Origin of tonic electrical activity patterns in the diaphragm of the fetal lamb

The respiratory pattern generator in fetal and postnatal life activates the phrenic nucleus and diaphragm muscle with phasic bursts of activity. In the fetus, diaphragmatic activity is also characterized by tonic activity patterns of unknown origin. We have examined whether such activity is diaphragmatic, or radiated from nearby ribcage muscles, by placing two sets of electrodes side-by-side in the costal portion of the diaphragm in five fetuses. The rationale for this approach is that if tonic activity, radiates to the diaphragm it should be recorded by both sets of electrodes and there should be no delay between the action potentials from each set of electrodes. Of 24 single tonic units identified, 15 were recorded from only one of the two sets of electrodes in the diaphragm. In the 9 tonic units recorded from both sets of electrodes, there was a time delay between the appearance of the action potentials in the two recordings (mean +/- S.E.M. 1.6 +/- 0.2 ms). This is the expected conduction delay along the muscle fibres separating the two electrodes. Since tonic diaphragmatic activity persisted in fetuses with the spinal cord transected rostral or caudal to the phrenic nucleus, we conclude that the spinal cord alone is sufficient to produce the tonic activity recorded from the fetal diaphragm but that the brain may also generate such activity.     

Influence of lung volume and electrode position on electromyography of the diaphragm

In cats anesthetized with Nembutal, electromyograms of the diaphragm (Edi) were recorded from an anchored esophageal electrode, a pair of silver hooks inserted in the paratendinous region, and a pair of silver hooks and a pair of clips of small surface inserted in the costal region of the diaphragm facing the rib cage at FRC but covered with lung tissue at FRC + 80 ml. When single supramaximal electrical stimuli were applied to an isolated phrenic nerve, changes in lung volume from RV to near TLC had a negligible effect on muscle potentials from esophageal or paratendinous hooks, but increased the amplitude of potentials recorded from peripheral hooks and clips. In addition, it was found that small displacements of the esophageal electrode caused substantial changes in the amplitude of the recorded muscle potentials. The integration of the Edi spontaneously generated during occluded inspirations, recorded from paratendinous hooks and the esophageal electrode was linearly related to transdiaphragmatic pressure up to 50 cmH2O at all lung volumes. Above that level, esophageal electrode recordings showed a curvilinear Edi/Pdi relationship, while hook recordings showed a rectilinear relationship.     

Diaphragm activation with intramuscular stimulation in dogs

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.     

A fractally coated, 1.3 mm2 high impedance pacing electrode

Minimizing the geometric surface area of pacing electrodes increases impedance and reduces the current drain during stimulation, provided that voltage (pulse-width) thresholds remain unchanged. This may be feasible by coating the electrode surface to increase the capacity of the electrode tissue interface and to diminish polarization. Ten unipolar, tined leads with a surface area of 1.3 mm2 and a "fractal" coating of iridium (Biotronik SD-V137) were implanted in the ventricle, and electrogram amplitude (unfiltered), slew-rate, pacing threshold (0.5 ms), and impedance (2.5 V; 0.5 ms) were measured by the 5311 PSA (Medtronic). On days 0. 2. 5. 10, 28, 90, 180, 360 postimplant, sensing threshold (up to 7.0 mV, measuring range 1-14 mV on day 360 only) and the strength duration curve (0.5-4.0 V; 0.03-1.5 ms; steps: 0.5 V; 0.01 ms, respectively) were determined, the minimum charge delivered per pulse (charge threshold), and the impedance were taken from pacemaker telemetry (Intermedics 294-03). Data were compared with those of an earlier series of 20 unipolar, tined TIR-leads (Biotronik) with a surface area of 10 mm2 and a @actal" coating of titanium nitride. With the model SD-V137 versus TIR, intraoperative electrogram amplitudes were 15.1 +/- 6.1 versus 14.4 +/- 3.9 mV (NS), slew rates 3.45 +/- 1.57 versus 1.94 +/- 1.06 V/s (P < 0.05), pacing thresholds 0.16 +/- 0.05 versus 0.52 +/- 0.15 V (P < 0.01) and impedance measurements 1,136 +/- 175 versus 441 +/- 73 omega (P < 0.0001), respectively. During follow-up, sensing thresholds were the same with both leads. Differences in pulse width thresholds lost its significance on day 28 but resumed on day 360 (SD-V137; 0.08 +/- 0.04 ms; TIR: 0.16 +/- 0.06 ms at 2.5 V; P < 0.01). With an electrode surface of 1.3 mm2, charge per pulse and impedance consistently differed from control, being 0.15 +/- versus 0.66 +/- 0.20 microC (P < 0.001) and 1,344 +/- 376 versus 538 +/- 79 omega respectively, one year after implantation (P < 0.0001). In summary, "fractally" coated small surface electrodes do not compromise sensing; by more than doubling impedance against controls they offer pacing thresholds (mainly in terms of charge) that are significantly lower than with the reference electrode.     

Medullary respiratory neuronal activity modulated by stimulation of the fastigial nucleus of the cerebellum

The ability of the rostral fastigial nucleus (FNr) of the cerebellum to modulate medullary respiratory neuronal activity was examined in 17 anesthetized, paralyzed and ventilated cats. A bipolar stimulating electrode was positioned into the FNr and tungsten microelectrodes used to record units within the nucleus tractus solitarius (NTS), nucleus ambiguus (NA) and nucleus retroambigualis (NRA). Transient stimuli (< 150 microA, 5-200 Hz) were delivered during inspiration or expiration, and the effects noted on medullary neuronal activity and the phrenic neurogram. The results showed that FNr stimulation: (1) modulated inspiratory and expiratory neuronal (ramp-, early- and late-inspiratory and stage I and II expiratory) discharges recorded from the NTS, NA and NRA (n = 67, 14 and 28) when stimuli (> or = 20-50 Hz) were delivered during either the inspiratory or expiratory phases; (2) terminated the burst durations of inspiratory (77%) and expiratory (94%) neurons with stimulus-response latencies of 28.2 +/- 3.1 ms (inspiratory) and 29.4 +/- 3.6 ms (expiratory); (3) elicited changes in phrenic neurogram concomitant with the effects noted on medullary neuronal activities; (4) failed to change heart rate and arterial blood pressure; and (5) did not affect medullary neuronal and phrenic nerve activity following kainic acid injection into the FNr. We conclude that activation of the FNr (likely its cell bodies) can modulate the respiratory output via influences on medullary respiratory-related neurons. The primary cerebellar effect across all sub-types of respiratory neurons was early termination.     

Putative projection of phrenic afferents to the limbic cortex in humans studied with cerebral-evoked potentials

Respiratory sensations may rely in part on cortical integration of respiratory afferent information. In an attempt to study such projections, we recorded evoked potentials at scalp and cervical sites in 10 normal volunteers undergoing transcutaneous phrenic stimulation (0.1-ms square pulses, intensity liminal for diaphragmatic activation, series of 600 shocks at 2 Hz). A negative cerebral component of peak latency (12.79 +/- 0.54 ms; N13) was constant, and a negative spinal component (7.09 +/- 1.04 ms; N7) could also be recorded, all results being reproducible over time. Monitoring of cardiac frequency, skin anesthesia, and stimulation adjacent to the phrenic nerve made the phrenic origin of N7 and N13 the foremost hypothesis. Increasing stimulation frequency and comparison with median nerve stimulation provided arguments for the neural nature of the signals and their cerebral origin. Recordings from intracerebral electrodes in a patient showed a polarity reversal of the evoked potentials at the level of the cingulate gyrus. In conclusion, phrenic stimulation could allow one to study projections of phrenic afferents to the central nervous system in humans. Their exact site and physiological meaning remain to be clarified.     

Effects of lung volume and fatigue on evoked diaphragmatic phonomyogram in normal subjects

BACKGROUND: A diaphragmatic phonomyogram (PMG) evoked by maximal phrenic nerve stimulation at end expiratory lung volume (FRC) has been previously described as a good index of changes in diaphragmatic contractility with fatigue. A study was undertaken to assess whether this conclusion could be extended to different lung volumes. METHODS: Diaphragmatic compound motor action potentials (CMAPs) were recorded on each side of the chest by the means of surface electrodes placed over the eight intercostal spaces in five healthy subjects. Diaphragmatic PMGs from both sides were recorded with condenser microphones fixed to the skin close to the CMAP recording electrodes. Oesophageal and gastric balloon tipped catheters were employed to measure transdiaphragmatic pressure twitches (TwPDI) which served as the standard measure of changes in diaphragmatic contractility. PMG and TwPDI responses were compared at different lung volumes over inspiratory capacity both before and after fatiguing inspiratory resistive loading. RESULTS: No consistent relationship was found in different subjects or on different days in the same subject between PMG and lung volume or between PMG and TwPDI. However, the PMG:CMAP ratio from both sides at any given lung volume decreased after fatigue in roughly the same proportion as the TwPDI. CONCLUSIONS: These results show that, although PMG can detect changes in diaphragmatic contractility caused by fatigue in normal subjects, lung volume changes need to be controlled and each subject should serve as his or her own control.     

Enhancement of signal quality in esophageal recordings of diaphragm EMG

The crural diaphragm electromyogram (EMGdi) is recorded from a sheet of muscle, the fiber direction of which is mostly perpendicular to an esophageal bipolar electrode. The region from which the action potentials are elicited, the electrically active region of the diaphragm (EAR(di)) and the center of this region (EAR(di ctr)) may vary during voluntary contractions in terms of their position with respect to an esophageal electrode. Depending on the bipolar electrode's position with respect to the EAR(di ctr), the EMGdi is filtered to different degrees. The objectives of the present study were to reduce these filtering effects on the EMGdi by developing an analysis algorithm referred to as the "double-subtraction technique." The results showed that changes in the position of the EAR(di ctr) by +/- 5 mm with respect to the electrode pairs located 10 mm caudal and 10 mm cephalad provided a systematic variation in the EMG power spectrum center-frequency values by +/- 10%. The double-subtraction technique reduced the influence of movement of the EAR(di ctr) relative to the electrode array on EMG power spectrum center frequency and root mean square values, increased the signal-to-noise ratio by 2 dB, and increased the number of EMG samples that were accepted by the signal quality indexes by 50%.     

Normal median near nerve potential

In routine studies of sensory nerve conduction, only fibers > or = 7 microns in diameter are analyzed. The late components which originate from thinner fibers are not detected. This explains why a normal sensory action potential (SAP) may be recorded in patients with peripheral neuropathies and sensory loss. In the present study we investigated the late component of the median SAP with a near nerve needle electrode technique in 14 normal volunteers (7 men and 7 women), aged 34.5 +/- 14.8 years. The stimulus consisted of rectangular pulses of 0.2-ms duration at a frequency of 1 Hz with an intensity at least 6 times greater than the threshold value for the main component. Five hundred to 2000 sweep averagings were performed. The duration of analysis was 40 or 50 ms and the wave analysis frequency was 200 (-6 dB/oct) to 3000 Hz (-12 dB/oct). We used an apparatus with a two-channel amplifier system, 200 M omega or more of entry impedance and a noise level of 0.7 microVrms or less. The main component mean amplitude, conduction velocity and latency and the late component mean amplitude, conduction velocity and latency were respectively (mean +/- SD): 26.5 +/- 5.42 microV, 56.8 +/- 5.42 m/s, 3.01 +/- 0.31 ms, 0.12 +/- 0.04 microV, 16.4 +/- 2.95 m/s and 10.6 +/- 2.48 ms. More sophisticated equipment has an internal noise of 0.6 microVrms. These data demonstrate that the technique can now be employed to study thin fiber neuropathies, like in leprosy, using commercial electromyographs, even in non-academic practices.     

Characteristics of a fast transient outward current in guinea pig trigeminal motoneurons

A fast transient voltage dependent outward current (TOC) in trigeminal motoneurons (TMNs) was studied in guinea pig brainstem slices by use of sharp electrodes in combination with single electrode voltage clamp techniques. In solutions containing TTX, low Ca2+/Mn2+ and 20 mM TEA this current activated around -55 to -60 mV from holding potentials negative to resting potential, obtained its peak amplitude within 5 ms and decayed as a single exponential with a time constant of 6-8 ms. Half maximal values for inactivation and activation were -72 and -37 mV, respectively. Bath application of 5 mM 4-AP suppressed this current by approximately 90% and eliminated the early depolarizing transient membrane rectification observed in response to a constant depolarizing current pulse, prolonged the action potential duration, and reduced the threshold voltage and delay to onset of the action potential. It is suggested that this current resembles the typical A-current observed in many CNS neurons and, as a result of its voltage and time dependent properties, could contribute to control of motoneuronal discharge and timing of burst onset during rhythmical jaw movements. Therefore, any cellular models of masticatory activity should include the properties of this current.     

Electrophysiological effects of acute dilatation in the isolated rabbit heart: cycle length-dependent effects on ventricular refractoriness and conduction velocity

BACKGROUND: Acute ventricular dilatation has important electrophysiological effects: Dilatation shortens action potential duration and refractoriness without an apparent effect on conduction velocity. These effects have been implicated as a potential mechanism of arrhythmias in patients with congestive failure. Because the influence of cycle length on these phenomena has not been studied, we examined the effects of dilatation during ventricular pacing at cycle lengths from 1000 to 150 ms. METHODS AND RESULTS: Thin epicardial layers were created in isolated, perfused rabbit left ventricles (n=7). A fluid filled latex balloon was secured in the left ventricle to dilate the left ventricle. Mapping was performed with 248 epicardial electrodes. Longitudinal conduction velocity (76+/-1 cm/s; mean+/-SEM) and transverse conduction velocity (26+/-1 cm/s) were not influenced by dilatation at any cycle length. In contrast, the effects of dilatation in decreasing left ventricular effective refractory period (ERP) were significantly greater at shorter drive cycle lengths: The decrease in ERP was 2+/-2 ms (a 1% change) at a drive cycle length of 1000 ms and 18+/-4 ms (a 20% change) at a drive cycle length of 150 ms. In 10 additional intact, isolated perfused rabbit hearts, dilatation decreased ERP to a greater degree during 250 ms drive cycle length pacing than during pacing at 400 ms (25+/-4 versus 16+/-3 ms; P=.01). CONCLUSIONS: Acute dilatation exaggerates the normal rate-dependent shortening of refractoriness but does not influence transverse or longitudinal conduction velocity. This observation suggests that the electrophysiological effects of acute dilatation may be greater during tachycardia than at slower cycle lengths. This may have implications for arrhythmias in patients with congestive heart failure.     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.     

The nucleus is the target for radiation-induced chromosomal instability

Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.     

Influence of recording site on CMAP amplitude on its variation over a length of nerve

The distinctions between blocking, abnormal temporal dispersion, and normal conduction require delineation of the normal change in amplitude of the compound muscle action potential (CMAP) over a length of nerve. Effects of the recording site on CMAP amplitude and on its variation were studied in median and ulnar nerves of 13 healthy subjects. CMAPs were recorded from three sites: halfway along the muscles and 1 cm distal and proximal. Elbow-wrist amplitude percentages (CMAP%) were calculated. CMAP amplitudes varied considerably between sites and subjects. Amplitudes were maximal at the middle site in only 16 of 26 nerves. The site of maximal amplitude could not be identified on the basis of thumb anatomy. CMAP% was not related to CMAP amplitude, and differed by up to 32% between adjacent sites. CMAP formation involves spatial factors (electrode site, limb position, and limb anatomy), temporal factors (dispersion), and their interaction, explaining why CMAP% can exceed 100%. The site of the recording electrode affects CMAP amplitude and CMAP% to clinically relevant degrees. Standardization of the recording site may improve reliability of CMAP% studies.     

Calcium current and inactivation in identified neurons in Hermissenda crassicornis

1. N-type (omega-conotoxin sensitive) calcium currents (ICa) were recorded in identified neurons in Hermissenda crassicornis using low-resistance patch electrodes (0.7 +/- 0.3 M omega; n = 101) under conditions that eliminated inward Na+ currents (choline ions substitution) and suppressed outward K+ currents (Cs+, tetraethylammonium, and 4-AP). Step depolarization from a holding potential of -60 mV to potentials above -30 mV elicited ICa, which peaked approximately 20 mV and declined with increasing depolarizations. 2. Evidence for a low-threshold current was present. Step depolarization from a more hyperpolarizing potentials (e.g., -90 mV) revealed a small shoulder (< 100 pA) at -60 to -40 mV that was sensitive to Co2+ and Ni2+. However, under the conditions examined here (holding potential of -60 mV), the high-voltage-activated current predominated. 3. Barium (Ba2+) and strontium (Sr2+) permeate the Ca2+ channel with similar activation kinetics (ease of permeation; Ba2+ > Ca2+ > Sr2+). Steady-state activation of permeability versus membrane potentials for Ca2+, Ba2+, and Sr2+ as charge carriers could be fitted with the Boltzmann equation, with half-activation voltage and slope factor of 2.9 and 7.7 mV for ICa, -13.1 mV and 7.8 for Ba2+ current (IBa) and -2.3 mV and 7.8 for Sr2+ current (ISr). The time course of activation was monotonic with time constant (tau) for ICa ranging from 2 to 8 ms. 4. The inactivation profile was complex. At negative step potentials (e.g., -20 mV), inactivation of the current was slow. Depolarization steps to relatively positive voltages (e.g., 10 mV) showed more rapid inactivation than those at more positive potentials (e.g., 40 mV). When extracellular Ca2+ was raised from 5 to 10 mM, a biphasic decay (tau fast of 25 +/- 4 ms; and tau slow of 473 +/- 64 ms; mean +/- SD, n = 9) was seen. Such an observation suggested a current-mediated inactivation. 5. With a pulse duration of approximately 350 ms, ISr showed inactivation whereas Ba2+ virtually removed the decay. However, IBa turned off with more prolonged depolarization. 6. A twin-pulse protocol was used to assess the voltage dependence of inactivation: an incomplete U-shaped inactivation curve was observed for ICa, IBa, and ISr. Channels available for inactivation were increased in the presence of Ca2+ ions. 7. Inactivation was further studied with the Ca2+ chelators, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and bis(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). With 10 mM of BAPTA, in the pipette, inactivation was reduced but not removed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polymorphic ventricular tachycardias induced by D-sotalol and phenylephrine in canine preparations of atrioventricular block: initiation in the conduction system followed by spatially unstable re-entry

OBJECTIVE: Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction system; and (2) the inhomogeneous prolongation of repolarisation intervals can provide refractory barriers for re-entrant activity. METHODS: Unipolar electrograms were recorded from 127 epicardial (EPI) sites with a sock electrode array as well as from intramural and endocardial sites during PVTs. Electrograms were analysed to generate isochronal maps and measure the spatial distribution of activation-recovery intervals (ARI). RESULTS: Under S (9.9-14.5 mg.l-1), spontaneously terminating PVTs (cycle length of 270 +/- 43 ms, n = 45) (mean +/- s.d.) occurred when a PE bolus (10-50 micrograms.kg-1) was injected. The first beat of the PVTs occurred with a coupling interval of several hundred ms to the preceding idioventricular beat (IDV) without any bridging activity and its earliest EPI breakthrough occurred in areas overlying the terminations of the right or left bundle branch. ARI values measured in IDV (295 +/- 47 ms) were significantly prolonged prior to PVT (462 +/- 92 ms). Prolongation was greater in apical than in basal epicardial areas, and at endocardial than epicardial sites (to > 500 ms). Maximum delays > 200 ms developed in the regions of marked ARI prolongation and, in later beats, circus movement re-entry occurred around refractory barriers, shifting between various regions of the ventricles. CONCLUSION: Thus, PVTs occurring spontaneously under conditions of delayed repolarisation originate from shifting sites in the ventricular conduction system and re-entrant activity shifting between various regions of the ventricle may occur in later beats of the more sustained arrhythmias.     

Atrial conduction abnormalities in patients with systemic progressive sclerosis

BACKGROUND: Atrial abnormalities in patients with progressive systemic sclerosis have not been evaluated in terms of intra-atrial conduction. We hypothesized that a delay in atrial conduction in these patients might produce diastolic abnormalities as well as atrial arrhythmias. OBJECTIVE: To evaluate the atrial function of patients with progressive systemic sclerosis by using echocardiography to measure the intra-atrial electromechanical activation coupling interval. METHODS: Twenty patients with progressive systemic sclerosis were assessed by Doppler echocardiography. Twenty age-matched healthy controls were also evaluated. Two-dimensional guided M-modes of ventricular long axes were recorded using simultaneous phono- and electrocardiograms of the apical four chamber view at the right lateral, septal and left lateral sites of the atrioventricular rings. Transmitral and tricuspid pulsed Doppler flow velocities were also recorded. Filtered P wave duration was measured on the signal averaged ECG to determine the duration of atrial electrical activation. RESULTS: There was a delay in P on the electrocardiogram (P) at the onset of atrial contraction on long axis M-modes at all three atrioventricular ring sites in patients with progressive systemic sclerosis as compared with controls (P-right; 56 +/- 13 vs 47 +/- 10 ms, P-septal; 74 +/- 14 vs 55 +/- 10 ms, and P-lateral; 93 +/- 16 vs 72 +/- 11 ms, P < 0.01). Inter-atrial conduction time [(P-lateral)-(P-right)] was delayed in patients with progressive systemic sclerosis, compared with healthy controls (37 +/- 15 vs 25 +/- 6 ms, P < 0.01). Mitral A waves acceleration and deceleration times were also decreased in the patients. The interval was prolonged between P to the onset and the peak of the A wave in transmitral flow. Duration of the filtered P wave was significantly prolonged in progressive systemic sclerosis as compared with controls (124 +/- 12 ms vs 106 +/- 8 ms, P < 0.01). PQ intervals, E waves and acceleration and deceleration times did not differ significantly in progressive systemic sclerosis vs, controls. The A wave acceleration rate on transmitral flow (peak A wave velocity/acceleration time) showed a significant correlation with inter-atrial conduction delay (r = 0.55, P < 0.01). CONCLUSIONS: Intra-atrial electromechanical coupling intervals were delayed in patients with progressive systemic sclerosis. Thus, the mechanical late diastolic filling time due to atrial contraction in the total diastolic phase was severely limited, and this resulted in a restricted mitral A wave. We should therefore evaluate patients with progressive systemic sclerosis for significant atrial abnormalities.     

Effects of left atrial dilatation on the endocardial atrial defibrillation threshold: a study in an ovine model of pacing induced dilated cardiomyopathy

Left atrial (LA) dilation is a common finding in patients with chronic atrial fibrillation (AF). Progressive dilatation may alter the atrial defibrillation threshold (ADFT). In our study, epicardial electrodes were implanted on the LA free wall and right ventricular apex of eight adult sheep. Large surface area, coiled endocardial electrodes were positioned in the coronary sinus and right atrium (RA). LA dilatation was induced by rapid ventricular pacing (190 beats/min) for 6 weeks and echocardiographically assessed weekly along with the ADFT (under propofol anesthesia). LA effective refractory period (ERP) was measured every 2-3 days using a standard extra stimulus technique and 400 ms drive. The AF cycle length (AFCL) was assessed from LA electrograms. During the 6 weeks of pacing the mean LA area increased from 6.1 +/- 1.5 to 21.3 +/- 2.4 cm2. There were no significant changes in the mean ADFT (122 +/- 15 V), circuit impedance (46 +/- 5 omega), or LA AFCL (136 +/- 23 ms). There was a significant increase in the mean LA ERP (106 +/- 10 ms at day 0, and 120 +/- 13 ms at day 42 of pacing). In this study, using chronically implanted defibrillation leads, the minimal energy requirements for successful AF were not significantly altered by ongoing left atrial dilatation. This finding is a further endorsement of the efficiency of the coronary sinus/RA shock vector. Furthermore, the apparent stability of the AF present may be a further indication of a link between the type of AF and the ADFT.     

Influence of acute lung volume change on contractile properties of human diaphragm

The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity. The reduction in T2 Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% of vital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responses elicited by low-frequency stimulations; this effect is distinct from and additional to the known length-tension relationship.