Effects of lidocaine on relation between defibrillation threshold and upper limit of vulnerability in open-chest dogs.

BACKGROUND. The purpose of the present study was to test the effects of lidocaine on the relation between the defibrillation threshold and the upper limit of vulnerability. METHODS AND RESULTS. The shock strength associated with a 50% probability of successful defibrillation (DFT50) and the shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 11 open-chest dogs by using the delayed up-down method before and during lidocaine (seven dogs) or normal saline (four dogs) infusion. The ventricles were paced at a cycle length of 300 msec. Shocks of various strengths were then given via a patch-patch electrode configuration on the anterior and posterior surfaces of the ventricle to determine the ULV50. Once ventricular fibrillation was induced, shocks were given 15-20 seconds later via the same electrode configuration to determine the DFT50. Lidocaine infusion resulted in a serum level of 15 +/- 4 micrograms/ml. This was associated with a lengthening of the QT interval but not with the widening of the QRS complex. In all dogs, both the ULV50 and the DFT50 increased significantly when tested during lidocaine infusion. Mean ULV50 during lidocaine infusion was 496 +/- 70 V or 13.1 +/- 4.3 J, which were significantly higher than the baseline values of 333 +/- 67 V or 5.3 +/- 2.2 J (p less than 0.001 for both voltage and energy). Mean DFT50 during lidocaine infusion was 407 +/- 41 V or 8.7 +/- 1.7 J, which were significantly higher than the baseline values of 300 +/- 38 V and 4.4 +/- 1.1 J (p = 0.004 for voltage and p = 0.013 for energy). The r values between the ULV50 and the DFT50 were 0.79 (p = 0.037) for voltage and 0.80 (p = 0.030) for energy at baseline and 0.85 (p = 0.016) for voltage and 0.88 (p = 0.009) for energy during the lidocaine infusion. However, the increments of the ULV50 (163 +/- 88 V or 7.8 +/- 4.6 J) were significantly greater than the increments of the DFT50 (107 +/- 51 V or 4.4 +/- 1.9 J, p = 0.035 for voltage and p = 0.023 for energy). Normal saline infusion did not alter DFT50 or ULV50. CONCLUSIONS. Lidocaine infusion significantly increases both ULV50 and DFT50. These results are compatible with the upper limit of vulnerability hypothesis of defibrillation. However, the greater increase of the upper limit of vulnerability than the defibrillation threshold with lidocaine infusion indicates that other factors may also need to be considered to explain the results.     

pH-dependent effects of lidocaine on defibrillation energy requirements in dogs

Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes. Results of defibrillation testing were used to derive 50% and 90% successful energy requirements (ED50 and ED90) using logistic regression and were compared with analysis of variance. Acidosis produced by hydrochloric acid infusion decreased the arterial pH from 7.40 +/- 0.05 (SD) to 7.18 +/- 0.03 (n = 8, p less than 0.01), but no significant change in ED90 was observed (14 +/- 4 to 16 +/- 6 J). Lidocaine infusion to therapeutic levels (4.2 +/- .07 micrograms/ml) at normal pH (7.42 +/- 0.02) increased ED90 from 13 +/- 3 to 17 +/- 3 J (n = 6, p less than 0.05), and subsequent acidosis (pH 7.19 +/- 0.02, p less than 0.01) exacerbated this effect of lidocaine on ED90 (22 +/- 5 J, p less than 0.05). Alkalosis produced by respirator hyperventilation increased the arterial pH from 7.41 +/- 0.03 to 7.60 +/- 0.03 (n = 8, p less than 0.01), with a fall in ED90 from 13 +/- 4 to 8 +/- 3 J (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cervical vagal nerve stimulation on defibrillation energy: a possible adjunct to efficient defibrillation

The efficacy of electrical defibrillation is considered to be related to the autonomic status. In search of a possible adjunct to enhance the therapeutic performance of an implantable cardioverter-defibrillator. we investigated whether parasympathetic manipulation by cervical vagal nerve stimulation (VNS) increases defibrillation efficacy. The effects of VNS on transcardiac defibrillation threshold (DFT) were assessed in 55 anesthetized dogs. In neurally intact dogs, right and left unilateral VNS at 10 mA for 7 seconds significantly decreased the DFT after 10 seconds of ventricular fibrillation (control: 3.1 +/- 0.9 J, right: 2.1 +/- 0.9 J [delta-35 +/- 12%, P < 0.0001], left: 2.2 +/- 0.8 J [delta-31 +/- 11%, P < 0.0005]), while bilateral VNS did not (2.8 +/- 1.0 J). In dogs with decentralized vagus nerves, both unilateral and bilateral VNS decreased the DFT. The extent of the VNS-induced decrease in DFT was dependent on the current and the duration of stimulation. We conclude that unilateral VNS decreases the DFT, while bilateral VNS paradoxically has no effect on the DFT unless the vagi are decentralized.     

Effects of pacing rate and timing of defibrillation shock on the relation between the defibrillation threshold and the upper limit of vulnerability in open chest dogs

To test the relation between the defibrillation threshold and the upper limit of vulnerability, the shock strength associated with 50% probability of successful defibrillation (DFT50) and that associated with 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 20 open chest dogs with use of the delayed up-down method, with pacing drive cycle lengths of 150 to 500 ms and either single 6-ms shocks (10 dogs) or 12-ms biphasic shocks (10 dogs) given at the mid-upslope, peak and mid-downslope of the T wave of electrocardiographic lead II. The shocks were given by means of a patch-patch configuration on the anterior and posterior surfaces of the heart, which was paced from a stimulating electrode attached to the left ventricular apex. Analysis of variance showed no statistically significant differences in ULV50 as determined with different pacing cycle lengths. For monophasic shocks, DFT50 (331 +/- 66 V or 5.8 +/- 2.7 J) was not significantly different from ULV50 determined at the mid-upslope of the T wave (318 +/- 64 V or 5 +/- 2 J). The correlation coefficients between the two values were 0.74 (p = 0.014) for voltage and 0.67 (p = 0.034) for energy. In contrast, DFT50 was significantly higher than ULV50 as determined at the peak of the T wave (219 +/- 43 V or 2.3 +/- 1 J) and mid-downslope of the T wave (200 +/- 38 V or 1.9 +/- 0.9 J). In three dogs, ventricular fibrillation could not be induced at the mid-downslope of the T wave with any baseline pacing (Si) cycle length.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of flecainide on defibrillation thresholds in the anesthetized dog

The effects of flecainide on defibrillation thresholds in 21 open chest, anesthetized dogs were studied. Defibrillation was accomplished using nontruncated exponential pulses delivered through two epicardial patches. Multiple shocks of varying energy were administered after 10 s of ventricular fibrillation in random order. The percent success was plotted against the energy delivered for each dog. A sigmoidal curve was fit to the data and the energy associated with 50% success (E50) calculated. Flecainide (n = 16) or saline solution (n = 5) was then infused and E50 again determined. Flecainide infusion produced mean (+/- standard error of the mean) plasma levels of 610 +/- 111 ng/ml. Defibrillation thresholds were obtainable in 10 of 16 dogs that received flecainide infusion. Flecainide infusion increased E50 by 75% (from 6.5 +/- 1.9 to 11.4 +/- 2.6 J) (P less than 0.05). Infusion of saline solution did not significantly affect defibrillation energy. Of 16 dogs that received flecainide infusion, 12 had one or more complications: 6 had ventricular fibrillation resistant to defibrillation, 6 developed severe hypotension after successful defibrillation and 5 had spontaneous ventricular fibrillation after successful defibrillation. These effects were not seen in any control dogs. Flecainide infusion significantly increases defibrillation threshold and has important adverse arrhythmic and hemodynamic effects in this experimental preparation.     

Improved defibrillation thresholds with large contoured epicardial electrodes and biphasic waveforms

A reduction in the shock strength required for defibrillation would allow use of a smaller automatic implantable cardioverter-defibrillator and would reduce the possibility of myocardial damage by the shock. Most internal defibrillation electrodes require 5 to 25 J for successful defibrillation in human beings and in dogs. In an attempt to lower the shock strength needed for defibrillation, we designed two large titanium defibrillation patch electrodes that were contoured to fit over the right and left ventricles of the dog heart, covering areas of approximately 33 and 39 cm2, respectively. In six anesthetized open-chest dogs, the electrodes were secured directly to the epicardium and ventricular fibrillation was induced by 60 Hz alternating current. Truncated exponential monophasic and biphasic shocks were given 10 sec later and defibrillation thresholds (DFTs) were determined. The DFT was 159 +/- 48 V, 3.2 +/- 1.9 J (mean +/- SD) for 10 msec monophasic shocks and 106 +/- 22 V, 1.3 +/- 0.4 J, for biphasic shocks with both phase durations equal to 5 msec (5-5 msec). The experiment was repeated in another six dogs in which the electrodes were secured to the pericardium. The mean DFT was not significantly higher than that for the electrodes on the epicardium: 165 +/- 27 V, 3.1 +/- 1.2 J for 10 msec monophasic shocks and 116 +/- 19 V, 1.6 +/- 0.5 J for 5-5 msec biphasic shocks. Low DFTs were also obtained with biphasic shocks in which the duration of the first phase was longer than that of the second.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrode system influence on biphasic waveform defibrillation efficacy in humans.

BACKGROUND. Several clinical studies have demonstrated a general superiority of biphasic waveform defibrillation compared with monophasic waveform defibrillation using epicardial lead systems. To test the breadth of utility of biphasic waveforms in humans, a prospective, randomized evaluation of defibrillation efficacy of monophasic and single capacitor biphasic waveform pulses was performed for two distinct nonthoracotomy lead systems as well as for an epicardial electrode system in 51 cardiac arrest survivors undergoing automatic defibrillator implantation. METHODS AND RESULTS. The configurations tested consisted of a right ventricular-left ventricular (RV-LV) epicardial patch-patch system, an RV catheter-chest patch (CP) nonthoracotomy system, and a coronary sinus (CS) catheter-RV catheter nonthoracotomy system. For each configuration, the defibrillation current and voltage waveforms were recorded via a digital oscilloscope to measure defibrillation threshold voltage, current, resistance, and stored energy. Biphasic waveform defibrillation proved more efficient than monophasic waveform defibrillation for the epicardial RV-LV system (4.8 +/- 4.1 versus 6.7 +/- 4.9 J, p = 0.047) and the nonthoracotomy RV-CP system (23.4 +/- 11.1 versus 34.3 +/- 10.4 J, p = 0.0042). Biphasic waveform defibrillation thresholds were not significantly lower than monophasic waveform defibrillation thresholds for the CS-RV nonthoracotomy system (15.6 +/- 7.2 versus 20.0 +/- 11.5 J, p = 0.11). Biphasic waveform defibrillation proved more efficacious than monophasic waveform defibrillation in 13 of 20 patients (65%) with RV-LV epicardial patches, 10 of 15 patients (67%) with an RV-CP nonthoracotomy system, and nine of 16 patients (56%) with an RV-CS nonthoracotomy system. CONCLUSIONS. Biphasic pulsing was useful with nonthoracotomy lead systems as well as with epicardial lead systems. However, the degree of biphasic waveform defibrillation superiority appeared to be electrode system dependent. Furthermore, for a few individuals, biphasic waveform defibrillation proved less efficient than monophasic waveform defibrillation, regardless of the lead system used.     

Relative effects of propranolol and timolol on ventricular fibrillation threshold and hemodynamics in the dog

The relationship between the antifibrillatory and hemodynamic effects of propranolol and timolol was tested in 32 dogs divided into three groups. In closed-chest animals (group 1), the maximal increase of the ventricular fibrillation threshold (VFT) from the control state was 67.3 +/- 22.6% (n = 5, p less than 0.01) for propranolol and 95.8 +/- 18.8% (n = 9, p less than 0.005) for timolol. These effects were paralleled by a decrease in the cardiac index of 34.7 +/- 10.2% (p less than 0.05) and 32.5 +/- 9.4% (p less than 0.02) for propranolol and timolol, respectively. The mean systemic arterial pressure (SAP) also decreased by 25.0 +/- 8.8% (p less than 0.05) and 19.2 +/- 5.1% (p less than 0.01). In open-chest animals (group 2), timolol increased the VFT by 86.6 +/- 27% (n = 5, p less than 0.05) and decreased the cardiac index by 57.3 +/- 6.3% (p less than 0.005) and the mean SAP by 28.5 +/- 2.9% (p less than 0.02). In open-chest animals with stabilized peripheral hemodynamics (group 3), VFT increased by 354 +/- 130% (p less than 0.05) and 437 +/- 144% (p less than 0.05) after the maximal administered doses of propranolol (n = 6) and timolol (n = 7), respectively. These results suggest that the electrophysiologic and hemodynamic effects of beta blockade are parallel and interdependent, with the hemodynamic deterioration markedly blunting the beneficial electrophysiologic effects.     

Success of chronic defibrillation and the role of antiarrhythmic drugs with the automatic implantable cardioverter/defibrillator

Because the automatic internal cardioverter defibrillator's long-term ability to reduce arrhythmic mortality in patients with ventricular tachycardia/fibrillation is unknown, it is important to determine whether the threshold for defibrillation changes over time. Serial defibrillation thresholds were measured in 23 patients over a mean replacement time of 24.8 +/- 7.5 months. In all cases the lead system was a superior vena cava coil to a left ventricular epicardial patch. The defibrillation threshold for the entire group increased from 12.3 +/- 4.7 J to 16.9 +/- 5.9 J (p less than 0.05). Striking increases in the defibrillation threshold were seen in the subgroup of patients taking amiodarone (from 10.9 +/- 4.3 J at implantation to 20.0 +/- 4.7 J at replacement, p less than 0.05). Defibrillation threshold decreased in patients taking no antiarrhythmic drugs or taking class I agents. Thus, the increase in mean defibrillation threshold was the result of an increase in the patients taking amiodarone. These data suggest that at initial implantation lead systems associated with the lowest defibrillation threshold should be used and the defibrillation threshold should be measured at generator change to guarantee an adequate margin of safety.     

Effects of acute and prolonged administration of propafenone on internal defibrillation in the pig.

Some antiarrhythmic sodium channel blocking drugs have been found to increase the energy necessary for internal defibrillation. Propafenone is a new drug that has been shown to be efficacious in the therapy of supraventricular and ventricular arrhythmias, and is of potential use in patients with defibrillators. The effects of short-term and prolonged propafenone administration on the internal defibrillation threshold (DFT) were determined in 43 pigs randomized to one of four groups: saline infusion (n = 10); propafenone infusion (n = 10); placebo administration for 8 days (n = 10); or propafenone administration for 8 days (n = 13). Two mesh electrodes were sutured on the right lateral and left lateral epicardial surface and current was delivered from the right electrode to the left electrode. Triplicate DFTs were obtained before and at 40 and 80 minutes after infusion of drug or placebo. In pigs receiving long-term administration, after baseline DFTs were obtained the electrodes were removed and the chest was closed. Following 8 days of drug or placebo administration, DFTs were redetermined. No changes were observed in the short- or long-term control groups. DFTs were lower after propafenone administration: either short-term infusion (20 +/- 6.2 joules at baseline; 15.6 +/- 5 joules at 40 minutes, p less than 0.05; 10.2 +/- 6 joules at 80 minutes, p less than 0.001) or long-term administration (17.8 +/- 2.6 joules at baseline versus 12 +/- 3.2 joules on drug, p less than 0.002). Decreased ventricular cycle lengths were found with acute administration of propafenone. Three pigs died during long-term administration of propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of nifedipine alone with propranolol alone for stable angina pectoris including hemodynamics at rest and during exercise

The effects of nifedipine (60 to 90 mg/day) and propranolol (240 mg/day) on symptoms, angina threshold and cardiac function were compared in a placebo-controlled, double-blind, crossover study. Five-week treatment periods with nifedipine and propranolol were compared with 2 weeks of placebo treatment in 21 men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. Compared with placebo, New York Heart Association functional class improved in patients equally with nifedipine (p = 0.001) and propranolol (p = 0.006). Frequency of chest pain decreased with nifedipine (p = 0.001) and propranolol (p = 0.01), and nitroglycerin consumption similarly decreased with both treatments. Nifedipine significantly delayed the onset of chest pain (p = 0.01) and 1 mm of ST-segment depression (p = 0.002) during bicycle exercise; smaller increases with propranolol were not statistically significant. A preferential clinical response to nifedipine (9 patients) or propranolol (6 patients) was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvements in ejection fraction at identical workloads, from 0.48 +/- 0.11 to 0.58 +/- 0.12 (p less than 0.001) and 0.56 +/- 0.14 (p less than 0.001), respectively. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14% (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of synthetic human atrial natriuretic peptide on the human coronary circulation in subjects with normal coronary arteries.

Atrial natriuretic peptide (ANP) is recognized as an "endogenous vasodilator". The purpose of this study was to determine the effects of a clinical therapeutic dose of synthetic alpha-human ANP on the coronary circulation in 15 subjects with normal coronary arteries and normal ventricular function. The epicardial coronary arterial diameter was measured by selective coronary arteriography. Coronary blood flow was estimated from the arterial cross-sectional area and the flow velocity determined using an subselective intracoronary Doppler catheter. ANP, 0.03 micrograms/min/kg given intravenously over 15 minutes, caused a dilation of the large epicardial coronary artery (n = 8): the diameter of the proximal left anterior descending artery dilated from 2.6 +/- 0.4 to 3.1 +/- 0.5 mm (p less than 0.01). Mean arterial pressure decreased from 89 +/- 5 to 83 +/- 5 mmHg (p less than 0.01); heart rate did not change during ANP infusion. Estimated coronary blood flow significantly increased (n = 6, p less than 0.01), and thus the coronary vascular resistance decreased after ANP infusion, suggesting an ANP-induced dilation of resistance vessels. The present study demonstrates that in human subjects a clinical dose of ANP by intravenous infusion dilates both the large epicardial and small resistance coronary vessels. These results suggest a potentially beneficial role for ANP in reducing the severity of myocardial ischemia in patients with ischemic heart disease.     

Lidocaine causes a reversible, concentration-dependent increase in defibrillation energy requirements

To investigate the influence of lidocaine on the energy requirements for internal defibrillation, lidocaine (n = 8) or saline solution (n = 12) was administered by intravenous infusion to 20 pentobarbital-anesthetized dogs, and the likelihood of successful defibrillation was examined at various shock energy levels before and after treatment. After lidocaine administration to a mean steady state concentration of 5.6 +/- 2.7 micrograms/ml, the mean energy required to achieve 50 and 90% success in defibrillation (E50 and E90) increased by 61.1 +/- 34.1% (mean +/- SD, p less than 0.005) and 47.1 +/- 28.6% (p less than 0.005), respectively. The steady state log lidocaine concentration correlated positively with the observed increase in E50 (r = 0.887, p less than 0.01) over a concentration range from 1.95 to 9.8 micrograms/ml. In a related experiment, lidocaine infusion was administered to five dogs and then abruptly discontinued. At energy levels achieving a mean 90.0 +/- 10.0% success in defibrillation before treatment, only 43.3 +/- 23.4% success was achieved after 60 minutes of the lidocaine infusion (p less than 0.01) at a mean plasma concentration of 8.4 +/- 2.1 micrograms/ml. The percent of successful defibrillations returned to baseline value (92.0 +/- 18.0%, p less than 0.01) after drug washout at a time when mean lidocaine concentration had declined to 1.8 +/- 0.5 microgram/ml. Lidocaine causes a reversible, concentration-dependent increase in the energy requirements for successful defibrillation; recommendations to administer lidocaine to patients with ventricular fibrillation resistant to defibrillation may need to be reviewed.     

Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia

This study evaluated the effects of transient coronary occlusion on the diameter of a nonischemic vessel or a nonischemic coronary segment proximal to the site of occlusion. Awake mongrel dogs chronically instrumented with dimension crystals, Doppler flow probes, and distal pneumatic occluders on the circumflex coronary arteries were subjected to transient 2-minute circumflex occlusions (n = 9) under constant heart rate (120 beats/min). Left ventricular end-diastolic pressure increased by 60% (from 10 +/- 1 to 16 +/- 2 mm Hg), and dP/dt decreased by 8% (from 2,048 +/- 130 to 1,885 +/- 110 mm Hg/sec); systemic hemodynamics were unaltered. Epicardial coronary diameter proximal to the site of occlusion decreased by 4.37% (from 3.62 +/- 0.25 to 3.46 +/- 0.29 mm, p less than 0.05). Constriction began 15-20 seconds after the onset of ischemia and progressed to maximum in 1-2 minutes. Combined alpha- and beta-receptor blockade (n = 8) with phentolamine (2 mg/kg) and propranolol (1 mg/kg) or cyclooxygenase inhibition (n = 5) with indomethacin (7.5 mg/kg) did not attenuate the ischemia-induced vasoconstriction response. Transient 2-minute occlusion of the left anterior descending coronary artery (n = 6) also elicited significant epicardial vasoconstriction in the circumflex coronary artery in the first minute (from 3.88 +/- 0.31 to 3.81 +/- 0.31 mm, p less than 0.05); the constriction was attenuated subsequently by an increase (25.5%) in circumflex flow. When left anterior descending occlusion was repeated (n = 6) with circumflex flow held constant, the ischemia-induced circumflex constriction was augmented; diameter decreased 3.7% (from 3.83 +/- 0.29 to 3.69 +/- 0.29 mm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of propranolol on resting and postextrasystolic potentiated left ventricular function in patients with coronary artery disease

The effect of propranolol on global and segmental left ventricular function at rest and after postextrasystolic potentiation was studied in 12 patients with chest pain. Heart rate was controlled with atrial pacing, and left ventricular cineangiograms were performed before and after 0.15 mg/kg of propranolol. During each ventriculogram a premature ventricular stimulus was introduced by means of a programmed stimulator. Propranolol decreased global left ventricular ejection fraction from 64 +/- 4.5 to 58 +/- 4.6 (p less than 0.03). Postextrasystolic potentiated global ejection fraction was not affected by propranolol (78 +/- 3.5 vs 73.6 +/- 3.4; p = NS). The area ejection fraction of the anteroapical region was decreased after propranolol (64 +/- 4.8 vs 52 +/- 6.5; p less than 0.01); however, the postextrasystolic potentiated area ejection fraction was not affected by propranolol (78 +/- 2.6 vs 71 +/- 4.6; p = NS). Frame by frame analysis of the ventriculograms demonstrated that propranolol depressed global and segmental left ventricular function by affecting the second one-third ejection fraction without influencing the first or third one-third ejection fraction. Propranolol has a small depressant effect on global and segmental left ventricular function in patients with coronary artery disease. Postextrasystolic potentiated global and segmental left ventricular function and early systolic ejection phase indices are not altered by propranolol and therefore may be useful in assessing left ventricular function in patients with coronary artery disease who are taking propranolol.     

Increasing fibrillation duration enhances relative asymmetrical biphasic versus monophasic defibrillator waveform efficacy

Biphasic waveforms reduce defibrillation threshold compared with corresponding monophasic waveforms. However, effects of fibrillation duration on relative efficacy of monophasic and biphasic waveforms are unknown. This study used a newly developed defibrillation model, the isolated right- and left-sided working rabbit heart, with epicardial defibrillation electrodes, to compare threshold for a monophasic waveform (5 msec rectangular) and an asymmetrical biphasic waveform (5 msec each pulse, V2 = 50% V1). Mean voltage defibrillation threshold (V50) was determined from sigmoidal probability of successful defibrillation versus shock intensity curves after 5, 15, and 30 seconds of fibrillation in a paired study with 10 hearts. Results showed that biphasic waveforms had significantly lower voltage and energy thresholds at all fibrillation durations and that their relative efficacy improved with increasing fibrillation duration. Biphasic voltage threshold was 38.2 +/- 2.2, 44.7 +/- 4.8, and 46.6 +/- 3.2 V after 5, 15, and 30 seconds of fibrillation compared with monophasic thresholds of 51.7 +/- 4.4 (p less than 0.002), 63.0 +/- 7.6 (p less than 0.05), and 72.1 +/- 3.9 V (p less than 0.005). Biphasic waveform energy threshold was 0.67 that for the monophasic waveform after 5 seconds of fibrillation (0.12 +/- 0.01 versus 0.18 +/- 0.03 J, p less than 0.05). The ratio between biphasic waveform threshold and monophasic waveform threshold (B/M) decreased to 0.62 at 15 seconds. At 30 seconds, B/M was 0.52 (0.17 +/- 0.02 versus 0.33 +/- 0.04 J, p less than 0.02). This study also showed that biphasic waveform threshold was a nonlinear function of monophasic waveform threshold so that improved biphasic defibrillator waveform efficacy was greatest for hearts having higher monophasic thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of propranolol and diltiazem alone and in combination on the recovery of left ventricular segmental function after temporary coronary occlusion and long-term reperfusion in conscious dogs

We evaluated the ability of propranolol and diltiazem alone and in combination to enhance the recovery of left ventricular (LV) segmental function during 1 month of reperfusion after two temporary occlusions of the left anterior descending coronary artery (LAD) in conscious dogs instrumented with ultrasonic crystals for the measurement of regional net systolic wall thickening (NET). LV segments were classified according to their contractile function after 1 hr of LAD occlusion: class 1, greater than 67% of preocclusion (control) NET; class 2, 0% to 66.9%; class 3, less than 0% (paradoxical systolic wall thinning). Propranolol (1 mg/kg iv) or diltiazem (20 micrograms/kg/min) was given 65 min after LAD occlusion in dogs that had 2 (group I) or 4 hr (group II) of LAD occlusion. Diltiazem plus propranolol (same doses) were given to another group of dogs that underwent 4 hr (but not 2) of LAD occlusion. Untreated control dogs received 25 ml of saline and underwent 2 or 4 hr of LAD occlusion. The NET of class 2 and 3 segments in group I control dogs increased significantly during 1 month of reperfusion, from 32 +/- 5% and -43 +/- 6% to 66 +/- 9% and 26 +/- 9%, respectively (p less than .05). Neither diltiazem nor propranolol enhanced the long-term recovery of these segments in group I dogs. However, diltiazem prevented further deterioration of contractile dysfunction observed in control dogs immediately after reperfusion in both segment classes. The NET of class 2 segments in group II control dogs after 4 weeks of reperfusion remained at levels observed during LAD occlusion: 30 +/- 4% to 37 +/- 12%. Class 3 NET increased from -33 +/- 5% to 12 +/- 12% with 1 month of reperfusion, but these segments were essentially akinetic. Propranolol or diltiazem alone did not produce significant overall increases in NET, but diltiazem again prevented further declines in NET of class 2 and 3 segments during early reperfusion. However, the combination of diltiazem and propranolol significantly enhanced overall recovery of class 2 NET in group II dogs (44 +/- 3% to 88 +/- 7%) and prevented the worsening of NET associated with early reperfusion. Compared with untreated dogs, propranolol plus diltiazem also significantly decreased the extent of histologic necrosis in class 2 and 3 segments as well as the macrohistochemically determined infarct size in group II dogs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sequential pulse internal defibrillation: is there an advantage to "switched" current pathways?

Sequential pulse internal defibrillation delivered via orthogonal current pathways has been postulated to improve defibrillation efficacy. The efficacy of twin truncated exponential sequential shocks was compared in four different defibrillation electrode configurations in six pentobarbital-anesthetized, open-chest dogs. Lead systems consisted of the conventional single current pathway spring-patch and patch-patch electrode configurations, as well as a multiple patch lead configuration, which utilized either a single (multiple patch-unswitched) or two different (multiple patch-switched) current pathways. Curves of percent successful defibrillation versus initial voltage and energy were constructed and the data were analyzed by logistic regression. The energy and initial voltage required for 50% successful defibrillation (E50 and V50, respectively) for each lead system were then compared. The E50 for the multiple patch-unswitched and switched lead systems (4.3 +/- 1.5 J and 4.6 +/- 1.7 J, respectively) were significantly lower than for the spring-patch (9.0 +/- 3.1 J; p less than .005) and patch-patch (6.6 +/- 1.2 J; p less than .005) lead systems. In addition, the V50 for the multiple patch-unswitched lead configuration (270.6 +/- 48.4 V) was significantly lower than that of all other lead systems (p less than .005). Therefore lead configurations utilizing multiple patch electrodes improve defibrillation efficacy over conventional lead systems, but there is no advantage to "switched" current pathways.     

Biphasic waveform external defibrillation thresholds for spontaneous ventricular fibrillation secondary to acute ischemia.

OBJECTIVES: The goal of this study was to determine if the defibrillation threshold (DFT) after spontaneous ventricular fibrillation (VF) secondary to acute ischemia differs from the DFT for electrically induced VF in the absence of ischemia in anesthetized, closed-chest dogs and pigs. BACKGROUND: The efficacy of external defibrillators has been tested mainly in animals and humans using E-VF, yet external defibrillators are often used in patients to halt S-VF. METHODS: Protocol 1: biphasic truncated exponential (BTE) waveform shocks were delivered through electrodes placed in an anterior-anterior (A-A) position (left and right lateral thorax) in nine dogs. After measuring the E-VF DFT, acute ischemia was induced with an angioplasty balloon in either the left anterior descending or left circumflex coronary artery, and the S-VF DFT was determined. Protocol 2: in a group of 12 pigs, the E-VF DFT and S-VF DFT were determined for electrodes in the A-A position and in the anterior-posterior position (A-P). Protocol 3: the E-VF DFT was determined in seven pigs. Then up to three shocks 1.5x the E-VF DFT were delivered to S-VF. If defibrillation did not occur, a step-up protocol was used until defibrillation occurred. RESULTS: Protocol 1: the DFT for E-VF was 65 +/- 28 J (mean +/- SD) compared with 226 +/- 97 J for S-VF, p < 0.05. Protocol 2: the DFT was 152 +/- 58 J for E-VF and 315 +/- 123 J for S-VF for A-A electrodes. The DFT was 100 +/- 43 J for E-VF and 206 +/- 114 J for S-VF for A-P electrodes. Protocol 3: 11/37 shocks of strength 1.5x E-VF DFT (182 +/- 40 J) stopped the arrhythmia. The episodes of S-VF not halted by these shocks required energy levels of up to 400 J for defibrillation. CONCLUSIONS: External defibrillation of S-VF induced by acute ischemia requires significantly more energy than VF induced by 60-Hz current in the absence of ischemia. A safety margin >1.5x the DFT for electrically induced VF may be necessary in BTE external defibrillators to defibrillate S-VF.     

Remodelling of the heart in DOCA-salt hypertensive rats by propranolol and by an alpha-2 agonist, rilmenidine

The effects of rilmenidine [(N-dicyclopropylmethyl) amino-2-oxazoline; S 3341], an alpha 2 agonist, on the hypertensive rat heart have been compared with those of propranolol, using a model of deoxycorticosterone acetate (DOCA)-salt hypertension. One week after nephrectomy and initial treatment with DOCA-salt, which was continued for an additional 7 weeks, the two drugs were added to the rats drinking water at a concentration of 10 mg/kg per day for rilmenidine and 15 mg/kg per day for propranolol. Both drugs had a slight and similarly significant antihypertensive effect at their respective concentrations [systolic blood pressure in controls, 141 +/- 15 mmHg (n = 20); after DOCA-salt, 209 +/- 22 mmHg (n = 24); after propranolol, 182 +/- 19 mmHg (n = 20, P less than 0.01); after rilmenidine, 192 +/- 15 mmHg (n = 19, P less than 0.05)]. They also lowered the systolic blood pressure x frequency product (P less than 0.001). Propranolol, but not rilmenidine, significantly reduced the left ventricular weight: body weight ratio [in controls, 2.00 +/- 0.2 mg/g; after DOCA-salt, 3.04 +/- 0.5 mg/g; after propranolol, 2.67 +/- 0.4 mg/g (P less than 0.05); after rilmenidine, 3.13 +/- 0.6 mg/g (P = NS)]. However, both propranolol and rilmenidine reduced left ventricular weight [in controls, 676 +/- 57 mg; after DOCA-salt, 827 +/- 114 mg; after propranolol, 732 +/- 108 mg (P less than 0.01); after rilmenidine, 760 +/- 100 mg (P less than 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)