Gwathmey J K, Liao R, Ingwall J S
Harvard Medical School Cardiovascular Diseases and Muscle Research Laboratories, Boston, MA 02115, USA.
Cardiovasc Res. 1995 Apr;29(4):475-81.
The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age.
After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile age ferrets, mechanical function (that is, isometric twitch force and passive stiffness), intracellular [Ca2+] using the calcium indicator aequorin, markers of myocardial energy supply, and quantified connective tissue content were studied.
It was previously found that there was a reduced peak isometric twitch force despite normal [Ca2+]i in juvenile banded ferrets age 10-12 weeks with right ventricular pressure overload hypertrophy (POHj). In the present study we report findings in banded weanling ferrets (POHw) age 7 weeks. POHw animals showed a similar degree of hypertrophy to that found in the POHj. However, there was a greater peak twitch force in hypertrophied muscles at higher [Ca2+]o. There was no difference in peak [Ca2+]i: -3.1(SEM 0.1) v -3.1(0.3) (log fractional luminescence) at 16 mM [Ca2+]o for control and POHw, respectively. Connective tissue content for control animals was 10(1)% versus 10(2)% in POHw. Despite a lack of quantitative change in connective tissue content or resting [Ca2+]i in POHw, passive stiffness in papillary muscles was increased. Retrospective analysis of tissue from POHj revealed a connective tissue content of 24(6.8)% (P << 0.001). Thus the decreased peak twitch force reported in POHj might in part be due to an increase in fibrous connective tissue. In this study, lactate dehydrogenase was significantly higher (38%) in POHw animals. In contradistinction, total creatine kinase activity and total creatine content were significantly less (22%) in hearts from POHj animals, indicating differences in myocyte remodelling despite similar degrees and durations of hypertrophy.
Comparison of POHw and POHj showed that, when there is restructuring of the extracellular space in terms of increased fibrosis, there is also molecular remodelling in the myocyte, as demonstrated by a decrease in the creatine kinase system.
比较幼年或断奶期接受肺动脉环扎术的雪貂，尽管右心室肥厚程度相似，但出现的峰值抽搐力差异。
对幼年和断奶期雪貂进行肺动脉环扎，诱导压力超负荷肥大后，研究其机械功能（即等长抽搐力和被动僵硬度）、使用钙指示剂水母发光蛋白测定细胞内[Ca2+]、心肌能量供应标志物以及量化的结缔组织含量。
先前发现，10 - 12周龄患有右心室压力超负荷肥大（POHj）的幼年环扎雪貂，尽管细胞内[Ca2+]正常，但等长峰值抽搐力降低。在本研究中，我们报告了7周龄环扎断奶期雪貂（POHw）的研究结果。POHw动物的肥大程度与POHj相似。然而，在较高的[Ca2+]o时，肥大肌肉中的峰值抽搐力更大。在16 mM [Ca2+]o时，对照组和POHw的峰值[Ca2+]i无差异：分别为-3.1（标准误0.1）和-3.1（0.3）（对数荧光分数）。对照组动物的结缔组织含量为10（1）%，而POHw为10（2）%。尽管POHw的结缔组织含量或静息[Ca2+]i缺乏定量变化，但乳头肌的被动僵硬度增加。对POHj组织的回顾性分析显示，结缔组织含量为24（6.8）%（P << 0.001）。因此，POHj中报告的峰值抽搐力降低可能部分归因于纤维结缔组织增加。在本研究中，POHw动物的乳酸脱氢酶显著更高（38%）。相反，POHj动物心脏中的总肌酸激酶活性和总肌酸含量显著更低（22%），表明尽管肥大程度和持续时间相似，但心肌细胞重塑存在差异。
POHw和POHj的比较表明，当细胞外空间因纤维化增加而发生重构时，心肌细胞也会发生分子重塑，如肌酸激酶系统的减少所示。
