The effects of lidocaine on the ventricular fibrillation threshold and primary ventricular fibrillation following acute experimental coronary occlusion

Summary Experiments were performed on 39 anaesthetized open-chest dogs (BW 16–33 kg) to examine the effect of lidocaine on the frequency of primary ventricular fibrillation (VF) and the time course of the ventricular fibrillation threshold (VFT) (train of stimuli-method) following acute coronary artery occlusion, and also to study the effects of lidocaine on the VFT of non-ischaemic heart at different therapeutic and high non-therapeutic doses. At effective plasma levels of lidocaine usually reached in clinical therapy (130–480 g/l) there was no measurable increase in VFT compared to control values. The drop in VFT following acute ligation of the left anterior descending coronary artery (LAD) was neither eliminated nor even merely diminished. After occlusion of the left circumflex coronary artery (CIR), the incidence of spontaneous VF was not reduced in comparison to a control group. With regard to the doses administered and the plasma levels of lidocaine achieved, only the application of clinically extremely high or toxic doses resulted in increases in VFT in the non-ischaemic heart.Therefore it cannot be expected that there exists a protective effect of clinically recommended doses of lidocaine in preventing primary VF during the early phase of arrhythmia following acute coronary occlusion.Dedicated to Prof. Dr. O. H. Arnold, Essen, to his 70th birthday     

Effects of ethmozine on ventricular fibrillation threshold in acute occlusion of the coronary artery in dogs

In experiments on dogs with acute left descending coronary artery occlusion, ethmozine (3 mg/kg) was tested for effects on the threshold of ventricular fibrillation occurring as a result of high-frequency electric stimulation. Two hours after occlusion, the fibrillation threshold became significantly lower than the control values. Ethmozine used in this period enhanced the ventricular fibrillation threshold in some experiments and diminished it in the others. Four hours following the occlusion, the fibrillation threshold did not differ from the control ones. Ethmozine given in this period caused a significant increase in the ventricular fibrillation threshold. It was concluded that 4 hours after the onset of experimental myocardial infarction are the minimal time period following which administration of ethmozine failed to decrease electric stability of the heart.     

The effects of ventricular fibrillation duration and site of initiation on the defibrillation threshold during early ventricular fibrillation

Objectives. The purpose of this study was to determine if the defibrillation threshold (DFT) is lower during the first few cycles of ventricular fibrillation (VF) than after 10 s of VF and, if so, if the effect is caused by local or global factors.Background. The DFT may be low very early during VF because: (1) for the first few cycles VF arises from a localized region close to a defibrillation electrode where the shock field is strong (local factors), or (2) during early VF the effects of ischemia and sympathetic discharge have not yet fully developed and the heart has not yet completely dilated (global factors).Methods. Protocol 1 included seven pigs in which a defibrillation electrode and a pacing catheter were both placed in the right ventricular apex. VF was induced by delivering a high current premature stimulus from the pacing catheter that should have caused reentry confined to the right ventricular apex for the first few cycles of VF. A bipolar electrogram was recorded from the tip of the defibrillation catheter. Using a three reversal up–down protocol, the DFT was determined for biphasic shocks delivered after 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 activations in this electrogram and after 10 s (control). Protocol 2 included seven pigs undergoing the same procedure as in protocol 1 except that an additional pacing catheter was placed in the left ventricle. Defibrillation thresholds were determined after 1, 2, 3, 4 and 5 VF activations following VF induction from the right ventricle (RV) or the left ventricle (LV) and after 10 s (control).Results. In protocol 1, the mean ± SD DFTs were lower during the first three cycles than after 10 s of VF (3.0 ± 4.1 J for the first VF cycle vs 15.8 ± 6.6 J after 10 s of VF, p < 0.05). In protocol 2, the DFT for the first few cycles of VF induced away from the defibrillation electrode in the LV (6.9 ± 1.4 J for the first VF cycle) was significantly lower than that after 10 s of VF (16.0 ± 2.2 J), whereas the DFT for the first few cycles induced near the defibrillation electrode in the right ventricular apex was significantly lower (2.3 ± 2.7 J for the first VF cycle) than that induced from the LV.Conclusions. This study demonstrates that the DFT is significantly lower during the first few VF cycles of VF than after 10 s of VF and that this decrease may be caused by both local factors and global factors. These results provide an impetus for exploring earlier shock delivery in implantable devices.     

Influence of sympathetic tone on ventricular fibrillation threshold during experimental coronary occlusion.

The effects of increased and decreased cardiac sympathetic tone and coronary occlusion on ventricular fibrillation were determined in 14 open chest dogs anesthetized with sodium pentobarbital. Heart rate was kept constant by pacing the right atrium at cycle lengths of 500 msec. Ventricular fibrillation threshold was measured by delivering 350 msec trains of constant current stimuli with a frequency of 100 hertz and 2 msec duration. The minimal current of the train that induced fibrillation was taken as the ventricular fibrillation threshold. In seven animals, the effects of stellate stimulation were studied. Ventricular fibrillation threshold was measured during control periods, after 2 minutes of cornoary occlusion, after 2 minutes of stellate stimulation and after 2 minutes of stellate stimulation and coronary occlusion. Coronary occlusion alone decreased ventricular fibrillation threshold an average of 35 percent of control valvues and stellate stimulation alone decreased the threshold an average of 42 percent of control values. The combination of both these interventions decreased ventricular fibrillation threshold an average of 63 percent of control values. The effects of stellate ablation were studied in seven animals. Ventricular fibrillation threshold was measured during control periods, and during coronary occlusion before and after stellate ganglionectomy. Stellectomy increased the threshold an average of 31 percent above control values. After stellectomy, coronary occlusion decreased ventricular fibrillation threshold by only 11 percent of control values, a value 26 percent higher than the threshold during coronary occlusion before stellectomy. These findings may have therapeutic implications for the management of arrhythmias in patients with acute myocardial infarction or some forms of central nervous system disease.     

Left ventricular diastolic dysfunction in coronary artery disease: effects of coronary revascularization.

Left ventricular diastolic dysfunction was studied globally and regionally in patients with coronary artery disease, and the effects of coronary revascularization were evaluated. A total of 25 patients with angina pectoris who had a stenotic lesion (greater than or equal to 90%) in only left anterior descending branch underwent coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) in 13 patients and coronary artery bypass graft (CABG) in 12]. Nine patients with normal coronary artery were studied as controls. Left ventricular volume and radial axes were measured on serial frames of one cardiac cycle by cine left ventriculography. The radial axes were drawn from the left ventricular gravity to left ventricular wall at every 20 degrees. Left ventricular filling fraction and distension rate of radial axes were calculated at the times of 25%, 50%, 75%, and 100% of diastolic period, 100% being end-diastole. Although there were no significant changes of the systolic function by revascularization, the filling fraction increased from 11.2 +/- 2.6 to 14.5 +/- 3.5% (p less than 0.001) at 25% time of diastole, from 29.9 +/- 4.9 to 32.5 +/- 5.0% (p less than 0.05) at 50% time in the PTCA group, and from 11.8 +/- 3.7 to 13.4 +/- 3.8% (p less than 0.01) at 25% time in the CABG group. The distension rate of radial axis to the anterior wall also increased significantly at 25% and 50% time of diastole after revascularization, and the change was marked in the PTCA group. However, these increases did not apply to the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial fibrillation in coronary artery disease

To answer whether atrial ischemia plays an important role in the genesis of atrial fibrillation in patients with coronary artery disease, we analyzed the electrocardiograms obtained at the time of coronary angiography and left ventriculography in 3220 consecutive patients. Atrial fibrillation was found in 74 (2.3%). Among those with significant coronary artery disease were 49 (66.2%) patients with atrial fibrillation and 88.5% with sinus rhythm (P<0.02). Angiograms of patients with atrial fibrillation and significant (>50%) coronary stenosis were re-evaluated and results compared to the control group which consisted of 108 consecutive patients who were in sinus rhythm at the time of coronary angiography. There were no differences between groups with respect to either frequency of injury to the right coronary artery and circumflex branch of left coronary artery or localization of the injury to this region (before or after atrial branch take-off). But patients with atrial fibrillation significantly more often had heart failure (55.1% versus 18.5%, P<0.001) and three vessel disease (30.5% versus 20.4%, P=0.05) as well as mitral valve insufficiency (20.4% versus 10.2%, P<0.05). In conclusion, in patients with coronary disease, systolic heart failure may be more important than atrial ischemia in causing atrial fibrillation.     

Chronic atrial fibrillation and coronary artery disease.

Retrospective study of the incidence of atrial fibrillation (AF) in 841 consecutive patients who had selective coronary arteriography and left ventricular catheterization from January 1, 1966 to December 31, 1976 was undertaken. There were 496 patients with coronary artery disease (CAD), 138 with valvular disease or cardiomyopathy, and 207 were normal. Chronic atrial fibrillation was present in 45 patients, of whom 35 has valvular disease or cardiomyopathy. One had coronary artery disease and 9 were normal. Chronic atrial fibrillation in coronary artery disease was rarely found.     

Electrocardiographic measures of ventricular repolarisation dispersion in patients with coronary artery disease susceptible to ventricular fibrillation

OBJECTIVE: To study electrocardiographic measures of ventricular repolarisation dispersion in patients prone to ventricular fibrillation compared with controls matched for the extent of coronary heart disease and the use of beta blockers. DESIGN: A case-control study. SETTING: Cardiovascular laboratory of a tertiary referral centre. PATIENTS: Fifty patients with documented ventricular fibrillation not associated with acute myocardial infarction, and their controls matched for sex, age, number of diseased coronary vessels, left ventricular ejection fraction, previous myocardial infarction and its location, and the use of beta blockers. MAIN OUTCOME MEASURES: Electrocardiographic measures of QT, JT, and Tend interval dispersions in a 12 lead electrocardiogram. RESULTS: The ventricular fibrillation patients compared to controls showed increased mean (SD) QTapex dispersion (53 (18) ms v 44 (18) ms, respectively; p < 0.01) and mean (SD) Tend dispersion (46 (17) ms v 38 (15) ms, respectively; p < 0.05). CONCLUSIONS: Increased QTapex and Tend dispersions are associated with a susceptibility to ventricular fibrillation even when the extent of the coronary heart disease and use of beta blockers are taken into consideration. However, because of a considerable overlap between the groups, measures of QT dispersion assessed from a 12 lead electrocardiogram do not provide clinically useful information for identification of patients at risk of sudden cardiac death.     

Significance of inducible ventricular fibrillation in patients with coronary artery disease and unexplained syncope

OBJECTIVES: This study was designed to determine the incidence and prognostic significance of inducible ventricular fibrillation (VF) in patients with coronary artery disease (CAD) and unexplained syncope. BACKGROUND: Current American College of Cardiology/American Heart Association practice guidelines recommend implantation of internal cardioverter-defibrillators (ICDs) in patients with unexplained syncope in whom either ventricular tachycardia (VT) or VF is inducible during electrophysiologic (EP) testing. Although the prognostic significance of inducible monomorphic VT is known, the significance of inducible VF remains undefined. METHODS: We evaluated 118 consecutive patients with CAD and unexplained syncope who underwent EP testing. Sustained monomorphic VT was inducible in 53 (45%) patients; in 20 (17%) patients, VF was the only inducible arrhythmia; and no sustained ventricular arrhythmia was inducible in the remaining 45 (38%) patients. The latter two groups of 65 (55%) patients make up the study population. RESULTS: There were 16 deaths among the study population during a follow-up period of 25.3 +/- 19.6 months. The overall one- and two-year survival in these patients was 89% and 81%, respectively. No significant difference in survival was observed between patients with and without inducible VF (80% power to detect a fourfold survival difference). CONCLUSIONS: In 17% of patients with CAD and unexplained syncope, VF is the only inducible ventricular arrhythmia. Within the limits of this pilot study, long-term follow-up of patients with and without inducible VF demonstrates no difference in survival between the two groups. Therefore, the practice of ICD implantation in patients with CAD, unexplained syncope and inducible VF, especially with triple ventricular extrastimuli, may merit reconsideration.     

The effects of the d- and l-optical isomers of propranolol on the ventricular fibrillation threshold

The minimum current required to induce ventricular fibrillation was determined in 22 sodium pentobarbital anesthetized open chest dogs in the presence of the d- or l-isomers of propranolol at concentrations of 0.2, 0.5, and 1.0 mg/kg. The hearts were paced from the right atrium at a constant basic cycle length of 350 msec and the current was delivered during the vulnerable period to the right ventricle as a 120 msec train of 4 msec square wave pulses at 100 Hz. The l-isomer of propranolol increased the ventricular fibrillation threshold (VFT) above control values at all concentrations; the maximum increase ranged from 17.8 to greater than 420.8% change from control. In contrast, the d-isomer caused only a small increase in the ventricular fibrillation threshold with the maximum increase ranging between 14.0 and 65.2% change from control. The maximum increase in VFT for the racemic mixture of propranolol was 44.7 to greater than 500.0% above control and was similar to the l-isomer alone. Since the beta-blocking potency of the l-isomer is 100 times the potency of the d-isomer we conclude that propranolol's action in increasing the ventricular fibrillation threshold is dependent on its beta-blocking effect.     

Effects of a thromboxane A2 synthetase inhibitor on ventricular fibrillation threshold during coronary artery occlusion and reperfusion

The effects of a new thromboxane A2 synthetase inhibitor (DP-1904) on electrical stability of the heart were tested in anesthetized, open chest dogs. The incidence of spontaneous ventricular arrhythmias, ventricular refractory period and ventricular fibrillation threshold (VFT) during ligation of the left anterior descending coronary artery (LAD) for 180 min and after reperfusion were measured as indices of stability. Ventricular fibrillation and ventricular tachycardia occurred spontaneously after ligation of LAD in 56% of 9 control dogs and 29% of 7 dogs which received intravenous DP-1904 (100 mg) before ligation of LAD (n.s.). In the control group, the ventricular refractory period decreased in the ischemic region; consequently, the difference in refractory period duration between the ischemic and non-ischemic regions (i.e., dispersion) increased 30 min after coronary ligation (7 +/- 9 ms vs 32 +/- 17 ms, p less than 0.05). The dispersion at 30 min after coronary ligation, though, was not affected in the DP-1904 treated group (2 +/- 4 ms vs 10 +/- 9 ms, n.s.). The VFT (determined with pulse trains) decreased from 28 +/- 5 mA to 15 +/- 11 mA (p less than 0.05) 30 min after coronary ligation in the control group, but was not affected (30 +/- 0 mA vs 27 +/- 4 mA) in the DP-1904 group. The plasma concentration of thromboxane B2 decreased after DP-1904 administration (baseline vs 30 min after coronary ligation: 475 +/- 165 pg/ml vs 165 +/- 74 pg/ml, n = 3, p less than 0.05), while the concentration of 6-keto-prostaglandin F1 alpha increased gradually. In conclusion, DP-1904 prevents a decline in electrical stability in the ischemic region of the canine heart during coronary occlusion.     

The initiation of ventricular tachycardia and fibrillation in experimental coronary artery occlusion

Ninety-four dogs were studied electrocardiographically following acute occlusion of the circumflex branch of the left coronary artery in an attempt to elucidate the electrogenesis of ventricular arrhythmias.

In terminal ventricular fibrillation, T wave interruption was invariably present, occurring at the peak or on the downslope of the T wave, and was progressively greater in two thirds of the recorded episodes. In nonterminal ventricular tachycardia, T wave cutoff (present in only one fourth of the episodes) was found near the end of the T wave and was progressively less in successive cardiac cycles.

The commonest type of T wave interruption associated with ventricular arrhythmias occurred when an extrasystolic T wave was interrupted by the QRS of the succeeding ventricular extrasystole (V by V type). This was not seen in isolated ventricular premature beats.

The drop in arterial pressure was quantitatively related to the degree of T wave interruption.     

Modification of ventricular fibrillation latency following coronary artery occlusion in the conscious pig.

Abrupt occlusion of the left anterior descending coronary artery was performed on 45 unanesthetized farm pigs in order to evaluate the relative effects on the latency to ventricular fibrillation (VFL) of 1) adaptation of the animals to the laboratory, and 2) beta-receptor blockade by propranolol. Compared to control values, VFL was greatly lengthened (i.e., VF delayed or prevented) by adaptation (P smaller than 0.01), was shortened by large (2 MG/KG) doses of racemic propranolol in unadapted animals (P smaller than 0.02), and was again increased while under the influence of the drug, by adaptation (P smaller than 0.051). Neither a lower (0.02 mg/kg) dose of racemic propranolol, 2 mg/kg of dextropropranolol, nor ventricular pacing to a higher heart rate had an effect on VFL. The results suggest that reduced psychological stress was very effective in retarding or preventing the onset of VF, that low doses of propranolol were ineffective, and that higher doses were deleterious in unadapted animals.