Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

Contrast‐enhanced computed tomography with myocardial three‐dimensional printing can guide treatment in symptomatic hypertrophic obstructive cardiomyopathy

PubMed Central

Hamatani, Yasuhiro; Amaki, Makoto; Kanzaki, Hideaki; Yamashita, Kizuku; Nakashima, Yasuteru; Shibata, Atsushi; Okada, Atsushi; Takahama, Hiroyuki; Hasegawa, Takuya; Shimahara, Yusuke; Sugano, Yasuo; Fujita, Tomoyuki; Shiraishi, Isao; Yasuda, Satoshi; Kobayashi, Junjiro

2017-01-01

Abstract Both surgical myectomy and percutaneous transluminal septal myocardial ablation are effective treatments for drug‐refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). However, in some cases, it is not easy to elucidate the abnormal structure of left ventricular outflow obstruction to adopt these treatments. Here, we presented a young female patient with drug‐refractory symptomatic HOCM. In this case, contrast‐enhanced computed tomography enabled us to assess the suitability of percutaneous transluminal septal myocardial ablation. By creating three‐dimensional printed models using computed tomography data, we could also visualize intracardiac structure and simulate the surgical procedure. A multimodality assessment strategy is useful for evaluating patients complicated with drug‐refractory symptomatic HOCM. PMID:29154429

Successful weaning of a left ventricular assist device implanted for ischemic heart failure.

PubMed

Beurtheret, Sylvain; Mordant, Pierre; Pavie, Alain; Leprince, Pascal

2010-10-01

We report the case of a patient stabilized under extra-corporeal membrane oxygenation after a refractory cardiogenic shock following myocardial infarction. Persistent left ventricular failure required secondary implantation of the left ventricular assist device (LVAD) HeartMate II. LVAD succeeded in the gradual recovery of myocardial contractility, allowing weaning of the device five months after implantation. Simultaneously, the patient beneficiated from coronary revascularization and resumed normal activity. This case emphasizes potential late recoveries after myocardial infarction complicated by left ventricular failure.

The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.

PubMed

Doksöz, Önder; Çeleğen, Kübra; Güzel, Orkide; Yılmaz, Ünsal; Uysal, Utku; İşgüder, Rana; Çeleğen, Mehmet; Meşe, Timur

2015-09-01

Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P < 0.05). Baseline variables assessed by conventional M-mode echocardiography showed no significant difference at month 6 (P > 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P < 0.05). Although mitral annulus tissue Doppler imaging studies showed no significant difference (P > 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P < 0.05). A 6-month duration ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Atrioventricular node functional remodeling induced by atrial fibrillation.

PubMed

Zhang, Youhua; Mazgalev, Todor N

2012-09-01

The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. To determine whether AVN undergoes functional remodeling during AF. AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls. Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Effect of Right Ventricular versus Biventricular Pacing on Electrical Remodeling in the Normal Heart

PubMed Central

Saba, Samir; Mehdi, Haider; Mathier, Michael A.; Islam, M. Zahadul; Salama, Guy; London, Barry

2010-01-01

Background Biventricular (BIV) pacing can improve cardiac function in heart failure by altering the mechanical and electrical substrates. We investigated the effect of BIV versus right ventricular (RV) pacing on the normal heart. Methods and Results Male New Zealand White rabbits (n=33) were divided into 3 groups: sham-operated (control), RV pacing, and BIV pacing groups. Four weeks after surgery, the native QT (p=0.004) interval was significantly shorter in the BIV group compared to the RV or sham-operated groups. Also, compared to rabbits in the RV group, rabbits in the BIV group had shorter RV ventricular effective refractory period (VERP) at all cycle lengths, and shorter LV paced QT interval during the drive train of stimuli and close to refractoriness (p<0.001 for all comparisons). Protein expression of the KVLQT1 was significantly increased in the BIV group compared to the RV and control groups, while protein expression of SCN5A and connexin43 was significantly decreased in the RV compared to the other study groups. Erg protein expression was significantly increased in both pacing groups compared to the controls. Conclusions In this rabbit model, we demonstrate a direct effect of BIV but not RV pacing on shortening the native QT interval as well as the paced QT interval during burst pacing and close to the VERP. These findings underscore the fact that the effect of BIV pacing is partially mediated through direct electrical remodeling and may have implications as to the effect of BIV pacing on arrhythmia incidence and burden. PMID:20042767

Lacosamide-Induced Recurrent Ventricular Tachycardia in the Acute Care Setting.

PubMed

Berei, Theodore J; Lillyblad, Matthew P; Almquist, Adrian K

2018-04-01

Lacosamide is a new-generation antiepileptic drug (AED) most commonly used adjunctively in the setting of partial-onset seizures refractory to traditional therapy. We describe the first case report, to our knowledge, of a patient who developed recurrent, sustained ventricular tachycardia with multiple administrations of lacosamide in an acute setting. A 70-year-old woman with a history significant for valvular heart disease was admitted to the inpatient cardiology service for worsening heart failure. On hospital day 7, she received a bioprosthetic aortic valve. Prior to surgery and immediately after, the patient's electrocardiogram (ECG) was normal. After developing multiple generalized tonic-clonic seizures refractory to levetiracetam, fosphenytoin, and valproic acid, the decision was made to initiate lacosamide. Two hours following the second lacosamide dose, the patient developed a wide complex QRS that transitioned into sustained ventricular tachycardia requiring electrical cardioversion. Sustained ventricular tachycardia occurred again, just hours after the third dose of lacosamide was given. Following cessation of lacosamide, the patient's QRS interval normalized and has since had no documented episodes of ventricular tachycardia. Clinicians should be aware of the potential for life-threatening rhythmic disturbances in patients initiated on lacosamide and the need for vigilant ECG, electrolyte, and drug-drug monitoring.

Emergency catheter ablation in critical patients

PubMed Central

Tebbenjohanns, Jürgen; Rühmkorf, Klaus

2010-01-01

Emergency catheter ablation is justified in critical patients with drug-refractory life-threatening arrhythmias. The procedure can be used for ablation of an accessory pathway in preexcitation syndrome with high risk of ventricular fibrillation and in patients with shock due to ischemic cardiomyopathy and incessant ventricular tachycardia. Emergency catheter ablation can also be justified in patients with an electrical storm of the implanted cardioverter-defibrillator or in patients with idiopathic ventricular fibrillation. PMID:20606793

Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat

NASA Technical Reports Server (NTRS)

Lehnert, Hendrik; Lombardi, Federico; Raeder, Ernst A.; Lorenzo, Antonio V.; Verrier, Richard L.; Lown, Bernard; Wurtman, Richard J.

1987-01-01

The effect of administering the serotonin precursor 5-l-hydroxytryptophan, in conjunction with a monamine oxidase inhibitor phenelzine and a l-amino acid decarboxylase inhibitor carbidopa, on neurochemical changes in the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid of the cat were investigated. Results showed that this drug regimen led to increases of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid by 330 and 830 percent, respectively. Concomitantly, the threshold of ventricular fibrillation was found to be elevated by 42 percent and the effective refractory period was prolonged by 7 percent; the efferent sympathetic neural activity was suppressed in the normal heart. The results indicate that the enhancement of central serotoninergic neurotransmission can reduce the susceptibility of the heart to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.

Vulnerability to ventricular fibrillation

NASA Astrophysics Data System (ADS)

Janse, Michiel J.

1998-03-01

One of the factors that favors the development of ventricular fibrillation is an increase in the dispersion of refractoriness. Experiments will be described in which an increase in dispersion in the recovery of excitability was determined during brief episodes of enhanced sympathetic nerve activity, known to increase the risk of fibrillation. Whereas in the normal heart ventricular fibrillation can be induced by a strong electrical shock, a premature stimulus of moderate intensity only induces fibrillation in the presence of regional ischemia, which greatly increases the dispersion of refractoriness. One factor that is of importance for the transition of reentrant ventricular tachycardia to ventricular fibrillation during acute regional ischemia is the subendocardial Purkinje system. After selective destruction of the Purkinje network by lugol, reentrant tachycardias still develop in the ischemic region, but they do not degenerate into fibrillation. Finally, attempts were made to determine the minimal mass of thin ventricular myocardium required to sustain fibrillation induced by burst pacing. This was done by freezing of subendocardial and midmural layers. The rim of surviving epicardial muscle had to be larger than 20 g. Extracellular electrograms during fibrillation in both the intact and the "frozen" left ventricle were indistinguishable, but activation patterns were markedly different. In the intact ventricle epicardial activation was compatible with multiple wavelet reentry, in the "frozen" heart a single, or at most two wandering reentrant waves were seen.

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

PubMed

Cesana, Francesca; Avalli, Leonello; Garatti, Laura; Coppo, Anna; Righetti, Stefano; Calchera, Ivan; Scanziani, Elisabetta; Cozzolino, Paolo; Malafronte, Cristina; Mauro, Andrea; Soffici, Federica; Sulmina, Endrit; Bozzon, Veronica; Maggioni, Elena; Foti, Giuseppe; Achilli, Felice

2017-10-01

Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

PubMed

Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David

2012-01-01

Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

Off-pump repair of a post-infarct ventricular septal defect: the 'Hamburger procedure'

PubMed Central

Barker, Thomas A; Ng, Alexander; Morgan, Ian S

2006-01-01

We report a novel off-pump technique for the surgical closure of post-infarct ventricular septal defects (VSDs). The case report describes the peri-operative management of a 76 year old lady who underwent the 'Hamburger procedure' for closure of her apical VSD. Refractory cardiogenic shock meant that traditional patch repairs requiring cardiopulmonary bypass would be poorly tolerated. We show that echocardiography guided off-pump posterior-anterior septal plication is a safe, effective method for closing post-infarct VSDs in unstable patients. More experience is required to ascertain whether this technique will become an accepted alternative to patch repairs. PMID:16722552

Massive Atenolol, Lisinopril, and Chlorthalidone Overdose Treated with Endoscopic Decontamination, Hemodialysis, Impella Percutaneous Left Ventricular Assist Device, and ECMO.

PubMed

Heise, C William; Beutler, David; Bosak, Adam; Orme, Geoffrey; Loli, Akil; Graeme, Kimberlie

2015-03-01

Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome. Aggressive medical intervention did not provide sufficient hemodynamic stability in this patient with refractory cardiogenic and distributive shock. Impella® percutaneous left ventricular assist device and extracorporeal membrane oxygenation provided support while the effects of the overdose subsided. We present concentrations demonstrating removal of atenolol with continuous venovenous hemodiafiltration. This is the first report of esophagogastroduo denoscopy decontamination of this overdose with a large pill fragment burden.

Renal sympathetic denervation modulates ventricular electrophysiology and has a protective effect on ischaemia-induced ventricular arrhythmia.

PubMed

Huang, Bing; Yu, Lilei; He, Bo; Lu, Zhibing; Wang, Songyun; He, Wenbo; Yang, Kang; Liao, Kai; Zhang, Ling; Jiang, Hong

2014-11-01

Recently, a beneficial effect of renal sympathetic denervation (RSD) has been seen in patients with ventricular electrical storm. However, the effect of RSD on ventricular electrophysiology remains unclear. Thirty-three mongrel dogs were included in the present study. Renal sympathetic denervation was performed by radiofrequency ablation of the adventitial surface of the renal artery. In group 1 (n = 8), programmed stimulation was performed before and after RSD to determine the ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties. The same parameters were measured in five other animals that underwent sham RSD to serve as controls. In group 2 (n = 10), acute myocardial ischaemia (AMI) was induced by ligating the proximal left anterior descending coronary artery after the performance of RSD, and the incidence of ventricular arrhythmia (VA) was calculated during 1 h of recording. In another 10 dogs (group 3), AMI was induced and VA was measured with sham RSD. In group 1, RSD significantly prolonged ventricular ERP and APD, reduced the maximal slope (Smax) of the restitution curve and suppressed APD alternans at each site. Renal sympathetic denervation also significantly decreased the spatial dispersion of ERP, APD and Smax. In the five control animals, no significant electrophysiological change was detected after sham RSD. The occurrence of spontaneous VA during 1 h of AMI in group 2 was significantly lower than that in group 3. These data suggest that RSD stabilizes ventricular electrophysiological properties in normal hearts and reduces the occurrence of VA in hearts experiencing AMI. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Ranolazine effectively suppresses atrial fibrillation in the setting of heart failure.

PubMed

Burashnikov, Alexander; Di Diego, José M; Barajas-Martínez, Hector; Hu, Dan; Zygmunt, Andrew C; Cordeiro, Jonathan M; Moise, N Sydney; Kornreich, Bruce G; Belardinelli, Luiz; Antzelevitch, Charles

2014-07-01

There is a critical need for safer and more effective pharmacological management of atrial fibrillation (AF) in the setting of heart failure (HF). This study investigates the electrophysiological, antiarrhythmic, and proarrhythmic effects of a clinically relevant concentration of ranolazine (5 μmol/L) in coronary-perfused right atrial and left ventricular preparations isolated from the hearts of HF dogs. HF was induced by ventricular tachypacing (2-6 weeks at 200-240 beats per minute; n=17). Transmembrane action potentials were recorded using standard microelectrode techniques. In atria, ranolazine slightly prolonged action potential duration but significantly depressed sodium channel current-dependent parameters causing a reduction of maximum rate of rise of the action potential upstroke, a prolongation of the effective refractory period secondary to the development of postrepolarization refractoriness, and an increase in diastolic threshold of excitation and atrial conduction time. Ranolazine did not significantly alter these parameters or promote arrhythmias in the ventricles. Ranolazine produced greater inhibition of peak sodium channel current in atrial cells isolated from HF versus normal dogs. A single premature beat reproducibly induced self-terminating AF in 10 of 17 atria. Ranolazine (5 μmol/L) suppressed induction of AF in 7 of 10 (70%) atria. In the remaining 3 atria, ranolazine reduced frequency and duration of AF. Our results demonstrate more potent suppression of AF by ranolazine in the setting of HF than previously demonstrated in nonfailing hearts and absence of ventricular proarrhythmia. The data suggest that ranolazine may be of benefit as an alternative to amiodarone and dofetilide in the management of AF in patients with HF. © 2014 American Heart Association, Inc.

Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

PubMed

Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

2017-10-01

Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Long-term outcome of surgical cryoablation for refractory ventricular tachycardia in patients with non-ischemic cardiomyopathy.

PubMed

Liang, Jackson J; Betensky, Brian P; Muser, Daniele; Zado, Erica S; Anter, Elad; Desai, Nimesh D; Callans, David J; Deo, Rajat; Frankel, David S; Hutchinson, Mathew D; Lin, David; Riley, Michael P; Schaller, Robert D; Supple, Gregory E; Santangeli, Pasquale; Acker, Michael A; Bavaria, Joseph E; Szeto, Wilson Y; Vallabhajosyula, Prashanth; Marchlinski, Francis E; Dixit, Sanjay

2018-03-01

Limited data exist on the long-term outcome of patients (pts) with non-ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to conventional therapies undergoing surgical ablation (SA). We aimed to investigate the long-term survival and VT recurrence in NICM pts with VT refractory to radiofrequency catheter ablation (RFCA) who underwent SA. Consecutive pts with NICM and VT refractory to RFCA who underwent SA were included. VT substrate was characterized in the electrophysiology lab and targeted by RFCA. During SA, previous RFCA lesions/scars were identified and targeted with cryoablation (CA; 3 min/lesion; target -150 °C). Follow-up comprised office visits, ICD interrogations and the social security death index. Twenty consecutive patients with NICM who underwent SA (age 53 ± 16 years, 18 males, LVEF 41 ± 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3, hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied. Percutaneous mapping/ablation in the electrophysiology lab was performed in 18 and 2 pts had primary SA. During surgery, 4.9 ± 4.0 CA lesions/pt were delivered to the endocardium (2) and epicardium (11) or both (7). VT-free survival was 72.5% at 1 year and over 43 ± 31 months (mos) (range 1-83mos), there was only one arrhythmia-related death. There was a significant reduction in ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 ± 4.9 vs. 2.3 ± 4.3 shocks/pt, P = 0.001). In select pts with NICM and VT refractory to RFCA, SA guided by pre-operative electrophysiological mapping and ablation may be a therapeutic option. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Growth Factor-Induced Mobilization of Cardiac Progenitor Cells Reduces the Risk of Arrhythmias, in a Rat Model of Chronic Myocardial Infarction

PubMed Central

Graiani, Gallia; Rossi, Stefano; Agnetti, Aldo; Stillitano, Francesca; Lagrasta, Costanza; Baruffi, Silvana; Berni, Roberta; Frati, Caterina; Vassalle, Mario; Squarcia, Umberto; Cerbai, Elisabetta; Macchi, Emilio; Stilli, Donatella; Quaini, Federico; Musso, Ezio

2011-01-01

Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs) appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI), lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60) or vehicle (V, n = 55), or sham operated (n = 18). In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP) without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration of mechanical function. In conclusion, local injection of GFs ameliorates electromechanical competence in chronic MI. Reduced arrhythmogenesis is attributable to prolongation of ERP resulting from improved intercellular coupling via increased expression of connexin43, and attenuation of unfavorable remodeling. PMID:21445273

Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling.

PubMed

Elvan, A; Wylie, K; Zipes, D P

1996-12-01

We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

Double simultaneous defibrillators for refractory ventricular fibrillation.

PubMed

Leacock, Benjamin W

2014-04-01

Out-of-hospital cardiac arrest is a leading cause of death in the United States. Ventricular fibrillation (VF) is the most common initial rhythm after cardiac arrest. To describe a novel approach to the patient with intractable VF after cardiac arrest. A 51-year old man presented in cardiac arrest after a ST-elevation myocardial infarction. He remained in VF despite receiving typical therapy including cardiopulmonary resuscitation, amiodarone, lidocaine, epinephrine, and five attempts at defibrillation with 200 J using a biphasic defibrillator. VF was eventually terminated with 400 J by the simultaneous use of two biphasic defibrillators. The patient had a full recovery. We present a case and supportive literature for a novel treatment of high-energy defibrillation in a patient with refractory VF. Copyright © 2014 Elsevier Inc. All rights reserved.

Hemodynamic Performance of a Novel Right Ventricular Assist Device (PERKAT).

PubMed

Kretzschmar, Daniel; Schulze, P Christian; Ferrari, Markus W

Acute right ventricular failure (RVF) is an increasing clinical problem and a life-threatening condition. Right ventricular assist devices represent a reasonable treatment option for patients with refractory RVF. We here present a novel percutaneously implantable device for right ventricular support. The PERKAT device is based on a nitinol stent cage, which is covered with valve-carrying foils. A flexible outlet trunk with a pigtail tip is connected to the distal part. The device is driven by an intra-aortic balloon pump (IABP) drive unit, which inflates/deflates a standard IABP-balloon placed within the stent cage. In-vitro evaluation was done in a liquid bath containing water or blood analog. The PERKAT device was tested in different afterload settings using two different IABP-balloons and varying inflation/deflation rates. We detected flow rates ranging from 1.97 to 3.93 L/min depending on the afterload setting, inflation/deflation rate, balloon size, and the medium used. Flow rates between water and blood analog were nearly comparable, and in the higher inflation/deflation rate settings slightly higher with water. Based on this promising in vitro data, the innovative percutaneously implantable PERKAT device has a potential to become a therapeutic option for patients with RVF refractory to medical treatment.

[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

PubMed

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.

PubMed

Joy, George; Whiskey, Eromona; Bolstridge, Mark; Porras-Segovia, Alejandro; McDonagh, Theresa A; Plymen, Carla M; Shergill, Sukhi S

2017-12-01

Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

PubMed

Xiong, Liang; Liu, Yu; Zhou, Mingmin; Wang, Guangji; Quan, Dajun; Shen, Caijie; Shuai, Wei; Kong, Bin; Huang, Congxin; Huang, He

2018-05-31

The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Optimal ECG Electrode Sites and Criteria for Detection of Asymptomatic Coronary Artery Disease at Rest and with Exercise.

DTIC Science & Technology

1985-12-01

dilating during peak workloads. By preventing dilation , circum- ferential atherosclerosis, even if minimal on angiography, can profoundly reduce myocardial...Depolarization on Refractoriness of Ischemic Canine Myocardium, J. Electrocardiol. 15(4):335, 1982. 127. Burgess, M.J., Green, L.S., Millar, K., Wyatt, R...Sympathetic Stimulation on Refractory Periods of Ischemic Canine Ventricular Myocardium, J. Electrocardiol. 15(1):1, 1982. 129. Burgess, M.J., Lux, R.L

T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

PubMed

Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

2015-02-01

In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electrical stimulation-based renal nerve mapping exacerbates ventricular arrhythmias during acute myocardial ischaemia.

PubMed

Huang, Bing; Zhou, Xiaoya; Wang, Menglong; Li, Xuefei; Zhou, Liping; Meng, Guannan; Wang, Yuhong; Wang, Zhuo; Wang, Songyun; Yu, Lilei; Jiang, Hong

2018-06-01

Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS. In another 20 acute myocardial infarction (AMI) canines, RNS (Group 3, n = 10) or sham RNS (Group 4, n = 10) was intermittently (1 min ON and 4 min OFF) performed for 1 h following AMI induction. The LSGNA and AMI-induced ventricular arrhythmias were analysed. In normal and HMI canines, although transient RNS significantly increased the LSGNA and facilitated the action potential duration (APD) alternans, it did not induce any ventricular arrhythmias and did not change the ventricular effective refractory period, APD or maximum slope of the APD restitution curve. In AMI canines, transient RNS significantly exacerbated LSG activation and promoted the incidence of ventricular arrhythmias. Transient RNS did not increase the risk of ventricular arrhythmias in normal or HMI hearts, but it significantly promoted the occurrence of ventricular arrhythmias in AMI hearts. Therefore, electrical stimulation-based renal nerve mapping may be unsafe in AMI patients and in patients with a high risk for malignant ventricular arrhythmias.

[Catheter ablation in patients with refractory cardiac arrhythmias with radiofrequency techniques].

PubMed

de Paola, A A; Balbão, C E; Silva Netto, O; Mendonça, A; Villacorta, H; Vattimo, A C; Souza, I A; Guiguer Júnior, N; Portugal, O P; Martinez Filho, E E

1993-02-01

evaluate the efficacy of radiofrequency catheter ablation in patients with refractory cardiac arrhythmias. twenty patients with refractory cardiac arrhythmias were undertaken to electrophysiologic studies for diagnosis and radiofrequency catheter ablation of their reentrant arrhythmias. Ten patients were men and 10 women with ages varying from 13 to 76 years (mean = 42.4 years). Nineteen patients had supraventricular tachyarrhythmias: One patient had atrial tachycardia and 1 atrial fibrillation with rapid ventricular rate, 5 patients had reentrant nodal tachycardia, 12 patients had reentrant atrioventricular tachycardia and 1 patient had right ventricular outflow tract tachycardia. the mean time of the procedure was 4.1 hours. The radiofrequency current energy applied was 40-50 V for 30-40 seconds. Ablation was successful in 18/20 (90%) patients; in 15/18 (83%) of successfully treated patients the same study was done for diagnosis and radiofrequency ablation. One patient had femoral arterial occlusion and was treated with no significant sequelae. During a mean follow-up of 4 months no preexcitation or reentrant tachycardia occurred. the results of our experience with radiofrequency catheter ablation of cardiac arrhythmias suggest that this technique can benefit an important number of patients with cardiac arrhythmias.

Minnesota Resuscitation Consortium's Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital Refractory Ventricular Fibrillation.

PubMed

Yannopoulos, Demetris; Bartos, Jason A; Martin, Cindy; Raveendran, Ganesh; Missov, Emil; Conterato, Marc; Frascone, R J; Trembley, Alexander; Sipprell, Kevin; John, Ranjit; George, Stephen; Carlson, Kathleen; Brunsvold, Melissa E; Garcia, Santiago; Aufderheide, Tom P

2016-06-13

In 2015, the Minnesota Resuscitation Consortium (MRC) implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out-of-hospital refractory ventricular fibrillation/ventricular tachycardia (VF/VT). We report the outcomes of the initial 3-month period of operations. Three emergency medical services systems serving the Minneapolis-St. Paul metro area participated in the protocol. Inclusion criteria included age 18 to 75 years, body habitus accommodating automated Lund University Cardiac Arrest System (LUCAS) cardiopulmonary resuscitation (CPR), and estimated transfer time from the scene to the cardiac catheterization laboratory of ≤30 minutes. Exclusion criteria included known terminal illness, Do Not Resuscitate/Do Not Intubate status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained return of spontaneous circulation after treatment with 3 direct current shocks and administration of 300 mg of intravenous/intraosseous amiodarone. Patients were transported to the University of Minnesota, where emergent advanced perfusion strategies (extracorporeal membrane oxygenation; ECMO), followed by coronary angiography and primary coronary intervention (PCI), were performed, when appropriate. Over the first 3 months of the protocol, 27 patients were transported with ongoing mechanical CPR. Of these, 18 patients met the inclusion and exclusion criteria. ECMO was placed in 83%. Seventy-eight percent of patients had significant coronary artery disease with a high degree of complexity and 67% received PCI. Seventy-eight percent of patients survived to hospital admission and 55% (10 of 18) survived to hospital discharge, with 50% (9 of 18) achieving good neurological function (cerebral performance categories 1 and 2). No significant ECMO-related complications were encountered. The MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

d,l-Sotalol reverses abbreviated atrial refractoriness and prevents promotion of atrial fibrillation in a canine model with left ventricular dysfunction induced by atrial tachypacing.

PubMed

Sakamoto, Tamotsu; Fujiki, Akira; Nakatani, Yosuke; Sakabe, Masao; Mizumaki, Koichi; Hashimoto, Norio; Inoue, Hiroshi

2009-10-01

This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction. Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 +/-4 and Sotalol 126 +/-5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes. d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA in an ATP-induced canine AF model.

Ablation and pacing: improving brain perfusion and cognitive function in patients with atrial fibrillation and uncontrolled ventricular rates.

PubMed

Efimova, Irina; Efimova, Nataliya; Chernov, Vladimir; Popov, Sergey; Lishmanov, Yuri

2012-03-01

The aim of our study was to determine if ablation and pacing improved brain perfusion (BP) and cognitive function (CF) in patients with medically refractory rapidly conducted atrial fibrillation (Med Refr RCAF). The study included 17 patients with Med Refr RCAF (average age 55.3 ± 4.5 years). All patients underwent brain single photon emission computed tomography scanning with (99m) Tc-hexamethylpropylene amine oxime and comprehensive neuropsychological testing before and after 3 months following pacemaker implantation. The BP was significantly lower in all regions in patients with Med Refr RCAF compared with the control group. The greatest BP decrease was revealed in the inferior frontal (P = 0.002) and posterior parietal (P = 0.024) brain regions. These patients showed cognitive deficit in 94%. There was a direct correlation between BP and CF parameters. Ablation followed by pacemaker implantation had a positive effect on BP and CF in all patients with Med Refr RCAF. Thus, BP increased in the right inferior frontal (P = 0.01), in the left superior frontal (P = 0.007), and in the left temporal (P = 0.005) cortex. These patients demonstrated improvements in immediate and delayed verbal memory, immediate and delayed visual memory, abstract mentation, attention, psychomotor speed, as well as in learning. Patients with atrial fibrillation and rapid ventricular rates refractory to medical treatment have marked signs of brain hypoperfusion and impaired CF. Ablation and pacing improve left ventricular systolic function, thereby increasing BP and improving CF. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

[Radioisotopic mapping of the arrhythmogenic focus in patients with chronic chagasic cardiomyopathy and sustained ventricular tachycardia].

PubMed

de Paola, A A; Balbão, C E; Castiglioni, M L; Barbieri, A; Mendonça, A; Netto, O S; Guiguer Júnior, N; Vattimo, A C; Souza, I A; Portugal, O P

1993-06-01

To localize the site of the origin of sustained ventricular tachycardia in chronic chagasic cardiomyopathy patients refractory to antiarrhythmic therapy by radionuclide angiography techniques. Five patients underwent radionuclide angiography by intravenous administration of 25mCi 99mTc. The images were obtained in sinus rhythm and during sustained ventricular tachycardia induced in the electrophysiologic laboratory for endocardial mapping. Amplitude and phase images were obtained resulting in a contraction wave synchronic to ventricular dispolarization. All patients had haemodynamic stability during the arrhythmia. One patient had incessant ventricular tachycardia. Mean ejection fraction was 0.38. In 4 patients the site of the origin of ventricular tachycardia was posterior and in one it was localized in the interventricular septum. There was identity in the site of the origin of ventricular tachycardia obtained by endocardial mapping or radionuclide angiography in all patients. The therapy was chemical ablation in 3 patients, surgical aneurysmectomy in one and pharmacologic therapy in the last patient. The site of the origin of ventricular tachycardia can be estimated by analyzing the contraction wave obtained by radionuclide angiography techniques in patients with hemodynamic stable sustained ventricular tachycardia.

[Effectiveness of nasal positive pressure ventilation in the management of acute refractory left ventricular insufficiency].

PubMed

Chesi, G; Pinelli, G; Galimberti, D; Navazio, A; Montanari, P

1994-04-01

Ehen refractory to optimal medical treatment cardiogenic pulmonary edema requires mechanical ventilation as a last therapeutic resource. In recent years an increasing number of authors reported their experience in the management of acute or subacute respiratory failure with non-invasive mechanical ventilation by nasal mask. Encouraged by the first promising results reported in literature we experimented this new therapeutic tool in a first group of seven elderly patients (mean age: 76.57--range: 65-89); they all had been admitted for severe cardiogenic pulmonary edema unresponsive to maximal doses of the conventional drugs available for treating acute decompensated heart failure. The enrolled patients were treated with intermittent ventilation administered by nasal mask at selected values of inspiratory positive airway pressure (IPAP) that were comprised between 10 and 20 cm H2O. At the same time an expiratory positive airway pressure (EPAP) at values comprised between 3 and 8 cm H2O was applied. Ventilation was continued for variable periods of 3-24 hours until acceptable values of PaO2 and PaCO2 were obtained. The ventilation modality was spontaneous, spontaneous-time or timed depending on the patients' level of consciousness at starting time. A good short-term outcome was achieved in all the patients regardless of the ventilation modality applied. The main blood gas alteration was severe hypercapnia with acidosis in three patients, while the other four presented critical hypoxemia unresponsive to simple oxygen supply even if delivered by high-flow Venturi mask. Four of our seven patients were discharged from hospital in satisfactory haemodynamic conditions; the remaining three died during hospitalization from refractory heart failure. In this our preliminary experience the therapeutic approach with nasal positive pressure ventilation (NPPV) and EPAP proved to be very effective to improve the signs and symptoms of acute refractory cardiogenic pulmonary edema as it avoided the need of invasive mechanical ventilation. It was well tolerated by all our patients; besides it was not difficult to use or time-consuming for physician and nurses. On the other hand it didn't modify our patients' medium or long-time prognosis which was strictly related to their preexisting left ventricular pump derangement.

Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

PubMed

Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

2008-09-01

Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

CSF Lumbar Drainage: A Safe Surgical Option in Refractory Intracranial Hypertension Associated with Acute Posttraumatic External Hydrocephalus.

PubMed

Manet, R; Schmidt, E A; Vassal, F; Charier, D; Gergelé, L

2016-01-01

External lumbar drainage (ELD) of cerebrospinal fluid (CSF) in posttraumatic refractory intracranial hypertension (ICHT) is controversial. We report our experience of ELD in ICHT associated with acute disturbance of CSF flow within subarachnoid spaces (SASs). Four adult patients admitted to the neurointensive care unit for severe TBI who presented with secondary ICHT are retrospectively reported. When refractory to second-tier therapy, if external ventricular drainage were not possible or failed, and in the absence of an indication for craniotomy to treat a mass lesion or decompressive craniectomy, we assessed the evolution of CSF volume within cranial SAS and checked the presence of basal cisterns and the absence of tonsillar herniation to evaluate interest in and the safety of ELD. As second-tier therapy failed to lower intracranial pressure (ICP; mean ICP 37 ± 5 mmHg), and computed tomography (CT) showed abnormally enlarged cranial SAS following traumatic subarachnoid hemorrhage, patients received ELD. ICP decreased, with immediate and long-term effect (mean ICP 5 mmHg ± 2 mmHg). There were no complications to report. Acute traumatic external hydrocephalus may explain some of the specific situations of secondary increased ICP, with a "normal" CT scan, that is refractory to medical treatment. In these situations, lumbar drainage should be considered to be a safe, minimally invasive, and effective surgical option.

Intrathecal chemotherapy for refractory disseminated medulloblastoma.

PubMed

Yoshimura, Junichi; Nishiyama, Kenichi; Mori, Hiroshi; Takahashi, Hideaki; Fujii, Yukihiko

2008-05-01

To analyze the effect of intrathecal (IT) chemotherapy for disseminated medulloblastoma. Twenty-one patients received IT chemotherapy using the chemotherapeutic agents of methotrexate (MTX) and nitrosoureas (ACNU, MCNU) including nine patients for residual leptomeningeal lesions after initial surgery and radiation, and 12 for a recurrence with leptomeningeal dissemination. Of these 21 patients, 12 received a lumbar and/or ventricular bolus injection of the chemotherapeutic agents, one received the ventriculolumbar perfusion of the agents, and eight received both the perfusion and bolus injection. The doses ranged from 6-7 mg/m(2) of ACNU for perfusion and 3-3.5 mg/m(2) of ACNU, MCNU, or MTX for the bolus injection, and the cycles were administered from 3 to 12 times for perfusion and from 5 to 54 times for the bolus injection. The effects of chemotherapy were assessed by both radiological and cytological examinations, and the clinical symptoms were also assessed. Radiological and/or cytological responses were observed in 10 of 21 patients (47.6%), including seven cases demonstrating a complete remission. The 5-year overall survival rate and 5-year survival rate after dissemination were 61.5 and 46.4%, respectively. Five patients who received a lumbar bolus injection of nitrosoureas experienced paraplegia and double incontinence. One patient who received a ventricular injection of nitrosoureas experienced truncal ataxia. IT chemotherapy was found to be effective in some cases with refractory disseminated medulloblastoma and it seems to be an appropriate treatment choice for leptomeningeal recurrence. However, the frequent bolus injections of nitrosoureas should be avoided to prevent the side effects.

Right ventricular longitudinal strain and right ventricular stroke work index in patients with severe heart failure: left ventricular assist device suitability for transplant candidates.

PubMed

Cameli, M; Bernazzali, S; Lisi, M; Tsioulpas, C; Croccia, M G; Lisi, G; Maccherini, M; Mondillo, S

2012-09-01

Right ventricular (RV) systolic function has a critical role in determining the clinical outcome and the success of using left ventricular assist devices in patients with refractory heart failure. RV deformation analysis by speckle tracking echocardiography (STE) has recently allowed the analysis of RV longitudinal function. Using cardiac catheterization as the reference standard, this study aimed to explore the correlation between RV longitudinal function by STE and RV stroke work index (RVSWI) among patients referred for cardiac transplantation. Right heart catheterization and transthoracic echo-Doppler were simultaneously performed in 47 patients referred for cardiac transplant assessment due to refractory heart failure (ejection fraction 25.1 ± 4.5%). Thermodilution RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging RV free-wall segments (free-wall RVLS). We also calculated. Tricuspid S' and tricuspid annular plane systolic excursion (TAPSE). No significant correlation was observed for TAPSE on tricuspid S' with RV stroke volume (r = 0.14 and r = 0.06, respectively). A close negative correlation between free-wall RVLS and RVSWI was found (r = -0.82; P < .0001). Furthermore, free-wall RVLS showed the highest diagnostic accuracy (area under the curve of 0.90) with good sensitivity and specificity of 95% and 91%, respectively, to predict depressed RVSWI using a cutoff value less than -11.8%. Among patients referred for heart transplantation, TAPSE and tricuspid S' did not correlate with invasively obtained RVSWI. RV longitudinal deformation analysis by STE correlated with RVSWI, providing a better estimate of RV systolic performance. Copyright © 2012 Elsevier Inc. All rights reserved.

Amiodarone Versus Lidocaine for Pediatric Cardiac Arrest Due to Ventricular Arrhythmias: A Systematic Review.

PubMed

McBride, Mary E; Marino, Bradley S; Webster, Gregory; Lopez-Herce, Jesús; Ziegler, Carolyn P; De Caen, Allan R; Atkins, Dianne L

2017-02-01

We performed a systematic review as part of the International Liaison Committee on Resuscitation process to create a consensus on science statement regarding amiodarone or lidocaine during pediatric cardiac arrest for the 2015 International Liaison Committee on Resuscitation's Consensus on Science and Treatment Recommendations. Studies were identified from comprehensive searches in PubMed, Embase, and the Cochrane Library. Studies eligible for inclusion were randomized controlled and observational studies on the relative clinical effect of amiodarone or lidocaine in cardiac arrest. Studies addressing the clinical effect of amiodarone versus lidocaine were extracted and reviewed for inclusion and exclusion criteria by the reviewers. Studies were rigorously analyzed thereafter. We identified three articles addressing lidocaine versus amiodarone in cardiac arrest: 1) a prospective study assessing lidocaine versus amiodarone for refractory ventricular fibrillation in out-of-hospital adults; 2) an observational retrospective cohort study of inpatient pediatric patients with ventricular fibrillation or pulseless ventricular tachycardia who received lidocaine, amiodarone, neither or both; and 3) a prospective study of ventricular tachycardia with a pulse in adults. The first study showed a statistically significant improvement in survival to hospital admission with amiodarone (22.8% vs 12.0%; p = 0.009) and a lack of statistical difference for survival at discharge (p = 0.34). The second article demonstrated 44% return of spontaneous circulation for amiodarone and 64% for lidocaine (odds ratio, 2.02; 1.36-3.03) with no statistical difference for survival at hospital discharge. The third article demonstrated 48.3% arrhythmia termination for amiodarone versus 10.3% for lidocaine (p < 0.05). All were classified as lower quality studies without preference for one agent. The confidence in effect estimates is so low that International Liaison Committee on Resuscitation felt that a recommendation to use of amiodarone over lidocaine is too speculative; we suggest that amiodarone or lidocaine can be used in the setting of pulseless ventricular tachycardia/ventricular fibrillation in infants and children.

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans.

PubMed

Zimerman, L I; Liberman, A; Castro, R R T; Ribeiro, J P; Nóbrega, A C L

2010-02-01

The cardiovascular electrophysiologic basis for the action of pyridostigmine, an acetylcholinesterase inhibitor, has not been investigated. The objective of the present study was to determine the cardiac electrophysiologic effects of a single dose of pyridostigmine bromide in an open-label, quasi-experimental protocol. Fifteen patients who had been indicated for diagnostic cardiac electrophysiologic study underwent two studies just before and 90-120 min after the oral administration of pyridostigmine (45 mg). Pyridostigmine was well tolerated by all patients. Wenckebach nodal anterograde atrioventricular point and basic cycle were not altered by pyridostigmine. Sinus recovery time (ms) was shorter during a 500-ms cycle stimulation (pre: 326 +/- 45 vs post: 235 +/- 47; P = 0.003) but not during 400-ms (pre: 275 +/- 28 vs post: 248 +/- 32; P = 0.490) or 600-ms (pre: 252 +/- 42 vs post: 179 +/- 26; P = 0.080) cycle stimulation. Pyridostigmine increased the ventricular refractory period (ms) during the 400-ms cycle stimulation (pre: 238 +/- 7 vs post: 245 +/- 9; P = 0.028) but not during the 500-ms (pre: 248 +/- 7 vs post: 253 +/- 9; P = 0.150) or 600-ms (pre: 254 +/- 8 vs post: 259 +/- 8; P = 0.255) cycle stimulation. We conclude that pyridostigmine did not produce conduction disturbances and, indeed, increased the ventricular refractory period at higher heart rates. While the effect explains previous results showing the anti-arrhythmic action of pyridostigmine, the clinical impact on long-term outcomes requires further investigation.

T-tubule Disruption Promotes Calcium Alternans in Failing Ventricular Myocytes: Mechanistic Insights from Computational Modeling

PubMed Central

Nivala, Michael; Song, Zhen; Weiss, James N.; Qu, Zhilin

2015-01-01

In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the mechanisms of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in “orphaned” RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. PMID:25450613

Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis

PubMed Central

Campanile, Alfonso; Sozzi, Fabiola B; Canetta, Ciro; Danzi, Gian Battista

2013-01-01

A 62-year-old woman with multiple myeloma and light-chain amyloidosis with significant heart involvement developed an in-hospital cardiac arrest. After cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage was restored, and the patient was admitted to the coronary care unit. A cardioverter-defibrillator was implanted, and it successfully intervened in two sustained ventricular tachycardia episodes and one ventricular fibrillation episode, which were recorded during hospitalization. After achieving discrete cardiac compensation, the patient was transferred to the emergency medicine department where she underwent chemotherapy for multiple myeloma. The patient died 40 days after admission from refractory heart failure. In the literature, there are studies that describe the use of cardioverter-defibrillator implantation in cardiac amyloidosis; however, at present, there is no evidence of a beneficial effect on survival with the use of this intervention. A high index of suspicion for amyloid heart disease and early diagnosis are critical to improving outcomes. PMID:24294034

Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis.

PubMed

Campanile, Alfonso; Sozzi, Fabiola B; Canetta, Ciro; Danzi, Gian Battista

2013-01-01

A 62-year-old woman with multiple myeloma and light-chain amyloidosis with significant heart involvement developed an in-hospital cardiac arrest. After cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage was restored, and the patient was admitted to the coronary care unit. A cardioverter-defibrillator was implanted, and it successfully intervened in two sustained ventricular tachycardia episodes and one ventricular fibrillation episode, which were recorded during hospitalization. After achieving discrete cardiac compensation, the patient was transferred to the emergency medicine department where she underwent chemotherapy for multiple myeloma. The patient died 40 days after admission from refractory heart failure. In the literature, there are studies that describe the use of cardioverter-defibrillator implantation in cardiac amyloidosis; however, at present, there is no evidence of a beneficial effect on survival with the use of this intervention. A high index of suspicion for amyloid heart disease and early diagnosis are critical to improving outcomes.

Thoracic Epidural Anesthesia Can Be Effective for the Short-Term Management of Ventricular Tachycardia Storm.

PubMed

Do, Duc H; Bradfield, Jason; Ajijola, Olujimi A; Vaseghi, Marmar; Le, John; Rahman, Siamak; Mahajan, Aman; Nogami, Akihiko; Boyle, Noel G; Shivkumar, Kalyanam

2017-10-27

Novel therapies aimed at modulating the autonomic nervous system, including thoracic epidural anesthesia (TEA), have been shown in small case series to be beneficial in treating medically refractory ventricular tachycardia (VT) storm. However, it is not clear when these options should be considered. We reviewed a multicenter experience with TEA in the management of VT storm to determine its optimal therapeutic use. Data for 11 patients in whom TEA was instituted for VT storm between July 2005 and March 2016 were reviewed to determine the clinical characteristics, outcomes, and role in management. The clinical presentation was incessant VT in 7 (64%), with polymorphic VT in 3 (27%) and monomorphic VT in 8 (73%). The underlying conditions were nonischemic cardiomyopathy in 5 (45%), ischemic cardiomyopathy in 3 (27%), and hypertrophic cardiomyopathy, Brugada syndrome, and cardiac lipoma in 1 (9%) each. Five (45%) had a complete and 1 (9%) had a partial response to TEA; 4 of the complete responders had incessant VT. All 4 patients with a documented response to deep sedation demonstrated a complete response to TEA. More than half of the patients with VT storm in our series responded to TEA. TEA may be effective and should be considered as a therapeutic option in patients with VT storm, especially incessant VT, who are refractory to initial management. Improvement in VT burden with deep sedation may suggest that sympathoexcitation plays a key role in perpetuating VT and predict a positive response to TEA. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Acute refractory hypoxemia after chest trauma reversed by high-frequency oscillatory ventilation: a case report

PubMed Central

2013-01-01

Introduction Polytrauma often results in significant hypoxemia secondary to direct lung contusion or indirectly through atelectasis, systemic inflammatory response, large volume fluid resuscitation and blood product transfusion. In addition to causing hypoxemia, atelectasis and acute lung injury can lead to right ventricular failure through an acute increase in pulmonary vascular resistance. Mechanical ventilation is often applied, accompanied with recruitment maneuvers and positive end-expiratory pressure in order to recruit alveoli and reverse atelectasis, while preventing excessive alveolar damage. This strategy should lead to the reversal of the hypoxemic condition and the detrimental heart–lung interaction that may occur. However, as described in this case report, hemodynamic instability and intractable alveolar atelectasis sometimes do not respond to conventional ventilation strategies. Case presentation We describe the case of a 21-year-old Caucasian man with severe chest trauma requiring surgical interventions, who developed refractory hypoxemia and overt right ventricular failure. After multiple failed attempts of recruitment using conventional ventilation, the patient was ventilated with high-frequency oscillatory ventilation. This mode of ventilation allowed the reversal of the hemodynamic effects of severe hypoxemia and of the acute cor pulmonale. We use this case report to describe the physiological advantages of high-frequency oscillatory ventilation in patients with chest trauma, and formulate the arguments to explain the positive effect observed in our patient. Conclusions High-frequency oscillatory ventilation can be used in the context of a blunt chest trauma accompanied by severe hypoxemia due to atelectasis. The positive effect is due to its capacity to recruit the collapsed alveoli and, as a result, the relief of increased pulmonary vascular resistance and subsequently the reversal of acute cor pulmonale. This approach may represent an alternative in case of failure of the conventional ventilation strategy. PMID:23855954

In vivo and in vitro antiarrhythmic effects of SSR149744C in animal models of atrial fibrillation and ventricular arrhythmias.

PubMed

Gautier, Patrick; Serre, Martine; Cosnier-Pucheu, Sylvie; Djandjighian, Laurent; Roccon, Alain; Herbert, Jean-Marc; Nisato, Dino

2005-02-01

SSR149744C (2-butyl-3-{4-[3-(dibutylamino)propyl]benzoyl}-1-benzofuran-5-carboxylate isopropyl fumarate) is a new noniodinated benzofuran derivative structurally related to amiodarone and dronedarone that is currently undergoing clinical trials as an antiarrhythmic agent. As SSR149744C exhibits electrophysiological and hemodynamic properties of class I, II, III, and IV antiarrhythmic agents, the aim of this study was to evaluate its acute intravenous (IV) or oral (PO) antiarrhythmic activities in in vitro and in vivo animal models of atrial and ventricular arrhythmias. In vagally induced atrial fibrillation (AF) in anesthetized dogs, SSR149744C (3 and 10 mg/kg IV) terminated AF in all 7 dogs and prevented reinduction in 4 out of 7 dogs; effective refractory periods of right atrium were dose-dependently and frequency-independently lengthened. In low-K+ medium-induced AF models, SSR149744C (0.1 to 1 microM) prevented AF in isolated guinea pig hearts in a concentration-dependent manner. At the ventricular level, SSR149744C (0.1 to 10 mg/kg IV and 3 to 90 mg/kg PO) prevented reperfusion-induced arrhythmias in anesthetized rats with a dose-effect relationship, and, at doses of 30 to 90 mg/kg PO, it reduced early (0-24 hours) mortality following permanent left coronary artery ligature in conscious rats. The present results show that SSR149744C is an effective antiarrhythmic agent in atrial fibrillation and in ventricular arrhythmias. Like amiodarone and dronedarone, its efficiency in these animal models of arrhythmias is likely be related to its multifactorial mechanism of action.

Electrophysiological and mechanical effects of caffeic acid phenethyl ester, a novel cardioprotective agent with antiarrhythmic activity, in guinea-pig heart.

PubMed

Chang, Gwo-Jyh; Chang, Chi-Jen; Chen, Wei-Jan; Yeh, Yung-Hsin; Lee, Hsiao-Yu

2013-02-28

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that exhibits cardioprotective and antiarrhythmic effects. The detailed mechanisms underlying these effects, however, are not entirely understood. The aim of this study was to elucidate the electromechanical effects of CAPE in guinea-pig cardiac preparations. Intracardiac electrograms, left ventricular (LV) pressure, and the anti-arrhythmic efficacy were determined using isolated hearts. Action potentials of papillary muscles were assessed with microelectrodes, Ca(2+) transients were measured by fluorescence, and ion fluxes were measured by patch-clamp techniques. In a perfused heart model, CAPE prolonged the atrio-ventricular conduction interval, the Wenckebach cycle length, and the refractory periods of the AV node and His-Purkinje system, while shortening the QT interval. CAPE reduced the occurrence of reperfusion-induced ventricular fibrillation and decreased LV pressure in isolated hearts. In papillary muscles, CAPE shortened the action potential duration and reduced both the maximum upstroke velocity and contractile force. In fura-2-loaded single ventricular myocytes, CAPE decreased cell shortening and the Ca(2+) transient amplitude. Patch-clamp experiments revealed that CAPE produced a use-dependent decrease in L-type Ca(2+) current (ICa,L) (IC50=1.1 μM) and Na(+) current (INa) (IC50=0.43 μM), caused a negative-shift of the voltage-dependent inactivation and a delay of recovery from inactivation. CAPE decreased the delayed outward K(+) current (IK) slightly, without affecting the inward rectifier K(+) current (IK1). These results suggest that the preferential inhibition of Ca(2+) inward and Na(+) inward currents by CAPE may induce major electromechanical alterations in guinea-pig cardiac preparations, which may underlie its antiarrhythmic action. Copyright © 2013 Elsevier B.V. All rights reserved.

First pediatric transatlantic air ambulance transportation on a Berlin Heart EXCOR left ventricular assist device as a bridge to transplantation.

PubMed

Tissot, Cecile; Buchholz, Holger; Mitchell, Max B; da Cruz, Eduardo; Miyamoto, Shelley D; Pietra, Bill A; Charpentier, Arnaud; Ghez, Olivier

2010-03-01

Mechanical circulatory devices are indicated in patients with refractory cardiac failure as a bridge to recovery or to transplantation. Whenever required, transportation while on mechanical support is a challenge and still limited by technical restrictions or distance. We report the first pediatric case of transatlantic air transportation on a Berlin Heart EXCOR ventricular assist device (Berlin Heart, Berlin, Germany) of a 13-yr-old American female who presented in cardiogenic shock with severe systolic dysfunction while vacationing in France. Rapid hemodynamic deterioration occurred despite maximal medical treatment, and she was supported initially with extracorporeal membrane oxygenation converted to a Berlin Heart EXCOR left ventricular assist device. Long-distance air transportation of the patient was accomplished 3 wks after implantation from Marseille, France, to Denver, Colorado. No adverse hemodynamic effects were encountered during the 13.5-hr flight (8770 km). The patient did not recover sufficient cardiac function and underwent successful orthotopic heart transplantation 3 months after the initial event. Our experience suggests that long-distance air transportation of pediatric patients using the Berlin Heart EXCOR mobile unit as a bridge to recovery or transplantation is feasible and appears safe.

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia.

PubMed

Kingma, J G; Linderoth, B; Ardell, J L; Armour, J A; DeJongste, M J; Foreman, R D

2001-08-13

Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

Reduction of atrial fibrillation by Tanshinone IIA in chronic heart failure.

PubMed

He, Zhifeng; Sun, Changzheng; Xu, Yi; Cheng, Dezhi

2016-12-01

The aim of the present study was to confirm the effect of Tanshinone IIA (TAN) on the prevention of AF in chronic heart failure (CHF), and to elucidate the underlying electrophysiological mechanisms for the antiarrhythmic effects of TAN at the level of the atrium in an experimental model of CHF. In 10 female rabbits, CHF was induced by rapid ventricular pacing, leading to a significant decrease in ejection fraction in the presence of a dilated left ventricle and atrial enlargement. Twelve rabbits were sham-operated and served as controls. Isolated hearts were perfused using the Langendorff method. Burst pacing was used to induce AF. Monophasic action potential recordings showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts compared with sham hearts. Infusion of acetylcholine (1μm) and isoproterenol (1μm) led to AF in all failing hearts and in 11 sham hearts. Simultaneous infusion of TAN (10μm) remarkably reduced inducibility of AF in 50% of sham and 50% of failing hearts. TAN had no effect on aAPD but significantly increased aERP, leading to a marked increase in atrial post-repolarization refractoriness. Moreover, TAN application moderately increased interatrial conduction time. TAN has been shown to be effective in reducing the inducibility of AF in an experimental model of AF. The antiarrhythmic effect is mainly due to prolongations of atrial post-repolarization refractoriness and a moderate increase in interatrial conduction time. Copyright © 2016. Published by Elsevier Masson SAS.

Applications of laser in ischemic heart disease in China

NASA Astrophysics Data System (ADS)

Chen, Mingzhe; Zhang, Yongzhen

1999-09-01

Current data demonstrate that laser coronary angioplasty is most useful in complex lesions not well suited for percutaneous transluminal coronary angioplasty (PTCA). It is not `stand-alone' procedure, and should be considered an adjunct to PTCA or stenting. To date, there are not data supporting reduction of restenosis. Direct myocardial revascularization (DMR), either transmyocardial revascularization (TMR) or percutaneous (catheter-based) myocardial revascularization (PMR), uses laser to create channels between ischemic myocardium and left ventricular cavity. Candidates include patients with chronic, severe, refractory angina and those unable to undergo angioplasty or bypass surgery because conduits or acceptable target vessels are lacking. Although the mechanisms of action of DMR have not yet been clearly elucidated, but several theories have been proposed, including channel patency, angiogenesis, and denervation. TMR, typically requiring open thoracotomy, is effective for improving myocardial perfusion and reducing angina. Pilot studies demonstrate that clinical application of PMR is feasible and safe and effective for decreasing angina. Late sequelae also remain to be determined. An ongoing randomized clinical trial is comparing PMR with conventional medical therapy in patients with severe, refractory angina and disease unamenable to angioplasty or bypass surgery.

Acidosis slows electrical conduction through the atrio-ventricular node

PubMed Central

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Acidosis slows electrical conduction through the atrio-ventricular node.

PubMed

Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes.

PubMed

Feng, Li; Gong, Jing; Jin, Zhen-yi; Li, Ning; Sun, Li-ping; Wu, Yi-ling; Pu, Jie-lin

2009-07-05

Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). SSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change. The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

Amiodarone in the treatment of refractory supraventricular and ventricular arrhythmias

PubMed Central

Wheeler, P. J.; Ingram, D. V.; Puritz, R.; Chamberlain, D. A.

1979-01-01

Amiodarone is an antiarrhythmic agent unrelated to other drugs in current use. It has been little used in Britain, and no formal clinical trials have been possible because the drug has not been licensed by the Committee on Safety of Medicines. Nevertheless it has unique properties which can be valuable in the treatment of a wide spectrum of arrhythmias, particularly supraventricular tachycardias. Amiodarone has a slow onset of action and is cumulative. A sustained action is therefore achieved without the need for frequent maintenance dosage. Fifty patients have been treated with amiodarone in maintenance doses ranging from 200 mg on alternate days to 200 mg twice daily either alone, or in combination with conventional therapy. All were resistant to conventional therapy alone or could not be treated with usual agents because of unwanted drug effects. Of 27 patients with supraventricular arrhythmias, 18 were completely controlled and the other 9 were markedly improved. Six of 8 patients with recurrent life-threatening ventricular arrhythmias were well controlled symptomatically. Results were predictably less satisfactory in 15 high risk post-infarction patients with malignant arrhythmias and severe myocardial damage, but 6 were probably improved as a result of amiodarone. All patients on maintenance therapy for 3 months or more developed corneal microdeposits. None has any visual symptoms or other ocular defect, and treatment has not been curtailed as a result of this well recognized effect which is believed to be reversible and benign. Amiodarone can control patients with otherwise refractory arrhythmias including some which are life-threatening. Formal clinical trials are needed to define accurately its future role in the prevention and treatment of serious rhythm disorders of the heart. PMID:432163

Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study.

PubMed

Pappone, Carlo; Vicedomini, Gabriele; Manguso, Francesco; Baldi, Mario; Pappone, Alessia; Petretta, Andrea; Vitale, Raffaele; Saviano, Massimo; Ciaccio, Cristiano; Giannelli, Luigi; Calovic, Zarko; Tavazzi, Luigi; Santinelli, Vincenzo

2012-02-07

The available amount of detailed long-term data in patients with Wolff-Parkinson-White syndrome is limited, and no prospective electrophysiological studies looking at predictors of malignant arrhythmia are available. Among 8575 symptomatic Wolff-Parkinson-White patients with atrioventricular reentrant tachycardia referred for electrophysiological test, 369 (mean age, 23±12.5 years) declined catheter ablation and were followed up. The primary end point of the study was to evaluate over a 5-year follow-up the predictors and characteristics of patients who develop malignant arrhythmias. After a mean follow-up of 42.1±10 months, malignant arrhythmias developed in 29 patients (mean age, 13.9±5.6 years; 26 male), resulting in presyncope/syncope (25 patients), hemodynamic collapse (3 patients), or cardiac arrest caused by ventricular fibrillation (1 patient). Of the remaining 340 patients, 168 (mean age, 34.2±9.0 years) remained asymptomatic up to 5 years, and 172 (mean age, 13.6±5.1 years) had benign recurrence, including sustained atrioventricular reentrant tachycardia (132 patients) or atrial fibrillation (40 patients). Compared with the group with no malignant arrhythmias, the group with malignant arrhythmias showed shorter accessory-pathway effective refractory period (P<0.001) and more often exhibited multiple accessory pathways (P<0.001), and atrioventricular reentrant tachycardia triggering sustained pre-excited atrial fibrillation was more frequently inducible (P<0.001). Multivariable analysis demonstrated that short accessory-pathway effective refractory period (P<0.001) and atrioventricular reentrant tachycardia triggering sustained pre-excited atrial fibrillation (P<0.001) were independent predictors of malignant arrhythmias. Symptomatic patients with Wolff-Parkinson-White syndrome generally have a good outcome, and predictors of malignant arrhythmias are similar to those reported for asymptomatic patients with ventricular pre-excitation.

Curvature effects on activation speed and repolarization in an ionic model of cardiac myocytes

NASA Astrophysics Data System (ADS)

Comtois, P.; Vinet, A.

1999-10-01

Reentry is a major mechanism underlying the initiation and perpetuation of many cardiac arrhythmias 12345. Stimulated ventricular myocytes give action potential characterized by a fast upstroke, a long-lasting plateau, and a late repolarization phase. The plateau phase determines the action potential duration (APD) during which the system remains refractory, a property essential to the synchronization of the heart cycle. The APD varies much with prematurity and this change has been shown to be the main determinant of the dynamics in models of paced cells and cable, and during reentry in the one-dimensional loop. Curvature has also been shown to be an important factor for propagation in experimental and theoretical cardiac extended tissue. The objective of this paper is to combine both curvature and prematurity effects in a kinematical model of propagation in cardiac tissue. First, an approximation of the ionic model is used to obtain the effects of curvature and prematurity on the speed of propagation, the APD, and the absolute refractory period. Two versions of the ionic model are studied that differ in their rate of excitability recovery. The functions are used in a kinematical model describing the propagation of period-1 solutions around an annulus.

Synergistic Effect of Dofetilide and Mexiletine on Prevention of Atrial Fibrillation.

PubMed

Liu, Guizhi; Xue, Xiaolin; Gao, Chuanyu; Huang, Jiaqi; Qi, Datun; Zhang, Yanzhou; Dong, Jian-Zeng; Ma, Chang-Sheng; Yan, Gan-Xin

2017-05-18

Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias. The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations. Dofetilide or mexiletine alone mildly to moderately prolonged atrial ERP, but their combined use produced a markedly rate-dependent increase in atrial ERP. Dofetilide (3 nmol/L) plus mexiletine (10 μmol/L) increased the ERP by 28.2% from 72.2±5.7 to 92.8±5.9 ms (n=9, P <0.01) at a pacing rate of 0.5 Hz and by 94.5% from 91.7±5.2 to 178.3±12.0 ms (n=9, P <0.01) at 3.3 Hz. Dofetilide plus mexiletine strongly suppressed AF inducibility. On the other hand, dofetilide at 10 nmol/L produced marked QT and T p-e prolongation, steeper QT-BCL and T p-e -BCL slopes, and induced early afterdepolarizations and torsade de pointes in the ventricular wedges. Mexiletine at 10 μmol/L reduced dofetilide-induced QT and T p-e prolongation, QT-BCL and T p-e -BCL slopes, and abolished early afterdepolarizations and torsade de pointes. In rabbits, combined use of dofetilide and mexiletine not only synergistically increases atrial ERP and effectively suppresses AF inducibility, but also markedly reduces QT liability and torsade de pointes risk posed by dofetilide alone. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Role of aminophylline in refractory heart failure: a comparison to the vasodilator sodium nitroprusside, the old and the new.

PubMed

DiBianco, R; Rosenfeld, S P; Katz, R J; Simpson, A G; Fletcher, R D; Singh, S

1980-08-01

Aminophylline [(theophylline ethylene diamine (TED)] reportedly improved cardiac hemodynamics by lowering vascular resistances and increasing contractility. TED as used clinically has not been compared to the vasodilator sodium nitroprusside (NP). To assess the relative hemodynamic effects of these two commonly used agents, the following comparison was made. Ten patients with congestive cardiomyopathy in chronic refractory heart failure [New York Heart Association (NYHA) class IV] were studied. All patients demonstrated cardiomegaly by chest x ray and echocardiography (LVd = 6.3 +/- 0.7 cm) and markedly abnormal hemodynamics during baseline observations (see Table I). Hemodynamic measurements at baseline were compared after TED infusion (mean blood level = 16 +/- 12 micrograms/m/TED) and during intravenous NP. No significant changes in heart rate occurred during either therapeutic intervention; a fall in mean arterial pressure of 10 mmHg (p < 0.01) was observed during NP therapy; atrioventricular (AV) block with ventricular fibrillation was successfully treated in one patient after TED. Theophylline ethylene diamine demonstrated no detectable cardiac hemodynamic effects 60--90 min post infusion despite proven blood levels, whereas NP exhibited distinctly beneficial effects in this patient group. Previous studies demonstrating improved hemodynamics occurring with TED have been limited to the time of infusion or within the following 40 min, a time when TED blood levels are maximum and therefore closest to toxicity. The results of this study suggest that TED demonstrates no beneficial hemodynamic effects in refractory heart failure as early as 1 h after infusion despite blood levels in the therapeutic range.

Nifekalant hydrochloride suppresses severe electrical storm in patients with malignant ventricular tachyarrhythmias.

PubMed

Washizuka, Takashi; Chinushi, Masaomi; Watanabe, Hiroshi; Hosaka, Yukio; Komura, Satoru; Sugiura, Hirotaka; Hirono, Takashi; Furushima, Hiroshi; Tanabe, Yasutaka; Aizawa, Yoshifusa

2005-12-01

Some patients with an implantable cardioverter-defibrillator (ICD) suffer from burst of inappropriate multiple discharges (severe electrical storm), and because the current therapeutic options are limited, the effect of nifekalant hydrochloride, a new class III drug, on severe electrical storm was investigated in the present study. Ninety-one consecutive patients treated with ICD were included in the study (M 70; mean age 58 years; left ventricular ejection fraction 45+/-15%). Severe electrical storm was defined as more than 10 ICD discharges within 1 h. During a mean follow-up period of 30+/-13 months, 41/91 (45%) patients had appropriate ICD therapy for arrhythmias and severe electrical storm occurred in 11 of them (12%) at 20+/-18 months after ICD implantation. The mean number of ICD discharges/h during severe electrical storm was 18+/-12. In 4 of 10 patients, severe electrical storm was successfully suppressed by a combination of deep sedation and beta-blocking agent; 6 other patients were refractory to this treatment, but severe electrical storm was successfully suppressed by intravenous administration of nifekalant hydrochloride with no adverse effects. Nifekalant hydrochloride is an effective and safe treatment for severe electrical storm.

Hypercalcemic crisis and primary hyperparathyroidism: Cause of an unusual electrical storm.

PubMed

Guimarães, Tatiana; Nobre Menezes, Miguel; Cruz, Diogo; do Vale, Sónia; Bordalo, Armando; Veiga, Arminda; Pinto, Fausto J; Brito, Dulce

2017-12-01

Hypercalcemia is a known cause of heart rhythm disorders, however its association with ventricular arrhythmias is rare. The authors present a case of a fifty-three years old male patient with a ischemic and ethanolic dilated cardiomyopathy, and severely reduced ejection fraction, carrier of cardiac resynchronization therapy (CRT) with cardioverter defibrillator (ICD), admitted in the emergency department with an electrical storm, with multiple appropriated ICD shocks, refractory to antiarrhythmic therapy. In the etiological investigation was documented severe hypercalcemia secondary to primary hyperparathyroidism undiagnosed until then. Only after the serum calcium level reduction ventricular tachycardia was stopped. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Hypothalamic Ventricular Ependymal Thyroid Hormone Deiodinases Are an Important Element of Circannual Timing in the Siberian Hamster (Phodopus sungorus)

PubMed Central

Bolborea, Matei; Wilson, Dana; Mercer, Julian G.; Ebling, Francis J. P.; Morgan, Peter J.; Barrett, Perry

2013-01-01

Exposure to short days (SD) induces profound changes in the physiology and behaviour of Siberian hamsters, including gonadal regression and up to 30% loss in body weight. In a continuous SD environment after approximately 20 weeks, Siberian hamsters spontaneously revert to a long day (LD) phenotype, a phenomenon referred to as the photorefractory response. Previously we have identified a number of genes that are regulated by short photoperiod in the neuropil and ventricular ependymal (VE) cells of the hypothalamus, although their importance and contribution to photoperiod induced physiology is unclear. In this refractory model we hypothesised that the return to LD physiology involves reversal of SD expression levels of key hypothalamic genes to their LD values and thereby implicate genes required for LD physiology. Male Siberian hamsters were kept in either LD or SD for up to 39 weeks during which time SD hamster body weight decreased before increasing, after more than 20 weeks, back to LD values. Brain tissue was collected between 14 and 39 weeks for in situ hybridization to determine hypothalamic gene expression. In VE cells lining the third ventricle, expression of nestin, vimentin, Crbp1 and Gpr50 were down-regulated at 18 weeks in SD photoperiod, but expression was not restored to the LD level in photorefractory hamsters. Dio2, Mct8 and Tsh-r expression were altered by SD photoperiod and were fully restored, or even exceeded values found in LD hamsters in the refractory state. In hypothalamic nuclei, expression of Srif and Mc3r mRNAs was altered at 18 weeks in SD, but were similar to LD expression values in photorefractory hamsters. We conclude that in refractory hamsters not all VE cell functions are required to establish LD physiology. However, thyroid hormone signalling from ependymal cells and reversal of neuronal gene expression appear to be essential for the SD refractory response. PMID:23637944

Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation.

PubMed

Hollis, Allison L; Lowery, Ashleigh V; Pajoumand, Mehrnaz; Pham, Si M; Slejko, Julia F; Tanaka, Kenichi A; Mazzeffi, Michael

2016-01-01

Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.

Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes.

PubMed

Müller, A; Linke, W; Klaus, W

1999-05-01

Crataegus extract is used in cardiology for the treatment of mild to moderate heart failure (NYHA II) in Germany. However, little is known about the electrophysiological actions of Crataegus extract in the heart. Recently, it was shown that Crataegus extract prolongs the refractory period in isolated perfused hearts and increases action potential duration in guinea pig papillary muscle. It was the aim of this study to find out the mechanism of the increase in action potential duration caused by Crataegus extract. Using the patch-clamp technique, we measured the effects of Crataegus extract (10 mg/l; flavonoid content: 2.25%, total procyanidin content: 11.3 +/- 0.4%) on the inward rectifier and the delayed rectifier potassium current in isolated guinea pig ventricular myocytes. To get some insight into the mechanism underlying the positive inotropic effect of Crataegus extract, we also looked for effects on the L-type calcium current. Crataegus extract slightly blocked both the delayed and the inward rectifier potassium current. The inhibition amounted to 25% and about 15%, respectively. This amount of inhibition of these repolarising currents is sufficient to explain the prolongation of action potential duration caused by Crataegus extract. To our surprise we could not detect any influence of Crataegus extract on the L-type calcium current. In summary, our results show that Crataegus extract blocks repolarising potassium currents in ventricular myocytes. This effect is similar to the action of class III antiarrhythmic drugs and might be the basis of the antiarrhythmic effects described for Crataegus extract. Our measurements of the L-type calcium current indicate that Crataegus extract's positive inotropic effect is not caused by phosphodiesterase inhibition or a beta-sympathomimetic effect.

Conversion to full sternotomy during minimal-access cardiac surgery: reasons and results during a 9.5-year experience.

PubMed

Tabata, Minoru; Umakanthan, Ramanan; Khalpey, Zain; Aranki, Sary F; Couper, Gregory S; Cohn, Lawrence H; Shekar, Prem S

2007-07-01

A hemisternotomy approach to minimal-access cardiac surgery is associated with a faster postoperative recovery because of reduced postoperative pain and improved respiratory function. Conversion to a full sternotomy is occasionally required for reasons that remain inadequately reported. Between January 1996 and June 2005, 907 cardiac surgical patients were planned for an upper hemisternotomy and 528 for a lower hemisternotomy. We retrospectively reviewed 45 patients who required conversion to a full sternotomy. Twenty-four (2.6%) of 907 patients required a conversion from upper hemisternotomy because of bleeding (n = 8), ventricular dysfunction (n = 5), refractory ventricular arrhythmia (n = 3), poor exposure (n = 2), and other causes (n = 6). Eight (33.3%) of 24 patients died perioperatively. Of the 883 patients who went on to have an operation through the upper hemisternotomy approach, the mortality was 1.7% (15/883). Twenty-one (4.0%) of 528 patients required conversion from a lower hemisternotomy because of poor exposure (n = 16), bleeding (n = 1), refractory ventricular arrhythmia (n = 3), and a retained venous cannula (n = 1). None of these patients died postoperatively. Of the 507 patients who went on to have an operation through the lower hemisternotomy approach, the mortality was 1.2% (6/507). Conversion to a full sternotomy occurs infrequently during minimal-access cardiac surgery. Upper hemisternotomy conversions are usually urgent after crossclamp removal and are often associated with serious morbidity and mortality. Conversely, lower hemisternotomy conversions are performed electively in the prebypass period because of poor exposure and are not associated with complications.

Comparison of Transplant Waitlist Outcomes for Pediatric Candidates Supported by Ventricular Assist Devices Versus Medical Therapy.

PubMed

Law, Sabrina P; Oron, Assaf P; Kemna, Mariska S; Albers, Erin L; McMullan, D Michael; Chen, Jonathan M; Law, Yuk M

2018-05-01

Ventricular assist devices have gained popularity in the management of refractory heart failure in children listed for heart transplantation. Our primary aim was to compare the composite endpoint of all-cause pretransplant mortality and loss of transplant eligibility in children who were treated with a ventricular assist device versus a medically managed cohort. This was a retrospective cohort analysis. Data were obtained from the Scientific Registry of Transplant Recipients. The at-risk population (n = 1,380) was less than 18 years old, either on a ventricular assist device (605 cases) or an equivalent-severity, intensively medically treated group (referred to as MED, 775 cases). None. The impact of ventricular assist devices was estimated via Cox proportional hazards regression (hazard ratio), dichotomizing 1-year outcomes to "poor" (22%: 193 deaths, 114 too sick) versus all others (940 successful transplants, 41 too healthy, 90 censored), while adjusting for conventional risk factors. Among children 0-12 months old, ventricular assist device was associated with a higher risk of poor outcomes (hazard ratio, 2.1; 95% CI, 1.5-3.0; p < 0.001). By contrast, ventricular assist device was associated with improved outcomes for ages 12-18 (hazard ratio, 0.3; 95% CI, 0.1-0.7; p = 0.003). For candidates 1-5 and 6-11 years old, there were no differences in outcomes between the ventricular assist device and MED groups (hazard ratio, 0.8 and 1.0, p = 0.43 and 0.9). The interaction between ventricular assist devices and age group was strongly significant (p < 0.001). This is a comparative study of ventricular assist devices versus medical therapy in children. Age is a significant modulator of waitlist outcomes for children with end-stage heart failure supported by ventricular assist device, with the impact of ventricular assist devices being more beneficial in adolescents.

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.

PubMed

Ozcan, Cevher; Jahangir, Arshad; Friedman, Paul A; Munger, Thomas M; Packer, Douglas L; Hodge, David O; Hayes, David L; Gersh, Bernard J; Hammill, Stephen C; Shen, Win-Kuang

2003-07-01

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.

Development of heart failure is independent of K+ channel-interacting protein 2 expression

PubMed Central

Speerschneider, Tobias; Grubb, Søren; Metoska, Artina; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2013-01-01

Abnormal ventricular repolarization in ion channelopathies and heart disease is a major cause of ventricular arrhythmias and sudden cardiac death. K+ channel-interacting protein 2 (KChIP2) expression is significantly reduced in human heart failure (HF), contributing to a loss of the transient outward K+ current (Ito). We aim to investigate the possible significance of a changed KChIP2 expression on the development of HF and proarrhythmia. Transverse aortic constrictions (TAC) and sham operations were performed in wild-type (WT) and KChIP2−/− mice. Echocardiography was performed before and every 2 weeks after the operation. Ten weeks post-surgery, surface ECG was recorded and we paced the heart in vivo to induce arrhythmias. Afterwards, tissue from the left ventricle was used for immunoblotting. Time courses of HF development were comparable in TAC-operated WT and KChIP2−/− mice. Ventricular protein expression of KChIP2 was reduced by 70% after 10 weeks TAC in WT mice. The amplitudes of the J and T waves were enlarged in KChIP2−/− control mice. Ventricular effective refractory period, RR, QRS and QT intervals were longer in mice with HF compared to sham-operated mice of either genotype. Pacing-induced ventricular tachycardia (VT) was observed in 5/10 sham-operated WT mice compared with 2/10 HF WT mice with HF. Interestingly, and contrary to previously published data, sham-operated KChIP2−/− mice were resistant to pacing-induced VT resulting in only 1/10 inducible mice. KChIP2−/− with HF mice had similar low vulnerability to inducible VT (1/9). Our results suggest that although KChIP2 is downregulated in HF, it is not orchestrating the development of HF. Moreover, KChIP2 affects ventricular repolarization and lowers arrhythmia susceptibility. Hence, downregulation of KChIP2 expression in HF may be antiarrhythmic in mice via reduction of the fast transient outward K+ current. PMID:24099801

Use of hypothermia in the intensive care unit

PubMed Central

Corry, Jesse J

2012-01-01

Used for over 3600 years, hypothermia, or targeted temperature management (TTM), remains an ill defined medical therapy. Currently, the strongest evidence for TTM in adults are for out-of-hospital ventricular tachycardia/ventricular fibrillation cardiac arrest, intracerebral pressure control, and normothermia in the neurocritical care population. Even in these disease processes, a number of questions exist. Data on disease specific therapeutic markers, therapeutic depth and duration, and prognostication are limited. Despite ample experimental data, clinical evidence for stroke, refractory status epilepticus, hepatic encephalopathy, and intensive care unit is only at the safety and proof-of-concept stage. This review explores the deleterious nature of fever, the theoretical role of TTM in the critically ill, and summarizes the clinical evidence for TTM in adults. PMID:24701408

Evaluation of the acute electrophysiologic effects of intravenous dronedarone, an amiodarone-like agent, with special emphasis on ventricular repolarization and acquired torsade de pointes arrhythmias.

PubMed

Verduyn, S C; Vos, M A; Leunissen, H D; van Opstal, J M; Wellens, H J

1999-02-01

In the anesthetized dog with complete chronic AV block (CAVB), we evaluated and compared the acute electrophysiologic effects of dronedarone i.v. (Dron, 2 times 2.5 mg/kg/10 min) and amiodarone i.v. (Amio, 2 times 5 mg/kg/10 min). This canine model with a high sensitivity for acquired torsade de pointes (TdP) provides an ideal substrate to evaluate ventricular repolarization abnormalities. Six ECG leads and two endocardial monophasic action potential (MAP) recordings in the left and right ventricle (LV and RV) were simultaneously recorded to measure QT time, action-potential duration (APD), interventricular dispersion (deltaAPD = LV(APD) - RV(APD)), early afterdepolarizations (EADs), ectopic beats (EBs), and TdP. Measurements were made at the spontaneous idioventricular rhythm (IVR) and 1,000-ms steady-state pacing. To investigate its short-term, antiarrhythmic properties, Dron was given after almokalant (0.12 mg/kg)-induced TdP. Furthermore, in another set of experiments, oral Dron (20 mg/kg, b.i.d) was given for 3 weeks to conscious CAVB dogs. Dron, i.v., shortened ventricular repolarization (QT, 435 +/- 60 to 360 +/- 55; LV(APD) 395 +/- 75 to 335 +/- 60 ms; p < 0.05), whereas IVR and ventricular effective refractory period (VERP, 225 +/- 30 to 230 +/- 30 ms) remained similar. Therefore the VERP/QT ratio increased (0.55 +/- 0.04 to 0.61 +/- 0.03; p < 0.05). Similar results were obtained with Amio, i.v.. Almokalant-induced TdP was characterized by an increased repolarization duration, deltaAPD, and EADs. Dron, i.v., suppressed the EADs, EBs, and TdP by a reduction and homogenization of repolarization (LV(APD), 505 +/- 110 to 455 +/- 80 ms, and deltaAPD, 110 +/- 55 to 65 +/- 40 ms). Long-term oral Dron increased the PP interval, CL-IVR, and QT(c) time. In contrast to oral treatment, Dron i.v. shortens ventricular repolarization parameters, resulting in suppression of EAD-dependent acquired TdP. The increased VERP/QT ratio after Dron i.v. may indicate an important second antiarrhythmic property.

Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof-of-Concept from Experimental Studies to Clinical VF

PubMed Central

KRUMMEN, DAVID E.; HAYASE, JUSTIN; VAMPOLA, STEPHEN P.; HO, GORDON; SCHRICKER, AMIR A.; LALANI, GAUTAM G.; BAYKANER, TINA; COE, TAYLOR M.; CLOPTON, PAUL; RAPPEL, WOUTER-JAN; OMENS, JEFFREY H.; NARAYAN, SANJIV M.

2016-01-01

Introduction Recent work has suggested a role for organized sources in sustaining ventricular fibrillation (VF). We assessed whether ablation of rotor substrate could modulate VF inducibility in canines, and used this proof-of-concept as a foundation to suppress antiarrhythmic drug-refractory clinical VF in a patient with structural heart disease. Methods and Results In 9 dogs, we introduced 64-electrode basket catheters into one or both ventricles, used rapid pacing at a recorded induction threshold to initiate VF, and then defibrillated after 18±8 seconds. Endocardial rotor sites were identified from basket recordings using phase mapping, and ablation was performed at nonrotor (sham) locations (7 ± 2 minutes) and then at rotor sites (8 ± 2 minutes, P = 0.10 vs. sham); the induction threshold was remeasured after each. Sham ablation did not alter canine VF induction threshold (preablation 150 ± 16 milliseconds, postablation 144 ± 16 milliseconds, P = 0.54). However, rotor site ablation rendered VF noninducible in 6/9 animals (P = 0.041), and increased VF induction threshold in the remaining 3. Clinical proof-of-concept was performed in a patient with repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Following biventricular basket insertion, VF was induced and then defibrillated. Mapping identified 4 rotors localized at borderzone tissue, and rotor site ablation (6.3 ± 1.5 minutes/site) rendered VF noninducible. The VF burden fell from 7 ICD shocks in 8 months preablation to zero ICD therapies at 1 year, without antiarrhythmic medications. Conclusions Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation. PMID:26179310

Sodium Nitroprusside Enhanced Cardiopulmonary Resuscitation Improves Short Term Survival in a Porcine Model of Ischemic Refractory Ventricular Fibrillation

PubMed Central

Yannopoulos, Demetris; Bartos, Jason A.; George, Stephen A.; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P.

2017-01-01

Introduction Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. Hypothesis SNPeCPR will increase short term (4-hour) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Methods Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5 minutes. Basic life support was performed for 10 minutes. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3 minutes. CPR continued for a total of 45 minutes, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60 minutes, if unsuccessful. SNPeCPR animals received 2 mg of SNP at minute 10 followed by 1 mg every 5 minutes until ROSC. Standard ACLS animals received 0.5 mg epinephrine every 5 minutes until ROSC. Primary endpoints were ROSC and 4-hour survival. Results All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-hour survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. Conclusion SNPeCPR significantly improved ROSC and 4-hour survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. PMID:27771299

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation.

PubMed

Yannopoulos, Demetris; Bartos, Jason A; George, Stephen A; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P

2017-01-01

Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Electrophysiological actions of somatostatin on the atrioventricular junction in sinus rhythm and reentry tachycardia.

PubMed Central

Webb, S C; Krikler, D M; Hendry, W G; Adrian, T E; Bloom, S R

1986-01-01

Because somatostatin, a neuroregulatory peptide, is found in abundance in the atria and atrioventricular node, its electrophysiological and antiarrhythmic properties were compared with those of verapamil in ten patients with paroxysmal atrioventricular tachycardia. During sinus rhythm, intravenous somatostatin slowed the heart rate whereas verapamil increased it. Though both agents prolonged atrioventricular conduction time and refractoriness, verapamil was more potent. They were equally effective at terminating reentry atrioventricular tachycardia, restoring sinus rhythm in six of seven patients. Whereas verapamil consistently blocked conduction in the atrioventricular node, somatostatin usually induced ventricular extrasystoles at the time of conversion. Somatostatin may have physiological importance in the neurohumoral control of cardiac impulse formation and conduction. PMID:2875723

Electrophysiological actions of somatostatin on the atrioventricular junction in sinus rhythm and reentry tachycardia.

PubMed

Webb, S C; Krikler, D M; Hendry, W G; Adrian, T E; Bloom, S R

1986-09-01

Because somatostatin, a neuroregulatory peptide, is found in abundance in the atria and atrioventricular node, its electrophysiological and antiarrhythmic properties were compared with those of verapamil in ten patients with paroxysmal atrioventricular tachycardia. During sinus rhythm, intravenous somatostatin slowed the heart rate whereas verapamil increased it. Though both agents prolonged atrioventricular conduction time and refractoriness, verapamil was more potent. They were equally effective at terminating reentry atrioventricular tachycardia, restoring sinus rhythm in six of seven patients. Whereas verapamil consistently blocked conduction in the atrioventricular node, somatostatin usually induced ventricular extrasystoles at the time of conversion. Somatostatin may have physiological importance in the neurohumoral control of cardiac impulse formation and conduction.

Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function.

PubMed

Broux, B; De Clercq, D; Decloedt, A; De Baere, S; Devreese, M; Van Der Vekens, N; Ven, S; Croubels, S; van Loon, G

2016-02-01

Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration. Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of Tricuspid Regurgitation on the Success of Atrioventricular Node Ablation for Rate Control in Patients With Atrial Fibrillation: The Node Blast Study.

PubMed

Reddy, Yeruva Madhu; Gunda, Sampath; Vallakati, Ajay; Kanmanthareddy, Arun; Pillarisetti, Jayasree; Atkins, Donita; Bommana, Sudharani; Emert, Martin P; Pimentel, Rhea; Dendi, Raghuveer; Berenbom, Loren D; Lakkireddy, Dhanunjaya

2015-09-15

Atrioventricular node (AVN) ablation is an effective treatment for symptomatic patients with atrial arrhythmias who are refractory to rhythm and rate control strategies where optimal ventricular rate control is desired. There are limited data on the predictors of failure of AVN ablation. Our objective was to identify the predictors of failure of AVN ablation. This is an observational single-center study of consecutive patients who underwent AVN ablation in a large academic center. Baseline characteristics, procedural variables, and outcomes of AVN ablation were collected. AVN "ablation failure" was defined as resumption of AVN conduction resulting in recurrence of either rapid ventricular response or suboptimal biventricular pacing. A total of 247 patients drug refractory AF who underwent AVN ablation at our center with a mean age of 71 ± 12 years with 46% being males were included. Ablation failure was seen in 11 (4.5%) patients. There were no statistical differences between patients with "ablation failure" versus "ablation success" in any of the baseline clinical variables. Patients with moderate-to-severe tricuspid regurgitation (TR) were much more likely to have ablation failure than those with ablation success (8 [73%] vs 65 [27%]; p = 0.003). All 11 patients with ablation failure had a successful redo procedure, 9 with right and 2 with the left sided approach. On multivariate analysis, presence of moderate-to-severe TR was found to be the only predictor of failure of AVN ablation (odds ratio 9.1, confidence interval 1.99 to 42.22, p = 0.004). In conclusion, moderate-to-severe TR is a strong and independent predictor of failure of AVN ablation. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcomes of patients with right ventricular failure on milrinone after left ventricular assist device implantation.

PubMed

Tsiouris, Athanasios; Paone, Gaetano; Brewer, Robert J; Nemeh, Hassan W; Borgi, Jamil; Morgan, Jeffrey A

2015-01-01

Previous studies have grouped together both patients requiring right ventricular assist devices (RVADs) with patients requiring prolonged milrinone therapy after left ventricular assist device (LVAD) implantation. We retrospectively identified 149 patients receiving LVADs and 18 (12.1%) of which developed right ventricular (RV) failure. We then separated these patients into those requiring RVADs versus prolonged milrinone therapy. This included 10 patients who were treated with prolonged milrinone and eight patients who underwent RVAD placement. Overall, the RV failure group had worse survival compared with the non-RV failure cohort (p = 0.038). However, this was only for the subgroup of patients who required RVADs, who had a 1, 6, 12, and 24 month survival of 62.5%, 37.5%, 37.5%, and 37.5%, respectively, versus 96.8%, 92.1%, 86.7%, and 84.4% for patients without RV failure (p < 0.001). Patients treated with prolonged milrinone therapy for RV failure had similar survivals compared with patients without RV failure. In the RV failure group, age, preoperative renal failure, and previous cardiac surgery were predictors of the need for prolonged postoperative milrinone. As LVADs become a more widely used therapy for patients with refractory, end-stage heart failure, it will be important to reduce the incidence of RV failure, as it yields significant morbidity and increases cost.

Cardiac resynchronisation therapy in the presence of left-to-right intracardiac shunting: more good than harm?

PubMed

Kyu, Kyu; Seow, Swee Chong; Wong, Raymond; Kojodjojo, Pipin

2016-03-17

An elderly Chinese man with moderately impaired left ventricular function, left bundle branch block and ST-elevation myocardial infarction complicated by ventricular septal rupture had class IV heart failure symptoms refractory to medical and surgical interventions. As a treatment of last resort, a cardiac resynchronisation therapy (CRT) pacemaker was implanted apprehensively, as preoperative concerns were raised whether CRT could exacerbate left-to-right shunting, hence negating the potential benefits of CRT. Introduction of CRT significantly improved the patient's haemodynamic status and symptoms, allowing for successful discharge home. To the best of our knowledge, this is the first report of a patient with severely symptomatic acute heart failure, widened QRS and active left-to-right intracardiac shunting, treated successfully with CRT. 2016 BMJ Publishing Group Ltd.

[Prevalence of target organ damage and factors associated with cardiovascular events in subjects with refractory hypertension].

PubMed

Armario, Pedro; Oliveras, Anna; Hernández Del Rey, Raquel; Poch, Esteban; Larrouse, María; Roca-Cusachs, Alex; de la Sierra, Alejandro

2009-06-27

To asses the prevalence of target organ damage (TOD) and factors associated with cardiovascular events in subjects with refractory hypertension. Cross-sectional study of 146 patients with clinical diagnosis of refractory hypertension. TOD was defined as the presence of microalbuminuria (MA), renal failure (RF), left ventricular hypertrophy (LVH) or left atrial enlargement (LAE). Cardiovascular events were defined as the antecedent of stroke, coronary heart disease, heart failure or peripheral arterial disease. 24-h ambulatory blood pressure monitoring was (ABPM) performed with a validated Spacelabs 90207. The prevalence of LVH was 62.3%, and LAE was observed in 27.7% of the subjects. The prevalence of RF was 28.1% and MA was found in 41,4%. An association between MA and LVH was observed. After adjusting by age, the urinary albumin excretion (UAE) correlated with clinical blood pressure (BP) and BP during 24-h ABPM, whereas LVMI correlated with ambulatory BP but not with clinical BP. The prevalence of previous cardiovascular events was 22% and in the multivariate regression analysis, UAE was the only independent factor associated with the antecedent of cardiovascular events. In subjects with refractory hypertension, the prevalence of TOD was high, and an association between heart and renal organ damage was observed. UAE was independently associated with the antecedent of cardiovascular disease.

Proof of concept study: renal sympathetic denervation for treatment of polymorphic premature ventricular complexes.

PubMed

Kiuchi, Márcio Galindo; E Silva, Gustavo Ramalho; Paz, Luis Marcelo Rodrigues; Chen, Shaojie; Souto, Gladyston Luiz Lima

2016-11-01

Polymorphic premature ventricular complexes (PVCs) are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, the relevance of sympathetic activation in patients with ventricular arrhythmias was reported, and this finding suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. We evaluated the effectiveness of the renal sympathetic denervation (RSD) in comparison to antiarrhythmic pharmacologic therapy in reducing polymorphic PVCs refractory to medication therapy and cardiac parameters assessed by 24-h Holter monitoring and cardiac magnetic resonance (CRM), respectively, in patients with structurally normal heart. Thirty-four patients were included in this study, 14 served as control, and 20 were treated with an ablation cardiac catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. All the patients included had polymorphic PVCs and structurally normal heart. Data were obtained at baseline at the 12th month of follow-up (sixth month after RSD or adjustment of antiarrhythmic dosage). In RSD group, we observed a significant decrease in the number of polymorphic PVCs from baseline 36,091 ± 3327 to 3, 6, 7 (first month after RSD, without drugs), and 12 months (sixth month after RSD, without drugs) of follow-up, 31,009 ± 3251, 20,411 ± 3820, 7701 ± 1549, and 1274 ± 749, respectively, in all patients, P < 0.0001 to all the comparisons between the mean of each time point with the mean of every other time point. No changes in mean 24-h ABPM and renal function in both groups were observed at 12th month of follow-up. However, 24-h Holter mean heart rate decreased in control group at 12th month of follow-up, which did not happen with the RSD group. At the sixth month post-RSD in comparison to baseline, a significant reduction in the number of polymorphic PVCs (∆ = -34,817 ± 3590, P < 0.0001) was observed, as well as, in CRM parameters such as left ventricular mass/body surface area (∆ = -5.4 ± 2.1 g/m 2 , P < 0.0001) and left ventricular ejection fraction (∆ = +3.0 ± 1.8 %, P < 0.0001). In comparison to control group at the same time point, these findings were statistically superior in RSD group (P > 0.05). A significant correlation was found between the Δ number of polymorphic PVCs at the sixth month (r = -0.6723, P = 0.0012) after the RSD and the total number of RSD ablated spots. Polymorphic PVCs refractory to medication therapy may be modifiable by RSD in patients without structural heart disease. Although encouraging, our data are preliminary and need to be validated in a large population and in long term.

Intractable Electrical Storm After Coronary Artery Bypass Grafting Originating in Abnormal Purkinje Fibers.

PubMed

Tokunaga, Chiho; Tsukada, Toru; Sakamoto, Hiroaki; Naruse, Yoshihisa; Yoshida, Kentaro; Sekiguchi, Yukio; Imai, Akito; Aonuma, Kazutaka; Hiramatsu, Yuji

2016-01-01

Electrical storm is a rare but critical complication following revascularization in patients with ischemic heart disease. We report the case of a 67-year-old man who developed drug refractory intractable electrical storm after emergent coronary artery bypass grafting for ischemic cardiomyopathy. The electrical storm was successfully eliminated by percutaneous endocardial radiofrequency catheter ablation targeting the abnormal Purkinje-related triggering ventricular premature contractions in a low-voltage zone. © 2015 Wiley Periodicals, Inc.

Carotid Doppler ultrasound findings in patients with left ventricular assist devices.

PubMed

Cervini, Patrick; Park, Soon J; Shah, Dipesh K; Penev, Irina E; Lewis, Bradley D

2010-12-01

Left ventricular assist devices (LVADs) have been used to treat advanced heart failure refractory to medical management, as bridge therapy to myocardial recovery, as bridge therapy to cardiac transplantation, or as destination therapy for patients with unfavorable transplant candidacy. Neurologic complications are some of the most common and devastating complications in these patients. Preoperative carotid ultrasound is, therefore, a standard evaluation in patients at risk for cerebrovascular disease. Postoperative carotid artery Doppler sonography is performed in those patients with neurologic symptoms. It is likely, therefore, that sonographers, radiologists, and other physicians working in a center where LVADs are implanted will likely encounter a carotid artery Doppler study in this patient group. To our knowledge, the carotid Doppler findings in these patients have never been published. We review the Doppler ultrasound findings in 6 patients after LVAD insertion.

Dyskalaemia following diffuse axonal injury: case report and review of the literature

PubMed Central

Cronin, David; Kaliaperumal, Chandrasekaran; Kumar, Ramanathan; Kaar, George

2012-01-01

Traumatic brain injury, and its management, commonly causes derangements in potassium balance. There are a number of recognised causative factors including head trauma, hypothermia and iatrogenic factors such as pharmacological agents and permissive cooling. We describe a case of a 19-year-old man with a severe traumatic brain injury. In a 36-h period, his intracranial pressure increased despite maximal medical therapy and he developed refractory hypokalaemia. Immediately following a decompressive craniectomy, the patient was noted to be profoundly hyperkalaemic; this led to the development of ventricular tachycardia and cardiac arrest, from which the patient did not recover. The effects of brain injury on potassium balance are not well appreciated; the effect of decompressive craniectomy on potassium (K+) balance has not been described previously. We would like to emphasise the potential effect of diffuse axonal injury, a severe form of brain injury and decompressive craniectomy on potassium balance. PMID:23060370

Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

PubMed

Kudenchuk, Peter J; Leroux, Brian G; Daya, Mohamud; Rea, Thomas; Vaillancourt, Christian; Morrison, Laurie J; Callaway, Clifton W; Christenson, James; Ornato, Joseph P; Dunford, James V; Wittwer, Lynn; Weisfeldt, Myron L; Aufderheide, Tom P; Vilke, Gary M; Idris, Ahamed H; Stiell, Ian G; Colella, M Riccardo; Kayea, Tami; Egan, Debra; Desvigne-Nickens, Patrice; Gray, Pamela; Gray, Randal; Straight, Ron; Dorian, Paul

2017-11-28

Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo ( P <0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge ( P =0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P =0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P =0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647. © 2017 American Heart Association, Inc.

Maintenance of ventricular fibrillation in heterogeneous ventricle.

PubMed

Arevalo, Hamenegild J; Trayanova, Natalia A

2006-01-01

Although ventricular fibrillation (VF) is the prevalent cause of sudden cardiac death, the mechanisms that underlie VF remain elusive. One possible explanation is that VF is driven by a single robust rotor that is the source of wavefronts that break-up due to functional heterogeneities. Previous 2D computer simulations have proposed that a heterogeneity in background potassium current (IK1) can serve as the substrate for the formation of mother rotor activity. This study incorporates IK1 heterogeneity between the left and right ventricle in a realistic 3D rabbit ventricle model to examine its effects on the organization of VF. Computer simulations show that the IK1 heterogeneity contributes to the initiation and maintenance of VF by providing regions of different refractoriness which serves as sites of wave break and rotor formation. A single rotor that drives the fibrillatory activity in the ventricle is not found in this study. Instead, multiple sites of reentry are recorded throughout the ventricle. Calculation of dominant frequencies for each myocardial node yields no significant difference between the dominant frequency of the LV and the RV. The 3D computer simulations suggest that IK1 spatial heterogeneity alone can not lead to the formation of a stable rotor.

Reduced intrinsic heart rate is associated with reduced arrhythmic susceptibility in guinea-pig heart.

PubMed

Osadchii, Oleg E

2014-12-01

In the clinical setting, patients with slower resting heart rate are less prone to cardiovascular death compared with those with elevated heart rate. However, electrophysiological adaptations associated with reduced cardiac rhythm have not been thoroughly explored. In this study, relationships between intrinsic heart rate and arrhythmic susceptibility were examined by assessments of action potential duration (APD) rate adaptation and inducibility of repolarization alternans in sinoatrial node (SAN)-driven and atrioventricular (AV)-blocked guinea-pig hearts perfused with Langendorff apparatus. Electrocardiograms, epicardial monophasic action potentials, and effective refractory periods (ERP) were assessed in normokalemic and hypokalemic conditions. Slower basal heart rate in AV-blocked hearts was associated with prolonged ventricular repolarization during spontaneous beating, and with attenuated APD shortening at increased cardiac activation rates during dynamic pacing, when compared with SAN-driven hearts. During hypokalemic perfusion, the inducibility of repolarization alternans and tachyarrhythmia by rapid pacing was found to be lower in AV-blocked hearts. This difference was ascribed to prolonged ERP in the setting of reduced basal heart rate, which prevented ventricular capture at critically short pacing intervals required to induce arrhythmia. Reduced basal heart rate is associated with electrophysiological changes that prevent electrical instability upon an abrupt cardiac acceleration.

Disseminated strongyloidiasis in a immunocompromised host.

PubMed

Mundkur, Suneel C; Aroor, Shrikiran; Jayashree, K

2011-12-01

Strongyloidiasis in an immunocompromised patient has the potential to be life threatening. We describe a boy who was on steroids for acute demyelinating myelitis and receiving antibiotics for E. coli UTI and meningitis. He developed anasarca, malabsorption, malnutrition and left ventricular failure. Duodenal biopsy revealed abundant rhabditiform larvae of Strongyloides stercoralis. The diagnosis went unsuspected and proved fatal. This emphasizes the need to have a high index of suspicion and early intervention for S. stercoralis in immunosuppressed persons who present with refractory gastrointestinal symptoms.

Optimal ECG (Electrocardiogram) Electrode Sites and Criteria for Detection of Asymptomatic Coronary Artery Disease at Rest and with Exercise.

DTIC Science & Technology

1985-12-01

a healthy coronary artery can increase flow ninefold by dilating during peak workloads. By preventing dilation , circum- ferential atherosclerosis...Ischemic Canine Myocardium, J. Electrocardiol. 15(4):335, 1982. 127. Burgess, M.J., Green, L.S., Millar, K., Wyatt, R., and Abildskov, J.A.: The...Refractory Periods of Ischemic Canine Ventricular Myocardium, J. Electrocardiol. 15(1):I, 1982. 129. Burgess, M.J., Lux, R.L., Wyatt, R.F., and Abildskov, J.A

Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea-pig heart.

PubMed

Osadchii, O E

2012-08-01

Endocardial pacing instituted to treat symptomatic bradycardia may nevertheless promote tachyarrhythmia in some pacemaker-implanted patients. We sought to determine the contributing electrophysiological mechanisms. Left ventricular (LV) monophasic action potential duration (APD(90)) and effective refractory periods were determined in perfused guinea-pig hearts along with volume-conducted ECG recordings during epicardial and endocardial stimulations. Consistent with electrotonic modulation of repolarization, APD(90) at a given (either epicardial or endocardial) recording site tended to be longer while pacing from the ipsilateral LV site as compared to stimulations applied at the opposite side of ventricular wall. As a result, the intrinsic transmural repolarization gradient was amplified during endocardial pacing while being significantly reduced upon epicardial stimulations. The maximum slope of APD(90) restitution was greater upon endocardial than epicardial pacing. The excitability was found to recur at earlier repolarization time point at endocardium than epicardium, thereby contributing to increased endocardial critical intervals for re-excitation. Premature extrasystolic beats could have been elicited at shorter coupling stimulation intervals and propagated with greater transmural conduction delay upon endocardial than epicardial stimulations. Endocardial site exhibited lower ventricular fibrillation thresholds and greater inducibility of tachyarrhythmia upon extrasystolic stimulations as compared to epicardium. Arrhythmic susceptibility in guinea-pig heart is greater during endocardial than epicardial pacing because of greater transmural APD(90) dispersion, steeper electrical restitution slopes, greater critical intervals for LV re-excitation and slower transmural conduction of the earliest premature ectopic beats. Further studies are warranted to determine whether these effects may contribute to proarrhythmia in paced human patients. © 2012 The Author Acta Physiologica © 2012 Scandinavian Physiological Society.

Effect of irbesartan on development of atrial fibrosis and atrial fibrillation in a canine atrial tachycardia model with left ventricular dysfunction, association with p53.

PubMed

Kataoka, Naoya; Nishida, Kunihiro; Kinoshita, Koshi; Sakamoto, Tamotsu; Nakatani, Yosuke; Tsujino, Yasushi; Mizumaki, Koichi; Inoue, Hiroshi; Kinugawa, Koichiro

2016-12-01

Effects of an angiotensin II receptor blocker, irbesartan (IRB), on the development of atrial fibrosis and atrial fibrillation (AF) were assessed in a canine model of atrial tachycardia remodeling (ATR) with left ventricular dysfunction, together with its possible association with involvement of p53. Atrial tachypacing (400 bpm for 4 weeks) was used to induce ATR in beagles treated with placebo (ATR-dogs, n = 6) or irbesartan (IRB-dogs, n = 5). Non-paced sham dogs served as control (Control-dogs, n = 4). ATR- and IRB-dogs developed tachycardia-induced left ventricular dysfunction. Atrial effective refractory period (AERP) shortened (83 ± 5 ms, p < 0.05), inter-atrial conduction time prolonged (72 ± 2 ms, p < 0.05), and AF duration increased (29 ± 5 s, p < 0.05 vs. baseline) after 4 weeks in ATR-dogs. ATR-dogs also had a larger area of atrial fibrous tissue (5.2 ± 0.5 %, p < 0.05 vs. Control). All these changes, except for AERP, were attenuated in IRB-dogs (92 ± 3 ms, 56 ± 3 ms, 9 ± 5 s, and 2.5 ± 0.7 %, respectively; p < 0.05 vs. ATR for each). In ATR-dogs, p53 expression in the left atrium decreased by 42 % compared with Control-dogs (p < 0.05); however, it was highly expressed in IRB-dogs (+89 % vs. ATR). Transforming growth factor (TGF)-β1 expression was enhanced in ATR-dogs (p < 0.05 vs. Control) but reduced in IRB-dogs (p < 0.05 vs. ATR). Irbesartan suppresses atrial fibrosis and AF development in a canine ATR model with left ventricular dysfunction in association with p53.

Refractory Hypertension Is not Attributable to Intravascular Fluid Retention as Determined by Intracardiac Volumes.

PubMed

Velasco, Alejandro; Siddiqui, Mohammed; Kreps, Eric; Kolakalapudi, Pavani; Dudenbostel, Tanja; Arora, Garima; Judd, Eric K; Prabhu, Sumanth D; Lloyd, Steven G; Oparil, Suzanne; Calhoun, David A

2018-06-04

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P =0.003) and had a greater proportion of women (75.0% versus 43%; P =0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m 2 ; P <0.001), posterior wall thickness (10.1±3.1 versus 7.7±1.5 mm; P =0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P <0.001). There was no difference in B-type natriuretic peptide levels and left atrial or ventricular volumes. Diastolic dysfunction was noted in RfHTN. Our findings demonstrate greater left ventricular hypertrophy without chamber enlargement in RfHTN, suggesting that antihypertensive treatment failure is not attributable to intravascular volume retention. © 2018 American Heart Association, Inc.

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

NASA Astrophysics Data System (ADS)

Connolly, Adam; Robson, Matthew D.; Schneider, Jürgen; Burton, Rebecca; Plank, Gernot; Bishop, Martin J.

2017-09-01

Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic. In this study, we sought to investigate how electric fields from implanted devices interact with the highly trabeculated human endocardial surface to better understand shock success in order to help optimise future clinical protocols. A bi-ventricular human computational model was constructed from high resolution (350 μm) ex-vivo MR data, including anatomically accurate endocardial structures. Monophasic shocks were applied between a basal right ventricular catheter and an exterior ground. Shocks of varying strengths were applied with both anodal [positive right ventricle (RV) electrode] and cathodal (negative RV electrode) polarities at different states of tissue refractoriness and during induced arrhythmias. Anodal shocks induced isolated positive VEs at the distal side of "detached" trabeculations, which rapidly spread into hyperpolarised tissue on the surrounding endocardial surfaces following the shock. Anodal shocks thus depolarised more tissue 10 ms after the shock than cathodal shocks where the propagation of activation from VEs induced on the proximal side of "detached" trabeculations was prevented due to refractory endocardium. Anodal shocks increased arrhythmia complexity more than cathodal shocks during failed anti-arrhythmia shocks. In conclusion, multiple detached trabeculations in the human ventricle interact with anodal stimuli to induce multiple secondary sources from VEs, facilitating more rapid shock-induced ventricular excitation compared to cathodal shocks. Such a mechanism may help explain inter-species differences in response to shocks and help to develop novel defibrillation strategies.

At the Atrioventricular Crossroads: Dual Pathway Electrophysiology in the Atrioventricular Node and its Underlying Heterogeneities

PubMed Central

George, Sharon A; Faye, N Rokhaya; Murillo-Berlioz, Alejandro; Lee, K Benjamin; Trachiotis, Gregory D; Efimov, Igor R

2017-01-01

The atrioventricular node (AVN) is a complex structure that performs a variety of functions in the heart. The AVN is primarily an electrical gatekeeper between the atria and ventricles and introduces a delay between atrial and ventricular excitation, allowing for efficient ventricular filling. The AVN is composed of several compartments that safely transmit electrical excitation from the atria to the ventricles via the fast or slow pathways. There are many electrophysiological differences between these pathways, including conduction time and electrical refractoriness, that increase the predisposition of the atrioventricular junction to arrhythmias such as atrioventricular nodal re-entrant tachycardia. These varied electrophysiological characteristics of the fast and slow pathways stem from their unique structural and molecular composition (tissue and cellular geometry, ion channels and gap junctions). This review summarises the structural and molecular heterogeneities of the human AVN and how they result in electrophysiological variations and arrhythmias. PMID:29326832

Advanced heart failure due to cancer therapy.

PubMed

Shah, Sachin; Nohria, Anju

2015-01-01

Certain chemotherapeutic agents and mediastinal irradiation can be cardiotoxic and place cancer survivors at risk for developing advanced heart failure (HF). Anthracyclines are the prototypical agents associated with left ventricular (LV) dysfunction. Newer agents including trastuzumab and certain tyrosine kinase inhibitors such as sunitinib can also cause cardiomyopathy. Cancer survivors with advanced HF refractory to standard medical management should be considered for advanced therapies, including mechanical circulatory support (MCS) and transplantation. While overall outcomes after MCS and transplantation are similar in cancer survivors compared to other etiologies of HF, patients with radiation-induced restrictive cardiomyopathy have a significantly worse prognosis after transplantation. The increased need for right ventricular (RV) support after MCS in cancer survivors necessitates a careful evaluation for pre-operative RV dysfunction. Special consideration must also be given to the risk for recurrent malignancy, neurocognitive dysfunction, and increased psychological needs in this patient population.

Extracorporeal circuit for Panton-Valentine leukocidin-producing Staphylococcus aureus necrotizing pneumonia.

PubMed

Lavoue, S; Le Gac, G; Gacouin, A; Revest, M; Sohier, L; Mouline, J; Jouneau, S; Flecher, E; Tattevin, P; Tadié, J-M

2016-09-01

To describe two cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) necrotizing pneumonia treated with ECMO, and complete pulmonary evaluation at six months. Retrospective analysis of two patients presenting with severe PVL-SA pneumonia who both underwent complete respiratory function testing and chest CT scan six months after hospital discharge. Indications for ECMO were refractory hypoxia and left ventricular dysfunction associated with right ventricular dilatation. Patients were weaned off ECMO after 52 and 5 days. No ECMO-related hemorrhagic complication was observed. Pulmonary function tests performed at six months were normal and the CT scan showed complete regression of pulmonary injuries. PVL-SA pneumonia is characterized by extensive parenchymal injuries, including necrotic and hemorrhagic complications. ECMO may be used as a salvage treatment without any associated hemorrhagic complication, provided anticoagulant therapy is carefully monitored, and may lead to complete pulmonary recovery at six months. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Therapeutic trial of granulocyte-colony stimulating factor for dilated cardiomyopathy in three dogs.

PubMed

Park, Chul; Yoo, Jong-Hyun; Jeon, Hyo-Won; Kang, Byeong-Teck; Kim, Jung-Hyun; Jung, Dong-In; Lim, Chae-Young; Lee, Hye-Jung; Hahm, Dae-Hyun; Woo, Eung-Je; Park, Hee-Myung

2007-09-01

Three dogs were presented to us for evaluation of cardiac problems. Electrocardiographic recordings revealed severe tachyarrhythmia and atrial fibrillation with ventricular tachycardia in 2 of the 3 dogs. The echocardiographic findings of the 3 dogs revealed markedly decreased fractional shortening and a marked increase in E-point septal separation. Based on the results of electrocardiographic and echocardiographic evaluation, the 3 dogs were diagnosed as dilated cardiomyopathy (DCM). The dogs were treated with conventional cardiac medication, but cardiac function did not improve and the clinical signs remained. We subsequently attempted treatment with granulocyte-colony stimulating factor (G-CSF; 10 microg/kg, subcutaneously). The specific purpose of G-CSF therapy for DCM was to improve cardiac function and a significant improvement in cardiac function was confirmed. The three dogs had no treatment side effects. This case report suggests that G-CSF might have therapeutic effects for medically refractory DCM in dogs.

Outcomes of patients with cardiogenic shock treated with TandemHeart® percutaneous ventricular assist device: Importance of support indication and definitive therapies as determinants of prognosis.

PubMed

Smith, LaVone; Peters, Anthony; Mazimba, Sula; Ragosta, Michael; Taylor, Angela M

2018-05-10

The objective of this study was to review the characteristics of patients in cardiogenic shock treated with TandemHeart ® percutaneous ventricular assist device (pVAD) to determine influential predictors of survival. The TandemHeart ® pVAD is used in the management of patients with cardiogenic shock resulting from a variety of conditions. Several studies have documented the efficacy of this therapy and outlined its complications. Still, there is little data to guide the effective and appropriate use of this resource. Patients referred for TandemHeart ® pVAD implant for refractory cardiogenic shock at the University of Virginia between September 2007 and October 2015 were retrospectively analyzed. Univariate analysis was used to identify predictors of mortality. Fifty-five patients underwent successful TandemHeart ® implant. Hemodynamics significantly improved following TandemHeart ® implant. Cardiac index increased from 1.8 ± 0.6 to 3.1 ± 1.0 L/min/m 2 (P = 0.007) and pulmonary capillary wedge pressure decreased from 30. 5 ± 9.9 to 19.6 ± 7.4 mmHg (P =0.0007). Survival was significantly influenced by implant indication with 23.8% surviving in bridge to recovery vs. 51% in bridge to LVAD or surgery (P = 0.04). In patients who did not receive definitive therapy, only 4 (13.8%) were weaned from TandemHeart ® support and survived to hospital discharge. Only younger age, 51.8 vs. 62.7 years, predicted survival to hospital discharge (P = 0.004). Mortality from refractory cardiogenic shock is high even with TandemHeart ® support. Our study found that patients with an exit strategy with either cardiac surgery or durable LVAD implant significantly influenced survival to hospital discharge. © 2018 Wiley Periodicals, Inc.

A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

PubMed

Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

2016-09-28

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.

PubMed

Nisbet, Ashley M; Camelliti, Patrizia; Walker, Nicola L; Burton, Francis L; Cobbe, Stuart M; Kohl, Peter; Smith, Godfrey L

2016-05-01

Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Emerging therapeutic targets in the short QT syndrome.

PubMed

Hancox, Jules C; Whittaker, Dominic G; Du, Chunyun; Stuart, A Graham; Zhang, Henggui

2018-05-01

Short QT Syndrome (SQTS) is a rare but dangerous condition characterised by abbreviated repolarisation, atrial and ventricular arrhythmias and risk of sudden death. Implantable cardioverter defibrillators (ICDs) are a first line protection against sudden death, but adjunct pharmacology is beneficial and desirable. Areas covered: The genetic basis for genotyped SQTS variants (SQT1-SQT8) and evidence for arrhythmia substrates from experimental and simulation studies are discussed. The main ion channel/transporter targets for antiarrhythmic pharmacology are considered in respect of potential genotype-specific and non-specific treatments for the syndrome. Expert opinion: Potassium channel blockade is valuable for restoring repolarisation and QT interval, though genotype-specific limitations exist in the use of some K + channel inhibitors. A combination of K + current inhibition during the action potential plateau, with sodium channel inhibition that collectively result in delaying repolarisation and post-repolarisation refractoriness is likely to be valuable in prolonging effective refractory period and wavelength for re-entry. Genotype-specific K + channel inhibition is limited by a lack of targeted inhibitors in clinical use, though experimentally available selective inhibitors now exist. The relatively low proportion of successfully genotyped cases justifies an exome or genome sequencing approach, to reveal new mediators and targets, as demonstrated recently for SLC4A3 in SQT8.

[Catheter ablation of ectopic incessant atrial tachycardia using radiofrequency. Reversion of tachycardiomyopathy].

PubMed

de Paola, A A; Mendonça, A; Balbão, C E; Tavora, M Z; da Silva, R M; Hara, V M; Guiguer Júnior, N; Vattimo, A C; Souza, I A; Portugal, O P

1993-10-01

A 8-year-old female patient with refractory incessant atrial tachycardia, very symptomatic and with left ventricular ejection fraction of 0.25. Electrophysiological study and endocardial mapping localized the site of the origin of atrial tachycardia in the superior right atrium. In this site 2 applications of radiofrequency current (25V, 20 and 50 seconds) resulted in termination of the atrial tachycardia. She was discharged off antiarrhythmic drugs and after 2 months ejection fraction was 0.52. She was completely asymptomatic 6 months after ablation procedure.

[Surgical cryoablation and left ventriculoplasty for electrical storm after acute myocardial infarction].

PubMed

Tobe, Satoshi; Yoshida, K; Adachi, K; Fukase, K; Tanimura, N; Yamaguchi, M

2008-03-01

A 65-year-old man was referred to our hospital to treat recent anterior myocardial infarction. Coronary artery angiography showed acute occlusion of left anterior descending coronary artery (LAD) and chronic occlusion of right coronary artery. After emergent percutaneous coronary intervention for LAD, drug-refractory electrical storm necessitating frequent electrical defibrillating cardioversion occurred. This patient successfully underwent surgical cryoablation, left ventriculoplasty and coronary revascularization. At 2 years and 10th month after the operation, he is well without limitation of daily activities and any evidence of myocardial ischemia and ventricular tachycardia.

Specific considerations with the automatic implantable atrial defibrillator.

PubMed

Jung, W; Wolpert, C; Esmailzadeh, B; Spehl, S; Herwig, S; Schumacher, B; Lewalter, T; Omran, H; Kirchhoff, P G; Lüderitz, B

1998-08-01

Internal atrial defibrillation has been evaluated as an alternative approach to the external technique for more than two decades. Previous studies in animals and humans have shown that internal atrial defibrillation is feasible with relatively low energies. The promising results achieved with internal atrial defibrillation have facilitated the development of an implantable atrial defibrillator (IAD). For any new therapy, it is imperative to demonstrate safety, efficacy, tolerability with improvement in quality of life, and cost-effectiveness compared with therapeutic options already available. Maintenance of sinus rhythm or prolonged duration in arrhythmia-free intervals should be demonstrated clearly with an IAD. Initial clinical experience with the Metrix system indicates stable atrial defibrillation thresholds, appropriate R wave synchronization markers, no shock-induced ventricular proarrhythmia, and excellent detection of atrial fibrillation (AF) with a specificity of 100%. Ventricular proarrhythmia has not been reported for correctly R wave synchronized low-energy shocks when closely coupled to RR intervals, and long-short cycles are avoided. Preliminary experience with the Metrix system suggests that the IAD may offer a therapeutic alternative for a subgroup of patients with drug-refractory, symptomatic, long-lasting, and infrequent episodes of AF. Further efforts must be undertaken to reduce the patient discomfort associated with internal atrial defibrillation in an attempt to make this new therapy acceptable to a larger patient population with AF.

A novel method to estimate safety factor of capture by a fetal micropacemaker.

PubMed

Vest, Adriana Nicholson; Zhou, Li; Bar-Cohen, Yaniv; Eli Loeb, Gerald

2016-07-01

We have developed a rechargeable fetal micropacemaker in order to treat severe fetal bradycardia with comorbid hydrops fetalis, a life-threatening condition in pre-term non-viable fetuses for which there are no effective treatment options. The small size and minimally invasive form factor of our design limit the volume available for circuitry and a power source. The device employs a fixed-rate and fixed-amplitude relaxation oscillator and a tiny, rechargeable lithium ion power cell. For both research and clinical applications, it is valuable to monitor the electrode-myocardium interface in order to determine that adequate pacemaker output is being provided. This is typically accomplished by observing the minimal stimulus strength that achieves threshold for pacing capture. The output of our simple micropacemaker cannot be programmatically altered to determine this minimal capture threshold, but a safety factor can be inferred by determining the refractory period for ventricular capture at a given stimulus strength. This is done by measuring the minimal timing between naturally occurring QRS complexes and pacing stimuli that successfully generate a premature ventricular contraction. The method was tested in a pilot study in four fetal sheep and the data demonstrate that a relative measure of threshold is obtainable. This method provides valuable real-time information about the electrode-tissue interface.

Advancements in mechanical circulatory support for patients in acute and chronic heart failure

PubMed Central

Csepe, Thomas A.

2017-01-01

Cardiogenic shock (CS) continues to have high mortality and morbidity despite advances in pharmacological, mechanical, and reperfusion approaches to treatment. When CS is refractory to medical therapy, percutaneous mechanical circulatory support (MCS) should be considered. Acute MCS devices, ranging from intra-aortic balloon pumps (IABPs) to percutaneous temporary ventricular assist devices (VAD) to extracorporeal membrane oxygenation (ECMO), can aid, restore, or maintain appropriate tissue perfusion before the development of irreversible end-organ damage. Technology has improved patient survival to recovery from CS, but in patients whom cardiac recovery does not occur, acute MCS can be effectively utilized as a bridge to long-term MCS devices and/or heart transplantation. Heart transplantation has been limited by donor heart availability, leading to a greater role of left ventricular assist device (LVAD) support. In patients with biventricular failure that are ineligible for LVAD implantation, further advancements in the total artificial heart (TAH) may allow for improved survival compared to medical therapy alone. In this review, we discuss the current state of acute and durable MCS, ongoing advances in LVADs and TAH devices, improved methods of durable MCS implantation and patient selection, and future MCS developments in this dynamic field that may allow for optimization of HF treatment. PMID:29268418

A novel method to estimate safety factor of capture by a fetal micropacemaker

PubMed Central

Vest, Adriana Nicholson; Zhou, Li; Bar-Cohen, Yaniv; Loeb, Gerald Eli

2016-01-01

We have developed a rechargeable fetal micropacemaker in order to treat severe fetal bradycardia with comorbid hydrops fetalis, a life-threatening condition in pre-term non-viable fetuses for which there are no effective treatment options. The small size and minimally invasive form factor of our design limit the volume available for circuitry and a power source. The device employs a fixed-rate and fixed-amplitude relaxation oscillator and a tiny, rechargeable lithium ion power cell. For both research and clinical applications, it is valuable to monitor the electrode-myocardium interface in order to determine that adequate pacemaker output is being provided. This is typically accomplished by observing the minimal stimulus strength that achieves threshold for pacing capture. The output of our simple micropacemaker cannot be programmatically altered to determine this minimal capture threshold, but a safety factor can be inferred by determining the refractory period for ventricular capture at a given stimulus strength. This is done by measuring the minimal timing between naturally occurring QRS complexes and pacing stimuli that successfully generate a premature ventricular contraction. The method was tested in a pilot study in 4 fetal sheep and the data demonstrate that a relative measure of threshold is obtainable. This method provides valuable real-time information about the electrode-tissue interface. PMID:27340134

Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson's Disease.

PubMed

Sharim, Justin; Yazdi, Daniel; Baohan, Amy; Behnke, Eric; Pouratian, Nader

2017-04-01

Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p < 0.0001), 0.206 (p = 0.00219), 0.168 (p = 0.0119), and 0.159 (p = 0.0136), respectively. Third ventricular width, gender, AC-PC distance, and age each account for 44.06% (21.38-65.69%, 95% CI), 20.82% (10.51-35.88%), 21.46% (8.28-37.05%), and 13.66% (2.62-28.64%) of the R 2 value, respectively. Effect size calculation was significant for a change in the GPi laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization. © 2016 International Neuromodulation Society.

Heart transplantation: review

PubMed Central

Mangini, Sandrigo; Alves, Bárbara Rubim; Silvestre, Odílson Marcos; Pires, Philippe Vieira; Pires, Lucas José Tachotti; Curiati, Milena Novaes Cardoso; Bacal, Fernando

2015-01-01

ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants. PMID:26154552

Changes in left ventricular repolarization and ion channel currents following a transient rate increase superimposed on bradycardia in anesthetized dogs.

PubMed

Rubart, M; Lopshire, J C; Fineberg, N S; Zipes, D P

2000-06-01

We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by approximately 6 and approximately 3 mV, respectively (P < 0.02), and prolonged action potential duration at 90% repolarization from 235+/-8 msec to 278+/-8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, Ito, over the range of physiologic frequencies, resulting from a approximately 30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, I(Ca.L), by 15% to 35 % between +10 and +60 mV; and (3) increases in peak density of the Ca2+-activated chloride current, I(Cl.Ca), by 30% to 120% between +30 and +50 mV. Frequency-dependent reduction in Ito combined with enhanced I(Ca.L) causes an increase in net inward current that may be responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward I(Ca.Cl).

Performance of a specific algorithm to minimize right ventricular pacing: A multicenter study.

PubMed

Strik, Marc; Defaye, Pascal; Eschalier, Romain; Mondoly, Pierre; Frontera, Antonio; Ritter, Philippe; Haïssaguerre, Michel; Ploux, Sylvain; Ellenbogen, Kenneth A; Bordachar, Pierre

2016-06-01

In Boston Scientific dual-chamber devices, the RYTHMIQ algorithm aims to minimize right ventricular pacing. We evaluated the performance of this algorithm determining (1) the appropriateness of the switch from the AAI(R) mode with backup VVI pacing to the DDD(R) mode in case of suspected loss of atrioventricular (AV) conduction and (2) the rate of recorded pacemaker-mediated tachycardia (PMT) when AV hysteresis searches for restored AV conduction. In this multicenter study, we included 157 patients with a Boston Scientific dual-chamber device (40 pacemakers and 117 implantable cardioverter-defibrillators) without permanent AV conduction disorder and with the RYTHMIQ algorithm activated. We reviewed the last 10 remote monitoring-transmitted RYTHMIQ and PMT episodes. We analyzed 1266 episodes of switch in 142 patients (90%): 207 (16%) were appropriate and corresponded to loss of AV conduction, and 1059 (84%) were inappropriate, of which 701 (66%) were related to compensatory pause (premature atrial contraction, 7%; premature ventricular contraction, 597 (56%); or both, 27 (3%)) or to a premature ventricular contraction falling in the post-atrial pacing ventricular refractory period interval (219, 21%) and 94 (10%) were related to pacemaker dysfunction. One hundred fifty-four PMT episodes were diagnosed in 27 patients (17%). In 85 (69%) of correctly diagnosed episodes, the onset of PMT was directly related to the algorithm-related prolongation of the AV delay, promoting AV dissociation and retrograde conduction. This study highlights some of the limitations of the RYTHMIQ algorithm: high rate of inappropriate switch and high rate of induction of PMT. This may have clinical implications in terms of selection of patients and may suggest required changes in the algorithm architecture. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Intra-Aortic Balloon Counterpulsation in Patients with Chronic Heart Failure and Cardiogenic Shock: Clinical Response and Predictors of Stabilization

PubMed Central

Sintek, Marc A.; Gdowski, Mark; Lindman, Brian R.; Nassif, Michael; Lavine, Kory J.; Novak, Eric; Bach, Richard G.; Silvestry, Scott C.; Mann, Douglas L.; Joseph, Susan M.

2015-01-01

Objective To characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock prior to implantation of a left ventricular assist device (LVAD). Background Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. Methods We identified 54 patients supported with IABP prior to LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. Results Clinical decompensation after IABP occurred in 23 (43%) patients. Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (p<0.01 for both). While baseline characteristics were similar between groups, right and left ventricular cardiac power indices (Cardiac power Index= Cardiac Index × Mean arterial pressure / 451)identified patients who were likely to stabilize (AUC=0.82). Conclusions Among patients with chronic systolic heart failure who develop cardiogenic shock, more than half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, both measures of work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support. PMID:26164215

Overview of adult congenital heart transplants

PubMed Central

Morales, David

2018-01-01

Transplantation for adult patients with congenital heart disease (ACHD) is a growing clinical endeavor in the transplant community. Understanding the results and defining potential high-risk patient subsets will allow optimization of patient outcomes. This review summarizes the scope of ACHD transplantation, the mechanisms of late ventricular dysfunction, the ACHD population at risk of developing heart failure, the indications and potential contraindications for transplant, surgical considerations, and post-transplant outcomes. The findings reveal that 3.3% of adult heart transplants occur in ACHD patients. The potential mechanisms for the development of late ventricular dysfunction include a morphologic systemic right ventricle, altered coronary perfusion, and ventricular noncompaction. The indications for transplant in ACHD patients include systemic ventricular failure refractory medical therapy, Fontan patients failing from chronic passive pulmonary circulation, and progressive cyanosis leading to functional decline. Transplantation in ACHD patients can be quite complex and may require extensive reconstruction of the branch pulmonary arteries, systemic veins, or the aorta. Vasoplegia, bleeding, and graft right ventricular dysfunction can complicate the immediate post-transplant period. The post-transplant operative mortality ranges between 14% and 39%. The majority of early mortality occurs in ACHD patients with univentricular congenital heart disease. However, there has been improvement in operative survival in more contemporary studies. In conclusion, the experience with cardiac transplantation for ACHD patients with end-stage heart failure is growing, and high-risk patient subsets have been defined. Significant strides have been made in developing evidence-based guidelines of indications for transplant, and the intraoperative management of complex reconstruction has evolved. With proper patient selection, more aggressive use of mechanical circulatory support, and earlier referral of patients with failing Fontan physiology, outcomes should continue to improve. PMID:29492392

An approach to ablate and pace:AV junction ablation and pacemaker implantation performed concurrently from the same venous access site.

PubMed

Issa, Ziad F

2007-09-01

Atrioventricular junction (AVJ) ablation combined with permanent pacemaker implantation (the "ablate and pace" approach) remains an acceptable alternative treatment strategy for symptomatic, drug-refractory atrial fibrillation (AF) with rapid ventricular response. This case series describes the feasibility and safety of catheter ablation of the AVJ via a superior vena caval approach performed during concurrent dual-chamber pacemaker implantation. A total of 17 consecutive patients with symptomatic, drug-refractory, paroxysmal AF underwent combined AVJ ablation and dual-chamber pacemaker implantation procedure using a left axillary venous approach. Two separate introducer sheaths were placed into the axillary vein. The first sheath was used for implantation of the pacemaker ventricular lead, which was then connected to the pulse generator. Subsequently, a standard ablation catheter was introduced through the second axillary venous sheath and used for radiofrequency (RF) ablation of the AVJ. After successful ablation, the catheter was withdrawn and the pacemaker atrial lead was advanced through that same sheath and implanted in the right atrium. Catheter ablation of the AVJ was successfully achieved in all patients. The median number of RF applications required to achieve complete AV block was three (range 1-10). In one patient, AV conduction recovered within the first hour after completion of the procedure, and AVJ ablation was then performed using the conventional femoral venous approach. There were no procedural complications. Catheter ablation of the AVJ can be performed successfully and safely via a superior vena caval approach in patients undergoing concurrent dual-chamber pacemaker implantation.

Contemporary Use of Veno-Arterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock in Acute Coronary Syndrome.

PubMed

Negi, Smita I; Sokolovic, Mladen; Koifman, Edward; Kiramijyan, Sarkis; Torguson, Rebecca; Lindsay, Joseph; Ben-Dor, Itsik; Suddath, William; Pichard, Augusto; Satler, Lowell; Waksman, Ron

2016-02-01

Refractory cardiogenic shock (RCS) in acute myocardial infarction (AMI) is associated with high rates of mortality. Smaller ventricular assist devices, such as the intraaortic balloon pump, provide limited support. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) offers more robust mechanical ventricular support, but is not widely utilized by interventional cardiologists. This study aimed to evaluate the patient characteristics and outcomes of VA-ECMO with RCS in the setting of AMI. A retrospective chart review of all VA-ECMO cannulations between 2009 and 2014 was performed, and patients with an indication of RCS in AMI were identified. A total of 15 patients underwent VA-ECMO placement for AMI with RCS. One-third of these patients presented with out-of-hospital cardiac arrest, and 60% had ST-elevation myocardial infarction. The Intraaortic balloon pump was placed in addition to VA-ECMO in 60% of patients. Median duration of VA-ECMO support was 45 hours. Successful wean off VA-ECMO was obtained in 50% of the patients, and vascular complications occurred in 53% of patients. The survival rate at discharge was 47%, and all survivors were alive at 30 days post discharge. VA-ECMO is infrequently used in patients for cardiopulmonary resuscitation in the AMI setting. When used judiciously, it has good clinical outcomes in this group of patients. However, use of VA-ECMO should be individualized based on vascular anatomy for best results. Close cooperation among interventional cardiologists, cardiovascular surgeons, cardiologists, cardiac intensivists, and perfusionists is essential for success of this therapy for RCS in AMI.

Cost-Effectiveness of Ventricular Assist Device Destination Therapy for Advanced Heart Failure in Duchenne Muscular Dystrophy.

PubMed

Magnetta, Defne A; Kang, JaHyun; Wearden, Peter D; Smith, Kenneth J; Feingold, Brian

2018-05-17

Destination ventricular assist device therapy (DT-VAD) is well accepted in select adults with medically refractory heart failure (HF) who are not transplant candidates; however, its use in younger patients with progressive diseases is unclear. We sought to evaluate the cost-effectiveness of DT-VAD in Duchenne muscular dystrophy (DMD) patients with advanced HF. We created a Markov-state transition model (5-year horizon) to compare survival, costs, and quality of life (QOL) between medical management and DT-VAD in DMD with advanced HF. Model input parameters were derived from the literature. We used sensitivity analyses to explore uncertainty around model assumptions. DT-VAD had higher costs ($435,602 vs. $125,696), survival (3.13 vs. 0.60 years), and quality-adjusted survival (1.99 vs. 0.26 years) than medical management. The incremental cost-effectiveness ratio (ICER) for DT-VAD was $179,086 per quality-adjusted life year (QALY). In sensitivity analyses that were widely varied to account for uncertainty in model assumptions, the DT-VAD strategy generally remained more costly and effective than medical management. Only when VAD implantation costs were <$113,142 did the DT-VAD strategy fall below the $100,000/QALY willingness-to-pay threshold commonly considered to be "cost-effective." In this exploratory analysis, DT-VAD for patients with DMD and advanced HF exceeded societal expectations for cost-effectiveness but had an ICER similar to the accepted practice of DT-VAD in adult HF patients. While more experience and research in this population is needed, our analysis suggests that DT-VAD for advanced HF in DMD should not be dismissed solely based on cost.

Electrical Storm: Incidence, Prognosis and Therapy.

PubMed

Sagone, Antonio

2015-12-01

The term "electrical storm" indicates a life-threatening clinical condition characterized by the recurrence of hemodynamically unstable ventricular tachycardia and/or ventricular fibrillation, in particular in patients with ICD implanted for primary or secondary prevention. Although there isn't a shared definition of electrical storm, nowadays the most accepted definition refers to three or more separate arrhythmia episodes leading to ICD therapies including antitachycardia pacing or shock occurring over a single 24 hours' time period. Clinical presentation can be dramatic and triggering mechanism are not clear at all yet, but electrical storm is associated with high mortality rates and low patients quality of life, both in the acute phase and in the long term. The first line therapy is based on antiarrhythmic drugs to suppress electrical storm, but in refractory patients, interventions such as catheter ablation or in some cases surgical cardiac sympathetic denervation might be helpful. Anyhow, earlier interventional management can lead to better outcomes than persisting with antiarrhythmic pharmacologic therapy and, when available, an early interventional approach should be preferred.

Heart failure and atrial fibrillation: current concepts and controversies.

PubMed Central

Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

1997-01-01

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

[Cardiac sarcoidosis: Diagnosis and therapeutic challenges].

PubMed

Cohen Aubart, F; Nunes, H; Mathian, A; Haroche, J; Hié, M; Le-Thi Huong Boutin, D; Cluzel, P; Soussan, M; Waintraub, X; Fouret, P; Valeyre, D; Amoura, Z

2017-01-01

Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and 18 FDG-TEP scanner, as well as from the stratification of the risk of ventricular tachycardia/fibrillation. Due to the rarity of the disease, there is no reliable prospective large study to guide therapeutic strategy for cardiac sarcoidosis. Corticosteroids are probably efficacious, in particular in case of atrio-ventricular block or moderate heart failure. Immunosuppressive drugs have not been largely studied but methotrexate could be helpful. In refractory forms, TNF-α antagonists have been used with success. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs.

PubMed

Shiroshita-Takeshita, Akiko; Sakabe, Masao; Haugan, Ketil; Hennan, James K; Nattel, Stanley

2007-01-23

Abnormal intercellular communication caused by connexin dysfunction may be involved in atrial fibrillation (AF). The present study assessed the effect of the gap junctional conduction-enhancing peptide rotigaptide on AF maintenance in substrates that result from congestive heart failure induced by 2-week ventricular tachypacing (240 bpm), atrial tachypacing (ATP; 400 bpm for 3 to 6 weeks), and isolated atrial myocardial ischemia. Electrophysiological study and epicardial mapping were performed before and after rotigaptide administration in dogs with ATP and congestive heart failure, as well as in similarly instrumented sham dogs that were not tachypaced. For atrial myocardial ischemia, dogs administered rotigaptide before myocardial ischemia were compared with no-drug myocardial ischemia controls. ATP significantly shortened the atrial effective refractory period (P=0.003) and increased AF duration (P=0.008), with AF lasting >3 hours in all 6-week ATP animals. Rotigaptide increased conduction velocity in ATP dogs slightly but significantly (P=0.04) and did not affect the effective refractory period, AF duration, or atrial vulnerability. In dogs with congestive heart failure, rotigaptide also slightly increased conduction velocity (P=0.046) but failed to prevent AF promotion. Rotigaptide had no statistically significant effects in sham dogs. Myocardial ischemia alone increased AF duration and impaired conduction (based on conduction velocity across the ischemic border and indices of conduction heterogeneity). Rotigaptide prevented myocardial ischemia-induced conduction slowing and AF duration increases. Rotigaptide improves conduction in various AF models but suppresses AF only for the acute ischemia substrate. These results define the atrial antiarrhythmic profile of a mechanistically novel antiarrhythmic drug and suggest that gap junction dysfunction may be more important in ischemic AF than in ATP remodeling or congestive heart failure substrates.

Bioelectronic block of paravertebral sympathetic nerves mitigates post-myocardial infarction ventricular arrhythmias.

PubMed

Chui, Ray W; Buckley, Una; Rajendran, Pradeep S; Vrabec, Tina; Shivkumar, Kalyanam; Ardell, Jeffrey L

2017-11-01

Autonomic dysfunction contributes to induction of ventricular tachyarrhythmia (VT). To determine the efficacy of charge-balanced direct current (CBDC), applied to the T1-T2 segment of the paravertebral sympathetic chain, on VT inducibility post-myocardial infarction (MI). In a porcine model, CBDC was applied in acute animals (n = 7) to optimize stimulation parameters for sympathetic blockade and in chronic MI animals (n = 7) to evaluate the potential for VTs. Chronic MI was induced by microsphere embolization of the left anterior descending coronary artery. At termination, in anesthetized animals and following thoracotomy, an epicardial sock array was placed over both ventricles and a quadripolar carousel electrode positioned underlying the right T1-T2 paravertebral chain. In acute animals, the efficacy of CBDC carousel (CBDCC) block was assessed by evaluating cardiac function during T2 paravertebral ganglion stimulation with and without CBDCC. In chronic MI animals, VT inducibility was assessed by extrasystolic (S1-S2) stimulations at baseline and under >66% CBDCC blockade of T2-evoked sympathoexcitation. CBDCC demonstrated a current-dependent and reversible block without impacting basal cardiac function. VT was induced at baseline in all chronic MI animals. One animal died after baseline induction. Of the 6 remaining animals, only 1 was reinducible with simultaneous CBDCC application (P < .002 from baseline). The ventricular effective refractory period (VERP) was prolonged with CBDCC (323 ± 26 ms) compared to baseline (271 ± 32 ms) (P < .05). Axonal block of the T1-T2 paravertebral chain with CBDCC reduced VT in a chronic MI model. CBDCC prolonged VERP, without altering baseline cardiac function, resulting in improved electrical stability. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Total Beta-Adrenoceptor Knockout Slows Conduction and Reduces Inducible Arrhythmias in the Mouse Heart

PubMed Central

Stöckigt, Florian; Brixius, Klara; Lickfett, Lars; Andrié, René; Linhart, Markus; Nickenig, Georg; Schrickel, Jan Wilko

2012-01-01

Introduction Beta-adrenoceptors (β-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (β1, β2, β3) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. TKO represents a unique mouse model mimicking total unselective medical β-blocker therapy in men. Electrophysiological characteristics of TKO have not yet been investigated in an animal model. Methods In vivo electrophysiological studies using right heart catheterisation were performed in 10 TKO mice and 10 129SV wild type control mice (WT) at the age of 15 weeks. Standard surface ECG, intracardiac and electrophysiological parameters, and arrhythmia inducibility were analyzed. Results The surface ECG of TKO mice revealed a reduced heart rate (359.2±20.9 bpm vs. 461.1±33.3 bpm; p<0.001), prolonged P wave (17.5±3.0 ms vs. 15.1±1.2 ms; p = 0.019) and PQ time (40.8±2.4 ms vs. 37.3±3.0 ms; p = 0.013) compared to WT. Intracardiac ECG showed a significantly prolonged infra-Hisian conductance (HV-interval: 12.9±1.4 ms vs. 6.8±1.0 ms; p<0.001). Functional testing showed prolonged atrial and ventricular refractory periods in TKO (40.5±15.5 ms vs. 21.3±5.8 ms; p = 0.004; and 41.0±9.7 ms vs. 28.3±6.6 ms; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p<0.001) and of ventricular tachycardias (0% vs. 26%; p<0.001) were significantly reduced. Conclusion TKO results in significant prolongations of cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. Our finding confirms the importance of β-AR in arrhythmogenesis and the potential role of unspecific beta-receptor-blockade as therapeutic target. PMID:23133676

A novel low-energy electrotherapy that terminates ventricular tachycardia with lower energy than a biphasic shock when antitachycardia pacing fails.

PubMed

Janardhan, Ajit H; Li, Wenwen; Fedorov, Vadim V; Yeung, Michael; Wallendorf, Michael J; Schuessler, Richard B; Efimov, Igor R

2012-12-11

The authors sought to develop a low-energy electrotherapy that terminates ventricular tachycardia (VT) when antitachycardia pacing (ATP) fails. High-energy implantable cardioverter-defibrillator (ICD) shocks are associated with device failure, significant morbidity, and increased mortality. A low-energy alternative to ICD shocks is desirable. Myocardial infarction was created in 25 dogs. Sustained, monomorphic VT was induced by programmed stimulation. Defibrillation electrodes were placed in the right ventricular apex, and coronary sinus and left ventricular epicardium. If ATP failed to terminate sustained VT, the defibrillation thresholds (DFTs) of standard versus experimental electrotherapies were measured. Sustained VT ranged from 276 to 438 beats/min (mean 339 beats/min). The right ventricular-coronary sinus shock vector had lower impedance than the right ventricular-left ventricular patch (54.4 ± 18.1 Ω versus 109.8 ± 16.9 Ω; p < 0.001). A single shock required between 0.3 ± 0.2 J to 5.9 ± 2.5 J (mean 2.64 ± 3.22 J; p = 0.008) to terminate VT, and varied depending upon the phase of the VT cycle in which it was delivered. By contrast, multiple shocks delivered within 1 VT cycle length were not phase dependent and achieved lower DFT compared with a single shock (0.13 ± 0.09 J for 3 shocks, 0.08 ± 0.04 J for 5 shocks, and 0.09 ± 0.07 J for 7 shocks; p < 0.001). Finally, a multistage electrotherapy (MSE) achieved significantly lower DFT compared with a single biphasic shock (0.03 ± 0.05 J versus 2.37 ± 1.20 J; respectively, p < 0.001). At a peak shock amplitude of 20 V, MSE achieved 91.3% of terminations versus 10.5% for a biphasic shock (p < 0.001). MSE achieved a major reduction in DFT compared with a single biphasic shock for ATP-refractory monomorphic VT, and represents a novel electrotherapy to reduce high-energy ICD shocks. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses.

PubMed

Broux, B; De Clercq, D; Decloedt, A; Vera, L; Devreese, M; Gehring, R; Croubels, S; van Loon, G

2018-05-01

Arrhythmias in horses may require long-term anti-arrhythmic therapy. Unfortunately, oral anti-arrhythmic drugs for use in horses are currently scarce. In human patients and small animals, sotalol, a β-blocker with class III anti-arrhythmic properties, is often used for long-term treatment. To determine the pharmacokinetics of sotalol at multiple oral dosages in unfasted horses, as well as the effects on electro- and echocardiographic measurements, right atrial and ventricular monophasic action potential (MAP) and effective refractory period (ERP). Placebo controlled, double-blinded experiment. Six healthy, unfasted Warmblood horses were given either 0, 2, 3 or 4 mg/kg bodyweight (bwt) sotalol orally (PO) twice daily (bid) for 9 days in a randomised cross-over design. Echocardiography and surface electrocardiography were performed and plasma concentrations of sotalol and right atrial and right ventricular MAPs and ERPs were determined at steady-state conditions. Statistical analysis was performed using a repeated measures univariate analysis with post hoc Bonferroni corrections. Calculated mean steady-state plasma concentrations determined by nonlinear mixed-effect modelling were 287 (range 234-339), 409 (359-458) and 543 (439-646) ng/mL for 2, 3 and 4 mg/kg bwt sotalol PO bid respectively. Sotalol significantly increased the QT interval and ERPs, but, despite increasing plasma concentrations, higher dosages did not result in a progressive increase in QT interval or ERPs. Echocardiographic and other electrocardiographic measurements did not change significantly. MAP durations at 90% repolarisation were not significantly different during sotalol treatment. Besides transient local sweating, no side effects were noted. Study size and ad libitum feeding of hay. Sotalol at a dose of 2, 3 and 4 mg/kg bwt PO bid increases the QT interval and ERP and might be a useful drug for long-term anti-arrhythmic therapy in horses. © 2017 EVJ Ltd.

Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

PubMed Central

Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

2016-01-01

Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

A KCNQ1 Mutation Causes a High Penetrance for Familial Atrial Fibrillation

PubMed Central

Bartos, Daniel C.; Anderson, Jeffrey B.; Bastiaenen, Rachel; Johnson, Jonathan N.; Gollob, Michael H; Tester, David J.; Burgess, Don E.; Homfray, Tessa; Behr, Elijah R.; Ackerman, Michael J.; Guicheney, Pascale; Delisle, Brian P.

2012-01-01

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease. Method and Results Candidate gene sequencing in five unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope, or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage-gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage-dependent gating. Conclusions The R231H variant causes a high penetrance for interfamilial early-onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF. PMID:23350853

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

PubMed

Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

2016-05-15

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. Copyright © 2016 Elsevier Inc. All rights reserved.

Short-term mechanical circulatory support as a bridge to durable left ventricular assist device implantation in refractory cardiogenic shock: a systematic review and meta-analysis.

PubMed

den Uil, Corstiaan A; Akin, Sakir; Jewbali, Lucia S; Dos Reis Miranda, Dinis; Brugts, Jasper J; Constantinescu, Alina A; Kappetein, Arie Pieter; Caliskan, Kadir

2017-07-01

Short-term mechanical circulatory support (MCS) is increasingly used as a bridge to decision in patients with refractory cardiogenic shock. Subsequently, these patients might be bridged to durable MCS either as a bridge to candidacy/transplantation, or as destination therapy. The aim of this study was to review support duration and clinical outcome of short-term MCS in cardiogenic shock, and to analyse application of this technology as a bridge to long-term cardiac support (left ventricular assist device, LVAD) from 2006 till June 2016. Using Cochrane Register of Trials, Embase and Medline, a systematic review was performed on patients with cardiogenic shock from acute myocardial infarction, end-stage cardiomyopathy, or acute myocarditis, receiving short-term MCS. Studies on periprocedural, post-cardiotomy and cardiopulmonary resuscitation support were excluded. Thirty-nine studies, mainly registries of heterogeneous patient populations (n = 4151 patients), were identified. Depending on the device used (intra-aortic balloon pump, TandemHeart, Impella 2.5, Impella 5.0, CentriMag and peripheral veno-arterial extracorporeal membrane oxygenation), mean support duration was (range) 1.6-25 days and the mean proportion of short-term MCS patients discharged was (range) 45-66%. The mean proportion of bridge to durable LVAD was (range) 3-30%. Bridge to durable LVAD was most frequently performed in patients with end-stage cardiomyopathy (22 [12-35]%). We conclude that temporary MCS can be used to bridge patients with cardiogenic shock towards durable LVAD. Clinicians are encouraged to share their results in a large multicentre registry in order to investigate optimal device selection and best duration of support. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Parasystole due to re-entry as the possible mechanism of ventricular parasystole with second-degree entrance block.

PubMed

Kinoshita, Shinji; Katoh, Takakazu; Yoshida, Hiroshi

2010-05-01

In 1974, Kinoshita reported a case of 'irregular parasystole' due to type I second-degree entrance block. Since then, many cases of such 'irregular' parasystole have been reported by us. To explain the mechanism of 'irregular' parasystole, two theories have been suggested, namely, 'electrotonic modulation' by Jalife and Moe, and 'type I second-degree entrance block' by us. On the contrary, in 1960, Kinoshita et al. reported a case of concealed bigeminy for the first time. The electrocardiographic findings in concealed bigeminy have suggested that there are dual re-entrant pathways with markedly long effective refractory periods in the re-entrant pathway. We have suggested that parasystole may be caused by re-entry in such re-entrant pathways. In this article, attempts are made to explain the mechanism of all the electrocardiographic findings in our cases of parasystole by 'parasystole due to re-entry'. Using 24 studies on parasystole and 21 studies on concealed extrasystoles that we have reported over 50 years, as well as three exemplary cases in this article, attempts are made to explain all electrocardiographic findings in parasystole by 'parasystole due to re-entry'. The electrocardiographic findings in our previous clinical cases of parasystole and concealed extrasystoles, as well as exemplary cases and diagrams in the present article, strongly suggest 'parasystole due to re-entry' as the mechanism of ventricular parasystole with second-degree entrance block.

Glue septal ablation: A promising alternative to alcohol septal ablation

PubMed Central

Aytemir, Kudret; Oto, Ali

2016-01-01

Hypertrophic cardiomyopathy (HCM) is defined as myocardial hypertrophy in the absence of another cardiac or systemic disease capable of producing the magnitude of present hypertrophy. In about 70% of patients with HCM, there is left ventricular outflow tract (LVOT) obstruction (LVOTO) and this is known as obstructive type of hypertrophic cardiomyopathy (HOCM). Cases refractory to medical treatment have had two options either surgical septal myectomy or alcohol septal ablation (ASA) to alleviate LVOT gradient. ASA may cause some life-threatening complications including conduction disturbances and complete heart block, hemodynamic compromise, ventricular arrhythmias, distant and massive myocardial necrosis. Glue septal ablation (GSA) is a promising technique for the treatment of HOCM. Glue seems to be superior to alcohol due to some intrinsic advantageous properties of glue such as immediate polymerization which prevents the leak into the left anterior descending coronary artery and it is particularly useful in patients with collaterals to the right coronary artery in whom alcohol ablation is contraindicated. In our experience, GSA is effective and also a safe technique without significant complications. GSA decreases LVOT gradient immediately after the procedure and this reduction persists during 12 months of follow-up. It improves New York Heart Association functional capacity and decrease interventricular septal wall thickness. Further studies are needed in order to assess the long-term efficacy and safety of this technique. PMID:27011786

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

PubMed Central

Stavrou, Brigitte M; Beck, Caroline; Flores, Nicholas A

2001-01-01

The structural conformation of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap4A and Ap5A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap4A and Ap5A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap4A has any electrophysiological or antiarrhythmic effects during ischaemia. Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfused guinea-pig hearts under constant flow conditions. The effects of 1 nM and 1 μM Ap4A and Ap5A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 μM Ap4A were studied during global low-flow ischaemia and reperfusion. At pH 7.4, Ap4A and Ap5A increased action potential duration (APD95) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap4A increased RP but the effects of Ap4A and Ap5A on perfusion pressure were attenuated. During ischaemia, Ap4A had no antiarrhythmic or electrophysiological effects. These data demonstrate the importance of extracellular pH in influencing the effects of Ap4A and Ap5A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia. PMID:11588119

Mazindol in narcolepsy and idiopathic and symptomatic hypersomnia refractory to stimulants: a long-term chart review.

PubMed

Nittur, Nandini; Konofal, Eric; Dauvilliers, Yves; Franco, Patricia; Leu-Semenescu, Smaranda; Cock, Valérie Cochen De; Inocente, Clara O; Bayard, Sophie; Scholtz, Sabine; Lecendreux, Michel; Arnulf, Isabelle

2013-01-01

Mazindol is a tricyclic, anorectic, non-amphetamine stimulant used in narcolepsy and obesity since 1970. This study aimed to evaluate the long-term benefit/risk ratio in drug-resistant hypersomniacs and cataplexy sufferers. By retrospective analysis of the patients' files in the hospitals of Paris-Salpêtrière (n=91), Montpellier (n=40) and Lyon (n=8), the benefit (Epworth Sleepiness Score (ESS), cataplexy frequency, authorization renewal) and tolerance (side-effects, vital signs, electrocardiogram and cardiac echography) of mazindol were assessed. The 139 patients (45% men) aged 36±15years (range: 9-74) suffered narcolepsy (n=94, 66% with cataplexy), idiopathic (n=37) and symptomatic hypersomnia (n=8) refractory to modafinil, methylphenidate and sodium oxybate. Under mazindol (3.4±1.3mg/day, 1-6mg) for an average of 30months, the ESS decreased from 17.7±3.5 to 12.8±5.1, with an average fall of -4.6±4.7 (p<0.0001) and the frequency of cataplexy fell from 4.6±3.1 to 2±2.8 episodes per week. The cataplexy was eliminated in 14.5% of patients, improved in 27.5%, and unchanged in 29% (missing data in 29%). The treatment was maintained long term in 83 (60%) patients, and stopped because of a lack of efficacy (22%) and/or secondary effects (9%). There was no pulmonary hypertension in the 45 patients who underwent a cardiac echography. The most common adverse effects were dry mouth (13%), palpitations (10%, including one with ventricular hyperexcitability), anorexia (6%), nervousness (6%) and headaches (6%). Mazindol has a long-term, favorable benefit/risk ratio in 60% of drug-resistant hypersomniacs, including a clear benefit on cataplexy. Copyright © 2012 Elsevier B.V. All rights reserved.

The challenges in the management of right ventricular infarction.

PubMed

Inohara, Taku; Kohsaka, Shun; Fukuda, Keiichi; Menon, Venu

2013-09-01

In recent years, right ventricular (RV) infarction seems to be underdiagnosed in most cases of acute myocardial ischaemia despite its frequent association with inferior-wall and, occasionally, anterior-wall myocardial infarction (MI). However, its initial management is drastically different from that of left ventricular MI, and studies have indicated that RV infarction remains associated with significant morbidity and mortality, even in the mechanical reperfusion era. The pathophysiology of RV infarction involves the interaction between the right and left ventricle (LV), and the mechanism has been clarified with the advent of diagnostic non-invasive modalities, such as echocardiography and cardiac magnetic resonance. In recent years, considerable progress has been made in the treatment of RV infarction; early revascularization remains the cornerstone of the management, and fluid resuscitation, with appropriate target selection, is necessary to maintain appropriate preload. Early recognition in intensive care with clear understanding of the pathophysiology is essential to improve its prognosis. In terms of management, the support strategy for RV dysfunction is different from that for LV dysfunction since the former may often be temporary. Along with early reperfusion, maintenance of an adequate heart rate and atrioventricular synchrony are essential to sustain a sufficient cardiac output in patients with RV infarction. In refractory cases, more intensive mechanical support is required, and new therapeutic options, such as Tandem-Heart or percutaneous cardiopulmonary support systems, are being developed.

Lessons learned from 150 continuous-flow left ventricular assist devices: a single institutional 7 year experience.

PubMed

Tsiouris, Athanasios; Paone, Gaetano; Nemeh, Hassan W; Brewer, Robert J; Borgi, Jamil; Hodari, Arielle; Morgan, Jeffrey A

2015-01-01

Continuous-flow (CF) left ventricular assist devices (LVADs) have become the standard of care for patients with advanced heart failure refractory to optimal medical therapy. The goal of this study was to review our 7 year single institutional experience with CF LVADs. Mean age was 50.4 + 12.5 (17-69) years for bridge-to-transplantation (BTT) patients and 57.6 + 10.4 (31-81) years for destination therapy (DT) patients (p < 0.001). Overall, 38 patients (26%) were female and 58 (41%) were African American. Etiology of heart failure was ischemic in 54 patients (37%) and nonischemic in 93 patients (63%). Overall survival at 30 days, 6 months, 12 months, and 2 years was 93%, 89%, 84%, and 81%, respectively. Gastrointestinal bleeding (GIB) was the most common complication (24%), followed by stroke (18%), right ventricular (RV) failure (18%), ventilator-dependent respiratory failure (10%), reoperation for bleeding (10%), and driveline infection (9%). These data demonstrate excellent survival with low mortality for both BTT and DT patients on long-term LVAD support. However, for LVAD therapy to become the gold standard for long-term treatment of end-stage heart failure and a plausible alternative to heart transplantation, we need to continue to improve the incidence of frequent postoperative complications, such as RV failure, driveline infections, strokes, and GIB.

Fatal cardiac glycoside poisoning due to mistaking foxglove for comfrey.

PubMed

Wu, I-Lin; Yu, Jiun-Hao; Lin, Chih-Chuan; Seak, Chen-June; Olson, Kent R; Chen, Hsien-Yi

2017-08-01

Accidental ingestion of foxglove (Digitalis purpurea) can cause significant cardiac toxicity. We report a patient who ingested foxglove mistaking it for comfrey and developed refractory ventricular arrhythmias. The patient died despite treatment with digoxin-specific antibody fragments (DSFab) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 55-year-old woman presented to the emergency department with nausea, vomiting and generalized weakness eight hours after drinking "comfrey" tea. She had bradycardia (54 beats/min) and hyperkalemia (7.6 mEq/L). Electrocardiogram revealed a first-degree atrioventricular conduction block with premature atrial contractions, followed by polymorphic ventricular tachycardia three hours after arrival. A serum digoxin level was 151.2 ng/mL. The patient developed ventricular fibrillation while waiting for Digibind infusion. Resuscitation was performed and an emergent VA-ECMO was set up. A total of eight vials of Digibind were given over the next 16 hours. She temporarily regained consciousness, but remained hemodynamically unstable and subsequently developed lower limb ischemia and multiple organ failure, and she expired on hospital day seven. A botanist confirmed that the plant was foxglove. The diagnosis of cardiac glycoside plant poisoning can be difficult in the absence of an accurate exposure history. In facilities where DSFab is unavailable or insufficient, early VA-ECMO might be considered in severely cardiotoxic patients unresponsive to conventional therapy.

Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig.

PubMed

Sun, Hong-Li; Chu, Wen-Feng; Dong, De-Li; Liu, Yan; Bai, Yun-Long; Wang, Xiao-Hui; Zhou, Jin; Yang, Bao-Feng

2006-04-01

Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole-cell patch clamp technique and confocal laser scanning microscopy, we found that As(2)O(3) significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)), inhibited delayed rectifier potassium currents (I(K)), and increased intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition. As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in ventricular myocytes during As(2)O(3) application.

Left cardiac sympathetic denervation: case series and technical report.

PubMed

McNamara, C; Cullen, P; Rackauskas, M; Kelly, R; O'Sullivan, K E; Galvin, J; Eaton, D

2017-08-01

Left cardiac sympathetic denervation (LCSD) is a surgical procedure that has been shown to have an antiarrhythmic and antifibrillatory effect. Evidence indicating its antiarrhythmic effect has been available for over 100 years. It involves the removal of the lower half of the stellate ganglion and T2-T4 of the sympathetic ganglia and is carried out as either a unilateral or bilateral procedure. With advancements in thoracic surgery, it can be safely performed via a minimally invasive Video-Assisted Thoracoscopic Surgery (VATS) approach resulting in significantly less morbidity and a shortened inpatient stay. LCSD provides a valuable treatment option for patients with life-threatening channelopathies and cardiomyopathies. This case series reports the preliminary paediatric and adult experience in the Republic of Ireland with LCSD and describes five cases recently treated in addition to an outline of the operative procedure employed. Of the five cases included, two were paediatric cases and three were adult cases. One of the paediatric patients had a diagnosis of the rare catecholaminergic polymorphic ventricular tachycardia (CPVT) and the other a diagnosis of long-QT syndrome. Both paediatric patients experienced excellent outcomes. Of the three adult patients, two benefitted greatly and remain well at follow-up (one inappropriate sinus tachycardia and one CPVT). One patient with idiopathic ventricular fibrillation unfortunately passed away from intractable VF despite all attempts at resuscitation. In this case series, we highlight that LCSD provides a critical adjunct to existing medical therapies and should be considered for all patients with life-threatening refractory arrhythmias especially those patients on maximal medical therapy.

Single-centre experience with the Thoratec paracorporeal ventricular assist device for patients with primary cardiac failure.

PubMed

Kirsch, Matthias; Vermes, Emmanuelle; Damy, Thibaud; Nakashima, Kuniki; Sénéchal, Mélanie; Boval, Bernadette; Drouet, Ludovic; Loisance, Daniel

2009-01-01

Temporary mechanical circulatory support may be indicated in some patients with cardiac failure refractory to conventional therapy, as a bridge to myocardial recovery or transplantation. To evaluate outcomes in cardiogenic shock patients managed by the primary use of a paracorporeal ventricular assist device (p-VAD). We did a retrospective analysis of demographics, clinical characteristics and survival of patients assisted with a Thoratec p-VAD. p-VADs were used in 84 patients with cardiogenic shock secondary to acute myocardial infarction (35%), idiopathic (31%) or ischaemic (12%) cardiomyopathy, myocarditis or other causes (23%). Before implantation, 23% had cardiac arrest, 38% were on a ventilator and 31% were on an intra-aortic balloon pump. Cardiac index was 1.6+/-0.5 L/min/m(2) and total bilirubin levels were 39+/-59 micromol/L. During support, 29 patients (35%) died in the intensive care unit and seven (10%) died after leaving. Forty-seven patients (56%) were weaned or transplanted, with one still under support. Despite significantly more advanced preoperative end-organ dysfunction, survival rates were similar in patients with biventricular devices (74%) and those undergoing isolated left ventricular support (24%) (63% versus 45%, respectively; p=0.2). Actuarial survival estimates after transplantation were 78.7+/-6.3%, 73.4+/-6.9% and 62.6+/-8.3% at 1, 3 and 5 years, respectively. Our experience validates the use of p-VAD as a primary device to support patients with cardiogenic shock. In contrast to short-term devices, p-VADs provide immediate ventricular unloading and pulsatile perfusion in a single procedure. Biventricular support should be used liberally in patients with end-organ dysfunction.

Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulse less ventricular tachycardia or ventricular fibrillation☆

PubMed Central

Valdes, Santiago O.; Donoghue, Aaron J.; Hoyme, Derek B.; Hammond, Rachel; Berg, Marc D.; Berg, Robert A.; Samson, Ricardo A.

2015-01-01

Aim To determine the association between amiodarone and lidocaine and outcomes in children with cardiac arrest with pulse less ventricular tachycardia (pVT) and ventricular fibrillation (VF). Background Current AHA guidelines for CPR and emergency cardiovascular care recommend amiodarone for cardiac arrest in children associated with shock refractory pVT/VF, based on a single pediatric study and extrapolation from adult data. Methods Retrospective cohort study from the Get With the Guidelines-Resuscitation database for in-patient cardiac arrest. Patients< 18 years old with pVT/VF cardiac arrest were included. Patients receiving amiodarone or lidocaine prior to arrest or whose initial arrest rhythm was unknown were excluded. Univariate analysis was performed to assess the association between patient and event factors and clinical outcomes. Multivariate analysis was performed to address independent association between lidocaine and amiodarone use and outcomes. Results Of 889 patients. 171 (19%) received amiodarone, 295 (33%) received lidocaine. and 82 (10%) received both. Return of spontaneous circulation (ROSC) occurred in 484/889 (54%), 24-h survival in 342/874 (39%), and survival to hospital discharge in 194/889 (22%}. Lidocaine was associated with improved ROSC (adjusted OR 2.02, 95% Cl 1.36-3 ). and 24-h survival (adjusted OR 1.66, 95% CI 1.11-2.49), but not hospital discharge. Amiodarone use was not associated with ROSC, 24 h survival, or survival to discharge. Conclusions For children with in-hospital pVT/VF, lidocaine use was independently associated with improved ROSC and 24-h survival. Amiodarone use was not associated with superior rates of ROSC, survival at 24 h. Neither drug was associated with survival to hospital discharge. PMID:24361455

Results of Cryoenergy and Radiofrequency-Based Catheter Ablation for Treating Ventricular Arrhythmias Arising From the Papillary Muscles of the Left Ventricle, Guided by Intracardiac Echocardiography and Image Integration.

PubMed

Rivera, Santiago; Ricapito, Maria de la Paz; Tomas, Leandro; Parodi, Josefina; Bardera Molina, Guillermo; Banega, Rodrigo; Bueti, Pablo; Orosco, Agustin; Reinoso, Marcelo; Caro, Milagros; Belardi, Diego; Albina, Gaston; Giniger, Alberto; Scazzuso, Fernando

2016-04-01

Catheter radiofrequency ablation of ventricular arrhythmias (VAs) arising from the left ventricle's papillary muscles has been associated with inconsistent results. The use of cryoenergy versus radiofrequency has not been compared yet. This study compares outcomes and complications of catheter ablation of VA from the papillary muscles of the left ventricle with either cryoenergy or radiofrequency. Twenty-one patients (40±12 years old; 47% males; median ejection fraction 59±7.3%) with drug refractory premature ventricular contractions or ventricular tachycardia underwent catheter cryoablation or radiofrequency ablation. VAs were localized using 3-dimensional mapping, multidetector computed tomography, and intracardiac echocardiography, with arrhythmia foci being mapped at either the anterolateral papillary muscle or posteromedial papillary muscles of the left ventricle. Focal ablation was performed using an 8-mm cryoablation catheter or a 4-mm open-irrigated radiofrequency catheter, via transmitral approach. Acute success rate was 100% for cryoenergy (n=12) and 78% for radiofrequency (n=9; P=0.08). Catheter stability was achieved in all patients (100%) treated with cryoenergy, and only in 2 (25%) patients treated with radiofrequency (P=0.001). Incidence of multiple VA morphologies was observed in 7 patients treated with radiofrequency (77.7%), whereas none was observed in those treated with cryoenergy (P=0.001). VA recurrence at 6 months follow-up was 0% for cryoablation and 44% for radiofrequency (P=0.03). Cryoablation was associated with higher success rates and lower recurrence rates than radiofrequency catheter ablation, better catheter stability, and lesser incidence of polymorphic arrhythmias. © 2016 American Heart Association, Inc.

Intra-aortic balloon pump combined with mechanical ventilation for treating patients aged > 60 years in cardiogenic shock: Retrospective analysis

PubMed Central

Liu, Hongwei; Wu, Xueping; Zhao, Xiaoning; Zhu, Ping

2016-01-01

Objective To examine if mechanical ventilation with positive end-expiratory pressure (PEEP) combined with intra-aortic balloon pump (IABP) provided a better outcome than IABP alone for the treatment of cardiogenic shock after acute myocardial infarction in patients aged > 60 years. Methods This was a retrospective analysis of data from patients in cardiogenic shock, refractory to pharmacological therapy and treated at a geriatric coronary care unit. Results Sixty-two patients were eligible for study inclusion: 33 received IABP alone; 29 received IABP combined with mechanical ventilation. Patients in the IABP + mechanical ventilation group had lower mean arterial blood pressure (BP), systolic BP and partial pressure of oxygen compared with the IABP group, indicating worse cardiac and pulmonary function. In addition, higher rates of pulmonary infection and renal insufficiency were observed in the IABP + mechanical ventilation group than in the IABP group. A statistically significant improvement of left ventricular function before and after treatment was observed in the IABP + mechanical ventilation group, but not in the IABP group. Pulmonary infection and renal insufficiency were risk factors for all-cause in-hospital mortality; successful revascularization was a negative risk factor. There was no between-group difference in survival. Conclusion Mechanical ventilation with an appropriate level of PEEP appears to enhance the beneficial effects of IABP on left ventricular function for patients in cardiogenic shock. PMID:27020597

STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND SIMILARITIES BETWEEN ATRIA AND VENTRICLES

PubMed Central

Filgueiras-Rama, David; Jalife, José

2016-01-01

Evidence accumulated over the last 25 years suggests that, whether in the atria or ventricles, fibrillation may be explained by the self-organization of the cardiac electrical activity into rapidly spinning rotors giving way to spiral waves that break intermittently and result in fibrillatory conduction. The dynamics and frequency of such rotors depend on the ion channel composition, excitability and refractory properties of the tissues involved, as well as on the thickness and respective three-dimensional fiber structure of the atrial and ventricular chambers. Therefore, improving the understanding of fibrillation has required the use of multidisciplinary research approaches, including optical mapping, patch clamping and molecular biology, and the application of concepts derived from the theory of wave propagation in excitable media. Moreover, translation of such concepts to the clinic has recently opened new opportunities to apply novel mechanistic approaches to therapy, particularly during atrial fibrillation ablation. Here we review the current understanding of the manner in which the underlying myocardial structure and function influence rotor initiation and maintenance during cardiac fibrillation. We also examine relevant underlying differences and similarities between atrial fibrillation and ventricular fibrillation and evaluate the latest clinical mapping technologies used to identify rotors in either arrhythmia. Altogether, the data being discussed have significantly improved our understanding of the cellular and structural bases of cardiac fibrillation and pointed toward potentially exciting new avenues for more efficient and effective identification and therapy of the most complex cardiac arrhythmias. PMID:27042693

Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failure.

PubMed

Chandra, Mini; Escalante-Alcalde, Diana; Bhuiyan, Md Shenuarin; Orr, Anthony Wayne; Kevil, Christopher; Morris, Andrew J; Nam, Hyung; Dominic, Paari; McCarthy, Kevin J; Miriyala, Sumitra; Panchatcharam, Manikandan

2018-04-01

Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte hypertrophy based on analysis of cell surface area. We found that lack of Lpp3 signaling was mediated through the activation of Rho and phospho-ERK pathways. There are increased levels of fetal genes Natriuretic Peptide A and B (Nppa and Nppb) expression indicating myocardial dysfunction. These mice also demonstrate mitochondrial dysfunction as evidenced by a significant decrease (P < 0.001) in the basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity as measured through mitochondrial bioenergetics. Histology and transmission electron microscopy of these hearts showed disrupted sarcomere organization and intercalated disc, with a prominent disruption of the cristae and vacuole formation in the mitochondria. Our findings suggest that LPA/LPP3-signaling nexus plays an important role in normal function of cardiomyocytes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Lasers in the treatment of ischemic heart disease in China

NASA Astrophysics Data System (ADS)

Zhang, Yongzhen; Chen, Mingzhe

2000-10-01

Myocardial revascularization by laser is a new treatment modality for chronic, severe, refractory angina in the patients with coronary heart disease that is not amenable to angioplasty (PTCA) or bypass surgery (CABG). Transmyocardial revascularization (TMR), typically requiring open thoracotomy, uses laser to create channels that would directly carry blood from left ventricular cavity into the ischemic myocardium. Current data indicate that TMR may provide these patients with improvement in angina severity, quality of life, and myocardial perfusion. The greatest potential future use of TMR is as an adjunct to CABG in patients with disease that prevents bypass grafting due to lack of distal targets or a conduit. Recently, as percutaneous (catheter-based) myocardial revascularization (PMR) has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle. The early results with PMR seem encouraging. Randomized clinical trial has demonstrated symptomatic improvement and increased exercise capacity. The risk: benefit ratio for PMR appears to be much more favorable than that for TMR. The mechanisms of action of them have not yet been clearly elucidated, and several theories have been proposed, including channel patency, angiogenesis, denervation, and placebo effect. The challenge of TMR/PMR is related to improvement of perioperative outcomes and long-term survival without worsening of left ventricular function. In future, it may be feasible to combine TMR/PMR with intramyocardial delivery of angiogenic growth factors to induce further new blood vessel formation.

Current views on neurostimulation in the treatment of cardiac ischemic syndromes.

PubMed

Jessurun, G A; DeJongste, M J; Blanksma, P K

1996-08-01

Most clinicians are still unacquainted with the beneficial effects of neurostimulation as an additional therapeutic strategy for severe angina pectoris. Patients with therapeutically refractory angina pectoris suffer from chest discomfort during minimal exercise, despite maximal tolerated antianginal drug therapy (at least 2 out of a beta-blocker, calcium-antagonist or long-acting nitrate). In these patients, revascularization procedures, such as a percutaneous transluminal coronary angioplasty or coronary artery bypass surgery, are often technically impossible because of diffuse coronary artery disease or should be withheld as a consequence of absolute contraindications such as severe left ventricular dysfunction. All patients have inoperable multivessel disease, experienced one or more myocardial infarctions, and were treated by earlier invasive interventions. This group of patients are severely physically and psychologically disabled by their intractable angina pectoris. Available published data and the neurostimulation experience of the authors are reviewed in relation to the treatment of cardiac ischemic syndromes. We conclude that neurostimulation is an effective therapeutic adjuvant for patients with severe angina pectoris unresponsive to standard treatment. This treatment modality appears to be safe, and a promising tool for other ischemic cardiac syndromes.

A simultaneous multichannel monophasic action potential electrode array for in vivo epicardial repolarization mapping.

PubMed

Sahakian, A V; Peterson, M S; Shkurovich, S; Hamer, M; Votapka, T; Ji, T; Swiryn, S

2001-03-01

While the recording of extracellular monophasic action potentials (MAPs) from single epicardial or endocardial sites has been performed for over a century, we are unaware of any previous successful attempt to record MAPs simultaneously from a large number of sites in vivo. We report here the design and validation of an array of MAP electrodes which records both depolarization and repolarization simultaneously at up to 16 epicardial sites in a square array on the heart in vivo. The array consists of 16 sintered Ag-AgCl electrodes mounted in a common housing with individual suspensions allowing each electrode to exert a controlled pressure on the epicardial surface. The electrodes are arranged in a square array, with each quadrant of four having an additional recessed sintered Ag-AgCl reference electrode at its center. A saline-soaked sponge establishes ionic contact between the reference electrodes and the tissue. The array was tested on six anesthetized open-chested pigs. Simultaneous diagnostic-quality MAP recordings were obtained from up to 13 out of 16 ventricular sites. Ventricular MAPs had amplitudes of 10-40 mV with uniform morphologies and stable baselines for up to 30 min. MAP duration at 90% repolarization was measured and shown to vary as expected with cycle length during sustained pacing. The relationship between MAP duration and effective refractory period was also confirmed. The ability of the array to detect local differences in repolarization was tested in two ways. Placement of the array straddling the atrioventricular (AV) junction yielded simultaneous atrial or ventricular recordings at corresponding sites during 1:1 and 2:1 AV conduction. Localized ischemia via constriction of a coronary artery branch resulted in shortening of the repolarization phase at the ischemic, but not the nonischemic, sites. In conclusion, these results indicate that the simultaneous multichannel MAP electrode array is a viable method for in vivo epicardial repolarization mapping. The array has the potential to be expanded to increase the number of sites and spatial resolution.

Rescue pulmonary vein isolation for hemodynamically unstable atrial fibrillation storm in a patient with an acute extensive myocardial infarction.

PubMed

Morishima, Itsuro; Sone, Takahito; Tsuboi, Hideyuki; Mukawa, Hiroaki

2012-11-26

New-onset atrial fibrillation in patients hospitalized for an acute myocardial infarction often leads to hemodynamic deterioration and has serious adverse prognostic implications; mortality is particularly high in patients with congestive heart failure and/or a reduced left ventricular ejection fraction. The mechanism of atrial fibrillation in the context of an acute myocardial infarction has not been well characterized and an effective treatment other than optimal medical therapy and mechanical hemodynamic support are expected. A 71 year-old male with an acute myocardial infarction due to an occlusion of the left main coronary artery was treated with percutaneous coronary intervention. He had developed severe congestive heart failure with a left ventricular ejection fraction of 34%. The systemic circulation was maintained with an intraaortic balloon pump, continuous hemodiafiltration, and mechanical ventilation until atrial fibrillation occurred on day 3 which immediately led to cardiogenic shock. Because atrial fibrillation was refractory to intravenous amiodarone, beta-blockers, and a total of 15 electrical cardioversions, the patient underwent emergent radiofrequency catheter ablation on day 4. Soon after electrical cardioversion, ectopies from the right superior pulmonary vein triggered the initiation of atrial fibrillation. The right pulmonary veins were isolated during atrial fibrillation. Again, atrial fibrillation was electrically cardioverted, then, sinus rhythm was restored. Subsequently, the left pulmonary veins were isolated. The stabilization of the hemodynamics was successfully achieved with an increase in the blood pressure and urine volume. Hemodiafiltration and amiodarone were discontinued. The patient had been free from atrial fibrillation recurrence until he suddenly died due to ventricular fibrillation on day 9. To the best of our knowledge, this is the first report of pulmonary vein isolation for a rescue purpose applied in a patient with hemodymically unstable atrial fibrillation complicated with an acute myocardial infarction. This case demonstrates that ectopic activity in the pulmonary veins may be responsible for triggering atrial fibrillation in the critical setting of an acute myocardial infarction and thus pulmonary vein isolation could be an effective therapeutic option.

Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts.

PubMed

Chorro, Francisco J; Trapero, Isabel; Such-Miquel, Luis; Pelechano, Francisca; Mainar, Luis; Cánoves, Joaquín; Tormos, Alvaro; Alberola, Antonio; Hove-Madsen, Leif; Cinca, Juan; Such, Luis

2009-11-01

Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+) exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1 microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor antagonist SCH-58261.

Effects of Frequent Hemodialysis on Ventricular Volumes and Left Ventricular Remodeling

PubMed Central

Greene, Tom; Chertow, Glenn M.; Kliger, Alan S.; Stokes, John B.; Beck, Gerald J.; Daugirdas, John T.; Kotanko, Peter; Larive, Brett; Levin, Nathan W.; Mehta, Ravindra L.; Rocco, Michael; Sanz, Javier; Yang, Phillip C.; Rajagopalan, Sanjay

2013-01-01

Summary Background and objectives Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling. Design, setting, participants, & measurements The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups. Results In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (−11.0% [95% confidence interval, −16.1% to −5.5%]), left ventricular end systolic volume (−14.8% [−22.7% to −6.2%]), right ventricular end diastolic volume (−11.6% [−19.0% to −3.6%]), and a trend for right ventricular end systolic volume (−11.3% [−21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial. Conclusions Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling. PMID:23970131

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

PubMed

Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

2016-05-01

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tension pneumomediastnum: A rare cause of acute intraoperative circulatory collapse in the setting of unremarkable TEE findings.

PubMed

Weaver, Jonathan B; Kumar, Avinash B

2017-02-01

Case report. Operating room. 25YF, ASA IV E who underwent an emergent decompressive craniectomy for refractory intracranial hypertension secondary to acute intracranial hemorhage. A 25Y caucasian female presented with acute intracranial hemorrhage with intraventricular extension secondary to Moya Moya disease. Post admisison, she underwent an emergent decompressive craniectomy for medically refractory intracranial hypertension. Introperatively (post dural closure and bone flap removal) the patient developed acutely worsening peak and plateau pressures followed by pulseless electrical activity necessitating CPR with epinephrine and Vasopressin before return of circulation before return of circulation. Intraoperative TEE done during return of circulation, was essentially non diagnostic, the patient had normal breath sounds throughout, and non-contributory bronchoscopy findings. EKG, arterial blood pressure, heart rate, resp. rate, introperative tranesophageal echocardiogram (TEE), Pulse oximetry, serial arterial blood gases, introperative bronchoscopy, ventilatory peak pressures. A post operative chest CT revealed extensive pneumomediastinum with subcutaneous emphysema. The focussed introperative echocardiogram showed preserved left ventricular function and no evidence of tamponade physiology. Tension pneumomediastinum was the likely etiologic factor for the acute hemodynamic collapse and should be considered in the differential diagnosis of intraoperative circulatory arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

Contemporary clinical trials in ventricular tachycardia and fibrillation: implications of ESVEM, CASCADE, and CASH for clinical management.

PubMed

Anderson, J L

1995-10-01

Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

Impact of left atrial volume reduction concomitant with atrial fibrillation surgery on left atrial geometry and mechanical function.

PubMed

Marui, Akira; Saji, Yoshiaki; Nishina, Takeshi; Tadamura, Eiji; Kanao, Shotaro; Shimamoto, Takeshi; Sasahashi, Nozomu; Ikeda, Tadashi; Komeda, Masashi

2008-06-01

Left atrial geometry and mechanical functions exert a profound effect on left ventricular filling and overall cardiovascular performance. We sought to investigate the perioperative factors that influence left atrial geometry and mechanical functions after the Maze procedure in patients with refractory atrial fibrillation and left atrial enlargement. Seventy-four patients with atrial fibrillation and left atrial enlargement (diameter > or = 60 mm) underwent the Maze procedure in association with mitral valve surgery. The maximum left atrial volume and left atrial mechanical functions (booster pump, reservoir, and conduit function [%]) were calculated from the left atrial volume-cardiac cycle curves obtained by magnetic resonance imaging. A stepwise multiple regression analysis was performed to determine the independent variables that influenced the postoperative left atrial geometry and function. The multivariate analysis showed that left atrial reduction surgery concomitant with the Maze procedure and the postoperative maintenance of sinus rhythm were predominant independent variables for postoperative left atrial geometry and mechanical functions. Among the 58 patients who recovered sinus rhythm, the postoperative left atrial geometry and function were compared between patients with (VR group) and without (control group) left atrial volume reduction. At a mean follow-up period of 13.8 months, sinus rhythm recovery rate was better (85% vs 68%, P < .05) in the VR group and maximum left atrial volume was less (116 +/- 25 mL vs 287 +/- 73 mL, P < .001) than in the control group. The maximum left atrial volume reduced with time only in the VR group (reverse remodeling). Postoperative booster pump and reservoir function in the VR group were better than in the control group (25% +/- 6% vs 11% +/- 4% and 34% +/- 7% vs 16% +/- 4%, respectively, P < .001), whereas the conduit function in the VR group was lower than in the control group, indicating that the improvement of the booster pump and reservoir function compensated for the conduit function to left ventricular filling. Left atrial reduction concomitant with the Maze procedure helped restore both contraction (booster pump) and compliance (reservoir) of the left atrium and facilitated left atrial reverse remolding. Left atrial volume reduction and postoperative maintenance of sinus rhythm may be desirable in patients with refractory AF and left atrial enlargement.

Intracerebroventricular opiate infusion for refractory head and facial pain

PubMed Central

Lee, Darrin J; Gurkoff, Gene G; Goodarzi, Amir; Muizelaar, J Paul; Boggan, James E; Shahlaie, Kiarash

2014-01-01

AIM: To study the risks and benefits of intracerebroventricular (ICV) opiate pumps for the management of benign head and face pain. METHODS: SSix patients with refractory trigeminal neuralgia and/or cluster headaches were evaluated for implantation of an ICV opiate infusion pump using either ICV injections through an Ommaya reservoir or external ventricular drain. Four patients received morphine ICV pumps and two patientS received a hydromorphone pump. Of the Four patients with morphine ICV pumps, one patient had the medication changed to hydromorphone. Preoperative and post-operative visual analog scores (VAS) were obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the pump dosage was adjusted at each outpatient clinic visit according to the patient’s pain level. RESULTS: All 6 patients had an intracerebroventricular opiate injection trial period, using either an Ommaya reservoir or an external ventricular drain. There was an average VAS improvement of 75.8%. During the trial period, no complications were observed. Pump implantation was performed an average of 3.7 wk (range 1-7) after the trial injections. After implantation, an average of 20.7 ± 8.3 dose adjustments were made over 3-56 mo after surgery to achieve maximal pain relief. At the most recent follow-up (26.2 mo, range 3-56), VAS scores significantly improved from an average of 7.8 ± 0.5 (range 6-10) to 2.8 ± 0.7 (range 0-5) at the final dose (mean improvement 5.0 ± 1.0, P < 0.001). All patients required a stepwise increase in opiate infusion rates to achieve maximal benefit. The most common complications were nausea and drowsiness, both of which resolved with pump adjustments. On average, infusion pumps were replaced every 4-5 years. CONCLUSION: These results suggest that ICV delivery of opiates may potentially be a viable treatment option for patients with intractable pain from trigeminal neuralgia or cluster headache. PMID:25133146

Right Ventricle Dysfunction and Pre Implantation Vasopressors in Refractory ARDS Supported by VV-ECMO.

PubMed

Lazzeri, Chiara; Bonizzoli, Manuela; Cianchi, Giovanni; Batacchi, Stefano; Guetti, Cristiana; Cozzolino, Morena; Bernardo, Pasquale; Peris, Adriano

2017-10-31

Acute respiratory distress syndrome (ARDS) has been shown to be frequently associated with haemodynamic instability requiring the use of vasopressors. To date, there is still some uncertainty in the use of veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) in haemodynamically unstable ARDS patients. We therefore assessed whether patients receiving pre ECMO vasopressors had a worse prognosis and, furthermore, we reviewed the factors associated with the use of pre ECMO vasopressors in 92 consecutive patients with refractory ARDS treated with VV-ECMO. All patients were submitted to an echocardiogram before implantation. In our series, 55 patients (59.7%) were given a vasopressor. Septic shock is the main cause of vasopressor requirement (45.5%). When compared with patients without vasopressors, the subgroup under vasopressors showed a significantly higher sequential organ failure assessment (SOFA) score (p=0.040), a lower pH (p=0.013), lower pO2 values (p=0.030) and higher lactate levels (p=0.024). A higher incidence of right ventricular (RV) dysfunction and of biventricular dysfunction were observed in patients under vasopressors (p=0.018 and p=0.036, respectively). The intensive care unit (ICU) mortality rate was 43.4% (40/92) with no difference between the two subgroups. In refractory ARDS requiring VV-ECMO infusion of vasopressors is needed in a high proportion of patients, who did not exhibit a worse prognosis when compared to haemodynamically stable patients. Pre ECMO echocardiography helps in characterising these patients since they showed a higher incidence of RV (and biventricular) dysfunction. According to our data, in ARDS patients refractory to conventional treatment, haemodynamic instability should not be considered a contraindication to VV-ECMO support. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Investigation of mechanisms and non-pharmacological therapy of cardiac arrhythmias

NASA Astrophysics Data System (ADS)

Vago, Hajnalka

Learning of mechanisms of arrhythmias may contribute substantially to the development of effective pharmacological and non-pharmacological therapeutic methods. Clinical relevance of endothelin-1 (ET-1), a strong vasoconstrictor and arrhythmogenic endogenous substrate, is not clarified yet. In our experimental studies, performed in the in situ canine heart, electrophysiological effects and the role in the pathomechanism of malignant ventricular tachyarrhythmias of endogenous and exogenous ET-1 was investigated. It has been proven in the in vivo ischaemia-reperfusion canine heart model, that during reperfusion ET-1 and big-ET levels increase in the coronary sinus, however there was no correlation between endothelin levels and electrophysiological changes. ET A-receptor antagonist darusentan does not prevent electrophysiological changes and development of ventricular tachyarrhythmias during ischaemia and reperfusion. On the contrary, during ischaemia endogenous ET-1 tends to show balancing effect. It has been proven that administration of high dose intracoronary ET-1 bolus has dual, ischaemic and direct, electrophysiological effect. It has been shown for the first time, that ET-1 causes monophasic action potential (MAP) and T-wave alternant. Our clinical study leads to the conclusion that previous atrial fibrillation, absence of preoperative beta-blocker treatment and combined heart surgery are strong predictors of atrial fibrillation following open heart surgery. The basis of new nonpharmacological therapies is the learning of pathomechanisms of arrhythmias and in some cases heart failure, which is an arrhythmogenic substrate. In our experimental study reliable MAP measurements, suitable for investigation of arrhythmogenesis, were performed for the first time using fractally coated ablation catheters during spontaneous rate and during stimulations. It has been proven that radiofrequency ablation affects significantly MAP parameters. In Hungary, we were the first to apply effectively biatrial pacemaker and biatrial cardioverter defibrillator for the prevention of paroxysmal atrial fibrillation. In the majority of patients frequency of paroxysmal atrial fibrillation decreased significantly due to biatrial stimulation or combined pharmacological and resynchronisation therapy. Parasymphathetic cardiac neurostimulation is a promising new non-pharmacological treatment option in certain types of arrhythmias. In our clinical study we were able to stimulate cardiac parasympathetic nerves innervating atrioventricular node achieving ventricular rate control during atrial tachyarrhythmias with chronically implanted coronary sinus lead. In our study biventricular pacemakers and cardioverter defibrillators were applied successfully in the treatment of drug refractory congestive heart failure combined with inter- and/or intraventricular conduction disturbances. AV sequential left sided chronic pacing using a single lead located in the coronary sinus has not been previously reported. Left sided DDD pacing was effective chronically in the improvement of the functional stage of patient suffering from congestive heart disease combined with left bundle branch block and binodal disease. Parallel with the investigation of pathomechanism of life-threatening ventricular tachyarrhythmias and the most common, clinically relevant atrial fibrillation due to recent technical development, we were able to support nonpharmacological therapeutic modalities, gaining popularity in clinical management, with novel observations.

Development of a patient decision aid for people with refractory angina: protocol for a three-phase pilot study

PubMed Central

2014-01-01

Background Refractory angina is a severe chronic disease, defined as angina which cannot be controlled by usual treatments for heart disease. This disease is frightening, debilitating, and difficult to manage. Many people suffering refractory have inadequate pain relief, continually revisit emergency departments for help, undergo repeated cardiac investigations, and struggle with obtaining appropriate care. There is no clear framework to help people understand the risks and benefits of available treatment options in Canada. Some treatments for refractory angina are invasive, while others are not covered by provincial health insurance plans. Effective care for refractory angina sufferers in Canada is critically underdeveloped; it is important that healthcare professionals and refractory angina sufferers alike understand the treatment options and their implications. This proposal builds on the recent Canadian practice guidelines for the management of refractory angina. We propose to develop a decision support tool in order to help people suffering from refractory angina make well-informed decisions about their healthcare and reduce their uncertainty about treatment options. Methods This project will be conducted in three phases: a) development of the support tool with input from clinical experts, the Canadian refractory angina guidelines, and people living with refractory angina, b) pilot testing of the usability of the tool, and c) formal preliminary evaluation of the effectiveness of the support tool to help people make informed decisions about treatment options. Discussion A decision support tool for refractory angina is needed and the available data suggest that by developing such a tool, we may be able to help refractory angina sufferers better understand their condition and the effectiveness of available treatment options (in their respective clinical settings) as well as their implications (e.g. risks vs. benefits). By virtue of this tool, we may also be able to facilitate identification and inclusion of patients’ values and preferences in the decision making process. This is particularly important as refractory angina is an intractable condition, necessitating that the selected course of treatment be lifelong. This study will yield a much needed patient decision aid for people living with refractory angina and pilot data to support a subsequent effectiveness study. PMID:24920518

Assessment and Management of Treatment-Refractory Obsessive-Compulsive Disorder in Children

PubMed Central

Bloch, Michael H.; Storch, Eric A.

2015-01-01

OBJECTIVE To review the assessment and treatment of treatment-refractory pediatric obsessive-compulsive disorder (OCD). METHOD A PubMed search was conducted to identify controlled trials in pediatric OCD. Additionally, practice guidelines for the treatment of adults and children were further reviewed for references in treatment-refractory OCD across the lifespan. RESULTS Pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy are effective treatments for pediatric OCD. Evidence suggests that CBT is additionally effective even in pediatric patients with refractory OCD symptoms. Antipsychotic augmentation, raising SSRI dosage, and several glutamate-modulating agents have some evidence of efficacy in adults with treatment-refractory OCD but have not been studied in pediatric populations. CONCLUSION Several pharmacological treatment options exist for children with refractory OCD symptoms. However, little evidence-based data exist to guide treatment for our most challenging pediatric OCD patients. Further research is needed to evaluate the efficacy/side-effect profile of commonly used interventions in treatment-refractory pediatric OCD. PMID:25791142

[Surgical therapy of life-threatening tachycardic cardiac arrhythmias in children].

PubMed

Frank, G; Schmid, C; Baumgart, D; Lowes, D; Klein, H; Kallfelz, H C

1989-05-01

Surgical techniques for tachyarrhythmias refractory to medical treatment are used with increasing frequency. Among 211 patients undergoing antiarrhythmic surgery 10 children (2 to 14 years old) were operated by electrophysiologically directed procedures. 7 patients suffered from WPW syndrome, 2 from focal atrial tachycardias and 1 from recurrent ventricular tachycardia following the repair of Fallot's tetralogy. In all cases preoperative electrophysiologic study and intraoperative mapping preceded operative ablation. Surgical treatment consisted of interruption of the bundle of Kent (3 right-sided, 2 left-sided, 3 septal), ablation of the atrial focus (1 right-sided, 1 left-sided) and right ventricular outflow tract incision. In 7 operations cryo-techniques were added. 2 children with WPW syndrome had two interventions because of tachycardia recurrences due to multiple accessory pathways. In 1 case a VVI-pacemaker was implanted postoperatively due to complete atrioventricular block. Another 2 children with prolonged postoperative bradycardia received a pacemaker prophylactically. Only the child with previous tetralogy of Fallot is still under antiarrhythmic medication while all other children are free of tachycardiac episodes. Our data confirm the efficacy of surgical treatment of tachyarrhythmias in children thereby abolishing the need for life-long antiarrhythmic medication.

Oral sirolimus: A possible treatment for refractory angina pectoris in the elderly.

PubMed

Mischie, Alexandru; Chanseaume, Sylvain; Gaspard, Philippe; Andrei, Catalina Liliana; Sinescu, Crina; Schiariti, Michele

2016-11-01

Refractory angina pectoris (RAP) is a clinical problem, frequently encountered in the elderly, associated with high health-care costs. Until recently, the goal of RAP treatment aimed at improving the quality of life (QoL) because it was thought that mortality rates were not different between stable angina pectoris and RAP. Our purpose was at determining whether any mortality rate difference exists and whether any novel therapeutical solution might be translated into clinical practice. We therefore performed a literature review to assess current optimal treatment of RAP patients, including all studies involving the use of oral sirolimus and stents, although no consistent evidence was found for any specific treatment to improve survival, apart from minor QoL amelioration. A large mortality difference was seen between RAP and stable angina pectoris. On the other hand, therapeutic approaches to RAP patients showed frequent complications and several contraindications, depending on the procedure. We propose to inhibit instead of stimulating angiogenesis, by giving oral sirolimus, an immunosuppressive drug, thereby decreasing the atherosclerotic process and its evolution. Sirolimus was shown to decrease left ventricular mass (thus indirectly decreasing myocardial oxygen needs and consumption). It might stop and, in some cases, even enable regression of plaque progression. Sirolimus side effects are mild to moderate and wash-out rapidly at treatment discontinuation. Compared with current therapies sirolimus treatment is more health-care cost efficient. It should be important to design a trial in RAP patients powered to reduce mortality and QoL increase. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Right ventricular longitudinal strain correlates well with right ventricular stroke work index in patients with advanced heart failure referred for heart transplantation.

PubMed

Cameli, Matteo; Lisi, Matteo; Righini, Francesca Maria; Tsioulpas, Charilaos; Bernazzali, Sonia; Maccherini, Massimo; Sani, Guido; Ballo, Piercarlo; Galderisi, Maurizio; Mondillo, Sergio

2012-03-01

Right ventricular (RV) systolic function has a critical role in determining the clinical outcome and success of using left ventricular assist devices (LVADs) in patients with refractory heart failure. Tissue Doppler and M-mode measurements of tricuspid systolic motion (tricuspid S' and tricuspid annular plane systolic excursion [TAPSE]) are the most currently used methods for the quantification of RV longitudinal function; RV deformation analysis by speckle-tracking echocardiography (STE) has recently allowed the analysis of global RV longitudinal function. Using cardiac catheterization as the reference standard, this study aimed at exploring the correlation between RV longitudinal function by STE and RV stroke work index (RVSWI) in patients referred for cardiac transplantation. Right-side heart catheterization and transthoracic echo Doppler were simultaneously performed in 41 patients referred for cardiac transplantation evaluation for advanced systolic heart failure. Thermodilution RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). Tricuspid S' and TAPSE were also calculated. No significant correlations were found for TAPSE or tricuspid S' with RVSWI (r = 0.14; r = 0.06; respectively). Close negative correlations between global RVLS and free-wall RVLS with the RVSWI were found (r = -0.75; r = -0.82; respectively; both P < .0001). Furthermore, free-wall RVLS demonstrated the highest diagnostic accuracy (area under the receiver operating characteristic (ROC) curve 0.90) and good sensitivity and specificity of 92% and 86%, respectively, to predict depressed RVSWI using a cutoff value of less than -11.8%. In a group of patients referred for heart transplantation, TAPSE and tricuspid S' did not correlate with invasively obtained RVSWI. RV longitudinal deformation analysis by STE correlated well with RVSWI, providing a better estimation of RV systolic performance. Copyright © 2012 Elsevier Inc. All rights reserved.

Catheter ablation for premature ventricular contractions and ventricular tachycardia in patients with heart failure.

PubMed

Kumar, Saurabh; Stevenson, William G; John, Roy M

2014-09-01

Ventricular arrhythmias (VA) are a significant contributor to morbidity and mortality in patients with heart failure (HF). Implantable cardioverter defibrillators are effective in reducing mortality, but do not prevent arrhythmia recurrence. There is increasing recognition that frequent premature ventricular contractions or repetitive ventricular tachycardia may also lead to new onset ventricular dysfunction or deterioration of ventricular function in patients with pre-existing HF. Suppression of the arrhythmia may lead to recovery of ventricular function. Catheter ablation has emerged as a safe and effective treatment option for reducing arrhythmia recurrence and for suppression of PVCs but its efficacy is governed by the nature of the arrhythmias, the underlying HF substrate and the accessibility of the arrhythmia substrates to ablation.

The effect of various sintering temperature on used refractory towards its physical properties

NASA Astrophysics Data System (ADS)

Sudibyo; Wulandari, Y. R.; Amin, M.; Azhar

2018-01-01

The used magnesia refractory from the kiln of cement industry was successfully recycled to new refractory using Kaolin as an adhesive. In this work, the temperatures of sintering were varied from 1000°C to 1500°C. The result shows that the increment temperature effects in sintering process will enhance refractory physical properties such as bulk density, cold crushing strength or pressure strength and thermal conductivity. Meanwhile, the porosity was decreased as the increase of the sintering temperature.

The effects of pure potassium channel blocker nifekalant and sodium channel blocker mexiletine on malignant ventricular tachyarrhythmias.

PubMed

Otuki, Sou; Hasegawa, Kanae; Watanabe, Hiroshi; Katsuumi, Goro; Yagihara, Nobue; Iijima, Kenichi; Sato, Akinori; Izumi, Daisuke; Furushima, Hiroshi; Chinushi, Masaomi; Aizawa, Yoshifusa; Minamino, Tohru

Patients with repetitive ventricular tachyarrhythmias - so-called electrical storm - frequently require antiarrhythmic drugs. Amiodarone is widely used for the treatment of electrical storm but is ineffective in some patients. Therefore, we investigated the efficacy of stepwise administration of nifekalant, a pure potassium channel blocker, and mexiletine for electrical storm. This study included 44 patients with repetitive ventricular tachyarrhythmias who received stepwise therapy with nifekalant and mexiletine for electrical storm. Nifekalant was initially administered, and mexiletine was subsequently added if nifekalant failed to control ventricular tachyarrhythmias. Nifekalant completely suppressed recurrences of ventricular arrhythmias in 28 patients (64%), including 6 patients in whom oral amiodarone failed to control arrhythmias. In 9 of 16 patients in whom nifekalant was partially effective but failed to suppress ventricular arrhythmias, mexiletine was added. The addition of mexiletine prevented recurrences of ventricular tachyarrhythmias in 5 of these 9 patients (56%). There was no death associated with electrical storm. In total, the stepwise treatment with nifekalant and mexiletine was effective in preventing ventricular tachyarrhythmias in 33 of 44 patients (75%). There was no difference in cycle length of the ventricular tachycardia, QRS interval, QT interval, or left ventricular ejection fraction between patients who responded to antiarrhythmic drugs and those who did not. During follow-up, 8 patients had repetitive ventricular tachyarrhythmia recurrences, and the stepwise treatment was effective in 6 of these 8 patients (75%). The stepwise treatment with nifekalant and mexiletine was highly effective in the suppression of electrical storm. Copyright © 2016. Published by Elsevier Inc.

Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.

PubMed

Li, Mengye; Hothi, Sandeep S; Salvage, Samantha C; Jeevaratnam, Kamalan; Grace, Andrew A; Huang, Christopher L-H

2017-06-01

Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention. The Epac activator 8-CPT (8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate) (VT in 1 of 7 hearts), and the RyR2 blocker dantrolene, either alone (0 of 11) or with 8-CPT (0 of 9) did not then increase VT incidence (P>.05). Both progressively increased pacing rates and programmed extrasystolic (S2) stimuli similarly produced no VT in untreated hearts (n=20 and n=9 respectively). 8-CPT challenge then increased VT incidences (5 of 7 and 4 of 8 hearts respectively; P<.05). However, dantrolene, whether alone (0 of 10 and 1 of 13) or combined with 8-CPT (0 of 10 and 0 of 13) did not increase VT incidence relative to those observed in untreated hearts (P>.05). 8-CPT but not dantrolene, whether alone or combined with 8-CPT, correspondingly increased AP latencies (1.14±0.04 (n=7), 1.04±0.03 (n=10), 1.09±0.05 (n=8) relative to respective control values). In contrast, AP durations, conditions for 2:1 conduction block and ventricular effective refractory periods remained unchanged throughout. We thus demonstrate for the first time that acute RyR2 activation reversibly induces VT in specific association with reduced CV. © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.

PubMed

Siddiqui, Mohammed; Judd, Eric K; Oparil, Suzanne; Calhoun, David A

2017-09-01

Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment. © 2017 American Heart Association, Inc.

Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis.

PubMed

Lin, Lung-Chang; Ouyang, Chen-Sen; Chiang, Ching-Tai; Yang, Rei-Cheng; Wu, Rong-Ching; Wu, Hui-Chuan

2014-11-01

Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy.

Treating Refractory Cardiogenic Shock With the TandemHeart and Impella Devices: A Single Center Experience

PubMed Central

Schwartz, Bryan G.; Ludeman, Daniel J.; Mayeda, Guy S.; Kloner, Robert A.; Economides, Christina; Burstein, Steven

2012-01-01

Background Patients with cardiogenic shock (CS) are routinely treated with intra-aortic balloon pumps (IABPs). The utility of 2 new percutaneous left ventricular assist devices (PLVADs), the Impella and TandemHeart, is unknown. The objective of this study was to describe the use of PLVADs for patients with CS at our institution. Methods All cases involving PLVADs in patients with CS between between January 1, 2008 and June 30, 2010 at a private, tertiary referral hospital were reviewed retrospectively. Results All 76 cases were identified (50 IABP only, 7 Impella, 19 TandemHeart). Most Impella (5/7) and TandemHeart (10/19) patients were initially treated with an IABP before "upgrading" for increased hemodynamic support. All 76 devices (100%) were initiated successfully. Percutaneous revascularization was attempted in 63 patients with angiographic success in 57 (90%). The incidences of major complications were similar between groups, except bleeding occurred less frequently with the IABP. Mean ejection fraction on presentation was 30.4±16.5% and increased by a mean of 6.6±11.4% (P < 0.001). With the institutional approach of treating patients with CS initially with vasopressors and IABPs, then upgrading to an Impella or TandemHeart device for patients refractory to IABP therapy, the overall mortality rate was 40%. Conclusion The Impella and TandemHeart devices can be initiated successfully in patients with CS, are associated with high rates of angiographic success during high risk percutaneous interventions and may benefit the myocardium during myocardial infarction. Randomized trials are warranted investigating use of the Impella and TandemHeart devices in patients with CS and in patients refractory to conventional IABP therapy. PMID:28348673

Extracorporeal life support in the treatment of colchicine poisoning.

PubMed

Boisramé-Helms, Julie; Rahmani, Hassène; Stiel, Laure; Tournoud, Christine; Sauder, Philippe

2015-01-01

Ingestions of Colchicum autumnale may lead to severe poisoning. It begins with gastrointestinal symptoms and leukocytosis, followed by multi-organ failure with shock and a possible late recovery phase. Mortality is highly dependent on the ingested dose. We report a case of accidental C. autumnale poisoning with refractory cardiogenic shock and eventual survival after extracorporeal life support (ECLS). A 68-year-old woman was admitted to the intensive care unit (ICU) on day 3 after ingestion of C. autumnale in a meal. She first suffered from nausea and vomiting leading to severe dehydration. She then developed multi-organ failure and refractory cardiogenic shock, with a mean arterial pressure nadir of 50 mmHg despite high doses of catecholamines and a left ventricular ejection fraction at 5-10%. Venous-arterial ECLS was therefore started at an initial rate of 3.5 L/min and 3,800 rev/min. Her symptoms also included pancytopenia on day 4 with diffuse bleeding requiring iterative blood product transfusion. Platelet and leukocyte count nadirs were 13 × 10(9)/L (normal range: 150-400 × 10(9)/L) and 0.77 × 10(9)/L (normal range: 4.2-10.7 × 10(9)/L), respectively. ECLS allowed good cardiac contractility recovery within a few days, with complications including bleeding made controllable. Indeed, because of hemostasis disorders, the patient presented hemoptysis and hematuria. She was treated with tranexamic acid and transfused with blood products. She received 15 erythrocyte concentrates, 13 platelet concentrates, and 7 fresh frozen plasma. ECLS was removed by day 10, with subsequent weaning from mechanical ventilation as well as from hemodialysis in the following days. This patient survives after the use of ECLS in Colchicum poisoning, with controllable complications. Thus, ECLS might be indicated to overcome the potentially refractory cardiogenic shock phase.

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

PubMed

Wink, Jeroen; de Wilde, Rob B P; Wouters, Patrick F; van Dorp, Eveline L A; Veering, Bernadette Th; Versteegh, Michel I M; Aarts, Leon P H J; Steendijk, Paul

2016-10-18

Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV 25 : -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia. Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844. © 2016 American Heart Association, Inc.

The differential contributions of pFC and temporo-parietal cortex to multimodal semantic control: exploring refractory effects in semantic aphasia.

PubMed

Gardner, Hannah E; Lambon Ralph, Matthew A; Dodds, Naomi; Jones, Theresa; Ehsan, Sheeba; Jefferies, Elizabeth

2012-04-01

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show "refractory effects"; that is, declining accuracy in cyclical word-picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

Use of the aortoatrial continuity as means of providing left ventricular assist support without entering the ventricle: a feasibility study.

PubMed

Friedman, Paul A; Kushwaha, Sudhir S; Bruce, Charles J; Park, Soon J; Ladewig, Dorothy J; Mikell, Susan B; Johnson, Susan B; Suddendorf, Scott H; Danielsen, Andrew J; Asirvatham, Samuel J

2011-06-01

Left ventricular assist devices (LVADs) are increasingly used to treat patients with refractory heart failure. Current-generation LVADs have major limitations, including the need for open chest surgery, limiting their widespread use. We hypothesized that the aortoatrial continuity could be used as a unique anatomic vantage point for entirely percutaneous LVAD placement. Forty human autopsied hearts were examined to ascertain the presence and define the dimensions of the continuity between the posterior aortic wall and the left atrium. In all cases, a "septum" between the aorta and left atrium was identified. In 3 animal experiments, a custom mechanical shunt was deployed in the wall between the left atrium and noncoronary cusp. With continuous intracardiac ultrasound imaging, and at necropsy, there was no evidence of device dislodgement, pericardial effusion, or aortic or coronary artery trauma noted. It is feasible to use the wall between the aorta and left atrium as an access route for a potentially entirely percutaneous LVAD. Such a system obviates the need for accessing the left ventricle, minimizing complications. In the future, such devices may allow widespread treatment of heart failure, malignant cardiac arrhythmia, and severe aortic and mitral valvular disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Usefulness of cardiac resynchronization therapy in the management of Doxorubicin-induced cardiomyopathy.

PubMed

Ajijola, Olujimi A; Nandigam, K Veena; Chabner, Bruce A; Orencole, Mary; Dec, G William; Ruskin, Jeremy N; Singh, Jagmeet P

2008-05-01

Doxorubicin is a widely used antineoplastic agent that may cause irreversible dilated cardiomyopathy. Doxorubicin-induced cardiomyopathy (DIC) can occur several years after exposure and carries a poor prognosis. Although cardiac resynchronization therapy (CRT) is a useful intervention in end-stage heart failure unresponsive to optimal medical therapies, its efficacy in DIC remains unknown. Four consecutive patients receiving CRT for DIC were evaluated before and after CRT. CRT resulted in improvements in the mean left ventricular ejection fraction at 1 month from 21+/-4.7% to 34+/-5% (p=0.03) and at 6 months (to 46+/-7.5%, p=0.01). CRT-induced reverse remodeling was observed, with a mean reduction in left ventricular internal diameter at end-diastole from 54.75+/-3.7 to 52.5+/-1.9 mm at 1 month (p=0.06) and further to 47+/-2.3 mm at 6 months (p=0.03). All patients experienced reductions in heart failure symptoms and improvements in New York Heart Association functional class (p<0.05). The impact of CRT was sustained over a follow-up of 18.5+/-3.5 months. In conclusion, this study suggests that patients with DIC, refractory to optimal pharmacologic therapy and meeting criteria for resynchronization device implantation, may achieve sustained benefit from CRT.

Wolff-Parkinson-White syndrome in the era of catheter ablation: insights from a registry study of 2169 patients.

PubMed

Pappone, Carlo; Vicedomini, Gabriele; Manguso, Francesco; Saviano, Massimo; Baldi, Mario; Pappone, Alessia; Ciaccio, Cristiano; Giannelli, Luigi; Ionescu, Bogdan; Petretta, Andrea; Vitale, Raffaele; Cuko, Amarild; Calovic, Zarko; Fundaliotis, Angelica; Moscatiello, Mario; Tavazzi, Luigi; Santinelli, Vincenzo

2014-09-02

The management of Wolff-Parkinson-White is based on the distinction between asymptomatic and symptomatic presentations, but evidence is limited in the asymptomatic population. The Wolff-Parkinson-White registry was an 8-year prospective study of either symptomatic or asymptomatic Wolff-Parkinson-White patients referred to our Arrhythmology Department for evaluation or ablation. Inclusion criteria were a baseline electrophysiological testing with or without radiofrequency catheter ablation (RFA). Primary end points were the percentage of patients who experienced ventricular fibrillation (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168 (206 asymptomatic) underwent ablation (RFA group). There were no differences in clinical and electrophysiological characteristics between the 2 groups except for symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually exclusively (13 of 15) in children (median age, 11 years), and was associated with a short accessory pathway antegrade refractory period (P<0.001) and atrioventricular reentrant tachycardia initiating atrial fibrillation (P<0.001) but not symptoms. In the RFA group, ablation was successful in 98.5%, and after RFA, no patients developed malignant arrhythmias or VF over the 8-year follow-up. Untreated patients were more likely to experience malignant arrhythmias and VF (log-rank P<0.001). Time-dependent receiver-operating characteristic curves for predicting VF identified an optimal anterograde effective refractory period of the accessory pathway cutoff of 240 milliseconds. The prognosis of the Wolff-Parkinson-White syndrome essentially depends on intrinsic electrophysiological properties of AP rather than on symptoms. RFA performed during the same procedure after electrophysiological testing is of benefit in improving the long-term outcomes. © 2014 American Heart Association, Inc.

Clinical Spectrum and Management of Heart Failure in Hypertrophic Cardiomyopathy.

PubMed

Maron, Barry J; Rowin, Ethan J; Udelson, James E; Maron, Martin S

2018-05-01

Heart failure (HF), characterized by excessive exertional dyspnea, is a common complication within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM). HF has become an increasingly prominent management issue with the reduction in sudden deaths due to use of implantable defibrillators in this disease. Exertional dyspnea ranges in severity from mild to severe (New York Heart Association functional classes II to IV) and not uncommonly becomes refractory to medical management, leading to progressive disability, but largely in the absence of pulmonary congestion and volume overload requiring hospitalization. HCM-related HF is most commonly due to dynamic mechanical impedance to left ventricular outflow produced by mitral valve systolic anterior motion, leading to high intracavity pressures. Surgical septal myectomy with low operative mortality (<1%) produces HF reversal and symptom relief in 90% to 95% of patients, while also conveying a survival benefit. Exercise echocardiography has assumed an important role in the evaluation of patients with HCM, i.e., by identifying candidates for septal reduction therapy with refractory HF when outflow gradients are present only with physiological exercise, distinguishing highly symptomatic nonobstructive patients as heart transplant candidates, and predicting future development of progressive HF. Notably, mortality directly attributable to HF has become exceedingly uncommon in HCM (<0.5%/year) in contrast with HF in non-HCM diseases (by 20-fold). In conclusion, HF in HCM is associated with diverse and complex pathophysiology, but a substantially more favorable prognosis than conventional non-HCM HF, and highly amenable to effective treatment options in the vast majority of patients. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Ambulatory extracorporeal membrane oxygenation with subclavian venoarterial cannulation to increase mobility and recovery in a patient awaiting cardiac transplantation

PubMed Central

Jacob, Samuel; MacHannaford, Juan C.; Chamogeorgakis, Themistokles; Gonzalez-Stawinski, Gonzalo V.; Felius, Joost; Rafael, Aldo E.; Malyala, Rajasekhar S.

2017-01-01

Venoarterial extracorporeal membrane oxygenation (ECMO) can provide temporary cardiopulmonary support for patients in hemodynamic extremis or refractory heart failure until more durable therapies—such as cardiac transplantation or a left ventricular assist device—can be safely implemented. Conventional ECMO cannulation strategies commonly employ the femoral artery and vein, constraining the patients to the supine position for the duration of ECMO support. We have recently adopted a modified cannulation approach to promote patient mobility, rehabilitation, and faster recovery and to mitigate complications associated with femoral arterial cannulation, such as limb ischemia and compartment syndrome. This technique involves cannulation of the subclavian artery and vein. The current case report details our recent experience with this approach in a critically ill patient awaiting cardiac transplantation. PMID:28405091

A time dependent anatomically detailed model of cardiac conduction

NASA Technical Reports Server (NTRS)

Saxberg, B. E.; Grumbach, M. P.; Cohen, R. J.

1985-01-01

In order to understand the determinants of transitions in cardiac electrical activity from normal patterns to dysrhythmias such as ventricular fibrillation, we are constructing an anatomically and physiologically detailed finite element simulation of myocardial electrical propagation. A healthy human heart embedded in paraffin was sectioned to provide a detailed anatomical substrate for model calculations. The simulation of propagation includes anisotropy in conduction velocity due to fiber orientation as well as gradients in conduction velocities, absolute and relative refractory periods, action potential duration and electrotonic influence of nearest neighbors. The model also includes changes in the behaviour of myocardial tissue as a function of the past local activity. With this model, we can examine the significance of fiber orientation and time dependence of local propagation parameters on dysrhythmogenesis.

Bard Denali inferior vena cava filter fracture and embolization resulting in cardiac tamponade: a device failure analysis.

PubMed

Kuo, William T; Robertson, Scott W

2015-01-01

A 46-year-old woman underwent inferior vena cava filter placement before bariatric surgery and returned within 6 months for routine removal. She complained of a 1-week history of severe chest pain, and during retrieval, two fractured filter components were identified including one arm in the right ventricle. The filter body and one fragment were successfully retrieved, but the fragment in the right ventricle was refractory to percutaneous retrieval. During open-heart surgery, the fragment was found traversing through the ventricular wall resulting in cardiac tamponade. Electron microscopic fragment analysis revealed high-cycle metal fatigue indicating the filter design failed to withstand this patient's natural inferior vena cava biomechanical motions. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

PubMed

Labidi, Asma; Serghini, Meriem; Ben Mustapha, Nadia; Fekih, Monia; Boubaker, Jalel; Filali, Azza

2014-11-01

Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies. The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease. Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease. Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial. Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

PubMed

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

[The reasonable use of right ventricular protection strategy in right ventricular outflow tract reconstruction].

PubMed

Zhang, Y; Yuan, H Y; Liu, X B; Wen, S S; Xu, G; Cui, H J; Zhuang, J; Chen, J M

2018-06-01

As a result of right ventricular outflow tract reconstruction, which is the important and basic step of complex cardiac surgery, the blood flow of right ventricular outflow tract is unobstructed, while pulmonary valve regurgitation and right heart dysfunction could be happened. These problems are often ignored in early days, more and more cases of right heart dysfunction need clinical intervention, which is quite difficult and less effective. How to protect effectively the right ventricular function is the focus. At present main methods to protect the right ventricular function include trying to avoid or reduce length of right ventricular incision, reserving or rebuilding the function of the pulmonary valve, using growth potential material for surgery. The protection of the right ventricular function is a systemic project, it involves many aspects, single measures is difficult to provide complete protection, only the comprehensive use of various protection strategy, can help to improve the long-term prognosis.

Simulation of meso-damage of refractory based on cohesion model and molecular dynamics method

NASA Astrophysics Data System (ADS)

Zhao, Jiuling; Shang, Hehao; Zhu, Zhaojun; Zhang, Guoxing; Duan, Leiguang; Sun, Xinya

2018-06-01

In order to describe the meso-damage of the refractories more accurately, and to study of the relationship between the mesostructured of the refractories and the macro-mechanics, this paper takes the magnesia-carbon refractories as the research object and uses the molecular dynamics method to instead the traditional sequential algorithm to establish the meso-particles filling model including small and large particles. Finally, the finite element software-ABAQUS is used to conducts numerical simulation on the meso-damage evolution process of refractory materials. From the results, the process of initiation and propagation of microscopic interface cracks can be observed intuitively, and the macroscopic stress-strain curve of the refractory material is obtained. The results show that the combination of molecular dynamics modeling and the use of Python in the interface to insert the cohesive element numerical simulation, obtaining of more accurate interface parameters through parameter inversion, can be more accurate to observe the interface of the meso-damage evolution process and effective to consider the effect of the mesostructured of the refractory material on its macroscopic mechanical properties.

Reduction of Serious Adverse Events Demanding Study Exclusion in Model Development: Extracorporeal Life Support Resuscitation of Ventricular Fibrillation Cardiac Arrest in Rats.

PubMed

Warenits, Alexandra-Maria; Sterz, Fritz; Schober, Andreas; Ettl, Florian; Magnet, Ingrid Anna Maria; Högler, Sandra; Teubenbacher, Ursula; Grassmann, Daniel; Wagner, Michael; Janata, Andreas; Weihs, Wolfgang

2016-12-01

Extracorporeal life support is a promising concept for selected patients in refractory cardiogenic shock and for advanced life support of persistent ventricular fibrillation cardiac arrest. Animal models of ventricular fibrillation cardiac arrest could help to investigate new treatment strategies for successful resuscitation. Associated procedural pitfalls in establishing a rat model of extracorporeal life support resuscitation need to be replaced, refined, reduced, and reported.Anesthetized male Sprague-Dawley rats (350-600 g) (n = 126) underwent cardiac arrest induced with a pacing catheter placed into the right ventricle via a jugular cannula. Rats were resuscitated with extracorporeal life support, mechanical ventilation, defibrillation, and medication. Catheter and cannula explantation was performed if restoration of spontaneous circulation was achieved. All observed serious adverse events (SAEs) occurring in each of the experimental phases were analyzed.Restoration of spontaneous circulation could be achieved in 68 of 126 rats (54%); SAEs were observed in 76 (60%) experiments. Experimental procedures related SAEs were 62 (82%) and avoidable human errors were 14 (18%). The most common serious adverse events were caused by insertion or explantation of the venous bypass cannula and resulted in lethal bleeding, cannula dislocation, or air embolism.Establishing an extracorporeal life support model in rats has confronted us with technical challenges. Even advancements in small animal critical care management over the years delivered by an experienced team and technical modifications were not able to totally avoid such serious adverse events. Replacement, refinement, and reduction reports of serious adverse events demanding study exclusions to avoid animal resources are missing and are presented hereby.

A calf model for left ventricular centrifugal mechanical assist.

PubMed

Mann, F A; Wagner-Mann, C C; Curtis, J J; Demmy, T L; Turk, J R

1996-06-01

The increased use of centrifugal mechanical assist (CMA) for treatment of refractory postcardiotomy cardiogenic shock highlights the need for experimental testing to improve clinical results. This report describes the preoperative conditioning, anesthetic and surgical technique, and postoperative management of a reliable calf model refined in this laboratory for in vivo subchronic (96 h) testing of CMA. Holstein bull calves (2 to 3 months old; mean body weight, 78 kg; n = 35) were instrumented for left ventricular CMA; 4 of these calves were sham-operated controls. Anesthetic recovery and postoperative restraint were accomplished in a specially designed crate to which each calf was preconditioned extensively. Younger calves were more readily conditioned and more tolerant of postoperative restraint than older calves. One calf died of ventricular fibrillation intraoperatively. One calf that had been heparinized developed uncontrollable hemothorax and died 12 h postoperatively. One calf prematurely dislodged his aortic cannula 15 h postoperatively and exsanguinated. Six calves developed pelvic limb paresis or paralysis because of lumbar spinal cord thromboembolism by 36 h postoperatively, and 3 of these calves were sacrificed by 42 h postoperatively. Fifteen calves required sedation in the first 12 h after the operation. Tachycardia associated with bottle feeding occurred in 15 calves. Second-degree atrioventricular block was noted frequently during deep relaxation. Postmortem examination demonstrated the absence of surgical wound and distant infection, security of cannulae in all but the calf that prematurely dislodged the aortic cannula, absence of thrombus formation at cannulation sites, and presence of thromboembolism in 51% of the calves. The incidence of thromboembolic lesions was not influenced by the need for chemical restraint, by the occurrence of feeding-associated tachycardia, or by the presence of atrioventricular block. There were no thromboembolic lesions in any of the sham-operated controls.

Transvenous versus open chest lead placement for resynchronization therapy in patients with heart failure: comparison of ventricular electromechanical synchronicity.

PubMed

Zhang, Hai-Bo; Meng, Xu; Han, Jie; Li, Yan; Zhang, Ye; Jiang, Teng-Yong; Zhao, Ying-Xin; Zhou, Yu-Jie

2017-04-01

Transvenous lead placement is the standard approach for left ventricular (LV) pacing in cardiac resynchronization therapy (CRT), while the open chest access epicardial lead placement is currently the most frequently used second choice. Our study aimed to compare the ventricular electromechanical synchronicity in patients with heart failure after CRT with these two different LV pacing techniques. We enrolled 33 consecutive patients with refractory heart failure secondly to dilated cardiomyopathy who were eligible for CRT in this study. Nineteen patients received transvenous (TV group) while 14 received open chest (OP group) LV lead pacing. Intra- and inter-ventricular electromechanical synchronicity was assessed by tissue Doppler imaging (TDI) before and one year after CRT procedure. Before CRT procedure, the mean QRS-duration, maximum time difference to systolic peak velocity among 12 left ventricle segments (LV Ts-12), standard deviation of time difference to systolic peak velocity of 12 left ventricle segments (LV Ts-SD), and inter-ventricular mechanical delay (IVMD) in OP and TV group were 166 ± 17 ms and 170 ± 21 ms, 391 ± 42 ms and 397 ± 36 ms, 144 ± 30 ms and 148 ± 22 ms, 58 ± 25 ms and 60 ± 36 ms, respectively (all P > 0.05). At one year after the CRT, the mean QRS-duration, LV Ts-12, LV Ts-SD, and IVMD in TV and OP group were 128 ± 14 ms and 141 ± 22 ms ( P = 0.031), 136 ± 37 ms and 294 ± 119 ms ( P = 0.023), 50 ± 22 ms and 96 ± 34 ms ( P = 0.015), 27 ± 11 ms and 27 ± 26 ms ( P = 0.86), respectively. The LV lead implantation procedure time was 53.4 ± 16.3 min for OP group and 136 ± 35.1 min for TV group ( P = 0.016). The mean LV pacing threshold increased significantly from 1.7 ± 0.6 V/0.5 ms to 2.3 ± 1.6 V/0.5 ms ( P < 0.05) in TV group while it remained stable in the OP group. Compared to conventional endovascular approach, open chest access of LV pacing for CRT leads to better improvement of the intraventricular synchronization.

[Changes of heart electrophysiological parameters after destruction of epicardial subplexuses that innervate sinoatrial node].

PubMed

Kulboka, Arūnas; Veikutis, Vincentas; Pauza, Dainius Haroldas; Lekas, Raimundas

2003-01-01

The aims of present study were to verify the topography of the intracardiac nerve subplexuses (INS) by using electrophysiological methods, its relations with sinoatrial (SA) node function and to investigate possibility of selective surgical SA node denervation. Fifteen mongrel dogs of either sex weighing 8 to 15 kg were used for electrophysiological studies. Both cervical vagosympathetic trunks were isolated and crushed by tight ligatures. Nervus subplexuses destructions were performed by cryocoagulation in three zones located around the right superior vena cava: ventral, lateral and dorsal. The sinus rhythm, SA node function recovery time, AV node conductivity, AV node and atrial effective refractory period were measured. Five experiments in each of three zones were performed. Experimental data show that destruction of the epicardial nerves has different effect on electrophysiological parameters. After destruction of the anterior zone of the right atrium the sinus rhythm decreased on an average by 11.6%; SA node function recovery time prolonged by 7.2%; AV node conductivity decreased by 13.1%; AV node effective refractory period prolonged by 12.9% and atrial effective refractory period, by 10.9 %. Measurements of electrophysiological parameters after intravenous injection of atropine sulphate show that sinus rhythm decreased on an average by 23.4%; SA node function recovery time increased by 9.1%; the conductivity of AV node decreased by 10.2%; AV node effective refractory period prolonged by 15.4% and atrial effective refractory period, by 13.2%. After destruction of the intracardiac nerves of the lateral zone, the sinus rhythm decreased by 15.7%; SA node function recovery time increased by 16.3%; AV node conductivity decreased by 8.3%; AV node effective refractory period and atrial effective refractory period prolonged by 11.9% and 10.0%, respectively. After the atropine sulphate intravenous injection, the sinus rhythm decreased on an average by 7.1%, SA node function recovery time prolonged by 7.1%, AV conductivity decreased by 9.1%, AV node effective refractory period increased by 12.4%, and atrial effective refractory period prolonged by 12.5%. After destruction of the nerves in the dorsal zone the changes of electrophysiological parameters were opposite to those obtained after destruction of the nerve tracts in the anterior or lateral zones: the sinus rhythm increased on an average by 4.3%; SA node function recovery time shortened by 8.8%; AV conductivity increased by 9.7%; AV node and atrial effective refractory period decreased by 12.3% and 12.1%, respectively. After intravenous atropine sulphate infusion, sinus rhythm decreased on an average by 8.3%; SA node function recovery time prolonged by 9.6%; AV node conductivity decreased by 5%; AV node and atrial effective refractory period prolonged by 4.2% and 5.2%, respectively. The average changes of electrophysiological parameters before and after INS destruction shows that cryocoagulation of ventral and lateral zones eliminates the effects of sympathetic tone to SA and AV nodal activity. Cryocoagulation of dorsal zone eliminates the effects of nervus vagus to both nodal structures. These findings shows the possibility alter or correct SA node function by making selective surgical SA node denervation.

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

PubMed Central

Workman, Antony J; Pau, Davide; Redpath, Calum J; Marshall, Gillian E; Russell, Julie A; Norrie, John; Kane, Kathleen A; Rankin, Andrew C

2009-01-01

Background Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective To investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes which could predispose to AF. Methods Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. Results The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period, ERP (209±8 ms; 52 cells, 18 patients vs 233±7 ms; 134 cells, 49 patients; P<0.05); confirmed by multiple linear regression analysis. The LV ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36±4%, n=15) than in those without LVSD (62±2%, n=31; P<0.05). In cells from patients with LVEF≤45%, the ERP and action potential duration at 90% repolarisation were shorter than in those from patients with LVEF>45%, by 24 and 18%, respectively. The LVEF and ERP were positively correlated (r=0.65, P<0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current was unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. Conclusion LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF. PMID:19324301

Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial.

PubMed

Kudenchuk, Peter J; Brown, Siobhan P; Daya, Mohamud; Morrison, Laurie J; Grunau, Brian E; Rea, Tom; Aufderheide, Tom; Powell, Judy; Leroux, Brian; Vaillancourt, Christian; Larsen, Jonathan; Wittwer, Lynn; Colella, M Riccardo; Stephens, Shannon W; Gamber, Mark; Egan, Debra; Dorian, Paul

2014-05-01

Despite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT). ALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after ≥1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score ≤3. The principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating. Results from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice. Copyright © 2014 Mosby, Inc. All rights reserved.

National experience with long-term use of the wearable cardioverter defibrillator in patients with cardiomyopathy.

PubMed

Lamichhane, Madhab; Gardiner, Joseph C; Bianco, Nicole R; Szymkiewicz, Steven J; Thakur, Ranjan K

2017-01-01

The wearable cardioverter defibrillator (WCD) is generally used for short periods of sudden cardiac death (SCD) risk; circumstances may occasionally result in prolonged use (over 1 year). The aim of this study was to determine the benefits and risks of prolonged use in patients with systolic heart failure (HF). ZOLL's post-market US database included adult patients (≥18 years) with ischemic and/or non-ischemic cardiomyopathy (ICM, NICM) and at least 1 year of use. Cox-regression was used to identify factors associated with survival with WCD use, and reasons for stopping use were entered as time-dependent factors. Among 220 patients, age (mean ± SD) 55.4 ± 14.8 years, WCD use 451.4 ± 289.9 days, and 67.3 % were male and their left ventricle ejection fraction (EF) averaged 20.9 ± 7.2 %. Eighty-nine (40.5 %) were continuing WCD use at the last follow-up. Thirty-six (16.4 %) and 56 (25.5 %) patients discontinued WCD use because of EF recovery and implantable cardioverter (ICD) implantation, respectively. Nine patients (4.1 %) received appropriate shock therapy for 13 episodes of sustained ventricular tachyarrhythmia with 12 (92.3 %) successful shocks. One patient died of refractory ventricular fibrillation. One patient died from sinus bradycardia transitioning to asystole. Eight patients (3.6 %) had nine episodes of non-fatal inappropriate shocks. Long-term use of the WCD is safe and effective. Recovery of EF was seen in significant number of patients even after 1 year of WCD use.

A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions.

PubMed

Carro, Jesús; Rodríguez, José Félix; Laguna, Pablo; Pueyo, Esther

2011-11-13

In this study, several modifications were introduced to a recently proposed human ventricular action potential (AP) model so as to render it suitable for the study of ventricular arrhythmias. These modifications were driven by new sets of experimental data available from the literature and the analysis of several well-established cellular arrhythmic risk biomarkers, namely AP duration at 90 per cent repolarization (APD(90)), AP triangulation, calcium dynamics, restitution properties, APD(90) adaptation to abrupt heart rate changes, and rate dependence of intracellular sodium and calcium concentrations. The proposed methodology represents a novel framework for the development of cardiac cell models. Five stimulation protocols were applied to the original model and the ventricular AP model developed here to compute the described arrhythmic risk biomarkers. In addition, those models were tested in a one-dimensional fibre in which hyperkalaemia was simulated by increasing the extracellular potassium concentration, [K(+)](o). The effective refractory period (ERP), conduction velocity (CV) and the occurrence of APD alternans were investigated. Results show that modifications improved model behaviour as verified by: (i) AP triangulation well within experimental limits (the difference between APD at 50 and 90 per cent repolarization being 78.1 ms); (ii) APD(90) rate adaptation dynamics characterized by fast and slow time constants within physiological ranges (10.1 and 105.9 s); and (iii) maximum S1S2 restitution slope in accordance with experimental data (S(S1S2)=1.0). In simulated tissues under hyperkalaemic conditions, APD(90) progressively shortened with the degree of hyperkalaemia, whereas ERP increased once a threshold in [K(+)](o) was reached ([K(+)](o)≈6 mM). CV decreased with [K(+)](o), and conduction was blocked for [K(+)](o)>10.4 mM. APD(90) alternans were observed for [K(+)](o)>9.8 mM. Those results adequately reproduce experimental observations. This study demonstrated the value of basing the development of AP models on the computation of arrhythmic risk biomarkers, as opposed to joining together independently derived ion channel descriptions to produce a whole-cell AP model, with the new framework providing a better picture of the model performance under a variety of stimulation conditions. On top of replicating experimental data at single-cell level, the model developed here was able to predict the occurrence of APD(90) alternans and areas of conduction block associated with high [K(+)](o) in tissue, which is of relevance for the investigation of the arrhythmogenic substrate in ischaemic hearts.

Treatment of Refractory Idiopathic Supraorbital Neuralgia Using Percutaneous Pulsed Radiofrequency.

PubMed

Luo, Fang; Lu, Jingjing; Ji, Nan

2018-02-26

No ideal therapeutic method currently exists for refractory idiopathic supraorbital neuralgia patients who do not respond to conservative therapy, including medications and nerve blocks. Pulsed radiofrequency is a neuromodulation technique that does not produce sequelae of nerve damage after treatment. However, the efficacy of percutaneous pulsed radiofrequency for the treatment of refractory idiopathic supraorbital neuralgia is still not clear. The purpose of our study was to evaluate the efficacy and safety of pulsed radiofrequency treatment of the supraorbital nerve for refractory supraorbital neuralgia patients. We prospectively investigated the long-term effects of ultrasound-guided percutaneous pulsed radiofrequency in the treatment of 22 refractory idiopathic supraorbital neuralgia patients. A reduction in the verbal pain numeric rating scale score of more than 50% was used as the standard of effectiveness. The effectiveness rates at different time points within 2 years were calculated. After a single pulsed radiofrequency treatment, the effectiveness rate at 1 and 3 months was 77%, and the rates at 6 months, 1 year, and 2 years were 73%, 64%, and 50%, respectively. Except for a small portion of patients (23%) who experienced mild upper eyelid ecchymosis that gradually disappeared after approximately 2 weeks, no obvious complications were observed. In conclusion, the results of our study demonstrate that for patients with refractory idiopathic supraorbital neuralgia, percutaneous pulsed radiofrequency may be an effective and safe treatment choice. © 2018 World Institute of Pain.

Cardiac arrest caused by sibutramine obtained over the Internet: a case of a young woman without pre-existing cardiovascular disease successfully resuscitated using extracorporeal membrane oxygenation.

PubMed

Bunya, Naofumi; Sawamoto, Keigo; Uemura, Shuji; Kyan, Ryoko; Inoue, Hiroyuki; Nishida, Junichi; Kouzu, Hidemichi; Kokubu, Nobuaki; Miura, Tetsuji; Narimatsu, Eichi

2017-07-01

Sibutramine is a weight loss agent that was withdrawn from the market in the USA and European Union because it increases adverse events in patients with cardiovascular diseases. However, non-prescription weight loss pills containing sibutramine can be still easily purchased over the Internet. A 21-year-old woman without history of cardiovascular diseases developed cardiac arrest. She was a user of a weight loss pills, containing sibutramine and hypokalemia-inducing agents, imported from Thailand over the Internet. She was successfully resuscitated without any neurological deficits by using extracorporeal membrane oxygenation for refractory ventricular fibrillation. This case indicates that sibutramine can cause cardiac arrest even in subjects without pre-existing cardiovascular disease when combined with agents that promote QT prolongation.

The electrophysiologic properties of esmolol, a short acting beta-blocker.

PubMed

Greenspan, A M; Spielman, S R; Horowitz, L N; Laddu, A; Senior, S

1988-04-01

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

Effect of short-term rapid ventricular pacing followed by pacing interruption on arterial blood pressure in healthy pigs and pigs with tachycardiomyopathy.

PubMed

Skrzypczak, P; Zyśko, D; Pasławska, U; Noszczyk-Nowak, A; Janiszewski, A; Gajek, J; Nicpoń, J; Kiczak, L; Bania, J; Zacharski, M; Tomaszek, A; Jankowska, E A; Ponikowski, P; Witkiewicz, W

2014-01-01

Ventricular tachycardia may lead to haemodynamic deterioration and, in the case of long term persistence, is associated with the development of tachycardiomyopathy. The effect of ventricular tachycardia on haemodynamics in individuals with tachycardiomyopathy, but being in sinus rhythm has not been studied. Rapid ventricular pacing is a model of ventricular tachycardia. The aim of this study was to determine the effect of rapid ventricular pacing on blood pressure in healthy animals and those with tachycardiomyopathy. A total of 66 animals were studied: 32 in the control group and 34 in the study group. The results of two groups of examinations were compared: the first performed in healthy animals (133 examinations) and the second performed in animals paced for at least one month (77 examinations). Blood pressure measurements were taken during chronic pacing--20 min after onset of general anaesthesia, in baseline conditions (20 min after pacing cessation or 20 min after onset of general anaesthesia in healthy animals) and immediately after short-term rapid pacing. In baseline conditions significantly higher systolic and diastolic blood pressure was found in healthy animals than in those with tachycardiomyopathy. During an event of rapid ventricular pacing, a significant decrease in systolic and diastolic blood pressure was found in both groups of animals. In the group of chronically paced animals the blood pressure was lower just after restarting ventricular pacing than during chronic pacing. Cardiovascular adaptation to ventricular tachycardia develops with the length of its duration. Relapse of ventricular tachycardia leads to a blood pressure decrease more pronounced than during chronic ventricular pacing.

Effects of Temperature, Oxygen Partial Pressure, and Materials Selection on Slag Infiltration into Porous Refractories for Entrained-Flow Gasifiers

NASA Astrophysics Data System (ADS)

Kaneko, Tetsuya Kenneth

The penetration rate of molten mineral contents (slag) from spent carbonaceous feedstock into porous ceramic-oxide refractory linings is a critical parameter in determining the lifecycle of integrated gasification combined cycle energy production plants. Refractory linings that withstand longer operation without interruption are desirable because they can mitigate consumable and maintenance costs. Although refractory degradation has been extensively studied for many other high-temperature industrial processes, this work focuses on the mechanisms that are unique to entrained-flow gasification systems. The use of unique feedstock mixtures, temperatures from 1450 °C to 1600 °C, and oxygen partial pressures from 10-7 atm to 10-9 atm pose engineering challenges in designing an optimal refractory material. Experimentation, characterization, and modeling show that gasifier slag infiltration into porous refractory is determined by interactions between the slag and the refractory that either form a physical barrier that impedes fluid flow or induce an increased fluid viscosity that decelerates the velocity of the fluid body. The viscosity of the slag is modified by the thermal profile of the refractory along the penetration direction as well as reactions between the slag and refractory that alter the chemistry, and thereby the thermo-physical properties of the fluid. Infiltration experiments reveal that the temperature gradient inherently present along the refractory lining limits penetration. A refractory in near-isothermal conditions demonstrates deeper slag penetration as compared to one that experiences a steeper thermal profile. The decrease in the local temperatures of the slag as it travels deeper into the refractory increases the viscosity of the fluid, which in turn slows the infiltration velocity of fluid body into the pores of the refractory microstructure. With feedstock mixtures that exhibit high iron-oxide concentrations, a transition-metal-oxide, the oxygen partial pressure of the operating atmosphere regulates the penetration of slag into refractory. The viscosity of the slag, which dictates its penetration rate, is influenced by the oxidation state of the Fe cation. Slag penetrations are shallower in oxidizing conditions than they are in reducing conditions because the iron-oxide from the slag solutions into the corundum-structured refractory and the slag is depleted of iron-oxide, increasing the viscosity of slags. Equally, the chemistries of both the refractory and slag materials dictate the course of penetration. Cr2O3-Al2O3 refractory limits mixed feedstock slag penetration through formation of a chromium spinel layer that functions as a physical obstacle against fluid flow. Al2O 3-SiO2 refractory limits eastern coal feedstock slag penetration as a result of refractory dissolution of SiO2, which increases the viscosity of slags. A physical model, which considers unidirectional fluid flow of slag through each pore of the porous microstructure of the refractory, sufficiently approximates the penetration depth of the slag into the refractory. Agreement between experiments and the physical model demonstrates that the slag is driven into the refractory by capillary pressure. Since the viscosity of the slag continuously changes as the slag travels through the inherent temperature gradient of the refractory lining, the model incorporates dynamic viscosities that are dependent on both temperature and composition to project depths that are unique to the experimental parameters. The significantly different length scales of the radial and penetration directions of the pores allows for the application of a lubrication approximation onto the momentum equation. This process produces an analytical solution that effectively envelopes the variable viscosity into a single term.

Shock Reduction With Antitachycardia Pacing Before and During Charging for Fast Ventricular Tachycardias in Patients With Implantable Defibrillators.

PubMed

Dallaglio, Paolo Domenico; Anguera, Ignasi; Martínez Ferrer, José B; Pérez, Luisa; Viñolas, Xavier; Porres, Jose Manuel; Fontenla, Adolfo; Alzueta, Javier; Martínez, Juan Gabriel; Rodríguez, Aníbal; Basterra, Nuria; Sabaté, Xavier

2017-12-11

Fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator are susceptible to antitachycardia pacing (ATP) termination. Some manufacturers allow programming 2 ATP bursts: before charging (BC) and during (DC) charging. The aim of this study was to describe the safety and effectiveness of ATP BC and DC for fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator in daily clinical practice. Data proceeded from the multicenter UMBRELLA trial, including implantable cardioverter-defibrillator patients followed up by the CareLink monitoring system. Fast ventricular tachycardias in the ventricular fibrillation zone until a cycle length of 200ms with ATP BC and/or ATP DC were included. We reviewed 542 episodes in 240 patients. Two ATP bursts (BC/DC) were programmed in 291 episodes (53.7%, 87 patients), while 251 episodes (46.3%, 153 patients) had 1 ATP burst only DC. The number of episodes terminated by 1 ATP DC was 139, representing 55.4% effectiveness (generalized estimating equation-adjusted 60.4%). There were 256 episodes terminated by 1 or 2 ATP (BC/DC), representing 88% effectiveness (generalized estimating equation-adjusted 79.3%); the OR for ATP effectiveness BC/DC vs DC was 2.5, 95%CI, 1.5-4.1; P <.001. Shocked episodes were 112 (45%) for ATP DC vs 35 (12%) for ATP BC/DC, representing an absolute reduction of 73%. The mean shocked episode duration was 16seconds for ATP DC vs 19seconds for ATP BC/DC (P=.07). The ATP DC in the ventricular fibrillation zone for fast ventricular tachycardia is moderately effective. Adding an ATP burst BC increases the overall effectiveness, reduces the need for shocks, and does not prolong episode duration. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease.

PubMed

Klein, L S; Shih, H T; Hackett, F K; Zipes, D P; Miles, W M

1992-05-01

Radiofrequency energy has been used safely and successfully to eliminate accessory pathways in patients with the Wolff-Parkinson-White syndrome and the substrate for atrioventricular nodal reentrant tachycardia. However, this form of ablation has had only limited success in eliminating ventricular tachycardia in patients with structural heart disease. In contrast, direct-current catheter ablation has been used successfully to eliminate ventricular tachycardia in patients with and without structural heart disease. The purpose of this study was to test whether radiofrequency energy can safely and effectively ablate ventricular tachycardia in patients without structural heart disease. Sixteen patients (nine women and seven men; mean age, 38 years; range, 18-55 years) without structural heart disease who had ventricular tachycardia underwent radiofrequency catheter ablation to eliminate the ventricular tachycardia. Two patients presented with syncope, nine with presyncope, and five with palpitations only. Mean duration of symptoms was 6.7 years (range, 0.5-20 years). Radiofrequency catheter ablation successfully eliminated ventricular tachycardia in 15 of 16 patients (94%). Sites of ventricular tachycardia origin included the high right ventricular outflow tract (12 patients), the right ventricular septum near the tricuspid valve (three patients), and the left ventricular septum (one patient). The only ablation failure was in a patient whose ventricular tachycardia arose from a region near the His bundle. An accurate pace map, early local endocardial activation, and firm catheter contact with endocardium were associated with successful ablation. Radiofrequency ablation did not cause arrhythmias, produced minimal cardiac enzyme rise, and resulted in no detectable change in cardiac function by Doppler echocardiography. Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease is effective and safe and may be considered as early therapy in these patients.

Inward Rectifier Potassium Channels Control Rotor Frequency in Ventricular Fibrillation

PubMed Central

Jalife, José

2009-01-01

Summary Ventricular fibrillation (VF) is the most important cause of sudden cardiac death. While traditionally thought to result from random activation of the ventricles by multiple independent wavelets, recent evidence suggests that VF may be determined by the sustained activation of a relatively small number of reentrant sources. In addition, recent experimental data in various species as well as computer simulations have provided important clues about its ionic and molecular mechanisms, particularly in regards to the role of potassium currents in such mechanisms. The results strongly argue that the inward rectifier current, Ik1, is an important current during functional reentry because it mediates the electrotonic interactions between the unexcited core and its immediate surroundings. In addition, IK1 is a stabilizer of reentry due to its ability to shorten action potential duration and reducing conduction velocity near the center of rotation. Increased I K1 prevents wavefront-wavetail interactions and thus averts rotor destabilization and breakup. Other studies have shown that while the slow component of the delayed rectifier potassium current, IKs, does not significantly modify rotor frequency or stability, it plays a major role in post-repolarization refractoriness and wavebreak formation. Therefore, the interplay between IK1 and the rapid sodium inward current (INa) is a major factor in the control of cardiac excitability and therefore the stability and frequency of reentry while IKs is an important determinant of fibrillatory conduction. PMID:19880073

A Case of a Cardiac Resynchronization Therapy-Defibrillator Exhibiting a Lower and Alternately Variable Basic Rate.

PubMed

Iwazaki, Keigo; Kojima, Toshiya; Murasawa, Takahide; Yokota, Jun; Tanimoto, Hikaru; Matsuda, Jun; Fukuma, Nobuaki; Matsubara, Takumi; Shimizu, Yu; Oguri, Gaku; Hasumi, Eriko; Kubo, Hitoshi; Chang, Kyungho; Fujiu, Katsuhito; Komuro, Issei

2018-05-30

A cardiac resynchronization therapy defibrillator (CRT-D) (Medtronic Inc. Protecta XT) was implanted in a 67-year-old man who had cardiac sarcoidosis with extremely low cardiac function. He had ventricular tachycardia which was controlled by catheter ablation, medication and pacing. The programmed mode was DDI, lower rate was 90 beats/minute, paced AV delay was 150 ms, and the noncompetitive atrial pacing (NCAP) function was programmed as 300 ms.After his admission for pneumonia and heart failure, we changed his DDI mode to a DDD mode because he had atrial tachycardia, which led to inadequate bi-ventricular pacing. After a while, there were cycle lengths which were longer than his device setting and alternately varied. We were able to avoid this phenomenon with AV delay of 120 ms and NCAP of 200 ms.NCAP is an algorithm which creates a gap above a certain period after the detection of an atrial signal during the postventricular atrial refractory period of the pacemaker. This is to prevent atrial tachycardia and repetitive non-reentrant ventriculoatrial (VA) synchrony in the presence of retrograde VA conduction. But in this case, NCAP algorithm induced much lower rate than the programmed basic lower rate. This situation produced some arrhythmias and exacerbated symptoms of heart failure. This had to be paid attention to, especially when the device was programmed at high basic heart rate.

[Long-term effects of hydroxychloroquine on metabolism of serum lipids and left ventricular structure and function in patients of systemic lupus erythematosus].

PubMed

Meng, Juan; Lu, Yuewu; Dong, Xin; Liu, Hongyan

2014-04-08

To observe the long-term effects of hydroxychloroquine treatment on blood lipids and left ventricular function of systemic lupus erythematosus (SLE) patients. A total of 72 SLE patients were randomly divided into 2 groups of hydroxychloroquine treatment (n = 36) and non-hydroxychloroquine (n = 36). The serum level of lipids, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), fractional shortening rate (FS), left ventricular ejection fraction (LVEF) and E/A ratio were measured before, 6 month, 12 month and 2 years after treatment. After long-term use of hydroxychloroquine, there were statistically differences in the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). And LVEDD, LVWPT and E/A were statistically different (P < 0.05) before and after hydroxychloroquine dosing. The long-term use of hydroxychloroquine may improve lipid metabolism and left ventricular function in SLE patients.

Refractory Hodgkin lymphoma.

PubMed

von Tresckow, Bastian; Engert, Andreas

2013-09-01

Despite the advances in the treatment of Hodgkin Lymphoma, patients with refractory disease still have a poor prognosis. Hodgkin Lymphoma can be refractory at first diagnosis or might become refractory later in the course of treatment. Both situations represent a therapeutic challenge. Intensified chemotherapy with BEACOPP escalated has been evaluated in early unfavourable and advanced Hodgkin Lymphoma and led to an improved tumour control and reduced rates of refractory disease. Furthermore, there is growing evidence for the role of tandem autologous transplant in breaking refractory disease. For patients relapsing after autologous transplant, more recent analyses have reported outcome and defined risk factors. The antibody drug conjugate brentuximab vedotin is a new, highly effective therapeutic option for these patients. Dose-reduced allogeneic transplant is a therapeutic alternative for patients relapsing after autologous transplant, but induction of a remission is the prerequisite for a successful allogeneic transplant. Brentuximab vedotin has been evaluated as a bridge to allogeneic transplant for patients refractory to conventional treatment. Recent therapeutic advances have improved the prognosis of Hodgkin Lymphoma by prevention or successful treatment of refractory disease. The use of new drugs such as brentuximab vedotin will hopefully further increase the cure rates.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

PubMed

Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

2015-01-08

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure

PubMed Central

Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

2015-01-01

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways. PMID:25567365

β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

PubMed

Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

2013-11-01

To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. 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. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. 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 β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -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 β1 -blocker showed similar effects on the arrhythmias in catheter lab. 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 β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Penetration and Effectiveness of Micronized Copper in Refractory Wood Species

PubMed Central

Civardi, Chiara; Van den Bulcke, Jan; Schubert, Mark; Michel, Elisabeth; Butron, Maria Isabel; Boone, Matthieu N.; Dierick, Manuel; Van Acker, Joris; Wick, Peter; Schwarze, Francis W. M. R.

2016-01-01

The North American wood decking market mostly relies on easily treatable Southern yellow pine (SYP), which is being impregnated with micronized copper (MC) wood preservatives since 2006. These formulations are composed of copper (Cu) carbonate particles (CuCO3·Cu(OH)2), with sizes ranging from 1 nm to 250 μm, according to manufacturers. MC-treated SYP wood is protected against decay by solubilized Cu2+ ions and unreacted CuCO3·Cu(OH)2 particles that successively release Cu2+ ions (reservoir effect). The wood species used for the European wood decking market differ from the North American SYP. One of the most common species is Norway spruce wood, which is poorly treatable i.e. refractory due to the anatomical properties, like pore size and structure, and chemical composition, like pit membrane components or presence of wood extractives. Therefore, MC formulations may not suitable for refractory wood species common in the European market, despite their good performance in SYP. We evaluated the penetration effectiveness of MC azole (MCA) in easily treatable Scots pine and in refractory Norway spruce wood. We assessed the effectiveness against the Cu-tolerant wood-destroying fungus Rhodonia placenta. Our findings show that MCA cannot easily penetrate refractory wood species and could not confirm the presence of a reservoir effect. PMID:27649315

Penetration and Effectiveness of Micronized Copper in Refractory Wood Species.

PubMed

Civardi, Chiara; Van den Bulcke, Jan; Schubert, Mark; Michel, Elisabeth; Butron, Maria Isabel; Boone, Matthieu N; Dierick, Manuel; Van Acker, Joris; Wick, Peter; Schwarze, Francis W M R

2016-01-01

The North American wood decking market mostly relies on easily treatable Southern yellow pine (SYP), which is being impregnated with micronized copper (MC) wood preservatives since 2006. These formulations are composed of copper (Cu) carbonate particles (CuCO3·Cu(OH)2), with sizes ranging from 1 nm to 250 μm, according to manufacturers. MC-treated SYP wood is protected against decay by solubilized Cu2+ ions and unreacted CuCO3·Cu(OH)2 particles that successively release Cu2+ ions (reservoir effect). The wood species used for the European wood decking market differ from the North American SYP. One of the most common species is Norway spruce wood, which is poorly treatable i.e. refractory due to the anatomical properties, like pore size and structure, and chemical composition, like pit membrane components or presence of wood extractives. Therefore, MC formulations may not suitable for refractory wood species common in the European market, despite their good performance in SYP. We evaluated the penetration effectiveness of MC azole (MCA) in easily treatable Scots pine and in refractory Norway spruce wood. We assessed the effectiveness against the Cu-tolerant wood-destroying fungus Rhodonia placenta. Our findings show that MCA cannot easily penetrate refractory wood species and could not confirm the presence of a reservoir effect.

Surgical ablation of ventricular tachycardia secondary to congenital ventricular septal aneurysm.

PubMed

Graffigna, A; Minzioni, G; Ressia, L; Vigano, M

1994-04-01

Three patients underwent surgical ablation for ventricular tachycardia resulting from an aneurysm of the membranous portion of the ventricular septum. Two patients had a definite history of cardiac murmur during infancy, and one of them was found at the time of operation to have a left-to-right shunt through the apex of the aneurysm. The earliest ventricular activation sites were located around the neck of the aneurysm and were ablated in 1 patient by encircling the endocardial ventriculotomy and by cryoablation in the remaining 2. After focus resection had been completed, aneurysm resection and ventricular septal reconstruction were performed. All patients were alive and free of ventricular tachycardia and did not need medication as of 61, 66, and 88 months postoperatively. Spontaneous closure of a ventricular septal defect may lead to the formation of an aneurysm in the ventricular septum that may sustain ventricular tachycardias. Such arrhythmias can be effectively treated using electrically guided surgical techniques.

The overloaded right heart and ventricular interdependence.

PubMed

Naeije, Robert; Badagliacca, Roberto

2017-10-01

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Extracorporeal shockwave myocardial therapy is efficacious in improving symptoms in patients with refractory angina pectoris--a multicenter study.

PubMed

Prasad, Megha; Wan Ahmad, Wan Azman; Sukmawan, Renan; Magsombol, Edward-Bengie L; Cassar, Andrew; Vinshtok, Yuri; Ismail, Muhammad Dzafir; Mahmood Zuhdi, Ahmad Syadi; Locnen, Sue Ann; Jimenez, Rodney; Callleja, Homobono; Lerman, Amir

2015-05-01

Medically refractory angina remains a significant health concern despite major advances in revascularization techniques and emerging medical therapies. We aimed to determine the safety and efficacy of extracorporeal shockwave myocardial therapy (ESMT) in managing angina pectoris. A single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II-IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3-6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT. The mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients. This multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.

Tricuspid regurgitation and right ventricular function after mitral valve surgery with or without concomitant tricuspid valve procedure.

PubMed

Desai, Ravi R; Vargas Abello, Lina Maria; Klein, Allan L; Marwick, Thomas H; Krasuski, Richard A; Ye, Ying; Nowicki, Edward R; Rajeswaran, Jeevanantham; Blackstone, Eugene H; Pettersson, Gösta B

2013-11-01

To study the effect of mitral valve repair with or without concomitant tricuspid valve repair on functional tricuspid regurgitation and right ventricular function. From 2001 to 2007, 1833 patients with degenerative mitral valve disease, a structurally normal tricuspid valve, and no coronary artery disease underwent mitral valve repair, and 67 underwent concomitant tricuspid valve repair. Right ventricular function (myocardial performance index and tricuspid annular plane systolic excursion) was measured before and after surgery using transthoracic echocardiography for randomly selected patients with tricuspid regurgitation grade 0, 1+, and 2+ (100 patients for each grade) and 93 with grade 3+/4+, 393 patients in total. In patients with mild (<3+) preoperative tricuspid regurgitation, mitral valve repair alone was associated with reduced tricuspid regurgitation and mild worsening of right ventricular function. Tricuspid regurgitation of 2+ or greater developed in fewer than 20%, and right ventricular function had improved, but not to preoperative levels, at 3 years. In patients with severe (3+/4+) preoperative tricuspid regurgitation, mitral valve repair alone reduced tricuspid regurgitation and improved right ventricular function; however, tricuspid regurgitation of 2+ or greater returned and right ventricular function worsened toward preoperative levels within 3 years. Concomitant tricuspid valve repair effectively eliminated severe tricuspid regurgitation and improved right ventricular function. Also, over time, tricuspid regurgitation did not return and right ventricular function continued to improve to levels comparable to that of patients with lower grades of preoperative tricuspid regurgitation. In patients with mitral valve disease and severe tricuspid regurgitation, mitral valve repair alone was associated with improved tricuspid regurgitation and right ventricular function. However, the improvements were incomplete and temporary. In contrast, concomitant tricuspid valve repair effectively and durably eliminated severe tricuspid regurgitation and improved right ventricular function toward normal, supporting an aggressive approach to important functional tricuspid regurgitation. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Tricuspid regurgitation and right ventricular function after mitral valve surgery with or without concomitant tricuspid valve procedure

PubMed Central

Desai, Ravi R.; Vargas Abello, Lina Maria; Klein, Allan L.; Marwick, Thomas H.; Krasuski, Richard A.; Ye, Ying; Nowicki, Edward R.; Rajeswaran, Jeevanantham; Blackstone, Eugene H.; Pettersson, Gösta B.

2014-01-01

Objectives To study the effect of mitral valve repair with or without concomitant tricuspid valve repair on functional tricuspid regurgitation and right ventricular function. Methods From 2001 to 2007, 1833 patients with degenerative mitral valve disease, a structurally normal tricuspid valve, and no coronary artery disease underwent mitral valve repair, and 67 underwent concomitant tricuspid valve repair. Right ventricular function (myocardial performance index and tricuspid annular plane systolic excursion) was measured before and after surgery using transthoracic echocardiography for randomly selected patients with tricuspid regurgitation grade 0, 1+, and 2+(100 patients for each grade) and 93 with grade 3+/4+, 393 patients in total. Results In patients with mild (<3+) preoperative tricuspid regurgitation, mitral valve repair alone was associated with reduced tricuspid regurgitation and mild worsening of right ventricular function. Tricuspid regurgitation of 2+or greater developed in fewer than 20%, and right ventricular function had improved, but not to preoperative levels, at 3 years. In patients with severe (3+/4+) preoperative tricuspid regurgitation, mitral valve repair alone reduced tricuspid regurgitation and improved right ventricular function; however, tricuspid regurgitation of 2+ or greater returned and right ventricular function worsened toward preoperative levels within 3 years. Concomitant tricuspid valve repair effectively eliminated severe tricuspid regurgitation and improved right ventricular function. Also, over time, tricuspid regurgitation did not return and right ventricular function continued to improve to levels comparable to that of patients with lower grades of preoperative tricuspid regurgitation. Conclusions In patients with mitral valve disease and severe tricuspid regurgitation, mitral valve repair alone was associated with improved tricuspid regurgitation and right ventricular function. However, the improvements were incomplete and temporary. In contrast, concomitant tricuspid valve repair effectively and durably eliminated severe tricuspid regurgitation and improved right ventricular function toward normal, supporting an aggressive approach to important functional tricuspid regurgitation. PMID:23010580

A benefit-risk assessment of class III antiarrhythmic agents.

PubMed

Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian; Sahebzadah, Naji; Køber, Lars

2002-01-01

With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart disease, and class IV drugs are avoided in heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of atrial fibrillation and sudden death. The population is becoming older and more patients survive for a longer time period with congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias. Amiodarone, sotalol, dofetilide, and ibutilide are examples of class III drugs that are currently available. Amiodarone and sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide suggest that patients with atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups that will benefit from prophylactic treatment with class III antiarrhythmic drugs may be found based on QT-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone and dofetilide have their place as second-line therapy except for patients with heart failure where they are first line therapy being the only drugs where the safety has been documented for this group of high risk patients.

Central-Approach Surgical Repair of Coarctation of the Aorta with a Back-up Left Ventricular Assist Device for an Infant Presenting with Severe Left Ventricular Dysfunction.

PubMed

Kim, Tae Hoon; Shin, Yu Rim; Kim, Young Sam; Kim, Do Jung; Kim, Hyohyun; Shin, Hong Ju; Htut, Aung Thein; Park, Han Ki

2015-12-01

A two-month-old infant presented with coarctation of the aorta, severe left ventricular dysfunction, and moderate to severe mitral regurgitation. Through median sternotomy, the aortic arch was repaired under cardiopulmonary bypass and regional cerebral perfusion. The patient was postoperatively supported with a left ventricular assist device for five days. Left ventricular function gradually improved, eventually recovering with the concomitant regression of mitral regurgitation. Prompt surgical repair of coarctation of the aorta is indicated for patients with severe left ventricular dysfunction. A central approach for surgical repair with a back-up left ventricular assist device is a safe and effective treatment strategy for these patients.

Ventricular fibrillation in an ambulatory patient supported by a left ventricular assist device: highlighting the ICD controversy.

PubMed

Boilson, Barry A; Durham, Lucian A; Park, Soon J

2012-01-01

Left ventricular assist devices (LVADs) provide an effective means of managing advanced pump failure as a means of bridging to cardiac transplantation or as permanent therapy. Although ventricular arrhythmias remain common post-LVAD implantation, such therapy may allow malignant arrhythmias to be tolerated hemodynamically. This report describes the clinical findings in a patient who had likely been in a ventricular tachyarrhythmia for several days and presented in ventricular fibrillation, ambulatory, and mentating normally. This report, with previous similar reports, is additive to the body of evidence that LVADs alter the physiologic impact of ventricular arrhythmias in advanced heart failure and highlights the need for thoughtful programming of implantable cardioverter defibrillator therapies in these patients.

The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

PubMed

Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

2015-02-01

Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

2015-04-01

A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of Early Inhaled Nitric Oxide Therapy in Fat Embolism Syndrome to Prevent Right Heart Failure

PubMed Central

Koyfman, Leonid; Kutz, Ruslan; Frenkel, Amit; Gruenbaum, Shaun E.; Zlotnik, Alexander; Klein, Moti

2014-01-01

Fat embolism syndrome (FES) is a life-threatening condition in which multiorgan dysfunction manifests 48–72 hours after long bone or pelvis fractures. Right ventricular (RV) failure, especially in the setting of pulmonary hypertension, is a frequent feature of FES. We report our experience treating 2 young, previously healthy trauma patients who developed severe hypoxemia in the setting of FES. Neither patient had evidence of RV dysfunction on echocardiogram. The patients were treated with inhaled nitric oxide (NO), and their oxygenation significantly improved over the subsequent few days. Neither patient developed any cardiovascular compromise. Patients with FES that have severe hypoxemia and evidence of adult respiratory distress syndrome (ARDS) are likely at risk for developing RV failure. We recommend that these patients with FES and severe refractory hypoxemia should be treated with inhaled NO therapy prior to the onset of RV dysfunction. PMID:25180103

Current pathophysiological concepts and management of pulmonary hypertension.

PubMed

Lourenço, André P; Fontoura, Dulce; Henriques-Coelho, Tiago; Leite-Moreira, Adelino F

2012-03-22

Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagnosed due mainly to the unspecific symptoms. Pulmonary arterial hypertension (PAH) has been extensively investigated. Pathophysiological knowledge derives mostly from experimental models. Paradoxically, common non-PAH PH forms remain largely unexplored. Drugs targeting lung vascular tonus became available during the last two decades, notwithstanding the disease progresses in many patients. The aim of this review is to summarize recent advances in epidemiology, pathophysiology and management with particular focus on associated myocardial and systemic compromise and experimental therapeutic possibilities. PAH, currently viewed as a panvasculopathy, is due to a crosstalk between endothelial and smooth muscle cells, inflammatory activation and altered subcellular pathways. Cardiac cachexia and right ventricular compromise are fundamental determinants of PH prognosis. Combined vasodilator therapy is already mainstay for refractory cases, but drugs directed at these new pathophysiological pathways may constitute a significant advance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Subaortic membrane mimicking hypertrophic cardiomyopathy.

PubMed

Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

2015-11-04

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. 2015 BMJ Publishing Group Ltd.

Subaortic membrane mimicking hypertrophic cardiomyopathy

PubMed Central

Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

2015-01-01

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. PMID:26538250

Total Artificial Heart Bridge to Transplantation for a Patient With Occult Intracardiac Malignancy: Case Report.

PubMed

Reich, H; Czer, L; Bannykh, S; De Robertis, M; Wolin, E; Amersi, F; Moriguchi, J; Kobashigawa, J; Arabia, F

2015-09-01

Malignancy is the leading cause of long-term morbidity and mortality after heart and other solid organ transplantation; therefore, great emphasis is placed on pre- and post-transplantation cancer screening. Even with meticulous screening during evaluation for heart transplant candidacy, an occult cancer may not be apparent. Here, we share the case of a 51-year-old man with refractory heart failure who underwent total artificial heart implantation as a bridge to transplantation with the surprise finding of an isolated deposit of metastatic carcinoid tumor nested within a left ventricular papillary muscle in his explanted heart. The primary ileal carcinoid tumor was identified and resected completely. After remaining cancer-free for 14 months, he was listed for heart transplantation and was transplanted 2 months later. He is currently 3.5 months out from heart transplantation and doing well, without evidence of recurring malignancy. Copyright © 2015 Elsevier Inc. All rights reserved.

Sotalol: An important new antiarrhythmic.

PubMed

Anderson, J L; Prystowsky, E N

1999-03-01

Sotalol, the most recently approved oral antiarrhythmic drug, has a unique pharmacologic profile. Its electrophysiology is explained by nonselective beta-blocking action as well as class III antiarrhythmic activity (including fast-activating cardiac membrane-delayed rectifier current blockade), which leads to increases in action potential duration and refractory period throughout the heart and in QT interval on the surface electrocardiogram. Its better hemodynamic tolerance than other beta-blockers may be a result of enhanced inotropy associated with class III activity. Sotalol's ability to suppress ventricular ectopy is similar to that of class I agents and better than that of standard beta-blockers. Unlike class I agents, its use in a postinfarction trial was not associated with increased mortality rate. Therapeutically, it has shown superior efficacy for prevention of recurrent ventricular tachycardia and ventricular fibrillation, which was the basis for its approval. In a randomized study, the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, sotalol was associated with an increased in-hospital efficacy prediction rate (by Holter monitor or electrophysiologic study), reduced long-term arrhythmic recurrence rate with superior tolerance, and lower mortality rate than class I ("standard") antiarrhythmic drugs. Sotalol was 1 of 2 drugs selected for comparison with implantable defibrillators in the recent National Institutes of Health Antiarrhythmics versus Implantable Defibrillator (AVID) study. Sotalol appears to be a preferred drug for use with implantable defibrillators; unlike some other agents (eg, amiodarone) it does not elevate and, indeed, may lower defibrillation threshold. Although unapproved for this use, sotalol is active against atrial arrhythmias. It has shown efficacy equivalent to propafenone and quinidine in preventing atrial fibrillation recurrence, but it is better tolerated than quinidine and provides excellent rate control during recurrence. Sotalol's major side effects are related to beta-blockade and the risk of torsades de pointes (acceptably small if appropriate precautions are taken). Unlike several other antiarrhythmics (eg, amiodarone), it has no pharmacokinetic drug-drug interactions, is not metabolized, and is entirely renally excreted. Initial dose is 80 mg twice daily, with gradual titration to 240 to 360 mg/day as needed. The daily dose must be reduced in renal failure. On the basis of favorable clinical trials and practice experience, sotalol has shown a steadily growing impact on the treatment of arrhythmias during its 5 years of market availability, a trend that is likely to continue.

Safety of transvenous low energy cardioversion of atrial fibrillation in patients with a history of ventricular tachycardia: effects of rate and repolarization time on proarrhythmic risk.

PubMed

Simons, G R; Newby, K H; Kearney, M M; Brandon, M J; Natale, A

1998-02-01

The objective of this study was to assess the safety and efficacy of transvenous low energy cardioversion of atrial fibrillation in patients with ventricular tachycardia and atrial fibrillation and to study the mechanisms of proarrhythmia. Previous studies have demonstrated that cardioversion of atrial fibrillation using low energy, R wave synchronized, direct current shocks applied between catheters in the coronary sinus and right atrium is feasible. However, few data are available regarding the risk of ventricular proarrhythmia posed by internal atrial defibrillation shocks among patients with ventricular arrhythmias or structural heart disease. Atrial defibrillation was performed on 32 patients with monomorphic ventricular tachycardia and left ventricular dysfunction. Shocks were administered during atrial fibrillation (baseline shocks), isoproterenol infusion, ventricular pacing, ventricular tachycardia, and atrial pacing. Baseline shocks were also administered to 29 patients with a history of atrial fibrillation but no ventricular arrhythmias. A total of 932 baseline shocks were administered. No ventricular proarrhythmia was observed after well-synchronized baseline shocks, although rare inductions of ventricular fibrillation occurred after inappropriate T wave sensing. Shocks administered during wide-complex rhythms (ventricular pacing or ventricular tachycardia) frequently induced ventricular arrhythmias, but shocks administered during atrial pacing at identical ventricular rates did not cause proarrhythmia. The risk of ventricular proarrhythmia after well-synchronized atrial defibrillation shocks administered during narrow-complex rhythms is low, even in patients with a history of ventricular tachycardia. The mechanism of proarrhythmia during wide-complex rhythms appears not to be related to ventricular rate per se, but rather to the temporal relationship between shock delivery and the repolarization time of the previous QRS complex.

Computational Analysis of Intra-Ventricular Flow Pattern Under Partial and Full Support of BJUT-II VAD.

PubMed

Zhang, Qi; Gao, Bin; Chang, Yu

2017-02-27

BACKGROUND Partial support, as a novel support mode, has been widely applied in clinical practice and widely studied. However, the precise mechanism of partial support of LVAD in the intra-ventricular flow pattern is unclear. MATERIAL AND METHODS In this study, a patient-specific left ventricular geometric model was reconstructed based on CT data. The intra-ventricular flow pattern under 3 simulated conditions - "heart failure", "partial support", and "full support" - were simulated by using fluid-structure interaction (FSI). The blood flow pattern, wall shear stress (WSS), time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated to evaluate the hemodynamic effects. RESULTS The results demonstrate that the intra-ventricular flow pattern is significantly changed by the support level of BJUT-II VAD. The intra-ventricular vortex was enhanced under partial support and was eliminated under full support, and the high OSI and RRT regions changed from the septum wall to the cardiac apex. CONCLUSIONS In brief, the support level of the BJUT-II VAD has significant effects on the intra-ventricular flow pattern. The partial support mode of BJUT-II VAD can enhance the intra-ventricular vortex, while the distribution of high OSI and RRT moved from the septum wall to the cardiac apex. Hence, the partial support mode of BJUT-II VAD can provide more benefit for intra-ventricular flow pattern.

Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe.

PubMed

Bonow, R O; Ostrow, H G; Rosing, D R; Cannon, R O; Lipson, L C; Maron, B J; Kent, K M; Bacharach, S L; Green, M V

1983-11-01

To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.

Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage.

PubMed

Carrasco, H A; Vicuña, A V; Molina, C; Landaeta, A; Reynosa, J; Vicuña, N; Fuenmayor, A; López, F

1985-12-01

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

Myocardial effective transverse relaxation time T2* Correlates with left ventricular wall thickness: A 7.0 T MRI study.

PubMed

Huelnhagen, Till; Hezel, Fabian; Serradas Duarte, Teresa; Pohlmann, Andreas; Oezerdem, Celal; Flemming, Bert; Seeliger, Erdmann; Prothmann, Marcel; Schulz-Menger, Jeanette; Niendorf, Thoralf

2017-06-01

Myocardial effective relaxation time T2* is commonly regarded as a surrogate for myocardial tissue oxygenation. However, it is legitimate to assume that there are multiple factors that influence T2*. To this end, this study investigates the relationship between T2* and cardiac macromorphology given by left ventricular (LV) wall thickness and left ventricular radius, and provides interpretation of the results in the physiological context. High spatio-temporally resolved myocardial CINE T2* mapping was performed in 10 healthy volunteers using a 7.0 Tesla (T) full-body MRI system. Ventricular septal wall thickness, left ventricular inner radius, and T2* were analyzed. Macroscopic magnetic field changes were elucidated using cardiac phase-resolved magnetic field maps. Ventricular septal T2* changes periodically over the cardiac cycle, increasing in systole and decreasing in diastole. Ventricular septal wall thickness and T2* showed a significant positive correlation, whereas the inner LV radius and T2* were negatively correlated. The effect of macroscopic magnetic field gradients on T2* can be considered minor in the ventricular septum. Our findings suggest that myocardial T2* is related to tissue blood volume fraction. Temporally resolved T2* mapping could be beneficial for myocardial tissue characterization and for understanding cardiac (patho)physiology in vivo. Magn Reson Med 77:2381-2389, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Emission spectrometric arcing procedure with minimal effect of chemical form of sample. [performed on refractory metal matrix composites

NASA Technical Reports Server (NTRS)

Gordon, W. A.

1975-01-01

Matrix effects related to the chemical form of analyzed materials were studied. An arc in argon was used which was buffered with silver chloride. The effect of chemical form was minimal for a variety of metals, oxides, and carbides representing the most refractory compounds and thermally stable metal-containing molecules. Only four of the most refractory materials known showed significant emission depressions due to incomplete volatilization in the arc system. These results are discussed in terms of vapor pressures of the solid materials placed on the anodes and dissociation reactions of the molecules in the gaseous environment.

Successful diuretics treatment of protein-losing enteropathy in Noonan syndrome.

PubMed

Mizuochi, Tatsuki; Suda, Kenji; Seki, Yoshitaka; Yanagi, Tadahiro; Yoshimoto, Hironaga; Kudo, Yoshiyuki; Iemura, Motofumi; Tanikawa, Ken; Matsuishi, Toyojiro

2015-04-01

There are few reports on successful high-dose spironolactone treatment of refractory protein-losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first-line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome. © 2015 Japan Pediatric Society.

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

PubMed

Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W

1999-02-01

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Autoantibodies against β1 receptor and AT1 receptor in type 2 diabetes patients with left ventricular dilatation.

PubMed

Zhao, Linshuang; Xu, Chunyan; Xu, Jinling

2014-01-01

To explore the relationship between the autoantibodies against the β1 and AT1 receptors and left ventricular dilatation in patients with type 2 diabetes (T2DM). The autoantibodies against the β1 and angiotensin II type 1 (AT1) receptors of T2DM patients with and without hypertension were screened by ELISA. Multiple logistic regression was used to analyze the risk factors for left ventricular dilatation. The reversing effect of left ventricular dilatation was evaluated after receptor blocker treatment. The positive rates of autoantibodies against the β1 and AT1 receptors (43.0 and 44.1%, respectively) in T2DM patients with hypertension were significantly higher than those in normotensive patients (16.0 and 10.4%, respectively; all p < 0.01). Furthermore, among T2DM patients with hypertension, the positive rates (61.4 and 64.9%, respectively) in patients with left ventricular dilatation were remarkably higher than those with normal left ventricular dimensions (34.4 and 36.1%, respectively; all p < 0.01). The presence of β1 receptor antibody and AT1 receptor antibody were risk factors for left ventricular dilatation (p < 0.05). The curative effect of metoprolol tartrate and valsartan in reversing left ventricular hypertrophy in the group positive for autoantibodies was much better than in the negative group. The findings show that autoantibodies against the β1 and AT1 receptors may play a role in predicting left ventricular dilatation in T2DM patients in combination with hypertension. Metoprolol tartrate and valsartan are effective and safe in the treatment of these patients. © 2014 S. Karger AG, Basel.

Adjustable, physiological ventricular restraint improves left ventricular mechanics and reduces dilatation in an ovine model of chronic heart failure.

PubMed

Ghanta, Ravi K; Rangaraj, Aravind; Umakanthan, Ramanan; Lee, Lawrence; Laurence, Rita G; Fox, John A; Bolman, R Morton; Cohn, Lawrence H; Chen, Frederick Y

2007-03-13

Ventricular restraint is a nontransplantation surgical treatment for heart failure. The effect of varying restraint level on left ventricular (LV) mechanics and remodeling is not known. We hypothesized that restraint level may affect therapy efficacy. We studied the immediate effect of varying restraint levels in an ovine heart failure model. We then studied the long-term effect of restraint applied over a 2-month period. Restraint level was quantified by use of fluid-filled epicardial balloons placed around the ventricles and measurement of balloon luminal pressure at end diastole. At 4 different restraint levels (0, 3, 5, and 8 mm Hg), transmural myocardial pressure (P(tm)) and indices of myocardial oxygen consumption (MVO2) were determined in control (n=5) and ovine heart failure (n=5). Ventricular restraint therapy decreased P(tm) and MVO2, and improved mechanical efficiency. An optimal physiological restraint level of 3 mm Hg was identified to maximize improvement without an adverse affect on systemic hemodynamics. At this optimal level, end-diastolic P(tm) and MVO2 indices decreased by 27% and 20%, respectively. The serial longitudinal effects of optimized ventricular restraint were then evaluated in ovine heart failure with (n=3) and without (n=3) restraint over 2 months. Optimized ventricular restraint prevented and reversed pathological LV dilatation (130+/-22 mL to 91+/-18 mL) and improved LV ejection fraction (27+/-3% to 43+/-5%). Measured restraint level decreased over time as the LV became smaller, and reverse remodeling slowed. Ventricular restraint level affects the degree of decrease in P(tm), the degree of decrease in MVO2, and the rate of LV reverse remodeling. Periodic physiological adjustments of restraint level may be required for optimal restraint therapy efficacy.

[Epilepsy, cognition and ketogenic diet].

PubMed

Garcia-Penas, J J

2018-03-01

Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

Ventriculostomy Simulation Using Patient-Specific Ventricular Anatomy, 3D Printing, and Hydrogel Casting.

PubMed

Ryan, Justin R; Chen, Tsinsue; Nakaji, Peter; Frakes, David H; Gonzalez, L Fernando

2015-11-01

Educational simulators provide a means for students and experts to learn and refine surgical skills. Educators can leverage the strengths of medical simulators to effectively teach complex and high-risk surgical procedures, such as placement of an external ventricular drain. Our objective was to develop a cost-effective, patient-derived medical simulacrum for cerebral lateral ventriculostomy. A cost-effective, patient-derived medical simulacrum was developed for placement of an external lateral ventriculostomy. Elastomeric and gel casting techniques were used to achieve realistic brain geometry and material properties. 3D printing technology was leveraged to develop accurate cranial properties and dimensions. An economical, gravity-driven pump was developed to provide normal and abnormal ventricular pressures. A small pilot study was performed to gauge simulation efficacy using a technology acceptance model. An accurate geometric representation of the brain was developed with independent lateral cerebral ventricular chambers. A gravity-driven pump pressurized the ventricular cavities to physiologic values. A qualitative study illustrated that the simulation has potential as an educational tool to train medical professionals in the ventriculostomy procedure. The ventricular simulacrum can improve learning in a medical education environment. Rapid prototyping and multi-material casting techniques can produce patient-derived models for cost-effective and realistic surgical training scenarios. Copyright © 2015 Elsevier Inc. All rights reserved.

Carbon transfer from magnesia-graphite ladle refractories to ultra-low carbon steel

NASA Astrophysics Data System (ADS)

Russo, Andrew Arthur

Ultra-low carbon steels are utilized in processes which require maximum ductility. Increases in interstitial carbon lower the ductility of steel; therefore, it is important to examine possible sources of carbon. The refractory ladle lining is one such source. Ladle refractories often contain graphite for its desirable thermal shock and slag corrosion resistance. This graphite is a possible source of carbon increase in ultra-low carbon steels. The goal of this research is to understand and evaluate the mechanisms by which carbon transfers to ultra-low carbon steel from magnesia-graphite ladle refractory. Laboratory dip tests were performed in a vacuum induction furnace under an argon atmosphere to investigate these mechanisms. Commercial ladle refractories with carbon contents between 4-12 wt% were used to investigate the effect of refractory carbon content. Slag-free dip tests and slag-containing dip tests with varying MgO concentrations were performed to investigate the influence of slag. Carbon transfer to the steel was controlled by steel penetrating into the refractory and dissolving carbon in dip tests where no slag was present. The rate limiting step for this mechanism is convective mass transport of carbon into the bulk steel. No detectable carbon transfer occurred in dip tests with 4 and 6 wt%C refractories without slag because no significant steel penetration occurred. Carbon transfer was controlled by the corrosion of refractory by slag in dip tests where slag was present.

Transient Outward K+ Current (Ito) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1.

PubMed

Choi, Bum-Rak; Li, Weiyan; Terentyev, Dmitry; Kabakov, Anatoli Y; Zhong, Mingwang; Rees, Colin M; Terentyeva, Radmila; Kim, Tae Yun; Qu, Zhilin; Peng, Xuwen; Karma, Alain; Koren, Gideon

2018-06-01

Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits. The results showed that shorter action potential duration in the right ventricle (RV) was associated with focal activity during pVT initiation. RV cardiomyocytes demonstrated higher incidence of EADs under 50 nmol/L isoproterenol. Voltage-clamp studies revealed that the transient outward potassium current (I to ) magnitude was 28% greater in RV associated with KChiP2 but with no differences in terms of calcium-cycling kinetics and other sarcolemmal currents. Perfusing with the I to blocker 4-aminopyridine changed the initial focal sites of pVT from the RV to the left ventricle, corroborating the role of I to in pVT initiation. Computer modeling showed that EADs occur preferentially in the RV because of the larger conductance of the slow-inactivating component of I to , which repolarizes the membrane potential sufficiently rapidly to allow reactivation of I Ca,L before I Kr has had sufficient time to activate. I to heterogeneity creates both triggers and an arrhythmogenic substrate in LQT1. In the absence of I Ks , I to interactions with I Ca,L and I Kr promote EADs in the RV while prolonging action potential duration in the left ventricle. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs. © 2018 American Heart Association, Inc.

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

PubMed

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

2009-01-28

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

PubMed

Abramov, Dmitry; Haglund, Nicholas A; Di Salvo, Thomas G

2017-08-01

Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function. We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance. Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs. 2079 ± 919 mmHg·mL/m 2 , p = 0.0007) to a much greater extent than right ventricular stroke work index (616 ± 346 vs. 654 ± 332, p = 0.053); however, patients with below median stroke work indices experienced a significant improvement in both left and right ventricular stroke work performance. Overall, milrinone reduced left and right ventricular filling pressures and pulmonary and systemic vascular resistance by approximately 20%. Despite an increase in pulmonary artery capacitance (2.3 ± 1.6 to 3.0 ± 2.0, p = 0.013) and a reduction in pulmonary vascular resistance (3.8 ± 2.3 to 3.0 ± 1.7 Wood units), milrinone did not reduce the transpulmonary gradient (13 ± 7 vs. 12 ± 6 mmHg, p = 0.252), the pulmonary artery pulse pressure (25 ± 10 vs. 24 ± 10, p = 0.64) or the pulmonary artery diastolic to pulmonary capillary wedge gradient (2.0 ± 6.5 vs. 2.4 ± 6.0, p = 0.353). Milrinone improved left ventricular stroke work indices to a greater extent than right ventricular stroke work indices and had beneficial effects on right ventricular net input impedance, predominantly via augmentation of left ventricular stroke volume and passive unloading of the pulmonary circuit. Patients who had the worst biventricular performance benefited the most from chronic milrinone infusion.

Right ventricular dysfunction affects survival after surgical left ventricular restoration.

PubMed

Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

2017-04-01

Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a ‘real-world’ UK health economic evaluation

PubMed Central

Parker, Matthew J; Guha, Neil; Stedman, Brian; Hacking, Nigel; Wright, Mark

2013-01-01

Objective To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. Design A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. Setting Secondary care. Patients Cirrhotic patients with refractory ascites. Main outcome measures We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. Results Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. Conclusions TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites. PMID:28839725

Intraarticular Pulsed Radiofrequency to Treat Refractory Lumbar Facet Joint Pain in Patients with Low Back Pain.

PubMed

Chang, Min Cheol; Cho, Yun-Woo; Ahn, Da Hyun; Do, Kyung Hee

2018-04-01

Many treatment techniques have been used for refractory lumbar facet joint pain; however, their efficacy has been controversial. In this study, we investigated the clinical efficacy and safety of intra-articular pulsed radiofrequency for the treatment of refractory lumbar facet joint pain in patients with low back pain. Twenty patients with refractory lumbar facet joint pain were recruited, and each patient was treated via intra-articular pulsed radiofrequency. The treatment effects were measured with a numerical rating scale, and the technical accuracy of intra-articular pulsed radiofrequency treatment was evaluated independently by 2 radiologists. Any adverse events or complications also were checked. We performed intra-articular pulsed radiofrequency treatment at 48 levels of the lumbar facet joints in 20 patients (5 men and 15 women; mean age, 64.50 ± 10.65 years) with refractory lumbar facet joint pain. Pain scores were significantly reduced at 1 month, 3 months, and 6 months after treatment (P < 0.05). The face validity revealed good intraarticular pulsed radiofrequency results in all 20 patients, without any serious adverse effects. Treatment using intra-articular pulsed radiofrequency is an alternative to other techniques in patients with refractory lumbar facet joint pain. Copyright © 2018 Elsevier Inc. All rights reserved.

Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a 'real-world' UK health economic evaluation.

PubMed

Parker, Matthew J; Guha, Neil; Stedman, Brian; Hacking, Nigel; Wright, Mark

2013-07-01

To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. Secondary care. Cirrhotic patients with refractory ascites. We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites.

Statins as anti-arrhythmics: a systematic review part II: effects on risk of ventricular arrhythmias.

PubMed

Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

2009-10-01

Recent studies have demonstrated that statins may possess anti-arrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of ventricular arrhythmias were identified through a systematic review of the published literature. Statins have been associated with a significant reductions in ventricular arrhythmia in cardiomyopathy patients with an implantable cardioverter defibrillator, although randomized trials have not been completed. Published data suggests that statins may possess anti-arrhythmic properties that reduce the propensity for ventricular arrhythmias. Most of this data is observational; more randomized, placebo-controlled trials are needed.

Right Ventricular Outflow Tract Septal Pacing Is Superior to Right Ventricular Apical Pacing

PubMed Central

Zou, Cao; Song, Jianping; Li, Hui; Huang, Xingmei; Liu, Yuping; Zhao, Caiming; Shi, Xin; Yang, Xiangjun

2015-01-01

Background The effects of right ventricular apical pacing (RVAP) and right ventricular outflow tract (RVOT) septal pacing on atrial and ventricular electrophysiology have not been thoroughly compared. Methods and Results To identify a more favorable pacing strategy with fewer adverse effects, 80 patients who had complete atrioventricular block with normal cardiac function and who were treated with either RVAP (n=42) or RVOT septal pacing (n=38) were recruited after an average of 2 years of follow‐up. The data from electrocardiography and echocardiography performed before pacemaker implantation and at the end of follow‐up were collected. The patients in the RVOT septal pacing and RVAP groups showed similar demographic and clinical characteristics before pacing treatments. After a mean follow‐up of 2 years, the final maximum P‐wave duration; P‐wave dispersion; Q‐, R‐, and S‐wave complex duration; left atrial volume index; left ventricular end‐systolic diameter; ratio of transmitral early diastolic filling velocity to mitral annular early diastolic velocity; and interventricular mechanical delay in the RVOT septal pacing group were significantly less than those in the RVAP group (P<0.05). The final left ventricular ejection fraction of the RVOT septal pacing group was significantly higher than that of the RVAP group (P<0.05). Conclusions Compared with RVAP, RVOT septal pacing has fewer adverse effects regarding atrial electrical activity and structure in patients with normal cardiac function. PMID:25896891

High-Intensity Interval Training for Severe Left Ventricular Dysfunction Treated with Left Ventricular Assist Device.

PubMed

Ugata, Yusuke; Wada, Hiroshi; Sakakura, Kenichi; Ibe, Tatsuro; Ito, Miyuki; Ikeda, Nahoko; Fujita, Hideo; Momomura, Shin-Ichi

2018-01-27

Aerobic training based on anaerobic threshold (AT) is well-known to improve cardiac function, exercise capacity, and long-term outcomes of patients with heart failure. Recent reports suggested that high-intensity interval training (HIIT) for patients with cardiovascular disease may improve cardiopulmonary exercise capacity. We present a 61-year-old male patient of severe left ventricular dysfunction with left ventricular assisted device (LVAD). Following HIIT for 8 weeks, exercise capacity and muscle strength have improved without worsening left ventricular function. Our case showed the possibility that HIIT was feasible and effective even in patients with LVAD.

Current and future developments in the field of central sleep apnoea.

PubMed

Bekfani, Tarek; Abraham, William T

2016-08-01

Central sleep apnoea (CSA) occurs in ∼30-50% of patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and in as much as in 18-30% of patients with preserved LVEF. In HF patients, it is characterized by periodic breathing also known as the Cheyne-Stokes respiration followed by pauses of breathing. Central sleep apnoea remains often unrecognized due to its chronic and insidious incidences. Patients may report excessive daytime somnolence, poor sleep quality, nocturnal angina, recurrent arrhythmias, refractory HF symptoms, or demonstrate abnormal respiratory pattern or apnoeas. The pathogenesis of CSA remains incompletely understood, but changes in CO2 above and below the apnoea threshold play a major role in its pathogenesis. The presence of CSA in patients with HF is associated with some neurohumoral and haemodynamic responses that are detrimental to the failing heart including increased morbidity and mortality. The development of successful therapies targeting CSA and its harmful downstream effects is therefore important. Several different therapies from medications to implantable devices have been tested with varying effects and primarily in small non-randomized and/or single-centre studies. Large studies to date have been disappointing, but therapeutic options targeting the physiology of the disease may herald a new era in understanding and treating CSA. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

The prevalence of early repolarization in Wolff-Parkinson-White syndrome with a special reference to J waves and the effects of catheter ablation.

PubMed

Yagihara, Nobue; Sato, Akinori; Iijima, Kenichi; Izumi, Daisuke; Furushima, Hiroshi; Watanabe, Hiroshi; Irie, Tadanobu; Kaneko, Yoshiaki; Kurabayashi, Masahiko; Chinushi, Masaomi; Satou, Masahito; Aizawa, Yoshifusa

2012-01-01

We determined the prevalence of J waves in the electrocardiograms (ECG) of 120 patients with Wolff-Parkinson-White syndrome in comparison with J-wave prevalence in a control group of 1936 men and women with comparable demographic and ECG characteristics and with normal atrioventricular conduction. J waves were present only during manifest preexcitation in 22 of 120 patients (18.3%), disappearing after catheter ablation and suggesting that J waves were associated with the presence of preexcitation. J waves were present in 19 (15.8%) of 120 patients only after ablation, apparently having been masked by early depolarization of the preexcited myocardial region, and in 22 patients (18.3%), J waves were not altered significantly by preexcitation. Thus, the overall J-wave prevalence was 52.5% (63/120) and, excluding those apparently due to preexcitation, 34.8% (41/120), both substantially higher than the prevalence (11.5%) in the control group (P < .001 for both). The patients with J waves appearing only during preexcitation were younger, predominantly females. The presence of J waves after ablation was associated with a history of atrial fibrillation and shorter ventricular effective refractory period. It is concluded that the prevalence of J waves is high in patients with Wolff-Parkinson-White syndrome and is influenced by manifest preexcitation. Copyright © 2012 Elsevier Inc. All rights reserved.

Single-site access robot-assisted epicardial mapping with a snake robot: preparation and first clinical experience.

PubMed

Neuzil, Petr; Cerny, Stepan; Kralovec, Stepan; Svanidze, Oleg; Bohuslavek, Jan; Plasil, Petr; Jehlicka, Pavel; Holy, Frantisek; Petru, Jan; Kuenzler, Richard; Sediva, Lucie

2013-06-01

CardioARM, a highly flexible "snakelike" medical robotic system (Medrobotics, Raynham, MA), has been developed to allow physicians to view, access, and perform complex procedures intrapericardially on the beating heart through a single-access port. Transthoracic epicardial catheter mapping and ablation has emerged as a strategy to treat arrhythmias, particularly ventricular arrhythmias, originating from the epicardial surface. The aim of our investigation was to determine whether the CardioARM could be used to diagnose and treat ventricular tachycardia (VT) of epicardial origin. Animal and clinical studies of the CardioARM flexible robot were performed in hybrid surgical-electrophysiology settings. In a porcine model study, single-port pericardial access, navigation, mapping, and ablation were performed in nine animals. The device was then used in a small, single-center feasibility clinical study. Three patients, all with drug-refractory VT and multiple failed endocardial ablation attempts, underwent epicardial mapping with the flexible robot. In all nine animals, navigation, mapping, and ablation were successful without hemodynamic compromise. In the human study, all three patients demonstrated a favorable safety profile, with no major adverse events through a 30-day follow-up. Two cases achieved technical success, in which an electroanatomic map of the epicardial ventricle surface was created; in the third case, blood obscured visualization. These results, although based on a limited number of experimental animals and patients, show promise and suggest that further clinical investigation on the use of the flexible robot in patients requiring epicardial mapping of VT is warranted.

Inward rectifier potassium channels control rotor frequency in ventricular fibrillation.

PubMed

Jalife, José

2009-11-01

Ventricular fibrillation (VF) is the most important cause of sudden cardiac death. While traditionally thought to result from random activation of the ventricles by multiple independent wavelets, recent evidence suggests that VF may be determined by the sustained activation of a relatively small number of reentrant sources. In addition, recent experimental data in various species as well as computer simulations have provided important clues about its ionic and molecular mechanisms, particularly in regards to the role of potassium currents in such mechanisms. The results strongly argue that the inward rectifier current, I(K1,) is an important current during functional reentry because it mediates the electrotonic interactions between the unexcited core and its immediate surroundings. In addition, I(K1) is a stabilizer of reentry due to its ability to shorten action potential duration and reduce conduction velocity near the center of rotation. Increased I(K1) prevents wave front-wave tail interactions and thus averts rotor destabilization and breakup. Other studies have shown that while the slow component of the delayed rectifier potassium current I(Ks) does not significantly modify rotor frequency or stability, it plays a major role in postrepolarization refractoriness and wave break formation. Therefore, the interplay between I(K1) and the rapid sodium inward current (I(Na)) is a major factor in the control of cardiac excitability and thus the stability and frequency of reentry, while I(Ks) is an important determinant of fibrillatory conduction.

Minimally Invasive Epicardial Pacemaker Implantation in Neonates with Congenital Heart Block.

PubMed

Costa, Roberto; Silva, Katia Regina da; Martinelli Filho, Martino; Carrillo, Roger

2017-10-01

Few studies have characterized the surgical outcomes following epicardial pacemaker implantation in neonates with congenital complete atrioventricular block (CCAVB). This study sought to assess the long-term outcomes of a minimally invasive epicardial approach using a subxiphoid access for pacemaker implantation in neonates. Between July 2002 and February 2015, 16 consecutive neonates underwent epicardial pacemaker implantation due to CCAVB. Among these, 12 (75.0%) had congenital heart defects associated with CCAVB. The patients had a mean age of 4.7 ± 5.3 days and nine (56.3%) were female. Bipolar steroid-eluting epicardial leads were implanted in all patients through a minimally invasive subxiphoid approach and fixed on the diaphragmatic ventricular surface. The pulse generator was placed in an epigastric submuscular position. All procedures were successful, with no perioperative complications or early deaths. Mean operating time was 90.2 ± 16.8 minutes. None of the patients displayed pacing or sensing dysfunction, and all parameters remained stable throughout the follow-up period of 4.1 ± 3.9 years. Three children underwent pulse generator replacement due to normal battery depletion at 4.0, 7.2, and 9.0 years of age without the need of ventricular lead replacement. There were two deaths at 12 and 325 days after pacemaker implantation due to bleeding from thrombolytic use and progressive refractory heart failure, respectively. Epicardial pacemaker implantation through a subxiphoid approach in neonates with CCAVB is technically feasible and associated with excellent surgical outcomes and pacing lead longevity.

Mechanism of reentry induction by a 9-V battery in rabbit ventricles

PubMed Central

Burton, Rebecca A. B.; Kalla, Manish; Nanthakumar, Kumaraswamy; Plank, Gernot; Bub, Gil; Vigmond, Edward J.

2014-01-01

Although the application of a 9-V battery to the epicardial surface is a simple method of ventricular fibrillation induction, the fundamental mechanisms underlying this process remain unstudied. We used a combined experimental and modelling approach to understand how the interaction of direct current (DC) from a battery may induce reentrant activity within rabbit ventricles and its dependence on battery application timing and duration. A rabbit ventricular computational model was used to simulate 9-V battery stimulation for different durations at varying onset times during sinus rhythm. Corresponding high-resolution optical mapping measurements were conducted on rabbit hearts with DC stimuli applied via a relay system. DC application to diastolic tissue induced anodal and cathodal make excitations in both simulations and experiments. Subsequently, similar static epicardial virtual electrode patterns were formed that interacted with sinus beats but did not induce reentry. Upon battery release during diastole, break excitations caused single ectopics, similar to application, before sinus rhythm resumed. Reentry induction was possible for short battery applications when break excitations were slowed and forced to take convoluted pathways upon interaction with refractory tissue from prior make excitations or sinus beats. Short-lived reentrant activity could be induced for battery release shortly after a sinus beat for longer battery applications. In conclusion, the application of a 9-V battery to the epicardial surface induces reentry through a complex interaction of break excitations after battery release with prior induced make excitations or sinus beats. PMID:24464758

Mechanism of reentry induction by a 9-V battery in rabbit ventricles.

PubMed

Bishop, Martin J; Burton, Rebecca A B; Kalla, Manish; Nanthakumar, Kumaraswamy; Plank, Gernot; Bub, Gil; Vigmond, Edward J

2014-04-01

Although the application of a 9-V battery to the epicardial surface is a simple method of ventricular fibrillation induction, the fundamental mechanisms underlying this process remain unstudied. We used a combined experimental and modelling approach to understand how the interaction of direct current (DC) from a battery may induce reentrant activity within rabbit ventricles and its dependence on battery application timing and duration. A rabbit ventricular computational model was used to simulate 9-V battery stimulation for different durations at varying onset times during sinus rhythm. Corresponding high-resolution optical mapping measurements were conducted on rabbit hearts with DC stimuli applied via a relay system. DC application to diastolic tissue induced anodal and cathodal make excitations in both simulations and experiments. Subsequently, similar static epicardial virtual electrode patterns were formed that interacted with sinus beats but did not induce reentry. Upon battery release during diastole, break excitations caused single ectopics, similar to application, before sinus rhythm resumed. Reentry induction was possible for short battery applications when break excitations were slowed and forced to take convoluted pathways upon interaction with refractory tissue from prior make excitations or sinus beats. Short-lived reentrant activity could be induced for battery release shortly after a sinus beat for longer battery applications. In conclusion, the application of a 9-V battery to the epicardial surface induces reentry through a complex interaction of break excitations after battery release with prior induced make excitations or sinus beats.

[An autopsy case of neonatal lactic acidosis].

PubMed

Giordano, G; Corradi, D; D'Adda, T; Melissari, M

2001-02-01

Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome oxidase, cause hereditary disorders which lead to modifications in cellular pH due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases include severe neonatal diseases and less severe forms of adult diseases. We report the case of lactic acidosis in a newborn girl who was delivered at 36 weeks of gestation and who died 3 months after birth. Her family history revealed a relative with tetraparesis and mental retardation. Her clinical findings, such as tonic-clonic convulsions and accumulation of pyruvate and lactic acid in blood, urine and cerebrospinal fluid, were refractory to treatment and developed soon after birth. Ultrasound scans of the brain some days before death revealed cerebral atrophy with ventricular dilatation and thinning of the corpus callosum and septum pellucidum. The clinical diagnosis of metabolic lactic acidosis was confirmed by macroscopic, microscopic and ultrastructural findings seen at autopsy. On macroscopic examination, the heart was hypertrophic, and the brain was atrophic with ventricular dilatation and thinning of corpus callosum. Small cystic lesions were present in the basal ganglia. On microscopic examination, the latter were characterized by loss of neurons, gliosis and capillary proliferation. Ultrastructural examination of the heart and skeletal muscle showed lysis of myofibrils, mitochondrial pleomorphism and hyperplasia, and crystalline inclusion in mitochondria and in the matrix compartment. In reporting this case, we emphasize the importance of accurate postmortem examination and clinical data for the diagnosis of metabolic lactic acidosis.

Investigating the Role of Interventricular Interdependence in Development of Right Heart Dysfunction During LVAD Support: A Patient-Specific Methods-Based Approach.

PubMed

Sack, Kevin L; Dabiri, Yaghoub; Franz, Thomas; Solomon, Scott D; Burkhoff, Daniel; Guccione, Julius M

2018-01-01

Predictive computation models offer the potential to uncover the mechanisms of treatments whose actions cannot be easily determined by experimental or imaging techniques. This is particularly relevant for investigating left ventricular mechanical assistance, a therapy for end-stage heart failure, which is increasingly used as more than just a bridge-to-transplant therapy. The high incidence of right ventricular failure following left ventricular assistance reflects an undesired consequence of treatment, which has been hypothesized to be related to the mechanical interdependence between the two ventricles. To investigate the implication of this interdependence specifically in the setting of left ventricular assistance device (LVAD) support, we introduce a patient-specific finite-element model of dilated chronic heart failure. The model geometry and material parameters were calibrated using patient-specific clinical data, producing a mechanical surrogate of the failing in vivo heart that models its dynamic strain and stress throughout the cardiac cycle. The model of the heart was coupled to lumped-parameter circulatory systems to simulate realistic ventricular loading conditions. Finally, the impact of ventricular assistance was investigated by incorporating a pump with pressure-flow characteristics of an LVAD (HeartMate II™ operating between 8 and 12 k RPM) in parallel to the left ventricle. This allowed us to investigate the mechanical impact of acute left ventricular assistance at multiple operating-speeds on right ventricular mechanics and septal wall motion. Our findings show that left ventricular assistance reduces myofiber stress in the left ventricle and, to a lesser extent, right ventricle free wall, while increasing leftward septal-shift with increased operating-speeds. These effects were achieved with secondary, potentially negative effects on the interventricular septum which showed that support from LVADs, introduces unnatural bending of the septum and with it, increased localized stress regions. Left ventricular assistance unloads the left ventricle significantly and shifts the right ventricular pressure-volume-loop toward larger volumes and higher pressures; a consequence of left-to-right ventricular interactions and a leftward septal shift. The methods and results described in the present study are a meaningful advancement of computational efforts to investigate heart-failure therapies in silico and illustrate the potential of computational models to aid understanding of complex mechanical and hemodynamic effects of new therapies.

Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

PubMed

Zhang, Youhua; Popović, Zoran B; Kusunose, Kenya; Mazgalev, Todor N

2013-01-01

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 μs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF. © 2012 Wiley Periodicals, Inc.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial.

PubMed

van der Bom, Teun; Winter, Michiel M; Bouma, Berto J; Groenink, Maarten; Vliegen, Hubert W; Pieper, Petronella G; van Dijk, Arie P J; Sieswerda, Gertjan T; Roos-Hesselink, Jolien W; Zwinderman, Aeilko H; Mulder, Barbara J M

2013-01-22

The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, Vo(2)peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3-28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2-14 g; P=0.01) in the placebo group than in the valsartan group. There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

Cardiac function in children with premature ventricular contractions: the effect of omega-3 polyunsaturated fatty acid supplementation.

PubMed

Oner, Taliha; Ozdemir, Rahmi; Doksöz, Onder; Genc, Dildar B; Guven, Baris; Demirpence, Savas; Yilmazer, Murat M; Yozgat, Yilmaz; Mese, Timur; Tavli, Vedide

2018-07-01

Premature ventricular contractions are accepted as benign in structurally normal hearts. However, reversible cardiomyopathy can sometimes develop. Omega-3 polyunsaturated fatty acids have anti-arrhythmic properties in animals and humans.AimWe evaluated left ventricular function in children with premature ventricular contractions with normal cardiac anatomy and assessed the impact of omega-3 fatty acid supplementation on left ventricular function in a prospective trial. A total of 25 patients with premature ventricular contraction, with more than 2% premature ventricular contractions on 24-hour Holter electrocardiography, and 30 healthy patients were included into study. All patients underwent electrocardiography, left ventricular M-mode echocardiography, and myocardial performance index testing. Patients with premature ventricular contraction were given omega-3 fatty acids at a dose of 1 g/day for 3 months, and control echocardiography and 24-hour Holter electrocardiography were performed. Neither placebo nor omega-3 fatty acids were given to the control group. Compared with the values of the control group, the patients with premature ventricular contraction had significantly lower fractional shortening. The myocardial performance index decreased markedly in the patient groups. The mean heart rate and mean premature ventricular contraction percentage of Group 2 significantly decreased in comparison with their baseline values after the omega-3 supplementation. In conclusion, premature ventricular contractions can lead to systolic cardiac dysfunction in children. Omega-3 supplementation may improve cardiac function in children with premature ventricular contractions. This is the first study conducted in children to investigate the possible role of omega-3 fatty acid supplementation on treatment of premature ventricular contractions.

Point-of-Care Ultrasonography to Assess Portal Vein Pulsatility and the Effect of Inhaled Milrinone and Epoprostenol in Severe Right Ventricular Failure: A Report of 2 Cases.

PubMed

Tremblay, Jan-Alexis; Beaubien-Souligny, William; Elmi-Sarabi, Mahsa; Desjardins, Georges; Denault, André Y

2017-10-15

This article describes 2 patients with severe acute right ventricular failure causing circulatory shock. Portal vein pulsatility assessed by bedside ultrasonography suggested clinically relevant venous congestion. Management included cardiac preload reduction and combined inhalation of milrinone and epoprostenol to reduce right ventricular afterload. Portal vein ultrasonography may be useful in assessing right ventricular function in the acutely ill patient.

Cost-utility analysis of intravenous immunoglobulin for the treatment of steroid-refractory dermatomyositis in Thailand.

PubMed

Bamrungsawad, Naruemon; Chaiyakunapruk, Nathorn; Upakdee, Nilawan; Pratoomsoot, Chayanin; Sruamsiri, Rosarin; Dilokthornsakul, Piyameth

2015-05-01

Intravenous immunoglobulin (IVIG) has been shown to be effective in treating steroid-refractory dermatomyositis (DM). There remains no evidence of its cost-effectiveness in Thailand. Our objective was to estimate the cost utility of IVIG as a second-line therapy in steroid-refractory DM in Thailand. A Markov model was developed to estimate the relevant costs and health benefits for IVIG plus corticosteroids in comparison with immunosuppressant plus corticosteroids in steroid-refractory DM from a societal perspective over a patient's lifetime. The effectiveness and utility parameters were obtained from clinical literature, meta-analyses, medical record reviews, and patient interviews, whereas cost data were obtained from an electronic hospital database and patient interviews. Costs are presented in $US, year 2012 values. All future costs and outcomes were discounted at a rate of 3% per annum. One-way and probabilistic sensitivity analyses were also performed. Over a lifetime horizon, the model estimated treatment under IVIG plus corticosteroids to be cost saving compared with immunosuppressant plus corticosteroids, where the saving of costs and incremental quality-adjusted life-years (QALYs) were $US4738.92 and 1.96 QALYs, respectively. Sensitivity analyses revealed that probability of response of immunosuppressant plus corticosteroids was the most influential parameter on incremental QALYs and costs. At a societal willingness-to-pay threshold in Thailand of $US5148 per QALY gained, the probability of IVIG being cost effective was 97.6%. The use of IVIG plus corticosteroids is cost saving compared with treatment with immunosuppressant plus corticosteroids in Thai patients with steroid-refractory DM. Policy makers should consider using our findings in their decision-making process for adding IVIG to corticosteroids as the second-line therapy for steroid-refractory DM patients.

[Effects of genistein on contractility of isolated right ventricular muscles in guinea pig].

PubMed

Wu, Jin-xia; Li, Hong-fang; Liu, Chong-bin; Tian, Zhi-feng

2008-11-01

To study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms. Isolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed. GEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)). GEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.

THE REFRACTORY PERIOD OF THE NORMALLY-BEATING DOG'S AURICLE; WITH A NOTE ON THE OCCURRENCE OF AURICULAR FIBRILLATION FOLLOWING A SINGLE STIMULUS

PubMed Central

Andrus, E. Cowles; Carter, Edward P.

1930-01-01

1. A method is described for determining the refractory period of the dog's auricle during the normal sinus rhythm. The advantages of the method are: (a) The total stimulating effects of repeated induction shocks are avoided. (b) The action current is recorded from a point one millimeter or less from the point of stimulation. (c) Alterations in the spontaneous rate of the auricle do not interfere with the accurate determination of the refractory period. 2. The values obtained for the normal refractory period and the changes produced by atropine and by stimulation of the vagus agree closely with those of previous observers. 3. The automatic features of the method make possible the determination of the refractory period under adrenalin. This drug brings about a distinct shortening of the refractory period but less than that produced by stimulation of the vagus. 4. During vagal stimulation a single induction shock, introduced soon after the end of the refractory period, frequently produces auricular fibrillation. The cause of this irregularity is discussed and its relation to clinical auricular fibrillation is suggested. PMID:19869696

Ketogenic diet treatment for pediatric super-refractory status epilepticus.

PubMed

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

2016-10-01

We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

PubMed

Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin

2016-11-01

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

InnovaSEC in Action: Cost-effectiveness of Barostim in the Treatment of Refractory Hypertension in Spain.

PubMed

Soto, Marcelo; Sampietro-Colom, Laura; Sagarra, Joan; Brugada-Terradellas, Josep

2016-06-01

In Spain, 0.3% of patients with hypertension are refractory to conventional treatment. The complications resulting from deficient control of this condition can lead to poor quality of life for the patient and considerable health care costs. Barostim is an implantable device designed to lower blood pressure in these patients. The aim of this study was to analyze the cost-effectiveness of Barostim compared with drug therapy in hypertensive patients refractory to conventional treatment (at least 3 antihypertensive drugs, including 1 diuretic agent). We used a Markov model adapted to the epidemiology of the Spanish population to simulate the natural history of a cohort of patients with refractory hypertension over their lifetime. Data on the effectiveness of the treatments studied were obtained from the literature, and data on costs were taken from hospital administrative databases and official sources. Deterministic and probabilistic sensitivity analyses were conducted. Barostim increased the number of quality-adjusted life years by 0.78 and reduced the number of hypertension-associated clinical events. The incremental cost-effectiveness ratio in a cohort of men reached 68 726 euros per year of quality-adjusted life. One of the main elements that makes this technology costly is the need for battery replacement. The results were robust. Barostim is not a cost-effective strategy for the treatment of refractory hypertension in Spain. The cost-effectiveness ratio could be improved by future reductions in the cost of the battery. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

[The effect of atrial pacing on left ventricular diastolic function and BNP levels in patients with DDD pacemaker].

PubMed

Apali, Zeynep; Bayata, Serdar; Yeşil, Murat; Arikan, Erdinç; Postaci, Nursen

2010-08-01

We aimed to investigate the effect of atrial pacing on left ventricular diastolic function and brain natriuretic peptide (BNP) levels in patients with DDD pacemaker. Thirty patients with complete atrio-ventricular (AV) block and DDD pacemaker were included. All patients had normal left ventricular systolic function. Echocardiographic diastolic function parameters (transmitral and tissue Doppler velocities during early (E and E') and late (A and A') filling) and NT-pro-BNP levels were evaluated prospectively during atrial sensing and pacing periods. Echocardiographic data were compared with paired sample t test and NT-pro-BNP levels were compared with Wilcoxon test. Echocardiographic E/A, E'/A', E/E' ratios were calculated as 0.72+/-0.34, 0.61+/-0.21 and 8.76+/-2.58 during atrial sensing period. Same parameters were found as 0.71+/-0.23, 0.64+/-0.16 and 8.93+/-3.16 respectively during atrial pacing period. Echocardiographic left ventricular diastolic function parameters were not significantly different during atrial pacing and atrial sensing periods. Median plasma NT-pro-BNP levels were measured as 142 pg/ml (min-max 47-563 pg/ml) and 147 pg/ml (min-max 33-1035 pg/ml) during atrial sensing and pacing periods respectively. These levels were not significantly different (p=0.86). The result of this study has shown that, atrial pacing has not any additional detrimental effect on left ventricular diastolic function parameters in paced patients with normal left ventricular systolic function.

Cannabinoid receptor 2 activation restricts fibrosis and alleviates hydrocephalus after intraventricular hemorrhage.

PubMed

Tan, Qiang; Chen, Qianwei; Feng, Zhou; Shi, Xia; Tang, Jun; Tao, Yihao; Jiang, Bing; Tan, Liang; Feng, Hua; Zhu, Gang; Yang, Yunfeng; Chen, Zhi

2017-01-01

Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats. Rats were randomized to receive JWH-133(CB2 agonist), SR144528 (CB2 antagonist) or saline. The lateral ventricular volumes, fibrosis in the subarachnoid space and ventricular wall, transforming growth factor-β 1(TGF-β1) in cerebrospinal fluid and brain tissue, and animal neurological scores were measured to evaluate the effects of CB2 in hydrocephalus following IVH. CB2 agonist JWH-133 significantly decreased the lateral ventricular volumes, improved the associated neurological deficits, down-regulated TGF-β1 expression, and alleviated fibrosis in the subarachnoid space and ventricular wall after IVH. All of these effects were reversed by SR144528. In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1. Copyright © 2016 Elsevier B.V. All rights reserved.

Right Ventricular Perfusion: Physiology and Clinical Implications.

PubMed

Crystal, George J; Pagel, Paul S

2018-01-01

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

[Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

PubMed

Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

2018-04-28

To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P<0.05); while IKs densities were significantly reduced [+60 mV: (0.36±0.03) pA/pF vs (0.58±0.05) pA/pF, P<0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval (P<0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

A study on the efficacy of rebamipide for patients with proton pump inhibitor-refractory non-erosive reflux disease.

PubMed

Adachi, Kyoichi; Furuta, Kenji; Miwa, Hiroto; Oshima, Tadayuki; Miki, Masaharu; Komazawa, Yoshinori; Iwakiri, Katsuhiko; Furuta, Takahisa; Koike, Tomoyuki; Shimatani, Tomohiko; Kinoshita, Yoshikazu

2012-06-01

Reflux symptoms in patients with non-erosive reflux disease (NERD) cannot be easily controlled by treatment with proton pump inhibitors (PPI). The anti-inflammatory function of rebamipide may be effective for protecting the esophageal mucosa. This prospective randomized multicenter placebo-controlled study was performed to clarify the efficacy of rebamipide for NERD patients whose reflux symptoms were refractory to PPI treatment. One hundred forty-nine patients were enrolled on the basis of a QUEST score of over 6 and absence of endoscopically proven esophageal mucosal breaks. All the patients were initially administered 15 mg of lansoprazole for 4 weeks, and the symptoms were then assessed using QUEST and GSRS. PPI-refractory patients were randomly assigned to administration of rebamipide or placebo t.i.d. for 4 weeks. Three of the 149 patients were lost to follow-up, and 60 among the remaining 146 patients were found to be PPI-refractory. Among these PPI-refractory patients, 31 were randomly assigned to a rebamipide group and 29 to a placebo group. At the end of drug administration, the QUEST and GSRS scores did not differ between the rebamipide and placebo groups, although a significantly higher proportion of patients in the rebamipide group showed amelioration of abdominal pain and diarrhea. Administration of rebamipide cannot effectively control reflux symptoms in NERD patients whose symptoms are refractory to PPI therapy.

Management of refractory epilepsy.

PubMed

Muñana, Karen R

2013-05-01

The term refractory epilepsy is utilized in veterinary medicine to describe a condition in which an animal with epilepsy fails to attain satisfactory seizure control or suffers intolerable side effects despite appropriate therapy with conventional antiepileptic drugs. Refractory epilepsy is an important problem in small animal practice as it occurs in approximately one-third of dogs with epilepsy. Consequently, there is much interest in identifying ways to more effectively treat this population of animals. More than a dozen new antiepileptic drugs have been approved for humans over the last 2 decades, and several of these drugs, including gabapentin, zonisamide, levetiracetam, and pregabalin, have been evaluated for the treatment of refractory seizures in veterinary patients. Nonmedical methods to treat poorly controlled epilepsy are also being explored. The 2 alternative forms of therapy that have shown the most promise in humans with epilepsy are electrical stimulation of the brain and dietary modification, both of which have also been evaluated in dogs. This overview summarizes the available data on pharmacologic as well as nonmedical treatment options for dogs and cats with refractory epilepsy. Although many forms of therapy are currently being utilized in clinical practice, our knowledge of the safety and efficacy of these treatments is limited. Additional randomized controlled trials are needed to better evaluate these novel therapies for refractory epilepsy in dogs and cats. © 2013 Elsevier Inc. All rights reserved.

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

PubMed

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

PubMed Central

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes.

PubMed

Matsutani, Daisuke; Sakamoto, Masaya; Kayama, Yosuke; Takeda, Norihiko; Horiuchi, Ryuzo; Utsunomiya, Kazunori

2018-05-22

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM. This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e' as a parameter of left ventricular diastolic function. A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e' ratio 13.7 ± 3.5-12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e' ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e' ratio. This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values. Trial registration UMIN Clinical Trials Registry UMIN000028141.

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

PubMed

Kaku, T; Sakurai, S; Furuno, Y; Yashiro, A; Nakashima, Y; Kuroiwa, A

1995-08-01

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.

Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

PubMed

del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime

2014-11-01

Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.

Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart.

PubMed

Osadchii, Oleg E

2016-01-01

Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms). Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

A Statistical Atrioventricular Node Model Accounting for Pathway Switching During Atrial Fibrillation.

PubMed

Henriksson, Mikael; Corino, Valentina D A; Sornmo, Leif; Sandberg, Frida

2016-09-01

The atrioventricular (AV) node plays a central role in atrial fibrillation (AF), as it influences the conduction of impulses from the atria into the ventricles. In this paper, the statistical dual pathway AV node model, previously introduced by us, is modified so that it accounts for atrial impulse pathway switching even if the preceding impulse did not cause a ventricular activation. The proposed change in model structure implies that the number of model parameters subjected to maximum likelihood estimation is reduced from five to four. The model is evaluated using the data acquired in the RATe control in atrial fibrillation (RATAF) study, involving 24-h ECG recordings from 60 patients with permanent AF. When fitting the models to the RATAF database, similar results were obtained for both the present and the previous model, with a median fit of 86%. The results show that the parameter estimates characterizing refractory period prolongation exhibit considerably lower variation when using the present model, a finding that may be ascribed to fewer model parameters. The new model maintains the capability to model RR intervals, while providing more reliable parameters estimates. The model parameters are expected to convey novel clinical information, and may be useful for predicting the effect of rate control drugs.

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

PubMed

Zuchinali, Priccila; Souza, Gabriela C; Pimentel, Maurício; Chemello, Diego; Zimerman, André; Giaretta, Vanessa; Salamoni, Joyce; Fracasso, Bianca; Zimerman, Leandro I; Rohde, Luis E

2016-12-01

The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74). Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. clinicaltrials.gov Identifier: NCT02045992.

Surgical treatment of tricuspid valve insufficiency promotes early reverse remodeling in patients with axial-flow left ventricular assist devices.

PubMed

Maltais, Simon; Topilsky, Yan; Tchantchaleishvili, Vakhtang; McKellar, Stephen H; Durham, Lucian A; Joyce, Lyle D; Daly, Richard C; Park, Soon J

2012-06-01

The HeartMate II (Thoratec Corp, Pleasanton, Calif) continuous-flow left ventricular assist device has emerged as the standard of care for patients with advanced heart failure. The objective of this study was to assess the safety and early effectiveness of concomitant tricuspid valve procedures in patients undergoing implantation of a HeartMate II device. From February 2007 to April 2010, 83 patients underwent HeartMate II left ventricular assist device implantation. Of these, 37 patients had concomitant tricuspid valve procedures (32 repairs, 5 replacements) for severe tricuspid regurgitation. The effects of a tricuspid valve procedure on tricuspid regurgitation and right ventricular remodeling were assessed comparing echocardiographic findings at baseline and 30 days after left ventricular assist device implantation. Overall survival was also compared. Patients undergoing a concomitant tricuspid valve procedure had more tricuspid regurgitation (vena contracta, 5.6 ± 2.1 mm vs 2.9 ± 2.0 mm; P < .001), worse right ventricular dysfunction (right ventricular end-diastolic area, 33.6 ± 6.2 mm vs 31.6 ± 8.5 mm; P = .05), higher mean right atrial pressure (17.4 ± 7.1 mm Hg vs 14.9 ± 5.1 mm Hg; P = .03), and a higher Kormos score (2.6 ± 2.1 vs 1.2 ± 1.4; P = .0008) preoperatively. One month after surgery, tricuspid regurgitation was worse in patients who underwent left ventricular assist device implantation alone (+18.6%), whereas it improved significantly in patients undergoing a concomitant tricuspid valve procedure (-50.2%) (P = .005). A corresponding significant reduction in right ventricular end-diastolic area (33.6% ± 6.2% vs 30.1% ± 9.7%; P = .03) and a trend toward better right ventricular function (55.5% ± 79.7% vs 35.7% ± 60.5%; P = .28) were noted in patients undergoing a concomitant tricuspid valve procedure. Survival was comparable between the 2 groups. In patients with severe tricuspid regurgitation undergoing left ventricular assist device implantation, a concomitant tricuspid valve procedure effectively reduces tricuspid regurgitation and promotes reverse remodeling of the right ventricle. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Flow-related Right Ventricular - Pulmonary Arterial Pressure Gradients during Exercise.

PubMed

Wright, Stephen P; Opotowsky, Alexander R; Buchan, Tayler A; Esfandiari, Sam; Granton, John T; Goodman, Jack M; Mak, Susanna

2018-06-06

The assumption of equivalence between right ventricular and pulmonary arterial systolic pressure is fundamental to several assessments of right ventricular or pulmonary vascular hemodynamic function. Our aims were to 1) determine whether systolic pressure gradients develop across the right ventricular outflow tract in healthy adults during exercise, 2) examine the potential correlates of such gradients, and 3) consider the effect of such gradients on calculated indices of right ventricular function. Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. Right ventricular and pulmonary artery pressures were simultaneously transduced, and cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analyzed offline. Summary data are reported as mean ± standard deviation or median [interquartile range]. No significant right ventricular outflow tract gradients were observed at rest (mean gradient = 4 [3-5] mmHg), and calculated effective orifice area was 3.6±1.0 cm2. Right ventricular systolic pressure increases during exercise were greater than that of pulmonary artery systolic pressure. Accordingly, mean gradients developed during light exercise (8 [7-9] mmHg) and increased during moderate exercise (12 [9-14] mmHg, p < 0.001). The magnitude of the mean gradient was linearly related to cardiac output (r2 = 0.70, p < 0.001). In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to blood flow rate.

Autologous hematopoietic stem cells for refractory Crohn's disease.

PubMed

DiNicola, C A; Zand, A; Hommes, D W

2017-05-01

Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

Proteome-wide analysis of Anopheles culicifacies mosquito midgut: new insights into the mechanism of refractoriness.

PubMed

Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Singh, Jagbir; Adak, Tridibesh; Sharma, Arun

2018-05-08

Midgut invasion, a major bottleneck for malaria parasites transmission is considered as a potential target for vector-parasite interaction studies. New intervention strategies are required to explore the midgut proteins and their potential role in refractoriness for malaria control in Anopheles mosquitoes. To better understand the midgut functional proteins of An. culicifacies susceptible and refractory species, proteomic approaches coupled with bioinformatics analysis is an effective means in order to understand the mechanism of refractoriness. In the present study, an integrated in solution- in gel trypsin digestion approach, along with Isobaric tag for relative and absolute quantitation (iTRAQ)-Liquid chromatography/Mass spectrometry (LC/MS/MS) and data mining were performed to identify the proteomic profile and differentially expressed proteins in Anopheles culicifacies susceptible species A and refractory species B. Shot gun proteomics approaches led to the identification of 80 proteins in An. culicifacies susceptible species A and 92 in refractory species B and catalogue was prepared. iTRAQ based proteomic analysis identified 48 differentially expressed proteins from total 130 proteins. Of these, 41 were downregulated and 7 were upregulated in refractory species B in comparison to susceptible species A. We report that the altered midgut proteins identified in naturally refractory mosquitoes are involved in oxidative phosphorylation, antioxidant and proteolysis process that may suggest their role in parasite growth inhibition. Furthermore, real time polymerase chain reaction (PCR) analysis of few proteins indicated higher expression of iTRAQ upregulated protein in refractory species than susceptible species. This study elucidates the first proteome of the midguts of An. culicifacies sibling species that attempts to analyze unique proteogenomic interactions to provide insights for better understanding of the mechanism of refractoriness. Functional implications of these upregulated proteins in refractory species may reflect the phenotypic characteristics of the mosquitoes and will improve our understandings of blood meal digestion process, parasite vector interactions and proteomes of other vectors of human diseases for development of novel vector control strategies.

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder.

PubMed

Xi, Er-Ping; Zhu, Jian; Zhu, Shui-Bo; Yin, Gui-Lin; Liu, Yong; Dong, Yong-Qiang; Zhang, Yu; Xia, Feng

2012-11-01

Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective.

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder

PubMed Central

Xi, Er-Ping; Zhu, Jian; Zhu, Shui-Bo; Yin, Gui-Lin; Liu, Yong; Dong, Yong-Qiang; Zhang, Yu; Xia, Feng

2012-01-01

OBJECTIVE: Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. METHODS: We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. RESULTS: Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. CONCLUSION: Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective. PMID:23184204

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN HEART

PubMed Central

Robinson, G. Canby; Draper, George

1911-01-01

In hearts showing auricular fibrillation mechanical stimulation of the right vagus nerve causes, as a rule, marked slowing or stoppage of ventricular rhythm, without producing any appreciable effect in the electrocardiographic record of the auricular fibrillation. The ventricular pauses are apparently due to the blocking of stimuli from the auricles. The force of ventricular systole is distinctly weakened for several beats after vagus stimulation, and ectopic ventricular systoles have been seen in several instances, apparently the result of the vagus action. There may, in some cases, be lowered excitability of the ventricles, while no constant change is seen in the size of the electrical complexes representing ventricular systole. PMID:19867466

Right ventricular effects of intracoronary delivery of mesenchymal stem cells (MSC) in an animal model of pressure overload heart failure.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-12-01

In a rat model of left ventricular pressure overload hypertrophy with biventricular failure, we studied the effects of intracoronary delivery of mesenchymal stem cells (MCS) upon right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in left ventricular fractional shortening of 25% from the baseline (relative 50% reduction), animals were randomized to an intracoronary injection of MSC (n=28) or PBS (n=20). Right ventricular hemodynamic assessment and measurement of local inflammatory markers, proapoptotic factors, and determinants of extracellular matrix remodeling were performed on post-transplantation day 7, 14, 21 or 28. MSC injection improved right ventricular systolic function in the MSC group compared to the control group (mean+/-SD, max dP/dt 772+/-272 mm Hg/s vs. 392+/-132 at 28 days, P<0.01). Diastolic function was similarly improved (mean+/-SD, max -dP/dt -558+/-171 mm Hg/s vs. -327+/-131 at 28 days, P<0.05). Right ventricular levels of IL-1, IL-6, TNF-alpha, bax, bak and p38 were significantly decreased in the MSC treated animals. Expression of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 declined in the MSC group compared with controls after 28 days. In this model of left ventricular pressure overload hypertrophy and biventricular failure, intracoronary delivery of MSC was associated with an improvement in the right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling.

Synergic effects of renin and aldosterone on right ventricular function in hypertension: a tissue Doppler study.

PubMed

Gregori, Mario; Giammarioli, Benedetta; Tocci, Giuliano; Befani, Alberto; Ciavarella, Giuseppino Massimo; Ferrucci, Andrea; Paneni, Francesco

2015-12-01

Right ventricular dysfunction (RVD) is associated with poor cardiovascular outcome. The renin-angiotensin-aldosterone system is involved in alterations of the left ventricular geometry and function. Detrimental effects of the renin-angiotensin-aldosterone system on the right ventricular function are being postulated, but data supporting this assumption are still lacking. The aim of the study was to assess the impact of hyperreninemia, hyperaldosteronism or their combination on right ventricular function in hypertensive individuals. Plasma renin activity (PRA) and plasma aldosterone concentrations (PACs) were measured in 116 hypertensive patients, divided as follows: normal PRA and PAC (n = 38); high PRA and normal PAC (hypereninemia) (n = 26); normal PRA and high PAC (hyperaldosternism) (n = 27); high PRA and PAC (HRA) (n = 25). Echocardiographic evaluation of the left and right ventricles (RV), including tissue Doppler imaging, was performed. RVD was identified by tissue Doppler Imaging-derived Myocardial Performance Index, calculated with a multisegmental approach. Indices of the right ventricular structure and function, as well as the prevalence of RVD, were higher in hyperreninemia and hyperaldosternism groups as compared with the normal group, and a further increase was observed in the HRA patients. Regression models showed a similar risk of RVD in the hyperreninemia and hyperaldosternism patients, regardless of systemic and pulmonary pressure, as well as left ventricular dysfunction. Notably, patients with both hyperreninemia and hyperaldosternism exhibited the strongest association with RVD as compared with patients with only hyperreninemia or hyperaldosternism. Isolated hyperreninemia or hyperaldosternism determines a similar impairment of the right ventricular function, whereas their combination is further detrimental. Renin and aldosterone may represent early biomarkers of right ventricular dysfunction in hypertension.

Papillary Muscle Repositioning as a Subvalvular Apparatus Preservation Technique in Mitral Stenosis Patients with Normal Left Ventricular Systolic Function

PubMed Central

Lafci, Gokhan; Cagli, Kerim; Korkmaz, Kemal; Turak, Osman; Uzun, Alper; Yalcinkaya, Adnan; Diken, Adem; Gunertem, Eren; Cagli, Kumral

2014-01-01

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function. We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups. The PMR group consisted of 48 patients and the MVR-only group of 67 patients. The 2 groups’ baseline characteristics and surgery-related factors (including perioperative mortality) were similar. During the 18-month follow-up, all echocardiographic variables showed a consistent improvement in the PMR group; the mean left ventricular ejection fraction deteriorated significantly in the MVR-only group. Comparison during follow-up of the magnitude of longitudinal changes revealed that decreases in left ventricular end-diastolic and end-systolic diameters and in left ventricular sphericity indices, and increases in left ventricular ejection fractions, were significantly higher in the PMR group than in the MVR-only group. This study suggests that, in patients with rheumatic mitral stenosis and preserved left ventricular systolic function, the addition of papillary muscle repositioning to valve replacement with a mechanical prosthesis improves left ventricular dimensions, ejection fraction, and sphericity index at the 18-month follow-up with no substantial undesirable effect on the surgery-related factors. PMID:24512397

Growth of left ventricular mass with military basic training in army recruits.

PubMed

Batterham, Alan M; George, Keith P; Birch, Karen M; Pennell, Dudley J; Myerson, Saul G

2011-07-01

Exercise-induced left ventricular hypertrophy is well documented, but whether this occurs merely in line with concomitant increases in lean body mass is unclear. Our aim was to model the extent of left ventricular hypertrophy associated with increased lean body mass attributable to an exercise training program. Cardiac and whole-body magnetic resonance imaging was performed before and after a 10-wk intensive British Army basic training program in a sample of 116 healthy Caucasian males (aged 17-28 yr). The within-subjects repeated-measures allometric relationship between lean body mass and left ventricular mass was modeled to allow the proper normalization of changes in left ventricular mass for attendant changes in lean body mass. To linearize the general allometric model (Y=aXb), data were log-transformed before analysis; the resulting effects were therefore expressed as percent changes. We quantified the probability that the true population increase in normalized left ventricular mass was greater than a predefined minimum important difference of 0.2 SD, assigning a probabilistic descriptive anchor for magnitude-based inference. The absolute increase in left ventricular mass was 4.8% (90% confidence interval=3.5%-6%), whereas lean body mass increased by 2.6% (2.1%-3.0%). The change in left ventricular mass adjusted for the change in lean body mass was 3.5% (1.9%-5.1%), equivalent to an increase of 0.25 SD (0.14-0.37). The probability that this effect size was greater than or equal to our predefined minimum important change of 0.2 SD was 0.78-likely to be important. After correction for allometric growth rates, left ventricular hypertrophy and lean body mass changes do not occur at the same magnitude in response to chronic exercise.

Different effects of prolonged exercise on the right and left ventricles.

PubMed

Douglas, P S; O'Toole, M L; Hiller, W D; Reichek, N

1990-01-01

To examine the functional consequences of the greater increase in right ventricular work with exercise, the effects of prolonged exercise on the right and left heart chambers were compared in 41 athletes before, at the finish (13 min) and after recovery (28 h) from the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike ride, 42.2 km run). Two-dimensional and Doppler echocardiograms were analyzed for left and right atrial and ventricular areas at end-diastole and end-systole, right and left ventricular inflow velocities and mitral and tricuspid regurgitation. After exercise, left ventricular and left and right atrial sizes were reduced, whereas right ventricular size increased (diastole: 21.4 to 24.2 cm2; systole: 15.8 to 18.2 cm2; p less than 0.01). The emptying fraction of all chambers was unchanged. Left but not right ventricular inflow showed an increase in peak velocity of rapid filling, whereas both atrial systolic velocities increased (26 to 38 cm/s tricuspid; 38 to 54 cm/s mitral; both p less than 0.01). Overall, the right ventricular early to atrial velocity ratio was reduced after exercise (1.56 to 1.17; p less than 0.05) and the left ventricular pattern was unchanged. The prevalence of tricuspid regurgitation was statistically unchanged (86% to 52%), although that of mitral regurgitation was greatly reduced (76% to 0%). Changes in all variables returned toward prerace values during recovery. Thus, in highly trained athletes, prolonged exercise causes differing responses of the right and left ventricles. These differences may be due to changes in right ventricular function, shape or compliance.

Left ventricular assist devices as destination therapy: a new look at survival.

PubMed

Park, Soon J; Tector, Alfred; Piccioni, William; Raines, Edward; Gelijns, Annetine; Moskowitz, Alan; Rose, Eric; Holman, William; Furukawa, Satoshi; Frazier, O Howard; Dembitsky, Walter

2005-01-01

The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.

Impact of Acute Coronary Syndrome Complicated by Ventricular Fibrillation on Long-term Incidence of Sudden Cardiac Death.

PubMed

Álvarez-Álvarez, Belén; Bouzas-Cruz, Noelia; Abu-Assi, Emad; Raposeiras-Roubin, Sergio; López-López, Andrea; González Cambeiro, María Cristina; Peña-Gil, Carlos; García-Acuña, José María; González-Juanatey, José Ramón

2015-10-01

There is little information on the effect of acute coronary syndrome complicated by ventricular fibrillation on the long-term incidence of sudden cardiac death. We analyzed this effect in a contemporary cohort of patients with acute coronary syndrome. We studied 5302 consecutive patients with acute coronary syndrome between December 2003 and December 2012. We compared mortality during and after hospitalization according to the presence or absence of ventricular fibrillation. Ventricular fibrillation was observed in 163 (3.1%) patients, and was early onset in 72.4% of these patients. In-hospital mortality was 36.2% in the group with ventricular fibrillation and 4.7% in the group without (p<.001). After a mean follow-up of 4.7 years (standard deviation, 2.6 years), mortality was 30.7% in the ventricular fibrillation group and 24.7% in the other group (P=.23). After adjusting for confounding variables, the presence of ventricular fibrillation was not associated with an increased risk of death in the follow-up period (hazard ratio=1.29; 95% confidence interval, 0.90-1.87). The cause of death was established in 72% of patients. The incidence of sudden death was 12.9% in the ventricular fibrillation group and 11.9% in the other group (P=.71). Cardiovascular-cause mortality was also similar between the 2 groups (35.5% and 34.4%, respectively. Patients with acute coronary syndrome complicated by ventricular fibrillation who survive the in-hospital phase do not appear to be at an increased risk of sudden cardiac death or other cardiovascular-cause death. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Combined application of alginate dressing and human granulocyte-macrophage colony stimulating factor promotes healing in refractory chronic skin ulcers.

PubMed

Huang, Guobao; Sun, Tangqing; Zhang, Lei; Wu, Qiuhe; Zhang, Keyan; Tian, Qingfen; Huo, Ran

2014-06-01

The aim of the present study was to evaluate the clinical therapeutic effect of the combined application of alginate and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the healing of refractory chronic skin ulcers. A single center, three arm, randomized study was performed at Jinan Central Hospital (Jinan, Shandong, China). A total of 60 patients with refractory chronic skin ulcers, which persisted for >1 month, were enrolled and randomly assigned into one of the following three groups: alginate dressing/rhGM-CSF group (group A), rhGM-CSF only group (group B) and conventional (vaseline dressing) group (group C). The wound area rate was measured, granulation and color were observed and pain was evaluated. The data were summarized and statistical analysis was performed. The results demonstrated that group A exhibited a significantly faster wound healing rate and lower pain score compared with the other groups (P<0.01). In conclusion, the combined application of alginate dressing and rhGM-CSF for the treatment of refractory chronic skin ulcers demonstrated significant advantages. It promoted the growth of granulation tissue, accelerated re-epithelialization and also effectively reduced wound pain, and thus improved the quality of life for the patient. This suggests that the combined application of alginate and rhGM-CSF may be an effective therapeutic strategy for the clinical treatment of refractory chronic skin ulcers.

Refractory Research Group - U.S. DOE, Albany Research Center [Institution Profile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, James P.

2004-09-01

The refractory research group at the Albany Research Center (ARC) has a long history of conducting materials research within the U.S. Bureau of Mines, and more recently, within the U.S. Dept. of Energy. When under the U.S. Bureau of Mines, research was driven by national needs to develop substitute materials and to conserve raw materials. This mission was accomplished by improving refractory material properties and/or by recycling refractories using critical and strategic materials. Currently, as a U.S. Dept of Energy Fossil Energy field site, research is driven primarily by the need to assist DOE in meeting its vision to developmore » economically and environmentally viable technologies for the production of electricity from fossil fuels. Research at ARC impacts this vision by: • Providing information on the performance characteristics of materials being specified for the current generation of power systems; • Developing cost-effective, high performance materials for inclusion in the next generation of fossil power systems; and • Solving environmental emission and waste problems related to fossil energy systems. A brief history of past refractory research within the U.S. Bureau of Mines, the current refractory research at ARC, and the equipment and capabilities used to conduct refractory research at ARC will be discussed.« less

Effects of Trichothecenes on Cardiac Cell Electrical Function

DTIC Science & Technology

1985-12-16

toxic effects . These studies demonstrated unequivocal reversible effects of certain mycotoxins on heart cell electrical activity. Preliminary studies...muscle cells shown in Figure 8 illustrate the typical effects of trichothecene mycotoxins in canine ventricular cells. T-2 tetraol, for 3xample...false tendon cells and V ventricular muscle cells (shown in Figure 8) illustrate the typical effects of trichothecene mycotoxins in canine cardiac

A clinical comparison between a new dual-chamber pacing mode-AAIsafeR and DDD mode.

PubMed

Xue-Jun, Ren; Zhihong, Han; Ye, Wang; Huifeng, Du; Jinrong, Zhang; Fang, Chen; Jihong, Guo

2010-02-01

The aim of this study was to compare the cross-follow-up results in DDD or AAISafeR mode and to describe the safety and effectiveness of this pacing mode. The Symphony 2450/2550 cardiac pacemakers were implanted in 30 patients with sick sinus syndrome between February 2006 and September 2006. They were randomized to the DDD mode or AAISafeR mode for 3 months and then crossed over to the alternate pacing modality for an additional 3 months. No AAISafeR-related adverse event was observed. All documented episodes of paroxysmal atrial ventricular block caused the immediate switch of the pacing mode from AAI to DDD. The cumulative percent ventricular pacing was significantly reduced in the AAISafeR mode compared with the DDD mode (0.9% [0%-3%] versus 51.3% [2%-91%] P = 0.001; 2.94% [0%-18%] versus 41.18% [0%-65%] P = 0.0001). After 3 months in DDD mode, left atrial diameter, left ventricular enddiastolic diameter, and left ventricular end-systolic diameter increased significantly and left ventricular ejection fraction decreased. However, no obvious changes appeared in 3 months of AAISafeR mode. Switches to DDD occurred during follow-up in 21 patients due to different-degree atrial ventricular block. The AAISafeR mode substantially reduces the amount of unnecessary right ventricular pacing in the bradycardia population and effectively prevents the deleterious effects on cardiac performance. An international randomized study will further ascertain the efficacy of this new pacing mode specifically in the prevention of heart failure hospitalization and atrial fibrillation.

Diastolic function of the nonfilling human left ventricle.

PubMed

Paulus, W J; Vantrimpont, P J; Rousseau, M F

1992-12-01

To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.

Aerodynamic and acoustic effects of ventricular gap.

PubMed

Alipour, Fariborz; Karnell, Michael

2014-03-01

Supraglottic compression is frequently observed in individuals with dysphonia. It is commonly interpreted as an indication of excessive circumlaryngeal muscular tension and ventricular medialization. The purpose of this study was to describe the aerodynamic and acoustic impact of varying ventricular medialization in a canine model. Subglottal air pressure, glottal airflow, electroglottograph, acoustic signals, and high-speed video images were recorded in seven excised canine larynges mounted in vitro for laryngeal vibratory experimentation. The degree of gap between the ventricular folds was adjusted and measured using sutures and weights. Data were recorded during phonation when the ventricular gap was narrow, neutral, and large. Glottal resistance was estimated by measures of subglottal pressure and glottal flow. Glottal resistance increased systematically as ventricular gap became smaller. Wide ventricular gaps were associated with increases in fundamental frequency and decreases in glottal resistance. Sound pressure level did not appear to be impacted by the adjustments in ventricular gap used in this research. Increases in supraglottic compression and associated reduced ventricular width may be observed in a variety of disorders that affect voice quality. Ventricular compression may interact with true vocal fold posture and vibration resulting in predictable changes in aerodynamic, physiological, acoustic, and perceptual measures of phonation. The data from this report supports the theory that narrow ventricular gaps may be associated with disordered phonation. In vitro and in vivo human data are needed to further test this association. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia.

PubMed

Yan, Dong; Cheng, Lu-feng; Song, Hong-Yan; Turdi, Subat; Kerram, Parhat

2007-08-01

Overdoses of haloperidol are associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. The aim of this experiment was to study the effect of haloperidol on the action potentials in cardiac Purkinje fibers and papillary muscles under normal and simulated ischemia conditions in rabbits and guinea pigs. Using the standard intracellular microelectrode technique, we examined the effects of haloperidol on the action potential parameters [action potential amplitude (APA), phase 0 maximum upstroke velocity (V(max)), action potential amplitude at 90% of repolarization (APD(90)), and effective refractory period (ERP)] in rabbit cardiac Purkinje fibers and guinea pig cardiac papillary cells, in which both tissues were under simulated ischemic conditions. Under ischemic conditions, different concentrations of haloperidol depressed APA and prolonged APD(90) in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 micromol/L) significantly depressed APA and prolonged APD(90), and from 1 micromol/L, haloperidol showed significant depression on V(max); ERP was not significantly affected. In guinea pig cardiac papillary muscles, the thresholds of significant reduction in APA, V(max), EPR, and APD(90) were 10, 0.3, 1, and 1 mumol/L, respectively, for haloperidol. Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD(90) in a concentration-dependent manner and precipitated the decrease in V(max) induced by ischemia. The shortening of ERP and APD(90) in papillary muscle action potentials may be inhibited by haloperidol.

[Surgery of refractory ischemic arrhythmia].

PubMed

Viganò, M; Graffigna, A; Salerno, G

1992-03-01

Since June 1980, 138 patients have undergone surgical treatment for refractory ventricular tachycardia due to ischemic heart disease. Electrically guided surgical ablation (EGSA) of the focus was performed in 117 patients, while 14 patients underwent application of automatic implantable cardioverter-defibrillator (AICD), and 8 patients underwent heart transplantation. During the whole period considered, among the EGSA patients an operative mortality of 13 patients was observed (11.4%), with a late mortality of another 14 patients (13.4%). Two early and six late recurrences were described, and 4 cases of sudden or unexplained death, with 2 cases clearly due to an arrhythmic event. Multivariate analysis showed preoperative ejection fraction lower than 25% as a powerful predictor of early mortality (32% vs 0%). Actuarial survival rate of patients with LVEF lower than 25% was 67 +/- 12% vs 95 +/- 2% at one year and 37 +/- 25% vs 94 +/- 8% at 8 years. A high operative mortality was then observed in patients who underwent aneurysmectomy alone or visually guided procedures as compared to electrically guided procedures (75% or 3 deaths out of 4 patients vs 8.5% or 10 out of 113 patients, respectively). Patients who received an AICD with or without associated procedures showed 1 case of in-hospital mortality and no late mortality; in 6 patients at least one shock was delivered; in two patients the AICD was implanted during an EGSA procedure, due to multiple or difficult origins of the arrhythmias. Of patients who underwent heart transplantation one case of later mortality was observed due to malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Refractory Cardiogenic Shock During Tramadol Poisoning: A Case Report.

PubMed

Belin, Nicolas; Clairet, Anne-Laure; Chocron, Sidney; Capellier, Gilles; Piton, Gaël

2017-04-01

Tramadol is a weak opioid analgesic indicated for the treatment of moderate to severe pain. Tramadol intoxication can be lethal, and this drug is frequently involved in voluntary overdose. Classically, tramadol intoxication is associated with neurological and respiratory side effects. In contrast, cardiac effects are poorly documented in the literature. We report a case of severe tramadol intoxication, with plasma concentration 20 times the toxic threshold, complicated by refractory cardiogenic shock, successfully treated by extra corporeal life support (ECLS) with a favorable cardiac outcome and ECLS weaning at day 10. Seizure, clonus, and nonreactive mydriasis were present during 4 days, and complete awakening was delayed to day 15. Poisoning caused by high doses of tramadol can lead to refractory cardiogenic shock, and ECLS can be considered as effective rescue therapy in this context.

Gastric Electric Stimulation for Refractory Gastroparesis: A Prospective Analysis of 151 Patients at a Single Center.

PubMed

Heckert, Jason; Sankineni, Abhinav; Hughes, William B; Harbison, Sean; Parkman, Henry

2016-01-01

Gastric electric stimulation (GES) is used to treat patients with refractory gastroparesis symptoms. However, the effectiveness of GES in clinical practice and the effect of GES on specific symptoms of gastroparesis are not well delineated. To determine the effectiveness of GES for treatment for refractory symptoms of gastroparesis, the improvement in specific symptoms of gastroparesis, and clinical factors impacting on outcome. Enterra GES was used to treat refractory gastroparesis symptoms. Patients filled out a symptom severity questionnaire (PAGI-SYM) prior to insertion. At each follow-up visit, the patient filled out PAGI-SYM and assessed their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS). One hundred and fifty-one patients (120 females) with refractory gastroparesis (72 diabetic, 73 idiopathic, 6 other) underwent GES. Of the 138 with follow-up (1.4 ± 1.0 years), the average CPGAS was 2.4 ± 0.3 (SEM): 104 patients (75 %) improved (CPGAS > 0) and 34 (25 %) did not (CPGAS ≤ 0). Sixty patients (43 %) were at least moderately improved (CPGAS score ≥4). Clinical improvement was seen in both diabetic and idiopathic patients with the CPGAS in diabetic patients (3.5 ± 0.3) higher in idiopathic patients (1.5 ± 0.5; p < 0.05). Symptoms significantly improving the most included nausea, loss of appetite, and early satiety. Vomiting improved in both diabetic and idiopathic patients although the diabetic subgroup experienced a significantly greater reduction in vomiting than the idiopathic subgroup. In this cohort of patients with refractory gastroparesis, GES improved symptoms in 75 % of patients with 43 % being at least moderately improved. Response in diabetics was better than in nondiabetic patients. Nausea, loss of appetite, and early satiety responded the best.

Atrial fibrillation and sudden cardiac death: catheter-based sensor and mapping system of the heart

NASA Astrophysics Data System (ADS)

Ramasamy, Mouli; Kumar, Prashanth S.; Varadan, Vijay K.

2017-04-01

Ventricular arrhythmias in the heart and the rapid heartbeat of ventricular tachycardia can lead to sudden cardiac death. This is a major health issue worldwide. What is needed is to develop a catheter based sensor and mapping approach which will provide the mechanisms of ventricular arrhythmia, and effectively prevent and treat the same, potentially save life.

Catheter ablation of fatal ventricular tachyarrhythmias storm in acute coronary syndrome--role of Purkinje fiber network.

PubMed

Enjoji, Yoshihisa; Mizobuchi, Masahiro; Muranishi, Hiromi; Miyamoto, Chinae; Utsunomiya, Makoto; Funatsu, Atsushi; Kobayashi, Tomoko; Nakamura, Shigeru

2009-12-01

Ventricular fibrillation (VF) or ventricular tachycardia (VT) storm is a life-threatening arrhythmia. Antiarrhythmic drugs (AADs) are not necessarily effective to rescue life from such conditions. Catheter ablation (CA) targeting triggering premature ventricular contractions (PVCs) of VF or VT that originates from Purkinje fiber network (PFN) is reported to be effective, especially in idiopathic patients. However, in condition of acute coronary syndrome (ACS), the efficacy of CA is not well understood. To clarify the usefulness of CA as an alternative way to AADs, we performed CA in four patients with VF or VT storm. The Purkinje potential was seen just before the myocardial ventricular wave during sinus rhythm that became more prominent and double components during the initiating PVC at the targeted area. Following CA, spontaneous episodes of VF or VT were no longer observed. CA is an efficacious way to bail out PFN-related VF or VT storm even in ACS.

Treatment of dilated cardiomyopathy with carvedilol in children.

PubMed

Erdoğan, Ilkay; Ozer, Sema; Karagöz, Tevfik; Celiker, Alpay; Ozkutlu, Süheyla; Alehan, Dursun

2009-01-01

We performed a study to examine the clinical use of carvedilol, its dosage and its effects on systolic functions in children. Twenty-one patients with dilated cardiomyopathy who were treated with carvedilol adjacent to standard heart failure therapy were enrolled in the study. Echocardiographic assessment was obtained before and during carvedilol therapy, and left ventricular fractional shortening and left ventricular ejection fraction were determined in order to estimate left ventricular function. At a follow-up of six months, left ventricular ejection fraction and fractional shortening significantly improved from 38 +/- 10% to 53 +/- 13% and from 19 +/- 6 % to 27 +/- 8%, respectively, following carvedilol treatment. The results of the present study indicate that carvedilol is well tolerated in children with dilated cardiomyopathy and there is a significant improvement in the clinical status and left ventricular ejection fraction in patients not responding to conventional therapy. Patient selection criteria, optimal timing of carvedilol therapy, its dosage and its long-term effects need to be investigated with multi-institutional trials and large numbers of patients.

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

PubMed

Yoran, C; Yellin, E L; Becker, R M; Gabbay, S; Frater, R W; Sonnenblick, E H

1979-04-01

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

Noninvasive estimation of assist pressure for direct mechanical ventricular actuation

NASA Astrophysics Data System (ADS)

An, Dawei; Yang, Ming; Gu, Xiaotong; Meng, Fan; Yang, Tianyue; Lin, Shujing

2018-02-01

Direct mechanical ventricular actuation is effective to reestablish the ventricular function with non-blood contact. Due to the energy loss within the driveline of the direct cardiac compression device, it is necessary to acquire the accurate value of assist pressure acting on the heart surface. To avoid myocardial trauma induced by invasive sensors, the noninvasive estimation method is developed and the experimental device is designed to measure the sample data for fitting the estimation models. By examining the goodness of fit numerically and graphically, the polynomial model presents the best behavior among the four alternative models. Meanwhile, to verify the effect of the noninvasive estimation, the simplified lumped parameter model is utilized to calculate the pre-support and the post-support left ventricular pressure. Furthermore, by adjusting the driving pressure beyond the range of the sample data, the assist pressure is estimated with the similar waveform and the post-support left ventricular pressure approaches the value of the adult healthy heart, indicating the good generalization ability of the noninvasive estimation method.

Ventricular ectopy in patients with left ventricular dysfunction: should it be treated?

PubMed

Chen, Taibo; Koene, Ryan; Benditt, David G; Lü, Fei

2013-01-01

Ventricular premature complexes (VPCs) are commonly encountered in patients with congestive heart failure (CHF). Frequent ventricular ectopy can be associated with deterioration of cardiac function and may lead to VPC-induced cardiomyopathy. VPC-induced inter- and/or intraventricular dyssynchrony has been postulated as the main mechanism underlying VPC-induced left ventricular dysfunction. For risk stratification, VPCs in the setting of CHF can not be regarded to be a benign arrhythmia as in an apparently healthy subject. However, any potential survival benefits to be derived from suppression of VPCs or nonsustained ventricular tachycardia in CHF may be offset by the negative inotropic and proarrhythmic effects of antiarrhythmic drugs and may be masked by the risk of death that is already high in this subgroup of patients. β-Blockers are currently considered to be the first-line therapy, with amiodarone as a back-up. Catheter ablation, although invasive and not without procedural risk, avoids the common adverse effects of currently available antiarrhythmic medications. From a standpoint of preventing or reversing left ventricular dysfunction, frequent VPCs should be treated earlier regardless of their site of origin or the presence of associated symptoms, such as palpitations. Catheter ablation may be the preferable approach in selected patients, particularly when β-blocker therapy has been ineffective or not tolerated. Copyright © 2013 Elsevier Inc. All rights reserved.

Is hydrotherapy an appropriate form of exercise for elderly patients with biventricular systolic heart failure?

PubMed Central

Sveälv, Bente Grüner; Täng, Margareta Scharin; Cider, Åsa

2012-01-01

Hydrotherapy (exercise in warm water) is considered to be a safe and beneficial method to use in the rehabilitation of stable heart failure patients, but there is little information on the effect of the increased venous return and enhanced preload in elderly patients with biventricular heart failure. We present a case of an elderly man who was recruited to participate in a hydrotherapy study. We compared echocardiographic data during warm water immersion with land measurements, and observed increases in stroke volume from 32 mL (land) to 42 mL (water), left ventricular ejection fraction from 22% to 24%, left ventricular systolic velocity from 4.8 cm/s to 5.0 cm/s and left atrioventricular plane displacement from 2.1 mm to 2.2 mm. By contrast, right ventricular systolic velocity decreased from 11.2 cm/s to 8.4 cm/s and right atrioventricular plane displacement from 8.1 mm to 4.7 mm. The tricuspid pressure gradient rose from 18 mmHg on land to 50 mmHg during warm water immersion. Thus, although left ventricular systolic function was relatively unaffected during warm water immersion, we observed a decrease in right ventricular function with an augmented right ventricular pressure. We recommend further investigations to observe the cardiac effect of warm water immersion on patients with biventricular systolic heart failure and at risk of elevated right ventricular pressure. PMID:23341846

The Effect of Perioperative Rescue Transesophageal Echocardiography on the Management of Trauma Patients

PubMed Central

Griffee, Matthew J.; Singleton, Andrew; Zimmerman, Joshua M.; Morgan, David E.; Nirula, Raminder

2018-01-01

To evaluate the effect of rescue transesophageal echocardiography (TEE) on the management of trauma patients, we reviewed imaging and charts of unstable trauma patients at a level I trauma center. Critical rescue TEE findings included acute right ventricular failure, stress cardiomyopathy, type B aortic dissection, mediastinal air, and dynamic left ventricular outflow tract obstruction. Left ventricular filling was classified as low (underfilled) in 57% of all cases. Rescue TEE revealed a variety of new diagnoses and led to a change in resuscitation strategy about half of the time. PMID:27301053

[Application of 1% lauromacrogol in the treatment of facial refractory hemangioma and vascular malformations].

PubMed

Wang, Yin; Zhu, Fei; Ning, Jin-long; Li, Xiao-jing; Liu, Ye

2012-11-01

To investigate the clinical effect of 1% lauromacrogol for the treatment of facial refractory hemangioma and vascular malformation. From Sept 2009 to Nov 2011, 55 patients (20 male, 35 female, 1 month to 30 years) with different types of facial hemangiorwa and vascular malformation about 1.0 cm x (0. 5-5.0) cm x 10.0 cm in size, underwent 1% lauromacrogol intratumor injection therapy. Generally, the injection dose, concentration, frequency were determined by the age of the patients, the volume and depth of the lesion. The dose was limited to 10 mg every time. The injection interval is 14 weeks. After followed up for 3-16 months, 41 cases were cured, 9 cases were greatly improved, and 5 were partially improved. Skin necrosis happened in only 2 cases. Lauromacrogol is safe, simple and effective as a sderosing agent for the treatment of facial refractory hemangioma and vascular malformation. It provides a new and alternative way for the treatment of facial refractory hemangioma and vascular malformation.

Post-repolarization refractoriness increases vulnerability to block and initiation of reentrant impulses in heterogeneous infarcted myocardium.

PubMed

Cabo, Candido

2015-10-01

Myocardial infarction causes remodeling of the tissue structure and the density and kinetics of several ion channels in the cell membrane. Heterogeneities in refractory period (ERP) have been shown to occur in the infarct border zone and have been proposed to lead to initiation of arrhythmias. The purpose of this study is to quantify the window of vulnerability (WV) to block and initiation of reentrant impulses in myocardium with ERP heterogeneities using computer simulations. We found that ERP transitions at the border between normal ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP transitions is a combination of electrotonic interaction between NZ and IZ cells and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP heterogeneities between NZ and IZ cells are more vulnerable to block and initiation of reentrant impulses than ERP heterogeneities between NZ cells. The relationship between coupling intervals of premature impulses (V1V2) and coupling intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature impulses the shorter the coupling interval between the premature and first reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship measured during initiation of reentrant impulses in canine infarcted hearts which is direct. (1) ERP transitions at the NZ-IZ border are abrupt as a consequence of PRR; (2) PRR increases the vulnerability to block and initiation of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships measured at ERP heterogeneities in the computer model and in experimental canine infarcts are not consistent. Therefore, it is likely that other mechanisms like micro and/or macro structural heterogeneities also contribute to initiation of reentrant impulses in infarcted hearts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Right ventricular exclusion and univentricular palliation for failed one and a half ventricle repair for Ebstein's anomaly.

PubMed

Sasikumar, Navaneetha; Krishna Manohar, Soman R; Philip, Saji; Cherian, Kottoorathu Mammen; Suresh Kumar, Raghavannair

2013-08-01

A 20 year-old male was diagnosed to have Ebstein's anomaly with severe right ventricular dysfunction. He was taken up for 1.5 ventricle repair. Post procedure, there was difficulty in weaning from cardiopulmonary bypass due to progressive right ventricular dilatation compromising the systemic output. An atrial septectomy did not help. Progressive right ventricular dilatation compressing the left ventricle, demonstrated on transoesophageal echocardiogram, prompted us to perform a right ventricular exclusion and univentricular palliation. The patient was successfully weaned off cardiopulmonary bypass and had a smooth postoperative recovery. Judicious use of right ventricular exclusion and univentricular palliation could be an effective bailout strategy in difficult surgical scenarios in Ebstein's anomaly. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Atrial and ventricular septal changes in ethanol vapour exposed chick embryos.

PubMed

Kamran, Kiran; Khan, Muhammad Yunus; Minhas, Liaqat Ali

2015-03-01

To study the effects of ethanol vapour exposure on development of atrial and ventricular septa of chick embryo. The experimental study was conducted at the College of Physicians and Surgeons, Islamabad, from 2006 to 2007. The experimental and control groups were further divided into three subgroups based on the day of sacrifice. The experimental group was exposed to ethanol vapours produced in a specially-designed vapour chamber and then compared with age-matched controls. There were 90 eggs in each of the two groups. The development of inter-ventricular septum completed at day 7 of development in chick embryo. Ethanol vapour exposure produced a small discontinuity at day 10 of development in a chick embryo which may be labelled as ventricular septal defect since ventricular development is completed by day 7. Interatrial septum formed till day 7 with small perforations which persisted till hatching. Ethanol vapour exposure may lead to ventricular septal defect.

Spatial resolution of pace mapping of idiopathic ventricular tachycardia/ectopy originating in the right ventricular outflow tract.

PubMed

Bogun, Frank; Taj, Majid; Ting, Michael; Kim, Hyungjin Myra; Reich, Stephen; Good, Eric; Jongnarangsin, Krit; Chugh, Aman; Pelosi, Frank; Oral, Hakan; Morady, Fred

2008-03-01

Pace mapping has been used to identify the site of origin of focal ventricular arrhythmias. The spatial resolution of pace mapping has not been adequately quantified using currently available three-dimensional mapping systems. The purpose of this study was to determine the spatial resolution of pace mapping in patients with idiopathic ventricular tachycardia or premature ventricular contractions originating in the right ventricular outflow tract. In 16 patients with idiopathic ventricular tachycardia/ectopy from the right ventricular outflow tract, comparisons and classifications of pace maps were performed by two observers (good pace map: match >10/12 leads; inadequate pace map: match < or =10/12 leads) and a customized MATLAB 6.0 program (assessing correlation coefficient and normalized root mean square of the difference (nRMSd) between test and template signals). With an electroanatomic mapping system, the correlation coefficient of each pace map was correlated with the distance between the pacing site and the effective ablation site. The endocardial area within the 10-ms activation isochrone was measured. The ablation procedure was effective in all patients. Sites with good pace maps had a higher correlation coefficient and lower nRMSd than sites with inadequate pace maps (correlation coefficient: 0.96 +/- 0.03 vs 0.76 +/- 0.18, P <.0001; nRMSd: 0.41 +/- 0.16 vs 0.89 +/- 0.39, P <.0001). Using receiver operating characteristic curves, appropriate cutoff values were >0.94 for correlation coefficient (sensitivity 81%, specificity 89%) and < or =0.54 for nRMSd (sensitivity 76%, specificity 80%). Good pace maps were located a mean of 7.3 +/- 5.0 mm from the effective ablation site and had a mean activation time of -24 +/- 7 ms. However, in 3 (18%) of 16 patients, the best pace map was inadequate at the effective ablation site, with an endocardial activation time at these sites of -25 +/- 12 ms. Pace maps with correlation coefficient > or =0.94 were confined to an area of 1.8 +/- 0.6 cm2. The 10-ms isochrone measured 1.2 +/- 0.7 cm2. The spatial resolution of a good pace map for targeting ventricular tachycardia/ectopy is 1.8 cm2 in the right ventricular outflow tract and therefore is inferior to the spatial resolution of activation mapping as assessed by isochronal activation. In approximately 20% of patients, pace mapping is unreliable in identifying the site of origin, possibly due a deeper site of origin and preferential conduction via fibers connecting the focus to the endocardial surface.

The effect of acute mechanical left ventricular unloading on ovine tricuspid annular size and geometry.

PubMed

Malinowski, Marcin; Wilton, Penny; Khaghani, Asghar; Brown, Michael; Langholz, David; Hooker, Victoria; Eberhart, Lenora; Hooker, Robert L; Timek, Tomasz A

2016-09-01

Left ventricular assist device (LVAD) implantation may alter right ventricular shape and function and lead to tricuspid regurgitation. This in turn has been reported to be a determinant of right ventricular (RV) failure after LVAD implantation, but the effect of mechanical left ventricular (LV) unloading on the tricuspid annulus is unknown. The aim of the study was to provide insight into the effect of LVAD support on tricuspid annular geometry and dynamics that may help to optimize LV unloading with the least deleterious effect on the right-sided geometry. In seven open-chest anaesthetized sheep, nine sonomicrometry crystals were implanted on the right ventricle. Additional nine crystals were implanted around the tricuspid annulus, with one crystal at each commissure defining three separate annular regions: anterior, posterior and septal. Left ventricular unloading was achieved by connecting a cannula in the left atrium and the aorta to a continuous-flow pump. The pump was used for 15 min at a full flow of 3.8 ± 0.3 l/min. Epicardial echocardiography was used to assess the degree of tricuspid insufficiency. Haemodynamic, echocardiographic and sonomicrometry data were collected before and during full unloading. Tricuspid annular area, and the regional and total perimeter were calculated from crystal coordinates, while 3D annular geometry was expressed as the orthogonal distance of each annular crystal to the least squares plane of all annular crystals. There was no significant tricuspid regurgitation observed either before or during LV unloading. Right ventricular free wall to septum diameter increased significantly at end-diastole during unloading from 23.6 ± 5.8 to 26.3 ± 6.5 mm (P = 0.009), but the right ventricular volume, tricuspid annular area and total perimeter did not change from baseline. However, the septal part of the annulus significantly decreased its maximal length (38.6 ± 8.1 to 37.9 ± 8.2 mm, P = 0.03). Annular contraction was not altered. The tricuspid annulus had a complex 3D saddle-shaped geometry that was unaffected during experimental conditions. In healthy sheep hearts, left ventricular unloading increased septal-free wall RV diameter and reduced the length of the septal annulus, without altering the motion or geometry of the tricuspid annulus. Acute left ventricular unloading alone in healthy sheep was not sufficient to significantly perturb tricuspid annular dynamics and result in tricuspid insufficiency. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A new electric method for non-invasive continuous monitoring of stroke volume and ventricular volume-time curves

PubMed Central

2012-01-01

Background In this paper a new non-invasive, operator-free, continuous ventricular stroke volume monitoring device (Hemodynamic Cardiac Profiler, HCP) is presented, that measures the average stroke volume (SV) for each period of 20 seconds, as well as ventricular volume-time curves for each cardiac cycle, using a new electric method (Ventricular Field Recognition) with six independent electrode pairs distributed over the frontal thoracic skin. In contrast to existing non-invasive electric methods, our method does not use the algorithms of impedance or bioreactance cardiography. Instead, our method is based on specific 2D spatial patterns on the thoracic skin, representing the distribution, over the thorax, of changes in the applied current field caused by cardiac volume changes during the cardiac cycle. Since total heart volume variation during the cardiac cycle is a poor indicator for ventricular stroke volume, our HCP separates atrial filling effects from ventricular filling effects, and retrieves the volume changes of only the ventricles. Methods ex-vivo experiments on a post-mortem human heart have been performed to measure the effects of increasing the blood volume inside the ventricles in isolation, leaving the atrial volume invariant (which can not be done in-vivo). These effects have been measured as a specific 2D pattern of voltage changes on the thoracic skin. Furthermore, a working prototype of the HCP has been developed that uses these ex-vivo results in an algorithm to decompose voltage changes, that were measured in-vivo by the HCP on the thoracic skin of a human volunteer, into an atrial component and a ventricular component, in almost real-time (with a delay of maximally 39 seconds). The HCP prototype has been tested in-vivo on 7 human volunteers, using G-suit inflation and deflation to provoke stroke volume changes, and LVot Doppler as a reference technique. Results The ex-vivo measurements showed that ventricular filling caused a pattern over the thorax quite distinct from that of atrial filling. The in-vivo tests of the HCP with LVot Doppler resulted in a Pearson’s correlation of R = 0.892, and Bland-Altman plotting of SV yielded a mean bias of -1.6 ml and 2SD =14.8 ml. Conclusions The results indicate that the HCP was able to track the changes in ventricular stroke volume reliably. Furthermore, the HCP produced ventricular volume-time curves that were consistent with the literature, and may be a diagnostic tool as well. PMID:22900831

Repetitive nonreentrant ventriculoatrial synchrony: An underrecognized cause of pacemaker-related arrhythmia.

PubMed

Sharma, Parikshit S; Kaszala, Karoly; Tan, Alex Y; Koneru, Jayanthi N; Shepard, Richard; Ellenbogen, Kenneth A; Huizar, Jose F

2016-08-01

Similar to endless loop tachycardia (ELT), repetitive nonreentrant ventriculoatrial synchrony (RNRVAS) is a ventriculoatrial (VA) synchrony pacemaker-mediated arrhythmia. RNRVAS was first described in 1990 and can only occur in the presence of retrograde VA conduction and dual-chamber or cardiac resynchronization devices with tracking (P-synchronous ventricular pacing such as DDD, DDDR) or nontracking pacing modes that allow AV-sequential pacing (DDI, DDIR). RNRVAS is promoted by (1) high lower rate limit or any feature that allows rapid pacing, (2) long AV intervals, or (3) long postventricular atrial refractory period (PVARP). In contrast to ELT, RNRVAS is a less well-recognized form of pacemaker-mediated arrhythmia; thus, unlike ELT, there are no specific device algorithms to prevent, recognize, and terminate RNRVAS. However, RNRVAS has been recently shown to occur frequently. We present a series of cases, some of which were found fortuitously. Owing to its clinical implications, we propose that algorithms should be developed to prevent, identify, and terminate RNRVAS. Published by Elsevier Inc.

Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study.

PubMed

Bohm, Philipp; Schneider, Günther; Linneweber, Lutz; Rentzsch, Axel; Krämer, Nadine; Abdul-Khaliq, Hashim; Kindermann, Wilfried; Meyer, Tim; Scharhag, Jürgen

2016-05-17

It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. Thirty-three healthy white competitive elite male master endurance athletes (age range, 30-60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m(2); P<0.001; right ventricular mass/body surface area, 36±7 and 24±5 g/m(2); P<0.001) and indexed left ventricular end-diastolic volume and right ventricular end-diastolic volume (left ventricular end-diastolic volume/body surface area, 104±13 and 69±18 mL/m(2); P<0.001; right ventricular end-diastolic volume/body surface area, 110±22 and 66±16 mL/m(2); P<0.001) were significantly increased in athletes in comparison with control subjects. Right ventricular ejection fraction did not differ between athletes and control subjects (52±8 and 54±6%; P=0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned. © 2016 American Heart Association, Inc.

Major new developments affecting treatment and prognosis in hypertension.

PubMed

Gubner, R S

1990-01-01

Joint studies of the ALIMDA and Society of Actuaries, notably those of 1935, 1959 and 1979, established that there is a progressive rise in cardiovascular mortality with successive increments in blood pressure. This has provided the basis of underwriting. The converse is not true, or at least has not been true until very recently. Drugs that effectively reduce blood pressure have been available for several decades, but reduction and maintenance of blood pressure is still accomplished in only a minority of hypertensives. Long-term trials employing a combination of drugs, i.e., diuretics, vasodilators and reserpine and subsequently beta-blockers, almost without fail have not shown that treatment with these agents significantly reduces heart disease mortality and sudden death. This has been attributed, perhaps without basis, to an unfavorable countering effect of increased lipid levels, aggravating this risk factor, and other undesirable metabolic effect of diuretics, such as hypokalemia and depletion of body magnesium, increasing the propensity to ventricular arrhythmias, hyperglycemia, worsening diabetes, and hyperuricemia. A survey of 674 persons with hypertension seen personally during the period 1985-89, who were under the care of approximately that many physicians, reveals striking changes in drug prescription and use during this brief period that portend a major change in the outlook of hypertension. Two classes of drugs have increased rapidly in popularity: these are the angiotensin-converting enzyme inhibitors (ACE inhibitors) and the calcium blockers. Both classes of drugs effectively lower blood pressure and have minimal side effects with good compliance. They act not only to reduce peripheral vascular resistance, but also locally in the heart muscle to directly cause left ventricular hypertrophy to regress, an effect of great consequence. The drugs used in former trials such as the vasodilators and diuretics have no effect on left ventricular hypertrophy, unlike the ACE inhibitors and calcium antagonists. Left ventricular hypertrophy is the key lesion in hypertension and is only in part due to increased work load imposed by elevated pressure. It is associated with elevated blood pressure, but not closely and occurs independently; ventricular myocytes as well as myocytes of the vasculature being stimulated to growth by angiotensin and calcium, potentiating the effect of norepinephrine. Left ventricular hypertrophy greatly increases the propensity to ventricular arrhythmias and sudden death, and is a prime cause of cardiac mortality and sudden death not only in hypertension, but also in obesity, aging and diabetes, in which conditions left ventricular hypertrophy also is very common.(ABSTRACT TRUNCATED AT 400 WORDS)

Dependence of intramyocardial pressure and coronary flow on ventricular loading and contractility: a model study.

PubMed

Bovendeerd, Peter H M; Borsje, Petra; Arts, Theo; van De Vosse, Frans N

2006-12-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

PubMed

Zhang, Ming; Wang, Ximin; Xie, Xinxing; Wang, Zhongsu; Liu, Xiaoyan; Guan, Juan; Wang, Weizong; Li, Zhan; Wang, Jiangrong; Gao, Mei; Hou, Yinglong

2015-10-01

Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN. © 2015 Wiley Periodicals, Inc.

Importance of the atrial channel for ventricular arrhythmia therapy in the dual chamber implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2000-12-01

Performance of dual chamber implantable cardioverter defibrillator (ICD) systems has been judged based on functioning of the ventricular tachycardia:supraventricular tachycardia (VT:SVT) discrimination criteria and DDD pacing. The purpose of this study was to evaluate the use of dual chamber diagnostics to improve the electrical and antiarrhythmic therapy of ventricular arrhythmias. Information about atrial and ventricular rhythm in relation to ventricular arrhythmia occurrence and therapy was evaluated in 724 spontaneous arrhythmia episodes detected and treated by three types of dual chamber ICDs in 41 patients with structural heart disease. Device programming was based on clinically documented and induced ventricular arrhythmias. In ambulatory patients, sinus tachycardia preceded ventricular arrhythmias more often than in the hospital during exercise testing. The incidence of these VTs could be reduced by increasing the dose of a beta-blocking agent in only two patients. In five patients in whom sinus tachycardia developed after onset of hemodynamic stable VT, propranolol was more effective than Class III antiarrhythmics combined with another beta-blocking agent with regard to the incidence of VT and pace termination. In all but three cases, atrial arrhythmias were present for a longer time before the onset of ventricular arrhythmias. During atrial arrhythmias, fast ventricular rates before the onset of ventricular rate were observed more often than RR irregularities and short-long RR sequences. Dual chamber diagnostics allowed proper interpretation of detection and therapy outcome in patients with different types of ventricular arrhythmia. The advantages of the dual chamber ICD system go further than avoiding the shortcomings of the single chamber system. Information from the atrial chamber allows better device programming and individualization of drug therapy for ventricular arrhythmia.

THE EFFECT OF RIGHT VENTRICULAR PACEMAKER LEAD POSITION ON FUNCTIONAL STATUS IN PATIENTS WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION.

PubMed

Mitov, Vladimir M; Perisic, Zoran; Jolic, Aleksandar; Kostic, Tomislav; Aleksic, Aleksandar; Aleksic, Zeljka

2016-07-01

The study was aimed at assessing the difference between the right ventricle apex versus the right ventricular outflow tract lead position in functional capacity in the patients with the preserved left ventricular ejection fraction after 12 months of pacemaker stimulation. This was a prospective, randomized, follow-up study, which lasted for 12 months. The study sample included 132 consecutive patients who were implanted with permanent anti-bradicardiac pacemaker. Regarding the right ventricular lead position the patients were divided into two groups: the right ventricle apex group consisting of 61 patients with right ventricular apex lead position. The right ventricular outflow tract group included 71 patients with right ventricular outflow tract lead position. Functional capacity was assessed by Minnesota Living With Heart Failure score, New York Heart Association class and Six Minute Walk Test. Left ventricular ejection fraction was assessed by echocardiography. Minnesota Living With Heart Failure score and New York Heart Association class had a statistically significant improvement in both study groups. The patients from right ventricle apex group walked 20.95% (p=O.03) more in comparison to starting values. The patients from right ventricular outflow tract group walked only 13.63% (p=0.09) longer distance than the startingoneConclusion. Analysis of tests of functional status New York Heart Association class and Minnesota Living With Heart Failure questionnaire showed an even improvement in the right ventricle apex and right ventricular outflow tract groups. Analysis of 6 minute walk test showed that only the patients with the preserved left ventricular ejection fraction from the right ventricle apex group had a significant improvement after 12 months of pacemaker stimulation..

Contribution of beta 1- and beta 2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (-)-atenolol.

PubMed Central

Lemoine, H.; Schönell, H.; Kaumann, A. J.

1988-01-01

1. (-)-Atenolol was used as a tool to assess the function of beta 1- and beta 2-adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for beta-adrenoceptor labelling with [3H]-(-)-bupranolol and adenylate cyclase assays. 2. The positive inotropic effects of (-)-noradrenaline were antagonized to a similar extent by (-)-atenolol in atrial and ventricular preparations. (-)-Atenolol consistently antagonized the effects of (-)-adrenaline to a lesser extent than those of (-)-noradrenaline in atrial preparations. In ventricular preparations (-)-atenolol antagonized the effects of low concentrations of (-)-adrenaline to a lesser extent than those of high concentrations. 3. pKB values (M) of (-)-atenolol, estimated with non-linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for beta 1-adrenoceptors and 6.0 for beta 2-adrenoceptors. 4. (-)-Atenolol inhibited the binding of [3H]-(-)-bupranolol to ventricular beta 1-adrenoceptors with a pKD (M) of 5.9 and to ventricular beta 2-adrenoceptors with a pKD of 4.6. 5. (-)-Atenolol inhibited the catecholamine-induced adenylate cyclase stimulation in the atrium and ventricle with pKB values of 5.8-6.4 for beta 1- and pKB values of 4.7-5.7 for beta 2-adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (-)-atenolol inherent to membrane preparations. 6. beta 1-Adrenoceptors mediate the maximum positive inotropic effects of (-)-noradrenaline in both the atrium and ventricle of man. beta 2-Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (-)-adrenaline in atrium. In contrast, ventricular beta 2-adrenoceptors mediated only submaximal effects of (-)-adrenaline. PMID:2851354

Evaluation of effect of atorvastatin on left ventricular systolic function in rats with myocardial infarction via 2D-STI technique.

PubMed

Hua, Yan; Xie, Manying; Yin, Jiabao; Wang, Yu; Gan, Ling; Sang, Ming; Sun, Xiaodong; Li, Mingyang; Liu, Shanjun; Xu, Jinzhi

2018-05-01

This report aims to evaluate the effect of atorvastatin (Ator) on left ventricular systolic function in myocardial infarction (MI) rats. Forty healthy adult Sprague-Dawley rats were randomly divided into four groups: Ator group, MI group, sham-operation group and normal group. The left anterior descending coronary arteries were ligated to establish the MI model; after modeling, the Ator group was treated with Ator for 4 consecutive weeks. The echocardiographic detection was performed; the left ventricular myocardial systolic peak velocities, strain and strain rates were analyzed using the 2D-STI technique. After 4 weeks, myocardial tissues were taken from all rats and received the pathological examination. Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in Ator group and MI group were increased after operation, but left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were decreased; myocardial function were decreased significantly (p<0.05). After Ator treatment, myocardial function at the 3rd and 4th week after operation increased significantly (p<0.05). After Ator treatment, LVEDD and LVESD decreased while LVEF and LVFS increased in Ator group at the 3rd and 4th week after operation compared with MI group (p<0.05). At the 4th week after operation, LVEDD and LVESD in Ator group were decreased compared with those at the 1st and 2nd week after operation, but LVEF and LVFS were increased compared with those at the 1st, 2nd and 3rd week after operation (p<0.05). Pathological examination showed that necrosis and fibrosis of myocardial cells and inflammatory reaction were obvious in MI group. The inflammatory reaction of myocardial cells and myocardial fibrosis were lighter in Ator group. Ator can effectively improve the left ventricular systolic function in MI rats, which could be related to the reduction of response to inflammation and fibrosis.

The Influence of refractoriness upon comprehension of non-verbal auditory stimuli.

PubMed

Crutch, Sebastian J; Warrington, Elizabeth K

2008-01-01

An investigation of non-verbal auditory comprehension in two patients with global aphasia following stroke is reported. The primary aim of the investigation was to establish whether refractory access disorders can affect non-verbal input modalities. All previous reports of refractoriness, a cognitive syndrome characterized by response inconsistency, sensitivity to temporal factors and insensitivity to item frequency, have involved comprehension tasks which have a verbal component. Two main experiments are described. The first consists of a novel sound-to-picture and sound-to-word matching task in which comprehension of environmental sounds is probed under conditions of semantic relatedness and semantic unrelatedness. In addition to the two stroke patients, the performance of a group of 10 control patients with non-vascular pathology is reported, along with evidence of semantic relatedness effects in sound comprehension. The second experiment examines environmental sound comprehension within a repetitive probing paradigm which affords assessment of the effects of semantic relatedness, response consistency and presentation rate. It is demonstrated that the two stroke patients show a significant increase in error rate across multiple probes of the same set of sound stimuli, indicating the presence of refractoriness within this non-verbal domain. The implications of the results are discussed with reference to our current understanding of the mechanisms of refractoriness.

Analysis of left ventricular mass in untreated men and in men treated with agalsidase-β: data from the Fabry Registry.

PubMed

Germain, Dominique P; Weidemann, Frank; Abiose, Ademola; Patel, Manesh R; Cizmarik, Marta; Cole, J Alexander; Beitner-Johnson, Dana; Benistan, Karelle; Cabrera, Gustavo; Charrow, Joel; Kantola, Ilkka; Linhart, Ales; Nicholls, Kathy; Niemann, Markus; Scott, C Ronald; Sims, Katherine; Waldek, Stephen; Warnock, David G; Strotmann, Jörg

2013-12-01

The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-β (recombinant human α-galactosidase A) on left ventricular hypertrophy. Longitudinal Fabry Registry data were analyzed from 115 men treated with agalsidase-β (1 mg/kg/2 weeks) and 48 untreated men. Measurements included baseline left-ventricular mass and at least one additional left-ventricular mass assessment over ≥ 2 years. Patients were grouped into quartiles, based on left-ventricular mass slopes. Multivariate logistic regression analyses identified factors associated with left ventricular hypertrophy progression. For men in whom treatment was initiated at the age of 18 to <30 years, mean left ventricular mass slope was -3.6 g/year (n = 31) compared with +9.5 g/year in untreated men of that age (n = 15) (P < 0.0001). Untreated men had a 3.4-fold higher risk of having faster increases in left-ventricular mass compared with treated men (odds ratio: 3.43; 95% confidence interval: 1.05-11.22; P = 0.0415). A baseline age of ≥ 40 years was also associated with left--ventricular hypertrophy progression (odds ratio: 5.03; 95% confidence interval: 1.03-24.49; P = 0.0457) compared with men younger than 30 years. Agalsidase-β treatment for ≥2 years may improve or stabilize left-ventricular mass in men with Fabry disease. Further investigations may determine whether early intervention and stabilization of LVM are correlated with clinical outcomes.

[Pharmacologic action profile of crataegus extract in comparison to epinephrine, amirinone, milrinone and digoxin in the isolated perfused guinea pig heart].

PubMed

Joseph, G; Zhao, Y; Klaus, W

1995-12-01

Using isolated perfused guinea pig hearts experiments were performed to investigate the influence of crataegus extract LI 132 (Faros 300, CRA) in comparison to other inotropic drugs--epinephrine (adrenaline, ADR), amrinone (AM), milrinone (MIL) and digoxin (DIG)--on different functional parameters, with special emphasis on the effective refractory period of the myocardium. The simultaneous registration of appropriate parameters allowed to relate the effect on the refractory period to the inotropic, chronotropic, dromotropic and coronary actions of these compounds at each concentration level. All substances--with the exception of CRA--shortened the effective refractory period concentration-dependently besides their known other functional effects (max.: 1 x 10(-5) mol/l ADR by 38%, 7 x 10(-7) mol/l DIG by 26%, 1 x 10(-4) mol/l MIL by 13% and 5 x 10(-4) mol/l AM by 1.6%). Related to the positive inotropy the shortening was most effective under MIL (1.32 ms/mN), followed by AM (0.65 ms/mN), DIG (0.40 ms/mN) and ADR (0.28 ms/mN). On the contrary, CRA produced a prolongation of the effective refractory period by maximally 10% resp. by 2.54 ms/mN. Thus, the pharmacologic profile of CRA differs from that of other inotropic compounds mainly in this parameter (with potentially reduced arrhythmogenic risk).

Alternative right ventricular pacing sites.

PubMed

Łuciuk, Dariusz; Łuciuk, Marek; Gajek, Jacek

2015-01-01

The main adverse effect of chronic stimulation is stimulation-induced heart failure in case of ventricular contraction dyssynchrony. Because of this fact, new techniques of stimulation should be considered to optimize electrotherapy. One of these methods is pacing from alternative right ventricular sites. The purpose of this article is to review currently accumulated data about alternative sites of cardiac pacing. Medline and PubMed bases were used to search English and Polish reports published recently. Recent studies report a deleterious effect of long term apical pacing. It is suggested that permanent apical stimulation, by omitting physiological conduction pattern with His-Purkinie network, may lead to electrical and mechanical dyssynchrony of heart muscle contraction. In the long term this pathological situation can lead to severe heart failure and death. Because of this, scientists began to search for some alternative sites of cardiac pacing to reduce the deleterious effect of stimulation. Based on current accumulated data, it is suggested that the right ventricular outflow tract, right ventricular septum, direct His-bundle or biventricular pacing are better alternatives due to more physiological electrical impulse propagation within the heart and the reduction of the dyssynchrony effect. These methods should preserve a better left ventricular function and prevent the development of heart failure in permanent paced patients. As there is still not enough, long-term, randomized, prospective, cross-over and multicenter studies, further research is required to validate the benefits of using this kind of therapy. The article should pay attention to new sites of cardiac stimulation as a better and safer method of treatment.

Apatinib in refractory radiation-induced brain edema: A case report.

PubMed

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-11-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Two patients were both diagnosed as refractory radiation-induced brain edema. Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

[Complex ventricular arrhythmias and carvedilol: efficacy in hemodialyzed uremic patients].

PubMed

Cice, G; Tagliamonte, E; Ferrara, L; Di Benedetto, A; Iacono, A

1998-06-01

Carvedilol has been shown to be effective in systemic hypertension and coronary artery disease in patients with end-stage renal disease, on maintenance hemodialysis. The aim of our study was to assess the effects of carvedilol on ventricular arrhythmias in these patients. Ninety-eight uremic patients maintained on hemodialysis, with complex ventricular arrhythmias (class III, IV and V of Lown's classification), not only during dialysis, were included in the study. They were divided into two groups, with mild-to-moderate hypertension or coronary artery disease. The efficacy and safety of carvedilol (50 mg/day) was compared to placebo in a 6-week randomized, double-blind study. Carvedilol significantly reduced, in both hypertensive and ischemic patients, total ventricular premature contractions (82.7 +/- 11.3 vs 358.1 +/- 73.9, p < 0.001; 88.3 +/- 24.4 vs 369.9 +/- 77.8, p < 0.001), repetitive ventricular premature contractions (1.3 +/- 1.3 vs 6.3 +/- 3.5, p < 0.001; 1.2 +/- 0.7 vs 6.9 +/- 2.6, p < 0.001) and episodes of ventricular tachycardia (1.1 +/- 1.2 vs 11.8 +/- 7.5, p < 0.001; 1.4 +/- 1.2 vs 14.0 +/- 8.3, p < 0.001). In placebo-treated patients, instead, these parameters were not significantly changed (329.1 +/- 76.5 vs 361.7 +/- 71.7, NS, and 324.6 +/- 79.7 vs 359.3 +/- 58.1, NS; 6.2 +/- 3.7 vs 7.3 +/- 3.7, NS, and 4.9 +/- 2.2 vs 6.1 +/- 3.2, NS; 9.8 +/- 6.3 vs 13.3 +/- 8.0, NS, and 9.0 +/- 6.2 vs 12.4 +/- 7.8, NS). Carvedilol confirmed a significant effect on myocardial ischemia and systemic hypertension. No significant side effects were reported. Ventricular arrhythmias are frequent in patients with end-stage renal disease maintained on hemodialysis. They are often due to an underlying cardiac disease, namely systemic hypertension with left ventricular hypertrophy and coronary artery disease. The results of our study show that the antiarrhythmic effect of carvedilol is linked, at least partly, to an improvement of the underlying cardiac disease. Uremic patients have a chronic increase in adrenergic tone, with a direct correlation between norepinephrine plasmatic concentration and frequence of premature ventricular contractions. Beta-blockers are very important in these patients because of their modulation on the adrenergic system. They also reduce potassium flow, from extracellular to intracellular fluid. Therefore carvedilol can affect the sudden hypokalemia occurring in the first phase of hemodialysis treatment, that may be an important cause of intradialytic arrhythmias.

Effect of Rice Husk Ash Insulation Powder on the Reoxidation Behavior of Molten Steel in Continuous Casting Tundish

NASA Astrophysics Data System (ADS)

Kim, Tae Sung; Chung, Yongsug; Holappa, Lauri; Park, Joo Hyun

2017-06-01

Rice husk ash (RHA) has been widely used as an insulation powder in steel casting tundish. Its effect on the reoxidation of molten steel in tundish as well as on the corrosion of magnesia refractory was investigated. The reoxidation of the steel, indicated by an oxygen pickup, was progressed by increasing the ratio of RHA to the sum of RHA and carryover ladle slag ( R ratio) greater than about 0.2. The increase of the silica activity in the slag layer promoted the self-dissociation of SiO2 from the slag layer into the molten steel, resulting in the silicon and oxygen pickup as the R ratio increased. The total number of reoxidation inclusions dramatically increased and the relative fraction of Al2O3-rich inclusions increased by increasing the R ratio. Hence, the reoxidation of molten steel in tundish might become more serious due to the formation of alumina-rich inclusions as the casting sequence increases. MgO in the refractory directly dissolved into the molten slag layer without forming any intermediate compound layer ( e.g., spinel), which is a completely different situation from the general slag-refractory interfacial reaction. A flow was possibly induced by the bursting of gas bubbles at the ash-slag (-refractory) interface, since the silica in the RHA powder continuously dissolved into the molten slag pool. Thus, the RHA insulation powder has a negative effect on the corrosion of MgO refractory.

[Results of fistulizing and Ahmed valve surgery for treatment of refractory glaucoma].

PubMed

Bikbov, M M; Babushkin, A E; Chaĭka, O V; Orenburkina, O I; Matiukhina, E N

2014-01-01

Surgical results of 76 patients (76 eyes) aged 25-79 years with secondary refractory glaucoma were analyzed. The best hypotensive effect and visual functions integrity were achieved with Ahmed valve implantation (86.7% and 83.3% of cases respectively); after conventional fistulizing surgery the hypotensive effect was observed in 45.5%, noncompromised vision--in 54.5% of cases. Tunnel trabeculectomy with iridocycloretraction led to normalization of intraocular pressure and stabilization of visual functions in 81.3% and 68.8% of cases respectively and thus can be considered as an alternative to fistulizing surgery in patients with secondary refractory glaucoma. Uveal glaucoma is a relative contraindication to Ahmed valve implantation, while neovascular glaucoma is that to tunnel trabeculectomy with iridocycloretraction.

Dyssynchronous Ventricular Activation in Asymptomatic Wolff-Parkinson-White Syndrome: A Risk Factor for Development of Dilated Cardiomyopathy

PubMed Central

Udink ten Cate, Floris EA; Wiesner, Nathalie; Trieschmann, Uwe; Khalil, Markus; Sreeram, Narayanswami

2010-01-01

A subset of children and adults with Wolff-Parkinson-White (WPW) syndrome develop dilated cardiomyopathy (DCM). Although DCM may occur in symptomatic WPW patients with sustained tachyarrhythmias, emerging evidence suggests that significant left ventricular dysfunction may arise in WPW in the absence of incessant tachyarrhythmias. An invariable electrophysiological feature in this non-tachyarrhythmia type of DCM is the presence of a right-sided septal or paraseptal accessory pathway. It is thought that premature ventricular activation over these accessory pathways induces septal wall motion abnormalities and ventricular dyssynchrony. LV dyssynchrony induces cellular and structural ventricular remodelling, which may have detrimental effects on cardiac performance. This review summarizes recent evidence for development of DCM in asymptomatic patients with WPW, discusses its pathogenesis, clinical presentation, management and treatment. The prognosis of accessory pathway-induced DCM is excellent. LV dysfunction reverses following catheter ablation of the accessory pathway, suggesting an association between DCM and ventricular preexcitation. Accessory pathway-induced DCM should be suspected in all patients presenting with heart failure and overt ventricular preexcitation, in whom no cause for their DCM can be found. PMID:20552060

Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

NASA Astrophysics Data System (ADS)

Gulothungan, G.; Malathi, R.

2018-04-01

Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.

Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

PubMed

Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

2008-12-01

To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Effects of 4 month exercise on left ventricular remodeling and autonomic nervous system in hypertensive patients.

PubMed

Zheng, Huan; Xie, Nanzi; Xu, Huifeng; Huang, Junling; Xie, Xiaoyun; Luo, Ming

2016-03-01

We sought to investigate effects of supervised exercise training on left ventricular remodeling, left ventricular function and autonomic nervous system of hypertensive patients without medication. Fifty borderline and mildly hypertensive patients were enrolled and randomly divided into 2 groups (25 in each). Exercise group received a 4 months' exercise program, prescribed according to their first cardiopulmonary exercise tests, while the control group received routine dietary recommendation. All patients underwent noradrenalin assay, cardiopulmonary exercise tests and echocardiographic studies at enrollment and 4 month follow-up. At baseline no statistically difference between the two groups were observed in clinical characteristics, echographic variants or cardiopulmonary test index. Four months later, exercise group showed higher values of VO2peak, Powermax (max workload), AT (anaerobic threshold), VO2AT (VO2 at anaerobic threshold), tAT (time from beginning to anaerobic threshold) and heart rate recovery compared to the control group (P<0.05). Additionally, systolic/diastolic blood pressure decreased significantly in the exercise group compared to the control group (P<0.05). Moreover, there was significant reduction in left ventricular mass index in the exercise group (P<0.01), and there was also an inverse correlation between changes in left ventricular mass index and heart rate recovery (r=-0.52, P<0.01). Four-month exercise training in borderline and mildly hypertensive patients not only decreased their blood pressure levels, but also induced an improvement of exercise capability, left ventricular remodeling and heart rate recovery. Heart rate recovery improvement was significantly associated with decrease of left ventricular mass index, which indicated that favorable adjustment in autonomic nervous system of exercise training might be an important pathway to reverse left ventricular remodeling.

Percutaneous extracorporeal life support for patients in therapy refractory cardiogenic shock: initial results of an interdisciplinary team.

PubMed

Guenther, Sabina; Theiss, Hans D; Fischer, Matthias; Sattler, Stefan; Peterss, Sven; Born, Frank; Pichlmaier, Maximilian; Massberg, Steffen; Hagl, Christian; Khaladj, Nawid

2014-03-01

Therapy refractory cardiogenic shock is associated with dismal outcome. Percutaneous implantation of an extracorporeal life support (ECLS) system achieves immediate cardiopulmonary stabilization, sufficient end-organ perfusion and reduction of subsequent multiorgan failure (MOF). Forty-one patients undergoing percutaneous ECLS implantation for cardiogenic shock from February 2012 until August 2013 were retrospectively analysed. Mean age was 52 ± 13 years, 6 (15%) were female. Mean pH values obtained before ECLS implantation were 7.15 ± 0.24, mean lactate concentration was 11.7 ± 6.4 mmol/l. Levels obtained 6 h after ECLS implantation were 7.30 ± 0.14 and 8.7 ± 5.0 mmol/l, respectively. In 23 patients (56%) cardiogenic shock resulted from an acute coronary syndrome in 13 (32%) from cardiomyopathy, in 5 (12%) from other causes. Twenty-seven (66%) had been resuscitated, in 14 (34%) implantation was performed under ongoing cardiopulmonary resuscitation (CPR). Of note, 97% of the acute coronary syndrome patients underwent percutaneous coronary intervention (PCI) either before ECLS implantation or under ECLS support. Extracorporeal life support implantation was performed on scene (Emergency Department, Cath Lab, Intensive Care Unit) by a senior cardiac surgeon and a trained perfusionist, in 8 cases (20%) in the referring hospital. Thirty-day mortality was 51% [21 patients, due to MOF (n = 14), cerebral complications (n = 6) and heart failure (n = 1)]. Logistic regression analysis identified 6-h pH values as an independent risk factor of 30-day mortality (P < 0.001, OR = 0.000, 95% CI 0.000-0.042). Neither CPR nor implantation under ongoing CPR resulted in significant differences. In 26 cases (63%), the ECLS system could be explanted, after mean support of 169 ± 67 h. Seven of these patients received cardiac surgery [ventricular assist device implantation (n = 4), heart transplantation (n = 1), other procedures (n = 2)]. Due to the evolution of transportable ECLS systems and percutaneous techniques implantation on scene is feasible. Extracorporeal life support may serve as a bridge-to-decision and bridge-to-treatment device. Neurological evaluation before ventricular assist device implantation and PCI under stable conditions are possible. Despite substantial mortality, ECLS implantation in selected patients by an experienced team offers additional support to conventional therapy as well as CPR and allows survival in patients that otherwise most likely would have died. This concept has to be implemented in cardiac survival networks in the future.

[The effect of hypothyroidism on cardiac function in dogs].

PubMed

Stephan, I; Nolte, I; Hoppen, H O

2003-06-01

The thyroid hormones have direct and indirect effects on the heart. So it is possible that depression of left ventricular function is associated with hypothyroidism. This publication describes cardiac findings (auscultation, electrocardiography, echocardiography) in ten hypothyroid dogs. Low heart rates, reduced R-amplitudes and bradycardic arrhythmias (first and second-degree AV block) were found on the electrocardiogram before treatment. On the echocardiograms most of the dogs showed reduced contractillity and reduced left ventricular wall thickness. Seven dogs were reexamined after levothyroxine supplementation. Effects of treatment were increased heart rates and R-amplitudes as well as disappearance of the bradycardic arrhythmias in electrocardiographic examination. The echocardiographic examination showed increased contractility and increased left ventricular wall thickness.

Loxoprofen sodium treatment for elderly men with refractory nocturia: effect on night-time urine production.

PubMed

Okada, Shinsuke; Watanabe, Hideki; Kojima, Yoshiyuki; Yanai, Yoshimasa; Sasaki, Shoichi; Kohri, Kenjiro

2008-05-01

We evaluated the efficacy of loxoprofen sodium for refractory nocturia. Twelve men (mean age, 75.1 +/- 5.7) with nocturia were enrolled in this study. All patients received 60 mg loxoprofen sodium prior to sleeping at night for 14 days. Nine of 12 patients (75%) felt more satisfaction than previous treatments. Patients were grouped into a loxoprofen sodium-effective (n = 7) and ineffective groups (n = 5) based on the results of the frequency-volume chart. In the effective group, interestingly, night-time urine volume showed significant reduction (P < 0.05). On the other hand, the average single voided volume at night and 24-h urine volume showed no significant change. There was a statistically significant difference in the night-time urine volume after treatment between groups (P < 0.01). Loxoprofen sodium is an effective treatment for some patients with refractory nocturia. The main effect mechanism of loxoprofen sodium may involve the reduction of night-time urine production.

Spinal cord activation differentially modulates ischaemic electrical responses to different stressors in canine ventricles.

PubMed

Cardinal, René; Ardell, Jeffrey L; Linderoth, Bengt; Vermeulen, Michel; Foreman, Robert D; Armour, J Andrew

2004-03-31

Spinal cord stimulation (SCS) represents an acceptable treatment modality for patients with chronic angina pectoris refractory to standard therapy, but its mechanism of action remains unclear. To develop an experimental paradigm to study this issue, ameroid (AM) constrictors were implanted around the left circumflex coronary artery (LCx) in canines. Six weeks later, unipolar electrograms were recorded from 191 sites in the LCx territory in the open-chest, anesthetized state under basal pacing at 150 beats/min. We investigated the effect of SCS on ST segment displacements induced in the collateral-dependent myocardium in response to two stressors: (i) transient bouts of rapid ventricular pacing (TRP: 240/min for 1 min) and (ii) angiotensin II administered to right atrial neurons via their coronary artery blood supply. ST segment responses to TRP consisted of ST segment elevation in central areas of the LCx territory and ST depression at more peripheral areas. Such responses were unchanged when TRP was applied under SCS. Shortening of repolarization intervals in the metabolically compromised myocardium in response to TRP was also unaffected by SCS. In contrast, ST segment responses to intracoronary angiotensin II, which consisted of increased ST elevation, were attenuated by SCS in 6/8 preparations. The modulator effects of SCS were greatest at sites at which the greatest responses to angiotensin II occurred in the absence of SCS. These data indicate that spinal cord stimulation may attenuate the deleterious effects that stressors exert on the myocardium with reduced coronary reserve, particularly stressors associated with chemical activation of the intrinsic cardiac nervous system. Copyright 2004 Elsevier B.V.

Assessments of the QT/QRS restitution in perfused guinea-pig heart can discriminate safe and arrhythmogenic drugs.

PubMed

Osadchii, Oleg E

2017-09-01

Drug-induced arrhythmia remains a matter of serious clinical concern, partly due to low prognostic value of currently available arrhythmic biomarkers. This study examined whether arrhythmogenic risks can be predicted through assessments of the rate adaptation of QT interval, ventricular effective refractory period (ERP), or the QT/QRS ratio, in perfused guinea-pig hearts. When the maximum restitution slope was taken as a metric of proarrhythmia, neither QT interval nor ERP measurements at progressively increased pacing rates were found to fully discriminate arrhythmogenic drugs (dofetilide, quinidine, flecainide, and procainamide) from those recognized as safe antiarrhythmics (lidocaine and mexiletine). For example, the slope of QT restitution was increased by dofetilide and quinidine, but remained unchanged by flecainide, procainamide, lidocaine, and mexiletine. With ERP rate adaptation, even though the restitution slope was increased by dofetilide, all class I agents reduced the slope value independently of their safety profile. The QRS measurements revealed variable drug effects, ranging from significant use-dependent conduction slowing (flecainide, quinidine, and procainamide) to only modest increase in QRS (lidocaine and mexiletine), or no change at all (dofetilide). However, with the QT/QRS rate adaptation, the restitution slope was significantly increased by all agents which have been reported to produce proarrhythmic effects (dofetilide, quinidine, flecainide, and procainamide), but not changed by lidocaine and mexiletine. These findings suggest that the slope of the QT/QRS rate adaptation can be considered as a novel electrophysiological biomarker in predicting potential arrhythmic risks associated with pharmacotherapy in cardiac patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the effects of continuous and pulsatile left ventricular-assist devices on ventricular unloading using a cardiac electromechanics model

PubMed Central

Lim, Ki Moo; Constantino, Jason; Gurev, Viatcheslav; Zhu, Renjun; Trayanova, Natalia A.

2012-01-01

Left ventricular-assist devices (LVADs) are used to supply blood to the body of patients with heart failure. Pressure unloading is greater for counter-pulsating LVADs than for continuous LVADs. However, several clinical trials have demonstrated that myocardial recovery is similar for both types of LVAD. This study examined the contractile energy consumption of the myocardium with continuous and counter-pulsating LVAD support to ascertain the effect of the different LVADs on myocardial recovery. We used a three-dimensional electromechanical model of canine ventricles, with models of the circulatory system and an LVAD. We compared the left ventricular peak pressure (LVPP) and contractile ATP consumption between pulsatile and continuous LVADs. With the continuous and counter-pulsating LVAD, the LVPP decreased to 46 and 10%, respectively, and contractile ATP consumption decreased to 60 and 50%. The small difference between the contractile ATP consumption of these two types of LVAD may explain the comparable effects of the two types on myocardial recovery. PMID:22076841

Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-20

B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; Richter Syndrome

Computerized mapping of fibrillation in normal ventricular myocardium

NASA Astrophysics Data System (ADS)

Chen, Peng-Sheng; Garfinkel, Alan; Weiss, James N.; Karagueuzian, Hrayr S.

1998-03-01

It is well known that the ability to fibrillate is intrinsic to a normal ventricle that exceeds a critical mass. The questions we address are how is ventricular fibrillation (VF) initiated and perpetuated in normal myocardium, and why is VF not seen more often in the general population if all ventricles have the ability to fibrillate. To study the mechanisms of VF, we used computerized mapping techniques with up to 512 channels of simultaneous multisite recordings for data acquisition. The data were then processed for dynamic display of the activation patterns and for mathematical analyses of the activation intervals. The results show that in normal ventricles, VF can be initiated by a single strong premature stimulus given during the vulnerable period of the cardiac cycle. The initial activations form a figure-eight pattern. Afterward, VF will perpetuate itself without any outside help. The self-perpetuation itself is due to at least two factors. One is that single wave fronts spontaneously break up into two or more wavelets. The second is that when two wavelets intersect perpendicular to each other, the second wavelet is broken by the residual refractoriness left over from the first wavelet. Mathematical analyses of the patterns of activation during VF revealed that VF is a form of chaos, and that transition from ventricular tachycardia (VT) to VF occurs via the quasiperiodic route. In separate experiments, we found that we can convert VF to VT by tissue size reduction. The physiological mechanism associated with the latter transition appears to be the reduction of the number of reentrant wave fronts and wandering wavelets. Based on these findings, we propose that the reentrant wave fronts and the wandering wavelets serve as the physiological equivalent of coupled oscillators. A minimal number of oscillators is needed for VF to perpetuate itself, and to generate chaotic dynamics; hence a critical mass is required to perpetuate VF. We conclude that VF in normal myocardium is a form of reentrant cardiac arrhythmia. A strong electrical stimulus initiates single or dual reentrant wave fronts that break up into multiple wavelets. Sometimes short-lived reentry is also generated during the course of VF. These organized reentrant and broken wavelets serve as coupled oscillators that perpetuate VF and maintain chaos. Although the ability to support these oscillators exists in a normal ventricle, the triggers required to generate them are nonexistent in the normal heart. Therefore, VF and sudden death do not happen to most people with normal ventricular myocardium.

Effect of Loss of Heart Rate Variability on T-Wave Heterogeneity and QT Variability in Heart Failure Patients: Implications in Ventricular Arrhythmogenesis.

PubMed

Nayyar, Sachin; Hasan, Muhammad A; Roberts-Thomson, Kurt C; Sullivan, Thomas; Baumert, Mathias

2017-06-01

Heart rate variability (HRV) modulates dynamics of ventricular repolarization. A diminishing value of HRV is associated with increased vulnerability to life-threatening ventricular arrhythmias, however the causal relationship is not well-defined. We evaluated if fixed-rate atrial pacing that abolishes the effect of physiological HRV, will alter ventricular repolarization wavefronts and is relevant to ventricular arrhythmogenesis. The study was performed in 16 subjects: 8 heart failure patients with spontaneous ventricular tachycardia [HFVT], and 8 subjects with structurally normal hearts (H Norm ). The T-wave heterogeneity descriptors [total cosine angle between QRS and T-wave loop vectors (TCRT, negative value corresponds to large difference in the 2 loops), T-wave morphology dispersion, T-wave loop dispersion] and QT intervals were analyzed in a beat-to-beat manner on 3-min records of 12-lead surface ECG at baseline and during atrial pacing at 80 and 100 bpm. The global T-wave heterogeneity was expressed as mean values of each of the T-wave morphology descriptors and variability in QT intervals (QTV) as standard deviation of QT intervals. Baseline T-wave morphology dispersion and QTV were higher in HFVT compared to H Norm subjects (p ≤ 0.02). While group differences in T-wave morphology dispersion and T-wave loop dispersion remained unaltered with atrial pacing, TCRT tended to fall more in HFVT patients compared to H Norm subjects (interaction p value = 0.086). Atrial pacing failed to reduce QTV in both groups, however group differences were augmented (p < 0.0001). Atrial pacing and consequent loss of HRV appears to introduce unfavorable changes in ventricular repolarization in HFVT subjects. It widens the spatial relationship between wavefronts of ventricular depolarization and repolarization. This may partly explain the concerning relation between poorer HRV and the risk of ventricular arrhythmias.

Synergistic Effect of Nitrogen and Refractory Material on TiN Formation and Equiaxed Grain Structure of Ferritic Stainless Steel

NASA Astrophysics Data System (ADS)

Lee, Mun Hyung; Park, Joo Hyun

2018-06-01

The effect of nitrogen content on the formation of an equiaxed solidification structure of Fe-16Cr steel was investigated. Moreover, two different kinds of refractory materials, i.e., alumina and magnesia, were employed to control the type of oxide inclusion. The characteristics of TiN(-oxide) inclusions were quantitatively analyzed in both molten steel and solidified samples. When the melting was carried out in the alumina refractory, the grain size continuously decreased with increasing nitrogen content. However, a minimum grain size was observed at a specific nitrogen content (approx. 150 ppm) when the steel was melted in the magnesia refractory. Most of the single TiN particles had a cuboidal shape and fine irregularly shaped particles were located along the grain boundary due to the microsegregation of Ti at the grain boundary during solidification. The type of TiN-oxide hybrid inclusion was strongly affected by the refractory material where Al2O3-TiN and MgAl2O4-TiN hybrid-type inclusions were obtained in the alumina and magnesia refractory experiments, respectively. The formation of oxide inclusions was well predicted by thermochemical computations and it was commonly found that oxide particles were initially formed, followed by the nucleation and growth of TiN. When the nitrogen content increased, the number density of TiN linearly increased in the alumina refractory experiments. However, the number of TiN exhibits a maximum at about [N] = 150 ppm, at which a minimum grain size was obtained in the magnesia refractory experiments. Therefore, the larger the number density of TiN, the smaller the primary grain size after solidification. The number density of TiN in the steel melted in the magnesia refractory was greater than that in the steel melted in the alumina refractory at given Ti and N contents, which was due to the lower planar lattice disregistry of MgAl2O4-TiN interface rather than that of Al2O3-TiN interface. When Δ T TiN (= difference between the TiN precipitation temperature and the liquidus of the steel) was 20 K to 40 K, the number density of effective TiN was maximized and thus, the grain size was minimized after solidification. Finally, although most of the TiN particles were smaller than 1 μm in the molten steel samples irrespective of the nitrogen content, TiN particles larger than 10 μm were observed in the solidified samples when the nitrogen content was greater than 150 ppm. The growth of TiN particles during melting and solidification was well predicted by the combinatorial simulation of the `Ostwald ripening model' based on the Lifshitz-Slyozov-Wagner theory in conjunction with the `Diffusion controlled model' using Ohnaka's microsegregation equation.

Synergistic Effect of Nitrogen and Refractory Material on TiN Formation and Equiaxed Grain Structure of Ferritic Stainless Steel

NASA Astrophysics Data System (ADS)

Lee, Mun Hyung; Park, Joo Hyun

2018-03-01

The effect of nitrogen content on the formation of an equiaxed solidification structure of Fe-16Cr steel was investigated. Moreover, two different kinds of refractory materials, i.e., alumina and magnesia, were employed to control the type of oxide inclusion. The characteristics of TiN(-oxide) inclusions were quantitatively analyzed in both molten steel and solidified samples. When the melting was carried out in the alumina refractory, the grain size continuously decreased with increasing nitrogen content. However, a minimum grain size was observed at a specific nitrogen content (approx. 150 ppm) when the steel was melted in the magnesia refractory. Most of the single TiN particles had a cuboidal shape and fine irregularly shaped particles were located along the grain boundary due to the microsegregation of Ti at the grain boundary during solidification. The type of TiN-oxide hybrid inclusion was strongly affected by the refractory material where Al2O3-TiN and MgAl2O4-TiN hybrid-type inclusions were obtained in the alumina and magnesia refractory experiments, respectively. The formation of oxide inclusions was well predicted by thermochemical computations and it was commonly found that oxide particles were initially formed, followed by the nucleation and growth of TiN. When the nitrogen content increased, the number density of TiN linearly increased in the alumina refractory experiments. However, the number of TiN exhibits a maximum at about [N] = 150 ppm, at which a minimum grain size was obtained in the magnesia refractory experiments. Therefore, the larger the number density of TiN, the smaller the primary grain size after solidification. The number density of TiN in the steel melted in the magnesia refractory was greater than that in the steel melted in the alumina refractory at given Ti and N contents, which was due to the lower planar lattice disregistry of MgAl2O4-TiN interface rather than that of Al2O3-TiN interface. When ΔT TiN (= difference between the TiN precipitation temperature and the liquidus of the steel) was 20 K to 40 K, the number density of effective TiN was maximized and thus, the grain size was minimized after solidification. Finally, although most of the TiN particles were smaller than 1 μm in the molten steel samples irrespective of the nitrogen content, TiN particles larger than 10 μm were observed in the solidified samples when the nitrogen content was greater than 150 ppm. The growth of TiN particles during melting and solidification was well predicted by the combinatorial simulation of the `Ostwald ripening model' based on the Lifshitz-Slyozov-Wagner theory in conjunction with the `Diffusion controlled model' using Ohnaka's microsegregation equation.

Economic impact of combination therapy with infliximab plus azathioprine for drug-refractory Crohn's disease: a cost-effectiveness analysis.

PubMed

Saito, Shota; Shimizu, Utako; Nan, Zhang; Mandai, Nozomu; Yokoyama, Junji; Terajima, Kenshi; Akazawa, Kouhei

2013-03-01

Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease. To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD. A decision analysis model is constructed to compare, over a time horizon of 1year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-α therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results. The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750. Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

An electrocardiographic scoring system for distinguishing right ventricular outflow tract arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia.

PubMed

Hoffmayer, Kurt S; Bhave, Prashant D; Marcus, Gregory M; James, Cynthia A; Tichnell, Crystal; Chopra, Nagesh; Moxey, Laura; Krahn, Andrew D; Dixit, Sanjay; Stevenson, William; Calkins, Hugh; Badhwar, Nitish; Gerstenfeld, Edward P; Scheinman, Melvin M

2013-04-01

Ventricular arrhythmias in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and idiopathic ventricular tachycardia (VT) can share a left bundle branch block/inferior axis morphology. We previously reported electrocardiogram characteristics during outflow tract ventricular arrhythmias that helped distinguish VT related to ARVD/C from idiopathic VT. To prospectively validate these criteria. We created a risk score by using a derivation cohort. Two experienced electrophysiologists blinded to the diagnosis prospectively scored patients with VT/premature ventricular contractions (PVCs) with left bundle branch block/inferior axis pattern in a validation cohort of 37 ARVD/C tracings and 49 idiopathic VT tracings. All patients with ARVD/C had their diagnosis confirmed based on the revised task force criteria. Patients with idiopathic VT were selected based on structurally normal hearts with documented right ventricular outflow tract VT successfully treated with ablation. The scoring system provides 3 points for sinus rhythm anterior T-wave inversions in leads V1-V3 and during ventricular arrhythmia: 2 points for QRS duration in lead I≥120 ms, 2 points for QRS notching, and 1 point for precordial transition at lead V5 or later. A score of 5 or greater was able to correctly distinguish ARVD/C from idiopathic VT 93% of the time, with a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 91%. We describe a simple scoring algorithm that uses 12-lead electrocardiogram characteristics to effectively distinguish right ventricular outflow tract arrhythmias originating from patients with ARVD/C versus patients with idiopathic VT. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial.

PubMed

Hadadzadeh, Mehdi; Hosseini, Seyed Habib; Mostafavi Pour Manshadi, Seyed Mohammad Yousof; Naderi, Nafiseh; Emami Meybodi, Mahmood

2013-01-01

Myocardial dysfunction is a major complication in cardiac surgery that needs inotropic support. This study evaluates the effect of milrinone on patients with low ventricular ejection fraction undergoing off- pump coronary artery bypass graft (OPCAB). The present study is designed to evaluate the effect of milrinone on myocardial dysfunction. Eighty patients with low ventricular ejection fraction (<35%), candidate for elective OPCAB, were enrolled in this study. They were randomly assigned to two groups. One group received milrinone (50 μg/kg) intravenously and another group received a saline as placebo followed by 24 hours infusion of each agent (0.5 μg/kg/min). Short outcome of patients such as hemodynamic parameters and left ventricular ejection fraction were variables evaluated. Serum levels of creatine phosphokinase, the MB isoenzyme of creatine kinase, occurrence of arrhythmias and mean duration of mechanical ventilation were significantly lower in milrinone group (P<0.05). The mean post operative left ventricular ejection fraction was significantly higher in milrinone group (P=0.031). There were no statistical significant differences between the two groups in terms of intra-aortic balloon pump, inotropic support requirement, myocardial ischemia, myocardial infarction, duration of inotropic support, duration of intensive care unit stay, mortality and morbidity rate. Administration of milrinone in patients undergoing OPCAB with low ventricular ejection fraction is useful and effective.

Wave Intensity Analysis of Right Ventricular Function during Pulsed Operation of Rotary Left Ventricular Assist Devices.

PubMed

Bouwmeester, J Christopher; Park, Jiheum; Valdovinos, John; Bonde, Pramod

2018-05-29

Changing the speed of left ventricular assist devices (LVADs) cyclically may be useful to restore aortic pulsatility; however, the effects of this pulsation on right ventricular (RV) function are unknown. This study investigates the effects of direct ventricular interaction by quantifying the amount of wave energy created by RV contraction when axial and centrifugal LVADs are used to assist the left ventricle. In 4 anesthetized pigs, pressure and flow were measured in the main pulmonary artery and wave intensity analysis was used to identify and quantify the energy of waves created by the RV. The axial pump depressed the intensity of waves created by RV contraction compared with the centrifugal pump. In both pump designs, there were only minor and variable differences between the continuous and pulsed operation on RV function. The axial pump causes the RV to contract with less energy compared with a centrifugal design. Diminishing the ability of the RV to produce less energy translates to less pressure and flow produced, which may lead to LVAD-induced RV failure. The effects of pulsed LVAD operation on the RV appear to be minimal during acute observation of healthy hearts. Further study is necessary to uncover the effects of other modes of speed modulation with healthy and unhealthy hearts to determine if pulsed operation will benefit patients by reducing LVAD complications.

Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

ClinicalTrials.gov

2017-07-14

Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory

Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study

PubMed Central

Borsje, Petra; Arts, Theo; van De Vosse, Frans N.

2006-01-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity. PMID:17048105

Association of Smoking, Sleep Apnea, and Plasma Alkalosis With Nocturnal Ventricular Arrhythmias in Men With Systolic Heart Failure

PubMed Central

Shukla, Rakesh; Wexler, Laura

2012-01-01

Background: Excess sudden death due to ventricular tachyarrhythmias remains a major mode of mortality in patients with systolic heart failure. The aim of this study was to determine the association of nocturnal ventricular arrhythmias in patients with low ejection fraction heart failure. We incorporated a large number of known pathophysiologic triggers to identify potential targets for therapy to reduce the persistently high incidence of sudden death in this population despite contemporary treatment. Methods: Eighty-six ambulatory male patients with stable low (≤ 45%) ejection fraction heart failure underwent full-night attendant polysomnography and simultaneous Holter recordings. Patients were divided into groups according to the presence or absence of couplets (paired premature ventricular excitations) and ventricular tachycardia (VT) (at least three consecutive premature ventricular excitations) during sleep. Results: In multiple regression analysis, four variables (current smoking status, increased number of arousals, plasma alkalinity, and old age) were associated with VT and two variables (apnea-hypopnea index and low right ventricular ejection fraction) were associated with couplets during sleep. Conclusions: We speculate that cessation of smoking, effective treatment of sleep apnea, and plasma alkalosis could collectively decrease the incidence of nocturnal ventricular tachyarrhythmias and the consequent risk of sudden death, which remains high despite the use of β blockades. PMID:22172636

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report

PubMed Central

PAPA, ANDREA ANTONIO; RAGO, ANNA; PETILLO, ROBERTA; D’AMBROSIO, PAOLA; SCUTIFERO, MARIANNA; FEO, MARISA DE; MAIELLO, CIRO; PALLADINO, ALBERTO

2017-01-01

Steinert’s disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Catecholamine-mediated arrhythmias in acute myocardial infarction. Experimental evidence and role of beta-adrenoceptor blockade.

PubMed

Opie, L H; Lubbe, W F

1979-11-24

Ventricular fibrillation is a major mechanism of sudden death. The cellular link between catecholamine activity and the development of serious ventricular arrhythmias may be in the formation of cyclic adenosine monophosphate (cAMP). Cyclic AMP and agents promoting cAMP accumulation allow development of slow responses which, especially in the presence of regional ischaemia, could develop into ventricular fibrillation. The role of beta-antagonist agents in the therapy of acute myocardial infarction is analysed in relation to the hypothesis linking cAMP and ventricular fibrillation. Reasons for the limited effectiveness of anti-arrhythmic therapy with beta-antagonist agents are given.

The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

PubMed

Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

2016-12-01

More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

Bumetanide is not capable of terminating status epilepticus but enhances phenobarbital efficacy in different rat models.

PubMed

Töllner, Kathrin; Brandt, Claudia; Erker, Thomas; Löscher, Wolfgang

2015-01-05

In about 20-40% of patients, status epilepticus (SE) is refractory to standard treatment with benzodiazepines, necessitating second- and third-line treatments that are not always successful, resulting in increased mortality. Rat models of refractory SE are instrumental in studying the changes underlying refractoriness and to develop more effective treatments for this severe medical emergency. Failure of GABAergic inhibition is a likely cause of the development of benzodiazepine resistance during SE. In addition to changes in GABAA receptor expression, trafficking, and function, alterations in Cl(-) homeostasis with increased intraneuronal Cl(-) levels may be involved. Bumetanide, which reduces intraneuronal Cl(-) by inhibiting the Cl(-) intruding Na(+), K(+), Cl(-) cotransporter NKCC1, has been reported to interrupt SE induced by kainate in urethane-anesthetized rats, indicating that this diuretic drug may be an interesting candidate for treatment of refractory SE. In this study, we evaluated the effects of bumetanide in the kainate and lithium-pilocarpine models of SE as well as a model in which SE is induced by sustained electrical stimulation of the basolateral amygdala. Unexpectedly, bumetanide alone was ineffective to terminate SE in both conscious and anesthetized adult rats. However, it potentiated the anticonvulsant effect of low doses of phenobarbital, although this was only seen in part of the animals; higher doses of phenobarbital, particularly in combination with diazepam, were more effective to terminate SE than bumetanide/phenobarbital combinations. These data do not suggest that bumetanide, alone or in combination with phenobarbital, is a valuable option in the treatment of refractory SE in adult patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Left ventricular rotation and torsion in patients with perimembranous ventricular septal defect.

PubMed

Zhuang, Yan; Yong, Yong-hong; Yao, Jing; Ji, Ling; Xu, Di

2014-03-01

Assessment of left ventricular (LV) rotation has become an important approach for quantifying LV function. In this study, we sought to analyze LV rotation and twist using speckle tracking imaging (STI) in adult patients with isolated ventricular septal defects. Using STI, the peak rotation and time to peak rotation of 6 segments in basal and apical short-axis were measured, respectively, in 32 patients with ventricular septal defect and 30 healthy subjects as controls. The global rotation of the 6 segments in basal and apical and LV twist versus time profile were drawn, the peak rotation and twist of LV were calculated. All the time to peak rotation/twist were expressed as a percentage of end-systole (end-systole = 100%). Left ventricular ejection fraction was measured by biplane Simpson method. In patients group, the peak rotation of posterior, inferior, and postsept wall in basal was higher(P ≤ 0.05) and LV twist was also higher (P ≤ 0.05) than healthy controls. There were no significant differences between 2 groups in the peak rotation of the other 9 segments and left ventricular ejection fraction. Different from the control group, the time to peak rotation of the 6 segments in basal were delayed and the global rotation of the base was delayed (P ≤ 0.05) in ventricular septal defect group. Left ventricular volume overload due to ventricular septal defect has significant effect on LV rotation and twist, and LV rotation and twist may be a new index predicting LV systolic function. © 2013, Wiley Periodicals, Inc.

Additional mechanism for left ventricular dysfunction: chronic pulmonary regurgitation decreases left ventricular preload in patients with tetralogy of Fallot.

PubMed

Ylitalo, Pekka; Jokinen, Eero; Lauerma, Kirsi; Holmström, Miia; Pitkänen-Argillander, Olli M

2018-02-01

Right ventricular dysfunction in patients with tetralogy of Fallot and significant pulmonary regurgitation may lead to systolic dysfunction of the left ventricle due to altered ventricular interaction. We were interested in determining whether chronic pulmonary regurgitation affects the preload of the left ventricle. In addition, we wanted to study whether severe chronic pulmonary regurgitation would alter the preload of the left ventricle when compared with patients having preserved pulmonary valve annulus. The study group comprised 38 patients with tetralogy of Fallot who underwent surgical repair between 1990 and 2003. Transannular patching was required in 21 patients to reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender-matched healthy volunteers were recruited. Cardiac MRI was performed on all study patients to assess the atrial and ventricular volumes and function. Severe pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11 had a transannular patch, but only two had a preserved pulmonary valve annulus. The ventricular preload volumes from both atria were significantly reduced in patients with severe pulmonary regurgitation, and left ventricular stroke volumes (44.1±4.7 versus 58.9±10.7 ml/m2; p<0.0001) were smaller compared with that in patients with pulmonary regurgitation <30 ml/m2 or in controls. In patients with tetralogy of Fallot, severe pulmonary regurgitation has a significant effect on volume flow through the left atrium. Reduction in left ventricular preload volume may be an additional factor contributing to left ventricular dysfunction.

Effect of Vaporizer Temperature on Ambient Non-Refractory Submicron Aerosol Composition and Mass Spectra Measured by the Aerosol Mass Spectrometer

EPA Science Inventory

Aerodyne Aerosol Mass Spectrometers (AMS) are routinely operated with a constant vaporizer temperature (Tvap) of 600^oC in order to facilitate quantitative detection of non-refractory submicron (NR-PM1) species. By analogy with other thermal desorption instrument...

[Wearable Automatic External Defibrillators].

PubMed

Luo, Huajie; Luo, Zhangyuan; Jin, Xun; Zhang, Leilei; Wang, Changjin; Zhang, Wenzan; Tu, Quan

2015-11-01

Defibrillation is the most effective method of treating ventricular fibrillation(VF), this paper introduces wearable automatic external defibrillators based on embedded system which includes EGG measurements, bioelectrical impedance measurement, discharge defibrillation module, which can automatic identify VF signal, biphasic exponential waveform defibrillation discharge. After verified by animal tests, the device can realize EGG acquisition and automatic identification. After identifying the ventricular fibrillation signal, it can automatic defibrillate to abort ventricular fibrillation and to realize the cardiac electrical cardioversion.

Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation.

PubMed

Corino, Valentina D A; Sandberg, Frida; Platonov, Pyotr G; Mainardi, Luca T; Ulimoen, Sara R; Enger, Steve; Tveit, Arnljot; Sörnmo, Leif

2014-11-01

During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data, and to support our findings with simulated data based on results from an electrophysiological study. Sixty patients (age 71 ± 9 years, 42 men) with permanent AF were included in the RATe control in Atrial Fibrillation (RATAF) study. Two 15 min segments, during baseline and metoprolol administration, starting at 2 pm were analysed in this study. Atrial fibrillatory rate (AFR), heart rate (HR), and AV nodal parameters were assessed. The AV nodal parameters account for the probability of an impulse not taking the fast pathway, the absolute refractory periods of the slow and fast pathways (aRPs and aRPf), representing the functional refractory period, and their respective prolongation in refractory period. In addition, simulated RR series were generated that mimic metoprolol administration through prolonged AV conduction interval and AV node effective refractory period. During metoprolol administration, AFR and HR were significantly decreased and aRP was significantly prolonged in both pathways (aRPs: 337 ± 60 vs. 398 ± 79 ms, P < 0.01; aRPf: 430 ± 91 vs. 517 ± 100 ms, P < 0.01). Similar results were found for the simulated RR series, both aRPs and aRPf being prolonged with metoprolol (aRPs: 413 ± 33 vs. 437 ± 43 ms, P = 0.01; aRPf: 465 ± 40 vs. 502 ± 69 ms, P = 0.02). The AV nodal parameters reflect expected changes after metoprolol administration, i.e. a prolongation in functional refractory period. The simulations confirmed that aRPs and aRPf may serve as an estimate of the functional refractory period. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Characteristics of refractory gastroesophageal reflux disease (GERD) symptoms -is switching proton pump inhibitors based on the patient's CYP2C19 genotype an effective management strategy?

PubMed

Takeuchi, Toshihisa; Oota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Sanomura, Makoto; Sakaguchi, Masahiro; Hayashi, Katsuyoshi; Hongoh, Yasushi; Itabashi, Tsukasa; Kitae, Hidehiro; Hoshimoto, Masahiro; Takeuchi, Nozomi; Higuchi, Kazuhide

2015-01-01

We investigated factors related to proton pump inhibitor (PPI) -refractory gastroesophageal reflux disease (GERD) symptoms, particularly with respect to acid, the CYP2C19 genotype and psychological aspects. Patients with an Frequency Scale for the Symptoms of GERD (FSSG) score of ≥8 after the initial treatment were switched to therapy with rabeprazole at a dose of 20 mg once daily for eight weeks. We investigated the rate of improvement in PPI-refractory GERD symptoms, background factors, the Hospital Anxiety and Depression Scale (HADS) score and the CYP2C19 genotype. Patients Sixty patients endoscopically diagnosed with reflux esophagitis within the past six months who had received omeprazole at a dose of 20 mg once daily for eight weeks or longer were enrolled. In 71.6% of the patients, the FSSG score decreased to <8 after treatment with omeprazole at a dose of 20 mg once daily for ≥8 weeks, resulting in improvements in their GERD symptoms. Significant factors related to omeprazole-refractory GERD symptoms included a longer disease duration (p=0.0004) and higher HADS score (p=0.01). Among the omeprazole-refractory cases, only 23.5% of the patients showed symptom improvement after switching to rabeprazole. There were no significant differences in the average scores for FSSG (p=0.089) or HADS (p=0.182), before or after the drug change. A total of 92% of the rabeprazole poor responders were homo/hetero extensive metabolizers for the CYP2C19 genotype. Our findings suggest that switching the PPI from omeprazole (20 mg once daily) to rabeprazole (20 mg once daily) is not a significant effective therapeutic strategy for improving PPI-refractory GERD symptoms, taking into consideration possible psychometric factors and patients who require stronger acid suppression than that achieved with a double dose of PPIs for PPI-refractory GERD symptoms.

Angiotensin II in Refractory Septic Shock.

PubMed

Antonucci, Elio; Gleeson, Patrick J; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

2017-05-01

Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

Dietary therapy is the best option for refractory nonsurgical epilepsy.

PubMed

Felton, Elizabeth A; Cervenka, Mackenzie C

2015-09-01

Ketogenic diet therapies for epilepsy have been described since the fifth century and published in scientific literature since the early 1900s. Since that time, the diet's popularity has waxed and waned as newer drugs and other treatments have been introduced. However, in recent years, dietary therapy for epilepsy has been increasingly accepted by physicians and desired by patients as an alternative to new drugs and neurostimulation. The introduction of less restrictive versions of the classic ketogenic diet, such as the modified Atkins diet (MAD), have led to increased numbers of adult patients with refractory epilepsy who are initiating dietary treatment. Approximately half of adults and children who start a ketogenic diet have a >50% seizure reduction, which is impressive given that these patients typically have medically refractory epilepsy. We believe that ketogenic dietary treatment is the best option for children and adults with refractory nonsurgical epilepsy due to its efficacy, rapid seizure reduction, synergistic effects with other antiseizure treatments, known and treatable side effects, potential to treat comorbid medical conditions, and worldwide availability. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

PubMed

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial.

PubMed

Lund, Mikael; Alexandersson von Döbeln, Gabriella; Nilsson, Magnus; Winter, Reidar; Lundell, Lars; Tsai, Jon A; Kalman, Sigridur

2015-01-13

Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. 40 patients participated (chemoradiotherapy, n=17; chemotherapy, n=23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p=0.02, p=0.01, and p=0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p=0.09 and p=0.09). NT-proBNP increased following chemoradiotherapy (p=0.05) but not after chemotherapy (p>0.99), and there was a trend towards an interaction effect (p=0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p=0.03) and was more pronounced after chemoradiotherapy with a trend towards an interaction effect (p=0.10). Neoadjuvant chemoradiotherapy but not chemotherapy before surgery for cancer of the esophagus or GE-junction seems to induce an acute negative effect on both systolic and diastolic left ventricular function. Future studies on neoadjuvant treatment for esophageal cancer are suggested to add measurements of cardiac function. Clinical Trials.gov NCT01362127 .

Exploration of Fecal Microbiota Transplantation in the Treatment of Refractory Diarrhea After Renal Transplantation.

PubMed

Gu, B; Bo, G Z; Ke, C

2018-06-01

Exploration of fecal microbiota transplantation in the treatment of refractory diarrhea after renal transplantation. Summarize the etiology of 120 cases with diarrhea after renal transplantation from 2014 to 2017 in our hospital. There were 4 recipients of refractory diarrhea who accepted fecal microbiota transplantation with informed consent, and we collected clinical data of stool and bacterial culture, gut microbiota analysis, graft function, electrolytes, immunosuppressant concentrations of prognostic evaluation of patients with fecal transplantation. The absorption of electrolyte is slightly higher and concentration of tacrolimus and creatinine were not significantly changed compared with before. Fecal microbiota transplantation provides a new choice to refractory diarrhea after renal transplantation as an innovative treatment, but the effectiveness of fecal microbiota transplantation needs long-term observation and further evaluation through large sample data. Copyright © 2018. Published by Elsevier Inc.

Effect of small-scale biomass gasification at the state of refractory lining the fixed bed reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janša, Jan, E-mail: jan.jansa@vsb.cz; Peer, Vaclav, E-mail: vaclav.peer@vsb.cz; Pavloková, Petra, E-mail: petra.pavlokova@vsb.cz

The article deals with the influence of biomass gasification on the condition of the refractory lining of a fixed bed reactor. The refractory lining of the gasifier is one part of the device, which significantly affects the operational reliability and durability. After removing the refractory lining of the gasifier from the experimental reactor, there was done an assessment how gasification of different kinds of biomass reflected on its condition in terms of the main factors affecting its life. Gasification of biomass is reflected on the lining, especially through sticking at the bottom of the reactor. Measures for prolonging the lifemore » of lining consist in the reduction of temperature in the reactor, in this case, in order to avoid ash fusion biomass which it is difficult for this type of gasifier.« less

Usefulness of a pleuroperitoneal shunt for treatment of refractory pleural effusion in a patient receiving maintenance hemodialysis.

PubMed

Habuka, Masato; Ito, Toru; Yoshizawa, Yuta; Matsuo, Koji; Murakami, Shuichi; Kondo, Daisuke; Kanazawa, Hiroshi; Narita, Ichiei

2018-03-23

Refractory pleural effusion can be a life-threatening complication in patients receiving maintenance hemodialysis. We report successful treatment of refractory pleural effusion using a Denver® pleuroperitoneal shunt in one such patient. A 54-year-old Japanese man, who had previously undergone left nephrectomy, was admitted urgently to our department because of a high C-reactive protein (CRP) level, right pleural effusion, and right renal abscess. Because antibiotics proved ineffective and his general state was deteriorating, he underwent emergency insertion of a thoracic drainage tube and nephrectomy, and hemodialysis was started. Although his general state improved slowly thereafter, the pleural effusion, which was unilateral and transudative, remained refractory and therefore he needed to be on oxygenation. To control the massive pleural effusion, a pleuroperitoneal shunt was inserted. Thereafter, his respiratory condition became stable without oxygenation and he was discharged. His general condition has since been well. Although pleural effusion is a common complication of maintenance hemodialysis, few reports have documented the use of pleuroperitoneal shunt to control refractory pleural effusion. Pleuroperitoneal shunt has been advocated as an effective and low-morbidity treatment for refractory pleural effusion, and its use for some patients with recurrent pleural effusion has also been reported, without any severe complications. In the present case, pleuroperitoneal shunt improved the patient's quality of life sufficiently to allow him to be discharged home without oxygenation. Pleuroperitoneal shunt should be considered a useful treatment option for hemodialysis patients with refractory pleural effusion.

Tioguanine in the treatment of refractory coeliac disease--a single centre experience.

PubMed

Tack, G J; van Asseldonk, D P; van Wanrooij, R L J; van Bodegraven, A A; Mulder, C J

2012-08-01

Refractory coeliac disease type I is a complicated form of coeliac disease characterised by primary or secondary resistance to a gluten-free diet with persisting or reoccurring intestinal villous atrophy and symptoms of malabsorption. Besides corticosteroids, azathioprine has been advocated for the treatment of refractory coeliac disease type I. However, tioguanine (TG) might be better tolerated and more efficacious owing to a simpler metabolism towards bioactivation. To evaluate tolerability and effectiveness of the nonconventional thiopurine derivative TG in refractory coeliac disease type I. Refractory coeliac disease type I patients treated with TG between June 2001 and November 2010 with a follow-up period of at least 1 year were included. Adverse events, laboratory values, 6-thioguanine nucleotide concentrations and rates of both clinical and histological response were evaluated at baseline and during follow-up. Twelve adult refractory coeliac disease type I patients were included. The median TG treatment duration was 14 months. Ten patients tolerated TG treatment on the long term, whereas two patients withdrew treatment due to adverse events. No nodular regenerative hyperplasia of the liver was observed. During follow-up clinical and histological response was observed in 83% and 78%, respectively. Corticosteroid dependency decreased by 50%. Tioguanine appears to be a convenient drug for the treatment of refractory coeliac disease type I based on higher histological and similar clinical response rates as compared with historical conventional therapies. © 2012 Blackwell Publishing Ltd.

Can anesthetic treatment worsen outcome in status epilepticus?

PubMed

Sutter, Raoul; Kaplan, Peter W

2015-08-01

Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Adding colchicine to immunosuppressive treatments; a potential option for biologics-refractory adult-onset Still's disease.

PubMed

Asano, Tomoyuki; Furuya, Makiko Yashiro; Sato, Shuzo; Kobayashi, Hiroko; Watanabe, Hiroshi; Suzuki, Eiji; Migita, Kiyoshi

2018-05-21

Adult-onset Still's disease (AOSD) is a rare inflammatory disorder characterized by the classical triad of daily spiking fever, arthritis, and typical salmon-colored rash. Resistance to first-line corticosteroids and second-line disease modified anti-rheumatic-drugs defines refractory AOSD, which mostly includes the polycyclic or chronic courses of the disease. Anti-cytokine therapies are recommended in AOSD patients who are refractory to traditional treatments. This is the first report on the efficacy of colchicine in a patient with AOSD which was refractory to immunosuppressive treatments including biologics. A 24-years Japanese female patient was referred to our hospital for the flare-up of AOSD under the combined treatments with steroid, immunosuppressants, and biologics. She was diagnosed with AOSD according to the Yamaguchi criteria, based on the presence of spiking fever, polyarthralgia, skin rash, and hyperferritinemia. Interleukin-6 or tumor necrosis factor-α blockade treatments were not effective, the oral administration of colchicine was stared under the immunosuppressive treatments with steroid and cyclosporine A (CyA). Colchicine treatment silenced the disease activity of AOSD. The dose of prednisolone was successfully tapered, and the elevated levels of C-reactive protein were normalized. Remission has been maintained for 13 months with the start of oral administration of colchicine. We concluded that colchicine is an alternative treatment in patients with refractory AOSD, particularly in those with impaired therapeutic effects against anti-cytokines therapies.

Radiological Insertion of Denver Peritoneovenous Shunts for Malignant Refractory Ascites: A Retrospective Multicenter Study (JIVROSG-0809)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugawara, Shunsuke, E-mail: suga_shun@hotmail.com; Sone, Miyuki; Arai, Yasuaki

Purpose: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites. Methods: A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data. Results: PVSs were successfully placed in allmore » patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor. Conclusions: Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS.« less

Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine.

PubMed

Albany, Costantine; Hever-Jardine, Mary P; von Herrmann, Katherine M; Yim, Christina Y; Tam, Janice; Warzecha, Joshua M; Shin, Leah; Bock, Sarah E; Curran, Brian S; Chaudhry, Aneeq S; Kim, Fred; Sandusky, George E; Taverna, Pietro; Freemantle, Sarah J; Christensen, Brock C; Einhorn, Lawrence H; Spinella, Michael J

2017-01-10

Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients.

Sequential big endothelin plasma levels in heart transplant recipients during bridging therapy and after successful heart transplantation.

PubMed

Strametz-Juranek, Jeanette; Pacher, Richard; Kos, Thomas; Woloszczuk, Wolfgang; Grimm, Michael; Zuckermann, Andreas; Stanek, Brigitte

2003-07-01

The purpose of this study was to investigate the impact of successful heart transplantation in patients with refractory heart failure receiving bridging therapy on sequential plasma levels of big endothelin, norepinephrine, atrial natriuretic peptide and aldosterone. Fourteen patients (2 women, 12 men) accepted for heart transplantation were studied. All had severe chronic heart failure refractory to optimized oral therapy with angiotensin-converting enzyme inhibitors and furosemide, were in New York Heart Association functional Class IV, and had a left ventricular ejection fraction of <15%, Right heart catheterization was performed in all patients (cardiac index 1.9 +/- 0.1 liters/min. m(2), pulmonary capillary wedge pressure 30 +/- 2 mmHg, systemic vascular resistance index 2,827 +/- 253 dyn. s/cm(5). m(2)). As bridging therapy, patients received either prostaglandin E(1), prostaglandin E(1) and dobutamine or dobutamine alone as a continuous infusion. Neurohumoral variables were measured prior to bridging therapy and 3.5 months before and 7 and 10 months after successful heart transplantation. Big endothelin, norepinephrine and atrial natriuretic peptide plasma levels decreased from 7.4 +/- 2.9 fmol/ml, 1112 +/- 686 pg/ml and 366 +/- 312 pg/ml to 6.0 +/- 4.5 fmol/ml, 720 +/- 503 pg/ml and 198 +/- 160 pg/ml, respectively, after bridging therapy, and further to 2.1 +/- 0.9 fmol/ml (p < 0.00001 vs baseline), 527 +/- 31 pg/ml (p < 0.02 vs baseline) and 115 +/- 70 pg/ml (p < 0.03 vs baseline), respectively, after cardiac transplantation. Aldosterone plasma levels decreased from 242 +/- 220 pg/ml to 183 +/- 142 pg/ml during bridging therapy and increased after heart transplantation to 252 +/- 189 pg/ml. Plasma creatinine levels increased from 1.2 +/- 0.4 mg/dl at baseline to 1.4 +/- 0.2 mg/dl after transplantation (NS). The study suggests that excessive overproduction of big endothelin, atrial natriuretic peptide and norepinephrine is predominantly related to pump failure and, after cardiac transplantation, a moderate spillover of big endothelin persists. Its specific origin, however, remains to be elucidated. Furthermore, our data suggest a protective effect of prostaglandin E(1) on kidney function after heart transplantation.

Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia

PubMed Central

Ardell, Jeffrey L.; Cardinal, René; Vermeulen, Michel; Armour, J. Andrew

2009-01-01

Populations of intrathoracic extracardiac neurons transduce myocardial ischemia, thereby contributing to sympathetic control of regional cardiac indices during such pathology. Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) modulates such local reflex control. In 10 anesthetized canines, middle cervical ganglion neurons were identified that transduce the ventricular milieu. Their capacity to transduce a global (rapid ventricular pacing) vs. regional (transient regional ischemia) ventricular stress was tested before and during SCS (50 Hz, 0.2 ms duration at 90% MT) applied to the dorsal aspect of the T1 to T4 spinal cord. Rapid ventricular pacing and transient myocardial ischemia both activated cardiac-related middle cervical ganglion neurons. SCS obtunded their capacity to reflexly respond to the regional ventricular ischemia, but not rapid ventricular pacing. In conclusion, spinal cord inputs to the intrathoracic extracardiac nervous system obtund the latter's capacity to transduce regional ventricular ischemia, but not global cardiac stress. Given the substantial body of literature indicating the adverse consequences of excessive adrenergic neuronal excitation on cardiac function, these data delineate the intrathoracic extracardiac nervous system as a potential target for neuromodulation therapy in minimizing such effects. PMID:19515981

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

PubMed

Keros, Sotirios; Buraniqi, Ersida; Alex, Byron; Antonetty, Annalee; Fialho, Hugo; Hafeez, Baria; Jackson, Michele C; Jawahar, Rachel; Kjelleren, Stephanie; Stewart, Elizabeth; Morgan, Lindsey A; Wainwright, Mark S; Sogawa, Yoshimi; Patel, Anup D; Loddenkemper, Tobias; Grinspan, Zachary M

2017-06-01

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Apatinib in refractory radiation-induced brain edema

PubMed Central

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-01-01

Abstract Rationale: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Patient concerns: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Diagnoses: Two patients were both diagnosed as refractory radiation-induced brain edema. Interventions: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Outcomes: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Lessons: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study. PMID:29145238

Effects of morphologic left ventricular pressure on right ventricular geometry and tricuspid valve regurgitation in patients with congenitally corrected transposition of the great arteries.

PubMed

Kral Kollars, Catharine A; Gelehrter, Sarah; Bove, Edward L; Ensing, Gregory

2010-03-01

Congenitally corrected transposition of the great arteries (CCTGA) is associated with tricuspid regurgitation (TR), which has been postulated to arise from the effect of ventricular septal position on the attachments of the tricuspid valve. This study was performed to determine the effect of left ventricular (LV) pressure on right ventricular (RV) and LV geometry and the degree of TR. Serial echocardiograms were reviewed from, 30 patients with CCTGA who underwent pulmonary artery banding to train the morphologic left ventricle (n = 14) or left ventricle-to-pulmonary artery conduit placement and ventricular septal defect closure in conjunction with physiologic repair (n = 16). The degree of TR, the LV/RV pressure ratio, RV and LV sphericity indexes, and tricuspid valve tethering distance and coaptation length were analyzed. After pulmonary artery banding, an increase in LV systolic pressure to > or =2/3 systemic resulted in a decrease in TR from severe to moderate (p = 0.02). The percentage of patients with severe TR decreased from 64% to 18% (p = 0.06). The RV sphericity index decreased (p = 0.05), and the LV sphericity index increased (p = 0.02). After left ventricle-to-pulmonary artery conduit placement, a decrease in LV pressure to < or =1/2 systemic resulted in an increase in TR from none to mild (p = 0.003). In conclusion, these data indicate that LV pressure in patients with CCTGA affects the degree of TR and that septal shift caused by changes in LV and RV pressure is an important mechanism. Copyright 2010. Published by Elsevier Inc.

Effects of Trichothecenes on Cardiac Cell Electrical Function

DTIC Science & Technology

1985-12-13

Figure 8 illustrate the typical effects of trichothecene mycotoxins in canine ventricular cells. T-2 tetraol, for example, reduced the total duration of...potentials from false tendon cells and ventricular muscle cells (shown in Figure 8) illustrate the typical effects of trichothecene mycotoxins in canine...the plateau (arrow) from 14 my to 4 my. Table 6 summarizes the effects of T-2 mycotoxin on the action potential parameters of false tendon cells and

Use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant

PubMed Central

Durães, André Rodrigues; Figueira, Fernando Augusto Marinho dos Santos; Lafayette, André Rabelo; Martins, Juliana de Castro Solano; Juliano Cavalcante de, Sá

2015-01-01

A 17-year-old Brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. Echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). After 48 hours with no clinical or hemodynamic improvement, an extracorporeal membrane oxygenation was implanted. The patient presented with hemodynamic, systemic perfusion and renal and liver function improvements; however, his cardiac function did not recover after 72 hours, and he was transfer to another hospital. Air transport was conducted from Salvador to Recife in Brazil. A heart transplant was performed with rapid recovery of both liver and kidney functions, as well as good graft function. Histopathology of the explanted heart showed chronic active myocarditis and amastigotes of Trypanosoma cruzi. The estimated global prevalence of T. cruzi infections declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Myocarditis is an inflammatory disease due to infectious or non-infectious conditions. Clinical manifestation is variable, ranging from subclinical presentation to refractory heart failure and cardiogenic shock. Several reports suggest that the use of extracorporeal membrane oxygenation in patients presenting with severe refractory myocarditis is a potential bridging therapy to heart transplant when there is no spontaneous recovery of ventricular function. In a 6-month follow-up outpatient consult, the patient presented well and was asymptomatic. PMID:26761479

A Phase 1-2 Multi-Center Study Evaluating Axicabtagene Ciloleucel in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

ClinicalTrials.gov

2018-06-18

Refractory Diffuse Large B Cell Lymphoma; Refractory Primary Mediastinal B Cell Lymphoma; Refractory Transformed Follicular Lymphoma; Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma; Relapsed/Refractory Large B Cell Lymphoma Including DLBCL, PMBCL, TFL and HGBCL After Two Systemic Lines of Therapy" in Phase 2 Expanded Cohorts

Ventricular Arrhythmic Storm after Initiating Sacubitril/Valsartan.

PubMed

Vicent, Lourdes; Juárez, Miriam; Martín, Irene; García, Jorge; González-Saldívar, Hugo; Bruña, Vanesa; Devesa, Carolina; Sousa-Casasnovas, Iago; Fernández-Avilés, Francisco; Martínez-Sellés, Manuel

Sacubitril/valsartan was approved recently for the treatment of patients with heart failure and reduced ejection fraction. We present 6 cases of ventricular arrhythmia, that occurred shortly after sacubitril/valsartan initiation, that required drug withdrawal. Other potential triggering factors of electrical storm were ruled out and, from the arrhythmic perspective, all of the patients were stable in the previous year. Our aim is to describe the possible association of sacubitril/valsartan with arrhythmic storm. This was an observational monocentric study performed in the first 7 months of sacubitril/valsartan commercialization in Spain (October 2016). All patients were included in the SUMA (Sacubitril/Varsartan Usado Ambulatoriamente en Madrid [Sacubitril/Valsartan Used in Outpatients in Madrid]) registry. Patients were consecutively enrolled on the day they started the drug. Ventricular arrhythmic storm was defined as ≥2 episodes of sustained ventricular arrhythmia or defibrillator therapy application in 24 h. From 108 patients who received the drug, 6 presented with ventricular arrhythmic storm (5.6%). Baseline characteristics were similar in the patients with and without ventricular arrhythmic storm. The total number of days that sacubitril/valsartan was administered to each patient was 5, 6, 44 (8 since titration), 84, 93, and 136 (105 since titration), respectively. Our data are not enough to infer a cause-and-effect relationship. Further investigations regarding a potential proarrhythmic effect of sacubitril/valsartan are probably needed. © 2018 S. Karger AG, Basel.

Terlipressin: vasopressin analog and novel drug for septic shock.

PubMed

Pesaturo, Adam B; Jennings, Heath R; Voils, Stacy A

2006-12-01

To review and assess available literature on chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical studies, adverse events, drug interactions, and dosing and administration of terlipressin in septic shock. A literature search of MEDLINE (1966-September 2006), International Pharmaceutical Abstracts (1970-September 2006), and Cochrane database (third quarter 2006) was conducted, using key terms of terlipressin, lypressin, triglycyl-lysine vasopressin, hemodynamic support, septic shock, vasopressor, and V1 receptor agonist. Bibliographies of relevant articles were reviewed for additional references. Available English-language literature, including abstracts, animal studies, preclinical studies, clinical trials, and review articles, were examined. Because of potentially favorable pharmacokinetics versus vasopressin and limited availability of vasopressin in some countries, the effects of terlipressin, a vasopressin analog, have been studied recently for the treatment of septic shock. When administered as a 1-2 mg intravenous dose in patients with septic shock, terlipressin increases mean arterial pressure, urine output, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work index while decreasing heart rate, cardiac output, lactate, and oxygen delivery and consumption index. It is unclear whether lower doses of terlipressin would produce a similar vasopressor response with fewer cardiopulmonary effects and whether the effects of the drug on oxygen transport indices are detrimental. Terlipressin is a promising investigational medication for treatment of septic shock. Small trials have shown terlipressin to have favorable effects on hemodynamics in patients with septic shock refractory to conventional vasopressor treatment. It should be used with extreme caution in patients with underlying cardiac or pulmonary dysfunction. Further studies are needed to verify safety, efficacy, and dosing of terlipressin in patients with septic shock, and its use cannot be recommended in lieu of vasopressin at this time.

Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.

PubMed

Lin, Zhenhao; Xing, Wenlu; Gao, Chuanyu; Wang, Xianpei; Qi, Datun; Dai, Guoyou; Zhao, Wen; Yan, Ganxin

2018-01-26

Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (I K ) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters. I K and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (I K s ) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, P =0.001; 12.73±0.34 versus 9.05±1.20, n=5, P =0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, P =0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (I K r ), resting membrane potential, AP amplitude, or maximal velocity of depolarization. VEGF inhibited I K s in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Efficacy and tolerability of levetiracetam for pediatric refractory epilepsy.

PubMed

Muramatsu, Kazuhiro; Sawaura, Noriko; Ogata, Tomomi; Makioka, Nishiki; Tomita, Keiko; Motojima, Toshino; Ida, Kuniko; Hazama, Kyoko; Arakawa, Hirokazu

2017-03-01

Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2years, (2) younger than 20years old, and (3) received oral levetiracetam treatment for ⩾6months. We assessed the relationships of these outcomes with MRI findings and ID status. Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Evaluation of training nurses to perform semi-automated three-dimensional left ventricular ejection fraction using a customised workstation-based training protocol.

PubMed

Guppy-Coles, Kristyan B; Prasad, Sandhir B; Smith, Kym C; Hillier, Samuel; Lo, Ada; Atherton, John J

2015-06-01

We aimed to determine the feasibility of training cardiac nurses to evaluate left ventricular function utilising a semi-automated, workstation-based protocol on three dimensional echocardiography images. Assessment of left ventricular function by nurses is an attractive concept. Recent developments in three dimensional echocardiography coupled with border detection assistance have reduced inter- and intra-observer variability and analysis time. This could allow abbreviated training of nurses to assess cardiac function. A comparative, diagnostic accuracy study evaluating left ventricular ejection fraction assessment utilising a semi-automated, workstation-based protocol performed by echocardiography-naïve nurses on previously acquired three dimensional echocardiography images. Nine cardiac nurses underwent two brief lectures about cardiac anatomy, physiology and three dimensional left ventricular ejection fraction assessment, before a hands-on demonstration in 20 cases. We then selected 50 cases from our three dimensional echocardiography library based on optimal image quality with a broad range of left ventricular ejection fractions, which was quantified by two experienced sonographers and the average used as the comparator for the nurses. Nurses independently measured three dimensional left ventricular ejection fraction using the Auto lvq package with semi-automated border detection. The left ventricular ejection fraction range was 25-72% (70% with a left ventricular ejection fraction <55%). All nurses showed excellent agreement with the sonographers. Minimal intra-observer variability was noted on both short-term (same day) and long-term (>2 weeks later) retest. It is feasible to train nurses to measure left ventricular ejection fraction utilising a semi-automated, workstation-based protocol on previously acquired three dimensional echocardiography images. Further study is needed to determine the feasibility of training nurses to acquire three dimensional echocardiography images on real-world patients to measure left ventricular ejection fraction. Nurse-performed evaluation of left ventricular function could facilitate the broader application of echocardiography to allow cost-effective screening and monitoring for left ventricular dysfunction in high-risk populations. © 2014 John Wiley & Sons Ltd.

Management of severe ischemic cardiomyopathy: left ventricular assist device as destination therapy versus conventional bypass and mitral valve surgery.

PubMed

Maltais, Simon; Tchantchaleishvili, Vahtang; Schaff, Hartzell V; Daly, Richard C; Suri, Rakesh M; Dearani, Joseph A; Topilsky, Yan; Stulak, John M; Joyce, Lyle D; Park, Soon J

2014-04-01

Patients with severe ischemic cardiomyopathy (left ventricular ejection fraction <25%) and severe ischemic mitral regurgitation have a poor survival with medical therapy alone. Left ventricular assist device as destination therapy is reserved for patients who are too high risk for conventional surgery. We evaluated our outcomes with conventional surgery within this population and the comparative effectiveness of these 2 therapies. We identified patients who underwent conventional surgery or left ventricular assist device as destination therapy for severe ischemic cardiomyopathy (left ventricular ejection fraction <25%) and severe mitral regurgitation. The era for conventional surgery spanned from 1993 to 2009 and from 2007 to 2011 for left ventricular assist device as destination therapy. We compared baseline patient characteristics and outcomes in terms of end-organ function and survival. A total of 88 patients were identified; 55 patients underwent conventional surgery (63%), and 33 patients (37%) received a left ventricular assist device as destination therapy. Patients who received left ventricular assist device as destination therapy had the increased prevalence of renal failure, inotrope dependency, and intra-aortic balloon support. Patients undergoing conventional surgery required longer ventilatory support, and patients receiving a left ventricular assist device required more reoperation for bleeding. Mortality rates were similar between the 2 groups at 30 days (7% in the conventional surgery group vs 3% in the left ventricular assist device as destination therapy group, P = .65) and at 1 year (22% in the conventional surgery group vs 15% in the left ventricular assist device as destination therapy group, P = .58). There was a trend toward improved survival in patients receiving a left ventricular assist device compared with the propensity-matched groups at 1 year (94% vs 71%, P = .171). The operative mortality and early survival after conventional surgery seem to be acceptable. For inoperable or prohibitive-risk patients, left ventricular assist device as destination therapy can be offered with similar outcomes. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Backward Response-Level Crosstalk in the Psychological Refractory Period Paradigm

ERIC Educational Resources Information Center

Miller, Jeff; Alderton, Mark

2006-01-01

Bottleneck models of psychological refractory period (PRP) tasks suggest that a Task 1 response should be unaffected by the Task 2 response in the same trial, because selection of the former finishes before selection of the latter begins. Contrary to this conception, the authors found backward response-level crosstalk effects in which Task 2…

Topiramate in Long-Term Treatment of Epilepsy in the Intellectually Disabled

ERIC Educational Resources Information Center

Arvio, M.; Sillanpaa, M.

2005-01-01

To study the effectiveness of topiramate (TPM) in refractory epilepsy in patients who have intellectual disability (ID). A representative population sample of 57 patients with ID (age range 261, mean 32.8) was administered add-on TPM for drug-refractory epilepsy. Results Seizure freedom for at least for 6months was attained by 10 (17%), and…

Long term durability of solid heartwood stakes treated with ACA or CCA

Treesearch

Mark E. Mankowski; Stan Lebow; Grant Kirker; Lee Gjovik

2017-01-01

Limited long-term field data exist evaluating the benefit of chemical wood preservatives on refractory wood species with abundant heartwood. The objective of this study was to determine the effectiveness of preservative-treated refractory solid heartwood comprised of southern pine, Douglas-fir, or Engelmann spruce. Non-incised and incised solid lumber of these species...

Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

PubMed Central

Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

1990-01-01

1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

The effect of postoperative medical treatment on left ventricular mass regression after aortic valve replacement.

PubMed

Helder, Meghana R K; Ugur, Murat; Bavaria, Joseph E; Kshettry, Vibhu R; Groh, Mark A; Petracek, Michael R; Jones, Kent W; Suri, Rakesh M; Schaff, Hartzell V

2015-03-01

The study objective was to analyze factors associated with left ventricular mass regression in patients undergoing aortic valve replacement with a newer bioprosthesis, the Trifecta valve pericardial bioprosthesis (St Jude Medical Inc, St Paul, Minn). A total of 444 patients underwent aortic valve replacement with the Trifecta bioprosthesis from 2007 to 2009 at 6 US institutions. The clinical and echocardiographic data of 200 of these patients who had left ventricular hypertrophy and follow-up studies 1 year postoperatively were reviewed and compared to analyze factors affecting left ventricular mass regression. Mean (standard deviation) age of the 200 study patients was 73 (9) years, 66% were men, and 92% had pure or predominant aortic valve stenosis. Complete left ventricular mass regression was observed in 102 patients (51%) by 1 year postoperatively. In univariate analysis, male sex, implantation of larger valves, larger left ventricular end-diastolic volume, and beta-blocker or calcium-channel blocker treatment at dismissal were significantly associated with complete mass regression. In the multivariate model, odds ratios (95% confidence intervals) indicated that male sex (3.38 [1.39-8.26]) and beta-blocker or calcium-channel blocker treatment at dismissal (3.41 [1.40-8.34]) were associated with increased probability of complete left ventricular mass regression. Patients with higher preoperative systolic blood pressure were less likely to have complete left ventricular mass regression (0.98 [0.97-0.99]). Among patients with left ventricular hypertrophy, postoperative treatment with beta-blockers or calcium-channel blockers may enhance mass regression. This highlights the need for close medical follow-up after operation. Labeled valve size was not predictive of left ventricular mass regression. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Bilirubin attenuates bufadienolide-induced ventricular arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated intracellular Na(+) levels.

PubMed

Ma, Hongyue; Zhang, Junfeng; Jiang, Jiejun; Zhou, Jing; Xu, Huiqin; Zhan, Zhen; Wu, Qinan; Duan, Jinao

2012-03-01

Bufadienolides, known ligands of the sodium pump, have been shown to inhibit the proliferation of several cancer cell types. However, their development to date as anticancer agents has been impaired by a narrow therapeutic margin resulting from their potential to induce cardiotoxicity. In the present study, we examined the effects of bilirubin, an endogenous antioxidant, on the cardiotoxicity of bufadienolides (derived from toad venom) in guinea-pigs. The results showed that bufadienolides (8 mg/kg) caused ventricular arrhythmias, conduction block, cardiac dysfunction and death in guinea-pigs. Pretreatment with bilirubin (75 and 150 mg/kg) significantly prevented bufadienolide-induced premature ventricular complexes, ventricular tachycardia, ventricular fibrillation and death. Bilirubin also markedly improved the inhibition of cardiac contraction in bufadienolide-treated guinea-pigs as evidenced by increases in left ventricular systolic pressure and decreases in left ventricular diastolic pressure in vivo. Furthermore, bilirubin significantly reduced the intracellular sodium content ([Na(+)]( i )) in ex vivo bufadienolide-stimulated guinea-pig ventricular myocytes loaded with the sodium indicator Sodium Green. An antitumor study showed that bilirubin did not compromise the ability of bufadienolides to inhibit gastric cancer cell MGC-803 proliferation. These results suggested that bilirubin can attenuate bufadienolide-induced arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated [Na(+)]( i ) and may improve bufadienolide therapeutic index in cancer treatment.

[Assessment of the right ventricular anatomy and function by advanced echocardiography: pathological and physiological insights].

PubMed

Lakatos, Bálint; Kovács, Attila; Tokodi, Márton; Doronina, Alexandra; Merkely, Béla

2016-07-01

Accurate assessment of right ventricular geometry and function is of high clinical importance. However, several limitations have to be taken into consideration if using conventional echocardiographic parameters. Advanced echocardiographic techniques, such as speckle-tracking analysis or 3D echocardiography are reliable and simple tools providing a cost-effective and non-invasive alternative of current modalities used to characterize the right ventricle. There is a growing interest in the diagnostic and prognostic value of these methods regarding pathological (right ventricular infarction, pulmonary hypertension, arrhythmogenic right ventricular dysplasia, follow-up of heart transplantation) and even physiological (athlete's heart) alterations of the right ventricle. Orv. Hetil., 2016, 157(29), 1139-1146.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massie, B.; Kramer, B.L.; Topic, N.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responsesmore » at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml and from 52 +/- 26 to 43 +/- 20 volume units, respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg. Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22+/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively. During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. This, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.« less

Experimental study on the effect of an artificial cardiac valve on the left ventricular flow

NASA Astrophysics Data System (ADS)

Wang, JiangSheng; Gao, Qi; Wei, RunJie; Wang, JinJun

2017-09-01

The use of artificial valves to replace diseased human heart valves is currently the main solution to address the malfunctioning of these valves. However, the effect of artificial valves on the ventricular flow still needs to be understood in flow physics. The left ventricular flow downstream of a St. Jude Medical (SJM) bileaflet mechanical heart valve (BMHV), which is a widely implanted mechanical bileaflet valve, is investigated with time-resolved particle image velocimetry in the current work. A tilting-disk valve is installed on the aortic orifice to guarantee unidirectional flow. Several post-processing tools are applied to provide combined analyses of the physics involved in the ventricular flow. The triple jet pattern that is closely related to the characteristics of the bileaflet valve is discussed in detail from both Eulerian and Lagrangian views. The effects of large-scale vortices on the transportation of blood are revealed by the combined analysis of the tracking of Lagrangian coherent structures, the Eulerian monitoring of the shear stresses, and virtual dye visualization. It is found that the utilization of the SJM BMHV complicates the ventricular flow and could reduce the efficiency of blood transportation. In addition, the kinematics of the bileaflets is presented to explore the effects of flow structures on their motion. These combined analyses could elucidate the properties of SJM BMHV. Furthermore, they could provide new insights into the understanding of other complex blood flows.

Simulation of acute haemodynamic outcomes of the surgical strategies for the right ventricular failure treatment in pediatric LVAD.

PubMed

Di Molfetta, Arianna; Ferrari, Gianfranco; Iacobelli, Roberta; Filippelli, Sergio; Fresiello, Libera; Gagliardi, Maria G; Toscano, Alessandro; Trivella, Maria G; Amodeo, Antonio

2015-12-01

Right ventricular failure (RVF) is one of the major complications during LVAD. Apart from drug therapy, the most reliable option is the implantation of RVAD. However, BIVAD have a poor prognosis and increased complications. Experiments have been conducted on alternative approaches, such as the creation of an atrial septal defect (ASD), a cavo-aortic shunt (CAS) including the LVAD and a cavo-pulmonary connection (CPC). This work aims at realizing a lumped parameter model (LPM) to compare the acute hemodynamic effects of ASD, CPC, CAS, RVAD in LVAD pediatric patients with RVF. Data of 5 pediatric patients undergoing LVAD were retrospectively collected to reproduce patients baseline hemodynamics with the LPM. The effects of continuous flow LVAD implantation complicated by RVF was simulated and then the effects of ASD, CPC, CAS and RVAD treatments were simulated for each patient. The model successfully reproduced patients' baseline and the hemodynamic effects of the surgical strategies. Simulating the different surgical strategies, an unloading of the right ventricle and an increment of left ventricular preload were observed with an improvement of the hemodynamics (total cardiac output: ASD +15%, CPC +10%, CAS +70% RVAD +20%; right ventricular external work: ASD -19%, CPC -46%, CAS -76%, RVAD -32%; left ventricular external work: ASD +12%, CPC +28%, RVAD +64%). The use of numerical model could offer an additional support for clinical decision-making, also potentially reducing animal experiments, to compare the outcome of different surgical strategies to treat RVF in LVAD.

Beneficiation and leaching study of a muti-Au carrier and low grade refractory gold ore

NASA Astrophysics Data System (ADS)

Li, W. J.; Song, Y. S.; Chen, Y.; Cai, L. L.; Zhou, G. Y.

2017-09-01

Detailed mineralogy and beneficiation and leaching study of a muti-Au carrier, low grade refractory gold ore from a beneficiation plant in Henan Province, China, was investigated. Mineral liberation analysis, scanning electron microscopy, element phase analysis and etc. by a mineral liberation analyser were used for mineralogical characterization study of this ore. The present work describes an experimental study on the effect of traditional parameters (such as grinding fineness and reagent regimes), middling processing method and flowsheet construction on the total recovery and the assay of the floatation concentrate. Two-step floatation and part of middling combined to the floatation tailing for gold leaching process resulted in high gold grade (g.t-1) and gold recovery (%) for this refractory gold ore. This process opens the possibilities of maximizing Au grade and recoveries in a muti-Au carrier and low grade refractory gold ore where low recoveries are common.

Dietary therapy is not the best option for refractory nonsurgical epilepsy.

PubMed

Vaccarezza, María Magdalena; Silva, Walter Horacio

2015-09-01

The ketogenic diet (KD) is currently a well-established treatment for patients with medically refractory, nonsurgical epilepsy. However, despite its efficacy, the KD is highly restrictive and constitutes a treatment with serious potential adverse effects, and often with difficulties in its implementation and compliance. Patients on the KD require strict follow-up and constant supervision by a medical team highly experienced in its management in order to prevent complications. Other alternative treatments for patients with refractory epilepsy include vagus nerve stimulation (VNS), new-generation antiepileptic drugs (AEDs), corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this review, we explain not only the difficulties of the KD as a therapeutic option for refractory epilepsy but also the benefits of other therapeutic strategies, which, in many cases, have proven to have better efficacy than the KD itself. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

PubMed

Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

2016-11-08

Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

Idiopathic ventricular tachycardia and fibrillation.

PubMed

Belhassen, B; Viskin, S

1993-06-01

Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healty patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellent.

A 2:1 AV rhythm: an adverse effect of a long AV delay during DDI pacing and its prevention by the ventricular intrinsic preference algorithm in DDD mode.

PubMed

Minamiguchi, Hitoshi; Oginosawa, Yasushi; Kohno, Ritsuko; Tamura, Masahito; Takeuchi, Masaaki; Otsuji, Yutaka; Abe, Haruhiko

2012-07-01

A 91-year-old woman received a dual-chamber pacemaker for sick sinus syndrome and intermittently abnormal atrioventricular (AV) conduction. The pacemaker was set in DDI mode with a 350-ms AV delay to preserve intrinsic ventricular activity. She complained of palpitation during AV sequential pacing. The electrocardiogram showed a 2:1 AV rhythm from 1:1 ventriculoatrial (VA) conduction during ventricular pacing in DDI mode with a long AV interval. After reprogramming of the pacemaker in DDD mode with a 250-ms AV interval and additional 100-ms prolongation of the AV interval by the ventricular intrinsic preference function, VA conduction disappeared and the patient's symptom were alleviated without increasing unnecessary right ventricular pacing. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

The application of microwave digestion in decomposing some refractory ore samples with solid fusion agent.

PubMed

Lu, Yan; Li, Gang; Liu, Wei; Yuan, Hongyan; Xiao, Dan

2018-08-15

It is known that most of the refractory ore are the basis of national economy and widely applied in various fields, however, the complexity of the chemical composition and the diversity of the crystallinity in the mineral phases make the sample pre-treatment of refractory ore still remains a challenge. In this work, the complete decomposition of the refractory ore sample can be achieved just by exposing the solid fusion agent and the refractory ore sample in the microwave irradiation environment for a few minutes, and induced by a drop of water. A digestion time of 15 min for 3.0 g solid fusion agent mixture of sodium peroxide/sodium carbonate (Na 2 O 2 /Na 2 CO 3 ) in a corundum crucible via microwave heating is sufficient to decompose 0.1 g refractory ore sample. An excellent microwave digestion solid agent should meet the following conditions, a good decomposition ability, an outstanding ability of absorbing microwave energy and converting it into heat quickly, a higher melting point than the decomposing temperature of the ore sample. In the research, the induction effect of water plays an important role for the microwave digestion. The energy which is released by the reaction of water and the solid fusion agent (Na 2 O 2 ) is the key to decompose refractory ore samples with solid fusion agent, which replenished the total energy required for the microwave digestion and made the microwave digestion completed successfully. This microwave digestion technique has good reproducibility and precision, RSD % for Mo, Fe, Ti, Cr and W in the refractory ore samples were all better than 6, except RSD % for Be of about 8 because of the influence of matrix-effect. Meanwhile, the analysis results of the elements in the refractory ore samples provided by the microwave digestion technique were all in good agreement with the analysis results provided by the traditional fusion method except for Cr in the mixture ore samples. In the study, the non-linear dependence of the electromagnetic and thermal properties of the solid fusion agent on temperature under microwave irradiation and the selective heating of microwave are fully applied in this simple microwave technique. Comparing to the traditional fusion decomposition method, this microwave digestion technique is a simple, economical, fast and energy-saving sample pre-treatment technique. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical trial design and rationale of the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) investigational device exemption clinical study protocol.

PubMed

Heatley, Gerald; Sood, Poornima; Goldstein, Daniel; Uriel, Nir; Cleveland, Joseph; Middlebrook, Don; Mehra, Mandeep R

2016-04-01

The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc., formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into clinical trials for durable circulatory support in patients with medically refractory advanced-stage heart failure. This centrifugal, fully magnetically levitated, continuous-flow pump is engineered with the intent to enhance hemocompatibility and reduce shear stress on blood elements, while also possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and destination therapy (DT) are established dichotomous indications for durable left ventricular assist device (LVAD) support, clinical practice has challenged the appropriateness of these designations. The introduction of novel LVAD technology allows for the development of clinical trial designs to keep pace with current practices. The prospective, randomized Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also St. Jude Medical, Inc.). The innovative trial design includes patients enrolled under a single inclusion and exclusion criteria , regardless of the intended use of the device, with outcomes ascertained in the short term (ST, at 6 months) and long term (LT, at 2 years). This adaptive trial design includes a pre-specified safety phase (n = 30) analysis. The ST cohort includes the first 294 patients and the LT cohort includes the first 366 patients for evaluation of the composite primary end-point of survival to transplant, recovery or LVAD support free of debilitating stroke (modified Rankin score >3), or re-operation to replace the pump. As part of the adaptive design, an analysis by an independent statistician will determine whether sample size adjustment is required at pre-specified times during the study. A further 662 patients will be enrolled to reach a total of 1,028 patients for evaluation of the secondary end-point of pump replacement at 2 years. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The abundance and relative volatility of refractory trace elements in Allende Ca,Al-rich inclusions - Implications for chemical and physical processes in the solar nebula

NASA Technical Reports Server (NTRS)

Kornacki, Alan S.; Fegley, Bruce, Jr.

1986-01-01

The relative volatilities of lithophile refractory trace elements (LRTE) were determined using calculated 50-percent condensation temperatures. Then, the refractory trace-element abundances were measured in about 100 Allende inclusions. The abundance patterns found in Allende Ca,Al-rich inclusions (CAIs) and ultrarefractory inclusions were used to empirically modify the calculated LRTE volatility sequence. In addition, the importance of crystal-chemical effects, diffusion constraints, and grain transport for the origin of the trace-element chemistry of Allende CAIs (which have important implications for chemical and physical processes in the solar nebula) is discussed.

Rehabilitation of the dominance of maxillary central incisors with refractory porcelain veneers requiring minimal tooth preparation.

PubMed

da Cunha, Leonardo Fernandes; Gonzaga, Carla Castiglia; Saab, Rafaella; Mushashe, Amanda Mahammad; Correr, Gisele Maria

2015-01-01

Central dominance is an important element of an esthetic smile. Color, form, and size have been suggested as tools for assessing the dominance of maxillary teeth. A spectrophotometer can be used to determine the value, hue, and chroma. Correct sizing of restorations according to the central incisor dominance principle improves not only esthetics but also aspects of occlusion, such as anterior guidance. Refractory porcelain systems can effectively restore the color, shape, emergence profile, and incisal translucency. This report illustrates the esthetic and occlusal rehabilitation of the dominance of maxillary central incisors using fabricated minimal thickness refractory porcelain veneers.

Spontaneous growth of polarizing refractory metal ‘nano-fins’

NASA Astrophysics Data System (ADS)

Tai, M. C.; Gentle, A. R.; Arnold, M. D.; Cortie, M. B.

2018-03-01

Traditional polymer polarizers degrade in harsh environments and at high temperatures, reducing the polarization effect. In contrast, polarizers produced with refractory metals have vastly improved thermal stability and resistance to harsh environments but are expensive to fabricate. Here we demonstrate prototype refractory metal wire grid polarizers produced by co-sputtering molybdenum and aluminum under specific conditions. Removal of the aluminum through selective dissolution enables the nanostructure array to transmit light. The polarization spans 500-1100 nm and the extinction ratio significantly increases to >100. Possessing broadband polarization and sufficient extinction ratios, the new polarizing film has potential applications in coatings for sunglasses, windows, pyrometers, scientific instruments, and LCD panels.

Additional Octreotide Therapy to Sirolimus Achieved a Decrease in Sirolimus-refractory Chylous Effusion Complicated with Lymphangioleiomyomatosis.

PubMed

Namba, Masashi; Masuda, Takeshi; Nakamura, Takashi; Horimasu, Yasushi; Miyamoto, Shintaro; Nakashima, Taku; Iwamoto, Hiroshi; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru

2017-12-15

Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control postoperative chylous effusion, in addition to the sirolimus therapy. This combination therapy reduced the chylothorax and chylous ascites. For patients with LAM, octreotide therapy in addition to sirolimus may be effective for treating sirolimus-refractory chylous effusion.

Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

ClinicalTrials.gov

2018-04-27

Blastic Plasmacytoid Dendritic Cell Neoplasm; Hepatosplenic T-Cell Lymphoma; HTLV-1 Infection; NK-Cell Lymphoma, Unclassifiable; Primary Systemic Anaplastic Large Cell Lymphoma, ALK-Negative; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Mycosis Fungoides; Refractory Adult T-Cell Leukemia/Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Mycosis Fungoides; Refractory Nasal Type Extranodal NK/T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

ClinicalTrials.gov

2018-03-12

Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Plasma Cell Myeloma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Plasma Cell Myeloma; Refractory T-Cell Non-Hodgkin Lymphoma

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

ClinicalTrials.gov

2018-05-02

High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; MYC Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Percutaneous and Endoscopic Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis.

PubMed

Helm, Standiford; Racz, Gabor B; Gerdesmeyer, Ludger; Justiz, Rafael; Hayek, Salim M; Kaplan, Eugene D; El Terany, Mohamed Ahamed; Knezevic, Nebojsa Nick

2016-02-01

Chronic refractory low back and lower extremity pain is frustrating to treat. Percutaneous adhesiolysis and spinal endoscopy are techniques which can treat chronic refractory low back and lower extremity pain.Percutaneous adhesiolysis is performed by placing the catheter into the tissue plane at the ventrolateral aspect of the foramen so that medications can be injected. Adhesiolysis is used both for pain caused by scarring which is not resistant to catheter placement and other sources of pain, including inflammation in the absence of scarring.Mechanical lysis of scars with a catheter may or may not be necessary for percutaneous adhesiolysis to be effective. Spinal endoscopy allows direct visualization of the epidural space and has the possibility to use laser energy to treat pathology. A systematic review of the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. To evaluate and update the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. The available literature on percutaneous adhesiolysis and spinal endoscopic adhesiolysis in treating persistent low back and leg pain was reviewed. The quality of each article used in this analysis was assessed. The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials to weak, based upon consensus, as developed by the U.S. Preventive Services Task Force (USPSTF) and modified by ASIPP. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015, and manual searches of the bibliographies of known primary and review articles. Pain relief of at least 50% and functional improvement of at least 40% were the primary outcome measures. Short-term efficacy was defined as improvement of 6 months or less; whereas, long-term efficacy was defined more than 6 months. For this systematic review, 45 studies were identified. Of these, for percutaneous adhesiolysis there were 7 randomized controlled trials and 3 observational studies which met the inclusion criteria. For spinal endoscopy, there was one randomized controlled trial and 3 observational studies. Based upon 7 randomized controlled trials showing efficacy, with no negative trials, there is Level I or strong evidence of the efficacy of percutaneous adhesiolysis in the treatment of chronic refractory low back and lower extremity pain. Based upon one high-quality randomized controlled trial, there is Level II to III evidence supporting the use of spinal endoscopy in treating chronic refractory low back and lower extremity pain. The evidence is Level I or strong that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain. Percutaneous adhesiolysis may be considered as a first-line treatment for chronic refractory low back and lower extremity pain. The evidence is Level II to III that spinal endoscopy is effective in the treatment of chronic refractory low back and lower extremity pain. Spinal pain, chronic low back pain, post lumbar surgery syndrome, epidural scarring, adhesiolysis, endoscopy, radicular pain.

Effect of the mitral valve on diastolic flow patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Jung Hee; Vedula, Vijay; Mittal, Rajat, E-mail: mittal@jhu.edu

2014-12-15

The leaflets of the mitral valve interact with the mitral jet and significantly impact diastolic flow patterns, but the effect of mitral valve morphology and kinematics on diastolic flow and its implications for left ventricular function have not been clearly delineated. In the present study, we employ computational hemodynamic simulations to understand the effect of mitral valve leaflets on diastolic flow. A computational model of the left ventricle is constructed based on a high-resolution contrast computed-tomography scan, and a physiological inspired model of the mitral valve leaflets is synthesized from morphological and echocardiographic data. Simulations are performed with a diodemore » type valve model as well as the physiological mitral valve model in order to delineate the effect of mitral-valve leaflets on the intraventricular flow. The study suggests that a normal physiological mitral valve promotes the formation of a circulatory (or “looped”) flow pattern in the ventricle. The mitral valve leaflets also increase the strength of the apical flow, thereby enhancing apical washout and mixing of ventricular blood. The implications of these findings on ventricular function as well as ventricular flow models are discussed.« less

Atrial fibrillation: effects beyond the atrium?

PubMed

Wijesurendra, Rohan S; Casadei, Barbara

2015-03-01

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with systemic inflammation, endothelial dysfunction, and adverse effects on the structure and function of the left ventricular myocardium that may be prognostically important. Here, we review the molecular and in vivo evidence that underpins current knowledge regarding the effects of human or experimental AF on the ventricular myocardium. Potential mechanisms are explored including diffuse ventricular fibrosis, focal myocardial scarring, and impaired myocardial perfusion and perfusion reserve. The complex relationship between AF, systemic inflammation, as well as endothelial/microvascular dysfunction and the effects of AF on ventricular calcium handling and oxidative stress are also addressed. Finally, consideration is given to the clinical implications of these observations and concepts, with particular reference to rate vs. rhythm control. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Age-related peculiarities of contractile activity of rat myocardium during blockade of hyperpolarization-activated currents.

PubMed

Zefirov, T L; Gibina, A E; Sergejeva, A M; Ziyatdinova, N I; Zefirov, A L

2007-09-01

Contractile activity of atrial and ventricular myocardial strips isolated from rats of various age was examined under conditions of blockade of non-selective hyperpolarization-activated cation currents. Addition of ZD7288, a blocker of non-selective hyperpolarization-activated cation currents, to the perfusion solution increased the contraction force of atrial and ventricular strips in 1-, 8-, and 20-week rats, but produced an opposite effect on contractile activity of atrial and ventricular strips in 3-week rats.

Using left-ventricular-only pacing to eliminate T-wave oversensing in a biventricular implantable cardiac defibrillator.

PubMed

Khoo, Clarence; Bennett, Matthew; Chakrabarti, Santabhanu; LeMaitre, John; Tung, Stanley K K

2013-02-01

A man aged 75 years and with nonischemic cardiomyopathy had implantation of a biventricular implantable cardiac defibrillator (ICD). Consistent biventricular pacing was limited by intermittent T-wave oversensing (TWOS). A strategy of left-ventricular-only pacing was used to eliminate TWOS. This strategy obviates the need to reduce ventricular sensitivity and thus may be an effective alternative to biventricular pacing complicated by TWOS. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The effect of acetyl strophanthidin on the hearts of normal dogs.

PubMed

Hayes, A H; McShane, W P; Sidell, F R

1970-05-01

1. The ED50 of acetyl strophanthidin for producing ventricular arrhythmias in normal dogs was 54.5 mug/kg intravenously.2. Doses up to and including those which caused ventricular tachycardia did not produce either atrial arrhythmias or significant aberration of A-V conduction.3. Although the classic digitalis-induced rate and e.c.g. waveform changes may appear after administration of acetyl strophanthidin, their presence or absence have no value in predicting the subsequent development of ventricular arrhythmias.

Effects of β-adrenergic receptor drugs on embryonic ventricular cell proliferation and differentiation and their impact on donor cell transplantation.

PubMed

Feridooni, Tiam; Hotchkiss, Adam; Baguma-Nibasheka, Mark; Zhang, Feixiong; Allen, Brittney; Chinni, Sarita; Pasumarthi, Kishore B S

2017-05-01

β-Adrenergic receptors (β-ARs) and catecholamines are present in rodents as early as embryonic day (E)10.5. However, it is not known whether β-AR signaling plays any role in the proliferation and differentiation of ventricular cells in the embryonic heart. Here, we characterized expression profiles of β-AR subtypes and established dose-response curves for the nonselective β-AR agonist isoproterenol (ISO) in the developing mouse ventricular cells. Furthermore, we investigated the effects of ISO on cell cycle activity and differentiation of cultured E11.5 ventricular cells. ISO treatment significantly reduced tritiated thymidine incorporation and cell proliferation rates in both cardiac progenitor cell and cardiomyocyte populations. The ISO-mediated effects on DNA synthesis could be abolished by cotreatment of E11.5 cultures with either metoprolol (a β 1 -AR antagonist) or ICI-118,551 (a β 2 -AR antagonist). In contrast, ISO-mediated effects on cell proliferation could be abolished only by metoprolol. Furthermore, ISO treatment significantly increased the percentage of differentiated cardiomyocytes compared with that in control cultures. Additional experiments revealed that β-AR stimulation leads to downregulation of Erk and Akt phosphorylation followed by significant decreases in cyclin D1 and cyclin-dependent kinase 4 levels in E11.5 ventricular cells. Consistent with in vitro results, we found that chronic stimulation of recipient mice with ISO after intracardiac cell transplantation significantly decreased graft size, whereas metoprolol protected grafts from the inhibitory effects of systemic catecholamines. Collectively, these results underscore the effects of β-AR signaling in cardiac development as well as graft expansion after cell transplantation. NEW & NOTEWORTHY β-Adrenergic receptor (β-AR) stimulation can decrease the proliferation of embryonic ventricular cells in vitro and reduce the graft size after intracardiac cell transplantation. In contrast, β 1 -AR antagonists can abrogate the antiproliferative effects mediated by β-AR stimulation and increase graft size. These results highlight potential interactions between adrenergic drugs and cell transplantation. Copyright © 2017 the American Physiological Society.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

PubMed

Gohean, Jeffrey R; George, Mitchell J; Pate, Thomas D; Kurusz, Mark; Longoria, Raul G; Smalling, Richard W

2013-01-01

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

PubMed Central

Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

1970-01-01

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.

PubMed

Fuenmayor, Abdel J; Solórzano, Moisés I; Gómez, Luisangelly

2016-10-01

We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device

PubMed Central

Gohean, Jeffrey R.; George, Mitchell J.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

2012-01-01

The purpose of this investigation is to utilize a computational model to compare a synchronized valveless pulsatile left ventricular assist device to continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous, pulsatile, valveless, dual piston positive displacement pump. These results were compared to measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared to the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device. PMID:23438771

Amiodarone and Catheter Ablation as Cardiac Resynchronization Therapy for Children with Dilated Cardiomyopathy and Wolff-Parkinson-White Syndrome

PubMed Central

Kim, Sung Hoon; Jeong, Soo In; Kang, I-Seok; Lee, Heung Jae

2013-01-01

Preexcitation by accessory pathways (APs) is known to cause dyssynchrony of the ventricle, related to ventricular dysfunction. Correction of ventricular dyssynchrony can improve heart failure in cases of dilated cardiomyopathy (DCMP) with preexcitation. Here, we report the first case of a child with DCMP and Wolff-Parkinson-White (WPW) syndrome treated with amiodarone and radiofrequency catheter ablation (RFCA) in Korea. A 7-year-old boy, who suffered from DCMP and WPW syndrome, showed improved left ventricular function and clinical functional class after treatment with amiodarone to eliminate preexcitation. QRS duration and left ventricular ejection fraction (LVEF) were inversely correlated with amiodarone dosage. After confirming the reduction of preexcitation effects in DCMP, successful RFCA of the right anterior AP resulted in LVEF improvement, along with the disappearance of preexcitation. Our findings suggest that ventricular dyssynchrony, caused by preexcitation in DCMP with WPW syndrome, can worsen ventricular function and amiodarone, as well as RFCA, which should be considered as a treatment option, even in young children. PMID:23407697

Preliminary Results From the C-Pulse OPTIONS HF European Multicenter Post-Market Study.

PubMed

Schulz, Antonia; Krabatsch, Thomas; Schmitto, Jan D; Hetzer, Roland; Seidel, Mirko; Dohmen, Pascal M; Hotz, Holger

2016-02-18

BACKGROUND The C-Pulse System is an extra-aortic balloon counterpulsation device. It is used to treat patients with heart failure disease in NYHA functional class III or ambulatory class IV. MATERIAL AND METHODS We present preliminary site-reported 6-month data from 3 centers in Germany as part of the prospective observational post-market OPTIONS HF study. RESULTS Between May 2013 and March 2014, the C-Pulse System was implanted in 8 patients (7 male) with a mean age of 61.6±9.3 years. Four had ischemic and 4 had non-ischemic cardiomyopathy. No stroke, myocardial infarction, major bleeding, or major infection due to the device were reported. One patient developed non-device-related refractory tachycardia with worsening heart failure 12 h after surgery and underwent left ventricular assist device implantation. Within 6 months of observation, functional status improved from NYHA III to II in 5 patients, and 2 remained in NYHA III. Mean left ventricular ejection fraction increased from 24.3±7.9% to 44.5±4.5% (p<0.0001). Mean Kansas City Cardiomyopathy Questionnaire overall score improved from 28.6±19.1 to 59.1±22.5 (p=0.0183). Six-minute walk test was performed in 6 out of 7 patients at follow-up. The mean distance improved from 252.0±85.1 m to 279.2±87.5 m (p>0.05). One patient was weaned off the device after 6 months of support. CONCLUSIONS The C-Pulse System provides a therapeutic option for patients with moderate-to-severe heart failure and seems to improve quality of life and cardiac function over time.

[Intravenous ablation of the atrio-ventricular junction in patients with supraventricular tachyarrhythmias].

PubMed

Drzewiecki, J; Trusz-Gluza, M; Wnuk-Wojnar, A; Jaklik, A; Czerwiński, C; Filipecki, A; Szydło, K; Ciemniewski, Z; Giec, L

1993-01-01

Since the first successful therapeutic DC ablation of the AV junction in 1986, we have treated 20 symptomatic patients with drug-refractory supraventricular tachyarrhythmias (average of 6 antiarrhythmic drugs prior to the ablation attempt). The primary rhythm disturbances necessitating ablation were: AV nodal reentrant tachycardia (50% of pts), atrial flutter or fibrillation, with an uncontrolled rapid ventricular response (40%), atrioventricular reentrant tachycardia using an accessory pathway (20%), atrial tachycardia (10%), and junctional reciprocating tachycardia (5%). Percutaneous catheter ablation of the AV junction was made by Gallagher's method. The USCI 4-polar catheter (7F) was used in 40% of pts, and bipolar Cordis catheter (5F) in the remaining 60%. 70% of pts received either one or two shocks, usually of 200 or 300 J during one session. Another 25% received stored cumulative energy from 800 to 1200 J (in two sessions), and one patient--1800 J (during three sessions). In 85% of pts, the immediate post-ablation conduction was third-degree AV block with the escape pacemaker, ranging from 20 to 50 beats/min., which was infra-His in 57%, and supra-His in 43% of pts. In 15% of pts were either first-degree AV block (10%) or normal AV conduction (5%). A His bundle deflection more than 0.2 mV was predictive of successful production of third-degree AV block. Except a mild and transient increase of indicating enzymes (CPK and CPK-MB) we did not observe any other serious complications directly related to the ablalation procedure. Follow-up study included 19 pts (time range from 2 to 56 months, mean 28).(ABSTRACT TRUNCATED AT 250 WORDS)

Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy

PubMed Central

Yamada, Satsuki; Nelson, Timothy J.; Crespo-Diaz, Ruben J.; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

2009-01-01

Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel sub-units. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional KATP channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. PMID:18669912

Embryonic stem cell therapy of heart failure in genetic cardiomyopathy.

PubMed

Yamada, Satsuki; Nelson, Timothy J; Crespo-Diaz, Ruben J; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

2008-10-01

Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K(+) (K(ATP)) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional K(ATP) channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is found at the end of this article.

Is increased positive end-expiratory pressure the culprit? Autoresuscitation in a 44-year-old man after prolonged cardiopulmonary resuscitation: a case report.

PubMed

Hagmann, Henning; Oelmann, Katrin; Stangl, Robert; Michels, Guido

2016-12-20

The phenomenon of autoresuscitation is rare, yet it is known to most emergency physicians. However, the pathophysiology of the delayed return of spontaneous circulation remains enigmatic. Among other causes hyperinflation of the lungs and excessively high positive end-expiratory pressure have been suggested, but reports including cardiopulmonary monitoring during cardiopulmonary resuscitation are scarce to support this hypothesis. We report a case of autoresuscitation in a 44-year-old white man after 80 minutes of advanced cardiac life support accompanied by continuous capnometry and repeated evaluation by ultrasound and echocardiography. After prolonged cardiopulmonary resuscitation, refractory electromechanical dissociation on electrocardiogram and ventricular akinesis were recorded. In addition, a precipitous drop in end-tidal partial pressure of carbon dioxide was noted and cardiopulmonary resuscitation was discontinued. Five minutes after withdrawal of all supportive measures his breathing resumed and a perfusing rhythm ensued. Understanding the underlying pathophysiology of autoresuscitation is hampered by a lack of reports including extensive cardiopulmonary monitoring during cardiopulmonary resuscitation in a preclinical setting. In this case, continuous capnometry was combined with repetitive ultrasound evaluation, which ruled out most assumed causes of autoresuscitation. Our observation of a rapid decline in end-tidal partial pressure of carbon dioxide supports the hypothesis of increased intrathoracic pressure. Continuous capnometry can be performed easily during cardiopulmonary resuscitation, also in a preclinical setting. Knowledge of the pathophysiologic mechanisms may lead to facile interventions to be incorporated into cardiopulmonary resuscitation algorithms. A drop in end-tidal partial pressure of carbon dioxide, for example, might prompt disconnection of the ventilation to allow left ventricular filling. Further reports and research on this topic are encouraged.

Basic and advanced paediatric cardiopulmonary resuscitation - guidelines of the Australian and New Zealand Resuscitation Councils 2010.

PubMed

Tibballs, James; Aickin, Richard; Nuthall, Gabrielle

2012-07-01

Guidelines for basic and advanced paediatric cardiopulmonary resuscitation (CPR) have been revised by Australian and New Zealand Resuscitation Councils. Changes encourage CPR out-of-hospital and aim to improve the quality of CPR in-hospital. Features of basic CPR include: omission of abdominal thrusts for foreign body airway obstruction; commencement with chest compression followed by ventilation in a ratio of 30:2 or compression-only CPR if the rescuer is unwilling/unable to give expired-air breathing when the victim is 'unresponsive and not breathing normally'. Use of automated external defibrillators is encouraged. Features of advanced CPR include: prevention of cardiac arrest by rapid response systems; restriction of pulse palpation to 10 s to diagnosis cardiac arrest; affirmation of 15:2 compression-ventilation ratio for children and for infants other than newly born; initial bag-mask ventilation before tracheal intubation; a single direct current shock of 4 J/kg for ventricular fibrillation (VF) and pulseless ventricular tachycardia followed by immediate resumption of CPR for 2 min without analysis of cardiac rhythm and avoidance of unnecessary interruption of continuous external cardiac compressions. Monitoring of exhaled carbon dioxide is recommended to detect non-tracheal intubation, assess quality of CPR, and to help match ventilation to reduced cardiac output. The intraosseous route is recommended if immediate intravenous access is impossible. Amiodarone is strongly favoured over lignocaine for refractory VF and adrenaline over atropine for severe bradycardia, asystole and pulseless electrical activity. Family presence at resuscitation is encouraged. Therapeutic hypothermia is acceptable after resuscitation to improve neurological outcome. Extracorporeal circulatory support for in-hospital cardiac arrest may be used in equipped centres. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus.

PubMed

Lin, Jainn-Jim; Chou, Cheng-Che; Lan, Shih-Yun; Hsiao, Hsiang-Ju; Wang, Yu; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Lin, Kuang-Lin

2017-09-01

Evidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. We retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. Thirty-five patients (23 boys; age range: 1-18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. Our results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Change of heart dimensions and function during pregnancy in goats.

PubMed

Szaluś-Jordanow, Olga; Czopowicz, Michał; Witkowski, Lucjan; Moroz, Agata; Mickiewicz, Marcin; Frymus, Tadeusz; Markowska-Daniel, Iwona; Bagnicka, Emilia; Kaba, Jarosław

2018-03-08

The study aimed to evaluate the effect of pregnancy on heart diameters and function in goats. Transthoracic echocardiography of 12 female dairy goats of two Polish regional breeds was performed. A Mindray M7 diagnostic ultrasound system with Phased Array transducer was used. Simultaneously, electrocardiography was recorded. All animals were examined four times - at mating season, at the end of the first trimester, at the end of the second trimester and just before kidding. Eleven measurements were taken each time: aortic and left atrial diameter (AoD and LAD), right and left ventricular internal diameter in diastole (RVIDd and LVIDd), left ventricular internal diameter in systole (LVIDs), inter-ventricular septum thickness in diastole and systole (IVSd and IVSd) and left ventricular posterior wall in diastole and systole (LVPWd and LVPWs), maximum left and right ventricular outflow tract velocity (RVOT Vmax and LVOT Vmax). Nine consecutive measurements were derived: the ratio of the left atrial diameter to the aortic diameter (AoD/LAD), left ventricular fractional shortening (FS%), left ventricular ejection fraction (EF%), maximum outflow tract pressure gradients (RVOT PGmax and LVOT PGmax), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV), stroke volume (SV) and cardiac output (CO). HR, LAD, LVPWs, IVSs increased significantly in the first trimester. AoD and RVIDd were significantly higher around parturition. LVIDd, FS%, EF%, SV and CO rose both in the first and third trimester. No measurement decreased during pregnancy. The study confirms that pregnancy causes changes in the heart size and functioning. Copyright © 2018. Published by Elsevier Ltd.

Ventricular distension and diastolic coronary blood flow in the anaesthetized dog.

PubMed

Gattullo, D; Linden, R J; Losano, G; Pagliaro, P; Westerhof, N

1993-01-01

There appears to be no agreement as to whether or not an increase in diastolic left ventricular pressure and/or volume can cause a decrease in diastolic coronary blood flow. We investigated the problem in the anaesthetized dog using a flaccid freely distensible latex balloon inserted into the left ventricle with the animal on extracorporeal circulation and the coronary perfusion pressure constant at about 45 mm Hg. Maximal vasodilatation and suppression of autoregulation in coronary vasculature was obtained by the intracoronary infusion of dipyridamole (10-40 mg/h). Ventricular volume was changed in steps of 10 ml from 10 to 70 ml and back to 10 ml, whilst recording coronary blood flow and left ventricular pressure in the left circumflex coronary artery. Over a range of ventricular volumes from 20 to 50 ml and a concomitant rise in diastolic ventricular pressure to about 20 mm Hg there was no change in the diastolic coronary flow. Only when the ventricular volume was more than two times the control value (i.e. exceeded 50 ml) and left ventricular pressure was more than 20 mm Hg, was there a decrease in coronary flow. During the return of the volume to the control level there was a fall in diastolic flow and ventricular contractility with respect to the values obtained when the volume was increased; these two effects were transient lasting less than 10 min. It was not considered that any of the three models of the coronary circulation, waterfall, intramyocardial pump or varying elastance model could explain our results.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal obesity, gestational weight gain and childhood cardiac outcomes: role of childhood body mass index.

PubMed

Toemen, L; Gishti, O; van Osch-Gevers, L; Steegers, E A P; Helbing, W A; Felix, J F; Reiss, I K M; Duijts, L; Gaillard, R; Jaddoe, V W V

2016-07-01

Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index. In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (g m(-2.7)), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling. A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index. Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.

Ventricular Effective Refraction Period and Ventricular Repolarization Analysis in Experimental Tachycardiomyopathy in Swine.

PubMed

Noszczyk-Nowak, Agnieszka; Pasławska, Urszula; Gajek, Jacek; Janiszewski, Adrian; Pasławski, Robert; Zyśko, Dorota; Nicpoń, Józef

2016-01-01

Swine are recognized animal models of human cardiovascular diseases. However, little is known on the CHF-associated changes in the electrophysiological ventricular parameters of humans and animals. The aim of this study was to analyze changes in the durations of ventricular effective refraction period (VERP), QT and QTc intervals of pigs with chronic tachycardia-induced tachycardiomyopathy (TIC). The study was comprised of 28 adult pigs (8 females and 20 males) of the Polish Large White breed. A one-chamber pacemaker was implanted in each of the 28 pigs. Electrocardiographic, echocardiographic and electrophysiological studies were carried out prior to the pacemaker implantation and at subsequent 4-week intervals. All electrocardiographic, echocardiographic and short electrophysiological study measurements in all swine were done under general anesthesia (propofol) after premedication with midazolam, medetomidine, and ketamine. No significant changes in the duration of QT interval and corrected QT interval (QTc) were observed during consecutive weeks of the experiment. The duration of the QTc interval of female pigs was shown to be significantly longer than that of the males throughout the whole study period. Beginning from the 12th week of rapid ventricular pacing, a significant increase in duration of VERP was observed in both male and female pigs. Males and females did not differ significantly in terms of VERP duration determined throughout the whole study period. Ventricular pacing, stimulation with 2 and 3 premature impulses at progressively shorter coupling intervals and an imposed rhythm of 130 bpm or 150 bpm induced transient ventricular tachycardia in one female pig and four male pigs. One episode of permanent ventricular tachycardia was observed. The number of induced arrhythmias increased proportionally to the severity of heart failure and duration of the experiment. However, relatively aggressive protocols of stimulation were required in order to induce arrhythmia in the studied pigs.

Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices.

PubMed

de Diego, Carlos; González-Torres, Luis; Núñez, José María; Centurión Inda, Raúl; Martin-Langerwerf, David A; Sangio, Antonio D; Chochowski, Piotr; Casasnovas, Pilar; Blazquéz, Julio C; Almendral, Jesús

2018-03-01

Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure (rEFHF). The precise mechanism remains unclear. The purpose of this study was to explore the effect of angiotensin-neprilysin inhibition on ventricular arrhythmias compared to angiotensin inhibition in rEFHF patients with an implantable cardioverter-defibrillator (ICD) and remote monitoring. We prospectively included 120 patients with ICD and (1) New York Heart Association functional class ≥II; (2) left ventricular ejection fraction ≤40%; and (3) remote monitoring. For 9 months, patients received 100% angiotensin inhibition with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), beta-blockers, and mineraloid antagonist. Subsequently, ACEi or ARB was changed to sacubitril-valsartan in all patients, who were followed for 9 months. Appropriate shocks, nonsustained ventricular tachycardia (NSVT), premature ventricular contraction (PVC) burden, and biventricular pacing percentage were analyzed. Patients were an average age of 69 ± 8 years and had mean left ventricular ejection fraction of 30.4% ± 4% (82% ischemic). Use of beta-blockers (98%), mineraloid antagonist (97%) and antiarrhythmic drugs was similar before and after sacubitril-valsartan. Sacubitril-valsartan significantly decreased NSVT episodes (5.4 ± 0.5 vs 15 ± 1.7 in angiotensin inhibition; P <.002), sustained ventricular tachycardia, and appropriate ICD shocks (0.8% vs 6.7% in angiotensin inhibition; P <.02). PVCs per hour decreased after sacubitril-valsartan (33 ± 12 vs 78 ± 15 in angiotensin inhibition; P <.0003) and was associated with increased biventricular pacing percentage (from 95% ± 6% to 98.8% ± 1.3%; P <.02). Angiotensin-neprilysin inhibition decreased ventricular arrhythmias and appropriate ICD shocks in rEFHF patients under home monitoring compared to angiotensin inhibition. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-10-24

CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

Refractory of Furnaces to Reduce Environmental Impact

NASA Astrophysics Data System (ADS)

Hanzawa, Shigeru

2011-10-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Extracellular Superoxide Dismutase Deficiency Exacerbates Pressure Overload–Induced Left Ventricular Hypertrophy and Dysfunction

PubMed Central

Lu, Zhongbing; Xu, Xin; Hu, Xinli; Zhu, Guangshuo; Zhang, Ping; van Deel, Elza D.; French, Joel P.; Fassett, John T.; Oury, Tim D.; Bache, Robert J.; Chen, Yingjie

2008-01-01

Extracellular superoxide dismutase (SOD) contributes only a small fraction to total SOD activity in the normal heart but is strategically located to scavenge free radicals in the extracellular compartment. To examine the physiological significance of extracellular SOD in the response of the heart to hemodynamic stress, we studied the effect of extracellular SOD deficiency on transverse aortic constriction (TAC)–induced left ventricular remodeling. Under unstressed conditions extracellular SOD deficiency had no effect on myocardial total SOD activity, the ratio of glutathione:glutathione disulfide, nitrotyrosine content, or superoxide anion production but resulted in small but significant increases in myocardial fibrosis and ventricular mass. In response to TAC for 6 weeks, extracellular SOD-deficient mice developed more severe left ventricular hypertrophy (heart weight increased 2.56-fold in extracellular SOD-deficient mice as compared with 1.99-fold in wild-type mice) and pulmonary congestion (lung weight increased 2.92-fold in extracellular SOD-deficient mice as compared with 1.84-fold in wild-type mice). Extracellular SOD-deficient mice also had more ventricular fibrosis, dilation, and a greater reduction of left ventricular fractional shortening and rate of pressure development after TAC. TAC resulted in greater increases of ventricular collagen I, collagen III, matrix metalloproteinase-2, matrix metalloproteinase-9, nitrotyrosine, and superoxide anion production. TAC also resulted in a greater decrease of the ratio of glutathione:glutathione disulfide in extracellular SOD-deficient mice. The finding that extracellular SOD deficiency had minimal impact on myocardial overall SOD activity but exacerbated TAC induced myocardial oxidative stress, hypertrophy, fibrosis, and dysfunction indicates that the distribution of extracellular SOD in the extracellular space is critically important in protecting the heart against pressure overload. PMID:17998475

Influence of collaterals on the left ventricular end-diastolic pressure and serum NT-proBNP levels in patients with coronary chronic total occlusion.

PubMed

Samadov, Fuad; Yesildag, Osman; Sari, Ibrahim; Atas, Halil; Akhundova, Aysel; Basaran, Yelda

2017-06-01

Although numerous studies have shown the protective effects of the well-developed coronary collaterals on left ventricular functions, the relationship between collateral grade and left ventricular end diastolic pressure has not been studied in chronic total occlusion patients. Also, there are conflicting data on the effect of collaterals on NT-proBNP levels. The aim of our study was to evaluate the relationship between coronary collateral circulation and left ventricular end diastolic pressure and NT-proBNP levels in chronic total occlusion patients. Study group was retrospectively selected from the patients who had undergone coronary angiography at our hospital between June 2011 and March 2013. Clinical, biochemical, angiographic and hemodynamic data of 199 consecutive patients having at least one totally occluded major epicardial coronary artery were evaluated. Coronary collateral circulation was graded according to Rentrop classification. While Rentrop grade 3 was defined as well-developed, all the remaining collateral grades were regarded as poor collaterals. Overall 87 patients were found to have good collaterals and 112 patients had poor collaterals. There was no significant difference between the patients with well- or poorly developed coronary collaterals with regard to left ventricular end diastolic pressure (16.84 ± 5.40 mmHg vs 16.10 ± 6.09, respectively, p  = 0,632) and log NT-proBNP (2.46 ± 0.58 vs 2.59 ± 0.76, respectively, p  = 0,335). In patients with coronary chronic total occlusion even well-developed coronary collaterals are not capable of protecting the rise of left ventricular end diastolic pressure and NT-proBNP levels which are reliable markers of the left ventricular dysfunction.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

NASA Astrophysics Data System (ADS)

Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 ° head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 ° upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alterating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Management of unstable arrhythmias in cardiogenic shock.

PubMed

Saidi, Abdulfattah; Akoum, Nazem; Bader, Feras

2011-08-01

Atrial and ventricular arrhythmias commonly arise in the setting of cardiogenic shock and often result in hemodynamic deterioration. Causative factors include myocardial ischemia, volume overload, and metabolic disturbances. Correcting these factors plays an important role in managing arrhythmias in this setting. Ventricular arrhythmias are more ominous compared to atrial arrhythmias but both require prompt intervention with electrical shock and anti-arrhythmic drug suppression. Coronary reperfusion is key to improving survival, including reducing the risk of sudden cardiac arrest, in acute myocardial infarction. Case series have also demonstrated the value of intra-aortic balloon pump counter-pulsation in suppressing ventricular arrhythmias in cardiogenic shock. The mechanism of arrhythmia suppression may be due to improved coronary perfusion and afterload reduction. Percutaneous ventricular assist device placement may be effective in this setting; however, data addressing this specific endpoint are lacking. Anti-arrhythmic drug options for ventricular and atrial arrhythmia suppression, in the setting of cardiogenic shock, are relatively limited. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone. The other Class III agents, sotalol and dronedarone, are excluded due to associated mortality observed in the SWORD and ANDROMEDA trials, respectively. Dofetilide is renally excreted and causes QT interval prolongation. Care should be taken to avoid excessive drug accumulation due to poor kidney perfusion and function. Dofetilide is approved for use for atrial arrhythmias and has not been studied for ventricular arrhythmia suppression. The DIAMOND-CHF trial established its safety in the setting of heart failure. Amiodarone is very effective in suppressing both atrial and ventricular arrhythmias. It is often the drug of choice in heart failure. Its off-label use for atrial arrhythmias is very common. Care should be taken with intravenous amiodarone to avoid hypotension.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

1998-01-01

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Reduction of I(Ca,L) and I(to1) density in hypertrophied right ventricular cells by simulated high altitude in adult rats.

PubMed

Chouabe, C; Espinosa, L; Megas, P; Chakir, A; Rougier, O; Freminet, A; Bonvallet, R

1997-01-01

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I(to1)) and in the L-type calcium current (I(Ca,L)) densities while there was no significant difference in the delayed rectifier current (I(K)) or in the inward rectifier current (I(K1)) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I(to 1) density was relatively more important than the decrease in I(Ca,L) density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I(to 1) and I(Ca,L) or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease in I(to 1) density might account for the lengthened action potential, or have a partial effect.

D-Sotalol: death by the SWORD or deserving of further consideration for clinical use?

PubMed

Doggrell, S A; Brown, L

2000-07-01

D-Sotalol is the dextro-rotatory isomer of sotalol and a class III anti-arrhythmic. D-Sotalol prolongs cardiac repolarisation by inhibiting the fast component of the delayed outward rectifying potassium channel. In animal studies, D-sotalol has been shown to be more effective in prolonging atrial, rather than ventricular, action potentials, suggesting that D-sotalol may be more effective against supra-ventricular than ventricular arrhythmias. Furthermore, in animal studies, D-sotalol induces after-depolarisations, which are predictors of pro-arrhythmic activity. D-Sotalol shows little or no reverse use dependence in animal and humans and has slow offset kinetics. This suggests that, in addition to being a preventative treatment for arrhythmias, D-sotalol may be effective at the start or during arrhythmia. As D-sotalol does not block the slow component of the delayed outward rectifying potassium channel, which is activated by the sympathetic nervous system, D-sotalol will not protect against sympathetic hyperactivity. D-Sotalol also has no effect on the K(ATP) channel, which is activated in ischaemia to shorten the action potential. Thus D-sotalol is less effective in ischaemia. Anti-arrhythmic activity with D-sotalol has been demonstrated in dog models of ventricular tachycardia and sudden death. Arrhythmias with D-sotalol have been demonstrated in an ischaemic guinea-pig ventricle model in the absence of action potentials. D-Sotalol is a weak beta-adrenoceptor antagonist and may also be a positive inotrope. In humans, D-sotalol has 100% systemic oral bioavailability, a terminal half-life of 7.2 h and is mainly excreted unchanged in the urine. Preliminary, mainly hospital-based, clinical trials showed that D-sotalol was effective in a variety of supraventricular and ventricular arrhythmias. However, a large clinical trial of D-sotalol as a preventative treatment for arrhythmias and sudden death after myocardial infarction, the SWORD trial, was terminated early because of increased mortality with D-sotalol. The group at greatest risk was those with a remote myocardial infarction and relatively good left ventricular function, the group that showed the lowest mortality when untreated. It is assumed that excessive prolongation of the action potential leading to pro-arrhythmia with D-sotalol, underlies the increased risk of death. However, there is little objective evidence in the SWORD trial to support this. Obviously D-sotalol should not be used in humans with a remote myocardial infarction and relatively good left ventricular function. D-Sotalol could still be considered for short-term hospital use in resistant arrhythmias and for longer-term use to prevent atrial fibrillation in those with remote myocardial infarction and poor left ventricular function.

Atypical auditory refractory periods in children from lower socio-economic status backgrounds: ERP evidence for a role of selective attention.

PubMed

Stevens, Courtney; Paulsen, David; Yasen, Alia; Neville, Helen

2015-02-01

Previous neuroimaging studies indicate that lower socio-economic status (SES) is associated with reduced effects of selective attention on auditory processing. Here, we investigated whether lower SES is also associated with differences in a stimulus-driven aspect of auditory processing: the neural refractory period, or reduced amplitude response at faster rates of stimulus presentation. Thirty-two children aged 3 to 8 years participated, and were divided into two SES groups based on maternal education. Event-related brain potentials were recorded to probe stimuli presented at interstimulus intervals (ISIs) of 200, 500, or 1000 ms. These probes were superimposed on story narratives when attended and ignored, permitting a simultaneous experimental manipulation of selective attention. Results indicated that group differences in refractory periods differed as a function of attention condition. Children from higher SES backgrounds showed full neural recovery by 500 ms for attended stimuli, but required at least 1000 ms for unattended stimuli. In contrast, children from lower SES backgrounds showed similar refractory effects to attended and unattended stimuli, with full neural recovery by 500 ms. Thus, in higher SES children only, one functional consequence of selective attention is attenuation of the response to unattended stimuli, particularly at rapid ISIs, altering basic properties of the auditory refractory period. Together, these data indicate that differences in selective attention impact basic aspects of auditory processing in children from lower SES backgrounds. Copyright © 2013 Elsevier B.V. All rights reserved.

Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet's disease.

PubMed

Iwata, Shigeru; Saito, Kazuyoshi; Yamaoka, Kunihiro; Tsujimura, Shizuyo; Nawata, Masao; Hanami, Kentaro; Tanaka, Yoshiya

2011-04-01

It is often difficult to manage refractory gastrointestinal tract complications of Behçet's disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3-5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.

Modeling the biomechanical influence of epilaryngeal stricture on the vocal folds: a low-dimensional model of vocal-ventricular fold coupling.

PubMed

Moisik, Scott R; Esling, John H

2014-04-01

PURPOSE Physiological and phonetic studies suggest that, at moderate levels of epilaryngeal stricture, the ventricular folds impinge upon the vocal folds and influence their dynamical behavior, which is thought to be responsible for constricted laryngeal sounds. In this work, the authors examine this hypothesis through biomechanical modeling. METHOD The dynamical response of a low-dimensional, lumped-element model of the vocal folds under the influence of vocal-ventricular fold coupling was evaluated. The model was assessed for F0 and cover-mass phase difference. Case studies of simulations of different constricted phonation types and of glottal stop illustrate various additional aspects of model performance. RESULTS Simulated vocal-ventricular fold coupling lowers F0 and perturbs the mucosal wave. It also appears to reinforce irregular patterns of oscillation, and it can enhance laryngeal closure in glottal stop production. CONCLUSION The effects of simulated vocal-ventricular fold coupling are consistent with sounds, such as creaky voice, harsh voice, and glottal stop, that have been observed to involve epilaryngeal stricture and apparent contact between the vocal folds and ventricular folds. This supports the view that vocal-ventricular fold coupling is important in the vibratory dynamics of such sounds and, furthermore, suggests that these sounds may intrinsically require epilaryngeal stricture.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

PubMed

Palazzuoli, Alberto; Silverberg, Donald S; Calabrò, Anna; Spinelli, Tommaso; Quatrini, Ilaria; Campagna, Maria S; Franci, Beatrice; Nuti, Ranuccio

2009-06-01

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

PubMed Central

Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

2016-01-01

Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

Prospective trial of biodegradable stents for refractory benign esophageal strictures after curative treatment of esophageal cancer.

PubMed

Yano, Tomonori; Yoda, Yusuke; Nomura, Shogo; Toyosaki, Kayo; Hasegawa, Hiromi; Ono, Hiroyuki; Tanaka, Masaki; Morimoto, Hiroyuki; Horimatsu, Takahiro; Nonaka, Satoru; Kaneko, Kazuhiro; Sato, Akihiro

2017-09-01

Biodegradable stents are reportedly effective for refractory benign esophageal strictures; however, little is known about their use in patients with refractory stricture after endoscopic submucosal dissection (ESD) or chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the effectiveness of biodegradable stents for these patients. Patients with refractory benign esophageal stricture with a dysphagia score (DS) of 2 or worse and for whom the passage of a standard size endoscope was not possible were eligible. The primary endpoint was the proportion of those who improved their DSs (% DS improved) at 12 weeks after stent placement, and the secondary endpoints were the proportion of those who improved their DSs at 24 weeks, dysphagia-free survival (DFS), and adverse events. Eighteen patients (men:women, 15:3; median age, 72 years; range, 53-80) were enrolled. Twelve patients improved their DS at 12 weeks (% DS improved, 66.7%; 90% CI, 44.6%-84.4%). Also, 8 of 11 patients (72.7%) after esophagectomy, 4 of 6 patients (66.7%) after ESD, and 3 of 4 patients (75%) after CRT improved at 12 weeks. Three patients who were treated with esophagectomy maintained their DS improvement at 24 weeks (% DS improved, 16.7%; 95% CI, 3.6%-41.4%). The median DFS was 14.1 weeks (95% CI, 13.0-19.0). One patient who had ESD and CRT developed an esophagobronchial fistula 3 months after stent placement. Biodegradable stents are effective and tolerable for refractory benign esophageal strictures after treatment for esophageal cancer; however, long-term efficacy was limited, especially after ESD or CRT. (Clinical trial registration number: UMIN000008054.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

PubMed

Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

2013-11-01

The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

[Effect of furazolidone quadruple regimen plus dental plaque removal procedures as rescue treatment of refractory Helicobacter pylori infection].

PubMed

Gao, Wen; Hu, Fu-lian; Wang, Xiao-min

2011-03-29

To observe the effect of furazolidone quadruple regimen plus dental plaque removal procedures as rescue treatment of refractory H. pylori infection. A total of 104 patients with H. pylori positive [(13)C-urea breath test (UBT) or rapid urease test positive] failing in previous treatment two or more were enrolled and divided into 2 groups. One group (n = 64) were given quadruple regimen [proton pump inhibitor (PPI) + bismuth + amoxicillin + furazolidone, 10 days] treatment and dental plaque removal treatment. And the others (n = 40) received only quadruple regimen treatment. The status of H. pylori was detected by (13)C-UBT at 4 weeks post-therapy and the eradication rates of two groups were compared. The eradication rate of quadruple regimen + dental treatment group was 85.9% (55/64) while that of the other group 72.5% (29/40) (P = 0.091). The PPI + bismuth quadruple regimen plus dental plaque removal procedures as rescue treatment may boost the eradication rate of refractory H. pylori infection patients. And the furazolidone quadruple therapy can be chosen for the treatment of refractory H. pylori infection. Oral H. pylori infection may play a role in the failure of H. pylori infection treatment.

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-20

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Botulinum toxin A for the Treatment of Overactive Bladder.

PubMed

Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

2016-02-29

The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

Effects of suture position on left ventricular fluid mechanics under mitral valve edge-to-edge repair.

PubMed

Du, Dongxing; Jiang, Song; Wang, Ze; Hu, Yingying; He, Zhaoming

2014-01-01

Mitral valve (MV) edge-to-edge repair (ETER) is a surgical procedure for the correction of mitral valve regurgitation by suturing the free edge of the leaflets. The leaflets are often sutured at three different positions: central, lateral and commissural portions. To study the effects of position of suture on left ventricular (LV) fluid mechanics under mitral valve ETER, a parametric model of MV-LV system during diastole was developed. The distribution and development of vortex and atrio-ventricular pressure under different suture position were investigated. Results show that the MV sutured at central and lateral in ETER creates two vortex rings around two jets, compared with single vortex ring around one jet of the MV sutured at commissure. Smaller total orifices lead to a higher pressure difference across the atrio-ventricular leaflets in diastole. The central suture generates smaller wall shear stresses than the lateral suture, while the commissural suture generated the minimum wall shear stresses in ETER.

Influence of the ventricular folds on a voice source with specified vocal fold motion1

PubMed Central

McGowan, Richard S.; Howe, Michael S.

2010-01-01

The unsteady drag on the vocal folds is the major source of sound during voiced speech. The drag force is caused by vortex shedding from the vocal folds. The influence of the ventricular folds (i.e., the “false” vocal folds that protrude into the vocal tract a short distance downstream of the glottis) on the drag and the voice source are examined in this paper by means of a theoretical model involving vortex sheets in a two-dimensional geometry. The effect of the ventricular folds on the output acoustic pressure is found to be small when the movement of the vocal folds is prescribed. It is argued that the effect remains small when fluid-structure interactions account for vocal fold movement. These conclusions can be justified mathematically when the characteristic time scale for change in the velocity of the glottal jet is large compared to the time it takes for a vortex disturbance to be convected through the vocal fold and ventricular fold region. PMID:20329852

Cavopulmonary Anastomosis in a Patient With Arrhythmogenic Right Ventricular Cardiomyopathy With Severe Right Ventricular Dysfunction.

PubMed

Vaidyanathan, Swaminathan; Kothandam, Sivakumar; Kumar, Rajesh; Indrajith, Sujatha Desai; Agarwal, Ravi

2017-01-01

A 26-year-old lady presented with exertional dyspnea, palpitations, central cyanosis, and oxygen saturations of 80% in room air. Her electrocardiogram, echocardiogram, and cardiac magnetic resonance were diagnostic of arrhythmogenic right ventricular dysplasia. There was no documented ventricular arrhythmia or syncopal episodes and Holter recordings were repeatedly normal. Cardiac hemodynamics showed right to left shunt through atrial septal defect, low pulmonary blood flow, normal atrial pressures, and minimally elevated right ventricular end-diastolic pressures. Since her presenting symptoms and cyanosis were attributed to reduced pulmonary blood flow, she underwent off-pump cavopulmonary anastomosis between right superior vena cava and right pulmonary artery. As we intended to avoid the adverse effect of extracorporeal circulation on the myocardial function and pulmonary vasculature, we did not attempt to reduce the size of the atrial septal defect. Her postoperative period was uneventful; oxygen saturation improved to 89% with significant improvement in effort tolerance. At 18-month follow-up, there were no ventricular arrhythmias on surveillance. The clinical presentation of this disease may vary from serious arrhythmias warranting defibrillators and electrical ablations at one end to right ventricular pump failure warranting cardiomyoplasty or right ventricular exclusion procedures at the other end. However, when the presentation was unusual with severe cyanosis through a stretched foramen ovale leading to reduced pulmonary blood flows, Glenn shunt served as a good palliation and should be considered as one of the options in such patients.

Infusion of adrenergic receptor agonists and antagonists into the locus coeruleus and ventricular system of the brain. Effects on swim-motivated and spontaneous motor activity.

PubMed

Weiss, J M; Simson, P G; Hoffman, L J; Ambrose, M J; Cooper, S; Webster, A

1986-04-01

These studies examined how pharmacological stimulation and blockade of alpha receptors would affect active motor behavior in rats. In experiment I, alpha-2 receptor antagonists (piperoxane, yohimbine) and agonists [clonidine, norepinephrine (NE)] were infused into various locations in the ventricular system of the brain, including the locus coeruleus region, and motor activity was measured. Activity was measured principally in a swim test but spontaneous (ambulatory) activity was also recorded while drugs were being infused. When infused into the locus coeruleus region, small doses of the antagonists piperoxane and yohimbine depressed activity in the swim test while infusion of the agonists clonidine and NE had the opposite effect of stimulating activity. These effects were highly specific to the region of the locus coeruleus, since infusions of these drugs into other nearby locations in the ventricular system or use of larger doses had different, often opposite effects. This was especially true of clonidine and NE which profoundly depressed activity when infused posterior to the locus coeruleus, particularly over the dorsal vagal complex. Infusion of small doses of these drugs into the lateral ventricle had effects similar to infusion into the locus coeruleus region, though less pronounced. Changes in spontaneous motor activity were also observed, but this measure differentiated the groups less well than did the swim test. In experiment II, the predominantly postsynaptic receptor agonists isoproterenol (beta agonist) and phenylephrine (alpha-1 agonist) were infused into the ventricular system. Since infusions of piperoxane and yohimbine into the locus coeruleus that decreased activity in experiment I increase the release of NE by blocking alpha-2 inhibitory receptors on cell bodies and dendrites of the locus coeruleus, experiment II tested whether ventricular infusion of predominantly postsynaptic receptor agonists would also decrease activity in the swim test. Both isoproterenol and phenylephrine produced this effect, but did so selectively with respect to dose and location of infusion in the ventricular system. These findings are consistent with recent results relating to the mechanism that underlies stress-induced depression of active behavior.

Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant

ClinicalTrials.gov

2017-10-03

Blastoid Variant Mantle Cell Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma

Development of refractories and related products for steel melting, finishing, and casting

NASA Astrophysics Data System (ADS)

Smirnov, A. N.

2013-06-01

The transformation of the consumption of refractories for the production, out-of-furnace treatment, and casting of steel is considered. The main trends in developing the refractory market are shown to be a significant decrease in the specific consumption of refractories per 1 t liquid steel and the predominant application of refractories based on magnesia raw materials and fused corundum for the working layers of melting units, ladles, and tundishes. The main trend in decreasing the specific costs of refractories is the development of refractories based on alternative sources of raw materials, which are cheaper and more available for refractory manufacturers.

Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2017-06-30

Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

PubMed

Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

2016-04-01

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

Wolff-Parkinson-white syndrome mimics a conduction disease.

PubMed

Marrakchi, S; Kammoun, I; Kachboura, S

2014-01-01

Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

PubMed Central

Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

2009-01-01

Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukeaemia (OPAL): a randomized open-label phase 2 study

PubMed Central

Cortes, Jorge; Feldman, Eric; Yee, Karen; Rizzieri, David; Advani, Anjali S.; Charman, Anthony; Spruyt, Richard; Toal, Martin; Kantarjian, Hagop

2017-01-01

Background Tosedostat is a novel oral aminopeptidase inhibitor with clinical activity in a previous phase I/II study in elderly patients with relapsed/refractory acute myeloid leukaemia (RR AML). We present the results of a randomised phase II study comparing two dosing regimes of tosedostat. Methods Patients aged ≥60 years with AML with relapse after a first complete remission (CR) lasting up to 12 months, or no prior CR, were randomised to receive as first salvage tosedostat 120 mg once daily for 6 months or 240 mg once daily for 2 months followed by 120 mg for 4 months. The primary endpoint was the proportion of patients who obtained a Complete Remission or Complete Remission with incomplete Platelet Recovery. The study was analysed on an intention to treat basis. The study was registered on clintrials.gov (NCT00780598) and the final study visit occurred in March 2011. Findings Seventy-three patients were treated with tosedostat. Seven patients (10%) achieved CR or a complete remission with incomplete platelet recovery (CRp): 2 of 38 (5%) in the 120 mg group and 5 of 35 (14%) in the 240 mg→120 mg group. The most common adverse events at grade 3 or worse were febrile neutropenia which occurred in 21/73 (29%) patients overall, 11/38 (29%) in the 120 mg group and 10/35 (29%) of the 240 mg→120 mg group, thrombocytopenia (16, 22%; 8, 21% and 8, 23%), fatigue (15, 21%; 7, 18% and 8, 23%), dyspnoea (12, 16%; 5, 13% and 7, 20%), pneumonia (10, 14%; 4, 11% and 6, 17%). There were 5 adverse events with an outcome of death, 3 in the 120 mg group and 2 in the 240 mg→120 mg group. The events were acute hepatitis, respiratory failure, pneumonia, atrial fibrillation and left ventricular dysfunction. Interpretation Tosedostat, at either dose schedule, has efficacy in older patients with relapsed or refractory AML, particularly those with prior myelodysplastic syndromes (MDS) or prior hypomethylating agent therapy. Additional studies of tosedostat including combination with hypomethylating agents and low dose cytarabine in patients with high risk MDS and AML are ongoing and/or planned. Funding The OPAL study was funded by Chroma Therapeutics Ltd, Abingdon, UK. PMID:23453583

Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series.

PubMed

Lauritsen, Clinton; Mazuera, Santiago; Lipton, Richard B; Ashina, Sait

2016-12-01

Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting. Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score of 3/10 was achieved and maintained for at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission were obtained as well as average baseline VAS scores prior to ketamine infusion. A phone interview was conducted for follow-up of migraine response in the 3 to 6 months following ketamine infusion. The study sample had a median age of 36.5 years (range 29-54) and 83% were women. Pre-treatment pain scores ranged from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12-0.42 mg/kg/hr). One patient reported a transient out-of-body hallucination following an increase in the infusion rate, which resolved after decreasing the rate. There were no other significant side effects. IV ketamine was safely administered in the hospital setting to patients with refractory chronic migraine. Treatment was associated with short term improvement in pain severity in 6 of 6 patients with refractory chronic migraine. Prospective placebo-controlled trials are needed to assess short term and long-term efficacy of IV ketamine in refractory chronic migraine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massie, B.; Kramer, B.L.; Topic, N.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responsesmore » at rest were decreases in left and right ventricular end-diastolic volumes from 388 + 81 to 350 + 77 ml (p < 0.01) and from 52 + 26 to 43 + 20 volume units (p < 0.01), respectively, and in their corresponding filling pressures, from 24 + 10 to 17 + 9 mm Hg and 10 + 5 to and + 5 mm Hg (both p < 0.01). Altough stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 + 6% to 22 + 5% and from 25 + 9% to 29 + 11%, respectively (both p < 0.01). During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. Thus, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.« less

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs.

PubMed

Kulier, A H; Novalija, E; Hogan, Q; Vicenzi, M N; Woehlck, H J; Bajic, J; Atlee, J L; Bosnjak, Z J

1999-12-01

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative cheilitis.

PubMed

Bhatia, Bhavnit K; Bahr, Brooks A; Murase, Jenny E

2015-06-01

Exfoliative cheilitis is a condition of unknown etiology characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic desquamation. It remains largely refractory to treatment, including corticosteroid therapy, antibiotics, antifungals, and immunosuppressants. We sought to evaluate the safety and efficacy of excimer laser therapy and narrowband ultraviolet B therapy in female patients with refractory exfoliative cheilitis. We reviewed the medical records of two female patients who had been treated unsuccessfully for exfoliative cheilitis. We implemented excimer laser therapy, followed by hand-held narrowband UVB treatments for maintenance therapy, and followed them for clinical improvement and adverse effects. Both patients experienced significant clinical improvement with minimal adverse effects with excimer laser therapy 600-700 mJ/cm 2 twice weekly for several months. The most common adverse effects were bleeding and burning, which occurred at higher doses. The hand-held narrowband UVB unit was also an effective maintenance tool. Limitations include small sample size and lack of standardization of starting dose and dose increments. Excimer laser therapy is a well-tolerated and effective treatment for refractory exfoliative cheilitis with twice weekly laser treatments of up to 700 mJ/cm 2 . Transitioning to the hand-held narrowband UVB device was also an effective maintenance strategy.

Transcutaneous stimulation of the posterior tibial nerve for treating refractory urge incontinence of idiopathic and neurogenic origin.

PubMed

Valles-Antuña, C; Pérez-Haro, M L; González-Ruiz de L, C; Quintás-Blanco, A; Tamargo-Diaz, E M; García-Rodríguez, J; San Martín-Blanco, A; Fernandez-Gomez, J M

2017-09-01

To assess the efficacy of treatment with transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with urge urinary incontinence, of neurogenic or nonneurogenic origin, refractory to first-line therapeutic options. We included 65 patients with urge urinary incontinence refractory to medical treatment. A case history review, a urodynamic study and a somatosensory evoked potentials (SEP) study were conducted before the TPTNS, studying the functional urological condition by means of a voiding diary. The treatment consisted of 10 weekly sessions of TPTNS lasting 30minutes. Some 57.7% of the patients showed abnormal tibial SEPs, and 42% showed abnormal pudendal SEPs. A statistically significant symptomatic improvement was observed in all clinical parameters after treatment with TPTNS, and 66% of the patients showed an overall improvement, regardless of sex, the presence of underlying neurological disorders, detrusor hyperactivity in the urodynamic study or SEP disorders. There were no adverse effects during the treatment. TPTNS is an effective and well tolerated treatment in patients with urge incontinence refractory to first-line therapies and should be offered early in the treatment strategy. New studies are needed to identify the optimal parameters of stimulation, the most effective treatment protocols and long-term efficacy, as well as its applicability to patients with a neurogenic substrate. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study.

PubMed

Gordin, Daniel; Fadl Elmula, Fadl Elmula M; Andersson, Bert; Gottsäter, Anders; Elf, Johan; Kahan, Thomas; Christensen, Kent Lodberg; Vikatmaa, Pirkka; Vikatmaa, Leena; Bastholm Olesen, Thomas; Groop, Per-Henrik; Olsen, Michael Hecht; Tikkanen, Ilkka

2017-10-01

To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of  ≥145 mm Hg, and/or a daytime diastolic ABPM of  ≥95 mm Hg after witnessed drug intake (including  ≥3 antihypertensive drugs, preferably including a diuretic). The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety. This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.

High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

PubMed

Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

2016-08-01

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.