| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Departments of Preclinical and Clinical Pharmacology, University of Florence, 50139, Florence, Italy, and
Internal Medicine, University of Florence, 50134, Florence, Italy
Abstract
Carbon monoxide (CO) is a signaling gas produced intracellularly by heme oxygenase (HO) enzymes using heme as a substrate. During heme breakdown, HO-1 and HO-2 release CO, biliverdin, and Fe2+. In this study, we investigated the effects of manipulation of the HO-1 system in an in vivo model of focal ischemia–reperfusion (FIR) in the rat heart. Male Wistar albino rats, under general anesthesia and artificial ventilation, underwent thoracotomy, the pericardium was opened, and a silk suture was placed around the left descending coronary artery; ischemia was induced by tightening the suture and was monitored for 30 min. Subsequently, the ligature was released to allow reperfusion lasting for 60 min. The first group of rats was sham operated and injected intraperitoneally (ip) with saline. The second group underwent FIR. The third group was treated ip 18 hr before FIR with hemin (4 mg/kg). The fourth group was pretreated ip 24 hr before FIR and 6 hr before hemin with zinc protoporphyrin IX (ZnPP-IX, 50 µg/kg). Specimens of the left ventricle were taken for determination of HO expression and activity, infarct size, malonyldialdehyde (MDA) production, and tissue calcium content. FIR led to a significant increase in the generation of MDA and notably raised tissue calcium levels. Induction of HO-1 by hemin significantly decreased infarct size, incidence of reperfusion arrhythmias, MDA generation, and calcium overload induced by FIR. These effects were prevented by the HO-1 inhibitor ZnPP-IX. The present experiments show that the concerted actions of CO, iron, and biliverdin/bilirubin modulate the FIR-induced myocardial injury.
Key Words: calcium transport • arrhythmia • cell proliferation • ischemia
This article has been cited by other articles:
|
|
 |
|
  K. Ueda, T. Ueyama, K.-i. Yoshida, H. Kimura, T. Ito, Y. Shimizu, M. Oka, Y. Tsuruo, and M. Ichinose Adaptive HNE-Nrf2-HO-1 pathway against oxidative stress is associated with acute gastric mucosal lesions Am J Physiol Gastrointest Liver Physiol, September 1, 2008; 295(3): G460 - G469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Natarajan, F. N. Salloum, B. J. Fisher, E. D. Ownby, R. C. Kukreja, and A. A. Fowler 3rd Activation of hypoxia-inducible factor-1 via prolyl-4 hydoxylase-2 gene silencing attenuates acute inflammatory responses in postischemic myocardium Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1571 - H1580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. L. Tang, K. Qian, Y. C. Zhang, L. Shen, and M. I. Phillips A Vigilant, Hypoxia-Regulated Heme Oxygenase-1 Gene Vector in the Heart Limits Cardiac Injury After Ischemia-Reperfusion In Vivo Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2005; 10(4): 251 - 263. [Abstract] [PDF]
|
|
|
|
 |
|
 C. D. Filippo, R. Marfella, S. Cuzzocrea, E. Piegari, P. Petronella, D. Giugliano, F. Rossi, and M. D'Amico Hyperglycemia in Streptozotocin-Induced Diabetic Rat Increases Infarct Size Associated With Low Levels of Myocardial HO-1 During Ischemia/Reperfusion Diabetes, March 1, 2005; 54(3): 803 - 810. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
