Nodal Arrhythmias Research Articles

Benefits from catheter ablation in patients with pulmonary hypertension: Recent advances.

Supraventricular tachycardia (SVT) is a frequent complication of pulmonary hypertension (PH). The most prevalent SVTs are atrial fibrillation (AF) and typical atrial flutter (AFL), followed by focal and macroreentrant atrial tachycardia (AT) and nodal arrhythmia (AV nodal reentry tachycardia or AV reentry tachycardia). SVT is frequently associated with functional deterioration and right ventricular failure in PH patients. According to some data, reestablishing sinus rhythm is associated with clinical improvement. Catheter ablation of typical AFL, nodal tachyarrhythmias, or other less complex focal ATs have been shown to be feasible, acutely effective, and safe in patients with PH. However, the long-term clinical outcome is modified by the recurrence of index arrhythmia and the onset of a new SVT. Due to right atrial dilatation, technical issues can arise when ablation is carried out. The role of catheter ablation in patients with AF or more complex AT is even less effective. The results mirror the success rate in the general AF population with non-paroxysmal AF. However, the data is limited, and electrophysiological procedures are also more often complicated by specific adverse events in a severely frail population. Despite these limitations, catheter ablation is the treatment of choice in less complex SVT, but the indications for AF ablation must be more individualized.

Junctional Ectopic Tachycardia Caused by Junctophilin-2 Expression Silencing Is Selectively Sensitive to Ryanodine Receptor Blockade

Junctional ectopic tachycardia (JET) is a potentially fatal cardiac arrhythmia. Hcn4:shJph2 mice serve as a model of nodal arrhythmias driven by ryanodine type 2 receptor (RyR2)-mediated Ca2+ leak. EL20 is a small molecule that blocks RyR2 Ca2+ leak. In a novel invivo model of JET, Hcn4:shJph2 mice demonstrated rapid conversion of JET to sinus rhythm with infusion of EL20. Primary atrioventricular nodal cells demonstrated increased Ca2+ transient oscillation frequency and increased RyR2-mediated stored Ca2+ leak which was normalized by EL20. EL20 was found to be rapidly degraded in mouse and human plasma, making it a potential novel therapy for JET.

Reduction in Junctophilin 2 Expression in Cardiac Nodal Tissue Results in Intracellular Calcium-Driven Increase in Nodal Cell Automaticity.

Spontaneously depolarizing nodal cells comprise the pacemaker of the heart. Intracellular calcium (Ca2+) plays a critical role in mediating nodal cell automaticity and understanding this so-called Ca2+ clock is critical to understanding nodal arrhythmias. We previously demonstrated a role for Jph2 (junctophilin 2) in regulating Ca2+-signaling through inhibition of RyR2 (ryanodine receptor 2) Ca2+ leak in cardiac myocytes; however, its role in pacemaker function and nodal arrhythmias remains unknown. We sought to determine whether nodal Jph2 expression silencing causes increased sinoatrial and atrioventricular nodal cell automaticity due to aberrant RyR2 Ca2+ leak. A tamoxifen-inducible, nodal tissue-specific, knockdown mouse of Jph2 was achieved using a Cre-recombinase-triggered short RNA hairpin directed against Jph2 (Hcn4:shJph2). In vivo cardiac rhythm was monitored by surface ECG, implantable cardiac telemetry, and intracardiac electrophysiology studies. Intracellular Ca2+ imaging was performed using confocal-based line scans of isolated nodal cells loaded with fluorescent Ca2+ reporter Cal-520. Whole cell patch clamp was conducted on isolated nodal cells to determine action potential kinetics and sodium-calcium exchanger function. Hcn4:shJph2 mice demonstrated a 40% reduction in nodal Jph2 expression, resting sinus tachycardia, and impaired heart rate response to pharmacologic stress. In vivo intracardiac electrophysiology studies and ex vivo optical mapping demonstrated accelerated junctional rhythm originating from the atrioventricular node. Hcn4:shJph2 nodal cells demonstrated increased and irregular Ca2+ transient generation with increased Ca2+ spark frequency and Ca2+ leak from the sarcoplasmic reticulum. This was associated with increased nodal cell AP firing rate, faster diastolic repolarization rate, and reduced sodium-calcium exchanger activity during repolarized states compared to control. Phenome-wide association studies of the JPH2 locus identified an association with sinoatrial nodal disease and atrioventricular nodal block. Nodal-specific Jph2 knockdown causes increased nodal automaticity through increased Ca2+ leak from intracellular stores. Dysregulated intracellular Ca2+ underlies nodal arrhythmogenesis in this mouse model.

Morphometry and comparative histology of sinus and atrioventricular nodes in humans and pigs and their relevance in the prevention of nodal arrhythmias

The cardiac conduction system is a network structure that allows the initiation and fast propagation of electrical impulses that trigger the electrical depolarization of the myocardial tissue. The purpose of this work is to study the histological and morphometric characteristics of the different components of the sinus and atrioventricular nodes in humans and pigs and their relationship with supraventricular arrhythmias.In this study, we describe the morphometry of the sinus and atrioventricular nodes of 10 adult humans and 10 pig hearts. A computerized morphometric study has been carried out, where we determined the number of cells that compose the nodes as well as different parameters related to their shape and size.The sinus node in human and pig is a compact structure, whose shape is oblong. Their cells (nodal and transitional cells) are pale and located in the center and the periphery, respectively. The atrioventricular node has also a shape oblong. P cells are pale in both species, but in humans, they are smaller than cardiomyocytes. The T cells are small and pale in both species, identified by hematoxylin-eosin and desmin stains. We have observed through a morphometric profile that the structure of sinus and atrioventricular nodes of pigs and humans show few differences. Pigs can be used as models for hemodynamic applications and experimental studies that include atrial electrical conduction and, in this way, prevent the presentation of arrhythmias that can generate sudden deaths in humans and pigs.

A randomized, double-blind, controlled clinical trial to evaluate the safety and immunogenicity of an intranasally administered trivalent inactivated influenza vaccine with adjuvant LTh(αK): A phase I study

BackgroundA nasal influenza vaccine has been available only in a live attenuated form, which limits the range of recipients to immune-competent individuals. The present study evaluated a newly developed intranasal inactivated influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT) derived from E. coli (LTh(αK)). MethodsThe study was a randomized, double-blind, controlled phase I trial to evaluate the safety and immunogenicity of an intranasal vaccine containing the trivalent influenza HA antigen (7.5 µg each of A/California/7/09 (H1N1)-like virus, A/Victoria/210/2009 (H3N2) virus, and B/Brisbane/60/2008-like virus) in combination with 4 different doses of adjuvant LTh(αK) (7.5, 15, 30 or 45 μg) and 22.5 μg of influenza HA antigen alone (control vaccine). The vaccine was intranasally administered on Days 0 and 7. A safety evaluation commenced for 180 days, and hemagglutination inhibition (HI) antibody titers and nasal HA-specific IgA titers on Day 0 and Day 28 were assessed to determine whether an immunogenic response was elicited. ResultsFrom November 2012 to September 2013, a total of 36 subjects were enrolled. Twenty-four subjects received an adjuvanted vaccine, and 12 subjects received a control vaccine. The most common adverse event (AE) was mild nasal discomfort, and systemic AEs were mild fatigue and headache. Only two subjects discontinued the study because of an AE (one had grade 3 fever, and one had nodal arrhythmia). In the group with 45 μg of LTh(αK), the seroprotection rates were 100%, 100% and 80%, and the nasal IgA conversion factors were 7.90, 7.46 and 12.27 for the A/H3N2, A/H1N1 and split B strains, respectively. Adjuvant LTh(αK) vaccine showed a significant enhancement in mucosal immunity in split B -specific IgA. ConclusionThe intranasal inactivated influenza vaccine is generally safe, and the LTh(αK)-adjuvanted vaccine is more immunogenic than non-adjuvanted control vaccine.ClinicalTrials.gov Identifier: NCT03293732.

Poređenje rezultata rutinskog i selektivnog postavljanja epikardijalnog pejsinga: iskustvajednog centra od 237 pacijenata

Objective: Recently, the use of epicar-dial pacing wires (EPW) has become the standard of care for patients undergoing open-heart surgery (OHS) at many cardiovascular surgery centers. However, the routine use of EPWs after OHS is increasingly questioning due to their potentially lethal complications and limited efficacy. Here, we aimed to investigate the impact of EPW placement on in-hospital mortality and to compare the frequency of the EPW related complications in patients receiving routine or selective EPW placement after elective OHS. Methods: A total of 237 patients undergoing OHS in our clinic (ORDU UN¤VERSTY TRA¤N¤NG AND RESEARCH HOSP¤TAL) were enrolled in this study. Study subjects were randomly assigned to one of the groups: Routine or selective EPW placement. In the latter, EPWs were placed according to the presence of intraoperative bradycardia with hemodynamic compromise , nodal or junctional arrhythmias, atrioventri-cular block or ventricular tachycardia. Results: There were 95 patients (40 %) receiving routine EPW and 142 (60%) patients receiving selective EPW. Active pacing was performed or required in 13 patients (5.4%). Five of them were in routine EPW group and 8 were in the selective EPW group (p = 0.902). Active pacing requirement was similar in coronary artery bypass grafting and valvular surgery (5% vs. 9%, p = 0.712, respectively). Permanent pacing was required in any of the subjects. Complications related to EPW occurred in 17 patients receiving routine EPW and 2 patients receiving selective EPW (p < 0.001). Routine EPW implantation was significantly correlated with the development of the complications (r = 0.309, p <0.001). Conclusion: Our findings indicate that the number of patients requiring temporary pacing after OHS is quite low and implementing an EPW is associated with potentially hazardous complications. Selective EPW placement compared to routine EPW placement is associated with fewer postoperative complications.

The genetic basis for inherited forms of sinoatrial dysfunction and atrioventricular node dysfunction.

The sinoatrial node (SAN) and the atrioventricular node (AVN) are the anatomical and functional regions of the heart which play critical roles in the generation and conduction of the electrical impulse. Their functions are ensured by peculiar structural cytological properties and specific collections of ion channels. Impairment of SAN and AVN activity is generally acquired,but in some cases familial inheritance has been established and therefore a genetic cause is involved. In recent years, combined efforts of clinical practice and experimental basic science studies have identified and characterized several causative gene mutations associated with the nodal syndromes. Channelopathies, i.e., diseases associated with defective ion channels, remain the major cause of genetically determined nodal arrhythmias; however, it is becoming increasingly evident that mutations in other classes of regulatory and structural proteins also have profound pathophysiological roles. In this review, we will present some aspects of the genetic identification of the molecular mechanism underlying both SAN and AVN dysfunctions with a particular focus on mutations of the Na, pacemaker (HCN), and Ca channels. Genetic defects in regulatory proteins and calcium-handling proteins will be also considered. In conclusion, the identification of the genetic defects associated with familial nodal dysfunction is an essential step for implementing an appropriate therapeutic treatment.

A37 Session 11: Cardiovascular Disease Intervention: Updates in catheter-based cardiac cryoablation

Cardiac cryoablation continues to remain a powerful tool in the management of cardiac arrhythmias. Historically, cryoablation was reserved for arrhythmias that were high-risk for collateral damage with traditional radiofrequency (RF) ablation. However, the recent availability of the cryoballoon has permitted cryoablation technology to be applied to a larger population of atrial fibrillation (AF) patients. As a result, cryoablation now accounts for greater than the historical 10–15% of all ablations. This review summarizes the recent clinical outcomes of cryoablation in managing supraventricular cardiac arrhythmias. Cumulatively, cryoablation is estimated to offer a 95–97% cure rate and a 9–11% recurrence rate when used for atrioventricular nodal reentrant tachycardia (AVNRT). Success appears to be related to catheter tip size with larger tips offering greater success. Peyrol et al. demonstrated that a larger tip 8 mm catheter results in outcomes that rival the best results from traditional RF ablation with reported 99% acute success and 5% long-term recurrence rate over 18 months. Success rates of 95–100% have been reported for atrioventricular tachycardia (AVRT); however, there is a higher recurrence rate of 20–30%. Atienze et al. performed a meta-analysis of patients with septal accessory pathways revealing an 84% acute success rate with a 21% recurrence rate. These results are inferior to those seen with RF. However, there were no reported cases of permanent AV block with cryoablation versus a 2.8% risk with RF. Data remains limited on ablating atrial tachycardia (AT) with no recent reports in the past year. 96% acute success and 12% recurrence have been previously reported. Manusama et al. have significantly contributed to the literature regarding the efficacy of cryoablation in treating typical atrial flutter. They have demonstrated a significant reduction in procedure time and number of lesions when ablating the cavotricuspid isthmus for typical atrial flutter with 10 mm and 15 mm cryoablation catheters. Overall success was reported 89% with minimal recurrence of Amazingly, there continues to be no reported cases of complete heart block requiring permanent pacemaker implantation with cryoablation when treating peri-AV nodal arrhythmias. Cryoablaton continues to gain traction as an alternative energy source for cardiac arrhythmia ablation. The advent of new catheters and mechanisms of cooling will continue to broaden the application of cardiac cryoablation as outcomes match or even excel those seen with RF.

Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias.The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node.We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats.We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats.

Surgical treatment of total anomalous pulmonary venous connection

To summarize the surgical treatment of total anomalous pulmonary venous connection (TAPVC). We retrospectively analyzed 49 patients with TAPVC as follows: 37 patients with supra-cardiac type in which 35 received anastomoses between the rear wall of the left atrium and the common pulmonary vein and the other 2 received anastomoses between the rear edge of the left atrium roof and the common pulmonary vein; another 12 patients with cardiac type who were incised the upper edge of coronary sinus, connected the common junction of pulmonary veins with the left atrium to form a new left atrium, and repaired the atrial septal defect with a pericardial patch. Forty-six patients recovered and 3 patients died. Thirty-eight patients were followed-up from 3 months to 8 years. The rest patients got fluent pulmonary vein drainage and their heart function resumed to NYHA I. TAPVC patients should be operated on immediately at definite diagnosis. The fluency of the common pulmonary vein-left atrium anastomoses and proper postoperative care can ensure a satisfactory outcome.

A Phase I Study of Telomerase-specific Replication Competent Oncolytic Adenovirus (Telomelysin) for Various Solid Tumors

A phase I clinical trial was conducted to determine the clinical safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. A single intratumoral injection (IT) of Telomelysin was administered to three cohorts of patients (1 x 10(10), 1 x 10(11), 1 x 10(12) viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen patients with a variety of solid tumors were enrolled. IT of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). hTERT expression was demonstrated at biopsy in 9 of 12 patients. Viral DNA was transiently detected in plasma in 13 of 16 patients. Viral DNA was detectable in four patients in plasma or sputum at day 7 and 14 post-treatment despite below detectable levels at 24 h, suggesting viral replication. One patient had a partial response of the injected malignant lesion. Seven patients fulfilled Response Evaluation Criteria in Solid Tumors (RECIST) definition for stable disease at day 56 after treatment. Telomelysin was well tolerated. Evidence of antitumor activity was suggested.

Comparison of the cardiac electrophysiological effects between doxazosin and bunazosin

In Langendorff-perfused adult rat heart with constant pressure at 80 mmHg, we found doxazosin, an alpha(1) adrenoceptor blocker, at 10 muM prolonged PR interval and induced occasional arrhythmia followed by complete inhibition of the sinus rhythm, whereas bunazosin, another alpha(1)-blocker, at same concentration did not. The results of voltage-clamp study showed that, at the concentration of 10 muM, doxazosin inhibited I (Na), I ( (Ca,L) ), I (to), and Iss without changing I (k1) but bunazosin only inhibited I ( (Ca,L) ) about 30%. Doxazosin also caused markedly negative shift of the I (Na) inactivation curve. In current-clamp study, doxazosin prolonged action potential duration in association with the decreased action potential amplitude and upstroke velocity, whereas bunazosin did not. We hypothesize that doxazosin-induced arrhythmia may result from the heterogeneous or different level of I ( (Ca,L) ) blockade of AV nodal tissue. In conclusion, the present study suggests that bunazosin is safer than doxazosin for long-term treatment in view of electrophysiological effect. However, the underlying mechanism of doxazosin induced nodal arrhythmia is still needed to be determined.

Severe Nodal Arrhythmia Following Direct Current Cardioversion for Atrial Flutter

A case of long-lasting nodal arrhythmia and severe hypotension following DC cardioversion for atrial flutter is presented. The patient, treated with the selective serotonin reuptake inhibitor sertraline and with sotalol, thiopental and digoxin, showed no sign of organic disease or drug intoxication. We suggest that drug interaction in combination with the DC shock and an altered sympaticus/parasympaticus balance during anaesthesia provoked the incident.

The Ventilatory and Oxygen Costs in the Anesthetized Rhesus Monkey of Inhaling Drugs Used in the Therapy and Diagnosis of Asthma

We examined in male Rhesus monkeys the effects on oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), heart and respiratory rates, and functional residual capacity (FRC) of breathing normal saline (NS), salbutamol (albuterol), methacholine (MCh), sodium cromoglycate (SCG), epinephrine (adrenaline), and terbutaline in doses commonly prescribed to human infants and children. We studied 10 anesthetized and intubated monkeys with a mean age and weight of 6.0 yr and 9.1 kg, respectively. VO2 increased over control, by 46.5% after salbutamol (p less than 0.0005), 25% after methacholine (p less than 0.001), 13.2% after epinephrine (p less than 0.01), and 16% after terbutaline (p less than 0.001), but it did not increase after either SCG or NS. VE increased by 82% after MCh and salbutamol (p less than 0.001), less dramatically after epinephrine and terbutaline at 50.5 and 31.5% (p less than 0.02 and p less than 0.001), respectively, and not at all after SCG and NS. Heart rate response was greatest after salbutamol, and nodal and ventricular arrhythmias were noted in four of 10 monkeys after MCh challenge. FRC did not change significantly except after salbutamol, where there was a small rise of 1.8 ml/kg (p less than 0.05).

Brief vagal bursts can induce Wenckebach arrhythmia.

We hypothesized that a brief burst of vagal stimulation applied in each cardiac cycle could elicit an atrioventricular (AV) nodal Wenckebach arrhythmia. Twenty-six dogs were anesthetized with pentobarbital sodium (30 mg/kg iv) and were given propranolol (1 mg/kg iv). We varied the timing of a vagal stimulus burst in steps of 25-50 ms relative to the onset of atrial or ventricular depolarization. In four of nine experiments, a Wenckebach arrhythmia occurred despite changing the timing of stimuli. By prolonging the effects of vagal stimulation on AV conduction with physostigmine, the timing of the stimuli no longer influenced the severity of the arrhythmia. We did experiments to open one of the feedback control loops; these results indicated that this arrhythmia has elements of a positive feedback control system. We also studied the effects of vagal stimulation on the arrhythmia during retrograde conduction. We found that the timing of vagal stimulation was critical in eliciting the arrhythmia in only 4 of the 10 dogs.

Atropine before Enflurane Anaesthesia: Effects on Cardiac Rhythm, Pulse Rate, Blood Pressure and Airway Secretion

The occurrence of cardiac arrhythmias and changes in pulse rate and blood pressure during mask anaesthesia with enflurane was investigated in 92 patients with special reference to the influence of atropine (0.01 mg kg-1 5 min before anaesthesia) and thiopental. The average duration of anaesthesia was a little less than 1 h in all four groups. More than five ventricular extrasystoles occurred in one patient (38 min after atropine). Supraventricular (mainly nodal) arrhythmias were significantly (P less than 0.005) more common in the atropine groups (15/45) than in the non-atropine groups (4/47). Following atropine, heart rate increased by about 25 beats min-1, whereas only very slight increases were seen in the non-atropine groups. Blood pressure fell at the induction but was almost back to normal at the end of anaesthesia. Blood pressure was unaffected by atropine. Slightly lower values of blood pressure were suggested in the thiopental groups, whereas thiopental did not modify cardiac rhythm or pulse rate. Suction of the pharynx was necessary in only one patient. In conclusion, the present study does not support the routine administration of atropine before enflurane anaesthesia with or without thiopental induction.

Cardiac arrhythmias in space: Role of vagotonia

Rhythm disorders observed in space have always been minor but they are not unfrequent. They include: ventricular or supra-ventricular extrasystoles, nodal arrhythmias, auriculo-ventricular conduction disorders. There are are several etiopathogenetic hypotheses: a strict selection must permit its elimination of an underlying heart disease; the potassium deficiency is often advanced but its role is not certain; the role of catecholamines is also discussed; the role of hypervagotony is extensively analysed as great clinical and electro-cardiographic evidence speaks for it. It can induce disorders which are more serious than those observed so far, particularly fibrillation or intermittent atrial flutter; weightlessness itself could partly condition the vagotonic state; and the effects of fluid shifts are also discussed from this point of view. The possible therapies for various atrial, nodal, ventricular disorders are reviewed, with greater detail for vagal atrial arrhythmias.

Ventricular Arrhythmias following Mitral Valve Replacement: Control with Intra-aortic Balloon Counterpulsation

Two patients with severe left ventricular failure (New York Heart Association's class 4) secondary to acute mitral insufficiency underwent mitral valve replacement after their condition had been stabilized by intra-aortic balloon counterpulsation. The need for hemodynamic support declined rapidly following valve replacement in both cases, but when the frequency of balloon counterpulsation was reduced, the immediate onset of life-threatening arrhythmias was noted. The resumption of 1:1 intra-aortic balloon counterpulsation always immediately abolished the arrhythmia. The dependency upon counterpulsation for arrhythmia suppression gradually diminished, and after a week the intra-aortic balloon was removed from the second patient, who subsequently made a complete recovery. The intra-aortic balloon was removed from the first patient four days after surgery and one day after its antiarrhythmic effect had been noted. Twenty-four hours later, this patient succumbed to a ventricular tachycardia which terminated in ventricular fibrillation. When no surgically correctable lesion is present, prolonged use of the intra-aortic balloon is recommended for all patients who develop ventricular or low nodal arrhythmias in response to decreasing the frequency of counterpulsation. As in our second patient, this will on occasion save a very high-risk patient.

Cardiovascular pharmacology of quazodine (MJ-1988), with particular reference to effects of myocardial blood flow and metabolic heat production.

1. The effects of intravenous infusions of quazodine (6,7-dimethoxy-4-ethylquinazoline; MJ-1988) on myocardial blood flow, myocardial metabolic heat production and on general haemodynamics have been studied in cats anaesthetized with sodium pentobarbitone.2. Quazodine (0.25 and 0.5 (mg/kg)/min for 10 min) decreased diastolic blood pressure, peripheral vascular resistance, systolic ejection time and left ventricular end-diastolic pressure. Heart rate, cardiac effort, output and external work and left ventricular dP/dt were markedly increased. These changes are indicative of increased myocardial contractility and peripheral vasodilatation.3. In a dose of (1.0 mg/kg)/min, quazodine had a more marked hypotensive effect, systolic pressure being significantly reduced, and had less effect on left ventricular dP/dt and cardiac effort. Calculated external cardiac work was slightly reduced and there were very occasional nodal arrhythmias.4. Changes in heart rate, aortic dP/dt and diastolic blood pressure induced by quazodine were unaffected by the previous administration of the beta-adrenoceptor blocking agent alprenolol in a dose (1.0 mg/kg) which abolished the effects of isoprenaline.5. In all doses, quazodine markedly increased local blood flow (by 70-540%) around an implanted myocardial heated thermocouple recorder. ;Corrected temperature', an index of local myocardial metabolic heat production, was almost unchanged and it is suggested that increased myocardial contractility, occurring with unchanged metabolic heat production and oxygen consumption, probably results from a concomitant decrease in intramural wall tension.

Left Atrial Parasystole

Although the criteria for the diagnosis of left atrial rhythms 1 Mirowski M. Left atrial rhythm. Diagnostic criteria and differentiation from nodal arrhythmias. Amer J Cardiol. 1966; 17: 203 Abstract Full Text PDF PubMed Scopus (46) Google Scholar ,2 Mirowski M. Ectopic rhythms originating anteriorly in the left atrium. Amer Heart J. 1967; 74: 299 Abstract Full Text PDF PubMed Scopus (18) Google Scholar are not universally accepted,8 evidence for the existence of automatic foci in the left atrium is gradually accumulating. 4 Mirowski M.Lau SH Bobb GA Steiner C. Damato AN Studies on left atrial automaticity Circulation Res (in press) Google Scholar The following electrocardiograms are important in this context since they suggest a parasystolic focus located in the left atrium.