Grandis D J, DelNido P J, Koretsky A P
Department of Medicine, Allegheny General Hospital/Medical College of Pennsylvania, Pittsburgh 15212, USA.
Am J Physiol. 1995 Aug;269(2 Pt 1):C472-9. doi: 10.1152/ajpcell.1995.269.2.C472.
This investigation studied the functional and energetic effects of the novel positive inotropic agent EMD-57033 and the negative inotropic agent 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the paced Langendorff-perfused rat heart. EMD-57033 is a calcium-sensitizing agent that has previously been shown to increase contractility without affecting calcium transients. Its effects were compared with that of dobutamine, which increases contractility by increasing calcium transient amplitude. EMD-57033 (2 microM) and dobutamine (0.2 microM) induced a 40% increase in developed pressure. Myocardial oxygen consumption (MVO2) increased significantly with dobutamine. However, there was no significant change in MVO2 with EMD-57033. There was no change in phosphate metabolite concentrations as detected by 31P-nuclear magnetic resonance with either agent. Lactate production and basal metabolism were unaffected by either agent. Thus EMD-57033 increased contractility in a more energetically economical manner than did dobutamine. Contractility was decreased with BAPTA, an intracellular calcium chelator that decreases contractility by binding free calcium. The metabolic effects of BAPTA (2.2 microM) were compared with those of verapamil (10 nM), an agent which decreases calcium fluxes. Both agents decreased developed pressure 60%. MVO2 decreased 14% with BAPTA and 50% with verapamil. Neither agent altered the concentrations of phosphate metabolites, lactate production, or basal metabolism. Thus BAPTA lowered contractility in a less energetically economical manner than verapamil. These data suggest that in rat hearts, inotropic agents with different effects on calcium handling have different effects on energetics.
本研究探讨了新型正性肌力药物EMD - 57033和负性肌力药物1,2 - 双(2 - 氨基苯氧基)乙烷 - N,N,N',N' - 四乙酸(BAPTA)对起搏Langendorff灌流大鼠心脏的功能和能量代谢的影响。EMD - 57033是一种钙增敏剂，此前已证明其可增加心肌收缩力而不影响钙瞬变。将其作用与多巴酚丁胺进行比较，多巴酚丁胺通过增加钙瞬变幅度来增加心肌收缩力。EMD - 57033(2 microM)和多巴酚丁胺(0.2 microM)使舒张末压升高40%。多巴酚丁胺使心肌耗氧量(MVO2)显著增加。然而，EMD - 57033处理后MVO2无显著变化。两种药物经31P - 核磁共振检测均未引起磷酸代谢物浓度改变。乳酸生成和基础代谢不受两种药物影响。因此，与多巴酚丁胺相比，EMD - 57033以更节能的方式增加心肌收缩力。BAPTA是一种细胞内钙螯合剂，通过结合游离钙降低心肌收缩力，可使心肌收缩力下降。将BAPTA(2.2 microM)的代谢作用与维拉帕米(10 nM)进行比较，维拉帕米可减少钙内流。两种药物均使舒张末压降低60%。BAPTA使MVO2降低14%，维拉帕米使MVO2降低50%。两种药物均未改变磷酸代谢物浓度、乳酸生成或基础代谢。因此，与维拉帕米相比，BAPTA以能量利用效率较低的方式降低心肌收缩力。这些数据表明，在大鼠心脏中，对钙处理有不同影响的肌力药物对能量代谢有不同影响。
