Impact of catheter-tissue contact force on lesion size during right ventricular outflow tract ablation in a swine model / 中华医学杂志(英文版)

BACKGROUND@#The catheter-tissue contact force (CF) is one of the significant determinants of lesion size and thus has a considerable impact on the effectiveness of ablation procedures. This study aimed to evaluate the impact of CF on the lesion size during right ventricular outflow tract (RVOT) ablation in a swine model.@*METHODS@#Twelve Guangxi Bama miniature male pigs weighing 40 to 50 kg were studied. After general anesthesia, a ThermoCool SmartTouch contact-sensing ablation catheter was introduced to the RVOT via the femoral vein under the guidance of the CARTO 3 system. The local ventricular voltage amplitude and impedance were measured using different CF levels. We randomly divided the animals into the following four groups according to the different CF levels: group A (3-9 g); group B (10-19 g); group C (20-29 g); and group D (30-39 g). Radiofrequency ablations were performed at three points in the free wall and septum of the RVOT in power control mode at 30 W for 30 s while maintaining the saline irrigation rate at 17 mL/min. At the end of the procedures, the maximum depth, surface diameter, and lesion volume were measured and recorded. A linear regression analysis was performed to determine the relationship between continuous variables.@*RESULTS@#A total of 72 ablation lesions were created in the RVOT of the 12 Bama pigs. The maximum depth, surface diameter, and volume of the lesions measured were well correlated with the CF (free wall: β = 0.105, β = 0.162, β = 3.355, respectively, P < 0.001; septum: β = 0.093, β = 0.150, β = 3.712, respectively, P < 0.001). The regional ventricular bipolar voltage amplitude, unipolar voltage amplitude, and impedance were weakly positively associated with the CF (β = 0.065, β = 0.125, and β = 1.054, respectively, P < 0.001). There was a significant difference in the incidence of steam pops among groups A, B, C, and D (free wall: F = 7.3, P = 0.032; septum: F = 10.5, P = 0.009); and steam pops occurred only when the CF exceeded 20 g. Trans-mural lesions were observed when the CF exceeded 10 g in the free wall, while the lesions in the septum were non-trans-mural even though the CF reached 30 g.@*CONCLUSIONS@#CF seems to be a leading predictive factor for the size of formed lesions in RVOT ablation. Maintaining the CF value between 3 and 10 g may be reasonable and effective for creating the necessary lesion size and reducing the risk of complications, such as steam pops and perforations.

A systematic review and meta-analysis on efficacy and safety of cardiac resynchronization therapy alone or in combination with implantable cardioversion defibrillation in patients with mild to severe heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of cardiac resynchronization therapy (CRT) alone or in combination with implantable cardioversion defibrillation (ICD) in patients with mild to severe heart failure.</p><p><b>METHOD</b>Electronic searches of MEDLINE, EMBASE, CENTREN and affiliated clinical trial registration data center, US Food and Drug Administration reports, CBMdisc, VIP, and CNKI databases from establishment to Dec 2010, using the search terms "CRT, heart failure", "biventricular pacer, heart failure", "biventricular pacing, heart failure", and "biventricular pacemaker, heart failure", were performed to identify randomized controlled trials (RCTs). Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs.</p><p><b>RESULTS</b>A total of 23 trials including 8521 patients were included. In patients with New York Heart Association (NYHA) class I/II, CRT improved left ventricular ejection fraction (LVEF) [weighted mean difference (WMD) = 0.05, 95% CI 0.01 - 0.08], reduced heart failure hospitalizations [risk ratio (RR) = 0.70, 95%CI 0.61 - 0.81] and all-cause mortality (RR = 0.78, 95%CI 0.65 - 0.93) with increasing complications (RR = 1.74, 95%CI 1.42 - 2.13). In patients with NYHA class III/IV, CRT improved LVEF (WMD = 0.03, 95%CI 0.01 - 0.05), reduced both heart failure hospitalizations (RR = 0.64, 95%CI 0.55 - 0.73) and all-cause mortality (RR = 0.80, 95%CI 0.70 - 0.91) without increasing complications (RR = 1.01, 95%CI 0.91 - 1.12). Compared with ICD alone, CRT in combination with ICD significantly improved LVEF (WMD = 0.03, 95%CI 0.00 - 0.06), reduced heart failure hospitalizations (RR = 0.73, 95%CI 0.64 - 0.82) and all-cause mortality (RR = 0.82, 95%CI 0.72 - 0.95) without increasing complications (RR = 1.36, 95%CI 0.91 - 2.03) in patients with NYHA class I-IV symptoms.</p><p><b>CONCLUSIONS</b>CRT offered additional benefits on top of standard medication for heart failure patients with ventricular dyssynchrony in terms of improving LV function, and reducing heart failure hospitalization and all-cause mortality, regardless of NYHA class. CRT offers also additional benefit in heart failure patients implanted with ICD. However, CRT is associated with more adverse events in patients with NYHA class I/II.</p>

The effect of mitochondrial oxidative stress and the expression of Bcl-2 and Bax proteins on cardiomyocyte apoptosis during hypoxia postconditioning / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate mitochondrial oxidative stress on cardiomyocyte apoptosis and the expression of Bcl-2 and Bax proteins in cardiac sarcolemma and mitochondria after application of hypoxia postconditioning and free radical scavengers.</p><p><b>METHODS</b>Primary cultured neonatal rat cardiomyocytes were exposed to 3 h hypoxia (H) followed by (1) 6 h of reoxygenation (R) (H/R), (2) 3 intermittent cycles of 5 min H and R before 6 h of R (PC), (3) application of superoxide dismutase (SOD) before PC (SOD+PC), (4) application of catalase (CAT) before PC (CAT+PC), and (5) application of SOD plus CAT before PC (SOD+CAT+PC). Cardiac sarcolemma and mitochondria were isolated by differential centrifugation. Mitochondrial reactive oxygen species (ROS) was detected with fluorescent probes (DCFH-DA) and cardiomyocyte apoptosis was detected with flow cytometry. The expressions of Bcl-2 and Bax proteins in cardiac sarcolemma and mitochondria were measured by Western blot.</p><p><b>RESULTS</b>Mitochondrial ROS reduced significantly in PC, SOD+PC, CAT+PC and especially in SOD+CAT+PC groups (all P<0.01). The number of apoptotic cardiomyocytes reduced significantly in PC, SOD+PC and CAT+PC (all P<0.01) but not in SOD+CAT+PC groups. Bcl-2 levels increased while Bax levels decreased in cardiac sarcolemma and mitochondria in PC, SOD+PC and CAT+PC groups (all P<0.01), Bcl-2 levels decreased and Bax levels increased in H/R and PC+SOD+CAT groups (all P<0.01).</p><p><b>CONCLUSIONS</b>PC attenuated H/R induced ROS and cardiomyocyte apoptosis, which might be mediated by upregulating the expression of Bcl-2 and downregulating the Bax in mitochondria and sarcolemma; SOD or CAT alone did not but SOD plus CAT attenuate the anti-apoptotic effect of hypoxia postconditioning; mitochondrial ROS thus plays an important role in PC's cardioprotection.</p>

A meta-analysis on efficacy of anti-platelet agents and anticoagulants for preventing stroke in patients with nonvalvular atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and security of anti-platelet and anticoagulant therapy on prevention of ischemic stroke in patients with nonvalvular atrial fibrillation (NAF).</p><p><b>METHODS</b>We searched PubMed, EMbase, CENTREN and its affiliated clinical trial registration data center, CBMdisc, VIP, and CNKI databases from establishment to Dec 2009 to identify randomized controlled trials (RCTs) covering the use of anti-platelet agents and anticoagulants for patients with NAF. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs.</p><p><b>RESULTS</b>Fourteen RCTs involving 15 880 patients were include. Compared with placebo or no use of anti-platelet drugs, antiplatelet therapy didn't reduce ischemic stroke (RR = 0.83, 95%CI 0.68 to 1.00, P = 0.05), systemic emboli (RR = 0.71, 95%CI 0.34 to 1.51, P = 0.38) and all-cause mortality (RR = 0.88, 95%CI 0.73 to 1.07, P = 0.21) while significantly increased the major bleeding (RR = 2.88, 95%CI 1.21 to 6.86, P = 0.02) in patients with NAF, intracranial hemorrhage was not affected by antiplatelet therapy in patients with atrial fibrillation (RR = 3.25, 95%CI 0.84 to 12.62, P = 0.09). Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the incidence of ischemic stroke (RR = 1.84, 95%CI 1.48 to 2.28, P < 0.01) and systemic emboli (RR = 1.94, 95%CI 1.24 to 3.03, P = 0.004) but significantly increased the incidence of intracranial hemorrhage (RR = 0.49, 95%CI 0.31 to 0.78, P = 0.003), did not affect all-cause mortality (RR = 1.06, 95%CI 0.90 to 1.23, P = 0.50) and the incidence of major bleeding (RR = 0.95, 95%CI 0.76 to 1.19, P = 0.66) in NAF patients.</p><p><b>CONCLUSIONS</b>Compared with the placebo and no use of anti-platelet drugs, anti-platelet therapy didn't reduce ischemic stroke and systemic emboli but increased the risk of major bleeding in NAF patients. Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the ischemic stroke and systemic emboli without increasing the risk of major bleeding, but significantly increased the incidence of intracranial hemorrhage in NAF patients. Since the study included RCTs with limited and less uniform outcome endpoints, the conclusions should be verified with RCTs with more uniform endpoints and longer follow-up time.</p>

Collagen spatial distribution in rapid atrial pacing dogs with or without superior vena cava and aortic root fat pad / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the collagen spatial distribution, collagen volume fraction (CVF) and Cx40, Cx43mRNA expressions in rapid atrial pacing dogs post vagal denervation by removing fat pad located between the medial superior vena cava and aortic root (SVC-Ao fat pad).</p><p><b>METHODS</b>Twenty-four dogs were randomly divided into unpaced sham operation group (S group, n = 8), Keeping SVC-Ao fat pad group (K group, n = 8) and Removing SVC-Ao fat pad group (R group, SVC-Ao fat pad was removed by surgical excision before pacing, n = 8). K and R groups were paced for six weeks. Six weeks later, all dogs were sacrificed, left atrium (LA), right atrium (RA), left atrial appendage (LAA), right atrial appendage (RAA) and atrial septum (AS) were collected and stained with HE or Masson Trichrome or frozen in liquid nitrogen for quantifying the expression of Cx40, Cx43 mRNA by Real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR).</p><p><b>RESULTS</b>Spatial distribution of collagen fibers as well as CVF between S and R group were similar (all P > 0.05). CVF was significantly higher in K group compared to R group, especially at LAA and AS locations (all P < 0.05). Cx40mRNA expression in K group was significantly decreased in LA, RA, and significantly increased in LAA, RAA and AS compared those in S group (all P < 0.05), significantly lower in LA and RA while significantly higher in LAA and RAA compared to R group (all P < 0.05). Cx43mRNA expression in K group was significantly reduced in LA, RA, LAA and RAA while significantly increased in AS compared to S group (all P < 0.05), significantly higher in LA, RA, RAA and AS while significantly lower in LAA compared to R group.</p><p><b>CONCLUSION</b>Pacing induced collagen remodeling and modulation on Cx40mRNA and Cx43 mRNA expressions could be partially attenuated by removing SVC-Ao fat pad suggesting vagal denervation plays a key role in the initiation and preservation of atrial fibrillation.</p>

Mitochondrial connexin43 and postconditioning protection in rabbits underwent myocardial ischemia/reperfusion injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the roles of mitochondrial connexin43 (Cx43) and mitochondrial ATP sensitive potassium channe1 (mitoK(ATP)+) in the postconditioning protection for rabbits underwent myocardial ischemia/reperfusion injury.</p><p><b>METHODS</b>In anesthetized open-chest rabbits, the left anterior descending artery (LAD) was occluded for 30 min and reperfused for 4 h and randomly divided into four groups (n = 16 each): sham operation group (Sham), ischemic reperfusion group (IR), ischemic postconditioning group (PC) and PC plus 5-HD, a specific mitoK(ATP)+ inhibitor (PC + 5-HD). Rabbits were sacrificed post 4 h reperfusion. Heart rate and the mean arterial pressure were recorded and plasma CK-MB and cTnI activity were measured at baseline, at the end of ischemia, and after 2 h and 4 h of reperfusion, respectively. Myocardial infarct size was determined and mitochondria structure was observed under electron microscope at the end of the experiment. Mitochondria were isolated and the protein content of the mitochondrial Cx43 was determined by Western blot.</p><p><b>RESULTS</b>Plasma CK-MB, cTnI activity and myocardial infarct size were significantly reduced in PC [(19.1 +/- 3.9)%] group compared to IR [(35.7 +/- 5.8)%] and PC + 5HD [(34.2 +/- 3.9)%] groups (all P < 0.01). Degree of mitochondria damage was significantly reduced in PC group compared to IR and PC + 5HD groups (all P < 0.01). The mitochondria Cx43 content was significantly decreased in IR group and PC + 5-HD group compared to sham group (all P < 0.05) and restored in PC group.</p><p><b>CONCLUSION</b>Ischemic postconditioning protected the heart from I/R injury by improving mitochondrial ultrastructure and by attenuating I/R induced decrease of mitochondria Cx43 expression. The protective effects of postconditioning was partly mediated by activating mitoK(ATP)+ pathway.</p>