Role of MgADP in the development of diastolic dysfunction in the intact beating rat heart
| Autor: | Matthias Spindler, James C.A. Hopkins, S. A. Camacho, Rong Tian, Jessica M. Halow, Michael E. Christe, Joanne S. Ingwall |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Diastole chemistry.chemical_element Myocardial Reperfusion Calcium Sarcomere Iodoacetamide chemistry.chemical_compound Ventricular Dysfunction Left Myosin Animals heterocyclic compounds Calcium metabolism Dose-Response Relationship Drug Chemistry musculoskeletal neural and ocular physiology Myocardium General Medicine musculoskeletal system Rats Adenosine Diphosphate Preload Adenosine diphosphate Biochemistry Ventricular pressure Biophysics tissues Glycolysis Research Article |
| Zdroj: | The Journal of clinical investigation. 99(4) |
| ISSN: | 0021-9738 |
| Popis: | Sarcomere relaxation depends on dissociation of actin and myosin, which is regulated by a number of factors, including intracellular [MgATP] as well as MgATP hydrolysis products [MgADP] and inorganic phosphate [Pi], pHi, and cytosolic calcium concentration ([Ca2+]c). To distinguish the contribution of MgADP from the other regulators in the development of diastolic dysfunction, we used a strategy to increase free [MgADP] without changing [MgATP], [Pi], or pHi. This was achieved by applying a low dose of iodoacetamide to selectively inhibit the creatine kinase activity in isolated perfused rat hearts. [MgATP], [MgADP], [Pi], and [H+] were determined using 31P NMR spectroscopy. The [Ca2+]c and the glycolytic rate were also measured. We observed an approximately threefold increase in left ventricular end diastolic pressure (LVEDP) and 38% increase in the time constant of pressure decay (P < 0.05) in these hearts, indicating a significant impairment of diastolic function. The increase in LVEDP was closely related to the increase in free [MgADP]. Rate of glycolysis was not changed, and [Ca2+]c increased by 16%, which cannot explain the severity of diastolic dysfunction. Thus, our data indicate that MgADP contributes significantly to diastolic dysfunction, possibly by slowing the rate of cross-bridge cycling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|