept of cytoprotection has been applied to many tissues afforded protection by drugs or endogenous chemicals against organelle, cyto- or histopathologic damage. We review here the "organoprotection" by lidocaine in rats and dogs as appraised by in vitro, ex vivo, and in vivo experiments with the stomach and heart, and as revealed at organelle to organ functional levels. Gastric mucosal lesions induced by 80% ethanol with 100 mM HCl on the ex vivo rat stomach were significantly reduced by lidocaine (2.2-4.4 mg/kg bolus followed by 66-132 micrograms/kg/min i. v. infusion). In anesthetized dogs with gastric corporeal lesions induced by increased gastric intraluminal pressure (50 mm Hg, 2.5 hrs), lidocaine (2.2 mg/kg bolus plus 66 micrograms/kg/min infusion) significantly reduced lesion severity. In the isolated rat heart, reperfusion after a 60 min period of ischemia induced localized cardiac mitochondrial swelling and disruption in ventricular apices which was greatly reduced if hearts were pretreated (15 min perfusion with lidocaine). In intact rats subjected to hemorrhagic shock, lidocaine pretreatment also facilitated shock resuscitation and reduced ultrastructural damage. In these diverse experiments, lidocaine organoprotection was likely mediated in part through reduction of ischemia induced organelle membrane damage and through reduction of reperfusion-induced superoxide and other oxygen-derived free radical related damage.
Pfeiffer
C J
CJ
Department of Veterinary Biosciences, VA-MD Regional College of Veterinary Medicine Virginia Polytechnic Institute and State University, Blacksburg 24061.
Keith
J C
JC
Cho
C H
CH
DeRolf
S
S
Pfeiffer
D C
DC
Misra
H P
HP
D000818:Animals; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000473:pathology; D013276:Stomach Ulcer / Q000517:prevention & control*
D008012:Lidocaine