scholarly journals Modulation of arrhythmias by isoproterenol in a rabbit heart model of d-sotalol-induced long Q-T intervals

2000 ◽  
Vol 279 (1) ◽  
pp. H15-H25 ◽  
Author(s):  
Joseph F. Spear ◽  
E. Neil Moore
Keyword(s):  
Rabbit Heart ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
Adrenergic Stimulation ◽  
Heart Model ◽  
Recovery Interval ◽  
Potential Map ◽  
Recovery Times ◽  
Mean Cycle ◽  
Temporal Dispersion

Sympathetic influences have been implicated in arrhythmias associated with both congenital and acquired long Q-T intervals. We recorded epicardial electrograms, a left ventricular endocardial monophasic action potential (MAP), and a bipolar electrocardiogram in 23 isolated rabbit hearts. Spontaneous focal arrhythmias appeared within 8–18 min following 92 μM d-sotalol in 15 of 23 hearts. The epicardial activation-recovery interval was shorter at baseline and increased to a significantly greater degree after d-sotalol administration in the hearts that developed focal activity. The standard deviation of the activation-recovery interval of the epicardial sites also increased. With the addition of 0.01 μM isoproterenol, the incidence of focal activity increased, and its mean cycle length was shortened by 7%. Also, myocardial recovery time in the epicardium was shortened to a greater degree than the endocardial MAP duration. It did not alter local epicardial heterogeneity of recovery but did increase the regional dispersion between epicardial recovery times, and the endocardial MAP duration. Therefore, β-adrenergic stimulation in the presence of d-sotalol favors the appearance of arrhythmias by increasing the propensity for closely coupled focal activity and the temporal dispersion of recovery.

Cardiac electrophysiological variables in blood-perfused and buffer-perfused, isolated, working rabbit heart

1996 ◽  
Vol 271 (2) ◽  
pp. H784-H789 ◽  
Author(s):  
A. M. Gillis ◽  
E. Kulisz ◽  
H. J. Mathison
Keyword(s):  
Ventricular Fibrillation ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
High Cardiac Output ◽  
Ventricular Afterload ◽  
Cardiac Hemodynamics ◽  
Perfused Hearts ◽  
Krebs Henseleit Buffer

Effects of crystalloid buffer and blood-buffer perfusates on cardiac electrophysiological parameters were compared in four groups of isolated, working rabbit hearts. Hearts were perfused with Krebs-Henseleit buffer or blood plus Krebs-Henseleit buffer (10% hematocrit) over a range of left ventricular afterload (30-100 cmH2O) and cardiac outputs (30-180 ml/min). Left ventricular monophasic action potential duration (APD) was significantly shorter at low afterload and high cardiac output in buffer-perfused (114 +/- 35 ms) compared with blood-perfused hearts (177 +/- 23 ms, P < 0.001). APD shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05), and APD was similar in blood-perfused (151 +/- 19 ms) compared with buffer-perfused hearts (142 +/- 24 ms, P = NS). Ventricular effective refractory period (VERP) was significantly shorter at low afterload in buffer-perfused (154 +/- 32 ms) compared with blood-perfused hearts (227 +/- 17 ms, P < 0.001). VERP shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05) and was similar in blood-perfused (166 +/- 26 ms) compared with buffer-perfused hearts (151 +/- 37 ms, P = NS). Determination of VERP was associated with induction of ventricular fibrillation in 10 of 15 buffer-perfused hearts, whereas ventricular fibrillation was not observed in blood-perfused hearts (P < 0.001). Thus significant differences in ventricular repolarization and cardiac hemodynamics are observed in working rabbit hearts perfused with a blood-buffer perfusate compared with a crystalloid buffer. Blood-perfused working hearts are electrophysiologically more stable.

Echocardiographic contrast agents and left ventricular contractility: Evaluation using an isolated rabbit heart model

1996 ◽  
Vol 9 (4) ◽  
pp. 452-461 ◽  
Author(s):  
Victor Mor-Avi ◽  
Sanjeev G. Shroff ◽  
Kimberly A. Robinson ◽  
Bernard P. Cholley ◽  
Arthur F. Ng ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Heart Model ◽  
Isolated Rabbit Heart

scholarly journals Effects of left ventricular pressure on sonicated albumin microbubbles: Evaluation using an isolated rabbit heart model

1994 ◽  
Vol 24 (7) ◽  
pp. 1779-1785 ◽  
Author(s):  
Victor Mor-Avi ◽  
Sanjeev G. Shroff ◽  
Kimberley A. Robinson ◽  
Arthur F. Ng ◽  
Bernard P. Cholley ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Heart Model ◽  
Isolated Rabbit Heart

Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart

1998 ◽  
Vol 274 (3) ◽  
pp. H817-H828 ◽  
Author(s):  
Joseph F. Spear ◽  
E. Neil Moore
Keyword(s):  
Recovery Time ◽  
Rabbit Heart ◽  
Monophasic Action Potential ◽  
Triggered Activity ◽  
Recovery Times ◽  
Local Recovery ◽  
Ion Channel Kinetics ◽  
Kinetics Of ◽  
Electrophysiological Effects ◽  
Activation Sequence

We used low temperature to slow ion channel kinetics and studied the electrophysiological effects of quinidine at different pacing rates in isolated rabbit hearts. Fifteen epicardial electrograms together with an endocardial monophasic action potential were recorded. Epicardial activation and local recovery times were measured. Arrhythmias together with the characteristics of their mode of induction and rate were analyzed by epicardial activation sequence mapping. In the presence of quinidine, arrhythmias consistent with both triggered activity and reentry were observed. At baseline, triggered activity was not inducible, even though at 25°C the recovery time was greater than that in the presence of quinidine at 36°C. Also, with quinidine, the incidence of triggered activity decreased at 30 and 25°C. Therefore prolongation of the recovery time per se does not cause triggered activity. Quinidine’s use-dependent effects on conduction and reverse use-dependent effects on recovery time were amplified by low temperatures. These findings can be understood in terms of the known temperature sensitivities of the kinetics of the membrane ion channels responsible for activation and recovery. The results demonstrate that temperature can be used as a tool to elucidate mechanisms of drug action.

scholarly journals High rate pacing guided by short-term variability of repolarization prevents imminent ventricular arrhythmias autonomically by an ICD

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Smoczynska ◽  
V Loen ◽  
A.A Hernandez ◽  
H.D.M Beekman ◽  
M Meine ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Torsade De Pointes ◽  
Left Ventricular ◽  
High Rate ◽  
Monophasic Action Potential ◽  
Funding Source ◽  
Short Term ◽  
Dispersion Of Repolarization ◽  
Temporal Dispersion ◽  
Short Term Variability

Abstract Background The anesthetized, chronic complete atrioventricular block (CAVB) dog model allows reproducible inducibility of Torsade de Pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr-blocker. High rate pacing (HRP) prevents ventricular arrhythmias, but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases prior to ventricular arrhythmias and has been proposed as a marker to guide HRP. Purpose A proof-of-principle study to show STV determined automatically and in real-time by an ICD can guide HRP to prevent imminent ventricular arrhythmias. Methods Eight CAVB dogs were implanted with an ICD (Medtronic, lead in the right ventricular (RV) apex), with software to automatically determine STV online (STV-ICD). STV was determined from the activation recovery interval (ARI) of 31 consecutive beats with the formula: STV = Σ|ARI(n+1) − ARI(n)|/(N*√2). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg i.v. in 5 minutes or until the first TdP). In the first experiment, the individual STV-ICD threshold was determined prior to the first arrhythmic event and programmed into the ICD. In a serial experiment, HRP was initiated automatically once the STV-ICD threshold was reached, by gradually increasing the heart rate to 100 bpm. Occurrence of TdPs was monitored for 10 minutes from the start of dofetilide infusion in both experiments. During HRP, STV was measured offline from RV electrograms (EGM) and left ventricular (LV) monophasic action potential durations (MAPD) (STV-offline). Results During the inducibility experiment, 8/8 dogs had repetitive TdPs and STV-ICD increased from 0.96±0.42 to 2.10±1.26 ms* (*p&lt;0.05). During the prevention experiment, all dogs reached the STV threshold. HRP decreased STV-offline from 2.02±1.12 to 0.78±0.28 ms*, which was accompanied by prevention of TdPs in 7/8 dogs* (Figure 1). Conclusion Temporal dispersion of repolarization, quantified as STV, can guide HRP automatically by an ICD to prevent ventricular arrhythmias. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Public Private Partnership

d-Sotalol: a new potent class III anti-arrhythmic agent

1985 ◽  
Vol 69 (5) ◽  
pp. 631-636 ◽  
Author(s):  
Peter Taggart ◽  
Peter Sutton ◽  
Robert Donaldson
Keyword(s):  
Bolus Injection ◽  
Dose Range ◽  
Parent Compound ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
Ventricular Pacing ◽  
Class Iii ◽  
Heart Rates ◽  
Potential Map ◽  
Similar Class

1. We have compared the effect of a new drug d-sotalol which has minimal β-blocking action with the parent (β-blocking) compound dl-sotalol on monophasic action potential (MAP) duration in open-chested dogs. In seven experiments d-sotalol was administered in intravenous bolus doses of 1.5, 3 and 6 mg/kg given at 10 min intervals. In a further seven experiments dl-sotalol was administered using the same dosage regimen. 2. The animals were anaesthetized with chloralose and urethane. Atrioventricular block was created by injection of the bundle of His with 0.1 ml of 40% formalin in order to ensure capture by ventricular pacing. After prior β-blockade with propranolol (0.25 mg/kg), simultaneous epicardial and endocardial MAP were recorded at paced heart rates of 100 and 150 beats/min after each bolus injection. d-Sotalol and dl-sotalol showed similar prolongation of MAP duration (measured at 90% repolarization) in both endocardial and epicardial recording at both paced heart rates. 3. These results show that the dextro-isomer of sotalol possesses similar class III action to the parent compound and that this action is homogeneous with respect to left ventricular endocardium and epicardium at heart rates of 100 beats/min and 150 beats/min over a wide dose range. d-Sotalol may be a useful anti-arrhythmic agent in man.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

Dobutamine responsiveness, PET mismatch, and lack of necrosis in low-flow ischemia: is this hibernation in the isolated rat heart?

2003 ◽  
Vol 285 (1) ◽  
pp. H316-H324 ◽  
Author(s):  
Richard Southworth ◽  
Pamela B. Garlick
Keyword(s):  
Rat Heart ◽  
Recovery Of Function ◽  
Electron Microscopic Examination ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Low Flow ◽  
Hibernating Myocardium ◽  
Heart Model ◽  
Electron Microscopic ◽  
Isolated Rat

The clinical hallmarks of hibernating myocardium include hypocontractility while retaining an inotropic reserve (using dobutamine echocardiography), having normal or increased [18F]fluoro-2-deoxyglucose-6-phosphate (18FDG6P) accumulation associated with decreased coronary flow [flow-metabolism mismatch by positron emission tomography (PET)], and recovering completely postrevascularization. In this study, we investigated an isolated rat heart model of hibernation using experimental equivalents of these clinical techniques. Rat hearts ( n = 5 hearts/group) were perfused with Krebs-Henseleit buffer for 40 min at 100% flow and 3 h at 10% flow and reperfused at 100% flow for 30 min (paced at 300 beats/min throughout). Left ventricular developed pressure fell to 30 ± 8% during 10% flow and recovered to 90 ± 7% after reperfusion. In an additional group, this recovery of function was found to be preserved over 2 h of reperfusion. Electron microscopic examination of hearts fixed at the end of the hibernation period demonstrated a lack of ischemic injury and an accumulation of glycogen granules, a phenomenon observed clinically. In a further group, hearts were challenged with dobutamine during the low-flow period. Hearts demonstrated an inotropic reserve at the expense of increased lactate leakage, with no appreciable creatine kinase release. PET studies used the same basic protocol in both dual- and globally perfused hearts (with 250MBq18FDG in Krebs buffer ± 0.4 mmol/l oleate). PET data showed flow-metabolism “mismatch;” whether regional or global,18FDG6P accumulation in ischemic tissue was the same as (glucose only) or significantly higher than (glucose + oleate) control tissue (0.023 ± 0.002 vs. 0.011 ± 0.002 normalized counts · s-1· g-1· min-1, P < 0.05) despite receiving 10% of the flow. This isolated rat heart model of acute hibernation exhibits many of the same characteristics demonstrated clinically in hibernating myocardium.

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