Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report.

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.

Temporary transvenous cardiac pacing: a survey on current practice.

BACKGROUND: Temporary transvenous cardiac pacing (TTCP) is a standard procedure in current practice, despite limited coverage in consensus guidelines. However, many authors reported several complications associated with TTCP, especially development of infections of cardiac implantable electronic devices (CIED). The aim of this survey was to provide a country-wide picture of current practice regarding TTCP. METHODS: Data were collected using an online survey that was administered to members of the Italian Association of Arrhythmology and Cardiac Pacing. RESULTS: We collected data from 102 physicians, working in 81 Italian hospitals from 17/21 regions. Our data evidenced that different strategies are adopted in case of acute bradycardia with a tendency to limit TTCP mainly to advanced atrioventricular block. However, some centers reported a greater use in elective procedures. TTCP is usually performed by electrophysiologists or interventional cardiologists and, differently from previous reports, mainly by a femoral approach and with nonfloating catheters. We found high inhomogeneity regarding prevention of infections and thromboembolic complications and in post-TTCP management, associated with different TTCP volumes and a strategy for management of acute bradyarrhythmias. CONCLUSION: This survey evidenced a high inhomogeneity in the approaches adopted by Italian cardiologists for TTCP. Further studies are needed to explore if these divergences are associated with different long-term outcomes, especially incidence of CIED-related infections.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats / Efeitos Bradicárdicos e Antiarrítmicos do D-Limoneno em Ratos

Abstract Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resumo Fundamento: O D-limoneno (DL) é um monoterpeno e o principal componente do óleo essencial de frutas cítricas. Ele apresenta atividades anti-hiperglicêmicas e vasodilatadoras. Objetivos: Este estudo avaliou os efeitos cardiovasculares e antiarrítmicos potenciais do DL em ratos. Métodos: Os parâmetros hemodinâmicos e eletrocardiográficos (ECG) foram mensurados em ratos Wistar machos que, sob anestesia, tiveram a aorta abdominal e a veia cava inferior canuladas e receberam eletrodos implantados subcutaneamente. Na abordagem in vitro, o coração foi removido e perfundido utilizando a técnica de Langendorff. O nível de significância adotado foi de 5% (p < 0,05). Resultados: DL, nas doses de 10, 20 e 40 mg/kg (i.v), produziu bradicardia intensa e persistente associada à hipotensão. A bradicardia com QTc prolongado foi observada no registro in vivo do ECG. No modelo in vivo de arritmia induzida por Bay K8644, DL (10 mg / kg) houve diminuição do escore da arritmia de 15,33 ± 3,52 para 4,0 ± 2,64 u.a (p < 0,05, n = 4). Em corações perfundidos isolados, o DL (10-3 M) promoveu reduções significativas na frequência cardíaca (de 228,6 ± 8,5 ms para 196,0 ± 9,3 bpm; p < 0,05) e na pressão desenvolvida do ventrículo esquerdo (de 25,2 ± 3,4 para 5,9 ± 1,8 mmHg; n = 5, p < 0,05). Conclusões: O DL produz bradicardia e atividade antiarrítmica no coração de ratos.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats.

BACKGROUND: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. OBJECTIVES: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. METHODS: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). RESULTS: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). CONCLUSIONS: DL produces bradycardia and antiarrhythmic activity in rat heart.

Visualization of tricuspid valve annulus for implantation of His bundle pacing in patients with symptomatic bradycardia.

BACKGROUND: His bundle pacing (HBP) is a physiological pacing modality, but HBP implantation remains a challenge. OBJECTIVE: This study explored the feasibility of using visualization of the tricuspid valve annulus (TVA) to locate the site for HBP. METHODS: During the lead placement in eight patients with symptomatic bradycardia, the TVA and tricuspid septal leaflet was revealed by contrast injection in the right ventricle under the fluoroscopic right anterior oblique view, and the target site for HBP was identified near the intersection of the tricuspid septal leaflet and the interventricular septum. On the basis of the imaging marker, the pacing lead was placed for HBP at either the atrial (aHBP) or ventricular side (vHBP). RESULTS: During the implantation, the pacing lead placement was attempted for aHBP in two patients, vHBP in five patients, and first for aHBP then vHBP in one patient. The aHBP was selective and had a capture threshold of 1.6 ± 0.5 V@ 1.0ms and R-wave amplitude of 1.2 ± 0.4 mV. Ventricular-side His bundle capture was selective in four patients and nonselective in two patients. The vHBP capture threshold was 0.8 ± 0.4 V@ 1.0ms (P < .05 vs aHBP) and R-wave amplitude was 4.1 ± 1.5 mV (P < .05 vs aHBP). At the final pacing programming of 3.0 V@ 1.0ms, vHBP was nonselective in all six patients and aHBP remained selective in two patients. Pacing parameters remained stable at 3 months. CONCLUSION: The location of the TVA and tricuspid septal leaflet revealed by right ventriculography can be used as a landmark to identify the HBP site.

Deep Negative Deflection in Unipolar His-Bundle Electrogram as a Predictor of Excellent His-Bundle Pacing Threshold Postimplant.

Background His-bundle pacing (HBP) is a physiological form of pacing. Although high capture thresholds are common, few predictors of low HBP threshold have been determined. We aimed to identify electrophysiological predictors. Methods Fifty-one patients (53% with atrioventricular block) underwent HBP for bradycardia with an intrinsic QRS duration of <120 ms. Attempts to anchor the HBP lead were guided by unipolar His-bundle electrograms (HB EGMs) recorded with an electrophysiology recording system. Patients were followed-up for >6 months. Results In total, 153 attempts at anchoring the HBP lead were made, of which, 45 achieved acceptable HBP thresholds (≤2.5 V at 1 ms). The amplitude of negative deflection in HB EGM and the selective HBP form at fixation were independently associated with achieving an acceptable threshold. A negative amplitude of ≥0.060 mV in HB EGM was determined as the optimal value for identifying the acceptable threshold. This deep negative HB EGM was recorded with an HBP threshold of 1.4±1.3 V (in 34 attempts), significantly lower than that of positive HB EGM without deep negative deflection (2.8±1.3 V, in 31 trials; or >5 V, in 38 trials). The permanent HBP lead remained with deep negative (≥0.060 mV) or positive HB EGMs in 28 and 14 patients, respectively, and with positive or negative HB injury current in 19 and 23 patients, respectively. During follow-up, increased HBP threshold of >1 V was significantly more prevalent in the positive HB EGM group. The HBP thresholds of deep negative HB EGM and HB injury current, but not of the selective HBP group, were significantly lower than the other subgroups during follow-up. Conclusions Deep negative HB EGM at fixation was associated with an excellent short-term HBP threshold, similar to HB injury current. Analysis of unipolar HB EGM postfixation may enable prediction of permanent HBP threshold.

Hemodynamic consequences of premature ventricular contractions: Association of mechanical bradycardia and postextrasystolic potentiation with premature ventricular contraction-induced cardiomyopathy.

BACKGROUND: The relationships between hemodynamic consequences of premature ventricular contractions (PVCs) and development of premature ventricular contraction-induced cardiomyopathy (PVC-CM) have not been investigated. OBJECTIVE: The purpose of this study was to correlate concealed mechanical bradycardia and/or postextrasystolic potentiation (PEP) to PVC-CM. METHODS: Invasive arterial pressure measurements from 17 patients with PVC-CM and 16 controls with frequent PVCs were retrospectively analyzed. PVCs were considered efficient (ejecting PVCs) when generating a measurable systolic arterial pressure. PEP was defined by a systolic arterial pressure of the post-PVC beat ≥5 mm Hg higher than the preceding sinus beat. Every PVC was analyzed for 10 minutes before ablation, and the electromechanical index (EMi = number of ejecting PVCs/total PVC) and postextrasystolic potentiation index (PEPi = number of PVCs with PEP/total PVC) were calculated. RESULTS: EMi was 29% ± 31% in PVC-CM and 78% ± 20% in controls (P <.0001). PEPi was 41% ± 28% in PVC-CM and 14% ± 10% in controls (P = .001). There was no control in groups of low EMi or high PEPi. EMi and PEPi were not significantly correlated to left ventricular dimensions or function in PVC-CM patients. PVC coupling interval was related to both ejecting PVCs and PEP. CONCLUSION: Patients with PVC-CM more often display nonejecting PVCs and PEP compared to controls.

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits.

This research was conducted to verify the structural and functional characteristics of mast cells in the electroacupuncture (EA) effects on bradycardia. First, we examined the mast cell density at PC 6, adjacent acupoint LU 7, and a non-acupoint. We tested the effects of EA at PC 6 on heart rate (HR) and blood pressure (BP) in rabbits with pituitrin-induced bradycardia. We also injected sodium cromolyn (Cro), a mast cell membrane stabilizer, at PC 6 30 min before EA to investigate if it affected the EA effects. The results showed that in both PC 6 and LU 7, the mast cell densities were higher than in the non-acupoint (P < 0.05). EA could induce mast cell degranulation at PC 6, which could be suppressed by sodium cromolyn (P < 0.05). EA improved HR, though the change was relatively small in the initial stage with a significant change at 35 min after modelling (P < 0.05). BP significantly improved at 10 min after the onset of pituitrin-induced bradycardia (P < 0.05). The EA effects on both HR and BP were suppressed by sodium cromolyn (P < 0.05). Therefore, we concluded that mast cells in the acupoint are important for the EA effects against pituitrin-induced bradycardia in rabbits.

Near Death Experience from Placement of an Intrathecal Catheter.

UNLABELLED: The management of pain due to cancer is challenging and often requires invasive therapy in addition to medication management. Intrathecal drug delivery is a form of advanced therapy that delivers medication locally in the intrathecal space while reducing systemic side effects associated with high doses of opioids. Although risks associated with intrathecal drug delivery are low, some common complications include dislodgement, kinking, or fracture of the catheter, bleeding, neurological injury, infection, and cerebrospinal leaks. We present a case of a 38-year-old woman with a medical history significant for stage IV breast cancer, L2 metastatic lesion, opioid tolerance, and chronic neck and low back pain who was admitted to the hospital for intractable pain. She had failed multiple interventional procedures in the past including lumbar medial nerve radiofrequency ablation, epidural steroid injection, and trigger point injections as well as a kyphoplasty at the L2 level. Failing both oral and parenteral opioid treatments, the decision was made to place an intrathecal pump in the patient. After placement of the intrathecal catheter and prior to any bolus of medication being given, the patient became bradycardic with a heart rate in the 20s and experienced a 10 second pause. The patient had intermittent bradycardia over the following days and symptoms resolved only after removal of the intrathecal catheter itself. To our knowledge, this is the first reported case with a complication of recurrent bradycardic and asystolic episodes prior to the administration of intrathecal opioid but shortly after placement of the intrathecal catheter itself. KEY WORDS: Intrathecal drug delivery, complications, cancer pain, intrathecal analgesia, bradycardia, opioids.

[A series of cases--too old for a pacemaker?]. / Eine Case Serie--Zu alt für einen Schrittmacher?

We report three patients with an age above 90 years presented with symptomatic bradycardia and higher grade AV block in our clinic. The oldest patient was 100 years. All three patients could be supplied safely and without complications with a dual chamber pacemaker. Our case series shows that a dual chamber pacemaker implantation is safe and feasible in patients in very advanced age. A surgical management with local anesthetic (lidocaine), fentanyl and midazolam in individual cases is possible. This and a short hospital stay reduce the risk of delirium. It is a group of patients, which will increase in the future and requires more intensive care than the standard pacemaker patient.

Transient A-V dissociation and severe hypotension due to consumption of Ayurvedic medicine--Vatsanabha (aconitum ferox).

A 24 year old married, well educated, female patient presented with complaints of giddiness and blackouts. On evaluation, patient had hypotension and bradycardia. ECG findings were suggestive of complete A-V dissociation. On detailed history patient revealed consumption. of Ayurvedic medicine Vatsanabha for arthritis. This study impresses upon the need for complete history talking and generating awareness regarding the correct and observed use of any drug including alternative medicines.

T-type calcium current contributes to escape automaticity and governs the occurrence of lethal arrhythmias after atrioventricular block in mice.

BACKGROUND: When complete atrioventricular block (AVB) occurs, infranodal escape rhythms are essential to prevent bradycardic death. The role of T-type Ca(2+) channels in pacemaking outside the sinus node is unknown. We investigated the role of T-type Ca(2+) channels in escape rhythms and bradycardia-related ventricular tachyarrhythmias after AVB in mice. METHODS AND RESULTS: Adult male mice lacking the main T-type Ca(2+) channel subunit Cav3.1 (Cav3.1(-/-)) and wild-type (WT) controls implanted with ECG telemetry devices underwent radiofrequency atrioventricular node ablation to produce AVB. Before ablation, Cav3.1(-/-) mice showed sinus bradycardia (mean±SEM; RR intervals, 148±3 versus 128±2 ms WT; P<0.001). Immediately after AVB, Cav3.1(-/-) mice had slower escape rhythms (RR intervals, 650±75 versus 402±26 ms in WT; P<0.01) but a preserved heart-rate response to isoproterenol. Over the next 24 hours, mortality was markedly greater in Cav3.1(-/-) mice (19/31; 61%) versus WT (8/26; 31%; P<0.05), and Torsades de Pointes occurred more frequently (73% Cav3.1(-/-) versus 35% WT; P<0.05). Escape rhythms improved in both groups during the next 4 weeks but remained significantly slower in Cav3.1(-/-). At 4 weeks after AVB, ventricular tachycardia was more frequent in Cav3.1(-/-) than in WT mice (746±116 versus 214±78 episodes/24 hours; P<0.01). Ventricular function remodeling was similar in Cav3.1(-/-) and WT, except for smaller post-AVB fractional-shortening increase in Cav3.1(-/-). Expression changes were seen post-AVB for a variety of genes; these tended to be greater in Cav3.1(-/-) mice, and overexpression of fetal and profibrotic genes occurred only in Cav3.1(-/-). CONCLUSIONS: This study suggests that T-type Ca(2+) channels play an important role in infranodal escape automaticity. Loss of T-type Ca(2+) channels worsens bradycardia-related mortality, increases bradycardia-associated adverse remodeling, and enhances the risk of malignant ventricular tachyarrhythmias complicating AVB.

[Atrial mechanical and electrical dysfunction in patient with Emery-Dreifuss muscular dystrophy reason of change in electrotherapeutical approach: frequent result of rare disease]. / Elektryczna i mechaniczna dysfunkcja przedsionków u pacjenta z dystrofia miesniowa Emery-Dreifussa przyczyna zmiany wyboru optymalnej formy elektroterapii: czeste powiklanie rzadkiej choroby.

We present a case of a 35 year-old male patient with Emery-Dreifuss muscular dystrophy diagnosed in the age of 12 who was assigned to dual chamber pacing system due to bradycardia primarily recognised as sinus node insufficiency with the atrio-ventricular nodal rhythm. During the procedure permanent electrical atrial stand-still without atrial capture were detected and the mode of stimulation was change to VVIR.

Effect of right ventricular pacing site on QRS width.

To assess the effect of various right ventricular pacing sites on QRS duration, we enrolled 50 patients (mean age, 64 ± 13 years; 36 men); 16 had bradycardia and 34 had tachycardia. The right ventricle was arbitrarily divided into 5 sections: high and low right ventricular outflow tract, mid septum, low septum, and apex. Right ventricular pacing was performed using an electrode catheter at each of the 5 sites. QRS duration was 162 ± 20 ms during high right ventricular outflow tract pacing, 143 ± 17 ms during low right ventricular outflow tract pacing, 151 ± 20 ms during mid-septal pacing, 163 ± 16 ms during low-septal pacing, and 167 ± 18 ms during apical pacing. Paced QRS duration was shorter during low right ventricular outflow tract and mid-septal pacing compared to apical pacing in 34 patients. There was a difference of 10 ms or less in the paced QRS duration between these pacing sites in the other 16 patients. QRS duration was shortest when the septum was paced in the right ventricle. However, QRS duration was similar during pacing in the septum and the apex in 32% of patients.

Abnormal response of superior sinoatrial node to sympathetic stimulation is a characteristic finding in patients with atrial fibrillation and symptomatic bradycardia.

BACKGROUND: We hypothesized that unresponsiveness of superior sinoatrial node (SAN) to sympathetic stimulation is strongly associated with the development of symptomatic bradycardia in patients with atrial fibrillation (AF). METHODS AND RESULTS: We performed 3D endocardial mapping in healthy controls (group 1, n=10) and patients with AF without (group 2, n=57) or with (group 3, n=15) symptomatic bradycardia at baseline and during isoproterenol infusion. Corrected SAN recovery time was abnormal in 0%, 11%, and 36% of groups 1, 2, and 3, respectively (P=0.02). At baseline, 90%, 26%, and 7% (P<0.001) of the patients had multicentric SAN activation patterns. For groups 1, 2, and 3, the median distance from the superior vena cava-right atrial junction to the most cranial earliest activation site (EAS) was 5.0 (25-75 percentile range, 3.5-21.3), 10.0 (4-20), and 17.5 (12-34) mm at baseline (P=0.01), respectively, and 4.0 (0-5), 5.0 (1-10), and 15.0 (5.4-33.3) mm, respectively, during isoproterenol infusion (P=0.01), suggesting an upward shift of EAS during isoproterenol infusion. However, although the EAS during isoproterenol infusion was at the upper one third of the crista terminalis in 100% of group 1 and 78% of group 2 patients, only 20% of group 3 patients showed a move of the EAS to that region (P<0.001). CONCLUSIONS: Superior SAN serves as the EAS during sympathetic stimulation in patients without AF and in most patients with AF without symptomatic bradycardia. In contrast, unresponsiveness of superior SAN to sympathetic stimulation is a characteristic finding in patients with AF and symptomatic bradycardia.