Li K, Rouleau J L
Department of Medicine, Institut de Cardiologie de Montréal, Quebec, Canada.
J Mol Cell Cardiol. 1995 Jun;27(6):1251-61. doi: 10.1016/s0022-2828(05)82387-9.
The objective of this study was to evaluate the tension-frequency relationship in normal and cardiomyopathic myocardium from one species with a negative or biphasic relationship, the hamster, and one with a positive relationship, the dog. Left ventricular papillary muscles from 100-day-old normal Syrian and cardiomyopathic (CHF-147) hamsters and right ventricular papillary muscles or trabeculae from normal mongrel dogs and dog with pacing-induced heart failure were used for the study. Stimulation frequency was varied from 1 to 90/min and isometric contractions recorded at each frequency prior to and after the addition of phenylephrine 10 microM. A tension-frequency relationship at varying extracellular calcium concentrations (1.25, 2.5 and 5.0 mM) was also constructed in normal hamster myocardium. Ryanodine 1.2 microM was added to a bath with normal hamster muscles and a force-frequency relationship constructed prior to and after adding phenylephrine 10 microM. A calcium dose-response curve in normal and cardiomyopathic dog myocardium was also constructed. Normal and cardiomyopathic hamster myocardium had a biphasic tension-frequency relationship with the increase in tension during the second phase being greater in normal v cardiomyopathic hamster myocardium (0.66 +/- 0.19 v 0.12 +/- 0.03 g/mm2, P < 0.05). The initial decrease in tension in response to increasing stimulation frequency was markedly attenuated in normal hamster myocardium by increasing extracellular calcium concentration. Developed tension was eliminated at lower stimulation rates by ryanodine such that when developed tension did occur, it increased with increasing stimulation rates. The addition of phenylephrine to hamster myocardium modified the tension-frequency relationship of both normal and cardiomyopathic dog myocardium and their response to phenylephrine were similar. In each case, tension increased progressively with increasing stimulation rate. Although the absolute increase in tension caused by increasing extracellular calcium was less in cardiomyopathic dog myocardium, the percent increase in tension and shortening was greater. We conclude that the tension-frequency relationship of normal and cardiomyopathic hamster myocardium are biphasic, with the initial negative phase being the result of limitations of sarcoplasmic reticulum calcium handling. Phenylephrine modifies this relationship to a uniphasic positive one, likely by its effects on both the sarcolemma and the sarcoplasmic reticulum. Also, the tension-frequency relationship of normal and cardiomyopathic dog myocardium are similar and unmodified by phenylephrine.
本研究的目的是评估仓鼠(其正常心肌和心肌病心肌呈现负相关或双相相关)和犬(其呈现正相关)这两种动物正常及心肌病心肌中的张力-频率关系。选用100日龄正常叙利亚仓鼠和患心肌病(CHF-147)的仓鼠的左心室乳头肌,以及正常杂种犬和起搏诱导心力衰竭犬的右心室乳头肌或小梁进行研究。刺激频率在1至90次/分钟之间变化,在加入10微摩尔去氧肾上腺素前后,记录每个频率下的等长收缩。还构建了正常仓鼠心肌在不同细胞外钙浓度(1.25、2.5和5.0毫摩尔)下的张力-频率关系。将1.2微摩尔的兰尼碱加入含有正常仓鼠肌肉的浴槽中,并在加入10微摩尔去氧肾上腺素前后构建力-频率关系。同时构建了正常和心肌病犬心肌的钙剂量-反应曲线。正常和心肌病仓鼠心肌呈现双相张力-频率关系,在第二阶段张力增加,正常仓鼠心肌比心肌病仓鼠心肌更大(0.66±0.19对0.12±0.03克/平方毫米,P<0.05)。通过增加细胞外钙浓度,正常仓鼠心肌中因刺激频率增加而导致的初始张力下降明显减弱。兰尼碱在较低刺激速率下消除了发展中的张力,因此当发展中的张力确实出现时,它会随着刺激速率的增加而增加。向仓鼠心肌中加入去氧肾上腺素改变了正常和心肌病犬心肌的张力-频率关系,且它们对去氧肾上腺素的反应相似。在每种情况下,张力随着刺激速率的增加而逐渐增加。尽管在心肌病犬心肌中,细胞外钙增加引起的张力绝对增加较小,但张力和缩短的百分比增加更大。我们得出结论,正常和心肌病仓鼠心肌的张力-频率关系是双相的,初始负相是肌浆网钙处理受限的结果。去氧肾上腺素可能通过其对肌膜和肌浆网的作用将这种关系改变为单相正相关关系。此外,正常和心肌病犬心肌的张力-频率关系相似,且不受去氧肾上腺素影响。