Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
J Thorac Cardiovasc Surg. 2011 Nov;142(5):1108-13, 1113.e1. doi: 10.1016/j.jtcvs.2011.08.007. Epub 2011 Sep 9.
Increased myocardial glucose-6-phosphate dehydrogenase (G6PD) activity occurs in heart failure. This study compared G6PD activity in 2 protocols of right ventricle (RV) systolic overload in young goats.
Twenty-seven goats were separated into 3 groups: sham (no overload), continuous (continuous systolic overload), and intermittent (four 12-hour periods of systolic overload paired with a 12-hour resting period). During a 96-hour protocol, systolic overload was adjusted to achieve a 0.7 RV/aortic pressure ratio. Echocardiographic and hemodynamic evaluations were performed before and after systolic overload every day postoperatively. After the study period, the animals were humanely killed for morphologic and G6PD tissue activity assessment.
A 92.1% and 46.5% increase occurred in RV and septal mass, respectively, in the intermittent group compared with the sham group; continuous systolic overload resulted in a 37.2% increase in septal mass. A worsening RV myocardial performance index occurred in the continuous group at 72 hours and 96 hours, compared with the sham (P < .039) and intermittent groups at the end of the protocol (P < .001). Compared with the sham group, RV G6PD activity was elevated 130.1% in the continuous group (P = .012) and 39.8% in the intermittent group (P = .764).
Continuous systolic overload for ventricle retraining causes RV dysfunction and upregulation of myocardial G6PD activity, which can elevate levels of free radicals by NADPH oxidase, an important mechanism in the pathophysiology of heart failure. Intermittent systolic overload promotes a more efficient RV hypertrophy, with better preservation of myocardial performance and and less exposure to hypertrophic triggers.
心力衰竭时心肌葡萄糖-6-磷酸脱氢酶（G6PD）活性增加。本研究比较了两种右心室（RV）收缩期超负荷方案中 G6PD 活性在年轻山羊中的变化。
27 只山羊被分为 3 组：假手术组（无超负荷）、持续组（持续收缩期超负荷）和间歇组（4 个 12 小时收缩期超负荷期与 12 小时休息期交替）。在 96 小时方案中，通过调整收缩期超负荷以实现 RV/aortic 压力比为 0.7。术后每天在收缩期超负荷前后进行超声心动图和血流动力学评估。研究期结束后，处死动物进行形态学和 G6PD 组织活性评估。
间歇组 RV 和室间隔质量分别增加 92.1%和 46.5%，与假手术组相比；连续收缩期超负荷导致室间隔质量增加 37.2%。与假手术组相比，连续组 RV 心肌收缩性能指数在 72 小时和 96 小时时恶化（P<0.039），在方案结束时与间歇组相比（P<0.001）。与假手术组相比，连续组 RV G6PD 活性升高 130.1%（P=0.012），间歇组升高 39.8%（P=0.764）。
连续收缩期超负荷用于心室再训练可导致 RV 功能障碍和心肌 G6PD 活性上调，从而通过 NADPH 氧化酶增加自由基水平，这是心力衰竭病理生理学的重要机制。间歇收缩期超负荷可促进更有效的 RV 肥大，更好地保留心肌功能，减少对肥大触发因素的暴露。
