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- Corino, Valentina D.A., et al.
(författare)
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Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation
- 2014. - January
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Ingår i: Computing in Cardiology 2014. - : Oxford University Press (OUP). - 2325-8861. - 9781479943463 - 9781479943470 ; 41, s. 889-892
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Konferensbidrag (refereegranskat)abstract
- The aim of this study was to evaluate changes in AV nodal properties during administration of metoprolol, using a novel ECG-based method for parameter estimation. The AV nodal parameters account for the probability of an impulse not passing through the fast pathway, the absolute refractory periods of the slow and fast pathways (aRPs and aRPf), representing the functional refractory period, and related prolongation in the respective refractory periods. Twenty patients (age 71±8 years, 14 men) with permanent AF from the RATe control in Atrial Fibrillation (RATAF) database were included in this study. Recordings during baseline and metoprolol administration were analyzed. Furthermore, simulated RR series were generated mimicking metoprolol administration. During metoprolol administration, aRP was significantly prolonged in both pathways (aRPs: 342±39 vs. 408±81 ms, p<0.001; aRPf: 432±74 vs. 527±83 ms, p<0.001). Similar results were found for the simulated RR series: both aRPs and aRPf were significantly prolonged with metoprolol. The AV nodal parameters reflect expected changes after metoprolol administration, i.e., a prolongation in functional refractory period. The simulations suggest that aRP may serve as an estimate of the functional refractory period.
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| 2. |
- Corino, Valentina D. A., et al.
(författare)
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Rate-Control Drugs Affect Variability and Irregularity Measures of RR Intervals in Patients with Permanent Atrial Fibrillation
- 2015
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 26:2, s. 137-141
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Tidskriftsartikel (refereegranskat)abstract
- Heart Rate Variability and Irregularity During AF IntroductionIrregularity measures have been suggested as risk indicators in patients with atrial fibrillation (AF); however, it is not known to what extent they are affected by commonly used rate-control drugs. We aimed at evaluating the effect of metoprolol, carvedilol, diltiazem, and verapamil on the variability and irregularity of the ventricular response in patients with permanent AF. Methods and ResultsSixty patients with permanent AF were part of an investigator-blind cross-over study, comparing 4 rate-control drugs (diltiazem, verapamil, metoprolol, and carvedilol). We analyzed five 20-minute segments per patient: baseline and the 4 drug regimens. On every segment, heart rate (HR) variability and irregularity of RR series were computed. The variability was assessed as standard deviation, pNN20, pNN50, pNN80, and rMSSD. The irregularity was assessed by regularity index, approximate (ApEn), and sample entropy. A significantly lower HR was obtained with all drugs, the HR was lowest using the calcium channel blockers. All drugs increased the variability of ventricular response in respect to baseline (as an example, rMSSD: baseline 171 47 milliseconds, carvedilol 229 +/- 58 milliseconds; P < 0.05 vs. baseline, metoprolol 226 +/- 66 milliseconds; P < 0.05 vs. baseline, verapamil 228 +/- 84; P < 0.05 vs. baseline, diltiazem 256 +/- 87 milliseconds; P < 0.05 vs. baseline and all other drugs). Only -blockers significantly increased the irregularity of the RR series (as an example, ApEn: baseline 1.86 +/- 0.13, carvedilol 1.92 +/- 0.09; P < 0.05 vs. baseline, metoprolol 1.93 +/- 0.08; P < 0.05 vs. baseline, verapamil 1.86 +/- 0.22 ns, diltiazem 1.88 +/- 0.16 ns). ConclusionModification of AV node conduction by rate-control drugs increase RR variability, while only -blockers affect irregularity.
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| 3. |
- Ressa, Anna, et al.
(författare)
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A System-wide Approach to Monitor Responses to Synergistic BRAF and EGFR Inhibition in Colorectal Cancer Cells
- 2018
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Ingår i: Molecular & Cellular Proteomics. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 1535-9476 .- 1535-9484. ; 17:10, s. 1892-1908
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Tidskriftsartikel (refereegranskat)abstract
- Intrinsic and/or acquired resistance represents one of the great challenges in targeted cancer therapy. A deeper understanding of the molecular biology of cancer has resulted in more efficient strategies, where one or multiple drugs are adopted in novel therapies to tackle resistance. This beneficial effect of using combination treatments has also been observed in colorectal cancer patients harboring the BRAF(V600E) mutation, whereby dual inhibition of BRAF(V600E) and EGFR increases antitumor activity. Notwithstanding this success, it is not clear whether this combination treatment is the only or most effective treatment to block intrinsic resistance to BRAF inhibitors. Here, we investigate molecular responses upon single and multi-target treatments, over time, using BRAF(V600E) mutant colorectal cancer cells as a model system. Through integration of transcriptomic, proteomic and phosphoproteomics data we obtain a comprehensive overview, revealing both known and novel responses. We primarily observe widespread up-regulation of receptor tyrosine kinases and metabolic pathways upon BRAF inhibition. These findings point to mechanisms by which the drug-treated cells switch energy sources and enter a quiescent-like state as a defensive response, while additionally compensating for the MAPK pathway inhibition.
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| 4. |
- Sandberg, Frida, et al.
(författare)
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Drug effect evaluation during permanent atrial fibrillation using an AV-node model
- 2013
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Ingår i: Computing in Cardiology 2013, CinC 2013. - 9781479908844 ; 40, s. 1243-1246
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Konferensbidrag (refereegranskat)abstract
- The purpose of the present study is to evaluate the effect of rate control drugs on the AV node characteristics during atrial fibrillation (AF) using a model-based approach. A statistical model of the AV nodal function is employed, defined by parameters which characterize the arrival rate of atrial impulses, the refractoriness of the fast and the slow AV-nodal pathway and the probability of atrial impulse to pass through either of the two pathways. The RATAF (RATe control in Atrial Fibrillation) study database consists of recordings from 60 patients with permanent AF at baseline and on treatment with metoprolol, verapamil, diltiazem and carvedilol, respectively. The resulting model parameter estimates indicate that the refractory period of the slow pathway as well as that of the fast pathway increased significantly during treatment with all four drugs. The results suggest that the proposed AV-node model can be used for non-invasive evaluation of the effect of rate control drugs.
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