ß-Bisabolene, a Sesquiterpene from the Essential Oil Extract of Opoponax (Commiphora guidottii), Exhibits Cytotoxicity in Breast Cancer Cell Lines.

The essential oils from Commiphora species have for centuries been recognized to possess medicinal properties. Here, we performed gas chromatography-mass spectrometry on the essential oil from opoponax (Commiphora guidotti) and identified bisabolene isomers as the main constituents of this essential oil. Opoponax essential oil, a chemical component; ß-bisabolene and an alcoholic analogue, α-bisabolol, were tested for their ability to selectively kill breast cancer cells. Only ß-bisabolene, a sesquiterpene constituting 5% of the essential oil, exhibited selective cytotoxic activity for mouse cells (IC50 in normal Eph4: >200 µg/ml, MG1361: 65.49 µg/ml, 4T1: 48.99 µg/ml) and human breast cancer cells (IC50 in normal MCF-10A: 114.3 µg/ml, MCF-7: 66.91 µg/ml, MDA-MB-231: 98.39 µg/ml, SKBR3: 70.62 µg/ml and BT474: 74.3 µg/ml). This loss of viability was because of the induction of apoptosis as shown by Annexin V-propidium iodide and caspase-3/7 activity assay. ß-bisabolene was also effective in reducing the growth of transplanted 4T1 mammary tumours in vivo (37.5% reduction in volume by endpoint). In summary, we have identified an anti-cancer agent from the essential oil of opoponax that exhibits specific cytotoxicity to both human and murine mammary tumour cells in vitro and in vivo, and this warrants further investigation into the use of ß-bisabolene in the treatment of breast cancers.

Implantable defibrillators with enhanced detection algorithms: detection performance and safety results from the PainFree SST study.

BACKGROUND: Implantable defibrillators (ICD) are highly effective in reducing arrhythmia-related mortality. ICD shock therapy has been shown to increase psychological distress, health care utilization, and is associated with increased mortality. The Protecta ICDs (Medtronic Inc., Minneapolis, MN, USA) have algorithms designed to reduce unnecessary and inappropriate shock therapy. METHODS AND RESULTS: The PainFree SmartShock™ Technology (PainFree SST) study is a prospective, multicenter, clinical trial with two consecutive phases, a premarket phase safety study and a postmarket phase effectiveness study. We report the results of the PainFree SST safety study. The premarket phase aimed to investigate safety in the first year postimplant, and to determine if the novel algorithms (T-wave discrimination, right ventricular lead noise discrimination and confirmation+) affect appropriate ventricular fibrillation (VF) detection. Patients (total: n = 246 [male 78%, mean age 63 year, primary prevention indication in 76%]) were implanted either with a Protecta XT dual-chamber ICD (n = 114 [46%]) or a defibrillator with cardiac resynchronization therapy (n = 132 [54%]). Appropriate VF detection was measured during VF induction at implantation when the novel algorithms were programmed ON. A two-second delay in VF detection was classified as clinically significant. No delay in VF detection was observed with all algorithms programmed ON. No unanticipated serious adverse device effects occurred during first year postimplant. CONCLUSION: The results of the premarket phase of the PainFree SST trial demonstrate the safety of the Protecta XT defibrillators. Detection of induced VF was not delayed with SmartShock™ algorithms ON.

The relationship between pacing site and induction or termination of sustained monomorphic ventricular tachycardia by antitachycardia pacing.

BACKGROUND: With the development of left ventricular pacing for cardiac resynchronization, there is an interest in the possibility of improving ventricular antitachycardia pacing (ATP) efficacy by pacing from the LV electrode(s). OBJECTIVE: This study assessed the efficacy of pacing delivered from the left coronary vein (LCV) compared to that delivered from the right ventricular apex (RVA) upon ventricular tachycardia (VT) induction and termination. METHODS: Sixty patients undergoing provocative ventricular electrophysiology (EP) studies in three centers were enrolled. Multipolar EP catheters were placed in the atrium, the RVA, and LCV. VT induction was attempted from the RVA and LCV in random order. Upon detection of monomorphic VT, burst ATP for up to 10 pulses at 88% VT cycle length was delivered from the RVA or LCV, in a random order, and crossed over when possible. Identical VT morphologies were reinduced to allow paired comparison of RVA versus LCV ATP. RESULTS: Data from 55 patients were analyzed. Thirty-four morphologically distinct monomorphic VT types were induced in 22 patients. ATP succeeded in 18 (55%) and VTs in 13 patients. RVA ATP terminated 15 of 23 (65%) VTs, and LCV ATP terminated 10 of 23 (43%) VTs (P = 0.14). ATP delivered ipsilateral to the earliest activation site required 5.0 + or - 2.6 pulses to terminate compared to 4.8 + or - 1.7 pulses when delivered from the contralateral site (P = 0.90). Paired comparison was possible for 13 VT morphologies in 11 patients. Paired RVA and LCV ATP efficacy was identical (54%vs 54%, P = 1.0). CONCLUSION: ATP delivered from a LCV lead offers no efficacy advantage over pacing from the RVA.

Initial Clinical Experience With a New Automated Antitachycardia Pacing Algorithm: Feasibility and Safety in an Ambulatory Patient Cohort.

BACKGROUND: Antitachycardia pacing (ATP) in implantable cardioverter-defibrillators (ICD) decreases patient shock burden but has recognized limitations. A new automated ATP (AATP) based on electrophysiological first principles was designed. The study objective was to assess the feasibility and safety of AATP in ambulatory ICD patients. METHODS AND RESULTS: Enrolled patients had dual chamber or cardiac resynchronization therapy ICDs, history of ≥1 ICD-treated ventricular tachycardias (VT)/ventricular fibrillation episode, or a recorded, sustained monomorphic VT. Detection was set to ventricular fibrillation number of intervals to detect=24/32, VT number of intervals to detect≥16, and a fast VT zone of 240 to 320 ms. AATP prescribed the components and delivery of successive ATP sequences in real time, using the same settings for all patients. ICD datalogs were uploaded every ≈3 months, at unscheduled visits, exit, and death. Episodes and adverse events were adjudicated by separate committees. Results were adjusted (generalized estimating equations) for multiple episodes. AATP was downloaded into the ICDs of 144 patients (121 men), aged 67.4±11.9 years, left ventricular ejection fraction 33.1±13.6% (n=137), and treated 1626 episodes in 49 patients during 14.5±5.1 months of follow-up. Datalogs permitted adjudication of 702 episodes, including 669 sustained monomorphic VT, 20 polymorphic VT, 10 supraventricular tachycardia, and 3 malsensing episodes. AATP terminated 39 of 69 (59% adjusted) sustained monomorphic VT in the fast VT zone, 509 of 590 (85% adjusted) in the VT zone, and 6 of 10 in the ventricular fibrillation zone. No supraventricular tachycardias converted to VT or ventricular fibrillation. No anomalous AATP behavior was observed. CONCLUSIONS: The new AATP algorithm safely generated ATP sequences and controlled therapy progression in all zones without need for individualized programing.

Sinus rhythm R-wave amplitude as a predictor of ventricular fibrillation undersensing in patients with implantable cardioverter-defibrillator.

BACKGROUND: Ventricular fibrillation (VF) is induced during implantable cardioverter-defibrillator (ICD) implantation to ensure that the ICD will sense, detect, and defibrillate VF. ICD implant guidelines state that the amplitude of the sinus rhythm R wave recorded from the ventricular electrogram should have amplitude ≥5 mV. No study has tested the relationship between sinus rhythm R-wave amplitude and VF sensing using modern, transvenous sensing electrodes. OBJECTIVE: The goal of this study was to determine whether there is a sinus rhythm R-wave amplitude cutoff that can be used to determine which patients are not at risk of VF undersensing. METHODS: A retrospective analysis of induced and spontaneous VF episodes from 2 clinical trials with 2022 patients was performed. Episodes with undersensing during the initial detection of VF were identified, and the distribution of sinus rhythm R-wave amplitudes for patients with and without VF undersensing was analyzed. RESULTS: Only 3% of analyzed induced VF episodes were considered to have VF undersensing, and none had clinically significant detection delays. There was no correlation between device-measured, rectified sinus rhythm R-wave amplitude and VF undersensing at the time of implantation or during follow-up, although <4% of patients had sinus rhythm R-waves with amplitude <3 mV. CONCLUSION: We analyzed true bipolar sensing of induced VF or spontaneous ventricular tachycardia/VF detected in the ICD VF zone. Sensing of VF was so reliable that clinically significant undersensing did not occur. Our findings do not support any recommended minimum sinus rhythm R wave to ensure reliable sensing of VF or the necessity of inducing VF to verify sensing for rectified sinus rhythm R-waves with amplitude ≥3 mV.

Hope for the best--plan for the worst: disaster preparedness in a strange new world.

In the last year, local, state and federal governments, as well as not-for-profit and private businesses, have had to examine how they would respond to a disaster. The responsibility to be well-prepared is especially important for hospitals for two reasons.