Effects of temperature control on hyperthermia-related cardiac dysfunction in a porcine model of cardiac arrest.

The outcome of cardiac arrest is worse when there is fever after spontaneous circulation is restored (ROSC). The purpose of this study was to investigate the mechanism of post-ROSC cardiac dysfunction after hyperthermia treatment and the effects of temperature control. Twenty-four male Bama minipigs were randomized into 3 groups (8 per group): CPR + controlled normothermia (CN), CPR + hyperthermia (HT), and CPR + therapeutic mild hypothermia (TMH). Defibrillation was given to pigs with ventricular fibrillation after 8 min of untreated fibrillation. Subsequently, these animals received the post-ROSC treatments of hyperthermia (38 °C), controlled normothermia (37 °C) or hypothermia (33 °C) according to the groups. Hemodynamic parameters, left ventricular ejection fraction, blood samples and myocardial tissues were assessed. At 24 h after the post-ROSC treatments, the pigs treated with hyperthermia showed increments in heart rate and plasma cardiac troponin I, and decreases in mean arterial pressure, cardiac index, and left ventricular ejection fraction, compared to those with the controlled normothermia pigs. However, the deterioration of the above parameters can be attenuated by TMH. The pigs in the TMH group also had a reduced percentage of apoptotic cardiomyocytes, an increased anti-apoptotic Bcl-2/Bax ratio and a decreased caspase-3 activity in myocardium, as compared with both controlled normothermia and hyperthermia pigs. In conclusion, hyperthermia is associated with a worse myocardial dysfunction. TMH improves hyperthermia-induced myocardial dysfunction by attenuating apoptosis in a porcine model of cardiac arrest.

Frequency Gradient Within Coronary Sinus Predicts the Long-Term Outcome of Persistent Atrial Fibrillation Catheter Ablation.

BACKGROUND: The coronary sinus (CS), as a junction of the atria, contributes to atrial fibrillation (AF) by developing unstable reentry, and isolating the atria by ablation at the CS could terminate AF. The present study evaluated whether AF activities at the CS in a subset of patients contributed to AF maintenance and predicted clinical outcome of ablation. METHODS AND RESULTS: We studied 122 consecutive patients who had a first-time radiofrequency ablation for persistent AF. Bipolar electrograms were obtained from multiple regions of the left atrium by a Lasso mapping catheter before ablation. Pulmonary vein isolation terminated AF in 12 patients (9.8%). Sequential stepwise ablation was conducted in pulmonary vein isolation nontermination patients and succeeded in 22 patients (18%). In the stepwise termination group, AF frequency in the proximal CS (CSp) was significantly higher (10.2±2.1 Hz versus 8.3±1.8 Hz, P<0.001), and the ratio of distal CS (CSd) to proximal CS (CSd/CSp ratio, 56.6%±10.11% versus 70.7%±9.8%, P<0.001) was significantly lower than that in the nontermination group. The stepwise logistic regression analysis indicated that the CSd/CSp ratio was an independent predictor with an odds ratio of 1.131 (95%CI 1.053-1.214; P=0.001). With a cutoff of 67%, the patients with lower CSd/CSp ratios had significantly better index and long-term outcomes than those with higher ratios during a follow-up of 46±18 months. CONCLUSIONS: Rapid repetitive activities in the musculature of the proximal CS may contribute to maintenance of AF after pulmonary vein isolation alone in persistent AF. A cutoff at 67%, of the CSd/CSp frequency ratio might be an indicator to stratify the subset of patients who might benefit from CS ablation.

The early stage of the atrial electroanatomic remodeling as substrates for atrial fibrillation in hypertensive patients.

BACKGROUND: Hypertension is one of the most important risk factors for atrial fibrillation (AF). Recent studies suggest right atrial remodeling in hypertensive patients may be associated with increased inducibility of AF. This study sought to characterize the electroanatomic features of left and right atria and pulmonary veins (PVs) in hypertensive patients. METHODS AND RESULTS: A prospective observational study was conducted on patients who underwent ablation for paroxysmal supraventricular tachycardia or paroxysmal AF. Electrophysiological features of the PVs and atria, including event-related potentials, conduction time, and inducibility and vulnerability of AF, were characterized during cardiac catheterization. Anatomic and hemodynamic features were assessed by using echocardiographic and computer tomography imaging. When 15 hypertensive patients with paroxysmal supraventricular tachycardia were compared with 17 normotensive patients with paroxysmal supraventricular tachycardia, the hypertensive patients had significantly shortened PV event-related potentials with increased dispersions (P<0.001) but slightly prolonged atrial event-related potentials (P=NS) and had prolonged interatrial and intra-atrial conduction times (P<0.001). Additionally, the hypertensive patients had increased vulnerability and inducibility of AF and prolonged duration of induced AF (P<0.01). All of these changes were more pronounced in hypertensive patients with paroxysmal AF. Anatomically, compared with the normotensive patients, the diameters of 4 PVs in the hypertensive patients with paroxysmal supraventricular tachycardia were significantly enlarged (P<0.01) and became more remarkable in hypertensive patients with paroxysmal AF (P<0.0001), although the diameter and volume index of the left atrium among 3 groups were similar. CONCLUSIONS: The hypertensive patients showed electroanatomic changes associated with increased vulnerability to AF, including shortened event-related potentials with increased dispersion, prolonged conduction time, and increased PV diameter, but these changes were not appreciated in the atria. Additionally, these changes became more dramatic in hypertensive patients with paroxysmal AF.

Biological properties of 6-gingerol: a brief review.

Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.

Substrate of complex fractionated atrial electrograms: evidence by pathologic analysis.

BACKGROUND: Ablation of complex fractionated atrial electrograms (CFAE) is an important adjunctive therapy in atrial fibrillation (AF). The present study was to elucidate the substrate underlying CFAE. METHODS: Nine adult mongrel dogs were involved in the present study. AF was induced through rapid atrial pacing with vagosympathetic nerve stimulation. CFAE was recorded during AF. Ablation was performed at CFAE sites. Based on the location of the ablation scar, the atrial specimens were divided into CFAE and non-CFAE sites. Serial sections of the atrium were stained respectively with hematoxylin-eosin (HE) and the general neural marker protein gene product 9.5 (PGP9.5). We compared the characteristics of the myocardium and the ganglionated plexus (GPs) distribution between the CFAE and non-CFAE sites. RESULTS: The myocardium of non-CFAE sites was well-organized with little intercellular substance. However, the myocardium in the CFAE site was disorganized with more interstitial tissue ((61.7 ± 24.3)% vs. (34.1 ± 9.2)%, P < 0.01). GPs in the CFAE site were more abundant than in non-CFAE sites ((34.45 ± 37.46) bundles/cm(2) vs. (6.73 ± 8.22) bundles/cm(2), P < 0.01). CONCLUSION: The heterogeneity of the myocardium and GPs distribution may account for the substrate of CFAE and serve as a potential target of ablation.

Effect of ablation of complex fractionated atrial electrogram on vagal modulation in dogs.

BACKGROUND: Clinical observations have shown that the complex fractionated atrial electrogram (CFAE) associates with ganglionated plexus activity in the cardiac autonomic nervous system. This study aimed to investigate the impact of CFAE ablation on vagal modulation to atria and vulnerability to develop atrial fibrillation (AF). METHODS: Ten adult mongrel dogs were involved. Cervical sympathovagal trunks were decentralized and sympathetic effects were blocked. CFAE was color tagged on the atrial 3-dimensional image and ablated during AF induced by S1S2 programmed stimulation plus sympathovagal trunk stimulation. Atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured on baseline and at vagal stimulation at 4 atrium sites. Serial tissue sections from ablative and control specimens received hematoxylin and eosin staining for microscopic examination. RESULTS: Most CFAE areas were localized at the right superior pulmonary quadrant, distal coronary sinus (CS(d)) quadrant, and proximal coronary sinus (CS(p)) quadrant (21.74%, separately). Sinus rhythm cycle length (SCL) shortening did not decrease significantly after ablation at the sites, including right atrial appendage, left atrial appendage, CS(d), and CS(p) (P > 0.05). ERP shortening during vagal stimulation significantly decreased after ablation (P < 0.01); the VW to vagal stimulation significantly decreased after ablation (P < 0.05). The architecture of individual ganglia altered after ablation. CONCLUSIONS: CFAE has an autonomic basis in dogs. The decreased SCL and ERP shortening to vagal stimulation after CFAE ablation demonstrate that CFAE ablation attenuates vagal modulation to the atria, thereby suppressing AF mediated by enhanced vagal activity. CFAE ablation could suppress AF mediated by enhanced vagal activity.

Concealed conduction and dual pathway physiology of the atrioventricular node.

INTRODUCTION: Both concealed conduction and dual pathway physiology are important electrophysiologic characteristics of the AV node. The interaction of AV nodal concealment and duality, however, is not clearly understood. METHODS AND RESULTS: The properties of AV conduction curves in the presence and absence of a conditioning blocked impulse were prospectively studied during premature atrial stimulation in 20 patients with AV nodal reentrant tachycardia before and after slow pathway ablation and in 14 control patients. AV nodal duality in the control conduction curve in the absence of a conditioning impulse was observed in 19 (95%) of 20 patients with AV nodal reentrant tachycardia. However, AV nodal duality in the modulated conduction curve in the presence of a blocked impulse was only identified in 2 (10%) of 20 patients (2/20 vs 19/20, P < 0.0001). The modulated curve was characterized by a significantly longer AV nodal effective and functional refractory periods compared to the control curve (P < 0.0001) in both patients with and without AV nodal reentry and in AV nodal reentry patients after successful slow pathway ablation. The maximum AH interval (AH(max)) of the modulated curve was significantly shorter than the control curve in both patients with (217 +/- 74 ms vs 347 +/- 55 ms, P < 0.0001) and without AV nodal reentry (178 +/- 50 ms vs 214 +/- 54 ms, P = 0.02). AH(max) of the control curve was significantly longer in AV nodal reentry patients than in controls (P < 0.0001). AH(max) of the modulated curve, however, was not significantly different between the two groups. After slow pathway ablation, AH(max) of the control curve was significantly reduced (347 +/- 55 ms vs 191 +/- 40 ms, P < 0.0001). Significant reduction in AH(max) of the modulated curve was not observed. CONCLUSION: An interaction of AV nodal concealed conduction and dual pathway physiology was demonstrated by our data. Slow pathway conduction of the AV node was prevented by the concealed beat in both patients with and without AV nodal reentry.