Abstract 1575: Cardiomyocyte Number Increases in Pressure Overload-Induced Hypertrophy
It is now clear that resident cardiac progenitor cells are present in the adult heart. This raises the possibility that new myocytes can be formed to increase the mass of the heart or to replace dying myocytes. The objective of this study was to determine if the number of left ventricular myocytes (LVM) increases during pressure overload (PO)-induced hypertrophy.
Methods: A band was placed around the ascending aorta of young cats (~1.1kg, age ~2 months) to induce PO. Heart size, LVM volume fraction, LVM size (volume and 2D surface area), nucleation, and cell cycle activity (Ki-67, bromodeoxyuridine (BrdU; subcutaneous infusion at 10mg/kg/day for 7 days) incorporation) were measured either 2 or 15 weeks after banding and compared to age-matched controls.
Results: (See Table⇓): Long-term aortic banding resulted in an 87% increase in heart weight (HW) when compared to age-matched control hearts (p=0.001). Myocyte volume increased by 36% (p=0.01). Changes in LVM volume after banding were associated with proportional changes in myocyte surface area (N=12, r2=0.9). Myocyte volume fraction does not change during PO-induced hypertrophy. We calculate (using a myocardial specific density of 1.06g/ml) that myocyte number must increase by 37.6% to account for the increase in mass in the left ventricle. Short-term aortic banding (1–2 weeks) resulted in a 31% increase in heart weight compared to age-matched controls (p<0.05) but no significant increase in myocyte volume (p=0.8). BrdU incorporated into approximately 1% of VMs. A disproportionately high percentage of mononucleated myocytes were BrdUPOS (3.09 ± 0.97% vs 0.72 ± 0.24% binucleated, p<0.05). Myocyte nucleation did not vary with banding (10.9 ± 0.8% mono-, 88 ± 0.7% binucleated control vs 11.7 ± 1.3% mono-, 86.9 ± 1.3% binucleated banded, N=41 and 20 hearts respectively, n=2500 myocytes/heart).
Conclusions: PO-induced increases in cardiac mass include an increase in the number of left ventricular myocytes.