Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts

2009 ◽  
Vol 297 (5) ◽  
pp. H1860-H1869 ◽  
Author(s):  
Francisco J. Chorro ◽  
Isabel Trapero ◽  
Luis Such-Miquel ◽  
Francisca Pelechano ◽  
Luis Mainar ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Receptor Antagonist ◽  
Rabbit Heart ◽  
Dominant Frequency ◽  
Mechanical Activity ◽  
Activation Process ◽  
Multiple Electrodes ◽  
Other Substances ◽  
Sch 58261 ◽  
Electrophysiological Effects

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 Ca2+ handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na+/Ca2+ exchanger blocker KB-R7943, propranolol, and the adenosine A2 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 μM, n = 9), propranolol (1 μM, n = 9), and SCH-58261 (1 μM, n = 9). Both the Na+/Ca2+ 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+/Ca2+ exchanger blocker KB-R7943 and by propranolol but not by the adenosine A2 receptor antagonist SCH-58261.

scholarly journals Detection of Ventricular Fibrillation Based on Ballistocardiography by Constructing an Effective Feature Set

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3524
Author(s):  
Rongru Wan ◽  
Yanqi Huang ◽  
Xiaomei Wu
Keyword(s):  
Ventricular Fibrillation ◽  
Cross Validation ◽  
Rhythmic Activity ◽  
Detection Algorithm ◽  
Motion Artifacts ◽  
Cardiac Monitoring ◽  
Mechanical Activity ◽  
Time Frequency ◽  
S Transform ◽  
Fatal Arrhythmia

Ventricular fibrillation (VF) is a type of fatal arrhythmia that can cause sudden death within minutes. The study of a VF detection algorithm has important clinical significance. This study aimed to develop an algorithm for the automatic detection of VF based on the acquisition of cardiac mechanical activity-related signals, namely ballistocardiography (BCG), by non-contact sensors. BCG signals, including VF, sinus rhythm, and motion artifacts, were collected through electric defibrillation experiments in pigs. Through autocorrelation and S transform, the time-frequency graph with obvious information of cardiac rhythmic activity was obtained, and a feature set of 13 elements was constructed for each 7 s segment after statistical analysis and hierarchical clustering. Then, the random forest classifier was used to classify VF and non-VF, and two paradigms of intra-patient and inter-patient were used to evaluate the performance. The results showed that the sensitivity and specificity were 0.965 and 0.958 under 10-fold cross-validation, and they were 0.947 and 0.946 under leave-one-subject-out cross-validation. In conclusion, the proposed algorithm combining feature extraction and machine learning can effectively detect VF in BCG, laying a foundation for the development of long-term self-cardiac monitoring at home and a VF real-time detection and alarm system.

scholarly journals Beneficial Electrophysiological Effects of Rotigaptide Are Unable to Suppress Therapeutic Hypothermia-Provoked Ventricular Fibrillation in Failing Rabbit Hearts With Acute Ischemia–Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui-Ling Lee ◽  
Po-Cheng Chang ◽  
Hung-Ta Wo ◽  
Hao-Tien Liu ◽  
Ming-Shien Wen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Fibrillation ◽  
Therapeutic Hypothermia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Acute Ischemia ◽  
Electrophysiological Studies ◽  
Electrophysiological Effects

Aims: Whether therapeutic hypothermia (TH) is proarrhythmic in preexisting failing hearts with acute ischemia–reperfusion (IR) injury is unknown. Additionally, the effectiveness of rotigaptide on improving conduction slowing in hearts with IR injury is ambiguous. We investigated the electrophysiological effects of TH and rotigaptide in failing rabbit hearts with acute IR injury and determined the underlying molecular mechanisms.Methods and Results: Heart failure was induced by right ventricular pacing (320 beats/min, 4 weeks). Rabbits with pacing-induced heart failure were randomly divided into TH (n = 14) and non-TH (n = 7) groups. The IR rabbit model was created by ligating the coronary artery for 60 min, followed by reperfusion for 15 min in vivo. Then, the hearts were excised quickly and Langendorff-perfused for simultaneous voltage and intracellular Ca2+ (Cai) optical mapping. Electrophysiological studies were conducted, and vulnerability to ventricular fibrillation (VF) was evaluated using pacing protocols. TH (33°C) was instituted after baseline studies, and electrophysiological studies were repeated. Rotigaptide (300 nM) was infused for 20 min, and electrophysiological studies were repeated under TH. Cardiac tissues were sampled for Western blotting. TH increased the dispersion and beat-to-beat variability of action potential duration (APD), aggravated conduction slowing, and prolonged Cai decay to facilitate spatially discordant alternans (SDA) and VF induction. Rotigaptide reduced the dispersion and beat-to-beat variability of APD and improved slowed conduction to defer the onset of arrhythmogenic SDA by dynamic pacing and elevate the pacing threshold of VF during TH. However, the effect of rotigaptide on TH-enhanced VF inducibility was statistically insignificant. TH attenuated IR-induced dysregulation of protein expression, but its functional role remained uncertain.Conclusion: Therapeutic hypothermia is proarrhythmic in failing hearts with acute IR injury. Rotigaptide improves TH-induced APD dispersion and beat-to-beat variability and conduction disturbance to defer the onset of arrhythmogenic SDA and elevate the VF threshold by dynamic pacing, but these beneficial electrophysiological effects are unable to suppress TH-enhanced VF inducibility significantly.

Contribution of adenosine to isoproterenol-stimulated prostacyclin production in rabbit heart

1992 ◽  
Vol 263 (1) ◽  
pp. H218-H225
Author(s):  
C. Cano ◽  
Z. Qureshi ◽  
S. Carter ◽  
K. U. Malik
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Rabbit Heart ◽  
Mechanical Function ◽  
Cgs 21680 ◽  
A1 Receptor ◽  
Prostacyclin Production ◽  
Prostacyclin Synthesis ◽  
A2 Receptors ◽  
Krebs Henseleit Buffer

This study investigated adenosine's contribution to isoproterenol-stimulated prostacyclin production, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output, and mechanical function in the isolated rabbit heart perfused with Krebs-Henseleit buffer. The isoproterenol-induced increase in 6-keto-PGF1 alpha was diminished by adenosine (10 microM), the A1 receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine (DPCPX 0.06 microM), and the A2 receptor agonist CGS-21680 (0.6 microM); CGS-21680 did not decrease heart rate (HR) or myocardial contractility (dP/dt(max)). The isoproterenol-induced increase in 6-keto-PGF1 alpha was potentiated by the A1 receptor agonist 1-deaza,2-chloro,N6-cyclopentyladenosine (DCCA, 0.6 microM) and the A2 receptor antagonist 3,7-dimethyl,1-propargylxanthine (DMPX, 6 microM). The isoproterenol-induced increase in dP/dt(max) and HR was diminished by adenosine, DCCA, and DMPX. DPCPX enhanced dP/dt(max) and HR and prevented the decrease by adenosine and DCCA of the isoproterenol-induced increase in HR and dP/dt(max); the increase by DCCA but not the decrease by adenosine in 6-keto-PGF1 alpha output was abolished. DMPX abolished the effect of adenosine and CGS-21680 to reduce isoproterenol-stimulated 6-keto-PGF1 alpha. These data suggest that adenosine generated in response to isoproterenol attenuates its effect on HR and dP/dt(max) through A1 receptors and on prostacyclin synthesis via A2 receptors.

scholarly journals Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern

2020 ◽  
Author(s):  
Balvinder S Handa ◽  
Xinyang Li ◽  
Nicoleta Baxan ◽  
Caroline H Roney ◽  
Anastasia Shchendrygina ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Gap Junction ◽  
Dominant Frequency ◽  
Diffuse Fibrosis ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Junction Coupling ◽  
Ventricular Fibrosis

Abstract Aims Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism. Methods and results Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P &lt; 0.001), increasing RA-sustained VF time (0 nM: 44 ± 6%, 80 nM: 94 ± 2%, P &lt; 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM: 5.4 ± 0.5, 80 nM: 48.2 ± 12.3, P &lt; 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM: 0.60 ± 0.05, 50 µM: 0.17 ± 0.03, P &lt; 0.001) and RA-sustained VF time decreased (0 µM: 61 ± 9%, 50 µM: 3 ± 2%, P &lt; 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF: 27 ± 7% vs. PF: 75 ± 5%, P &lt; 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF: 0.67 ± 0.05 vs. CF: 0.33 ± 0.03, P &lt; 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411 ± 266 ms vs. compact: 354 ± 38 ms, P &lt; 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs. Conclusion The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.

Sign in / Sign up

Export Citation Format

Share Document