High rate of right ventricular infarction after ligation of mid left anterior descending artery in rats
Received 18 April 2005; received in revised form 19 April 2005; accepted 20 April 2005.
Abstract
Background
The left anterior descending artery (LAD) supplies the left ventricle in humans. LAD ligation has been commonly used in rats to induce left ventricular (LV) infarction for research purposes. However, the myocardial supply territories of LAD are not well established in rats. We measured the infarction zone in rats after ligation of the mid-LAD.
Methods
Twenty-four male Sprague–Dawley rats weighing 300–350 g were selected for LAD ligation for the induction of ischemic cardiomyopathy. The surgery was performed under full anesthesia. Left-sided thoracotomy was performed through cuts in the fifth and sixth ribs. Ligation of the LAD was performed 1 to 2 mm distal to a line between the left border of the pulmonary conus and the right border of the left atrial appendage. LAD was ligated after the first diagonal and septal branches. After 24 h, the hearts were removed and stained with Tetrazolium Tetrachloride (TTC) for the detection of infracted areas.
Results
Ligation of LAD induces 85% infarction of the right anterior free wall and anterior right ventricular septum and induces 100% infarction of the anterior free wall of the left ventricle and anterior septum. Infarction after LAD ligation extends all the way to the distal of the ligation site down to the apex of the heart.
Conclusions
Mid-LAD ligation after the first septal and diagonal branches causes substantial right ventricular infarction in addition to LV infarct in rats. Therefore, the hemodynamic effect of right ventricle infarct should be considered in research involving LAD ligation in rats.
The left anterior descending artery (LAD) supplies mainly the left ventricle in humans. Right ventricular infarct in the setting of LAD occlusion is rare and occurs in 7–13% of isolated antroseptal infarction in humans [1], [2], [3]. LAD ligation has been commonly used in rats to induce left ventricular (LV) infarction for research purposes. However, the myocardial supply territory of LAD in rats is not described in the literature. Any right ventricular involvement during LAD ligation would cause hemodynamic changes independent of LV infarction and interference with an experimental model of ischemic LV dysfunction. The goal of this study was to evaluate the extent of infarction in rats after ligation of the mid-LAD.
2. Methods
Twenty-four Sprague–Dawley male rats weighing 300–350 g were selected for LAD ligation for the induction of ischemic cardiomyopathy. The surgery was performed under full anesthesia. Left-sided thoracotomy was performed through cuts in the fifth and sixth ribs. After opening the pericardium, ligation of the LAD was performed 1 to 2 mm distal to the line between the left border of the pulmonary conus and the right border of left atrial appendage. LAD was ligated after the first diagonal and septal branches with 4.0 silk suture. After 24 h, the hearts were removed and stained with Tetrazolium Tetrachloride (TTC) for the detection of infracted areas. This study was approved by an animal welfare committee.
3. Results
Mid-LAD ligation induces 85% infarction of the right anterior free wall and anterior right ventricular septum (Fig. 1, Fig. 2, Fig. 3, Fig. 4). It also induces 100% infarction of the anterior free wall, apex of LV, and anterior septum involving approximately 45% of LV mass. Infarction after the LAD ligation extends all the way to the distal of the ligation site down to the apex of the heart. Right ventricular infarction was extensive in some rats. Mortality rate immediately after LAD ligation was 15%, and all occurred in rats with right ventricular infarction.
Fig. 4. Apical involvement of left and right ventricular free wall after mid-LAD ligation.
4. Discussion
The anatomical distribution of coronary artery in rats has not been studied in detail, and there are no studies available to document the ischemic territory of LAD. LAD ligation has been extensively used in animal research [4], [5], [6], [7]. Most research is involved in measuring the hemodynamic effect of medications after the induction of infarct in LAD [3], [4], with the assumption that the left ventricle is the major chamber affected after LAD ligation. However, in our study, we found a very high rate (up to 85%) of right ventricular infarction after LAD ligation. Furthermore, an immediate mortality of 15% occurred in rats with right ventricular infarction. This finding is surprising. Right ventricular infarctions usually occur in the setting of right coronary artery occlusion in humans [8]. The occurrence of right ventricular infarction is rare in the setting of antroseptal infarct and is reported to be 7–13% in humans [1], [2], [3]. This very high rate of right ventricular infarction in rats can cause substantial interference with the hemodynamic data measured after LAD ligation. Based on our data, the involvement of the right ventricle should be considered and accounted in research involving LAD ligation in rats to avoid misinterpretation of hemodynamic data. LAD ligation has been associated with up to 50% mortality in rats and was thought to be due to LV failure [9], [10], [11]. However, based on our study, we find that right ventricular infarction was present in all rats who died immediately after LAD ligation, suggesting that the high mortality rate of LAD ligation in rats could partially be explained by the high rate of right ventricular infarction. We suggest that LAD ligation needs to be standardized and that new anatomical locations need to be found for LAD ligation. This could potentially decrease the risk of right ventricular infarct and mortality in rats and provide more accurate hemodynamic studies of LV infarction models.
5. Conclusions
Mid-LAD ligation after the first septal and diagonal branches cause substantial right ventricular infarction in addition to LV infarct in rats, and all immediate mortality occurred in rats with right ventricular infarction. Therefore, the hemodynamic effect of right ventricle infarct should be considered in research involving LAD ligation in rats.
Acknowledgments
We would like to thank Ms. Gale Good for her support and editing of this manuscript.
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aDivision of Endocrinology, Department of Medicine, University of California, Irvine Medical Center, Orange, CA 92868, USA
bDivision of Cardiology, University of California, Irvine Medical Center, Orange, CA 92868, USA
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