Incremental programming of atrial anti-tachycardia pacing therapies in bradycardia-indicated patients: effects on therapy efficacy and atrial tachyarrhythmia burden.

AIMS: Efficacy of pace-termination of atrial arrhythmias (ATP) may depend on atrial cycle length and regularity. Whether device programming of ATP therapies can improve ATP efficacy and alter atrial tachyarrhythmia burden is unknown. METHODS AND RESULTS: ATP efficacy was evaluated in 61 patients (39 males; 66 +/- 10 years) with a standard indication for pacing, 95% with a history of AT/AF. Each patient was implanted with a novel DDDRP pacemaker capable of delivering ATP therapy. ATP efficacy and AT/AF frequency and burden were compared within each patient during a period of nominal ATP programming (NP) followed by a period of aggressive incremental programming (IP). Adjusted ATP-termination efficacy was higher during IP than during NP (54.8% vs 37.9%, P < 0.05). No differences in AT/AF frequency (3.3 +/- 5.9 vs 3.2 +/- 6.9 day(-1)) or burden (18 +/- 28% vs 18 +/- 29%) were observed comparing NP with IP. The majority of episodes during both the NP (81%) and IP (77%) periods terminated within 10 min. Episodes lasting 24 h or more accounted for only 0.4% of the episodes in both groups. but accounted for 38% of the average burden during NP and 51% during IP. CONCLUSIONS: Device programming of ATP therapies can influence the number of treated episodes and the efficacy of ATP therapies although arrhythmic frequency and burden may not change. Total atrial arrhythmia burden is disproportionately influenced by long (>24 h) episodes.

Outcome of percutaneous coronary angioplasty (PTCA) performed in a low-volume institution by low-volume operators, evaluated by means of the one-month major adverse cardiac event rate.

BACKGROUND: Since an inverse relationship between percutaneous coronary angioplasty (PTCA) case-load and in-hospital major adverse cardiac events (MACE) exists, we intended to evaluate the performance of low-volume PTCA operators, during the first year of our interventional program, by applying the more accurate index represented by the MACE rate within the first month. METHODS: The data relative to both the PTCA procedure and the control visit 3-4 weeks later, were retrospectively reviewed. Death, myocardial infarction and need for revascularization were the end-points evaluated, both globally and with respect to the individual operators. RESULTS: During 1999, 61 consecutive patients (53M, 8F; mean age: 59.9+/-10.4 years) were treated by two full-trained operators. Stable angina was the indication in 75% of cases. Comorbidities as diabetes and prior revascularization, were present in 16 and 5% of cases, respectively. Multivessel procedures were performed in 33% of cases, with a total number of lesions of 84 (77% A/B1 type). Stents were implanted in 70% of cases, as a bail-out in 12%. Procedural success rate was 93%. Overall one-month MACE rate was 3.3%, accounted for by 1 in-hospital emergency coronary surgery occurred to operator 1 (3.6% one-month MACE rate) and 1 elective coronary operation performed in a stable patient previously treated by operator 2 (3% one-month MACE rate). CONCLUSIONS: PTCA performed in a low-volume center by low-volume operators is not necessarily associated with a poor outcome, provided that adequate selection of low-risk cases is accomplished. Although only 52% of the Italian centers met in 1999 the recommended volume standards, reaching optimal case-load should anyway be pursued. Some time should however be conceded, provided that close monitoring of one-month MACE rate shows adequate performance of both the institution and the operators.

Efficacy of pacing therapies for treating atrial tachyarrhythmias in patients with ventricular arrhythmias receiving a dual-chamber implantable cardioverter defibrillator.

BACKGROUND: Although overdrive pacing for treating atrial flutter is well established, the efficacy of device-based atrial pacing for treating spontaneous atrial tachyarrhythmias in patients with implantable cardioverter defibrillators (ICD) is unknown. This study evaluated the efficacy of novel pacing therapies for treating atrial tachyarrhythmias in patients receiving a dual-chamber ICD to treat ventricular tachyarrhythmias. METHODS AND RESULTS: A Jewel AF ICD was implanted in 537 patients with ventricular arrhythmia who were followed for 11.4+/-8.2 months (74% had a documented history of atrial tachyarrhythmias). The device discriminated atrial tachycardia (AT) from atrial fibrillation (AF) on the basis of cycle length and regularity, and it used 3 different methods of overdrive atrial pacing (Ramp, Burst+, and 50-Hz burst) to treat AT episodes and one method (50-Hz burst) to treat AF episodes. Pacing successfully terminated 59% of 1500 spontaneous AT episodes in 127 patients and 30% of 880 AF episodes in 101 patients (P<0.001). With AT and AF episodes combined, pacing efficacy was 48%. Pacing efficacy was significantly reduced at AT cycle lengths

Clinical experience with a dual-chamber implantable cardioverter defibrillator to treat atrial tachyarrhythmias.

INTRODUCTION: This study evaluated the safety and efficacy of a new dual-chamber implantable cardioverter defibrillator (ICD) to detect and treat atrial tachyarrhythmias in patients with drug-refractory atrial fibrillation (AF) and no indication for a ventricular ICD. METHODS AND RESULTS: A dual-chamber ICD (Medtronic 7250 Jewel AF) was implanted in 144 of 146 patients. The device discriminates atrial tachycardia from AF based on cycle length and regularity, and uses atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 12.6+/-6.2 months. Use of antiarrhythmic drugs was 63% at baseline and did not change over time. Kaplan-Meier estimates of 12-month complication-free survival, device therapy survival, and patient survival were 85%, 91%, and 98%, respectively. Positive predictive accuracy of spontaneous atrial tachyarrhythmia detection was 99%, while atrial overdrive pacing and shocks terminated 40% and 87% of treated episodes, respectively. Median duration of successfully treated episodes was 8.9 minutes versus 144 minutes for the therapy failures. There was no reduction in the use of patient-activated shock therapy over time; at the 12-month follow-up evaluation, 94% of patients were in sinus rhythm. Ventricular tachyarrhythmias (67 episodes) were detected and appropriately treated in 7.6% of patients. CONCLUSION: This dual-chamber ICD appears to be safe and well tolerated in patients with drug-refractory symptomatic atrial tachyarrhythmias. The device, used in combination with drugs, effectively treats atrial tachyarrhythmias with pacing and/or shock therapies and decreases the median episode duration. In addition, the device protects from ventricular tachyarrhythmias in patients with AF and structural heart disease.

Current perspectives The diagnosis of acute pulmonary embolism. A review of the literature and current clinical practice.

The optimal approach to the diagnosis of acute pulmonary embolism is still controversial. The poor sensitivity and specificity of most of the clinical manifestations, the suboptimal accuracy of the majority of the laboratory and instrumental examinations and the highly variable local availability of the diagnostic resources, makes it in fact difficult for a univocal strategy to be adopted. Recently published practical guidelines, however, support the use of lung scanning (either ventilation/perfusion or only perfusion) as a first-line imaging test, since this approach allows for a correct diagnosis in most patients, after careful history taking, physical examination and electrocardiogram, chest X-ray and arterial blood gas analysis performance. When lung scanning is non-diagnostic, either serial non-invasive (i.e. ultrasonographic) evaluation of the lower limbs or pulmonary angiography should follow. Growing evidence is accumulating on the use of spiral computed tomography scanning either as an alternative or as a complement to lung scanning, while echocardiography should be reserved for the bedside evaluation of critically ill patients, when more validated techniques are not readily available. The role of plasma D-dimer measurement has yet to be defined, especially in hospitalized patients. In current clinical practice, however, these recommendations seem to be only partially followed. Depending in fact on the different characteristics of the populations examined in the seven available studies reporting on this issue, the use of the different diagnostic techniques appears highly variable. Although a standard diagnostic pathway does not seem applicable to all patients with suspected acute pulmonary embolism, further work is nonetheless needed in order to identify in different patient subsets the diagnostic approach capable of minimizing the use of diagnostic resources while obtaining the greatest amount of information.

A multifilamented electrode in the middle cardiac vein reduces energy requirements for defibrillation in the pig.

OBJECTIVE: To compare the defibrillation efficacy of a novel lead system placed in the middle cardiac vein with a conventional non-thoracotomy lead system. METHODS: In eight pigs (weighing 35-71 kg), an electrode was advanced transvenously to the right ventricular apex (RV), with the proximal electrode in the superior caval vein (SCV). Middle cardiac vein (MCV) angiography was used to delineate the anatomy before a three electrode system (length 2 x 25 mm + 1 x 50 mm) was positioned in the vein. An active housing (AH) electrode was implanted in the left pectoral region. Ventricular fibrillation was induced and biphasic shocks were delivered by an external defibrillator. The defibrillation threshold was measured and the electrode configurations randomised to: RV-->AH, RV+MCV-->AH, MCV-->AH, and RV-->SCV+AH. RESULTS: For these configurations, mean (SD) defibrillation thresholds were 27.3 (9.6) J, 11.9 (2.9) J, 15.2 (4.3) J, and 21.8 (9.3) J, respectively. Both electrode configurations incorporating the MCV had defibrillation thresholds that were significantly less than those observed with the RV-->AH (p < 0.001) and RV-->SCV+AH (p < 0.05) configurations. Necropsy dissection showed that the MCV drained into the coronary sinus at a location close to its orifice (mean distance = 2.7 (2.2) mm). The MCV bifurcated into two main branches that drained the right and left ventricles, the left branch being the dominant vessel in the majority (6/7) of cases. CONCLUSIONS: Placement of specialised defibrillation electrodes within the middle cardiac vein provides more effective defibrillation than a conventional tight ventricular lead.

Reduction in defibrillation threshold using an auxiliary shock delivered in the middle cardiac vein.

Defibrillation in the middle cardiac vein (MCV) has been shown to reduce ventricular defibrillation thresholds (DFTs). Low amplitude auxiliary shock (AS) from an electrode sutured to the left ventricle at thoracotomy have also been shown to reduce DFT if delivered immediately prior to a biphasic shock (between the ventricular RV and superior vena caval (SVC) electrodes). This study investigates the impact on DFT of an AS shock from a transvenously placed MCV lead system. A standard defibrillation electrode was positioned in the RV in eight anesthetized pigs (35-43 kg). A 50 x 1.8-mm electrode was inserted in the MCV through an 8 Fr angioplasty guide catheter. A 150-V (leading edge) monophasic AS was delivered (95 microF capacitor) from the MCV-->Can with three different pulse widths (3, 5, 7 ms). A primary biphasic shock (PS) (95 microF capacitor, phase 1: 44% tilt, 1.6-ms extension and phase 2: 2.5-ms fixed duration) was delivered from the RV-->Can +/- AS. The four configurations were randomized and DFTs (PS + AS) assessed using a modified binary search. Ventricular fibrillation (VF) was induced with 60 Hz AC followed 10 seconds later by the test shock. The DFTs were compared using repeated measures analysis of variance (ANOVA). All configurations incorporating AS produced significant (P < 0.05) reduction in the DFT compared to no AS (13.8 +/- 7.4 J). There was no difference in the efficacy of differing pulse widths (P > 0.05); 3 ms (11.0 +/- 5.4 J), 5 ms (11.5 +/- 6.0), and 7 ms (10.6 +/- 5.3 J). In conclusion, delivering an AS from a transvenous lead system deployed in the MCV reduces the DFT by 23% compared to a conventional RV-->Can shock alone.

Increased defibrillation threshold with right-sided active pectoral can.

UNLABELLED: The aim of this study was to identify the optimal position on the chest wall to place an implant able cardioverter defibrillator in a two-electrode system, consisting of a right ventricular electrode and active can. METHODS AND RESULTS: Defibrillation thresholds (DFT) were measured in 10 anaesthetised pigs (weight 33-45 kg). An Angeflextrade mark lead was introduced transvenously to the right ventricular apex. The test-can (43 cc) was implanted submuscularly in each of four locations: left pectoral (LP), right pectoral (RP), left lateral (LL) and apex (A). The sequence in which the four locations were tested was randomized. Ventricular fibrillation (VF) was induced using 60 Hz alternating current. Rectangular biphasic shocks were delivered 10 seconds after VF induction. The DFT was measured using a modified four-reversal binary search. The results of the four configurations were: LP, 14.6+/- 4.0 J; RP, 18.8+/- 4.2 J; LL, 14.7+/- 4.1 J; A, 14.9+/- 3.1 J. Repeated measures analysis of variance showed that the DFT of RP was significantly higher than LP, LL and A (p < 0.05). CONCLUSIONS: Implanting an active can in the RP position increases the DFT by 29% compared to LP, LL and A sites. The can position on the left thorax does not appear to have a significant influence on DFT.

Cardioprotective effects of the aminopeptidase P inhibitor apstatin: studies on ischemia/reperfusion injury in the isolated rat heart.

Aminopeptidase P and angiotensin-converting enzyme (ACE) are responsible for the metabolism of exogenously administered bradykinin in the coronary circulation of the rat. It has been shown that ACE inhibitors decrease cytosolic enzyme release from the ischemic rat heart and reduce reperfusion-induced ventricular arrhythmias by increasing endogenous levels of bradykinin. It was hypothesized that the aminopeptidase P inhibitor apstatin could do the same. In an isolated perfused rat heart preparation subjected to global ischemia and reperfusion, both apstatin and ramiprilat (an ACE inhibitor) significantly decreased creatine kinase (CK) and lactate dehydrogenase (LDH) release. The difference between the postischemia and preischemia levels of released CK was reduced 68% by apstatin and 68% by ramiprilat compared with control. The corresponding reductions in LDH release were 74% for apstatin and 81% for ramiprilat. A combination of the inhibitors was not significantly better than either one alone. Apstatin and ramiprilat also significantly reduced the duration of reperfusion-induced ventricular fibrillation by 69 and 61%, respectively. The antiarrhythmic effect of apstatin was reversed by HOE140, a bradykinin B2-receptor antagonist, suggesting that apstatin is acting by potentiating endogenously formed bradykinin. The results demonstrate that the aminopeptidase P inhibitor apstatin is cardioprotective in this model of cardiac ischemia/ reperfusion injury.

Inspiration induced by phrenic nerve stimulation increases internal defibrillation energy requirements.

INTRODUCTION: The purpose of this study was to systematically evaluate the effects of active inspiration induced by phrenic nerve stimulation on the energy required for 50% successful defibrillation (E50). METHODS AND RESULTS: Shocks (95-microF biphasic waveform) were delivered after 10 seconds of ventricular fibrillation between a right ventricular coil and left pectoral test can in ten anesthetized pigs (25 to 37 kg). Using a 1-J step size, the E50 was determined with an up/down, three-reversal method. Positive-pressure ventilation was halted just before fibrillation, and shocks were delivered during expiration or at the end of 2 seconds of bilateral phrenic stimulation (50 Hz, 0.3 msec, 5 to 6 V). Phrenic stimulation produced inspiratory volumes that were 15.3 +/- 1.7 mL/kg (mean +/- SD). The E50 was 9.8 +/- 1.9 J during expiration and increased to 13.0 +/- 1.7 during inspiration (P = 0.001). The leading-edge voltage at the E50 was 451 +/- 46 V during expiration and 519 +/- 33 V during inspiration (P = 0.001). The leading-edge current at the E50 was 9.7 +/- 1.0 A during expiration and increased to 11.3 +/- 1.4 A during inspiration (P = 0.002). The average impedance was 47.8 +/- 2.7 omega during expiration and 47.3 +/- 3.3 omega during inspiration (P = 0.12). CONCLUSION: Inspiration induced by phrenic stimulation results in a 31% increase in the E50 compared with expiration. The decrease in shock efficacy occurs in the absence of a change in impedance. Active inspiration may alter the distribution of the electrical field leading to a decrease in shock efficacy.

A systematic evaluation of conventional and novel transvenous pathways for defibrillation.

INTRODUCTION: Conventional implantable cardioverter defibrillators employ endocardial (shock) electrodes with a lead located in the right ventricular apex (RV) and a "hot-can" electrode located subcutaneously in the left pectoral region. In the event of a high defibrillation threshold (DFT) a third electrode is frequently employed in the superior vena cava (SVC). We report the comparison of conventional and novel locations of additional electrodes with the RV/Can configuration, in a porcine model. METHOD: In 12 anesthetized pigs (30-45 kg), endocardial defibrillation electrodes were randomized to the following locations: RV/Can, RV/Can + SVC, RV/Can + main pulmonary artery (MPA) and RV/Can + left pulmonary artery wedge position (PAW), RV/Can + high inferior vena cava (HIVC), RV/Can + Low inferior vena cava (LIVC). Ventricular fibrillation (VF) was induced using 60 Hz alternating current. After 10 seconds VF a rectangular biphasic shock was delivered by the ARD9000 (Angeion Corp). The DFT was determined for each configuration using a modified four-reversal binary search. All configurations were compared using a repeated measures analysis of variance (ANOVA) statistical test and the five 3-electrode configurations were compared to the RV/Can position using a Dunnett test. RESULTS: Mean DFTs: RV = 21.5 +/- 4.8 J, SVC = 16.8 +/- 4.7 J (p < 0.05 vs. RV), HIVC = 21.1 +/- 4.7 J (p <. 0.05), LIVC = 19.1 +/- 5.7 J (p <. 0.05 vs. RV), MPA = 16.0 +/- 5.8 J (p < 0.01), PAW = 17.5 +/- 4.6 J (p < 0.05 vs. RV). CONCLUSIONS: Relative to the RV/can configuration the addition of a third electrode in the PA, PAW or SVC significantly reduces the DFT in the pig. The addition of an electrode to the IVC did not significantly reduce the DFT in our model.

Low voltage direct current delivered through unipolar transvenous leads: an alternate method for the induction of ventricular fibrillation.

The induction of VF during testing of an ICD may not always be possible using either burst pacing or high energy T wave shocks. The purpose of this study was to evaluate the effectiveness of low energy DC stimulation for inducing VF in a porcine model. The VFT was measured using constant voltage stimuli and a step-up method in ten anesthetized pigs (25-30 kg). Stimuli of different durations (0.5, 1.0, 2.0 s) were delivered (unsynchronized) between a right ventricular apical coil and a subcutaneous test can. Current was measured from the voltage drop across a series resistor (10 omega). With anodal stimulation, VF required 6.4 +/- 0.2 V compared to 13.8 +/- 0.6 V with cathodal stimulation (P < 0.001). The current required to induce VF (measured 10 ms after the stimulus onset) was 58.3 +/- 2.2 mA with anodal stimulation and 119.3 +/- 4.7 mA with cathodal stimulation (P < 0.001). Stimulus duration did not significantly influence the voltage or current required for VF induction. In 6 of the 10 pigs, synchronizing a 0.5-second stimulus to the R wave did not significantly alter the VFT compared to same stimulus synchronized to mid-upslope of the T wave. The results indicate that VF can be consistently induced through transvenous electrodes by passing unsynchronized DC for 0.5-2 seconds. The induction of VF required about 50% less current and voltage with anodal stimulation. It should be possible to induce VF with the DC voltage available from the internal battery source of an ICD.

The middle cardiac vein--a novel pathway to reduce the defibrillation threshold.

UNLABELLED: Defibrillation energy requirements of epicardial implantable cardioverter defibrillator systems are generally lower than endovascular systems currently used. The former has the disadvantage of requiring a thoracotomy and so has a greater morbidity and mortality than an endovascular procedure. The middle cardiac vein (MCV) is an epicardial structure that is accessible by a non-thoracotomy approach. This study investigated the merits of ventricular defibrillation from the middle cardiac vein. METHODS AND RESULTS. Defibrillation thresholds (DFT) were measured in 10 anesthetized pigs, weighing 34.5 +/- 44.1 kg (mean 39 kg). An Angeflex electrode (1.7 mm x 50 mm) was introduced via the left external jugular vein to the right ventricular apex. The MCV was identified with standard angiography techniques and a 4080 (Angeion Corp.) defibrillation electrode (1.6 mm x 65 mm) introduced into the vein. An active can was implanted in the left subpectoral region. The defibrillation thresholds (DFT) of the following defibrillation configurations were assessed using a modified four-reversal binary search: RV-->Can, RV + MCV-->Can and MCV-->Can. The DFT's for the three configurations were 15.5 +/- 2.8 J, 10.8 +/- 3.4 J and 13.7 +/- 2.4 J. Analysis of variance showed that the DFT with the RV + MCV combination was significantly less than the RV alone (p < 0.05) CONCLUSIONS: Defibrillation is possible through the MCV and that incorporating an electrode in the MCV with RV-Can configuration can reduce the DFT by 30%.

Improved efficacy of anodal biphasic defibrillation shocks following a failed defibrillation attempt.

Although it is generally assumed that defibrillation becomes more difficult when the duration of VF is prolonged, after a failed defibrillation attempt, there is little information on the defibrillation efficacy of multiple shocks delivered at the same energy. The purpose of this study was to systematically examine the efficacy of a second shock delivered at the same or reversed polarity after a failed first shock. Defibrillation was attempted after 10 seconds of VF in 12 pigs (30-56 kg) using biphasic waveforms and a nonthoracotomy lead system. Shock energy was held constant for the first and second shocks at 50%-90% of the DFT. The second shock was delivered 10 seconds after a failed first shock. First and second shock polarity (first phase) was randomized to (+, +), (+, -), (-, -), (-, +). The incidence of successful defibrillation (for all polarities) was 12.3% for first and 49.1% for second shocks (P < 0.0001). Anodal first shocks had a 17.2% incidence of success as opposed to a 7.4% incidence of success with cathodal first shocks (P = 0.001). Anodal second shocks had a 55.5% incidence of success compared to a 42.7% incidence of success with cathodal second shocks (P = 0.008). There was no significant benefit from polarity reversal after a failed first shock (P = 0.29). In conclusion, less energy is required for successful defibrillation by a second shock after a failed first. The optimal configuration for first and second shocks is with the RV as anode. Polarity reversal of a second shock after a failed first does not affect the probability of second shock success.

Downregulation of sarcoplasmic reticulum Ca(2+)-ATPase during progression of left ventricular hypertrophy.

To determine whether reduced sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) (SERCA2) activity contributes to delayed myocardial relaxation during chronic left ventricular hypertrophy (LVH) progression, LVH was produced in rats by abdominal aortic coarctation. Systolic and diastolic functions were assessed in vivo 8 and 16 wk after surgery, and compositional alterations in LV myocardium [SERCA2 concentration, myosin heavy chain (MHC) isoenzymes, and tissue collagen] were correlated with the development of prolonged isovolumic relaxation and impaired cardiac performance over time. Myocardial relaxation was prolonged in 8-wk banded rats, despite normal isovolumic systolic function and LV end-diastolic pressure (LVEDP). No significant alterations in SERCA2 protein, beta-MHC, or fibrillar collagen levels were observed at this early time point. In contrast, LV SERCA2, beta-MHC, and fibrillar collagen concentrations were all significantly altered in 16-wk banded rats. These late compositional changes were associated with reduced cardiac performance, as manifested by a significant elevation in LVEDP (14 +/- 2 mmHg). The 34% decrease in SERCA2 protein was associated with reduced SR Ca2+ uptake and an even greater reduction (76%) in SERCA2 mRNA. SERCA2 mRNA levels were also significantly reduced to 43 +/- 10% of sham-operated rats 8 wk after banding, despite unchanged SERCA2 protein levels and normal SR Ca2+ uptake. These results argue against a significant contribution of SERCA2 downregulation to the subtle alterations in myocardial relaxation observed in compensated LVH. However, the early reduction in SERCA2 mRNA levels may serve as a molecular marker for impaired cardiac performance during the transition from compensated LVH to heart failure.

Baroreflex sensitivity assessed by complex demodulation of cardiovascular variability.

We used complex demodulation of cardiac interval and systolic arterial blood pressure oscillations in the low-frequency band (0.04 to 0.14 Hz) to investigate baroreceptor control of heart rate. Baroreflex sensitivity was defined as the instantaneous amplitude of complex-demodulated oscillations in the RR interval divided by the instantaneous amplitude of complex-demodulated oscillations in systolic blood pressure. We evaluated the method using both simulated and actual data obtained from 33 healthy nonsmokers during supine and standing postures. To test the validity and reliability of the method, we compared the mean values of baroreflex sensitivity calculated using complex demodulation with the values obtained using power spectral analysis and sequential analysis of spontaneous variations in blood pressure and RR interval. All three methods applied to the simulated data yielded the same values of baroreceptor sensitivity. Mean values of baroreflex sensitivity assessed by complex demodulation of the actual data were similar to those calculated by both power spectral analysis and sequential analysis (13.9 +/- 5.2 versus 13.7 +/- 6.7 or 14.3 +/- 6.5 ms/mm Hg for supine and 7.3 +/- 2.8 versus 7.0 +/- 3.0 or 7.2 +/- 2.8 ms/mm Hg for standing, respectively). In addition, a significant correlation existed between the values obtained by complex demodulation and power spectral analysis (r = .97, P = .0001) and sequential analysis (r = .98, P = .0001). Furthermore, complex demodulation-derived baroreflex sensitivity fluctuated across time during both the supine and standing postures, and this could not be discerned by power spectral analysis. The results indicate that complex demodulation provides a dynamic assessment of baroreflex sensitivity and may be a useful tool in exploring reflex autonomic control of the cardiovascular system.

Sympathetic influences on electrical and mechanical alternans in the canine heart.

OBJECTIVE: The aim was to investigate the influence of the sympathetic nervous system on the induction of mechanical and electrical alternans in the intact canine heart. METHODS: Experiments were performed on 8 open-chest dogs anesthetized with sodium pentobarbital. A micromanometer-tipped catheter was used to measure left ventricular pressure, dp/dt and the time constant of isovolumic relaxation. Rapid atrial pacing was used to induce alternans and the left stellate ganglion was stimulated electrically to alter sympathetic tone. The longest pacing cycle length that showed a significant alternation in peak systolic pressure was defined as the alternans threshold. Electrical alternans was detected by comparing the ST-T area in the surface ECG (lead II) on alternate beats. RESULTS: The alternans threshold was 305(s.e.m. 10.4) ms under control conditions and decreased to 271(12.1), 225(33.4), and 177(6.2)ms, as the frequency of left stellate stimulation was increased to 1, 2, and 5 Hz, respectively (P < 0.001). Tau and peak -dp/dt began to alternate at the same pacing cycle length as peak +dp/dt and peak systolic pressure. Electrical alternans was only observed during mechanical alternans and the ST-T area of the strong beat was 243(143)% greater than the ST-T area of the weak beat (P < 0.001). Timolol (1 mg.kg-1) blocked the effect of left stellate stimulation (1 and 2 Hz) on mechanical and electrical alternans. CONCLUSIONS: Left sympathetic activation causes a frequency-dependent reduction in the threshold cycle length for global mechanical and electrical alternans. Alternation in relaxation occurs at the same pacing cycle length as does alternation in contraction. Repolarization alternans in the surface ECG appears to reflect underlying mechanical events.

Reflex vagal control of atrial repolarization.

The reflex vagal control of atrial repolarization was investigated in eight open-chest, anesthetized dogs. A monophasic action potential was recorded from the right atrium, and the action potential duration to 90% repolarization (APD90) was determined every cardiac cycle. beta-Adrenergic receptors were blocked with timolol (0.1 mg/kg). Under baseline conditions, sinus slowing during sinus arrhythmia was accompanied by a significant shortening of APD90 (24 +/- 4.0 ms). Transient occlusion (30 s) of the descending thoracic aorta increased systolic aortic pressure from 138 +/- 2.8 to 181 +/- 3.3 mmHg (P < 0.01). Heart rate decreased from 99 +/- 3.6 to 42.5 +/- 3.4 beats/min (P < 0.01), and APD90 shortened from 168 +/- 5.1 to 94 +/- 3.3 ms (P < 0.01). Release of the occlusion caused arterial hypotension (95 +/- 2.8 mmHg) and an overshoot in both rate (126 +/- 5.2 beats/min) and APD90 (189 +/- 2.3 ms). Aortic occlusion during atrial pacing (130-160 beats/min) decreased APD90 from 147 +/- 7.0 to 78 +/- 3.4 ms (P < 0.01). Cervical vagotomy or atropine eliminated changes in rate and APD90 evoked by aortic occlusion. The results indicate that there is parallel central vagal control of both sinus rate and atrial repolarization. Sinus bradycardia during reflex vagal activation does not prevent the acceleration of atrial repolarization.