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Time course of right ventricular remodeling in rats with experimental myocardial infarction
Matthias Nahrendorf1, Kai Hu, Daniela Fraccarollo
1Department of Internal Medicine, 97080 Würzburg, Germany. M.Nahrendorf@medizin.uni-wuerzburg.de
Abstract:
Right ventricular (RV) weight increases dependent on time after myocardial infarction (MI) and on MI size. The sequential changes in RV volume and hemodynamics and their relations to left ventricular (LV) remodeling after MI are unknown. We therefore examined the time course of RV remodeling in rats with LV MI. MI was produced by left coronary artery ligation. Four, eight, and sixteen weeks later, LV and RV hemodynamic measurements were performed and pressure-volume curves were obtained. For serial measurement of RV volumes and performance, cine-MRI was performed 2 and 8 wk after MI. The ratios of beta-myosin heavy chain (MHC) to alpha-MHC and skeletal to cardiac alpha-actin were determined for the RV and LV after large MI or sham operation. RV weight increased in rats with MI, as did RV volume. RV pressure-volume curves were shifted toward larger volumes 16 wk after large MI. RV systolic pressure increased gradually over time; however, the gain in RV weight was always in excess of RV systolic pressure. The ratios of skeletal to cardiac alpha-actin and beta-MHC to alpha-MHC were increased after MI in both ventricles in a similar fashion. Because RV wall stress was not increased after infarction, mechanical factors may not conclusively explain hypertrophy, which maintained balanced loading conditions for the RV even after large LV infarction.
Insights
Right ventricular (RV) weight and volume increase after myocardial infarction (MI). This cardiac remodeling occurs independently of increased RV pressure, suggesting non-hemodynamic factors contribute to RV hypertrophy following heart attack.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Myocardial infarction (MI) significantly impacts cardiac function.
- Left ventricular (LV) remodeling after MI is well-studied, but right ventricular (RV) changes remain less understood.
- The temporal relationship between RV remodeling and LV changes after MI requires further investigation.
Purpose of the Study:
- To investigate the time course of RV remodeling after experimental LV myocardial infarction in rats.
- To analyze sequential changes in RV volume, hemodynamics, and cardiac gene expression.
- To explore the relationship between RV remodeling and LV remodeling post-MI.
Main Methods:
- Myocardial infarction was induced in rats via left coronary artery ligation.
- Hemodynamic measurements and pressure-volume loops were obtained at 4, 8, and 16 weeks post-MI.
- Serial RV volume and performance were assessed using cine-MRI at 2 and 8 weeks.
- Ratios of myosin heavy chain (MHC) and actin isoforms were quantified in both ventricles.
Main Results:
- RV weight and volume progressively increased over time after MI.
- RV pressure-volume loops shifted towards larger volumes 16 weeks post-MI.
- RV weight gain exceeded increases in RV systolic pressure, indicating hypertrophy independent of elevated pressure.
- Altered expression of MHC and actin isoforms occurred similarly in both RV and LV.
Conclusions:
- RV remodeling, characterized by increased weight and volume, occurs predictably after LV myocardial infarction.
- Hypertrophy of the RV is not solely driven by increased wall stress or systolic pressure.
- Molecular changes in contractile proteins contribute to RV adaptation following infarction, maintaining balanced loading conditions.