Abstract 130: The Diversity of Coronary Artery and Myocardial Infarction in Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jiqiu Chen ◽  
Delaine K Ceholski ◽  
Lifan Liang ◽  
Roger Hajjar

Low reliability and reproducibility in heart failure research has been a major concern. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. Methods: MI was induced by left coronary artery (LCA) ligation. Echocardiography was used to measure cardiac function after MI. The coronary artery was casted with resin and visualized with fluorescent imaging in ex vivo. LCA characteristics and MI size were analyzed individually in each animal. MI size was correlated with LV function by echocardiography. Results: Coronary anatomy varies widely amongst animals, posing challenges for surgical ligation and resulting in inconsistent MI size data post-ligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches were unique in every animal. When the main LCA trunk was ligated, this resulted in a large MI, but when a single branch was ligated, MI size varied significantly due to differing levels of LCA ligation and differing amounts of territory supplied by the branches. During the ligation procedure, nearly 40% of LCAs were not grossly visible to the surgeon. In these situations, the surgeon commonly blindly sutures a wider and deeper area of tissue in an attempt to ensure that the LCA is caught and ligated. Paradoxically, these situations have greater odds of resulting in smaller MIs. Conclusion: The current study offers evidence of anatomical LCA diversity and the problems this poses for creating a consistent heart failure model by LCA ligation in mice. Carefully recognizing the inevitable individual variation of coronary anatomy in mice is essential to restoring reliability of the LCA ligation model of heart failure.

2017 ◽  
Vol 313 (2) ◽  
pp. H275-H282 ◽  
Author(s):  
Jiqiu Chen ◽  
Delaine K. Ceholski ◽  
Lifan Liang ◽  
Kenneth Fish ◽  
Roger J. Hajjar

Low reliability and reproducibility in heart failure models are well established. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. MI was induced by left coronary artery (LCA) ligation. The coronary artery was casted with resin and visualized with fluorescent imaging ex vivo. LCA characteristics and MI size were analyzed individually in each animal, and MI size was correlated with left ventricular (LV) function by echocardiography. Coronary anatomy varies widely in mice, posing challenges for surgical ligation and resulting in inconsistent MI size postligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches are unique in each animal. When the main LCA trunk is ligated, this results in a large MI, but when a single branch is ligated, MI size is variable due to differing levels of LCA ligation and area supplied by the branches. During the ligation procedure, nearly 40% of LCAs are not grossly visible to the surgeon. In these situations, the surgeon blindly sutures a wider and deeper area of tissue in an attempt to catch the LCA. Paradoxically, these situations have greater odds of resulting in smaller MIs. In conclusion, variation in MI size and LV function after LCA ligation in mice is difficult to avoid. Anatomic diversity of the LCA in mice leads to inconsistency in MI size and functional parameters, and this is independent of potential technical modifications made by the operator. NEW & NOTEWORTHY In the present study, we demonstrate that left coronary artery diversity in mice is one of the primary causes of variable myocardial infarction size and cardiac functional parameters in the left coronary artery ligation model. Recognition of anatomic diversity is essential to improve reliability and reproducibility in heart failure research.


1999 ◽  
Vol 277 (1) ◽  
pp. H388-H398 ◽  
Author(s):  
You-Tang Shen ◽  
Joseph J. Lynch ◽  
Richard P. Shannon ◽  
Richard T. Wiedmann

A heart failure model was developed using conscious pigs subjected to serial myocardial infarctions followed by intermittent rapid ventricular pacing. Aortic and atrial catheters, left ventricular (LV) pressure gauge, LV dimension crystals, ascending aortic flow probe, pacing leads, and two coronary artery occluders were implanted in 15 pigs. The initial distal left circumflex coronary artery (LCX) occlusion produced a modest infarct, i.e., 18 ± 3% of LV, and the second proximal LCX occlusion, performed 48 h later, enlarged the infarct to 33 ± 2% of the LV with only modest changes in LV function. Thereafter, the pigs were subjected to ventricular pacing at 220 beats/min, which was maintained for 7 days and terminated for 3 days. This pacing cycle was repeated two more times and resulted in significantly impaired LV function and systemic hemodynamics. For example, after the second cycle of pacing, LV rate of pressure change (dP/d t, −41 ± 4% from 2,778 ± 112 mmHg/s), velocity of circumferential fiber shortening ( Vcf: −53 ± 6% from 1.1 ± 0.1 s−1), and cardiac index (CI: −42 ± 5% from 122 ± 4 ml ⋅ min−1⋅ kg−1) were reduced significantly, whereas LV end-diastolic diameter (EDD: +34 ± 6% from 39 ± 2 mm), total peripheral resistance (TPR: +75 ± 16% from 0.79 ± 0.05 U), and mean left atrial pressure (LAP) (+21 ± 1 mmHg from 5 ± 1 mmHg) were increased significantly. Importantly, 3 wk after cessation of the final pacing cycle, LV dP/d t (−40 ± 5%), Vcf(−48 ± 9%), and CI (−30 ± 4%) remained depressed, whereas LV EDD (+39 ± 5%), TPR (+43 ± 9%), and LAP (+13 ± 4 mmHg) were still increased. In contrast, hemodynamic impairment in six conscious pigs subjected to pacing only did not persist when pacing was terminated. Thus this model could provide a unique opportunity to study both the effects of preclinical therapeutic interventions and the mechanisms involved in the development of heart failure.


2017 ◽  
Vol 9 (3) ◽  
pp. 368-370 ◽  
Author(s):  
Arshid Mir ◽  
Harold M. Burkhart ◽  
Kumar Ponniah ◽  
Kent Ward

Coronary artery anomalies are known to be associated with truncus arteriosus (common arterial trunk). Delineation of coronary anatomy preoperatively is important to avoid complications intraoperatively and postoperatively. We report the case of a 12-year-old boy with repaired truncus arteriosus who presented with moderate to severe truncal valve regurgitation and severe conduit stenosis. He was noted to have intramural left main coronary artery on a transesophageal echocardiogram performed preoperatively.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xiaoyan Li ◽  
Xuejun Jliang ◽  
Tao Wang ◽  
Taol Lin ◽  
Congxin Huang ◽  
...  

Myocardial infarction and the subsequent heart failure remain among the world’s prominent health challenges. Other studies have demonstrated that bio-derived materials improve cardiac function after implantation for angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricle (LV) function through its prevention of paradoxical systolic bulging. Infarction was induced in rabbit myocardium by coronary artery ligation. In sham-operated rabbits (n = 5), a suture was tied loosely around the left anterior descending coronary artery without ligating it. 7 dayslater, 100μl α-cyclodextrin (CD) solution and 100μl poly (ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly (ethylene glycol)(MPEG-PCL-MPEG) solution (n = 7) was injected simultaneously through Duploject applicator into the infarcted myocardium. Solid hydrogel matrix formed by linear MPEG-PCL-MPEG polymer threading into the cavities of the α-cyclodextrin after mixing. Injection of phosphate buffered saline (PBS) served as controls (n = 7). 28 days after the treatments, histological analysis indicated that injection of hydrogel prevented scar expansion and wall thinning compared with group ( P < 0.05) without more microvessel density in infarcted myocardium ( P = 0.70).By echocardiography, LV ejection fraction was significantly greater in the hydrogel group (56.09 ± 8.42%) than the control group (37.26 ± 6.36%, P = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 ± 0.33 cm and 1.74 ± 0.30cm in the control group, respectively. Smaller LV end-diastolic diameter (1.61 ± 0.26cm, P = 0.005) and smaller end-systolic diameter (1.17 ± 0.23cm, P = 0.001) were found in the hydrogel group. These results suggest that α-CD/MPEG-PCL-MPEG hydrogel injection could serve structural and mechanical support of an injured LV replacing some of the functions of the damaged ECM and thus prevented paradoxical motion serves, which may eventually lead to LV remodeling and dilation prevention. Our study should initiate further experimental and clinical studies exploring potential approaches to the treatment of postinfarction heart failure.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yariv Gerber ◽  
Susan A Weston ◽  
Maurice E Sarano ◽  
Sheila M Manemann ◽  
Alanna M Chamberlain ◽  
...  

Background: Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined. Subjects and Methods: Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data. Results: During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table). Conclusions: The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.


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