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Selective microembolization of the circumflex coronary artery in an ovine model: Dilated, ischemic cardiomyopathy and
Gretel Monreal1, Mark A Gerhardt, Atsushi Kambara
1Department of Anesthesiology, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Insights
Cardiac remodeling progresses for up to two years after coronary microembolization, leading to dilated, ischemic cardiomyopathy. This ovine model offers insights into heart failure progression and therapeutic strategies.
Area of Science:
- Cardiovascular Science
- Heart Failure Research
- Animal Models
Background:
- Ventricular remodeling post-myocardial infarction is unpredictable.
- Cardiac dysfunction was induced in an ovine model.
- The study investigated the long-term progression of ventricular remodeling.
Purpose of the Study:
- To test the hypothesis that ventricular remodeling progresses for up to 24 months post-coronary microembolization.
- To characterize the natural history of ventricular remodeling in a large animal model.
Main Methods:
- Sheep underwent weekly selective microembolization of the circumflex coronary artery (LCx).
- Intervention continued until left ventricular ejection fraction stabilized below 35% for two consecutive weeks.
- Hemodynamic and echocardiographic assessments were performed at various time points up to 24 months.
Main Results:
- The end-systolic pressure-volume relationship slope decreased significantly by 4 months.
- Left ventricular ejection fraction decreased and stabilized at a reduced level by 5 months and persisted through 24 months.
- Significant increases in left ventricular end-systolic and end-diastolic areas were observed over 24 months.
Conclusions:
- Selective LCx microembolization induces progressive left ventricular dysfunction and dilated, ischemic cardiomyopathy.
- Ventricular remodeling continues for up to 2 years, even after ejection fraction stabilization.
- This ovine model is a valuable platform for studying heart failure progression and evaluating therapies.
Background:
Ventricular remodeling often occurs after myocardial infarction, yet the natural history remains unpredictable because of the chronicity of the process and therapeutic interventions involved. We induced cardiac dysfunction in an ovine model via selective microembolization of the circumflex coronary artery (LCx) to test the hypothesis that ventricular remodeling progresses following coronary microembolization for up to 24 months. Methods and results Sheep underwent weekly selective microembolization of the LCx until left ventricular ejection fraction stabilized <35% for 2 consecutive weeks. In a subgroup carried out to 4 months, the end-systolic pressure-volume relationship slope decreased from 2.3+/-0.6 (baseline) to 1.3+/-0.5 at month 4 (P<.05). In a second group, echocardiography at 24 months, the ejection fraction decreased from 51+/-3% (baseline) to 25+/-2% (month 5) (P<.05) and stabilized through month 24 (23+/-5%, P<.05), whereas left ventricular end-systolic area and left ventricular end-diastolic area increased by 222% and 98%, respectively, through month 24.
Conclusions:
Selective microembolization of the LCx induces left ventricular dysfunction followed by dilated, ischemic cardiomyopathy, which continues to progress for up to 2 years despite stabilization of left ventricular ejection fraction. This model of ventricular remodeling secondary to microinfarction may be a useful experimental platform for large animal heart failure investigations.
