Lim H, Fallavollita J A, Hard R, Kerr C W, Canty J M
Veterans Affairs Western New York Healthcare System and the Departments of Medicine, Anatomy, Physiology, and Biophysics at the State University of New York at Buffalo School of Medicine and Biomedical Sciences, 14214, USA.
Circulation. 1999 Dec 7;100(23):2380-6. doi: 10.1161/01.cir.100.23.2380.
Myocyte apoptosis is seen in ischemic heart disease, but whether it can occur after reversible ischemia or independent of necrosis and replacement fibrosis is unknown.
Pigs were instrumented with a stenosis of the left anterior descending coronary artery to chronically reduce coronary flow reserve over a period of 3 months. At this time, there was viable dysfunctional myocardium having the physiological features of hibernating myocardium. Resting subendocardial perfusion was reduced to 0.65+/-0.08 (mean+/-SEM) mL. min(-1). g(-1) in hibernating myocardium of instrumented pigs compared with 0.98+/-0.14 mL. min(-1). g(-1) in myocardium of sham-operated pigs (P<0.05). There was a critical limitation in subendocardial flow during vasodilation to 0.78+/-0.20 mL. min(-1). g(-1) in instrumented pigs versus 3. 24+/-0.50 mL. min(-1). g(-1) in sham-operated pigs (P<0.001). Histology revealed a regional reduction in myocyte nuclear density to 995+/-100 nuclei/mm(2) in hibernating myocardium from the instrumented group versus 1534+/-65 nuclei/mm(2) in myocardium from the sham-operated group (P<0.05), regional myocyte hypertrophy (myocyte volume per nucleus, 14 183+/-2594 in the instrumented group versus 9130+/-1301 microm(3) in the sham group; P<0.05), and minimal increases in connective tissue (5.8+/-0.9% in the instrumented group versus 3.0+/-0.2% in the sham group, P<0.05). Necrosis was not identified, but apoptosis was increased from 30+/-9 myocytes per 10(6) myocyte nuclei in myocardium from the sham group to 220+/-77 myocytes per 10(6) myocyte nuclei in hibernating myocardium (P<0.05).
These findings indicate that reversible ischemia in an area of chronically reduced coronary flow reserve induces regional myocyte loss via an apoptotic mechanism. This may contribute to the progression of chronic coronary disease to heart failure and explain the lack of complete functional recovery after revascularization in hibernating myocardium.
心肌细胞凋亡见于缺血性心脏病，但它是否能在可逆性缺血后发生，或独立于坏死和替代性纤维化发生尚不清楚。
对猪进行左前降支冠状动脉狭窄手术，在3个月的时间里慢性降低冠状动脉血流储备。此时，存在具有冬眠心肌生理特征的存活功能失调心肌。与假手术猪心肌的0.98±0.14 mL·min⁻¹·g⁻¹相比，手术猪冬眠心肌的静息心内膜下灌注降至0.65±0.08（均值±标准误）mL·min⁻¹·g⁻¹（P<0.05）。在血管扩张时，手术猪的心内膜下血流存在严重受限，为0.78±0.20 mL·min⁻¹·g⁻¹，而假手术猪为3.24±0.50 mL·min⁻¹·g⁻¹（P<0.001）。组织学检查显示，手术组冬眠心肌的心肌细胞核密度区域性降低至995±100个细胞核/mm²，而假手术组心肌为1534±65个细胞核/mm²（P<0.05），区域性心肌细胞肥大（手术组每个细胞核的心肌细胞体积为14183±2594μm³，假手术组为9130±1301μm³；P<0.05），结缔组织有轻微增加（手术组为5.8±0.9%，假手术组为3.0±0.2%，P<0.05）。未发现坏死，但凋亡从假手术组心肌每10⁶个心肌细胞核中有30±9个心肌细胞增加到冬眠心肌每10⁶个心肌细胞核中有220±77个心肌细胞（P<0.05）。
这些发现表明，在冠状动脉血流储备长期降低的区域发生的可逆性缺血通过凋亡机制诱导区域性心肌细胞丢失。这可能导致慢性冠状动脉疾病进展为心力衰竭，并解释了冬眠心肌血运重建后功能未完全恢复的原因。
