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Left ventricular remodeling in myocardial hibernation
1Division of Cardiology, Hartford Hospital, the University of Connecticut School of Medicine, 06102, USA.
Insights
Regional left ventricular dysfunction and myocardial hibernation, even without extensive infarction, can trigger left ventricular remodeling. This suggests myocardial necrosis is not essential for remodeling following regional dysfunction.
Area of Science:
- Cardiovascular Research
- Cardiac Physiology
- Myocardial Remodeling
Background:
- Left ventricular (LV) remodeling is a known consequence of extensive myocardial infarction.
- Previous studies established this link in both animal models and human subjects.
- The current study investigates if regional LV dysfunction, without significant infarction, can initiate remodeling.
Purpose of the Study:
- To determine if regional LV dysfunction with myocardial hibernation, in the absence of transmural or extensive infarction, can initiate LV remodeling.
- To explore the role of coronary stenosis in inducing these changes.
- To assess the reversibility of functional deficits and remodeling.
Main Methods:
- A severe left anterior descending coronary artery stenosis was induced in 13 pigs to reduce coronary flow by approximately 40%.
- Regional coronary flow, wall thickening, lactate production, and pH were monitored.
- LV end-diastolic volume and mass were measured at baseline, immediately after stenosis, and after 7 days.
Main Results:
- Reduced coronary flow induced acute myocardial ischemia, evidenced by decreased wall thickening, lactate production, and pH.
- Pigs exhibited significant regional LV dysfunction and reduced LV ejection fraction.
- LV end-diastolic volume and LV mass increased after 7 days of myocardial hibernation.
- Regional function recovered in pigs after restoration of coronary flow, with minimal infarction in most animals.
Conclusions:
- LV remodeling can be initiated by regional dysfunctional hibernating myocardium caused by severe coronary stenosis.
- Myocardial necrosis is not a prerequisite for LV remodeling in response to regional dysfunction.
- These findings highlight a mechanism for remodeling independent of extensive infarction.
Background:
Left ventricular (LV) remodeling as a consequence of extensive myocardial infarction has been well established in animal and human studies. This study was designed to determine whether regional LV dysfunction with myocardial hibernation without transmural or extensive infarction could initiate the remodeling process.
Methods And Results:
A severe left anterior descending coronary artery stenosis was created to reduce resting flow by approximately 40% (from 0.99+/-0.10 to 0.56+/-0.11 mL x min(-1) x g[-1]) and was maintained for 7 days in 13 pigs. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening, from 37+/-3% at baseline to 9+/-7%, regional lactate production and a decrease in regional coronary venous pH. All pigs had significant regional LV dysfunction and reduced LV ejection fraction (41+/-11%). The LV end-diastolic volume increased from 59+/-9 mL at baseline to 74+/-13 mL immediately after placement of the stenosis and to 78+/-17 mL 7 days later with hibernating myocardium. The LV mass did not change immediately (60+/-8 g baseline versus 59+/-11 g immediately after creation of the stenosis) but increased modestly yet significantly to 67+/-15 g after 7 days of myocardial hibernation subtending the severe LAD stenosis. The reductions of coronary flow and wall thickening were unchanged at 7 days, whereas myocardial lactate production recovered. By 4 weeks after restoration of LAD flow, regional function had recovered in all 7 pigs with follow-up. Of the 13 pigs, 6 were free from any evidence of myocardial infarction, and 4 had patchy necrosis involving less than 6% of the area at risk.
Conclusions:
LV remodeling, which is commonly associated with extensive myocardial infarction, can be initiated by regional dysfunctional hibernating myocardium resulting from a severe coronary stenosis. Myocardial necrosis is not a prerequisite for LV remodeling in response to regional dysfunction.