Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts.
Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+) exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1 microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor antagonist SCH-58261.
Chorro
Francisco J
FJ
Cardiology Service, Univ. Clinic Hospital, Avda. Blasco Ibañez 17, Valencia 46010, Spain. Francisco.J.Chorro@uv.es
Trapero
Isabel
I
Such-Miquel
Luis
L
Pelechano
Francisca
F
Mainar
Luis
L
Cánoves
Joaquín
J
Tormos
Alvaro
A
Alberola
Antonio
A
Hove-Madsen
Leif
L
Cinca
Juan
J
Such
Luis
L
D000200:Action Potentials; D058917:Adenosine A2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005583:Fourier Analysis; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D009470:Muscle Spindles / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011817:Rabbits; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011743:Pyrimidines; D043683:Receptors, Adenosine A2; D019831:Sodium-Calcium Exchanger; D014230:Triazoles; D011433:Propranolol; D013890:Thiourea