VT Duration Research Articles

Incidental arrhythmias during atrial fibrillation screening in a hospital-based patient population

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Screening for atrial fibrillation may reveal other, incidental arrhythmias of relevance. We sought to describe such incidental arrhythmias in the prospective STARFIB cohort study, which screened for silent atrial fibrillation in hospitalized patients aged 65-84 years. Method Patients included in the STARFIB cohort study had up to three 7-day Holter ECGs, performed in two-month intervals. We analysed all the 7-day Holter ECGs of study participants for the presence of one of the following incidental arrhythmias: 1) sick-sinus-syndrome (SSS), defined as sinus arrest of ≥3 seconds duration; 2) second or higher degree atrioventricular block (AVB); 3) sustained atrial tachycardia of ≥30 seconds duration (AT); and 4) sustained ventricular tachycardia of ≥30 seconds duration (VT). Results A total of 2’077 Holter ECGs were performed in 794 patients (mean age 74.7 years; 49% females), resulting in a mean cumulative duration of an analyzable ECG signal of 414±136 hours per patient. We found incidental arrhythmias in 94 patients (11.8%). Among these were SSS in 14 patients (1.8%), AVB in 41 (5.2%), AT in 41 (5.2%), and VT in two (0.3%). The median pause duration in SSS was 4 seconds and SSS resulted in pacemaker implantation in one patient with a pause of 9 seconds duration. The most severe type of AVB found per patient was second degree AVB type Wenkebach in 23 patients (2.9%), second degree AVB type Mobitz or 2:1 AV conduction in 10 patients (1.3%) and complete AVB in 8 (1%; maximum pause 18 seconds). AVB led to pacemaker implantation in 9 patients (1.1%). The median duration and heart rate of AT was 2.2 minutes and 144 bpm, respectively. Initiation of betablocker therapy was recommended in 3 patients (0.4%) due to symptomatic AT. The duration and heart rate of VT was 3 minutes at 216 bpm in one patient and 38 seconds at 150 bpm in another. The former patient with VT experienced syncope and an ICD was implanted, whereas in the latter the betablocker dose was increased. One patient died from a non-cardiac cause during a Holter ECG, which showed progressive bradycardia and finally asystole. Conclusion Incidental arrhythmias were frequently discovered during screening for atrial fibrillation and resulted in device therapy in 1.4% of our cohort patients.

Efficacy of epicardial and endocardial ablation in the prevention of ventricular tachycardia in arrythmogenic right ventricular cardiomyopathy- a meta analysis

Abstract Introduction Ventricular tachycardia is a major complication associated with increased risk of sudden cardiac death in arrhythmogenic ventricular cardiomyopathy. Recurrence of VT status post catheter endocardial ablation with conventional mapping is a evolving discussion in management of VT prevention in ARVC. With the evolution of new mapping techniques to locate ectopic foci of VT, a combination of endo- and epicardial catheter ablation have proven to be efficacious in the prevention of frequency of VT recurrence and its duration. Methods Using PubMed, Ovid (MEDLINE) and Cochrane database we searched using the MeSH terms including: “arrhythmogenic right ventricular cardiomyopathy”, “arrhythmogenic right ventricular dysplasia”, “monomorphic ventricular tachycardia”, “polymorphic ventricular Tachycardia”, “endocardial catheter ablation”, “epicardial catheter ablation”. The primary outcomes were to assess VT frequency and duration status post endocardial or epicardial or a combination of both types of ablation. The secondary outcome includes sudden cardiac arrest or sudden cardiac death after procedure. ANOVA with post HOC analysis was performed using SPSS v.26 (IBM Corp, NY, USA) Results A total of 33 studies included 1437 patients with a mean male=67%. The data analysis showed a mean VT prevention for endocardial ablation was 65%, epicardial 78%, and for combined epi-endocardial was 89% (figure-1). The mean procedural mortality rate was 2%. In order to test the hypothesis that combined epi-endocardial ablation was more successful in the prevention of VT recurrence, we performed a one-way analysis of variance (ANOVA). The analysis was statistically significant F(2,14)=5.879, 95% CI, p=0.014. Post Hoc test (Tukey HSD test) with multiple comparisons indicated that patients who underwent combined epi-endocardial ablation experienced a statistically significant difference in VT prevention of 89% (95% CI p=0.01) compared to only endocardial ablation, mean VT prevention of 65% (95% CI, p=0.189) or only epicardial, mean VT prevention of 78% (95% CI, p=0.353). Conclusion With new mapping techniques, use of endocardial, and epicardial ablation is linked to decrease VT frequency, duration, ICD shocks, and sudden cardiac death in patients with ARVC in cohorts with prior failure of antiarrhythmics. Total VT Prevention across target sites Funding Acknowledgement Type of funding source: None

T7. UPDATED INDIVIDUAL PARTICIPANT DATA META-ANALYSIS CONFIRMS LOWER LEVELS OF THE GLIAL MARKER TSPO IN PSYCHOSIS PATIENTS

BackgroundTreatment targeting the immune system is a promising new approach in schizophrenia. In search for tools for stratification and treatment monitoring, much effort has been invested in the use of positron emission tomography (PET) and radioligands binding to a glial marker, the 18 kDa translocator protein (TSPO). We previously demonstrated lower TSPO in psychosis patients in an individual participant data (IPD) meta-analysis of studies using second generation TSPO radioligands (Plavén-Sigray et al., 2018). Subsequently, a summary-statistics meta-analysis, including one newly published study, showed no difference (Marques et al., 2019). Here, the aim was to repeat the IPD analysis including this new sample, and an additional unpublished dataset in first episode psychosis patients. The primary objective was to re-evaluate the hypotheses of 1) higher or 2) lower or 3) no difference in radioligand binding between patients and healthy control subjects. Secondary objectives were to assess the effects of antipsychotic medication on TSPO binding, as well as relationships between TSPO binding and disease duration and symptom measures.MethodsIndividual participant data were obtained from PET studies that 1) used a second generation TSPO radioligand, 2) reported distribution volume (VT) values in brain in patients with psychosis as compared to healthy controls, and 3) reported TSPO affinity type of all participants. The outcome measure was VT in frontal cortex (FC), temporal cortex (TC) and hippocampus (HIP). Bayes factors (BF) were applied to examine the relative support for higher, lower, or no-change of TSPO levels in patients compared to healthy controls.ResultsIndividual participant data from seven studies were included, amounting to 99 patients with first-episode psychosis or schizophrenia and 109 healthy control subjects. In all regions investigated, BF showed moderate to strong support (BF > 5) for lower VT in patients as compared to no difference, and strong support (BF > 10) for lower VT compared to higher VT in patients. Mean patient-control differences in standardized VT values were -0.41 for FC (95%CI -0.67 to -0.15, p = 0.0022), -0.38 for TC (95%CI -0.64 to -0.12, p = 0.0048) and -0.53 for HIP (95% CI -0.79 to -0.27, p = 0.0001). The mean change in standardized VT due to medication was 0.10 for FC (CI95% -0.10 to 0.30, p = 0.615), -0.08 for TC (CI95% -0.32 to 0.48, p = 0.666) and 0.08 for HIP (CI95% -0.46 to 0.30, p = 0.682). No association was observed between VT and disease duration or symptom levels (all p > 0.526).DiscussionIn this updated IPD meta-analysis including two new datasets, we found moderate to strong support for lower TSPO in psychosis patients compared to control subjects. In vitro data has shown a lack of correspondence between TSPO and pro-inflammatory activation, also recently confirmed in a post-mortem study in schizophrenia. Hence, based on the present results no firm conclusions can be made regarding the pro- versus anti-inflammatory status of glial cells in psychosis patients. Additional work is needed to understand the biological relevance of the observed lower TSPO in patients.

Cardioprotective properties of the platelet P2Y12 receptor inhibitor prasugrel on cardiac ischemia/reperfusion injury.

The effects of prasugrel, a third-generation thienopyridine, on myocardial infarction, and ischemia-induced ventricular arrhythmias was evaluated in open-chest anesthetized rats. The role of protein kinase C and phosphoinositide 3-kinase pathways in these effects was also examined. The effect of P2Y12 receptor inhibition by prasugrel (3-10mg/kg, po) on infarct size after 30-min coronary artery occlusion and 120-min reperfusion or on arrhythmias after 7-min coronary occlusion and 7-min reperfusion was evaluated. In the control group, 31.25 ± 3.01% of the risk zone infarcted. At both prasugrel doses, infarct size was significantly smaller than that in the control group: 5.03 ± 0.81% for 3mg/kg (p < 0.0001), and 8.78 ± 2.04% for 10mg/kg (p < 0.0001). The protein kinase C antagonist chelerythrine abolished the anti-infarct effect of prasugrel at 24.77 ± 1.73% as did the phosphoinositide 3-kinase antagonist wortmannin abolished the anti-infarct effect of prasugrel at 27.45 ± 2.74%. Ten mg/kg prasugrel reduced the duration of VT (p = 0.0152 vs control), and wortmannin, but not chelerythrine, reversed the effect of prasugrel on arrhythmias (p = 0.0295). The selective P2Y12 inhibitor prasugrel provides effective protection against myocardial infarction and ischemia-induced ventricular arrhythmias in rats. As in ischemic postconditioning, protein kinase C and phosphoinositide 3-kinase signaling pathways play a role in this protection.

Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality.

"Lung-protective ventilation" describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) PaO2/fractional inspired oxygen tension (FIO2), (2) postoperative pulmonary complications, and (3) 30-day mortality. We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative PaO2/FIO2 while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality. Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4-6), median delivered VT was 520 mL (interquartile range = 460-580), and median driving pressure was 15 cm H2O (13-19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = -6.04; 95% CI, -8.22 to -3.87; P < .001), median FIO2 (B = -0.30; 95% CI, -0.50 to -0.10; P = .003), and hours with driving pressure >16 cm H2O (B = -5.40; 95% CI, -7.2 to -4.2; P < .001) were associated with decreased postoperative PaO2/FIO2. Higher postoperative PaO2/FIO2 ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331-0.740; P = .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366-0.606; P < .001, model C-statistic of 0.820). Intraoperative time with VT >500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00-1.20; P = .042). In patients requiring postoperative intubation after noncardiac surgery, increased median FIO2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative PaO2/FIO2. Intraoperative duration of VT >500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative PaO2/FIO2 ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative PaO2/FIO2 may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.

Abstract 16830: Late Removal of a pLVAD Increases Mortality

Objective: The impact of the timing of removal of a percutaneous left ventricular assist device (pLVAD) during VT ablation on outcomes is uncertain. We compare the outcomes of patients with early (≤ 24 hours) versus late (&gt;24 hours) removal of pLVAD during VT ablation. Methods: We reviewed the data of 27 male patients who underwent VT ablation with pre-emptive pLVAD support between March 2013 to November 2017. There were 2 groups: (1) Early removal group: pLVAD was removed in ≤ 24 hours after VT ablation (n = 18), (2) Late removal group: pLVAD was removed &gt; 24 hours (n = 9). Results: There was no significant difference of age (67.33 ± 12.67 vs. 60.67 ± 14.93 yrs, p = 0.236), Diabetes (both 33.3%), ICMP (56% vs. 44%, p = 0.60), COPD (16.7% vs. 11.1%, p = 0.71), VT storm (both 22.2%), procedure duration (391.5 ± 70.76 vs. 395.67 ± 126.32 min, p = 0.912) between the 2 groups. There was a trend towards longer VT duration during the procedure in Group 2 (28.00 ± 27.16 vs. 60.4 ± 25.1 min, p = 0.148). The LVEF in group 1 is significantly higher (28.09% ± 9.44% vs. 20.00 ± 2.50%, p = 0.019). The 90-day mortality was higher in group 2 (11.1% vs. 44.4%, p = 0.025). Conclusions: Late removal (&gt;24 hours) of a pLVAD for VT ablation is associated with an increased 90-day mortality. Severely depressed LVEF and potentially prolonged time in VT may predict poorer outcomes despite pLVAD support. Figure 1 Kaplan-Meier Survival Curve of the patients with structural heart disease undergoing catheter ablation of ventricular tachycardia under the support of percutaneous left ventricular assist device (pLVAD) (group 1: patient had pLVAD removed ≤ 24 hours after VT ablation; group 2: patient had pLVAD removed &gt;24 hours after VT ablation)

Sudden cardiac death after acute heart failure hospital admission: insights from ASCEND-HF.

The incidence of and factors associated with sudden cardiac death (SCD) early after an acute heart failure (HF) hospital admission have not been well defined. We assessed SCD and ventricular arrhythmias in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, which included patients with acute HF with reduced or preserved ejection fraction. SCD, resuscitated SCD (RSCD), and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) were adjudicated from randomization through 30 days and were combined into a composite endpoint. Baseline characteristics associated with this composite were determined by logistic regression. RSCD and VT/VF were included as time-dependent variables in a Cox model evaluating the association of these variables with 180-day all-cause mortality. Among 7011 patients, the 30-day all-cause mortality rate was 3.8%; SCD accounted for 17% of these deaths. The 30-day composite event rate was 1.8% (n = 121). Ten patients had more than one event with 30-day Kaplan-Meier event rates of 0.6% for SCD [95% confidence interval (CI) 0.5%-0.9%, n = 43], 0.4% for RSCD (95% CI 0.2%-0.5%, n = 24), and 0.9% for VT/VF (95% CI 0.7%-1.2%, n = 64). In the multivariable model, chronic obstructive pulmonary disease, history of VT, male sex, and longer QRS duration were associated with SCD, RSCD, or VT/VF. A RSCD or VT/VF event was associated with higher 180-day mortality (adjusted hazard ratio 6.6, 95% CI 4.8-9.1, P < 0.0001). Approximately 2% of patients admitted for acute HF experienced SCD, RSCD, or VT/VF within 30 days of admission, and SCD accounted for 17% of all deaths within 30 days.

Cardioprotective Effects of Methanolic Extract of Scrophularia frigida on Ischemia-Reperfusion-Induced Injuries in Isolated Rat Heart.

Myocardial infarction is a common presentation of coronary artery disease and the leading cause of death worldwide. The present study investigated potential resistance to ischemia-reperfusion (I/R) injuries following administration of methanolic (MeOH) extract of Scrophularia frigida (S. frigida) in isolated rat heart. Male Wistar rat hearts (n= 8-10) were isolated and allowed to equilibrate for 20 min, and then subjected to 30 min regional ischemia followed by 120 min reperfusion. In the control group, Krebs-Henseleit (K/H) solution was perfused. However, in the treatment groups K/H solution containing 1, 5, and 10 µg/cc of extract was infused. In addition, total phenol, total flavonoid content and antioxidant property were evaluated and extract was subjected to phytochemical analysis. Administration of extract improved the flow rate, developed pressure as well as max and min left ventricular dp/dt. Number and duration of VT were significantly reduced by all extract concentrations in ischemic phase. In reperfusion phase, significant decreases in single and total arrhythmias were seen. Furthermore, concentrations of 5 and 10 µg/cc of extract remarkably decreased the infarct size. Generally, the methanolic extract of S. frigida exhibited a protective effect against I/R-induced injures, which might be due to the antioxidant activiies of iridoids and phenolics.

Real world utilization and impact of the wearable cardioverter-defibrillator in a community setting

IntroductionThe wearable cardioverter-defibrillator (WCD) is used in patients at risk for sudden cardiac death (SCD) but not immediate candidates for intracardiac defibrillator (ICD) implantation. MethodsWe performed a single center retrospective study of patients prescribed WCD upon hospital discharge from January 2002 to October 2015. Clinical characteristics were obtained from the hospital electronic database and device data from Zoll LifeVest database. ResultsOf 140 patients, 62% were men, 85.9% were African-American and mean age was 58.2 ± 15.5 years. Ischemic cardiomyopathy was present in 45 (32%) and non-ischemic cardiomyopathy in 64 patients (46%). Mean left ventricular ejection fraction (EF) was 0.28 ± 0.4. WCD was worn for 7657 patient-days (21 patient-years), with each patient using WCD for median of 43 days (IQR: 7–83 days), and daily mean use 17.3 ± 7.5 h. There were a total of 6 (4.2%) WCD shocks of which 2 (1.4%) were appropriate (one for VT, one for VF) and 4 (2.8%) were inappropriate (2 had supraventricular tachycardia, 2 had artifact). Two patients who received appropriate shocks were African-American with non-ischemic cardiomyopathy (EF<20%), non-sustained VT and wide QRS duration. Upon termination of WCD use, 45 (32%) received ICD while EF improved in 34 patients (32%). ConclusionsIn a predominantly minority, community setting, WCD compliance is high and use is effective in aborting SCD. However, inappropriate shocks do occur. A significant proportion of patients did not ultimately require ICD implantation suggesting this may be a cost-effective strategy in patients at risk of SCD.

Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia.

BackgroundMyocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress.Material/MethodsRats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB).ResultsCreatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods.ConclusionsAngiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats.

Esmolol activates endogenous neurokinin activity inhibiting infarction-induced arrhythmias in rats: Novel mechanisms of anti-arrhythmia

Endogenous neurokinin and adrenergic mechanisms might co-participate in the pathology of acute myocardial infarction (MI). This study sought to investigate the role of endogenous neurokinin and its relationship with β1-adrenergic mechanism in the infarction induced arrhythmias.In 60min of MI in rats, the contents of substance P (SP), a native agonist of neurokinin 1 receptor (NK1-R), norepinephrine (NE), NK1-R and β1-adrenergic receptor in the myocardium at risk of ischemia were examined and the ventricular arrhythmias were analyzed. The effects of pretreatment with D-SP (152ng/kg), a specific antagonist of NK1-R, esmolol (10mg/kg), a specific blocker of β1-adrenergic receptor, and a combination of the two blockers were studied. The results showed that the overlaps of up-regulation of NE, SP and the increase of ventricular arrhythmias were observed. D-SP exacerbated the episodes and duration of VT & VF by 54% and 104%, respectively (all P<0.05). Esmolol inhibited the morbidity rate, the episodes and the duration of VT & VF by 66%, 92% and 95%, respectively. Surprisingly, esmolol significantly attenuated the arrhythmogenic effect of D-SP throughout the MI, beyond the time span of esmolol action, during which a significant up-regulation of the NK1-R (by 19%, P<0.05) was detected.In conclusion, the findings of this study may indicate an anti-arrhythmic effect of endogenous neurokinin mechanism, through the activation of which, via up-regulation of NK1 receptor, esmolol may exert its anti-arrhythmic action at the early time of acute myocardial infarction.

Inter-individual differences in breathing pattern at high levels of incremental cycling exercise in healthy subjects

Interindividual differences in the rate of changes in tidal volume (VT) and respiratory frequency (fR) were examined during a maximal incremental cycling exercise. The gain of the inspiratory off-switch reflex was inferred from the VT vs. inspiratory duration (Ti) relationship. Some subjects also executed a static handgrip exercise, used as a “non-dynamic” exercise trial to study patterning of breathing.Above the ventilatory threshold (VTh), two patterns of response were identified: in group 1, the rate of change in VT significantly increased, while in group 2 the breakpoint of ventilation solely resulted from fR increase. After the respiratory compensation point, a tachypnoeic response always occurred. A leftward shift of the VT vs. Ti relationship, i.e., an inspiratory off-switch reflex, was measured during the handgrip in group 2 subjects as well as marked fR variations.Our study identifies two different patterns of breathing after the VTh. The subjects who present a tachypnoeic response to exercise above the VTh have a higher sensitivity to pulmonary inflation and their tachypnoeic response was ubiquitous during a maximal handgrip test.

Resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart.

RESULTS of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H) solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min with normal K/H solution. In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (P<0.001), 138±48 (P<0.01), 142±37 (P<0.001) and 157±40 (P<0.01), respectively. Number and duration of VT and time spent in reversible VF were also reduced by honey. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (P<0.001), respectively. Postischemic administration of natural honey in global ischemia showed protective effects against ischemia/reperfusion (I/R) injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects.

Minocycline attenuates ischemia-induced ventricular arrhythmias in rats

Minocycline has been shown to protect against myocardial ischemia–reperfusion injury. This study investigated the effects of minocycline on ischemia-induced ventricular arrhythmias in rats. Anesthetized male rats were once treated with minocycline (45 mg/kg, i.p.) 1 h before ischemia in the absence and/or presence of 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002, 0.3 mg/kg, i.v., a PI3K inhibitor) and 5-hydroxydecanoic acid [5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium (K ATP) channels] which were once injected 10 min before ischemia and then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed. L-type Ca 2+ current was measured by the patch-clamp technique. During the 30-minute ischemia, minocycline significantly reduced the incidence of ventricular fibrillation (VF) (P < 0.05). The duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by minocycline compared to those in myocardial ischemia group (P < 0.05 for all). Administration of LY294002 or 5-HD abolished the protective effects of minocycline on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (P < 0.05 for all). In addition, minocycline inhibited L-type Ca 2+ currents of normal myocardial cell membrane in a dose-dependent manner. This study suggested that minocycline could attenuate ischemia-induced ventricular arrhythmias in rats in which PI3K/Akt signaling pathway, mitochondrial K ATP channels and L-type Ca 2+ channels may be involved .

Ventricular Tachycardia on Previous Myocardial Infarction: Effective by Nifekalant, Bepridil and Two Sessions of Catheter Ablation

A 74-year-old man with previous myocardial infarction and CABG was admitted our hospital because of sustained VT. VT’s cycle length (CL) was 460 ms and QRS morphology was RBBB+LAD (VT1). As he had intestinal pneumonia, amiodarone was contraindicated. Thus we started nifekalant and d-sotalol. VT was controlled by nifekalant, but relapsed and became uncontrollable after discontinuation of nifekalant, even with increased dosage of d-sotalol. Temporary pacing from RVA wasn’t effective, and QT interval became be more prolonged after increased dosage of nifekalant and d-sotalol. Thus catheter ablation was performed. Clinical VT couldn’t induced by programmed stimulations at RVA and RVOT. Perfect pacemap site was existed at inferoseptal wall. At this site, purkinje potential preceded ventricular potential. Radiofrequency (RF) energy was delivered around this site. Next evening, altenated VT was appeared. QRS morphologies were LBBB+LAD (VT2, CL: 440 ms) and RBBB+superior axis (VT3, CL: 520 ms). After we administration of nifekalant, VT was supressed. After ICD implantation, we stopped d-sotalol and started bepridil. VT duration became shorter, but its frequency showed no change. We performed catheter ablation again because of repetitive VT. VT couldn’t induced on this session, either. RF energy was delivered at perfect (VT2, midseptal) and good (VT3, inferoseptal, slightly anterior of VT1) pacemap site. Linear lesion was made in low voltage zone between two pacemap sites and between septal and anterior wall. After ablation, VT dissappeared with low dose bepridil. Conclusion: Alterated VT modified by focal ablation was effective linear ablation at low voltage zone and pottasium channel blocker.

Differential action of two prolactin isoforms on ischemia-and re-perfusion-induced arrhythmias in rats in vivo

The different influences of one of the PRL isoforms (PRL I) on the cardiovascular system have been described in the past. Our goal was to establish an appropriate iv dose of 2 PRL isoforms (PRL I and PRL II) in intact rats. After establishing this dose, PRL I (0.01 mg/kg) or PRL II (0.001 mg/kg) was administered in bolus 10 min before left anterior descending coronary artery occlusion (7 min) followed by re-perfusion (15 min). We then aimed to study and compare the effects of these isoforms on ischemia- and re-perfusion-induced arrhythmias in the ischemia and re-perfusion-induced arrhythmias model in rats. Mortality index, ventricular fibrillation and tachycardia (VF, VT) incidence and duration, systolic, diastolic, and mean arterial blood pressure, heart rate and myocardial index of oxygen consumption [pressure rate product (PRP)] were measured and calculated. Both PRL isoforms reduced animal mortality (from 50 to 18.75 and 25%, respectively). PRL II significantly reduced VF incidence (to 25%) as well as VT duration (18.21 ± 3.09) and these effects were markedly different from PRL I and from the control group (p<0.05). Both PRL reduced PRP in the recovery phase (p<0.05). We proved that supraphysiological doses of PRL isoforms administered in bolus could protect against sudden cardiac death as well as severe arrhythmias episodes during re-perfusion. Because of PRL's positive influence on the cardiovascular system and as an endogenous, well-tolerated substance, it might be of potential clinical use.

Modulation of cardiac response to ischemia/reperfusion in hypertensive rats exposed to chronic social stress

Chronic psychosocial stress (S) impairs vascular regulation leading to hypertension (H). However, modulation of cardiac response to ischemia/reperfusion injury (I/R) by S is not fully characterized, in particular, in hypertensive animals. We explored tolerance to I/R in WKY and SHR rats exposed to 8 w of crowding S induced by caging 5 rats/cage (200 cm2/rat), while controls (C) were kept 4 rats/cage (480 cm2/rat). S did not affect left ventricular (LV) weight in any group, however, it amplified increased BP and reduced elevation of cardiac NOS activity in SHR rats. Neither did S modified myocardial function in hearts of both groups under baseline conditions. Ischemic challenge (25_min I/40_min R) revealed markedly impaired recovery of LV developed pressure (LVDP) in C_SHR (15±6% of baseline value vs. 60±1.5% in the control WKY group; P<0.05) and increased susceptibility to lethal arrhythmias (incidence of SVF 25% and duration of VT 84±22 s vs. SVF 0% and VT 30±12 s in C_WKY; P<0.05). S altered contractile recovery in the WKY group (LVDP 32±5%; P<0.05) and exacerbated arrhythmias (incidence of SVF 40%, duration of VT 70±20 s; P<0.05 vs. unstressed WKY). In contrast, SVF was completely suppressed in stressed SHR hearts, in conjunction with shorter episodes of VT (22±5 s) and better recovery of LVDP (47±12%; P<0.05 vs. unstressed SHR). Conclusion: chronic psychosocial stress represents a higher risk of lethal arrhythmias and contractile failure in normotensive rats exposed to an acute ischaemic challenge indicating a potential development of cross effect of adaptation in hypertensive individuals.

Cerebral Oxygenation During Defibrillator Threshold Testing of Implantable Cardioverter Defibrillators

The induction of ventricular fibrillation (VF) during defibrillator threshold testing of implantable cardioverter defibrillators (ICD) provokes global cerebral hypoperfusion and impaired oxygen delivery. Limited data are available on the neurophysiological effects of defibrillator threshold testing. Near infrared spectroscopy (NIRS) can noninvasively measure changes in specific chromophores, which reflect cerebral oxygenation at the intravascular and mitochondrial levels. We performed a prospective trial using NIRS to analyze cerebral cortical oxygenation during defibrillator threshold testing. Eleven patients (men = 9; age = 64 +/- 11 years: LVEF = 44 +/- 11%) underwent subpectoral ICD implantation and defibrillator threshold testing under general anesthesia. A NIRO 300 spectrometer was used to measure the absolute changes in the concentrations of oxyhemoglobin, de-oxyhemoglobin, and cytochrome c oxidase copper moiety during each procedure. The mean arterial blood pressure was monitored simultaneously. The mean number of defibrillator threshold tests was two (range 2-6). Twenty-six episodes of VF (duration 13.1 +/- 9.7 seconds; cycle length 230.2 +/- 20.8 ms) and two episodes of VT (duration 15 +/- 2.8 seconds; cycle length 320 +/- 11.3 ms) were induced. Each episode of VF and VT resulted in a decrease in the mean arterial blood pressure to 23.9 +/- 7.5 mmHg (p < or = 0.05) and oxyhemoglobin (-4.2 +/- 1.7 micromol/L; p < or = 0.05) and an increase in de-oxyhemoglobin (2.7 +/- 1.4 micromol/L). There was no change in the cytochrome c oxidase copper moiety redox status (0.09 +/- 0. 30 micromol/L). Our results suggest that impaired oxygen delivery during induced VF and VT does not affect oxygen availability at the cellular intra-mitochondrial level.

Comparative Physiologic Effects of Noninvasive Assist-Control and Pressure Support Ventilation in Acute Hypercapnic Respiratory Failure

To compare the effects of noninvasive assist-control ventilation (ACV) and pressure support ventilation (PSV) by nasal mask on respiratory physiologic parameters and comfort in acute hypercapnic respiratory failure (AHRF). A prospective randomized study. A medical ICU. Fifteen patients with COPD and AHRF were consecutively and randomly assigned to two noninvasive ventilation (NIV) sequences with ACV and PSV mode, spontaneous breathing (SB) via nasal mask being used as control. ACV and PSV settings were always subsequently adjusted according to patient's tolerance and air leaks. Fraction of inspired oxygen did not change between the sequences. ACV and PSV mode strongly decreased the inspiratory effort in comparison with SB. The total inspiratory work of breathing (WOBinsp) expressed as WOBinsp/tidal volume (VT) and WOBinsp/respiratory rate (RR), the pressure time product (PTP), and esophageal pressure variations (deltaPes) were the most discriminant parameters (p<0.001). ACV most reduced WOBinsp/VT (p<0.05), deltaPes (p<0.05), and PTP (0.01) compared with PSV mode. The surface diaphragmatic electromyogram activity was also decreased >32% as compared with control values (p<0.01), with no difference between the two modes. Simultaneously, NIV significantly improved breathing pattern (p<0.01) with no difference between ACV and PSV for VT, RR, minute ventilation, and total cycle duration. As compared to SB, respiratory acidosis was similarly improved by both modes. The respiratory comfort assessed by visual analog scale was less with ACV (57.23+/-30.12 mm) than with SB (75.15+/-18.25 mm) (p<0.05) and PSV mode (81.62+/-25.2 mm) (p<0.01) in our patients. During NIV for AHRF using settings adapted to patient's clinical tolerance and mask air leaks, both ACV and PSV mode provide respiratory muscle rest and similarly improve breathing pattern and gas exchange. However, these physiologic effects are achieved with a lower inspiratory workload but at the expense of a higher respiratory discomfort with ACV than with PSV mode.

Antiarrhythmic effects of DHA-As on ventricular arrhythmias in rat and dog hearts

DHA-Ascorbic acid (DHA-As), a new derivative of docosahexaenoic acid (DHA) was tested for its possible antiarrhythmic effects on coronary artery ligation/reperfusion arrhythmias in rat hearts, and adrenaline-induced arrhythmias in canine hearts. DHA-As (3 mg/kg i.v.) did not change the total duration of VT, and tended to suppress the incidence of VT, VF and mortality of reperfusion in rat hearts. The heart rate, QT90 and systolic blood pressure did not change, and the diastolic blood pressure was decreased by DHA-As in the rat hearts. DHA-As significantly decreased the arrhythmic ratio only at two time points (14 and 15 min after injection), and also decreased the heart rate and mean blood pressure in canine hearts. In conclusion, DHA-As tended to suppress the reperfusion-induced arrhythmias in rat hearts. However, the change was not statistically significant. In addition, DHA-As has a weak suppressing effect on adrenaline-induced arrhythmia.