C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) may persist due to structural changes in the atria that are promoted by inflammation. C-reactive protein (CRP), a marker of systemic inflammation, predicts cardiovascular events and stroke, a common sequela of AF. We hypothesized that CRP is elevated in patients with atrial arrhythmias. METHODS AND RESULTS: Using a case-control study design, CRP in 131 patients with atrial arrhythmias was compared with CRP in 71 control patients. Among arrhythmia patients, 6 had frequent atrial ectopy or tachycardia, 86 had paroxysmal AF, 39 had persistent AF lasting >30 days, and 70 had lone arrhythmias. CRP was higher in arrhythmia than in control patients (median, 0.21 versus 0.096 mg/dL; P<0.001). Arrhythmia patients in AF within 24 hours before sampling had higher CRP than those in sinus rhythm (0.30 versus 0.15 mg/dL; P<0.001). CRP in controls was not different than in patients with atrial ectopy or tachycardia. Lone arrhythmia patients had a CRP of 0.21 mg/dL, which was not significantly lower than arrhythmia patients with structural heart disease (CRP, 0.23 mg/dL) but higher than controls (P=0.002). Persistent AF patients had a higher CRP (0.34 mg/dL) than paroxysmal AF patients (0.18 mg/dL; P=0.008); both groups had higher CRP levels than controls (P

Management of atrial flutter.

Atrial flutter is a macroreentrant arrhythmia that is associated with cardiovascular and pulmonary disease. In the United States, 200,000 new cases of atrial flutter can be expected to develop every year with a male to female ratio of over 2:1. This arrhythmia is associated with atrial fibrillation in over half the cases. It is also associated with an increased risk of thromboembolic complications, but less than that is seen with atrial fibrillation. The most common form of atrial flutter involves a large reentrant circuit within the right atrium, encircling the tricuspid annulus. Other, less common forms of atrial flutter may involve other anatomic barriers, atriotomy scars, and infarcted areas of the atria. Treatment of atrial flutter often involves electrical cardioversion and/or antiarrhythmic medications. Type I and Type III antiarrhythmic drugs are often used to terminate or prevent recurrent episodes and Type II (beta-blockers) and Type IV (calcium channel blockers) can be used to control the ventricular rate during atrial flutter. However, antiarrhythmic drugs alone control atrial flutter in only 50% to 60% of patients. Since the early 1990s, radiofrequency catheter ablation has been used to interrupt the reentrant circuit and prevent recurrences of atrial flutter. Radiofrequency ablation is acutely successful in over 90% of cases and avoids the long-term toxicity seen with antiarrhythmic drugs. Advanced mapping techniques and newer methods of delivering the radiofrequency lesions are being used to delineate unusual forms of atrial flutter and to minimize fluoroscopic exposure during the procedure.

Voltage dependence of ICD lead polarization and the effect of iridium oxide coating.

Nonthoracotomy leads (NTLs) with an iridium oxide (IROX) coating exhibit lower defibrillation thresholds (DFTs) than uncoated NTLs. We tested whether adding an IROX coating to an active pectoral can would influence defibrillation efficacy. However, the primary purpose of this study was to examine the impedance changes that occur at different voltages for uncoated titanium NTLs and identical NTLs with an IROX coating. We studied anesthetized pigs with an NTL placed in the right ventricle and coupled this to an active pectoral can. Biphasic waveform DFTs were obtained for the four NTLs and can combinations: uncoated NTL and uncoated can, uncoated NTL and IROX can, IROX NTL and uncoated can, and IROX NTL and IROX can. The respective energy DFTs were: 23.6 +/- 6.9, 24.1 +/- 6.7, 21.3 +/- 6.0, and 21.4 +/- 7.0 J. The IROX NTL DFTs were significantly lower (P < 0.05) than the uncoated NTL DFTs (either can), confirming our previous study. We then used a low tilt monophasic waveform to assess impedance changes. The impedance rise for each NTL/can combination was measured at 50, 100, 300, and 700 V. Comparisons of impedance changes between voltage levels showed that the impedance rise was inversely related to voltage and was greatest with uncoated NTLs. The IROX coating of the NTL reduced the impedance rise at all shock voltages, but was particularly beneficial at the lower voltages. No advantage was seen when the pectoral can was coated with IROX regardless of which NTL was used. Our results suggest that low voltage applications, such as atrial defibrillation, would benefit most from the IROX-coated NTL, and further studies are warranted in this area.

Higher energy synchronized external direct current cardioversion for refractory atrial fibrillation.

OBJECTIVES: We sought to evaluate the safety and efficacy of higher energy synchronized cardioversion in patients with atrial fibrillation refractory to standard energy direct current (DC) cardioversion. BACKGROUND: Standard external electrical cardioversion fails to restore sinus rhythm in 5% to 30% of patients with atrial fibrillation. METHODS: Patients with atrial fibrillation who failed to achieve sinus rhythm after at least two attempts at standard external cardioversion with 360 J were included in the study. Two external defibrillators, each connected to its own pair of R-2 patches in the anteroposterior position, were used to deliver a synchronized total of 720 J. RESULTS: Fifty-five patients underwent cardioversion with 720 J. Mean weight was 117 +/- 23 kg (body mass index 48.3 +/- 4.1 kg/m2). Structural heart disease was present in 76% of patients. Mean left ventricular ejection fraction was 45 +/- 12%. Atrial fibrillation was present for over three months in 55% of the patients. Sinus rhythm was achieved in 46 (84%) of the 55 patients. No major complications were observed. No patient developed hemodynamic compromise and no documented cerebrovascular accident occurred within one month after cardioversion. Of the 46 successful cardioversions, 18 patients (39%) remained in sinus rhythm over a mean follow-up of 2.1 months. CONCLUSIONS: External higher energy cardioversion is effective in restoring sinus rhythm in patients with atrial fibrillation refractory to standard energy DC cardioversion. This method is safe and does not result in clinical evidence of myocardial impairment. It may be a useful alternative to internal cardioversion because it could be done within the same setting of the failed standard cardioversion and obviates the need to withhold protective anticoagulation for internal cardioversion.

Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required? Yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications.

OBJECTIVES: We sought to determine the yield of in-hospital monitoring for detection of significant arrhythmia complications in patients starting sotalol therapy for atrial arrhythmias and to identify factors that might predict safe outpatient initiation. BACKGROUND: The need for hospital admission during initiation of antiarrhythmic therapy has been questioned, particularly for sotalol, with which proarrhythmia may be dose related. METHODS: The records of 120 patients admitted to the hospital for initiation of sotalol therapy were retrospectively reviewed to determine the incidence of significant arrhythmia complications, defined as new or increased ventricular arrhythmias, significant bradycardia or excessive corrected QT (QTc) interval prolongation. RESULTS: Twenty-five patients (20.8%) experienced 35 complications, triggering therapy changes during the hospital period in 21 (17.5%). New or increased ventricular arrhythmias developed in 7 patients (5.8%) (torsade de pointes in 2), significant bradycardia in 20 (16.7%) (rate <40 beats/min in 13, pause >3.0 s in 4, third-degree atrioventricular block in 1, permanent pacemaker implantation in 3) and excessively prolonged QTc intervals in 8 (6.7%) (dosage reduced or discontinued in 6). Time to the earliest detection of complications was 2.1 +/- 2.5 (mean +/- SD) days after initiation of sotalol, with 22 of 25 patients meeting criteria for complications within 3 days of monitoring. Baseline electrocardiographic intervals or absence of heart disease failed to distinguish a low risk group. Multivariate analysis identified absence of a pacemaker as the only significant predictor of arrhythmia complications (p = 0.022). CONCLUSIONS: Because clinically significant complications can be detected with in-hospital monitoring in one of five patients starting sotalol therapy, hospital admission is warranted for initiation of sotalol. Patients without pacemakers are at higher risk for these complications.

Effects of respiration phase on ventricular defibrillation threshold in a hot can electrode system.

The impedance of defibrillation pathways is an important determinant of ventricular defibrillation efficacy. The hypothesis in this study was that the respiration phase (end-inspiration versus end-expiration) may alter impedance and/or defibrillation efficacy in a "hot can" electrode system. Defibrillation threshold (DFT) parameters were evaluated at end-expiration and at end-inspiration phases in random order by a biphasic waveform in ten anesthetized pigs (body weight: 19.1 +/- 2.4 kg; heart weight: 97 +/- 10 g). Pigs were intubated with a cuffed endotracheal tube and ventilated through a Drager SAV respirator with tidal volume of 400-500 mL. A transvenous defibrillation lead (6 cm long, 6.5 Fr) was inserted into the right ventricular apex. A titanium can electrode (92-cm2 surface area) was placed in the left pectoral area. The right ventricular lead was the anode for the first phase and the cathode for the second phase. The DFT was determined by a "down-up down-up" protocol. Statistical analysis was performed with a Wilcoxon matched pair test. The median impedance at DFT for expiration and inspiration phases were 37.8 +/- 3.1 omega, and 39.3 +/- 3.6 omega, respectively (P = 0.02). The stored energy at DFT for expiration and inspiration phases were 5.7 +/- 1.9 J and 6.0 +/- 1.0 J, respectively (P = 0.594). Shocks delivered at end-inspiration exhibited a statistically significant increase in electrode impedance in a " hot can" electrode system. The finding that DFT energy was not significantly different at both respiration phases indicates that respiration phase does not significantly affect defibrillation energy requirements.

Iridium oxide-coated defibrillation electrode: reduced shock polarization and improved defibrillation efficacy.

BACKGROUND: Transvenous implantable cardioverter-defibrillator (ICD) leads are designed to deliver electric shocks to the heart for termination of ventricular dysrhythmias. However, the efficiency of different lead materials has not been well studied. This study compares an ICD lead coated with iridium oxide (IROX), a material that reduces shock-induced polarization, with an otherwise identical, uncoated lead. METHODS AND RESULTS: The defibrillation threshold (DFT) was determined in 13 swine with both IROX-coated and uncoated ICD leads paired with an uncoated "can" electrode. The leads were exchanged through a Teflon sheath to reproduce the intracardiac position. The delivered energy DFT of the IROX-coated lead was 15.9+/-5.4 J and was significantly lower than the delivered energy DFT of the uncoated lead (19.1+/-5.1 J; P<.006). The initial lead impedance was equivalent in both leads (IROX, 41.7+/-5.8 omega; uncoated, 41.3+/-4.7 omega; P=NS) at DFT. However, the impedance rose by 7.3+/-2.0 omega during the first phase and by 3.7+/-2 omega during the second phase with the uncoated lead, whereas the corresponding impedance change was 1.0+/-0.3 omega during phase 1 and 1.6+/-0.5 omega during phase 2 (P<.01 each phase) when the IROX-coated lead was used. CONCLUSIONS: This study shows that an IROX coating of this lead system significantly lowers the DFT energy in the swine model. The blunting of the impedance rise by the IROX coating that is seen is consistent with a reduction in electrode polarization.

Additional lead improves defibrillation efficacy with an abdominal 'hot can' electrode system.

BACKGROUND: Although the left prepectoral site is preferred for "hot can" placement, this site is unavailable in some patients. We evaluated the influence of electrode location on defibrillation thresholds with alternative hot can and transvenous lead configurations. METHODS AND RESULTS: Three interrelated studies were performed. In group 1, the importance of hot can location was investigated by pairing a right ventricular lead to five different hot can placement sites in seven pigs. The defibrillation energies for right pectoral, left pectoral, left subaxillary, and right and left abdominal hot can sites were 20.3+/-2.7,* 15.9+/-3.8, 14.9+/-2.5, 32.0+/-3.4,* and 30.0+/-3.4 J,* respectively (*P<.005 versus left pectoral and left subaxillary sites). In group 2, the value of a three-electrode configuration with an abdominal hot can placement was investigated by adding a subclavian vein lead to the pectoral or abdominal hot can configurations in seven pigs. The defibrillation energies for left pectoral and abdominal sites were 18.6+/-4.2 and 29.0+/-5.8 J (P=.0001), respectively. The addition of a right or left subclavian vein lead with an abdominal hot can reduced the threshold to 19.3+/-4.2* or 18.8+/-3.2,* respectively (*P=.0001 versus abdominal site). In group 3, the contribution of the abdominal hot can electrode to the three-electrode configuration was tested by a comparison with two purely transvenous two-electrode configurations in six pigs. The defibrillation energy (19.9+/-3.2 J) for the abdominal hot can with a subclavian vein lead was lower than the transvenous lead configurations with a subclavian vein (29.0+/-2.5 J, P=.0001) or a superior vena cava lead (30.7+/-3.7 J, P=.0001). The right ventricular lead was the sole cathode during the first phase of the biphasic shock in all experiments. CONCLUSIONS: Defibrillation energy depends on the hot can placement site. The addition of a subclavian vein lead with an abdominal hot can improves defibrillation efficacy to the level of the pectoral placement and is better than a purely transvenous lead configuration.

The mechanisms responsible for lack of reproducible induction of atrioventricular nodal reentrant tachycardia.

INTRODUCTION: AV nodal reentrant tachycardia (AVNRT) is not always reproducibly inducible. The purpose of this study was to determine the mechanisms responsible for the lack of reproducible induction of AVNRT. METHODS AND RESULTS: The induction of AVNRT was assessed with atrial burst pacing, and with atrial and ventricular programmed stimulation, each with one and two extrastimuli, in 103 patients with AVNRT. The stimulation protocol was repeated 10 times in the baseline state, during isoproterenol infusion, and after atropine administration, or until AVNRT was induced in 7 of 10 attempts. The mechanisms responsible for < 7 of 10 inductions were classified as: (1) the inability to achieve critical AH prolongation; (2) fast pathway block; and (3) slow pathway block. The induction endpoint was achieved in 90 patients: 55 in the baseline state, 34 during isoproterenol infusion, and 1 after atropine. The mechanism of noninducibility in the baseline state (n = 48) was the inability to achieve a critical AH interval in 20%, fast pathway block in 49%, and slow pathway block in 31% (P = 0.02). During isoproterenol administration (n = 14) and after atropine administration (n = 13), the three mechanisms were equally responsible for nonreproducible induction of AVNRT. CONCLUSIONS: The induction of AVNRT is poorly reproducible in approximately 10% of patients. In the baseline state, the most common reason for the inability to reproducibly induce AVNRT is fast pathway block. In the presence of isoproterenol or atropine, each of the three mechanisms was equally responsible for noninducibility of AVNRT.

Atrioventricular node properties in patients with accessory pathways.

A study during the era of surgical ablation suggested that atrioventricular (AV) nodal conduction is faster in patients with accessory pathways than in controls. In the present study, AV nodal characteristics were studied in 30 patients who underwent radiofrequency ablation of an accessory pathway and compared to 23 control patients. Sinus cycle length, AH and HV intervals, AV block cycle length, ventriculoatrial (VA) block cycle length, AV nodal effective refractory period, and VA effective refractory periods were measured in control and postablation accessory pathway patients before and after autonomic blockade with 0.04 mg/kg of atropine and 0.2 mg/kg of propranolol. The mean sinus cycle length in the control and accessory pathway groups did not differ significantly at baseline (798 +/- 211 and 766 +/- 156 msec, respectively) or after autonomic blockade (654 +/- 98 and 649 +/- 108 msec, respectively). The mean AH interval in the accessory pathway group (77 +/- 15 msec) was significantly shorter than in the control group (91 +/- 22 msec; p < 0.05) at baseline; however, there was no difference after autonomic blockade. No other significant differences were observed between the accessory pathway and control groups. These results demonstrate that AV nodal properties of patients with accessory pathways are not significantly different from controls and suggest that previously reported differences may have been due to selection bias.

Atrial electrogram characteristics in patients with and without atrioventricular nodal reentrant tachycardia.

BACKGROUND: Multicomponent atrial electrograms and "slow pathway potentials" are helpful in identifying target sites for radiofrequency catheter ablation of the slow pathway in patients with atrioventricular (AV) nodal reentrant tachycardia. The purpose of this study was to compare the atrial electrograms recorded at various locations in the right atrium in patients with and without AV nodal reentrant tachycardia to assess the specificity of multicomponent atrial electrograms and possible slow pathway potentials both for the posteroseptal right atrium and for patients with AV nodal reentrant tachycardia. METHODS AND RESULTS: In 25 patients with AV nodal reentrant tachycardia and 23 control patients without AV nodal reentrant tachycardia or dual AV nodal physiology, atrial electrograms with an AV ratio of < or = 1:2 were recorded at the posteroseptal right atrium near the coronary sinus ostium and in the right atrium near the posterior, lateral, and anterior aspects of the tricuspid annulus. Attempts were made to identify broad, multicomponent, and double atrial electrograms. There were no significant differences between the patients with and without AV nodal reentrant tachycardia in the mean number of deflections in the atrial electrograms or in the mean duration of the atrial electrograms recorded at any of the atrial sites. In all patients, the number of atrial electrogram deflections and the atrial electrogram duration were significantly greater at the posteroseptal position than at the other three atrial sites. The prevalence of potentials with the appearance of slow pathway potentials in the posterior septum was similar in patients with and without AV nodal reentrant tachycardia (68% and 70%, respectively). The prevalence of these potentials was 6% to 25% at the other three atrial sites (P < .005 compared with the posterior septum). CONCLUSIONS: The atrial electrogram characteristics that have been found to be useful in identifying effective posteroseptal slow pathway ablation sites in patients with AV nodal reentrant tachycardia are equally prevalent in patients without AV nodal reentrant tachycardia or dual AV nodal physiology. Atrial electrograms in the posteroseptal area are broader and contain more deflections than at other areas in the right atrium, possibly because of conduction properties of the posterior transitional zone that are independent of the presence of AV nodal reentrant tachycardia.

Assessment of pacing maneuvers used to validate anterograde accessory pathway potentials.

Four pacing maneuvers have been proposed to validate an anterograde accessory pathway potential (APP): (1) atrial pacing to induce complete block between the atrial electrogram and the APP; (2) ventricular pacing to advance the APP without altering the timing of the atrial electrogram; (3) atrial pacing to induce complete block between the APP and the ventricular electrogram; and (4) ventricular pacing to advance the ventricular electrogram without altering the timing of the APP. The purpose of this study was to assess these validation techniques by applying them to electrograms that simulated APPs but which were known to be atrial in origin. In 32 patients undergoing an electrophysiology procedure, a split atrial electrogram containing two components separated by at least 30 msec (mean 54 +/- 15 msec) was recorded. Using an atrial extrastimulus technique, complete block between the two components of the atrial electrogram (criterion 1) could never be induced, but complete block between the second component of the atrial electrogram and the ventricular electrogram (criterion 3) consistently was induced. Using a ventricular extrastimulus technique, the second component of the atrial electrogram consistently could be advanced by 10 to 40 msec without altering the timing of the first component (criterion 2). In addition, with ventricular pacing, the ventricular electrogram consistently was advanced without altering the timing of the two components of the atrial electrogram (criterion 4). In conclusion, among the four pacing maneuvers used to validate an anterograde APP, the only one that may be specific for an APP is the ability to induce complete block between the atrial electrogram and the APP.

Outcome of endocardial resection in 33 patients with coronary artery disease: correlation with ventricular tachycardia morphology.

The results in 33 patients with ventricular tachycardia (VT) treated by endocardial resection were reviewed, with special emphasis on the presence of single or multiple morphologies preoperatively and intraoperatively. Multiple VT morphologies were induced in 16 patients and a single VT morphology was induced in the remaining 17. Intraoperative programmed stimulation failed to induce VT in eight patients and visually-directed endocardial resection was performed. The remaining patients underwent map-guided resection. The surgical success rate did not correlate with any morphologic characteristics of the VT, such as bundle branch block pattern or axis. In addition, concordance of VT morphologies preoperatively and intraoperatively before resection did not correlate with the surgical success rate. However, patients in whom multiple morphologies of VT were induced intraoperatively had a significantly higher success rate (100%) compared with those patients in whom only a single morphology was induced intraoperatively (50%, p < 0.05). Long-term follow-up was maintained in 26 patients. Ventricular tachycardia recurred in two patients and VF recurred in two others who did not have inducible VT 1 week after endocardial resection. In conclusion, neither the preoperative morphologic characteristics of VT nor discordance between the morphologies of VT induced preoperatively and in the operating room influenced the outcome of endocardial resection. However, the surgical success rate is higher when multiple morphologies of VT are inducible in the operating room than when only one VT morphology is inducible.

Direct activation of cardiac adrenergic nerve endings by defibrillator shocks.

Defibrillator shocks ranging in intensity from three to nine times current threshold were delivered to four isolated, metabolically supported, beating canine hearts. The shocks produced an immediate, current-dependent depression of left ventricular isovolumic systolic pressure. This depression was transient, reproducible, and was followed by a transient overshoot in ventricular systolic pressure. Then 1 mg propranolol hydrochloride in 1 ml H2O was injected into the coronary arterial supply of the isolated heart, and the shocks were repeated. The magnitude of the immediate cardiac depression after shock was unchanged; however, the time required for full recovery of left ventricular systolic pressure to a pre-shock control value was prolonged. In addition, the transient overshoot in ventricular systolic pressure seen in the untreated state was absent. These results are consistent with the hypothesis that defibrillatory shocks produce a direct activation of cardiac adrenergic nerves, which aid in recovery of ventricular contractility following defibrillator shocks.

Potassium efflux from myocardial cells induced by defibrillator shock.

A transient, dose-dependent cardiac depression was produced by defibrillator shocks in an isolated, working canine heart preparation perfused with oxygenated arterial blood from a support dog. Accompanying this depression was an efflux of potassium (K+), forced out of the myocardial cells by the passage of defibrillating current. The transient increase in extracellular K+ concentration was recorded graphically in the venous outflow. It was found that 5-msec rectangular wave shocks, from three to ten times defibrillatory current threshold, released dose-related pulses of K+. It is concluded that because K+ is a myocardial depressant, at least part of the myocardial depression after defibrillation is caused by the release of K+ from the myocardial cells.

Aortic baroreceptor characteristics in dogs with chronic high output failure.

It has been shown that the arterial baroreflex is depressed in heart failure. The role of alterations in afferent discharge as a possible mechanism for this depression has not been investigated previously. Single unit aortic baroreceptor activity was recorded from six normal dogs and from nine dogs, each with a chronic aorto-caval fistula (AVF). At the time of the acute experiment, mean arterial blood pressure (MABP) was not significantly different in the two groups of dogs; however, pulse pressure was significantly higher in the AVF dogs (45.7 +/- 2.4 mm Hg vs, 24.4 +/- 2.0 mm Hg; p less than 0.001). Left ventricular end-diastolic pressure (LVEDP) was higher in the AVF dogs (31.3 +/- 2.0 vs 5.6 +/- 1.8 mm Hg; p less than 0.001). AVF dogs had elevated heart weight/body weight ratios. The relationship of systolic aortic pressure to systolic discharge was examined by changing aortic pressure with aortic and vena caval occluders. The peak gain (normalized to maximum discharge) averaged 2.19 +/- 0.27 in the normal dogs compared to 1.15 +/- 0.09 in the AVF group (p less than 0.01). Saturation pressures and maximum discharge rates were greater in the AVF dogs although the threshold pressures were not different in the two groups. This data suggests that there is an attenuated response of aortic baroreceptor discharge in dogs with chronic volume overload and this abnormality may partially be responsible for the abnormal baroreflex in heart failure.

Acute aortic stenosis in the conscious dog: effects of inotropic state on heart rate.

Effects of acute distension of the left ventricle on heart rate were studied in conscious, instrumented dogs. In intact dogs, increasing left ventricular (LV) systolic pressure by a maximum of 77.6 +/- 3.6 mmHg from a control of 123.1 +/- 3.6 and LV end-diastolic pressure by a maximum of 24.1 +/- 2.0 mmHg from a control of 8.5 +/- 1.3 did not result in any consistent change in heart rate. Reduction of arterial pressure with sodium nitroprusside caused an increase in heart rate to 143.9 +/- 13.8 beats/min. With baroreceptors unloaded, increasing LV pressure by a similar degree as in the control group now resulted in consistent and significant bradycardia. Removal of arterial baroreceptors in a final group of dogs abolished the baroreflex. Increasing LV pressure by aortic stenosis now resulted in a stimulus-dependent decrease in heart rate that was significantly greater than that in the nitroprusside group. Both administration of atropine and bilateral cervical vagotomy abolished bradycardia. The second part of this study was concerned with effects of increases in LV inotropic state on heart rate change evoked by aortic stenosis. Each group was infused with intracoronary epinephrine. Infusion of epinephrine (12.5-50.0 ng . kg-1 . min-1) significantly increased LV dP/dt without any significant change in heart rate or mean arterial blood pressure. Aortic stenosis during epinephrine infusion did not result in any significant difference in heart rate responses in any group studied. It is concluded that LV distension can cause a reduction in heart rate that is opposed by the presence of arterial baroreceptors and that increases in LV myocardial contractility do not have any effect on the magnitude of this response.

Functional cardiac depression caused by defibrillator shocks. Quantitation of the safety factor for electrical defibrillation.

The overdose shock strengths required to depress ventricular contraction were determined for damped sinusoidal current in 7 metabolically supported, isolated contracting canine hearts. Each heart was suspended in an isoresistive and isotonic solution-through which the defibrillating shocks were delivered. Defibrillation thresholds were determined with standard damped sine wave shocks of 4.4-5.5 msec duration. Then overdose shocks were delivered and the depressant effect on systolic left ventricular pressure was measured for shocks of 3-12 times threshold current. The minimum (threshold) current and energy densities required to defibrillate were 59.5 +/- 4.6 mA/cm2 (average) and 3.12 +/- 0.2 mJ/cm3. Increasing the shock strength above threshold produced a concomitant reduction of postshock left ventricular systolic pressure. The current and energy densities required to produce 50% depression (TD50) of left ventricular systolic pressure were 5.0 and 24.1 times the threshold current and energy densities respectively, indicating a wide safety margin using this criterion.