Induction of left ventricular remodeling and dysfunction in the recipient heart after donor heart myocardial infarction: new insights into the pathologic role of tumor necrosis factor-alpha from a novel heterotopic transplant-coronary ligation rat model.

Abstract

OBJECTIVES:

The present study investigated the effects of tumor necrosis factor (TNF)-alpha and angiotensin II (ANG II) on cardiac remodeling and dysfunction at the early stage of acute myocardial infarction (MI) by using a novel heterotopic cardiac transplantation-coronary ligation model.

BACKGROUND:

A recent clinical study has demonstrated a possible role of monocytosis in the development of left ventricular (LV) remodeling in patients with acute MI reperfusion.

METHODS:

We performed isogenic heterotopic cardiac transplantation and simultaneous coronary ligation to produce MI in the donor heart and to evaluate the hearts of both donors and recipients in Lewis rats.

RESULTS:

A significant decrease in LV fractional shortening and positive rate of rise in LV pressure and a significant increase in LV end-diastolic dimension/body weight and LV end-diastolic pressure were observed in the recipient hearts in the ligation group on day 7. TNF-alpha was significantly elevated not only in the plasma but also in the recipient hearts in the ligation group. In contrast, ANG II was significantly increased only in the infarct region of the donor hearts, but not in the plasma. Furthermore, the recipients' transient LV remodeling and dysfunction were completely abolished by the intravenous administration of a TNF-alpha antagonist. CONCLUSIONS; We developed a novel cardiac transplantation-coronary ligation model capable of inducing MI in the absence of downstream hemodynamic effects and allowing differential quantification of indexes of cardiac remodeling in vivo, including the local and remote effects of ANG II and TNF-alpha on cardiac remodeling.

• Authors: Hiroshi Nakamura, Seiji Umemoto, George Naik, Gordon Moe, Satoko Takata, Peter Liu, Masunori Matsuzaki
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 42 Issue 1 Pg. 173-81 (Jul 02 2003) ISSN: 0735-1097 [Print] United States
• PMID: 12849679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Angiotensin II

Topics

• Angiotensin II (physiology)
• Animals
• Disease Models, Animal
• Heart Transplantation (physiology)
• Immunohistochemistry
• Male
• Rats
• Rats, Inbred Lew
• Receptors, Tumor Necrosis Factor (antagonists & inhibitors)
• Stroke Volume
• Transplantation, Heterotopic
• Tumor Necrosis Factor-alpha (analysis, physiology)
• Ventricular Dysfunction, Left (physiopathology)
• Ventricular Remodeling (physiology)