Evaluation of the regional responsivity to ryanodine of human myocardium from patients with idiopathic dilated cardiomyopathy and secondary cardiomyopathies.
The aim of the study was to compare the contractile response to ryanodine of human heart preparations taken from right and left ventricles of patients affected by idiopathic (IDCM) and secondary (SCM) end-stage dilated cardiomyopathies. Right and left ventricle myocardial strips were obtained from hearts of patients undergoing orthotopic heart transplantation and suspended in an oxygenated bath (T = 35 degrees C; stimulation frequency = 0.5 Hz). After an equilibration period, a cumulative dose-response curve for contractility (peak tension) was obtained with ryanodine (0.5, 1, 2, 4, 8, 16, 32, 64 microM). Basal contractility was not significantly different between right and left ventricles or between IDCM and SCM preparations. Ryanodine reduced peak myocardial tension but failed to completely suppress it, even at concentrations which achieved maximum effect. Ryanodine effect still persisted after a 45'-60' washout. The concentration-effect curves from IDCM right ventricle, IDCM left ventricle, SCM right ventricle and SCM left ventricle were compared: IDCM left ventricle was less sensitive to ryanodine than IDCM right ventricle and SCM left ventricle, while no difference was detectable between SCM left ventricle and SCM right ventricle. Thus, the overall sensitivity ranking was: IDCM left ventricle < IDCM right ventricle = SCM right ventricle = SCM left ventricle. IDCM left ventricle showed, in addition, a biphasic response with a shift from negative to positive inotropic effect at concentrations higher than approximately 10 microM. These findings indicate that the cardio-depressant effect of ryanodine, a drug which interferes with intracellular Ca release from the sarcoplasmic reticulum, differs quantitatively and qualitatively in IDCM left ventricle from both IDCM right ventricle and SCM left ventricle. This suggests that some specific alteration in the intracellular Ca signalling in IDCM exists and, from a methodological point of view, stresses the need for a "bi-ventricular" approach to studying biochemical and functional abnormalities of advanced congestive heart failure.
Padrini
R
R
Department of Pharmacology, University of Padua, Padova, Italy.
Panfili
M
M
Testolin
L
L
Pesarin
F
F
Piovan
D
D
Magnolfi
G
G
Livi
U
U
Casarotto
D
D
Dalla Volta
S
S
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D012433:Ryanodine / Q000008:administration & dosage*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D012433:Ryanodine; D002118:Calcium