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Purpose: The purpose of this paper is to explore the effect of monetary policy on bank risk in the banking system in some MENA countries. It explores how some economic and credit indicators affect the level of risk in the banking sector. It combines many factors that could affect banks’ risk appetite such as macroeconomic conditions, banks’ credit size and lending growth. The authors use nonperforming loans as a proxy for banking sector risks. At first, the authors have analyzed the linear relationship between monetary policy and credit risk. As mentioned above, nonlinearity is expected in the underlying relationship, and, thus, they have investigated the nonlinear relationship to deeply analyse the relationship using the dynamic panel threshold model, as stimulated by Kremer et al.(2013). Threshold models have gained a great importance in economics and finance for modelling nonlinear behaviour. Threshold models are useful in showing the turning points in the behaviour of financial and economic indicators. This technique has been applied in this study to study the effect of monetary policy on credit risk. Design/methodology/approach: This paper is divided into the following sections: Section 2 which previews the recent literature; Section 3 which includes some stylized facts about the relationship between credit risk and monetary policy; Section 4 which deals with the model and methodology; Section 5 which handles the data sources and discusses the results, and finally Section 6 which is the conclusion. The paper adopts dynamic panel threshold model of Kremer et al.(2013). Findings: The results show that the relationship between monetary policy and credit risk is positive and significant to a certain threshold, 6.3. If the lending interest rate is higher than 6.3, this increases the credit risk in the banking sector, because increasing the lending interest rate imposes huge burdens on the borrowers, and, therefore, the bad loans and nonperforming loans become more likely. Thus, the MENA countries need to decrease the lending interest rate to be less than 6.3 to reduce the effect of monetary policy on credit risk. Further, these results are qualitatively robust regarding the inclusion of additional control variables, using alternative threshold variables and further endogeneity checks of the credit risk, such as Risk premium and the squared term of the lending interest rate. The results of taking the risk premium and the squared term of the lending interest rate as a threshold served the analysis and confirmed the positive relationship between monetary policy and credit risk above a certain threshold. As for the risk premium, the relationship below the threshold was negative and significant. Other related research points might be a good avenue for the future research such as applying this approach to micro data of banks from different MENA countries. Also, more sophisticated approaches like time-varying panel approach to assess the relationship over the time can be applied. Originality/value: The importance of this paper lies in the fact that it does not only study the effect of time, but it also focuses on the panel data about some economic and credit indicators in the MENA region for the first time. This is because central banks in the MENA region have common characteristics and congruous level of economic growth. Therefore, to study how the monetary policy affects those countries’ credit risks in their lending policies, this requires careful analysis of how the central banks in this region might behave to control default risks.

Background: Ablation therapy is the treatment of choice in antiarrhythmic drugrefractory atrial fibrillation (AF). It is performed by either cryoballoon ablation (CBA) or radiofrequency ablation. CBA is gaining popularity due to simplicity with similar efficacy and complication rate compared with RFA. In this meta-analysis, we compare the recurrence rate of AF and the complications from CBA versus RFA for the treatment of AF. Methods: We systematically searched PubMed for the articles that compared the outcome of interest. The primary outcome was to compare the recurrence rate of AF between CBA and RFA. We also included subgroup analysis with complications of pericardial effusion, phrenic nerve palsy and cerebral microemboli following ablation therapy. Results: A total of 24 studies with 3527 patients met our predefined inclusion criteria. Recurrence of AF after CBA or RFA was similar in both groups (RR: 0.84; 95% CI: 0.65, 1.07; I2=48%, Cochrane p=0.16). In subgroup analysis, heterogeneity was less in paroxysmal AF (I2=0%, Cochrane p=0.46) compared to mixed AF (I2=72%, Cochrane p=0.003). Procedure and fluoroscopy time was less by 26.37 and 5.94 minutes respectively in CBA compared to RFA. Complications, pericardial effusion, and silent cerebral microemboli, were not different between the two groups, however, phrenic nerve palsy was exclusively present only in CBA group. Conclusion: This study confirms that the effectiveness of CBA is similar to RFA in the treatment of AF with the added advantages of shorter procedure and fluoroscopy times.

ObjectiveIncreasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population.MethodsForty consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), interleukin-1 (IL-1)) were compared with patients with active rheumatoid arthritis (RA), comorbidity or healthy controls. An additional 46 patients with different inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12; others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled, and corrected QT (QTc) and cytokine levels were measured during active disease and after a CRP decrease of >75% subsequent to therapy.ResultsIn the TdP cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a definite inflammatory disease identifiable in 18/40 cases (acute infections, n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but not TNFα and IL-1, was ~15–20 times higher than in controls, and comparable to RA patients. In the inflammatory cohort, where QTc prolongation was common (mean values: 456.6±30.9 ms), CRP reduction was associated with IL-6 level decrease and significant QTc shortening (−22.3 ms).ConclusionThe data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy.

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This article is a report of an international symposium, endorsed by the Section on Sports Cardiology of the European Association for Cardiovascular Prevention and Rehabilitation, the Italian Society of Sports Cardiology, and the Italian Federation of Sports Medicine, which was held within the 11th International Workshop on Cardiac Arrhythmias (Venice Arrhythmias 2009, Venice, Italy, October 2009). The following main topics were discussed during the symposium: the role of novel diagnostic examinations to assess the risk of sudden death in athletes, controversies on arrhythmic risk evaluation in athletes, controversies on the relationship between sports and arrhythmias, and controversies on antiarrhythmic treatment in athletes.

Management of Sudden Cardiac Death (SCD) is undergoing a radical change in direction. It is becoming increasingly appreciated that besides depressed left ventricular systolic function and the conventional risk stratification tools, new markers for plaque vulnerability, enhanced thrombogenesis, specific genetic alterations of the autonomic nervous system, cardiac sarcolemmal and contractile proteins, and familial clustering may better segregate patients with atherosclerotic coronary artery disease who are at high risk for SCD from those who may suffer from nonfatal ischemic events. Better understanding of pathophysiological processes, such as postmyocardial infarction remodeling, the transition from compensated hypertrophy to heart failure, and the increased cardiovascular risk of coronary artery disease in the presence of diabetes or even a prediabetic state will help to improve both risk stratification and management. The rapidly developing fields of microchips technology and proteomics may allow rapid and cost-effective mass screening of multiple risk factors for SCD. The ultimate goal is to identify novel methods for risk stratification, risk modification, and prevention of SCD that could be applied to the general public at large.

In the last decade there have been considerable advances in the understanding of the pathophysiology of malignant ventricular tachyarrhythmias (VA) and Sudden Cardiac Death (SCD). Over 80 of SCD occurs in patients with organic heart disease. However, approximately 10-15 of SCD occurs in the presence of structurally normal heart and the majority of those patients are young. In this group of patients, changes in genes encoding cardiac ion channels produce modification of the function of the channel resulting in an electrophysiological substrate of VA and SCD. Collectively these disorders are referred to as Cardiac Ion Channelopathies. The 4 major syndromes in this group are: The Long QT Syndrome (LQTS), the Brugada Syndrome (BrS), the Short QT Syndrome (SQTS), and the Catecholaminergic Polymorphic VT (CPVT). Each of these syndromes includes multiple subtypes with different and sometimes complex genetic abnormalities of cardiac ion channels. Many are associated with other somatic and neurological abnormalities besides the risk of VA and SCD. The current management of cardiac ion channelopathy could be summarized as follows: 1) in symptomatic patients, the implantable cardioverter defibrillator (ICD) is the only viable option; 2) in asymptomatic patients, risk stratification is necessary followed by the ICD, pharmacotherapy, or a combination of both. A genotype-specific approach to pharmacotherapy requires a thorough understanding of the molecular-cellular basis of arrhythmogenesis in cardiac ion channelopathies as well as the specific drug profile.

Management of Sudden Cardiac Death (SCD) is undergoing a radical change in direction. It is becoming increasingly appreciated that besides depressed left ventricular systolic function and the conventional risk stratification tools, new markers for plaque vulnerability, enhanced thrombogenesis, specific genetic alterations of the autonomic nervous system, cardiac sarcolemmal and contractile proteins, and familial clustering may better segregate patients with atherosclerotic coronary artery disease who are at high risk for SCD from those who may suffer from nonfatal ischemic events. Better understanding of pathophysiological processes, such as postmyocardial infarction remodeling, the transition from compensated hypertrophy to heart failure, and the increased cardiovascular risk of coronary artery disease in the presence of diabetes or even a prediabetic state will help to improve both risk stratification and management. The rapidly developing fields of microchips technology and proteomics may allow rapid and cost-effective mass screening of multiple risk factors for SCD. The ultimate goal is to identify novel methods for risk stratification, risk modification, and prevention of SCD that could be applied to the general public at large.

Torsade de pointes ventricular tachyarrhythmia in the long QT syndrome is a prime example of how molecular biology, ion channel, and cellular and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and the acquired long QT syndrome are caused by abnormalities (intrinsic, acquired, or both) of the ionic currents underlying ventricular repolarization. In this review, the continually unraveling molecular biology of congenital long QT syndrome is discussed. The various pharmacologic agents associated with the acquired long QT syndrome are listed. Although it is difficult to predict which patients are at risk for torsade de pointes, careful assessment of the risk to benefit ratio is important before prescribing drugs known to cause QT prolongation. The in vivoelectrophysiologic mechanism of torsade de pointes in the long QT syndrome is described, using as a paradigm the anthopleurin-A canine model, a surrogate for LQT3. The characteristic association of torsade de pointes with T-wave alternans and short-long cardiac sequences is discussed, with emphasis on electrophysiologic mechanisms. Finally, the expanding knowledge of genetic mutations other than long QT syndrome associated with polymorphic ventricular tachyarrhythmia is emphasized.

Type I diabetic cardiomyopathy has consistently been shown to be associated with decrease of repolarising K+ currents, but the mechanisms responsible for the decrease are not well defined. We investigated the streptozotocin (STZ) rat model of type I diabetes. We utilized RNase protection assay and Western blot analysis to investigate the message expression and protein density of key cardiac K+ channel genes in the diabetic rat left ventricular (LV) myocytes. Our results show that message and protein density of Kv2.1, Kv4.2, and Kv4.3 are significantly decreased as early as 14 days following induction of type I diabetes in the rat. The results demonstrate, for the first time, that insulin-deficient type I diabetes is associated with early downregulation of the expression of key cardiac K+ channel genes that could account for the depression of cardiac K+ currents, Ito-f and Ito-s. These represent the main electrophysiological abnormality in diabetic cardiomyopathy and is known to enhance the arrhythmogenecity of the diabetic heart. The findings also extend the extensive list of gene expression regulation by insulin.

Objectives: This study was conducted to determine the optimal target heart rate (HR) for the use of exercise‐induced T‐wave alternans (TWA) as an index for risk of malignant ventricular tachyarrhythmias.

OBJECTIVES

Because time-domain (TD) analysis of the signal-averaged ECG (SAECG) has some limitations that limit its use, several frequency-domain analysis techniques were developed in an attempt to improve the dignostic ability of the SAECG. However, it is not known how reliable these techniques are at detecting late potentials. This prospective study compares the short-term reproducibility of 4 analysis techniques: TD analysis, spectral temporal mapping (STM), spectral turbulence analysis (STA), and acceleration spectrum analysis (ASA), in a large series of normal patients and post-myocardial infarction (MI) patients. Two consecutive SAECGs were recorded in 634 patients that were divided into 3 groups: 117 remote MI patients undergoing programmed electrical stimulation for the inducibility of ventricular tachycardia (Group 1), 407 consecutive acute MI survivors (Group 2), and in 110 healthy volunteers (Group 3). The diagnostic reproducibility of the 4 techniques was evaluated by comparing rates of inconsistent results (1 normal and the other abnormal). The numeric reproducibility for each technique was assessed by comparing the normalized differences of each single SAEGG parameter between the 2 recordings. inconsistent results of diagnostic reproducibility were observed in 4.1%, 6.9%, 9.8%, and 18.0%, with TD, STA, ASA, and STM, respectively. Comparisons of these rates were significantly different (P<.05) except between STA and ASA (P=.07). The numeric reproducibility was highes for TD parameters, lowest for STM factors of normality, and intermediate for STA and ASA indices. TD analysis remains the most reproducible SAECG analysis technique, whereas STM showed the worst reproducibility, which limits its clinical applicability. STA and ASA provide an acceptable intermediate reproducibility, the former being slightly, although not significantly, more reproducible than the latter.

OBJECTIVES

Background

Late clinical and hemodynamic evaluations in 18 patients with ventricular aneurysmectomy and aorta-coronary bypass are presented. Ten patients had significant obstructive lesions in two major vessels (55 per cent), and 6 had extensive three vessel disease (33 per cent). In 13 patients, 21 aorta-coronary saphenous bypass grafts were performed in addition to aneurysmectomy. The operative mortality rate was 11 per cent. One patient died suddenly 5 months after the operation (one year mortality rate 17 per cent). The 15 surviving patients have been followed up for 12 to 41 months (average 24 months). Clinical results were considered excellent in 2 patients who have been asymptomatic (Class I, N.Y.H.A.). Nine others were considered to have good clinical results (Class II). Five patients have continued to have congestive heart failure and angina on minimal effort (Class III or IV). Six of the 11 patients considered to have excellent or good results underwent postoperative hemodynamic studies 6 to 34 months after the operation. A significant increase in cardiac index was documented in all 6 patients. Paradoxic movement was not detected in any of the postoperative ventriculograms. Five of the seven venous grafts inserted were patent. Elevated left ventricular end-diastolic pressure (LVEDP), low cardiac index, and a persistent dyskinetic area in the left ventricle were found in 2 patients considered to have poor clinical results. Clinical and hemodynamic evaluations have shown a significant improvement in most patients surviving ventricular aneurysmectomy. However, postoperative systemic embolism, myocardial infarction, progression of coronary artery disease, transient cerebral ischemic attacks, graft occlusion, arrhythmias, and mitral regurgitation in previously prolapsed mitral valve leaflets account for progressive disability and limited activity after a successful operation.

To study the influence of left bundle branch block (LBBB) on the signal-averaged electrocardiogram (SAECG), quantitative and qualitative analyses of SAECG parameters were undertaken in 48 patients with electrocardiographic evidence of intrinsic LBBB and in 39 patients with a “normal” surface QRS duration (<120 msec) who underwent right ventricular pacing-induced LBBB. We assumed pacing of the right ventricular apex to be a suitable model of this conduction defect. Sustained monomorphic ventricular tachycardia (SMVT) was inducible in 16 of 48 patients with intrinsic LBBB and in 23 of 39 patients with pacing-induced LBBB. Utilizing a filter setting of 25 to 250 Hz, late potentials were defined as a total filtered QRS duration ≥120 msec, a root mean square voltage in the terminal 40 msec (RMS 40) of ≤25 μV, and the duration of signals < 40 μV (LAS 40) of ≥38 msec. Only RMS 40 and LAS 40 criteria were used in patients with LBBB. Prolongation of LAS 40 and fragmentation of signals in the terminal portion of the filtered QRS were characteristic of all patients with LBBB aberration. Of those patients with intrinsic LBBB, the mean total filtered QRS duration, RMS 40, and LAS 40 for inducible and noninducible patients were significantly different (170 ± 28, 16 ± 10, 55 ± 24, and 153 ± 18 msec, 25 ± 10 μV, 33 ± 16.9 msec; p= 0.04, 0.009, and 0.007, respectively). Noninducible patients with a normal QRS duration demonstrated a 60% decrement in the mean RMS 40 value during pacing-induced LBBB. These changes resulted in a 59% false positive incidence of late potentials during pacing-induced LBBB. This correlated with a similarly low mean RMS 40 value in patients with intrinsic LBBB and no inducible SMVT, hence giving rise to a false positive incidence of late potentials of 63%. Since “standard” RMS 40 and LAS 40 criteria resulted in low specificity and positive predictive value, new parameters were selected and analyzed. The combination of RMS 40 ≤ 17 μV plus LAS 40 ≥ 55 msec yielded the best overall statistical result, with a sensitivity, specificity, and total predictive accuracy of 69%, 81%, and 77%, respectively. in conclusion: (1) A reduction of RMS 40, prolongation of LAS 40, and fragmentation of signals in the terminal portion of the filtered QRS are charateristics of LBBB. (2) New RMS 40 and LAS 40 criteria for late potentials possessed higher total predictive accuracy for inducible sustained monomorphic VT than “standard” criteria in patients with LBBB.

The evolution of second-degree atrioventricular block in the His-Purkinje system was studied in four patients with acute myocardial infarction, utilizing continuous electrocardiographic monitoring and serial His bundle recordings. Three patients had anterior wall infarction; all developed acute right bundle-branch block and two also showed a left anterior hemiblock one to four hours prior to onset of second-degree atrioventricular block. The fourth patient had an old anteroseptal infarction and chronic right bundle-branch block and left anterior hemiblock; he developed second-degree atrioventricular block following an acute lateroposterior infarction. His bundle electrograms were obtained during the insertion of a temporary ventricular pacemaker within the first 24 hours of onset of chest pain. A second His bundle electrogram was obtained during removal of the temporary pacemaker 7 to 14 days after the first recording. In all cases the block was localized in the His-Purkinje system. In three patients the first His bundle recording showed second-degree atrioventricular block with minimal increment of delay in conduction (3 to 10 msec) prior to the blocked beat (equivalent of Mobitz type 2 block). The second His bundle electrogram showed the development of significant increment of delay in conduction (35 to 210 msec) prior to block (equivalent of Wenckebach conduction). The fourth patient illustrated the reverse order of the observations seen in the other three. Three patients showed resumption of 1:1 atrioventricular conduction; however, when one patient was challenged with rapid atrial pacing, he developed repetitive block in the His-Purkinje system.

Following myocardial Infarction (MI) the heart undergoes a process of remodeling characterized by considerable hypertrophy of the non-infarcted myocardium. We have recently characterized the molecular basis of key electrophysiologic alterations that may provide insight into the arrhythmogenecity of post-MI remodeled hypertrophied myocardium. To further characterize other key alterations in the pattern of cardiac gene expression in a time-dependent manner, we have measured mRNA and immunoreactive protein levels of selective cardiac genes in the remodeled hypertrophied left-ventricular (LV) myocardium of rats, 3 and 21 days after left-coronary ligation and compared the results with sham-operated rats. RNase protection assay was performed to assess the expression of c-fos, atrial natriuretic factor (ANF), brain natriuretic factor (BNF),α2/3isoform of Na–K ATPase, cardiacα/βisoform of myosin heavy chain (MHC). Compared to the sham group, the expression of c-foswas increased 10-fold (P<0.02) in the MI group on day 3, but unlike other overload hypertrophy models, the expression remained elevated by three-fold on day 21. Similar to other overload models, the ANF and BNF expression increased significantly. No alterations were observed in the expression of cardiacα-actin. There was reexpression of the fetal isogene form of MHC and Na–K ATPase after MI. Theβ-MHC mRNA levels, the fetal isoform of MHC, returned to basal levels after 21 days. After an initial five-fold decrease the adult isoform of αNa–K ATPase,α2Na–K ATPase mRNA, returned to control levels and similar changes were seen in the corresponding protein levels. These findings indicate that during LV remodeling and hypertrophy following MI, there is an upregulation of early response genes and fetal isogene expression. The pattern of activation, however, is distinct from that observed in other overload models, indicating the possible involvement of alternate signal transduction pathways.

In 40 anesthetized dogs, malignant ventricular arrhythmias were studied in the late myocardial infarction period (3 to 20 days) after the phase of increased ventricular automaticity had subsided. Arrhythmias were induced by atrial pacing by means of regular stimulation or pacing with long-short cycle sequences. The latter involved the insertion of premature stimuli into regular pacing sequences as well as introduction of abrupt pauses into regular pacing rhythms. Arrhythmias could not be induced 10 to 20 days after infarction (eight dogs) or in sham-operated animals. In 27 dogs studied 3 to 9 days after myocardial infarction, re-entrant ventricular arrhythmias were consistently evoked by atrial pacing with long-short cycle sequences. Of these 27 dogs, only six had ventricular arrhythmias during regular pacing (50 to 350 beats per minute). The rate in each instance (115 to 260; average 200 beats per minute) remained within a critically narrow range (± 5 to 10 beats per minute). Activation delay in the epicardium of the infarct zone was consistently prolonged immediately after a long-short cycle sequence. Ventricular arrhythmias were always preceded by marked fractionation and delay of ischemic-zone epicardial electrograms when induced by long-short sequences in atrial pacing. In the six animals with critical, rate-dependent ventricular ectopia, complex patterns of underlying epicardial activation delay were recorded in the infarct zone. These included Wenckebach sequences of delayed portions of the electrograms and appeared as trigeminal and quadrigeminal rhythms on the standard electrocardiogram. This study indicates that in the dog, 3 to 9 days after myocardial infarction, re-entrant ventricular arrhythmias arising in the epicardium of the infarct zone are always evoked by atrial pacing with long-short cycle sequences. Abnormalities of refractoriness, particularly postrepolarization refractoriness, are related to both ischemia and abrupt heart rhythm changes, and they are implicated in the induction of these arrhythmias. Regular pacing over a wide range of heart rates less commonly resulted in arrhythmias. Re-entrant ventricular arrhythmias could not be provoked in dogs 10 to 20 days after myocardial infarction by either rapid heart rates or sudden changes in rhythm (long-short cycle sequences).

Patch-clamp recordings from ventricular myocytes of neonatal rats identified ionic channels that open in response to membrane stretch caused by negative pressures (1 to 6 cm Hg) in the electrode. The stretch response, consisting of markedly increased channel opening frequency, was maintained, with some variability, during long (>40 seconds) stretch applications. The channels have a conductance averaging 120 pS in isotonic KCl, have a mean reversal potential 31 mV depolarized from resting membrane potential, and do not require external Ca++ for activation. The channels appear to be relatively non-selective for cations. Since they are gated by physiological levels of tension, stretch-activated channels may represent, a cellular control system wherein beat-to-beat tension and/or osmotic balance modulate a portion of membrane conductance.

Enhanced susceptibility to toxic arrhythmias by digitalis administration has been reported in clinical and experimental myocardial infarction. To investigate the mechanism responsible for this phenomenon, the effects of superfusion with normal Tyrode's solution and super-fusion with Tyrode's solution containing 4 × 10−8Mof ouabain in ischemic Purkinje fibers were compared. Ischemic Purkinje fibers of small endocardial preparations from 1 day old myocardial infarcts in 18 dogs were used for the study. During control conditions, these endocardial preparations demonstrated delayed afterde-polarizations and triggered activity. Superfusion with normal Tyrode's solution resulted in a gradual increase in maximal diastolic potential and action potential amplitude, a decrease in delayed afterdepolarization amplitude and slowing and termination of triggered activity. Superfusion for 90 minutes with Tyrode's solution containing ouabain resulted in: 1) an increase in the magnitude of delayed afterdepolarizations in preparations demonstrating subthreshold delayed afterdepolarizations, 2) sustainment of triggered activity in preparations showing nonsustained triggered activity, and 3) shortening of cycle lengths of the triggered activity in preparations demonstrating sustained triggered activity before superfusion with ouabain. These effects occurred despite the gradual increase in maximal diastolic potential and action potential amplitude. Superfusion of normal Purkinje fibers with Tyrode's solution containing 4 × 10−8Mof ouabain for 90 minutes did not result in delayed afterdepolarizations or triggered activity. Thus, ouabain at a concentration that has no toxic effect on normal Purkinje fibers may enhance arrhythmias in ischemic Purkinje fibers by increasing the magnitude of delayed afterdepolarizations and enhancing triggered activity.

One to 5 days after one-stage ligation of the left anterior descending coronary artery in dogs, reentrant excitation can be induced by programmed premature stimulation in the surviving electrophysiologically abnormal, thin epicardial layer overlying the infarct. In experiments in four dogs, reentrant excitation occurred “spontaneously” during a regular sinus or atria) rhythm. A tachycardia-dependent Wenckebach conduction sequence in a potentially reentrant pathway was the initiating mechanism for spontaneous reentrant tachycardias and was the basis for both manifest and concealed reentrant extrasystolic rhythms. In all dogs showing spontaneous reentry, reentrant excitation could also be induced by premature stimulation at cycle lengths much shorter than those associated with spontaneous reentry, and induced reentrant circuits were always different from those during spontaneous reentry. In two dogs, the reentrant circuit was located intramurally in close proximity to a patchy septal infarction.

Although a strong clinical association exists between congenital heart block (CHB) and an immune response to SSA/Ro and SSB/La proteins, a causative role of these antibodies in the pathogenesis is just emerging. In a preliminary report, we have demonstrated that IgG fractions isolated from the sera of mothers whose children have CHB are arrhythmogenic in the human fetal heart. To more precisely define the arrhythmogenic effect of anti-SSA/Ro-SSB/La antibodies, we used the readily available rat heart model to record: 1) ECGs from Langendorff beating hearts;2) action potentials from atrioventricular (AV) nodal preparations;3) L-type Ca currents, ICaat the whole-cell and single channel levels; and 4) other currents such as the transient outward K+current,Ito, the inward rectifier K+current,IK1, and the Na+current,INa. Perfusion of hearts with purified IgG (800 µg/mL), isolated from the serum of a mother with SSA/Ro and SSB/La antibodies whose child had CHB, resulted in bradycardia associated with 2:1 AV block. Simultaneous action potentials were recorded from dissected atrial and AV nodal areas of the rat heart. Superfusion of these preparations with the same mother's IgG fraction resulted in 2:1 AV block followed by complete inhibition of AV nodal action potential. Because AV nodal electrogenesis is largely dependent on ICa, the effect of these antibodies on ICawas subsequently determined. Superfusion of myocytes with whole serum or purified IgG (80 µg/mL) from the same mother consistently inhibited whole cell ICa, ensemble average Ba2+currents (IBa) and open state probability, po, without affecting the channel conductance. IgG had no significant effect on Ito,IK1, or INa. Whole sera and IgG fractions from a healthy mother with no detectable anti-SSA/Ro or SSB/La antibodies did not inhibit ICaorIBa. These results demonstrate that IgG containing anti-SSA/Ro and -SSB/La antibodies induces complete AV block in beating hearts and in multicellular preparations, thus implicating a preferential interaction of these autoantibodies with Ca channels and/or associated regulatory proteins. This is consistent with the observed inhibition of Ca channels that may be a critical factor contributing to the pathogenesis of CHB.

Of 1125 patients with acute myocardial infarction admitted to Mount Sinai Medical Center in 1971 and 1972, 292 (28.8 percent) had intraventricular conduction defects. In 210 of the 292 patients with intraventricular conduction defect, it was possible to determine if the conduction defect was present before the infarction (Group 1, 123 patients) or developed acutely with the infarction (Group 2, 87 patients). Of the 210 patients, 52.8 percent died (mean age 72.1 years). Fifty-three patients in Group 1 and 18 patients in Group 2 had isolated left axis deviation (LAD). The mortality was 35 percent and 28 percent respectively. This difference was not significant (p > 0.60). Sixty-four of the 210 patients presented with a left bundle branch block (LBBB) pattern. The overall mortality of 54 percent was the same in both groups. Right bundle branch block (RBBB), with either normal axis, left (LAD) or right axis deviation (RAD), was found in 74 patients. Of 40 patients in Group 1, 62 percent died, and of 35 patients in Group 2, 80 percent expired. Again this difference was not significant (p > 0.10). In 13 of 25 patients with RBBB in Group 1, death was possibly related to progression of the conduction defect The use of prophylactic temporary pacing is suggested for these patients.

The goal of this study was to establish guidelines for the prognostic use of the time domain signal-averaged electrocardiogram (ECG) after myocardial infarction.

Commercial intravenous amiodarone has been reported to have antiarrhythmic actions and to cause only mild hypotension in humans. In the dog, however, amiodarone was observed to cause severe hypotension. Since commercial intravenous amiodarone is amiodarone compound (50 mg/ml) dissolved in water with polysorbate 80 (Tween 80) (100 mg/ml), the effects of amiodarone in ethanol (5 mg/kg) and polysorbate 80 < 10 mg/kg) were studied individually, and in combination in anesthetized dogs. Commercial intravenous amiodarone and polysorbate 80 caused at least a 60 drop in mean blood pressure and left ventricular maximum dP/dtfor at least 30 min, whereas amiodarone in ethanol did not. The drop in blood pressure was not principally due to peripheral vasodilation. Therefore, in dogs the diluent polysorbate 80 is the major cause of severe hypotension resulting from commercial intravenous amiodarone. These studies show that commercial intravenous amiodarone produces results different in dogs than has been previously reported in humans. Therefore: (a) canine models for studying the antiarrhythmic actions of commercial intravenous amiodarone would produce results complicated by severe hypotension: and (b) polysorbate 80 is not an inert substance, but is a potent cardiac depressant.

Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

Isochronal maps of ventricular activation were analyzed in dogs 1 to 5 days after infarction utilizing a 64 channel multiplexer. Only dogs in which circus movement reentry could not be induced by a single premature stimulus were analyzed. Reentrant rhythms could be successfully induced equally by multiple (double or triple) premature stimuli and by burst pacing. Successive premature stimuli as well as successive beats during burst pacing resulted in progressively longer arcs of functional conduction block or slower circulating wave fronts, or both, that succeeded in reexciting myocardial zones on the proximal side of the arc of block to initiate reentry. However, for manifest reentry to be induced by burst pacing, the paced run had to be terminated after the beat that resulted in a critical degree of conduction delay. Otherwise, reentrant activation could be confined (concealed) by the subsequent paced wave front, which could also arrive earlier to the reentrant circuit zone of slow conduction resulting in block and interruption of reentry. Termination of a paced run after this beat would not result in reentry. If the paced run was extended past this beat, a new sequence of ventricular activation patterns characterized by progressively longer arcs of block or slower conduction, or both, developed again. The number of beats in a paced run that could initiate reentry varied with the cycle length of pacing, as well as in different experiments, and was difficult to standardize. It is therefore concluded that random burst pacing as a technique for induction of reentrant rhythms should probably be abandoned in favor of multiple premature stimulation.

In this work the electrophysiologic mechanisms of ventricular arrhythmias have been briefly summarized. Ventricular arrhytmias can be caused either by pacemaker activity or by reentrant excitation. Enhancement of normal automaticy can generate a parasystolic rhythm in normal fibers. Abnormal automaticity may arise fom fibers in which maximum diastolic potential has been reduced by a variety of interventions. Triggered activity is caused by either an early (EAD) or delayed (DAD) afterdepolarization and requires a prior normal action potential for initiation. While there is growing evidence that EAD-induced triggered activity plays a significant role in the Long QTU syndrome and Torsade de Pointes, no clinical arrhythmias has definitely been ascribed to DADs, although DADs have been recorded in man after acute digoxin intoxication.

Patch-clamp recordings from ventricular myocytes of neonatal rats identified ionic channels that open in response to membrane stretch caused by negative pressures (1 to 6 cm Hg) in the electrode. The stretch response, consisting of markedly increased channel opening frequency, was maintained, with some variability, during long (>40 seconds) stretch applications. The channels have a conductance averaging 120 pS in isotonic KCl, have a mean reversal potential 31 mV depolarized from resting membrane potential, and do not require external Ca++ for activation. The channels appear to be relatively non-selective for cations. Since they are gated by physiological levels of tension, stretch-activated channels may represent, a cellular control system wherein beat-to-beat tension and/or osmotic balance modulate a portion of membrane conductance.