1,720,989 research outputs found
Ryanodine Receptor Modulator, Dantrolene Sodium, Improves Survival Following Ventricular Fibrillation
Background: Ventricular fibrillation (VF) is associated with dysfunctional cardiac calcium cycling and poor survival. We hypothesized dantrolene improves survival following VF by stabilizing calcium dysregulation.
Methods: VF was induced in 26 healthy Yorkshire pigs and left untreated for 4 min followed by 3 min of CPR and defibrillation. Dantrolene was infused during CPR. Rabbit hearts (n=14) were studied to evaluate the effect of dantrolene on VF-induced calcium cycling dysfunction. Results: Survival was higher in the dantrolene group. (85% vs. 39%, P=0.01) Dantrolene-treated pigs required significantly lower defibrillation energy level. (150J vs. 650J, P<0.05) Systolic pressure was significantly higher during the post-defibrillation period in the dantrolene group. (P=0.001) In rabbit hearts, dantrolene significantly mitigated the amplitude of VF-induced diastolic calcium elevations and increased the calcium alternans threshold. (P<0.05) Conclusion: Our findings suggest dantrolene facilitates successful defibrillation, prevents myocardial stunning and improves survival following VF. The effects are mediated through normalizing the VF-induced dysfunctional calcium cycling.MAS
Ryanodine Receptor Modulator, Dantrolene Sodium, Improves Survival Following Ventricular Fibrillation
Background: Ventricular fibrillation (VF) is associated with dysfunctional cardiac calcium cycling and poor survival. We hypothesized dantrolene improves survival following VF by stabilizing calcium dysregulation.
Methods: VF was induced in 26 healthy Yorkshire pigs and left untreated for 4 min followed by 3 min of CPR and defibrillation. Dantrolene was infused during CPR. Rabbit hearts (n=14) were studied to evaluate the effect of dantrolene on VF-induced calcium cycling dysfunction. Results: Survival was higher in the dantrolene group. (85% vs. 39%, P=0.01) Dantrolene-treated pigs required significantly lower defibrillation energy level. (150J vs. 650J, P<0.05) Systolic pressure was significantly higher during the post-defibrillation period in the dantrolene group. (P=0.001) In rabbit hearts, dantrolene significantly mitigated the amplitude of VF-induced diastolic calcium elevations and increased the calcium alternans threshold. (P<0.05) Conclusion: Our findings suggest dantrolene facilitates successful defibrillation, prevents myocardial stunning and improves survival following VF. The effects are mediated through normalizing the VF-induced dysfunctional calcium cycling.MAS
The Role of KATP-channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts
Background: Modulation of ischemia-dependent pathways alters electrophysiological evolution of ventricular fibrillation(VF).
Hypothesis: 1)There is regional disease-related expression of KATP-channels in human cardiomyopathic hearts. 2)KATP-channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness(ΔERP).
Methods and Results: Electric mapping of control(n=6) and treatment(n=9) (10 μmol/L glibenclamide) isolated human cardiomyopathic hearts was performed. Spontaneous defibrillation and KATP-subunit gene expression were studied. Spontaneous VF termination occurred in 1/6 control and 7/8 treated hearts (P=0.026). After 180 seconds of ischemia, LV transmural dispersion in VF cycle length was observed(p=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP-subunit on the endocardium compared with the epicardium(P<0.02). In ischemic rat heart model, ΔERP was verified with pacing protocols (36±5ms vs 4.9±4ms, p=0.019).
Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation by attenuating ischemia-dependent ΔERP during VF.MAS
The Role of KATP-channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts
Background: Modulation of ischemia-dependent pathways alters electrophysiological evolution of ventricular fibrillation(VF).
Hypothesis: 1)There is regional disease-related expression of KATP-channels in human cardiomyopathic hearts. 2)KATP-channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness(ΔERP).
Methods and Results: Electric mapping of control(n=6) and treatment(n=9) (10 μmol/L glibenclamide) isolated human cardiomyopathic hearts was performed. Spontaneous defibrillation and KATP-subunit gene expression were studied. Spontaneous VF termination occurred in 1/6 control and 7/8 treated hearts (P=0.026). After 180 seconds of ischemia, LV transmural dispersion in VF cycle length was observed(p=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP-subunit on the endocardium compared with the epicardium(P<0.02). In ischemic rat heart model, ΔERP was verified with pacing protocols (36±5ms vs 4.9±4ms, p=0.019).
Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation by attenuating ischemia-dependent ΔERP during VF.MAS
Model of Electrophysiology and Metabolism of The Heart
Electrical and metabolic activities of the heart are closely connected, however, the dynamics of this relationship remains unclear. In this thesis, the relationship between the electrophysiology and metabolism of the heart is studied. Using mouse heart in Langendorff set-up and an optical system to measure NADH and calcium concurrently in endocardium of the mouse heart, the effect of heart rate on metabolism is studied. Based on the experimental measurements, a mathematical model of metabolism and electrophysiology of the heart is constructed and used for exploring new drug therapeutic strategies.M.H.Sc
Model of Electrophysiology and Metabolism of The Heart
Electrical and metabolic activities of the heart are closely connected, however, the dynamics of this relationship remains unclear. In this thesis, the relationship between the electrophysiology and metabolism of the heart is studied. Using mouse heart in Langendorff set-up and an optical system to measure NADH and calcium concurrently in endocardium of the mouse heart, the effect of heart rate on metabolism is studied. Based on the experimental measurements, a mathematical model of metabolism and electrophysiology of the heart is constructed and used for exploring new drug therapeutic strategies.M.H.Sc
Role of 9-PHEnanthrol on Ventricular Fibrillation Substrate Characteristics of Spontaneously Hypertensive Rat: An Optical Mapping-based Study
Background: Higher expression of the Transient receptor potential melastatin 4 (TRPM4) channels in the ventricle is associated with poor repolarization reserve in the spontaneous hypertensive rat (SHR). The role of TRPM4 inhibition by 9-phenanthrol (PHE) on ventricular electrophysiology in SHR is unknown. Methods: Explanted hearts from SHRs (n=10) and WKY rats (n=10) of 10-14 months of age were subjected to LV epicardial optical mapping for voltage and calcium transient following treatment with 9-PHE (20µM) or vehicle in Langendorff-setup. Hearts were then subjected to rapid electrical pacing to induce ventricular fibrillation (VF). LV tissues from SHR hearts were collected for protein analysis. Results: APD alternans was higher in WKY rats with 9-PHE treatment (p <0.0001). In SHR (p=0.001) and WKY (p<0.0001) rats, epicardial conduction velocity was reduced by 9-PHE treatment. 9-PHE treatment was associated with a reduction in VF dominant frequency in SHR hearts (p = 0.01).M.Sc
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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