Related Experiment Video
Updated: Jul 13, 2026

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Cardioplegic ischemia or reperfusion: which is a main trigger for tumor necrosis factor production?
Dmitry Pevni1, Inna Frolkis, Itzhak Shapira
1Department of Cardiothoracic Surgery, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Background:
Tumor necrosis factor alpha (TNF-alpha) is a key cytokine in the pathogenesis of ischemia-reperfusion injury (I/R) that also possesses negative inotropic and direct cardiotoxic effects. We investigated whether myocardial ischemia and/or reperfusion is the trigger for TNF-alpha synthesis and whether TNF-alpha release is time dependent.
Methods:
Isolated rat hearts undergoing 30 min of coronary perfusion with modified Krebs-Henseleit solution followed by cardioplegic arrest for 60 min of global cardioplegic normothermic ischemia (GCI) and 30 min of reperfusion using a modified Langendorff model. Myocardial TNF-mRNA expression and TNF-alpha protein levels in effluent from the coronary sinus were measured at baseline and then after 15, 30, and 60 min of GCI and after 10 and 30 min of reperfusion.
Results:
GCI induced myocardial TNF-alpha mRNA expression and elevation protein TNF-alpha levels in a time-dependent manner after 30 min of ischemia from 78+/-17 pg/ml to 915+/-287 pg/ml after 60 min (p<0.0015). Reperfusion did not cause time-dependent increase of TNF-alpha synthesis and release but was accompanied by progressive decrease of left ventricular (LV) function. There was a correlation between TNF-alpha protein levels and depression of LV function immediately after GCI but not with TNF-alpha protein levels at 30 min of reperfusion.
Conclusion:
This study demonstrated that myocardial ischemia rather than reperfusion is the main trigger for time-dependent TNF-alpha synthesis. Depression of LV function during reperfusion correlated significantly only with TNF-alpha levels at the end of GCI.
Related Concept Videos
Cellular Injury IV: Necrosis
Transient Ischemic Attack l: Introduction
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Ischemic Stroke ll: Pathophysiology
Cytotoxic Edema: Pathophysiology
The Extrinsic Apoptotic Pathway
