Abstract:
:1. Effects of a newly developed phosphodiesterase (PDE) III inhibitor, E-1020, on intracellular calcium transients were compared with those of isoproterenol (ISO) in isolated single myocytes from failing hearts secondary to pulmonary hypertension induced by monocrotaline injection. Myocytes were isolated by enzyme digestion using a Langendorff apparatus. Changes in intracellular calcium concentrations ([Ca2+]i) were recorded using a fura-2 fluorescence microscopic technique. Cyclic AMP contents of the hearts were measured by radio-immunoassay. 2. Myocytes from failing hearts showed Ca2+ transients with a low peak (low amplitude) and delayed decline of Ca2+ transients. Both ISO and E-1020 increased peak [Ca2+]i, max + d[Ca2+]i/dt, and max - d[Ca2+]i/dt in a concentration-dependent manner while both agents decreased T80L (time to 80% decline of amplitude from peak light). The concentrations which increased peak [Ca2+]i by 50% were 1.6 x 10(-9) mol/L of ISO and 2 x 10(-6) mol/L of E-1020. These concentrations increased cAMP in the heart to the same levels. Analysis of the effects of both agents on peak [Ca2+]i versus max - d[Ca2+]i/dt showed that ISO is much more effective on peak [Ca2+]i while E-1020 is more effective on max - d[Ca2+]i/dt. 3. These results showed that the effects of ISO and E-1020 on the parameters of intracellular Ca2+ transients of single myocytes from failing hearts are slightly different, and suggest that E-1020 may improve diastolic function as well as systolic function in failing hearts.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Honda M,Kuramochi T,Ishinaga Y,Kuzuo H,Tanaka K,Morioka S,Enomoto K,Takabatake Tdoi
10.1111/j.1440-1681.1994.tb02663.xsubject
Has Abstractpub_date
1994-12-01 00:00:00pages
1001-8issue
12eissn
0305-1870issn
1440-1681journal_volume
21pub_type
杂志文章abstract::1. Landrace swine were identified as malignant hyperpyrexia susceptible (MHS) or control by the contracture responses of gracilis muscle fibre bundles to 3% halothane, 2 mmol/l caffeine and 80 mmol/l KCl. The effects of calmodulin-antagonist drugs on the contractile behaviour of control and MHS preparations were inves...
journal_title:Clinical and experimental pharmacology & physiology
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journal_title:Clinical and experimental pharmacology & physiology
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章
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