Gustafson L A, Van Beek J H
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3118-23. doi: 10.1152/ajpheart.2000.279.6.H3118.
The purpose of this study was to develop a technique for determination of the dynamic regulation of oxidative myocardial metabolism in the mouse. The response time of myocardial oxygen consumption (MVO(2)) to a step in heart rate was determined in Langendorff-perfused mouse hearts. We examined the effect of glucose-only perfusate and glucose combined with 1, 3, or 6 mM pyruvate. Left ventricular systolic pressure (LVSP) decreased, yet the rate-pressure product (RPP) and MVO(2) increased with upward steps in heart rate. Pyruvate increased LVSP, RPP, and MVO(2) at the lower concentrations; however, when 6 mM pyruvate was added, LVSP and RPP became depressed while MVO(2) remained elevated. The mean response time of oxygen consumption to a step in heart rate from 270 to 350 beats/min was 9.8 s (n = 7) in the glucose-only perfused hearts. Perfusion with glucose plus 6 mM pyruvate decreased the response time to 5.3 s. These results are similar to those found in the rabbit heart and lay the groundwork for further examination of the dynamic regulation of oxidative myocardial metabolism in genetically altered mice. We concluded that the activation time of oxidative phosphorylation in the mouse is similar to that in larger species, despite the high mitochondrial content and natural heart rate of the mouse.
本研究的目的是开发一种用于测定小鼠心肌氧化代谢动态调节的技术。在Langendorff灌注的小鼠心脏中测定心肌耗氧量（MVO₂）对心率阶跃变化的反应时间。我们研究了仅含葡萄糖的灌注液以及葡萄糖与1、3或6 mM丙酮酸组合的灌注液的作用。随着心率逐步升高，左心室收缩压（LVSP）降低，但心率-压力乘积（RPP）和MVO₂升高。较低浓度的丙酮酸可提高LVSP、RPP和MVO₂；然而，当添加6 mM丙酮酸时，LVSP和RPP降低，而MVO₂仍保持升高。在仅用葡萄糖灌注的心脏中，耗氧量对心率从270次/分钟升至350次/分钟阶跃变化的平均反应时间为9.8秒（n = 7）。用葡萄糖加6 mM丙酮酸灌注可将反应时间缩短至5.3秒。这些结果与在兔心脏中发现的结果相似，为进一步研究基因改变小鼠心肌氧化代谢的动态调节奠定了基础。我们得出结论，尽管小鼠的线粒体含量高且心率快，但小鼠氧化磷酸化的激活时间与较大物种相似。
