Pulmonary vascular disease associated with parasitic infection--the role of schistosomiasis.

Parasitic diseases have been known to cause pulmonary vascular lesions. Schistosomiasis is the most common parasitic disease associated with pulmonary arterial hypertension, although other trematodes have been implicated. Systematic evaluation of and interest in this problem have been rekindled because of the current availability of pulmonary arterial hypertension treatment.

Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus.

We investigated the pulmonary vascular effects of prophylactic use of sildenafil, a specific phosphodiesterase-5 inhibitor, in late-gestation fetal lambs with chronic pulmonary hypertension. Fetal lambs were operated on at 129 +/- 1 days gestation (term = 147 days). Ductus arteriosus (DA) was compressed for 8 days to cause chronic pulmonary hypertension. Fetuses were treated with sildenafil (24 mg/day) or saline. Pulmonary vascular responses to increase in shear stress and in fetal PaO2 were studied at, respectively, day 4 and 6. Percent wall thickness of small pulmonary arteries (%WT) and the right ventricle-to-left ventricle plus septum ratio (RVH) were measured after completion of the study. In the control group, DA compression increased PA pressure (48 +/- 5 to 72 +/- 8 mmHg, P < 0.01) and pulmonary vascular resistance (PVR) (0.62 +/- 0.08 to 1.15 +/- 0.11 mmHg x ml(-1) x min(-1), P < 0.05). Similar increase in PAP was observed in the sildenafil group, but PVR did not change significantly (0.54 +/- 0.06 to 0.64 +/- 0.09 mmHg x ml(-1) x min(-1)). Acute DA compression, after brief decompression, elevated PVR 25% in controls and decreased PVR 35% in the sildenafil group. Increased fetal PaO2 did not change PVR in controls but decreased PVR 60% in the sildenafil group. %WT and RVH were not different between groups. Prophylactic sildenafil treatment prevents the rise in pulmonary vascular tone and altered vasoreactivity caused by DA compression in fetal lambs. These results support the hypothesis that elevated PDE5 activity is involved in the consequences of chronic pulmonary hypertension in the perinatal lung.

Morphological algebraic models of the TU-wave patterns/in idiopathic long QT syndrome.

A computer-assisted analysis of the TU-complex morphology was employed to characterize repolarization abnormalities in LQTS and to assess arrhythmic risk. Electrocardiograms (ECGs) were collected from 14 idiopathic LQTS patients (seven without symptoms and seven with a history of syncope or cardiac arrest) and from 14 sex- and age-matched normal subjects. Digitized TU-wave patterns from V2-V6 precordial leads were analyzed. The morphologies of the T and U waves were modeled by an algebraic sum of differences between two pairs of action potential-like curves of different shape and duration so that the whole TU complex was approximated by (S1-S2)+(L1-L2). By finding the best fit model of the digitized TU-wave signal, the amplitude and duration of each decomposition curve were determined for each lead. The following 'secondary' parameters were then derived: (a) the ratio between the sum of the amplitudes of the two long (L1 and L2) and the two short (S1 and S2) decomposition curves (A-ratio), (b) the highest A-ratio found in V2 to V6 (A-ratio(max)), and (c) the model-derived durations of the T-wave, U-wave and TU-complex. Conventional measures of RR and QTc intervals and of QT dispersion did not differ between symptomatic and asymptomatic LQTS patients. Modeled QT interval was significantly longer in the symptomatic than in the asymptomatic LQTS patients and in asymptomatic LQTS patients than in the controls. In addition, symptomatic LQTS patients had a longer S2 and T-wave duration in most leads than normal subjects. Conversely, modeled QU interval and U-wave duration did not significantly differ between the three groups. Compared to normal subjects, the amplitudes of S1, S2, L1 and L2 in the LQTS patients were not significantly different in most leads. A-ratio and A-ratio(max) were greater in symptomatic than asymptomatic LQTS patients and in the latter than in controls. A cut-off value of 0.90 of A-ratio(max) separated all symptomatic (1.34+/-0.38) from all asymptomatic patients (0.60+/-0.21). Although the correlation between model parameters and cellular substrate is at present unclear, it is possible that the morphological alterations described by the model are related to the arrhythmogenic mechanism(s) of the idiopathic LQTS.

A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease.

BACKGROUND: Antiarrhythmic drugs are still used for the treatment of ventricular tachyarrhythmias, in combination with implantable cardioverter-defibrillators or without them. AIM OF THE STUDY: In a double-blind randomized crossover design, the short- and long-term efficacy and safety of oral dofetilide or oral sotalol were compared in 135 patients with ischaemic heart disease and inducible sustained ventricular tachycardia. METHODS: The inducibility of ventricular tachycardia was determined by programmed electrophysiological stimulation at baseline. Patients were then blindly randomized to receive either oral dofetilide 500 microg twice daily or oral sotalol 160 mg twice daily, for 3 to 5 days. Suppression of inducible ventricular tachycardia on the drug was then assessed by programmed electrophysiological stimulation. After a wash-out period of at least 2.5 days, the patients received the alternative treatment for 3 to 5 days. Suppression of inducible ventricular tachycardia on the alternate drug was again determined by programmed electrophysiological stimulation. Selection of long-term treatment was allocated blindly according to programmed electrophysiological stimulation results. RESULTS: During the acute phase, 128 patients received both dofetilide and sotalol. Sixty-seven patients were responders to either drug. Forty-six patients (35.9%) were responders to dofetilide compared with 43 (33.6%) to sotalol (P=ns). Only 23 patients responded to both dofetilide and sotalol. Adverse events, deemed to be treatment related, were seen in 2.3% of patients receiving dofetilide and 8.6% of patients receiving sotalol (P=0.016). Three patients on dofetilide had torsade de pointes. Two patients receiving sotalol died during the acute phase (one was arrhythmic death, and the other was due to heart failure). During the long-term phase, two of 42 patients (4.8%) receiving dofetilide and three of 27 patients (11.1%) receiving sotalol withdrew from treatment due to lack of efficacy. Overall, during the long-term phase, 23.8% of the patients receiving dofetilide and 37.0% of the patients receiving sotalol, withdrew from treatment with a similar pattern of withdrawals for the two drugs. CONCLUSION: Dofetilide was as efficacious as sotalol in preventing the induction of sustained ventricular tachycardia. There was no concordance in the response rate in two-thirds of the patients. Dofetilide was significantly better tolerated during the acute phase than sotalol. Both dofetilide and sotalol were well tolerated during the long term with no statistically significant difference in the adverse events.

Repolarization changes in a double-blind crossover study of dofetilide versus sotalol in the treatment of ventricular tachycardia.

UNLABELLED: The aim of this study was to determine whether a therapeutic response to Class III antiarrhythmic drugs is related to predictable changes in repolarization on the electrocardiogram (ECG). A group of 57 patients with ischemic heart disease and inducible ventricular tachycardia (VT) at electrophysiological study (EPS) were selected from a population enrolled in a randomized double-blind crossover study of dofetilide (500 micrograms bid) versus sotalol (160 mg bid). ECGs were analyzed blindly, and RR, QT (maximum value/12 leads), QTc (Bazett's formula), QT dispersion (QTmax-QTmin over 12 leads) and QTc dispersion, were calculated at baseline and on the third day of treatment (4 hours after dosing), when patients underwent EPS to test the effects of study drugs on VT inducibility. RESULTS: At EPS 21 patients were responders to dofetilide and 22 to sotalol. On day 3, a significant increase in QT and QTc and decrease in QT and QTc dispersion, compared to baseline, was measured in responders and nonresponders, with both dofetilide and sotalol. No significant difference in QTc or QT dispersion between responders and nonresponders was observed in either treatment group. In conclusion, treatment with dofetilide and sotalol was associated with an increase in QT and QTc, and a decrease in QT and QTc dispersion. In contrast with previous reports, a differential effect on QT or QTc dispersion was not observed in drug responders versus nonresponders.

Algebraic decomposition of the TU wave morphology patterns.

In principle, the T wave results from the differences in durations of action potentials (AP) of different ventricular regions. Based on this concept, a mathematical model has been developed that represents the TU wave morphology as a summation of four AP-like functions: TU = S1 - S2 + L1 - L2. The sigmoidal shape of AP-like curves is produced by Hill's equation V(t) = a . tn/(bn + tn). Each of the decomposition functions is characterized by two parameters: the amplitude at the beginning of QRS (Amax), and the duration at 5% of Amax (D95). The set of four decomposition functions leads to eight parameters that provide detailed characteristics of the TU wave morphology. The model was validated using 170 TU wave complexes recorded digitally in leads V2-V6 from 22 normal subjects and 12 patients with abnormal TU wave morphologies (negative, biphasic, and notched T waves). The electrocardiographic signals were sampled at 100 Hz and a best-fit procedure was used to obtain the decomposition. In all cases the coefficients of correlation between original TU patterns and their mathematical models were > or = 0.99. The mean absolute difference between the observed and modeled values of the TU patterns was similar in cases with normal and abnormal TU wave morphologies (4.65 +/- 0.41 microV vs 5.19 +/- 0.48 microV respectively) demonstrating that the model is capable of describing and categorizing various TU patterns by a set of eight numerical parameters.

Reduction of ischemia-induced electrophysiologic abnormalities by glucose-insulin infusion.

OBJECTIVES: This study was designed to determine the effects of glucose-insulin infusion on ischemia-induced changes in extracellular potassium ([K+]o) accumulation and the associated electrophysiologic abnormalities in the canine heart. BACKGROUND: Although glucose-insulin-potassium infusion has been shown to limit myocardial injury in acute ischemia, its effect on ischemia-induced electrophysiologic alterations has not been investigated. METHODS: Recordings of [K+]o and local electrograms from the normal, border and ischemic zones were obtained during serial (10-min) left anterior descending coronary artery occlusions in the control state and after infusion of glucose-insulin (eight dogs), glucose alone (six dogs) or insulin alone (eight dogs). RESULTS: Glucose-insulin infusion caused significant reduction in the rise of [K+]o during the entire period of ischemia in both ischemic and border zones associated with significant improvement in the degree of intramyocardial conduction delay. At 10 min of ischemia, [K+]o was reduced from a mean control level of 15.9 +/- 3.7 to 10.1 +/- 4.3 mmol/liter (p < 0.005) in the ischemic zone and from 6.8 +/- 1.9 to 5.5 +/- 1.1 mmol/liter (p < 0.05) in the border zone. The electrogram duration was shortened from a mean control value of 102 +/- 13 to 78 +/- 12 ms in the ischemic zone and from 79.2 +/- 7.8 to 58.1 +/- 6.6 ms in the border zone (p < 0.005). Glucose alone caused significant reduction in [K+]o during the initial 6 min of ischemia, only in the ischemic zone. Conversely, insulin caused no changes in [K+]o accumulation during ischemia. Neither glucose nor insulin alone had any effect on ischemia-induced intramyocardial conduction delay. CONCLUSIONS: The present study demonstrated that the combination of glucose and insulin is essential for the salutary effect of reducing [K+]o accumulation during ischemia and improving the associated intramyocardial conduction delay. It could be postulated that glucose in the presence of insulin increases the glycolytic flux, thereby providing adequate adenosine triphosphate for suppressing the cardiac adenosine triphosphate-sensitive potassium ion channels. The latter are, at least partially, responsible for the [K+]o rise in the early phase of ischemia. This study highlights the antiarrhythmic potential of interventions that modulate the metabolic consequences of ischemia.

Three decades of antiarrhythmic therapy.

Over the last several decades there has been an impressive expansion in the study and management of cardiac arrhythmias. New developments in diagnostic and interventional clinical electrophysiology as well as research at the cellular tissue and whole heart levels have improved our understanding of the mechanisms of arrhythmias and have allowed the development of new and effective treatment modalities. During the 1960s (Early Decade-Enabling) the first lifesaving measures such as cardiac resuscitation, external defibrillation, and temporary pacing were introduced in the new coronary care units. Cardiac catheterization and reproducible techniques for recording of intracardiac potentials were developed. The decade of 1970 to 1980 (Middle Decade-Diagnosis) was characterized by the development of programmed stimulation for initiation and termination of arrhythmias. This represented a real revolution in clinical cardiology that led to the understanding of the nature of several tachyarrhythmias and related them to experimental mechanisms of arrhythmogenesis. In the same decade, two other diagnostic tools emerged for assessing cardiac arrhythmias and monitoring the efficacy of antiarrhythmic drug therapy: ambulatory ECG monitoring and exercise testing. In addition, the impact of antiarrhythmic drugs on ionic currents was studied and drug classifications based on these properties appeared. The decade 1980-1990 (Recent Decade-Therapy), witnessed the development of interventional electrophysiology techniques such as transcatheter ablation, and the use of cardiac surgery for the ablation of arrhythmogenic substrates. Another major advance was the design of implantable devices capable of recognizing tachyarrhythmias and treating them by programmed stimulation or defibrillation shocks. In parallel, the efficacy and safety of antiarrhythmic drugs has been reassessed and new compounds are being developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic effects on reentrant ventricular rhythms in subacute myocardial infarction.

BACKGROUND: Reentry has been shown to be a mechanism of ventricular arrhythmias elicited by programmed premature stimulation in the subacute ischemic period of dogs subjected to myocardial infarction. The spatial distribution of refractoriness in these hearts has been shown to play an important part in the formation of functional arcs of conduction block during programmed ventricular stimulation. Because the adrenergic nervous system influences cardiac arrhythmias and myocardial infarction can directly affect sympathetic innervation in the heart, we investigated the role of the sympathetic nervous system on reentry in the canine heart 4 days after infarction. METHODS AND RESULTS: The influences of adrenergic stimuli on the initiation of reentrant ventricular excitation were studied using a 128-channel computerized recording system in the canine heart 4 days after ligation of the left anterior descending coronary artery. Bilateral stimulation of the ansae subclavia preferentially improved conduction of premature beats in the normal zones. This corresponded to an improvement in excitability, as measured by a decrease in stimulus strength at the same premature coupling interval as control. Consequently, the effective refractory period was preferentially shortened at normal sites but not at ischemic sites. Both of these changes contributed to a shift of the arc of functional conduction block toward more normal tissue. As a result, sites proximal to the arc of functional conduction block had more time to recover excitability and thereby were available to be reexcited by the distal activation wave front. Conversely, intravenous infusion of norepinephrine preferentially shortened the effective refractory period of sites in the ischemic zone, thereby indicating that denervation hypersensitivity had occurred at these sites. The spatial dispersion of refractoriness and the arc of functional conduction block were significantly reduced in size. As a consequence, previously inducible reentrant rhythms were no longer inducible. CONCLUSIONS: Sympathetic stimulation can be considered an arrhythmogenic intervention, whereas norepinephrine infusion may be considered antiarrhythmic in this experimental model.

Dofetilide, a novel class III antiarrhythmic agent.

Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent.

The electrophysiological effects of flosequinan.

We have evaluated the acute electrophysiological effects of flosequinan in 18 patients with normal ventricular function. Following intravenous infusion of flosequinan 100 mg over 1 h, mean (SD) systolic blood pressure fell from 131 +/- 19 to 120 +/- 22 mmHg (P less than 0.02) and there was significant shortening of sinus cycle length (732 +/- 151 to 575 +/- 93 ms, P less than 0.001), AH interval (110 +/- 45 to 71 +/- 19 ms, P less than 0.01), QRS duration (98 +/- 28 to 91 +/- 26 ms, P less than 0.02) and QT interval (373 +/- 47 to 337 +/- 35 ms, P less than 0.001), but no change in sinus node recovery time, intra-atrial conduction time, HV interval or the corrected QTc interval. There was a reduction in both anterograde atrioventricular Wenckebach cycle length (299 +/- 53 to 259 +/- 52 ms, P less than 0.01) and retrograde ventriculoatrial Wenckebach cycle length (375 +/- 77 to 300 +/- 56 ms, P less than 0.01). There was no change in atrial or ventricular effective refractory period (ERP) but atrial functional refractory period (FRP) shortened (233 +/- 31 to 212 +/- 24 ms, P = 0.07) as did ventricular FRP (249 +/- 24 to 234 +/- 21 ms, P less than 0.01). Patients received an oral dose of flosequinan 50 mg 12 h later. By 24 h, sinus cycle length, QRS duration and the QT interval had all returned towards baseline values, but ventricular ERP had lengthened (199 +/- 22 to 215 +/- 26 ms, P less than 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of postural changes versus exercise on the electrophysiologic parameters of the accessory pathway.

The electrophysiologic profile of the accessory pathway was studied in 17 patients (mean age +/- standard deviation 32 +/- 14 years) with Wolff-Parkinson-White (WPW) syndrome who were either lying down in a supine position, standing, or undergoing isometric or dynamic treadmill exercise. There were significant decreases in the PP interval after isometric exercise, standing and dynamic exercise (supine 764 +/- 224, standing 638 +/- 146, isometric 605 +/- 170, treadmill 455 +/- 86 ms; p less than 0.05). Both anterograde and retrograde accessory pathway refractory periods were measured after a constant drive of 400 ms during lying down supine, standing and isometric and treadmill exercise (Bruce protocol stage II). There was no significant decrease in the anterograde accessory pathway refractory period during isometric exercise (lying down 265 +/- 22 to isometric exercise 256 +/- 13 ms, p less than 0.05), but there were significant decreases (p less than 0.05) during standing (246 +/- 24 ms) and treadmill exercise (235 +/- 17 ms). The retrograde accessory pathway refractory period also showed a significant decrease (supine 272 +/- 16, isometric 267 +/- 23, standing 249 +/- 15, treadmill 237 +/- 17 ms; p less than 0.05). The relative change in refractory periods was greater when patients changed from lying down to standing than when they changed from standing to treadmill exercise, despite obvious higher adrenergic neuronal activities during exercise. These findings suggest that testing the accessory pathway during free standing can give a reliable indication of the sensitivity of the accessory pathway to sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Myopotential interference in unipolar rate responsive pacemakers.

The effects of myopotential interference on unipolar rate responsive pacemakers were assessed in 22 patients. Six types of pacemakers (from four manufacturers) were studied: five TX2 (QT sensing), seven Biorate (five RDP3 and two MB-1, respiratory rate sensing), seven Activitrax (activity sensing), two Medtronic 2503 (dP/dt sensing), and one Sensolog P703 (activity sensing). Provocative tests using arm exercises were performed in both VVI and rate responsive modes. At nominal sensitivity settings (1.8-2.5 mV), 55% of these patients were myopotential positive for at least 1 provocative test. Pressing the palms together was found to be the most sensitive provocative test. Rate response was achieved with treadmill exercise (all patients), hyperventilation (RDP3 and MB-1) and tapping (Activitrax) or wobbling the pacemaker in its pocket (Sensolog). During continued rate acceleration, myopotential interference was induced by arm exercises. The duration of inhibition was shorter when the provocative tests were performed during rate response compared to that occurred at rest. Short periods of myopotential interference resulted in temporary inhibition of pacing but rate response continued immediately on removal of the interference. In one patient with a RDP3 pacemaker, a prolonged episode of myopotential interference during treadmill exercise resulted in reversion of the pacemaker to the interference mode. Appropriate adjustment of the sensitivity setting effectively controlled the symptoms in most patients. However, one patient with a QT sensing pacemaker and symptomatic myopotential interference required programming to the VVT pacing mode. Two out of five patients with RDP3 required pacemaker replacement because of uncontrolled myopotential interference.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of exercise performance of six rate-adaptive right ventricular cardiac pacemakers.

Single chamber cardiac pacemakers capable of automatically adjusting the rate according to body requirements have become an important means of physiologic pacing in patients with bradycardias. Such pacemakers are dependent on a nonatrial sensor of physiologic needs to optimize the rate response. Fifty rate-adaptive right ventricular pacemakers were implanted in 46 patients with a mean age of 60 +/- 4 years (mean +/- standard error of the mean). There were 2 types of activity-sensing pacemakers (Activitrax and Sensolog 702), the QT-sensing pacemakers (TX2 and Quintech), 2 types of respiratory-sensing pacemakers (Biorate [RDP3 and MB1] and Meta) and a rate-adaptive pacemaker that senses right ventricular dP/dt (Deltatrax). The rate responses of a group of 9 volunteers of similar age (62 +/- 2 years) were also included for comparison. Improvement in exercise duration in the rate-adaptive mode compared to the constant-rate ventricular pacing (VVI) mode was achieved during randomized symptom-limited treadmill exercise (from 26 to 49%). Compared with the sinus responses, the activity-sensing pacemakers responded most appropriately in speed. However, their rate responses were not related to workload and had lower correlations with estimated oxygen consumption (r = 0.7 and 0.47 for Activitrax and Sensolog, respectively). Respiratory-sensing pacemakers responded more appropriately in magnitude (r greater than 0.8) although their rate responses were slower. All pacemakers studied either showed no response or a reverse-rate response to the Valsalva maneuver. It is concluded that the currently available rate-adaptive ventricular pacemakers improve exercise performance compared with VVI pacemakers in patients with bradycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of 50 Hz external electrical interference on implanted cardiac pacemakers.

The effects of injected 50 Hz alternating current on the function of cardiac pacemakers has been observed in 18 patients with implanted unipolar VVI units. Current, in the range 0-600 microA was applied via electrodes attached to the patients' upper body and feet and fed from a specially designed current injection unit at the bedside. Most implanted pacemakers reverted to interference mode in the current range 29-250 microA. At current levels just below the reversion current all units developed irregular and inappropriate pacing. This current level was pacemaker dependent and varied in the range 27-246 microA. The total reversion current depended on the location of the injecting electrodes and on the patients' posture. The sensitivity of the units to injected interference was increased by deep inspiration. Temporary pacing catheters fitted to an additional ten patients were used to monitor the interference voltage which would be sensed by an implanted unit. This voltage was similarly dependent on patient posture and on deep respiration. Current injection has proved to be a safe, controllable and reproducible method of testing the sensitivity of implanted pacemakers to 50 Hz external interference.

Rate modulation by arm movements of the respiratory dependent rate responsive pacemaker.

The rate response to arm movements of the respiratory dependent rate responsive pacemaker (RDP3, Biotec) was assessed in four patients implanted with this pacemaker. The pacemaker was implanted in the left prepectoral region and the auxiliary impedance measuring electrode positioned subcutaneously over the right second intercostal space with its tip lateral to the mid-clavicular line. The lower rate of the pacemaker was programmed to 75 bpm. While holding the breath, swinging arm movements (30 times) resulted in rate acceleration. The peak rate was faster when the arm on the side of the auxiliary electrode was swung (mean +/- SEM, 117 +/- 8 compared to 130 +/- 5 bpm, P less than 0.5). The mean rate response of the subjects to brief treadmill exercise (Bruce stage I) performed with both hands holding the support rails, swinging the right arm only, swinging left arm only and swinging both arms were 108, 140, 135 and 128 bpm respectively. Impedance measurement confirmed the significant influence of arm movements on thoracic "impedance" changes, which was mainly caused by electrode motion artifacts affecting the two electrode measuring system. This effect was dependent on the relative positions of the impedance measuring electrodes (i.e., between the pacemaker casing the auxiliary lead). Subsequently the auxiliary lead of the respiratory pacemaker (MB-1, and Biorate) was implanted in the lower part of the chest on the right sternal edge in another patient. Rate acceleration was only observed when the arm on the side of the pacemaker was swung. As arm movements often accompany physical activities, pacing rate can be affected and should be considered when programming this pacemaker.

Clinical cardiac electrophysiologic evaluation of the positive inotropic agent, DPI 201-106.

DPI201-106 is a new positive inotropic agent. The cardiac electrophysiology of 16 patients was studied before and during DPI 201-106 administration (loading dose of intravenous DPI 201-106, 1.8 mg kg-1 h-1 administered over 10 min, followed by a maintenance dose of 0.2 mg kg-1 h-1). DPI 201-106 had no effect on the sinus node. The AH interval during fixed-rate atrial pacing became prolonged during DPI 201-106 infusion. There was a significant prolongation of the QT interval [QT (corrected), 417 +/- 22 to 502 +/- 35 ms, P less than 0.05; QT (atrial pacing at 600 ms), 374 +/- 17 to 419 +/- 23 ms, P less than 0.05; QT (ventricular pacing at 600 ms), 409 +/- 37 to 449 +/- 30 ms, P less than 0.05]. The ventricular effective refractory period significantly prolonged during DPI 201-106 administration (242 +/- 21 to 287 +/- 56 ms, P less than 0.05), but the supernormal-period duration decreased. The atrial effective refractory period was shortened in four patients and prolonged in one (261 +/- 67 to 240 +/- 53 ms, NS). The corrected atrial repolarization time (PTac) shortened significantly during DPI 210-106 infusion (479 +/- 26 to 445 +/- 22 ms at 20 min of the maintenance dose, P less than 0.05). Atrial fibrillation was initiated in five patients during DPI infusion, but no ventricular arrhythmia was provoked. These findings suggest that DPI 201-106 has novel differential electrophysiological effects on atria and ventricles.

Pacing techniques in the prophylaxis of junctional reentry tachycardia.

Atrial premature beats (APBs) which encounter sufficient AV delay may initiate junctional reentry tachycardia (JRT). This form of initiation may be prevented by rendering part of the reentry circuit refractory by artificial stimulation following an APB which would otherwise initiate JRT. Two such approaches have been suggested: preexcitation pacing, that is, ventricular stimulation with a short AV delay triggered by atrial depolarization; and preemptive pacing, which consists of early atrial stimulation coupled to the initiating APB. We compared these approaches and describe them as follows. Ten patients with JRT (six with atrioventricular reentry and four with AV nodal reentry) were studied. Against a background of regular atrial drive, the range of coupling intervals over which a stimulated APB initiated JRT (tachycardia initiation window) was determined (control). The tachycardia initiation window was also measured when a second atrial stimulus followed the initiating APB 20 ms after atrial recovery (preemptive pacing) or when a ventricular stimulus closely followed the initiating APB with an AV delay of 65 ms (preexcitation pacing). The tachycardia initiation window in response to an isolated APB was also assessed following regular AV pacing with a short (65 ms) AV delay (preconditioning pacing) and the effect of preexcitation pacing following the initiating APB was also assessed after a similar drive (combined preconditioning and preexcitation pacing). All protocols were performed at two basic drive cycle lengths. The results are arranged for the slow and fast drives, respectively, and were as follows: control initiating windows--49.5, 28.5 ms; preemptive pacing initiation windows--151, 38 ms; preexcitation pacing initiation windows--26, 23.5 ms; preconditioning pacing initiation windows--45.5, 35 ms; combined preconditioning and preexcitation pacing initiation windows--10.0, 2.5 ms. Whereas preemptive pacing tended to widen the tachycardia initiation windows (a proarrhythmic effect) the combination of preconditioning and preexcitation pacing considerably reduced the possibility of JRT initiation by an atrial premature beat.

Rapid autonomic tone regulation of atrioventricular nodal conduction in man.

The changes in P-P intervals and atrioventricular nodal (AVN) conduction during the Valsalva maneuver were studied in 17 patients. In spite of a significant decrease in the sinus P-P interval during phase II of the maneuver (733 +/- 143 to 520 +/- 86 msec, p less than 0.005) and prolongation during phase IV (884 +/- 171 msec, p less than 0.01), there was no change in the AH interval (control: 78 +/- 15: phase II: 76 +/- 15: phase IV: 72 +/- 14 msec, N.S.). In six patients consecutive P-P intervals during phase II were recorded in solid-state memory and were used to trigger pacing of the high right atrium at rest. This showed a significant increase in the AH interval (75 +/- 10 to 123 +/- 45 msec, p less than 0.05). Valsalva maneuver during constant rate atrial pacing resulted in a significant decrease in the AH interval during phase II (115 +/- 36 to 80 +/- 15 msec, p less than 0.001). During phase IV there was prolongation of the AH interval (156 +/- 58 msec) but in 11 patients (61%) a variable degree of Wenckebach periodicity appeared. Thus autonomic tone modulates the changes in AVN conduction induced during physiologic heart rate variation, resulting in maintenance of adequate 1:1 AVN conduction.