Thrombin receptor and ventricular arrhythmias after acute myocardial infarction.

Abstract

The mechanism mediating the development of ventricular arrhythmia (VA) after acute myocardial infarction (AMI) is still uncertain. Thrombin receptor (TR) activation has been proven to be arrhythmogenic in many other situations, and we hypothesize that it may participate in the genesis of post-AMI VA. Using a left coronary artery ligation rat model of AMI, we found that a local injection of hirudin into the left ventricle (LV) significantly reduced the ratio of VA durations to infarction sizing, whereas injection of thrombin receptor-activating peptide (TRAP) increased the ratios of VA duration to infarction sizing. The effects of TR activation on whole-cell currents were investigated in isolated myocytes. TRAP increased a glibenclamide-sensitive outward current. Pretreatment of rats with glibenclamide (4 mg/kg intraperitoneally) eliminated the effects of a local injection of TRAP on the ratios of VA durations to infarction sizing. TR mRNA and protein expression in the ischemic left ventricle had reached its peak by 20 min postligation in the rat AMI model (P < 0.05). TR-immunoreactive myocytes were observed in infarcted LV but were seldom seen in the right ventricle or in the normal heart. By 60 min, TR transcript levels had returned to control levels. We conclude that increased TR activation and expression in the infarcted LV after AMI may contribute to VA through a mechanism involving glibenclamide-sensitive potassium channels.

• Authors: Lilong Tang, Chunyu Deng, Ming Long, Anli Tang, Shulin Wu, Yugang Dong, Louis D Saravolatz, Julius M Gardin
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) 2008 Mar-Apr Vol. 14 Issue 3-4 Pg. 131-40 ISSN: 1076-1551 [Print] England
• PMID: 18224254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Hirudins
• Hypoglycemic Agents
• Peptide Fragments
• Potassium Channels
• Receptors, Thrombin
• thrombin receptor peptide SFLLRNP
• Glyburide

Topics

• Animals
• Arrhythmias, Cardiac
• Cells, Cultured
• Coronary Occlusion
• Fibrinolytic Agents (metabolism)
• Glyburide (metabolism)
• Heart Ventricles (cytology, metabolism, pathology)
• Hirudins (metabolism)
• Humans
• Hypoglycemic Agents (metabolism)
• Male
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Myocytes, Cardiac (cytology, metabolism)
• Patch-Clamp Techniques
• Peptide Fragments (metabolism)
• Potassium Channels (metabolism)
• Rats
• Rats, Wistar
• Receptors, Thrombin (genetics, metabolism)
• Ventricular Function, Left (physiology)