OBJECTIVE: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. METHODS: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca(2+) and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca(2+)-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na(+)/Ca(2+)-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. RESULTS: In 72 muscle preparations of SR patients contractile force was 10.9+/-1.8 mN/mm(2) compared to 3.3+/-0.9 mN/mm(2) (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na(+)/Ca(2+)-exchanger was upregulated by 67% in atria of AF patients. CONCLUSIONS: AF-induced atrial contractile dysfunction is not due to beta-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca(2+)-channel and an increased Ca(2+) extrusion via the Na(+)/Ca(2+)-exchanger seem to be responsible for the depressed contractility in remodeled atria.
OBJECTIVE: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. METHODS: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca(2+) and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca(2+)-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na(+)/Ca(2+)-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. RESULTS: In 72 muscle preparations of SR patients contractile force was 10.9+/-1.8 mN/mm(2) compared to 3.3+/-0.9 mN/mm(2) (n=48, P<0.01) in AFpatients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AFpatients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AFpatients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na(+)/Ca(2+)-exchanger was upregulated by 67% in atria of AFpatients. CONCLUSIONS:AF-induced atrial contractile dysfunction is not due to beta-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca(2+)-channel and an increased Ca(2+) extrusion via the Na(+)/Ca(2+)-exchanger seem to be responsible for the depressed contractility in remodeled atria.
Authors: Evelin Seppet; Margus Eimre; Nadezhda Peet; Kalju Paju; Ehte Orlova; Mati Ress; Sirje Kõvask; Andres Piirsoo; Valdur A Saks; Frank N Gellerich; Stephan Zierz; Enn K Seppet Journal: Mol Cell Biochem Date: 2005-02 Impact factor: 3.396
Authors: Patrick Müller; Johannes Maier; Johannes-Wolfgang Dietrich; Sebastian Barth; Daniel P Griese; Fabian Schiedat; Attila Szöllösi; Philipp Halbfass; Karin Nentwich; Markus Roos; Joachim Krug; Anja Schade; Rainer Schmitt; Andreas Mügge; Thomas Deneke Journal: J Interv Card Electrophysiol Date: 2015-06-06 Impact factor: 1.900
Authors: Torsten Christ; Nadiia Rozmaritsa; Andreas Engel; Emanuel Berk; Michael Knaut; Katharina Metzner; Manuel Canteras; Ursula Ravens; Alberto Kaumann Journal: Proc Natl Acad Sci U S A Date: 2014-07-14 Impact factor: 11.205