Low-Intensity Ultrasound Modulation May Prevent Myocardial Infarction-induced Sympathetic Neural Activation and Ventricular Arrhythmia.

BACKGROUND: Low-intensity focused ultrasound (LIFU) has been shown to be a beneficial tool for autonomic nervous system modulation, but its effect on the left stellate ganglion (LSG) remains unknown. OBJECTIVE: To seek the effect of LIFU on myocardial infarction (MI)-induced LSG activation and ventricular arrhythmias (VAs). METHODS: In this study, 20 dogs were included and randomly divided into the LIFU (LIFU & MI, n = 8), Sham (sham LIFU & MI, n = 8), and Control group (sham LIFU & sham MI, n = 4). For each LIFU intervention (1.0-2.0 W, 10 minutes) of the LSG, the LSG function, ventricular effective refractory period (ERP), and temperature were tested pre-intervention and postintervention. Thereafter, MI was induced by left anterior artery ligation and VAs were recorded for 1 hour. At the end, both the LSG and the heart were extracted for biomedical and histological analysis. RESULTS: In the Sham group, no significant change was shown in ventricular ERP or LSG function for any intensity settings of sham LIFU intervention when compared with the group baseline. In the LIFU group, however, both 1.5 and 2.0 W LIFU modulation of LSG resulted in significant prolongation of ERP and attenuation of LSG function. Furthermore, the incidence of VAs was significantly attenuated in the LIFU group compared with the Sham group. Moreover, histological analysis showed that no damage or apoptosis was observed in LSG although a statistically significant increase was shown in temperature (maximal increase <1°C) with 1.5 and 2.0 W LIFU intervention. CONCLUSION: LIFU stimulation may be a safe and beneficial tool for LSG attenuation and VA prevention in the MI canine model.

Proof of principle of a novel co-pulsating intra-ventricular membrane pump.

In this proof of principle study, we investigated the effectiveness and safety of hemodynamic support with the Intra-Ventricular Membrane Pump (IVMP). The IVMP was implanted into the apex of the left ventricle. Hemodynamic assessment was performed in six ex vivo beating porcine hearts (PhysioHeart platform). The cardiac output (CO), mean arterial pressure (MAP), coronary flow (CF) and pulse pressure (PP) were obtained before and during IVMP support and reported as means ± standard deviations. In two additional visualization experiments, the integrity of the mitral valve was assessed during IVMP support. We found a significant increase of the CO (+1.4 ± 0.2 L/min, P < .001), MAP (+13 ± 6 mm Hg, P = .008), CF (+0.23 ± 0.1 L/min, P = .004), and PP (+15 ± 4 mm Hg, P = .002) during IVMP support, when compared to baseline. No interference of the IVMP with mitral valve function was observed. An increase of premature ventricular complexes (PVC) was observed during support with the IVMP (mean PVC-burden 4.3% vs. 0.7% at baseline), negatively influencing hemodynamic parameters. The IVMP is able to significantly improve hemodynamic parameters in a co-pulsatile fashion, without hampering the function of the mitral valve. These findings provide a basis for future development of a catheter-based IVMP.

Noninvasive light emitting diode therapy: A novel approach for postinfarction ventricular arrhythmias and neuroimmune modulation.

BACKGROUND: Sympathetic neural activation plays a key role in the incidence and maintenance of acute myocardial infarction (AMI) induced ventricular arrhythmia (VA). Furthermore, previous studies showed that AMI might induce microglia and sympathetic activation and that microglial activation might contribute to sympathetic activation. Recently, studies showed that light emitting diode (LED) therapy might attenuate microglial activation. Therefore, we hypothesized that LED therapy might reduce AMI-induced VA by attenuating microglia and sympathetic activation. METHODS: Thirty anesthetized rats were randomly divided into three groups: the Control group (n = 6), AMI group (n = 12), and AMI + LED group (n = 12). Electrocardiogram (ECG) and left stellate ganglion (LSG) neural activity were continuously recorded. The incidence of VAs was recorded during the first hour after AMI. Furthermore, we sampled the brain and myocardium tissue of the different groups to examine the microglial activation and expression of nerve growth factor (NGF), interleukin-18 (IL-18), and IL-1ß, respectively. RESULTS: Compared to the AMI group, LED therapy significantly reduced the incidence of AMI-induced VAs (ventricular premature beats [VPB] number: 85.08 ± 13.91 vs 27.5 ± 9.168, P < .01; nonsustained ventricular tachycardia (nSVT) duration: 34.39 ± 8.562 vs 9.005 ± 3.442, P < .05; nSVT number: 18.92 ± 4.52 vs 7.583 ± 3.019, P < .05; incidence rate of SVT/VF: 58.33% vs. 8.33%, P < .05) and reduced the LSG neural activity (P < .01) in the AMI + LED group. Furthermore, LED significantly attenuated microglial activation and reduced IL-18, IL-1ß, and NGF expression in the peri-infarct myocardium. CONCLUSION: LED therapy may protect against AMI-induced VAs by suppressing sympathetic neural activity and the inflammatory response.

Ventricular arrhythmia burst is an independent indicator of larger infarct size even in optimal reperfusion in STEMI.

OBJECTIVE: We hypothesized that ventricular arrhythmia (VA) bursts during reperfusion phase are a marker of larger infarct size despite optimal epicardial and microvascular perfusion. METHODS: 126 STEMI patients were studied with 24h continuous, 12-lead Holter monitoring. Myocardial blush grade (MBG) was determined and VA bursts were identified against subject-specific background VA rates in core laboratories. Delayed-enhancement cardiovascular magnetic resonance imaging was used to determine infarct size. RESULTS: In the group with MBG 3 no significant differences were found for baseline characteristics between burst versus no burst (102 vs. 24). In those with optimal epicardial and microvascular reperfusion (TIMI 3, stable ST-recovery, and MBG 3), VA burst was associated with larger infarct size (N=102/126; median 11.0 vs. 5.1%; p=0.004). CONCLUSION: In the event of MBG 3, VA bursts were associated with significantly larger infarct size even if optimal epicardial and microvascular reperfusion was present.

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

OBJECTIVES: The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. METHODS: Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4(+) T and CD8(+) T cells were measured. RESULTS: The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4 ± 0.9%, 3.7 ± 0.7%, and -0.4 ± 0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3 ± 1.8 and -11.5 ± 2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9 ± 0.2, 0.8 ± 0.1, and 0.2 ± 0.2, respectively). The circulating number of CD8(+) T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687 ± 317/µL, 3,454 ± 787/µL, and 1,928 ± 457/µL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. CONCLUSIONS: Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.

Accelerated sinus rhythm prevents catecholaminergic polymorphic ventricular tachycardia in mice and in patients.

RATIONALE: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia (VA). OBJECTIVE: To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. METHODS AND RESULTS: Using CPVT mouse models (Casq2(-/-) and RyR2(R4496C/+) mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia in 86% of Casq2(-/-) mice (6/7) and significantly reduced the VA score (atropine: 0.6±0.2 versus vehicle: 1.7±0.3; P<0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2(-/-) and in 7 of 8 (88%) RyR2(R4496C/+) mice and significantly reduced ventricular premature beats in both CPVT models (P<0.05). Rapid pacing also prevented spontaneous calcium waves and triggered beats in isolated CPVT myocytes. In humans, heart rate dependence of CPVT was evaluated by screening a CPVT patient registry for antiarrhythmic drug-naïve individuals that reached >85% of their maximum-predicted heart rate during exercise testing. All 18 CPVT patients who fulfilled the inclusion criteria exhibited VA before reaching 87% of maximum heart rate. In 6 CPVT patients (33%), VA were paradoxically suppressed as sinus heart rates increased further with continued exercise. CONCLUSIONS: Accelerated supraventricular rates suppress VAs in 2 CPVT mouse models and in a subset of CPVT patients. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced ventricular tachycardia in treatment-refractory CPVT patients.

Local ß-adrenergic stimulation overcomes source-sink mismatch to generate focal arrhythmia.

RATIONALE: ß-Adrenergic receptor stimulation produces sarcoplasmic reticulum Ca(2+) overload and delayed afterdepolarizations in isolated ventricular myocytes. How delayed afterdepolarizations are synchronized to overcome the source-sink mismatch and produce focal arrhythmia in the intact heart remains unknown. OBJECTIVE: To determine whether local ß-adrenergic receptor stimulation produces spatiotemporal synchronization of delayed afterdepolarizations and to examine the effects of tissue geometry and cell-cell coupling on the induction of focal arrhythmia. METHODS AND RESULTS: Simultaneous optical mapping of transmembrane potential and Ca(2+) transients was performed in normal rabbit hearts during subepicardial injections (50 µL) of norepinephrine (NE) or control (normal Tyrode's solution). Local NE produced premature ventricular complexes (PVCs) from the injection site that were dose-dependent (low-dose [30-60 µmol/L], 0.45±0.62 PVCs per injection; high-dose [125-250 µmol/L], 1.33±1.46 PVCs per injection; P<0.0001) and were inhibited by propranolol. NE-induced PVCs exhibited abnormal voltage-Ca(2+) delay at the initiation site and were inhibited by either sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase inhibition or reduced perfusate [Ca(2+)], which indicates a Ca(2+)-mediated mechanism. NE-induced PVCs were more common at right ventricular than at left ventricular sites (1.48±1.50 versus 0.55±0.89, P<0.01), and this was unchanged after chemical ablation of endocardial Purkinje fibers, which suggests that source-sink interactions may contribute to the greater propensity to right ventricular PVCs. Partial gap junction uncoupling with carbenoxolone (25 µmol/L) increased focal activity (2.18±1.43 versus 1.33±1.46 PVCs per injection, P<0.05), which further supports source-sink balance as a critical mediator of Ca(2+)-induced PVCs. CONCLUSIONS: These data provide the first experimental demonstration that localized ß-adrenergic receptor stimulation produces spatiotemporal synchronization of sarcoplasmic reticulum Ca(2+) overload and release in the intact heart and highlight the critical nature of source-sink balance in initiating focal arrhythmias.

Dronedarone versus amiodarone in preventing premature ventricular contractions in an in vitro model of "border zone".

OBJECTIVE: To compare the acute ability of amiodarone and dronedarone (a noniodinated benzofuran derivative with a pharmacologic profile similar to amiodarone) to prevent premature ventricular contractions (PVCs) occurrence. METHODS: We used an in vitro model of rabbit right ventricle mimicking the "border zone" existing between normal and ischemic/reperfused regions to test acute electrophysiological effects of dronedarone and amiodarone both at 1 and 10 µmol/L. RESULTS: Similar to amiodarone, dronedarone affected action potential parameters with multichannel blocking properties. Dronedarone at both concentrations was equivalent to amiodarone regarding PVCs occurrence, except regarding extrasystoles occurrence during the reperfusion period (dronedarone, 10 µmol/L, was superior to amiodarone with extrasystoles incidence at 33% and 50%, respectively vs. 92% in controls, P < 0.05). Both dronedarone and amiodarone systematically induced conduction blocks during simulated ischemia (in 100% of preparations vs. 42% in controls, P < 0.05) and a marked decrease of Vmax (to 24 and 23 V/s at 10 minutes of ischemia with 1 and 10 µmol/L dronedarone versus 65 V/s in controls, P < 0.05), thus indicating class 1 antiarrhythmic effects. Both dronedarone and amiodarone at 10 µmol/L induced an increase of APD90 dispersion between normal and ischemic regions, without pro-arrhythmic effects. CONCLUSIONS: Dronedarone and amiodarone have very similar electrophysiological effects in this in vitro model of border zone and were both efficient in preventing PVCs occurrence particularly through a class 1 antiarrhythmic effect.

Carotid baroreceptor stimulation prevents arrhythmias induced by acute myocardial infarction through autonomic modulation.

: Electrical carotid baroreceptor stimulation (CBS) has shown therapeutic potential for resistant hypertension and heart failure by resetting autonomic nervous system, but the impacts on arrhythmias remains unclear. This study evaluated the effects of CBS on ventricular electrophysiological properties in normal dog heart and arrhythmias after acute myocardial infarction (AMI). In the acute protocol, anesthetized open chest dogs were exposed to 1 hour left anterior descending coronary occlusion as AMI model. Dogs were received either sham treatment (Control group, n = 8) or CBS (CBS group, n = 8), started 1 hour before AMI. CBS resulted in pronounced prolongation of ventricular effective refractory period and reduction of the maximum action potential duration restitution slope (from 0.85 ± 0.15 in the baseline state to 0.67 ± 0.09 at the end of 1 hour, P < 0.05) before AMI. Number of premature ventricular contractions (277 ± 168 in the Control group vs. 103 ± 84 in the CBS group, P < 0.05) and episodes of ventricular tachycardia/ventricular fibrillation (7 ± 3 in the Control group vs. 3 ± 2 in the CBS group, P < 0.05) was decreased compared with the control group during AMI. CBS buffered low-frequency/high-frequency ratio raise during AMI. Ischemic size was not affected by CBS. CBS may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone.

Effects of Nardostachys chinensis on spontaneous ventricular arrhythmias in rats with acute myocardial infarction.

OBJECTIVES: To investigate the effects and mechanisms of Nardostachys chinensis (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial infarction (AMI). METHODS: Seventy-two rats were randomly divided into the control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24). Premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular myocardium was measured by immunohistochemistry, Western blot, and real-time RT-PCR. RESULTS: Compared with the control, metoprolol and NC decreased the VF incidence (50% vs. 4.2%, P < 0.001, and 50% vs. 12.5%, P = 0.005, respectively). There was a steady decrease in the cumulative number of PVCs and VTs within 4 hours from ligating in 3 groups. Compared with the control, metoprolol and NC reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol and NC decreased the infarct size of the left ventricular tissue (55.98% ± 6.20% vs. 39.13% ± 4.53%, P < 0.001, and 55.98% ± 6.20% vs. 42.39% ± 3.44%, P < 0.001, respectively). The results from immunohistochemistry, Western blot, and real-time RT-PCR showed that the protein expression of Cx43 in the control group was significantly lower than that in the metoprolol and NC groups in the infarcted zone. CONCLUSIONS: NC decreased the incidence of spontaneous ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data of the present study indicated that NC may be a promising drug in the future to prevent patients with AMI from lethal ventricular arrhythmias in prehospital setting.

Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter isolated from ambient air by attenuating oxidative stress.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by particulate matter (PM) isolated from ambient air and linked to prolonged repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin (CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT-protein transduction domain (TAT-CryAB). ECGs were measured before and after tracheal exposure of diesel exhaust particles (DEP) and each intervention in adult Sprague-Dawley rats. After endotracheal exposure of DEP (200 µg/mL for 30 minutes, n=11), QT intervals were prolonged from 115±14 ms to 144±20 ms (p=0.03), and premature ventricular contractions were observed more frequently (0% vs. 44%) than control (n=5) and TAT-Cry (n=5). However, DEP-induced arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n=5). In optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP infusion of 12.5 µg/mL (n=12) increased apicobasal action potential duration (APD) differences from 2±6 ms to 36±15 ms (p<0.001), APD restitution slope from 0.26±0.07 to 1.19±0.11 (p<0.001) and ventricular tachycardia (VT) from 0% to 75% (p<0.001). DEP infusion easily induced spatially discordant alternans. However, the effects of DEP were prevented by TAT-CryAB (1mg/kg, n=9). In rat myocytes, while DEP increased reactive oxygen species (ROS) generation and phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a small heat shock protein, might prevent the arrhythmogenic effects of PM by attenuating ROS generation and CaMKII activation.

ß1-Adrenoceptor blocker aggravated ventricular arrhythmia.

OBJECTIVES: To assess the impact of ß1 -adrenoceptor blockers (ß1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. METHODS: From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. ß1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. RESULTS: Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during ß1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated ß1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and ß1 -blocker showed similar effects on the arrhythmias in catheter lab. CONCLUSIONS: In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of ß1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia.

Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation.

Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague-Dawley rats, QT interval was increased from 115.0±14.0 to 142.1±18.4ms (p=0.02) after endotracheal exposure of DEP (200µg/ml for 30min, n=5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p=0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5mmol/L, n=3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5µg/ml for 20min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5mmol/L, n=5), nifedipine (10µmol/L, n=5), and active Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1µmol/L, n=5), but not by thapsigargin (200nmol/L) plus ryanodine (10µmol/L, n=5) and inactive CaMKII blockade, KN 92 (1µmol/L, n=5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5µg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation.

The value of defibrillator far-field electrograms for ablation of idiopathic ventricular fibrillation.

We report a case of idiopathic ventricular fibrillation treated by catheter ablation of the monomorphic initiating premature beat. The initiating focus was identified using intacardiac defibrillator electrograms (EGMs).

Recurrence of RVOT PVCs with a marked shift of its exit point. Gradual elimination of arrhythmogenic focus by multisite approach.

We present a case of recurrent outflow tract arrhythmia despite repeated ablations. Premature ventricular contractions (PVCs) morphology suggested a right-sided focus. However, electrograms preceding PVCs were recorded from the right and left outflow tracts, distal coronary sinus, and right sinus of Valsalva. Arrhythmia was eliminated after radiofrequency (RF) applications delivered from different sites. We conclude that, in patients with recurrent outflow tract PVCs, mapping all the sites mentioned above may be necessary to find the earliest activation site and carry out successful ablation. In some patients, RF applications from multiple sites may be necessary to completely eliminate arrhythmia.

Chewing reduces sympathetic nervous response to stress and prevents poststress arrhythmias in rats.

Reducing stress is important in preventing sudden death in patients with cardiovascular disease, as stressful events may cause autonomic imbalance and trigger fatal arrhythmias. Since chewing has been shown to inhibit stress-induced neuronal responses in the hypothalamus, we hypothesized that chewing could ameliorate stress-induced autonomic imbalance and prevent arrhythmias. To test this hypothesis, we analyzed changes in radiotelemetered electrocardiograms in rats that were allowed to chew a wooden stick during a 1-h period of immobilization stress. Chewing significantly reduced the occurrence of ventricular premature beats (VPBs) and complex ventricular ectopy after immobilization and prevented stress-induced prolongation of the QT interval of VPBs throughout the 10-h experimental period. It also prevented prolongation of the QRS complex and fluctuations in the QT interval in normal sinus rhythm beats preceding VPBs during both immobilization and in the poststress period. Fast Fourier transform-based spectral analysis of heart-rate variability further showed that chewing significantly inhibited the stress-induced increase in the power ratio of low-to-high frequency activity (LF/HF: a marker of sympathetic activity) during immobilization and in addition was associated with blunting of the stress-induced increase in plasma noradrenaline observed at the termination of immobilization. Similar suppressive effects on the occurrence of VPBs and the LF/HF were observed in rats that were administered the ß-adrenergic blocker propranolol before immobilization. These results indicate that chewing can ameliorate sympathetic hyperactivity during stress and prevent poststress arrhythmias and suggest that chewing may provide a nonpharmacological and cost-effective treatment option for patients with a high risk of stress-induced fatal arrhythmia.

Late effect of early hypoxic disturbance in the rat heart: gender differences.

Perinatal hypoxemia may have serious long-term effects on the adult cardiovascular system and may lead to sex-dependent changes in cardiac tolerance to acute ischemia in adult life. The aim of the study was to answer the question whether gonadectomy of the male and female rats in the early phase of ontogenetic development affects the late effect of perinatal hypoxia. Pregnant Wistar rats were placed into a normobaric hypoxic chamber (12 % O(2)) 7 days before the expected date of delivery. Newborn pups were kept in the chamber with their mothers for another 5 days after birth. After hypoxic exposure all animals were kept for 3 months in room air. Some of the pups were gonadectomized right after removal from the hypoxic chamber. Ventricular arrhythmias were assessed on isolated perfused hearts. Castration did not influence arrhythmogenesis in the adult normoxic or perinatally hypoxic female hearts. Nevertheless, the number of arrhythmias was decreased in perinatally hypoxic gonadectomized males. In conclusion, we have shown that perinatal normobaric hypoxia increased cardiac tolerance to acute ischemia in adult male rats; however, it had no late effect in females. Gonadectomy did not affect arrhythmogenesis in both normoxic and hypoxic female hearts, whereas in males significantly decreased the number of arrhythmias.

High-resolution esophageal manometry with ECG monitoring for management of premature ventricular complexes-associated dysphagia.

We report a novel technique for diagnosing a new cause of esophageal dysphagia in a patient without organic heart and esophageal disease. A coincidence between intermittent esophageal dysphagia and cardiac arrhythmia, frequent premature ventricular complexes (PVC) were confirmed by clinical observation, simultaneous ECG monitoring, and motility study. High-resolution esophageal manometry (HRM) revealed abnormal peristaltic waves only during frequent PVC. Abnormal peristaltic waves and PVC disappeared simultaneously and completely within 15 min after intravenous infusion of antiarrhythmic agent (140 mg propafenone). Oral treatment with antiarrhythmic drugs was not tolerated or ineffective. Complete remission of PVC and dysphagia was achieved immediately after radiofrequency catheter ablation of arrhythmogenic focus located in the right ventricular outflow tract. This case demonstrates a new technique for the management of a syndrome called "PVC-associated dysphagia" that can be mediated by cardioesophageal reflex. Interdisciplinary cooperation and simultaneous HRM with ECG monitoring may confirm the diagnosis and guide effective treatment.

Effect of Hemidesmus indicus on ischemia-reperfusion injury in the isolated rat heart.

The root extract of Hemidesmus indicus (Linn.) R. Br. (Asclepiadaceae) (HI) was studied for its cardioprotective effect in Langendorff-perfused rat hearts. HI was perfused for 15 min at a concentration of 0.09 g/L prior to 30 min global ischemia/120 min reperfusion (I/R). Recovery of functional parameters, reperfusion arrhythmias, and infarct size (TTC staining) served as the end-points. After 15 min of perfusion with HI, the left ventricular developed pressure (LVdevP) and HR (heart rate) were not altered significantly (p>0.05), as compared with the pre-drug values. During R, HI showed a significantly higher (p<0.05) recovery of LVdevP at nearly all time points. The recovery of maximal rate of pressure development (+dP/dtmax) and left ventricular end-diastolic pressure (LVEDP) at 40 min of R were significantly better than in non-treated controls. There was also a significant reduction in the total number of ventricular premature beats (VPB) and duration of ventricular tachycardia (VT). HI can protect ischemic myocardium against contractile dysfunction and reperfusion-induced arrhythmias and reduce the extent of irreversible tissue damage following I/R in rat hearts.