Propranolol inhibits IK(Ado) by competetive A1-receptor interaction

Brandts, Bodo; Dirkmann, Daniel; Borchard, Rolf; Wickenbrock, Ingo; Bracht, M. van; Prull, M.W.; Trappe, Hans‐Joachim

doi:10.1007/s00392-004-0094-0

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…Results from a representative experiment are shown in Figure 6A. The IC 50 s of compounds tested were in good correlation with data obtained by other types of assays [9][10][11][12][13][14][15][16] (Table 1). For example, IC 50 s for isoproterenol 10 and verapamil 13 tested in other models were 13 nM (isolated rabbit cardiomyocytes) and 167 nM (isolated guinea pig hearts), respectively.…”

Section: Assessment Of Positive and Negative Chronotrope Effectssupporting

confidence: 80%

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPSC Cells

Sirenko¹,

Crittenden²,

et al. 2013

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A large percentage of drugs fail in clinical studies due to cardiac toxicity; thus, development of sensitive in vitro assays that can evaluate potential adverse effects on cardiomyocytes is extremely important for drug development. Human cardiomyocytes derived from stem cell sources offer more clinically relevant cell-based models than those presently available. Human-induced pluripotent stem cell-derived cardiomyocytes are especially attractive because they express ion channels and demonstrate spontaneous mechanical and electrical activity similar to adult cardiomyocytes. Here we demonstrate techniques for measuring the impact of pharmacologic compounds on the beating rate of cardiomyocytes with ImageXpress Micro and FLIPR Tetra systems. The assays employ calcium-sensitive dyes to monitor changes in Ca 2+ fluxes synchronous with cell beating, which allows monitoring of the beat rate, amplitude, and other parameters. We demonstrate here that the system is able to detect concentration-dependent atypical patterns caused by hERG inhibitors and other ion channel blockers. We also show that both positive and negative chronotropic effects on cardiac rate can be observed and IC 50 values determined. This methodology is well suited for safety testing and can be used to estimate efficacy and dosing of drug candidates prior to clinical studies.

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Section: Assessment Of Positive and Negative Chronotrope Effectssupporting

confidence: 80%

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPSC Cells

Sirenko¹,

Crittenden²,

et al. 2013

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“…On the other hand, beta adrenergic receptors bind to the same stimulatory G-proteins [31,32]. Therefore, theoretically it can be judged that inhibitors of such receptors may decrease activation of the corresponding G-proteins, which eventually lead to decreased cellular concentration of cAMP and reduced response to dipyridamole infusion [17,26,33]. Based on these facts, others concluded that “much of the coronary vasodilation associated with hypoxia is dependent on adrenergic activation and that adenosine may only play a role in sustained hypoxic vasodilation when adrenergic receptors are intact” [33].…”

Section: Discussionmentioning

confidence: 99%

“…Some previous studies suggest that acute beta-blocker administration may reduce the presence and severity of myocardial perfusion defects with dipyridamole stress [8-17]. Nevertheless, most of such studies have been performed with short-term or acute beta-blocker treatment, some after intravenous administration, rather than after long-term oral beta-blocker treatment so that their methods differ from the usual clinical scenario encountered in many patients referring for dipyridamole myocardial perfusion imaging (DMPI) [8-17].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, most of such studies have been performed with short-term or acute beta-blocker treatment, some after intravenous administration, rather than after long-term oral beta-blocker treatment so that their methods differ from the usual clinical scenario encountered in many patients referring for dipyridamole myocardial perfusion imaging (DMPI) [8-17]. Few studies suggested that coronary flow reserve measured by means of positron emission tomography (PET) is improved in stenosis-dependent segments of the myocardium during long-term beta-blocker treatment, thereby b-blockers may decrease the contrast between ischemic and non-ischemic myocardium during hyperemia induced by dipyridamole [18].…”

Section: Introductionmentioning

confidence: 99%

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Withholding or continuing beta-blocker treatment before dipyridamole myocardial perfusion imaging for the diagnosis of coronary artery disease? A randomized clinical trial

et al. 2013

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BackgroundAlthough it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI).MethodsAs a randomized clinical trial, one hundred twenty patients (103 male and 17 female) with angiographically confirmed CAD who were on long-term beta blocker therapy (≥3 months) enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60) in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60) without discontinuation of beta-blockers prior to DMPI.ResultsNo significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility) in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096). Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001); however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898). The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7%) was not statistically different from group B (90%).ConclusionBeta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.

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Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

et al. 2009

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Propranolol inhibits IK(Ado) by competetive A1-receptor interaction

Cited by 3 publications

References 23 publications

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPSC Cells

Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using iPSC Cells

Withholding or continuing beta-blocker treatment before dipyridamole myocardial perfusion imaging for the diagnosis of coronary artery disease? A randomized clinical trial

Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

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