Isoprenaline Infusion Research Articles

Deletion of the metabolic transcriptional coactivator PGC1β induces cardiac arrhythmia.

Peroxisome proliferator-activated receptor-γ coactivators PGC1α and PGC1β modulate mitochondrial biogenesis and energy homeostasis. The function of these transcriptional coactivators is impaired in obesity, insulin resistance, and type 2 diabetes. We searched for transcriptomic, lipidomic, and electrophysiological alterations in PGC1β(-/-) hearts potentially associated with increased arrhythmic risk in metabolic diseases. Microarray analysis in mouse PGC1β(-/-) hearts confirmed down-regulation of genes related to oxidative phosphorylation and the electron transport chain and up-regulation of hypertrophy- and hypoxia-related genes. Lipidomic analysis showed increased levels of the pro-arrhythmic and pro-inflammatory lipid, lysophosphatidylcholine. PGC1β(-/-) mouse electrocardiograms showed irregular heartbeats and an increased incidence of polymorphic ventricular tachycardia following isoprenaline infusion. Langendorff-perfused PGC1β(-/-) hearts showed action potential alternans, early after-depolarizations, and ventricular tachycardia. PGC1β(-/-) ventricular myocytes showed oscillatory resting potentials, action potentials with early and delayed after-depolarizations, and burst firing during sustained current injection. They showed abnormal diastolic Ca(2+) transients, whose amplitude and frequency were increased by isoprenaline, and Ca(2+) currents with negatively shifted inactivation characteristics, with increased window currents despite unaltered levels of CACNA1C RNA transcripts. Inwardly and outward rectifying K(+) currents were all increased. Quantitiative RT-PCR demonstrated increased SCN5A, KCNA5, RYR2, and Ca(2+)-calmodulin dependent protein kinase II expression. PGC1β(-/-) hearts showed a lysophospholipid-induced cardiac lipotoxicity and impaired bioenergetics accompanied by an ion channel remodelling and altered Ca(2+) homeostasis, converging to produce a ventricular arrhythmic phenotype particularly during adrenergic stress. This could contribute to the increased cardiac mortality associated with both metabolic and cardiac disease attributable to lysophospholipid accumulation.

Myocardial necroses produced by intravenous infusion of isoprenaline into rats.

Abstract Intravenous infusion of isoprenaline in doses of 2,20,200,2000 μg/kg per min over 20 min into heparinized Wistar rats results in myocardial necroses and a rise in SGPT activity, erythrocyte sedimentation rate and leucocytosis. A quantitative method for estimation of intensity and distribution of myocardial necrotic foci is described. The intensity of myocardial lesions is observed linearly related to the infused isoprenaline at 2, 20 and 200 μg/kg per min. Damaged areas are mainly found in subendocardial and apical regions of left ventricle.

Interaction between imipramine-like agents and catecholamine-induced hyperthemia.

Abstract Imipramine-like drugs potentiate the hyperthermic response obtained by infusion of noradrenaline, adrenaline and isoprenaline. In addition to this effect, desipramine increases the hyperthermic response induced by L-dopa (in monoamine oxidase blocked rats), reserpine (immediately after intravenous injection) and dexamphetamine. On the contrary, other types of hyperthermia, such as the one induced by phenethylamine in monoamine oxidase treated rats, and that by yeast, were not increased by desipramine. These results are discussed in relation to the mechanism of action of antidepressant drugs.

Radiofrequency Catheter Ablation of Life-Threatening Ventricular Arrhythmias Caused by Left Ventricular Metastatic Infiltration

Metastases to the cardiac ventricles are rare and, unfortunately, often follow a rapidly fatal course.1,2 Occasionally, they cause symptomatic ventricular arrhythmias (VAs) for which limited therapeutic options exist, such as antiarrhythmic drugs, whereas the use of catheter ablation, to our knowledge, has never been reported to date. We present the case of a 27-year-old man with a metastatic tumor in the left ventricle and intractable malignant VAs. In February 2009, the patient had been diagnosed with a gluteal sarcoma and initially treated with combined chemotherapy (including anthracyclines) and radiation. Since December 2009, a mild reduction in left ventricular ejection fraction (45%) was detected, and since January 2010, frequent monomorphic premature ventricular contractions (PVCs) and nonsustained ventricular tachycardias (VTs) were documented. Treatment with amiodarone proved helpful, and no life-threatening VAs could be induced on standard electrophysiological study.3 Since April 2010, however, the patient suffered from multiple drug-refractory episodes of sustained VT and ventricular fibrillation, requiring several direct current shocks (Figure 1). His left ventricular ejection fraction had remained stable. Electrical storm resulted in immediate hemodynamic instability and dramatically affected his quality of life. The patient was referred to our institution, where multiple antiarrhythmic drug combinations were tested, both orally and intravenously, allowing a relative stabilization of cardiac rhythm. Cardiac MRI showed a T2-hyperintense, weakly gadolinium-enhanced area at the basis of the anterior papillary muscle, compatible with metastatic infiltration (Figure 2, online-only Data Supplement Movie 1). An oncology consultation hypothesized a life expectancy of <6 months. After about 2 weeks, the recurrence of multiple episodes of VT and ventricular fibrillation required intensive care treatment with deep sedation and assisted ventilation, but still VAs could not be controlled. Thus, a repeat electrophysiological evaluation and radiofrequency …

A supraventricular tachycardia with two atrial activation sequences: What is the mechanism?

Case presentation A 62-year-old woman presented with a history of paroxysmal regular palpitations. She did not have any structural heart disease. Treatment with antiarrhythmic drugs was stopped 5 half-lives before the electrophysiological study. Basic intervals were normal. On right ventricular (RV) apical pacing 500 ms in the basal state, the ventriculoatrial (VA) conduction pattern was distal to proximal in the coronary sinus (CS) and the earliest atrial signal (A) was in the His bundle electrogram (Figure 1A). The VA block cycle length was 410 ms. During isoprenaline infusion, the VA block cycle length was 300 ms, with the earliest A at the His and a CS atrial activation pattern that was proximal to distal (Figure 1B). During infusion of isoprenaline, a sustained narrow-QRS tachycardia with 1:1 VA relationship started spontaneously. The initiation was with a spontaneous atrial premature depolarization (Figure 2), and termination was with a ventricular signal (V). The tachycardia cycle length (VV) and HH interval were constant at 320 ms. However, the CS activation sequence was distal to proximal at times and proximal to distal at other times. The VA interval changed from 130 to 156 ms as the CS activation pattern switched from a distal-to-proximal pattern to a proximal-to-distal one (Figure 3). What is the tachycardia mechanism?

WISE‐2005: prolongation of left ventricular pre‐ejection period with 56 days head‐down bed rest in women

This study tested the hypothesis that prolonged physical deconditioning affects the coupling of left ventricular depolarization to its ejection (the pre-ejection period, PEPi) and that this effect is minimized by exercise countermeasures. Following assignment to non-exercise (Control) and exercise groups (Exercise), 14 females performed 56 days of continuous head-down tilt bed rest. Measurements of the electrocardiogram (ECG) and stroke volume (Doppler ultrasound) during supine rest were obtained at baseline prior to (Pre) and after (Post) the head-down tilt bed rest (HDBR) period. Compared with Pre, the PEPi was increased following head-down tilt bed rest (main effect, P < 0.005). This effect was most dominant in the Control group [Pre = 0.038 ± 0.06 s (s.d.) versus Post = 0.054 ± 0.011 s; P < 0.001]. In the Exercise group, PEPi was 0.032 ± 0.005 s Pre and 0.038 ± 0.018 s Post; P= 0.08. Neither the QRS interval nor cardiac afterload was modified by head-down tilt bed rest in Control or Exercise groups. Low-dose isoprenaline infusion reversed the head-down tilt bed rest-induced delay in the PEPi. These results suggest that head-down tilt bed rest leads to a delayed onset of systolic ejection following left ventricular depolarization in a manner that is affected little by the exercise countermeasure but is related to β-adrenergic pathways. The delayed onset of systole following head-down tilt bed rest appears to be related to mechanism(s) affecting contraction of the left ventricle rather than its depolarization.

Treatment with atorvastatin partially protects the rat heart from harmful catecholamine effects

Atorvastatin blunts the response of cardiomyocytes to catecholamines by reducing isoprenylation of G gamma subunits. We examined whether atorvastatin exerts similar effects in vivo and protects the rat heart from harmful effects of catecholamines. Rats were treated with atorvastatin (1 or 10 mg/kg x day) or H(2)O for 14 days per gavage. All three animal groups were subjected to restraint stress on day 10 and to infusions of isoprenaline (ISO; 1 mg/kg x day) or NaCl via minipumps for the last 4 days. Heart rate was measured by telemetry, left ventricular atrial natriuretic peptide (ANP) transcript levels by RT-PCR, and left atrial contractile function in organ baths. Heart rate was similar in all six study groups. In animals pre-treated with water, infusion of ISO induced an increase in heart-to-body weight ratio (HW/BW) by approximately 20%, an increase in ANP mRNA by approximately 350%, and a reduction in the inotropic effect of isoprenaline in left atrium by approximately 50%. In animals pre-treated with high-dose atorvastatin, the effects of ISO on HW/BW, ANP, and left atrial force were approximately 40, 50, and 40% smaller, respectively. Low dose atorvastatin had similar, albeit smaller effects. Atorvastatin treatment of NaCl-infused rats had only marginal effects. In cardiac homogenates from atorvastatin-treated rats (both NaCl- and ISO-infused), G gamma and G alpha(s) were partially translocated from the membrane to the cytosol. In the rat heart, treatment with atorvastatin results in translocation of cardiac membrane G gamma and G alpha(s) to the cytosol. This mechanism might contribute to protecting the heart from harm induced by chronic isoprenaline infusion without affecting heart rate.

Serum insulin following isoprenaline in normal and diabetic persons.

Serum insulin and blood sugar were investigated in ten normal-weight diabetics with maturity-onset diabetes and in 12 controls before and after intravenous injection of 25 gm d-glucose without and during simultaneous infusion of isoprenaline 2 µg/min. A significant increase in serum insulin concentration was found after isoprenaline in both groups, both before and after injection of glucose. The increase in serum insulin level in the diabetics after isoprenaline was found to be normal, although the increase in insulin concentration following glucose was greatly reduced. It is concluded that in patients with maturity-onset diabetes there is presumably a defect of the glucose turnover in the B cells, whereas the process of insulin secretion itself is normal.

Short‐term β‐adrenergic regulation of leptin, adiponectin and interleukin‐6 secretion in vivo in lean and obese subjects

Adipose tissue and skeletal muscle are endocrine organs, secreting substances that have been implicated in obesity-related disorders. This study examined short-term beta-adrenergic regulation of circulating leptin, adiponectin and interleukin-6 (IL-6) concentrations and secretion from abdominal subcutaneous adipose tissue and muscle (IL-6) in vivo in lean and obese subjects. Systemic concentrations and net fluxes of leptin, adiponectin and IL-6 across abdominal subcutaneous adipose tissue and forearm skeletal muscle (IL-6) were assessed before and during beta-adrenergic stimulation (intravenous isoprenaline infusion) in 13 lean and 10 obese men. Basal circulating leptin concentrations were higher in the obese (p < 0.001), while circulating adiponectin (p = 0.45) and IL-6 concentrations (p = 0.41) were not different between groups. beta-Adrenergic stimulation decreased leptin concentrations in both groups (p < 0.01), but did not reduce net abdominal subcutaneous adipose tissue leptin release. Increased leptin clearance and/or decreased leptin secretion from other fat depots may explain the reduction in leptin concentrations. Adiponectin concentrations remained unchanged during beta-adrenergic stimulation in both groups. beta-Adrenergic stimulation increased IL-6 concentration, which was more pronounced in the obese (p = 0.01 vs. lean). This cannot be explained by increased IL-6 release per unit abdominal subcutaneous adipose tissue and muscle but might be because of the increased fat mass and fat-free mass at whole-body level. Short-term beta-adrenergic stimulation decreases leptin concentrations, which cannot be explained by reduced net leptin release from abdominal subcutaneous adipose tissue, while it elevates IL-6 concentration partly by increased release from this fat depot and muscle. Finally, beta-adrenergic stimulation has no short-term regulatory role in adiponectin secretion.

Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men

Aims/hypothesisObesity is characterised by increased triacylglycerol storage in adipose tissue. There is in vitro evidence for a blunted beta-adrenergically mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of obese individuals and evidence for this at the whole-body level in vivo. We hypothesised that the beta-adrenergically mediated effect on lipolysis in abdominal SAT is also impaired in vivo in obese humans.MethodsWe investigated whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h [2H5]glycerol infusions. Arterio–venous concentration differences were measured in 13 lean and ten obese men after an overnight fast and during intravenous infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat free mass)−1 min−1].ResultsLean and obese participants showed comparable fasting glycerol uptake by SAT (9.7 ± 3.4 vs 9.3 ± 2.5% of total release, p = 0.92). Furthermore, obese participants showed an increased whole-body beta-adrenergically mediated lipolytic response versus lean participants. However, their fasting lipolysis was blunted [glycerol rate of appearance: 7.3 ± 0.6 vs 13.1 ± 0.9 μmol (kg fat mass)−1 min−1, p < 0.01], as was the beta-adrenergically mediated lipolytic response per unit SAT [Δ total glycerol release: 140 ± 71 vs 394 ± 112 nmol (100 g tissue)−1 min−1, p < 0.05] compared with lean participants. Net triacylglycerol flux tended to increase in obese compared with lean participants during beta-adrenergic stimulation [Δ net triacylglycerol flux: 75 ± 32 vs 16 ± 11 nmol (100 g tissue)−1 min−1, p = 0.06].Conclusions/interpretationWe demonstrated in vivo that beta-adrenergically mediated lipolytic response is impaired systematically and in abdominal SAT of obese versus lean men. This may be important in the development or maintenance of increased triacylglycerol stores and obesity.

The pattern of activation of the sympathetic nervous system during tilt-induced syncope

A 49-year-old patient with a history of situational syncope and minimal electrocardiographic signs of accessory pathway is described. The evidence for pre-excitation was present only during the sympathetic activation caused by exercise testing and isoprenaline infusion. This phenomenon served as an indicator of significant adrenergic drive to the heart after the tilt-induced syncope. The meaning of the observed electrocardiographic changes in the course of neurocardiogenic reaction and its contribution to the understanding of the sympatho-vagal balance during vasovagal syncope is discussed. The lack of preexcitation signs during syncope and its appearance several seconds after the syncope-related sinus pause indicates sympathetic withdrawal before and shortly after the asystole. The possible pathophysiological mechanisms are discussed.

Short runs of irregular narrow QRS tachycardia: What is the mechanism?

u W t m A 23-year-old man without structural heart disease unerwent an electrophysiological (EP) study because of short pisodes of palpitations occurring at rest but more freuently during moderate exercise. During a 24-hour 3-chanel electrocardiogram (ECG) recording, multiple symptomtic episodes of palpitations occurred. A representative xample is given in Figure 1A. Baseline measurements uring the EP study were normal except for a jump in the trioventricular (AV) conduction curve. No tachycardia could e induced. Isoprenaline infusion resulted in short runs of a arrow complex tachycardia. A 12-lead ECG (Figure 1B) nd intracardiac recordings are shown (Figure 2). What is he most likely mechanism of this tachycardia?

β‐Adrenergic receptor desensitization in man: insight into post‐exercise attenuation of cardiac function

Desensitization of the β‐adrenoreceptors (β‐AR) may contribute to a post‐exercise reduction in left ventricular (LV) function. However, attenuation of the chronotropic and inotropic responses to a β‐AR agonist may depend upon alterations in parasympathetic tone. Furthermore, changes in cardiac output and LV diastolic function in response to a β‐AR agonist, pre‐ to post‐prolonged exercise, remain unclear. Seven trained males (mean ±s.d., age 27 ± 6 years) performed 4 h of ergometer rowing. Peak heart rate (HR) and LV systolic and diastolic functional responses to incremental isoproterenol (isoprenaline) infusion (2, 4 and 6 μg kg min−1) were assessed after vagal blockade (glycopyrrolate, 1.2 mg). LV systolic function was assessed by the pressure/volume ratio (systolic blood pressure/end systolic volume) and , whilst diastolic function was evaluated as peak early and late transmitral filling velocities. Following exercise, the pressure/volume ratio decreased by 25% (P &lt; 0.05), whereas was unchanged (P &gt; 0.05). The early/late filling ratio was reduced by 36% after exercise, due to an elevation in late LV filling (P &lt; 0.01). The increase in HR response to isoproterenol infusion was blunted post‐exercise at both 4 and 6 μg kg min−1 (127 ± 7 and 132 ± 6 beats min−1) compared with pre‐exercise (138 ± 8 and 141 ± 12 beats min−1, P &lt; 0.05). Additionally, the pressure/volume ratio and were blunted post‐exercise in response to isoproterenol (P &lt; 0.05). In contrast, diastolic function was similar before and after exercise during isoproterenol infusion (P &gt; 0.05). Desensitization of the β‐AR contributes to an attenuated left ventricular systolic but not diastolic function following prolonged exercise.

Right diaphragmatic paralysis following endocardial cryothermal ablation of inappropriate sinus tachycardia

Inappropriate sinus tachycardia (IST) is a rare disorder amenable to catheter ablation when refractory to medical therapy. Radiofrequency (RF) catheter modification/ablation of the sinus node (SN) is the usual approach, although it can be complicated by right phrenic nerve paralysis. We describe a patient with IST, who had symptomatic recurrences despite previous acutely successful RF SN modifications, including the use of electroanatomical mapping/navigation system. We decided to try transvenous cryothermal modification of the SN. We used 2 min applications at -85 degrees C at sites of the earliest atrial activation guided by activation mapping during isoprenaline infusion. Every application was preceded by high output stimulation to reveal phrenic nerve proximity. During the last application, heart rate slowly and persistently fell below 85 bpm despite isoprenaline infusion, but right diaphragmatic paralysis developed. At 6 months follow-up, the patient was asymptomatic and the diaphragmatic paralysis had partially resolved. This is the first report, we believe, of successful SN modification for IST by endocardial cryoablation, although this case also demonstrates the considerable risk of right phrenic nerve paralysis even with this ablation energy.

Determination of left ventricular volume changes by intracardiac conductance using a biventricular electrode configuration

The feasibility of determining left ventricular (LV) volume changes by LV conductance measurements with an implantable device was investigated in an animal model. The haemodynamic state of six mongrel dogs was altered by overpacing with rates up to 140 bpm and by isoprenaline infusion with dosages up to 0.2 microg/kg/min. The LV conductance, aortic blood flow, and LV and aortic pressure were recorded. Conductance measurements were carried out using the two electrodes of a bipolar right ventricular pacing lead for current injection and two epicardial leads screwed into the mid-lateral LV wall for measuring the resulting voltage. Stroke conductance (SY) was correlated with the LV stroke volume (LVSV), which was computed from the aortic flow. The LVSV rose to 188+/-14% with increasing isoprenaline dosage. A strong correlation between the LV conductance SY and the LVSV was found (mean r=0.97). The LVSV decreased to 68+/-8% with an increasing pacing rate. Again, a strong correlation between SY and LVSV was found (mean r=0.89). This animal study confirms the feasibility of assessing changes in LVSV by determining the LV intracardiac conductance. This creates the possibility of continuous haemodynamic monitoring with implantable devices.

P4-109: Right diaphragmatic paralysis following endocardial cryothermal ablation of inappropriate sinus tachycardia

Inappropriate sinus tachycardia (IST) is a rare disorder amenable to catheter ablation when refractory to medical therapy. Radiofrequency (RF) catheter modification/ablation of the sinus node (SN) is the usual approach, although it can be complicated by right phrenic nerve paralysis. We describe a patient with IST, who had symptomatic recurrences despite previous acutely successful RF SN modifications, including the use of electroanatomical mapping/navigation system. We decided to try transvenous cryothermal modification of the SN. We used 2 min applications at 2858C at sites of the earliest atrial activation guided by activation mapping during isoprenaline infusion. Every application was preceded by high output stimulation to reveal phrenic nerve proximity. During the last application, heart rate slowly and persistently fell below 85 bpm despite isoprenaline infusion, but right diaphragmatic paralysis developed. At 6 months follow-up, the patient was asymptomatic and the diaphragmatic paralysis had partially resolved. This is the first report, we believe, of successful SN modification for IST by endocardial cryoablation, although this case also demonstrates the considerable risk of right phrenic nerve paralysis even with this ablation energy.

Paradoxical effect of ajmaline in a patient with Brugada syndrome

The typical Brugada ECG pattern consists of a prominent J-wave associated with ST-segment elevation localized in the right precordial leads V1-V3. In many patients, the ECG presents periods of transient normalization and the Brugada-phenotype can be unmasked by the administration of class-I antiarrhythmics. Reports have documented the heterogeneity of the Brugada syndrome ECG-phenotype characterized by unusual localization of the ECG abnormalities in the inferior leads. Case report A 51-year-old man, without detectable structural heart disease, was referred to us because of a history of syncope, dizziness, and palpitations. The ECG showed a J-wave and ST-segment elevation in the right precordial leads, suggesting Brugada syndrome. As other causes of the ECG abnormalities were excluded, the patient underwent an electrophysiological study that documented easy induction of ventricular fibrillation. During infusion of ajmaline, new prominent J-waves and ST-segment elevation appeared in the inferior leads, whereas the basal ECG abnormalities in the right precordial leads normalized. After infusion of isoprenaline, the ECG-pattern resumed the typical Brugada pattern. An implantable cardioverter-defibrillator was recommended. In our patient, the double localization of the typical Brugada-pattern and the paradoxical effect of ajmaline on the ECG abnormalities confirmed the possibility of a phenotype heterogeneity in the Brugada syndrome.

Alterations of the preproenkephalin system in cardiac hypertrophy and its role in atrioventricular conduction

The goal of this study was to investigate alterations of the endogenous opioid system in cardiac hypertrophy, to elucidate mechanisms of preproenkephalin (ppENK) gene expression, and to assess effects of endogenous opioids on myocardial contractility and atrioventricular conduction. Hypertrophy was induced by ligation of a renal artery (2K1C) or chronic isoprenaline infusion (ISO). ppENK and opioid receptor (mu-, delta-, kappa-OR) mRNA expression was quantified by Northern blot and quantitative RT-PCR, respectively. Isolated cardiac myocytes and non-myocytes from neonatal rat heart were used for cell culture experiments. Overall expression of OR in the heart was markedly lower than in brain tissue, with kappa-OR being the most abundant isoform in the heart. We did not observe differences in kappa-OR expression in ventricular and atrial myocardium. In contrast, delta-OR expression was markedly higher in atria than in ventricles. Mu-OR expression in the heart was below the detection limit of the developed qRT-PCR assay. In left ventricular myocardium, ppENK mRNA levels were significantly increased in 2K1C rats but decreased in ISO rats. Cell culture experiments from neonatal rat hearts revealed that myocytes and non-myocytes express ppENK mRNA. In these cells, receptor-dependent and -independent stimulation of the beta-adrenergic signalling pathway caused an increase in ppENK mRNA. Furthermore, inactivation of inhibitory G-proteins by pertussis toxin increased basal and noradrenaline-stimulated ppENK mRNA expression. The physiological significance of myocardial opioids was investigated in isolated perfused rat hearts. Opioid receptor antagonists (nor-BNI, naltrindol) and the enkephalinase inhibitor CPL had no effect on contractility but significantly altered atrioventricular conduction. These observations suggest that the cardiac opioid system is activated in cardiac hypertrophy. Pressure overload and stimulation of the beta-adrenergic signalling pathway have been identified as a possible mechanism leading to increased ppENK expression, which may contribute to opioid system activation. Finally, endogenous opioids modulate the dromotropic response to catecholamine stimulation. The latter finding raises the possibility that endogenous opioids may contribute to the pathogenesis of arrhythmias.

Slow pathway ablation in children with documented reentrant supraventricular tachycardia not inducible during invasive electrophysiologic study

Radiofrequency catheter ablation (RFA) has become the procedure of choice for permanent therapy of atrioventricular nodal reentrant tachycardia (AVNRT). This report presents our experience with atrio-ventricular node (AVN) modification in patients with documented narrow complex reentrant SVT, but no evidence for an accessory pathway, and no inducible tachyarrhythmia during invasive electrophysiology (EP) study. The study population consists of nine children, age range 6-13 years (median 9) with previously documented SVT who had no tachyarrhythmia inducible during EP study (at baseline and following isoprenaline infusion). Eight of the 9 EP studies were performed under general anesthesia, and one under conscious sedation. An accessory pathway was excluded in all patients by appropriate atrial and ventricular extrastimulus pacing techniques. Eight of the nine patients had dual AV nodal physiology, and one had single AV nodal echo beats. The slow AV nodal pathway was empirically ablated, by applying RF lesions in the right inferoseptal AV groove, achieving catheter tip temperature of 50 degrees C. The appearance of an accelerated junctional rhythm during RF application was deemed to denote a successful application site. AV conduction during RF application was confirmed by incremental atrial pacing. The catheter position, and its relation to the compact AV node was constantly monitored using the LocaLisa navigation system. The end-point was absence of dual AVN physiology, and/or AV nodal echo beats. Successful slow pathway ablation was achieved in all patients. One patient appeared to have two separate slow pathways with different locations and two AH-jumps, which were both successfully ablated. None of the patients had evidence of temporary or permanent AV block at follow-up (median duration 9 months, range 4 to 36 months); none has had recurrence of symptoms or documented tachyarrhythmia. In children with structurally normal hearts, a previously documented SVT, absence of an accessory pathway and noninducibility of SVT during EP study, empirical slow pathway ablation appears to be justified.

Paradoxical effect of isoprenaline infusion

Isoprenaline (isoproterenol) is a beta-adrenergic drug, used to increase the heart rate and, during electrophysiological study, to facilitate the induction of supraventricular (SVT) and ventricular tachycardias (VT). Decrease in heart rate during isoprenaline infusion is a rare phenomenon. The purpose of the study was to evaluate the incidence, the possible mechanisms, and the significance of a paradoxical bradycardia induced by isoprenaline infusion. Electrophysiological study was performed for the evaluation of tachycardias (n = 551) or dizziness/syncope (n = 214) in 765 patients aged from 15 to 85 years. The study was negative in the basal state, and was repeated after isoprenaline infusion (2-4 microg/min). In 714 patients, this perfusion increased the heart rate to 100-140 bpm. A bradycardia was noted in 51 patients (7%). Two bradyarrhythmias were noted: (1) sinus or junctional bradycardia (cycle length - 10%) occurred in 43 patients, aged 15-70 years, generally studied for unexplained syncope (n = 37); a young age (40+/-16 years), syncope (n = 37) and absence of heart disease (n = 27) were more frequent than that in patients without isoprenaline-induced sinus or junctional bradycardia; another arrhythmia (SVT or VT) was induced in seven patients with syncope, five with heart disease and two without; six young patients (<50 years) had no syncope and were studied for SVT or VT; (2) eight patients, aged 65+/-11 years, developed second-degree atrioventricular (AV) block which was supraHisian (n = 4) or infraHisian (n = 4); they were studied for exercise-related syncope; they had no signs of myocardial ischaemia and AV block was reproduced by ajmaline testing: isoprenaline revealed organic conduction disturbance. The occurrence of paradoxical bradycardia was a rare finding during isoprenaline infusion (7%); sinus or junctional bradycardia was a sign of hypervagotonia, but was without clinical significance in 35% of these patients. The development of second-degree AV block was always pathological and associated with AV conduction disturbances, which occurred spontaneously during exercise. Isoprenaline infusion appeared to be a simple means to detect organic AV conduction disturbance in patients complaining of exercise or stress-related dizziness/syncope and unable to perform exercise test.