Influence of collateral flow reduction on electrophysiologic properties of preexisting ischemic area and inducibility of ventricular arrhythmias in the dog

Electrophysiologic properties of the left ventricle, vulnerability to ventricular arrhythmias and regional myocardial blood flow (RMBF) of the left ventricle were examined during superposition of acute ischemia on a healed myocardial infarction. The left circumflex coronary artery (LCX) was ligated in 13 dogs with a 28-day-old anteroapical infarction. Six (46%) of 13 dogs had reproducible ventricular tachycardia in response to programmed ventricular stimulation before LCX ligation. Ventricular fibrillation could be induced in 2 of these 6 dogs. After LCX ligation, 11 (85%) of 13 dogs had ventricular arrhythmias induced by ventricular stimulation. Nine of 13 dogs had ventricular tachycardia and 7 of 13 dogs had ventricular fibrillation. The heterogeneity of the effective refractory period (delta ERP) and the local intraventricular conduction time (LIVCT) in the border and the infarct zones of the left ventricle increased significantly after LCX ligation. RMBF in the border and the infarct zones were markedly decreased by LCX ligation. The magnitude of reduction of RMBF was correlated significantly with the prolongation of LIVCT. In conclusion, acute critical reduction of the collateral blood supply causes a more heterogeneous refractory period and conduction delay in the preexisting ischemic area of the heart, increasing the vulnerability to lethal ventricular arrhythmias.     

Localization of coronary artery narrowings by applying R-wave amplitude correction to exercise-induced ST depression in angina pectoris and single-vessel coronary artery narrowing

This study investigated whether coronary artery narrowings can be localized by applying R-wave amplitude correction to exercise-induced ST depression in multiple unipolar precordial lead electrocardiography using 20 electrodes covering the left chest wall. Ten normal subjects and 29 patients with stable angina pectoris and single-vessel coronary artery narrowing (greater than or equal to 75% luminal diameter stenosis in only 1-vessel) participated. Of the 29 patients, 5 had left main coronary artery disease (CAD), 14 had left anterior descending CAD, 4 had right CAD and 6 had left circumflex CAD. The exercise-induced ST depression with R-wave amplitude correction was defined as the exercise-induced ST depression divided by the R-wave amplitude. The 20 points of the lead system were divided into 4 areas: the left main, left anterior descending, right and left circumflex coronary arteries. Coronary artery narrowing was supposed to be in an artery corresponding to the area where the maximal value of the exercise-induced ST depression with and without R-wave amplitude correction was situated. By applying R-wave amplitude correction, the diagnostic ability of localization of coronary artery narrowings was improved significantly from 52% to 86% (p less than 0.005). In particular, localization of the left main coronary artery narrowing was correctly diagnosed in 100% (5 of 5) of angina pectoris patients with left main CAD.     

Predicting coronary artery disease with treadmill stress testing: changes in R-wave amplitude compared with ST segment depression.

Coronary angiograms and treadmill stress tests were reviewed independently in 108 nonconsecutively selected cases. There were 16 patients (15%) with infarcts on ECG. Changes in R-wave amplitude and ST segments during exercise were evaluated to determine the sensitivity and specificity of each as a predictor of coronary artery disease (CAD). ST segment changes had a sensitivity of 49%, and a specificity of 74%. The sensitivity increased to 55% when infarcts were excluded. R-wave amplitude changes had a sensitivity of 68% and a specificity of 84%. The sensitivity increased to 78% when infarcts were excluded. An index formed by the sum of the change in R-wave amplitude and the magnitude of ST segment change yielded a sensitivity of 76% and specificity of 78%. The sensitivity increased to 84% when infarcts were excluded. There was no statistical difference between specificities for each criteria. Of those patients with an R-wave amplitude decrease, 69% had no coronary artery atherosclerosis, while 31% had significant lesions. Of those patients with no change or an increase in R-wave amplitude, 83% had coronary artery atherosclerosis, while 17% were normal. Of the 83% with coronary artery atherosclerosis, 81% had two and three vessel disease, while only 19% had single vessel disease. No change or an increase in R-wave amplitude during treadmill stress testing is a more reliable indicator of CAD in our laboratory than ST segment changes.     

Reperfusion ventricular tachyarrhythmias: Correlation with antecedent coronary artery occlusion tachyarrhythmias and duration of myocardial ischemia

The incidence and severity of reperfusion ventricular tachyarrhythmias were correlated with: (1) the duration of antecedent acute coronary artery occlusion and (2) the incidence, severity, and time course of ventricular tachyarrhythmias occurring during the antecedent period of coronary occlusion in 98 dogs studied postligation for 5 to 60 minutes. The incidence of reperfusion ventricular fibrillation (VF) increased significantly as coronary artery ligation periods were lengthened from 5 minutes to either 20 minutes (2 of 19 dogs vs 12 of 18 dogs,p < 0.001) or 30 minutes (16 of 24,p < 0.001), but notably decreased when reperfusion was delayed further from 30 minutes to 60 minutes after coronary artery ligation (4 of 18 dogs,p < 0.001). Seven dogs were resuscitated from VF during coronary ligation and all seven suffered VF on reperfusion, whereas 37 dogs were arrhythmia-free during ligation and only one (3%,p < 0.001) had VF on reperfusion, in addition, reperfusion ventricular tachyarrhythmias correlated with the occurrence of both immediate ventricular tachyarrhythmias (those peaking at 5 to 6 minutes postligation) and delayed ventricular tachyarrhythmias (those peaking at 18 minutes' postligation) of the antecedent acute ligation period. These observations provide a further basis for improved clinical understanding and management of potentially malignant tachyarrhythmias consequent to early myocardial reperfusion following acute myocardial ischemia and infarction.     

Spontaneous and electrically induced ventricular arrhythmias during acute ischemia superimposed on 2 week old canine myocardial infarction

The arrhythmogenic effect of acute reversible myocardial ischemia before and 2 weeks after experimental myocardial infarction was investigated in 37 dogs that underwent reversible 10 min occlusion of the first major marginal branch of the left circumflex coronary artery. Subsequently, 24 of the dogs underwent experimental myocardial infarction with permanent left anterior descending coronary ligation, and 13 dogs served as sham-operated controls. Two weeks later, an open chest programmed electrical stimulation was performed in the 13 sham-operated and 24 postinfarction dogs to determine its accuracy in predicting the ventricular arrhythmias that develop during a subsequent episode of acute reversible ischemia. After programmed electrical stimulation, the left circumflex marginal branch was reversibly occluded for 10 min at the same site. The incidence of spontaneous ventricular fibrillation during reversible left circumflex marginal coronary occlusion did not differ from the first to the second study in sham-operated dogs, whereas in the postinfarction dogs, it increased from 13% before infarction to 54% after infarction (p = 0.005). The outcome of programmed electrical stimulation predicted spontaneous ventricular arrhythmias during coronary occlusion in only 21% of the postinfarction dogs. The accuracy of programmed electrical stimulation was 42% and its predictive value was 47% in detecting the dogs with spontaneous ventricular fibrillation. Regional myocardial blood flow measurements by microsphere technique identified the severity of reversible ischemia in the infarct border and periinfarction zones as a correlate of spontaneous ventricular fibrillation during coronary occlusion. In contrast, total infarct size correlated with electrically induced but not with spontaneous ventricular arrhythmias.     

Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.

A specially prepared dog model of myocardial infarction was used to test the efficacy of the long-chain polyunsaturated fish oil omega 3 fatty acids eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) acids to prevent ischemia-induced malignant cardiac arrhythmias. The dogs had sustained a prior experimental myocardial infarction from ligation of the left anterior descending coronary artery, and a hydraulic cuff was implanted around the left circumflex artery at that operation. After recovery from that procedure the animals were tested during a treadmill exercise test. With compression of the left circumflex artery sensitive animals will predictably develop ventricular fibrillation (VF). In such prepared dogs an emulsion of fish oil fatty acids was infused i.v. over a 50- to 60-min period just before the exercise-plus-ischemia test, and the effect on development of VF was recorded. The infusion was 100 ml of a 10% (vol/vol) emulsion of a fish oil concentrate containing 70% omega 3 fatty acids with free eicosapentaenoic acid and docosahexaenoic acid composing 33.9% and 25.0% of that total, respectively. Alternatively, some animals similarly received an emulsion containing 5 ml of the free fatty acid concentrate plus 5 ml of a triacylglyerol concentrate containing 65% omega 3 fatty acids with eicosapentaenoic acid and docosahexaenoic acid composing 34.0% and 23.6% of that total, respectively. In seven of eight animals the infusion of the fish oil emulsion completely prevented the acute occurrence of VF in the susceptible animals (P < 0.005). In five of five of these animals the subsequent exercise-plus-ischemia test after a similar infusion of an emulsion in which soy bean oil replaced the fish oil fatty acid concentrates resulted in prompt development of VF. Possible mechanisms for this protective effect of omega 3 fatty acids against exercise and ischemia-induced malignant arrhythmias are considered.     

Effects of verapamil and lidocaine in a canine model of sudden coronary death

The efficacy of verapamil and lidocaine for treating ischemia-induced arrhythmias was determined in a conscious canine model with a previous myocardial infarction remote from the ischemic area. Temporary (up to 5.5 minutes) occlusion of the circumflex coronary artery was made in eight conscious dogs that had sustained an anterior myocardial infarction 13 to 35 days previously. Each dog served as its own control. Ventricular arrhythmias were observed in 100% of control experiments but in only 25% of experiments after verapamil pretreatment at 0.4 mg/kg body weight. Repetitive ventricular complexes, defined as two or more consecutive ventricular complexes terminating spontaneously in sinus rhythm, were seen in 88% of control experiments and 13% of verapamil experiments, whereas ventricular fibrillation was seen in 6% of control experiments but in no verapamil experiment. Thus, verapamil abolished arrhythmias or reduced the grade of arrhythmias in all dogs. Six of the eight dogs were also tested with lidocaine pretreatment at one or two doses resulting in mean plasma levels of 3.8 +/- 2.0 micrograms/ml. Ventricular arrhythmias were seen in 92% of control experiments and 100% of lidocaine experiments. The incidence of ventricular fibrillation increased from 8% in control to 60% in lidocaine experiments. It is concluded that verapamil may prevent severe ischemia-induced arrhythmias after a recent myocardial infarction, whereas lidocaine may in some cases aggravate arrhythmias.     

Nonsustained polymorphic ventricular tachycardia induced by electrical stimulation in 3 week old canine myocardial infarction

To study the electrophysiology of ventricular tachycardia 3 to 4 weeks after myocardial infarction in a canine model, an anteroapical transmural infarct was created in 40 dogs by ligation of the left anterior descending coronary artery. An average of 25 days after myocardial infarction 32 dogs that survived the infarction and 4 control dogs with a sham operation underwent open chest electrophysiologic study. No ventricular arrhythmias could be induced by any mode of ventricular stimulation in any of the four control animals. Twenty-seven of 32 dogs with myocardial infarction had reproducible ventricular arrhythmias in response to ventricular stimulation. In 17 animals sustained uniform ventricular tachycardia could be reproducibly initiated by programmed ventricular stimulation. In another 10 dogs with myocardial infarction, the same modes of ventricular stimulation reproducibly initiated ventricular fibrillation. Seven of these 10 dogs also manifested reproducible nonsustained polymorphic ventricular tachycardia, characterized by beat to beat variation in QRS complex configuration and cycle length, in response to programmed ventricular stimulation. Nonsustained polymorphic ventricular tachycardia and sustained uniform ventricular tachycardia were rarely observed in the same dog and appeared to have different underlying mechanisms.     

Experimental coronary artery ligation in conscious dogs six months after bilateral cardiac sympathectomy

The effects of left circumflex coronary artery (LCA) occlusion six months after bilateral cardiac sympathectomy on mortality, arrhythmias, and myocardial norepinephrine were studied with functional and histologic assessment of sympathetic regeneration. Bilateral stellate ganglionectomy, thoracic sympathectomy, and ansectomy (BSTG) were performed on 23 dogs and denervation was confirmed by electrical stimulation. Six months later, the LCA was ligated by a two-stage technique in these dogs (BSTG-6 mo.) and 23 control dogs in the conscious state. All dogs were autopsied at death or after 48 hours. Mortality at 15 minutes from ventricular fibrillation (VF) was 22 per cent in BSTG-6 mo. dogs and 52 per cent in control animals (p < 0.05). Mortality in the two groups at 24 hours was 44 per cent and 65 per cent, respectively. Before LCA occlusion, sinus arrhythmia was present in 23 per cent of the BSTG-6 mo. dogs and 82 per cent of the control animals. A significantly greater percentage increase in the sinus cardiac rate one minute after LCA occlusion was present in control dogs compared to BSTG-6 mo. dogs (p < 0.005). There was a later onset of ventricular arrhythmias, lesser incidence of ventricular premature beats (VPB) and ventricular tachycardia (VT), and a shorter duration of VT in BSTG-6 mo. dogs than in control animals. Myocardial norepinephrine levels were similar in BSTG-6 mo. and control dogs and fell after coronary occlusion by a comparable degree in the healthy and infarcted ventricles in both groups. Upper thoracic spinal cord stimulation (SCS) produced a mean 10 per cent increase in heart rate of three dogs four weeks after BSTG; and a 21 per cent increase in five BSTG-6 mo. animals in contrast with a 78 per cent increase in five control animals. Only one BSTG-6 mo. dog showed an almost normal (68 per cent) response to SCS. Histologic studies showed neural regeneration on the right side in one out of four BSTG-6 mo. dogs. Thus after six months, BSTG still confered a protective effect from VF following experimental coronary occlusion in conscious dogs, especially in the early, most critical period following myocardial infarction. Functional and histologic studies demonstrated sympathetic re-innervation in 20 to 25 per cent of the BSTG-6 mo. dogs.     

Cyclic AMP levels in the plasma and ischemic myocardium and free fatty-acid levels in the serum following coronary artery ligation in dogs: relation to ventricular fibrillation

This study was designed to shed light on the biochemical causes of serious ventricular arrhythmias in the early stage of acute myocardial infarction (AMI). Fourteen mongrel dogs were divided into 2 groups. One group was subjected to coronary ligation by placing silk sutures around the LAD coronary artery about 1.5 cm from its origin. All the dogs of this group were found to have ventricular tachycardia and fibrillation, starting approximately 18 min. After ligation, associated with regional accumulation of myocardial cAMP in the ischaemic zone. The increase of cAMP started about 10-15 min. before the onset of the arrhythmia. In contrast, the control group had only sutures placed without ligation and was not found to have change in myocardial cAMP within 35 min and arrhythmias at the same time. Both plasma cAMP and serum FFA were studied, but no significant changes were found. It is concluded that myocardial cAMP may play an important role in the genesis of ventricular arrhythmias in the acute ischaemic heart and it may be one of the arrhythmogenic factors to evoke ventricular arrhythmias.     

Carbon monoxide and lethal arrhythmias in conscious dogs with a healed myocardial infarction

Environmental studies suggested that exposure to carbon monoxide (CO) increases cardiovascular mortality among patients with coronary artery disease. We investigated whether, in dogs with a healed anterior myocardial infarction at low and high risk for ventricular fibrillation, acute exposure to CO has adverse effects during acute myocardial ischemia combined with exercise. One month after myocardial infarction, 17 dogs had ventricular fibrillation and 16 survived during the combined exercise and ischemia test. These tests were then repeated in all dogs with different concentrations of carboxyhemoglobin (COHb) (from 5% to 15%). With 15% COHb, heart rate (HR) at rest and during exercise was higher (p less than 0.05) than in the control tests. Surprisingly, the reflex HR response to acute ischemia was also altered; namely, the HR reduction characteristic of the low-risk animals was anticipated and accentuated (-31 +/- 25 versus 2 +/- 30 beats/min, p less than 0.05). Conversely, the HR increase characteristic of the high-risk group was reduced by CO (44 +/- 52 versus 72 +/- 43 beats/min, p less than 0.05). With 15% COHb, malignant arrhythmias occurred in two of the low-risk dogs and in none of the high-risk dogs. In the latter, CO was tested with a combination of exercise work load and myocardial ischemia duration not associated with ventricular fibrillation (VF) in the control condition. This study demonstrated that brief exposure to CO (1) profoundly alters the reflex HR response to exercise and to acute myocardial ischemia and (2) does not enhance the occurrence of malignant arrhythmias in conscious dogs with a healed myocardial infarction.     

Disparity of reperfusion arrhythmias after reversible myocardial ischemia in open chest and conscious dogs

Myocardial reperfusion after brief, reversible ischemia is frequently associated with malignant arrhythmias in experimental animals. These observations have been extrapolated to humans despite being restricted to anesthetized, open chest preparations. No data are available regarding the incidence of reperfusion arrhythmias after reversible (less than 20 minutes) ischemia in the conscious state. Thus, reperfusion arrhythmias after a 15 minute occlusion of the left anterior descending coronary artery were compared in 24 open chest dogs (17 anesthetized with pentobarbital and 7 with chloralose plus urethane) and 25 conscious, unsedated, trained dogs. The incidence of all rhythm disorders (single premature ventricular complexes, pairs, ventricular tachycardia and fibrillation) was markedly and significantly lower in conscious than in either pentobarbital- or chloralose-anesthetized dogs. The disparity was not accounted for by differences in coronary collateral flow, coronary reactive hyperemia or occluded bed size. The conscious animals, however, exhibited lower heart rates and arterial pressures during reperfusion than did the open chest dogs, suggesting a lower level of adrenergic stimulation, which might have contributed to the reduced incidence of reperfusion arrhythmias. Coronary reperfusion after 15 minutes of occlusion is unlikely to precipitate ventricular tachyarrhythmias in the conscious, trained dog, even after severe ischemia. The occurrence of these rhythm disorders in anesthetized models may reflect the influence of surgical trauma or excessive adrenergic activity, or both. Reperfusion arrhythmias after reversible ischemia may be considerably less common in the clinical setting than previously postulated on the basis of open chest animal experiments.     

Transient alterations of the QRS complex and ST segment during percutaneous transluminal balloon angioplasty of the right and left circumflex coronary arteries

The dynamic QRS amplitude changes that appear during 1-vessel percutaneous transluminal coronary angioplasty of the right and left circumflex coronary arteries were studied in 20 patients using continuous 3-lead electrocardiographic recordings representing leads aVF, V2 and V5. The balloon inflations that produced the greatest extent of ST-segment deviation were identified for each lead ("maximally ischemic periods"). QRS amplitude measurements were performed manually at both the PR and shifted J-ST baselines at 10-second intervals during these periods to determine that baseline from which the R and S waves most nearly maintained their control amplitudes. There was no significant baseline relation for either the R or the S waves in leads V2 and V5 during ischemia. However, the R-wave changes in lead aVF were significantly associated with the PR- versus the J-ST-segment baseline (p = 0.007); the S wave, when it occurred, had no tendency for either baseline. The electrocardiographic records were also examined visually for characteristics of left posterior (inferior) "periischemic block" likely to occur uniquely in patients with a dominant right or left circumflex occlusion. There were 2 patients with obstruction of the right circumflex artery who exhibited the characteristics of periischemic block during percutaneous transluminal coronary angioplasty, as evidenced by an increase in R-wave duration, amplitude or both in lead aVF.     

Transient ischaemia induced by rapid cardiac pacing results in myocardial preconditioning.

STUDY OBJECTIVE--The aim was to determine whether rapid ventricular pacing can protect against the ventricular arrhythmias occurring during a subsequent coronary artery occlusion. DESIGN--The effect was examined of two 2 min periods of pacing (300 beats.min-1) in chloralose-urethane anaesthetised dogs on a subsequent 25 min coronary artery occlusion. Ventricular arrhythmias, ST segment elevation, and inhomogeneity of conduction were analysed. EXPERIMENTAL MATERIAL--25 anaesthetised mongrel dogs in a restricted body weight range were used. MEASUREMENTS AND MAIN RESULTS--Preocclusion pacing reduced the severity of occlusion induced ST segment elevation, degree of inhomogeneity, and arrhythmias: ventricular premature beats were reduced from 528(SEM 40) to 136(45), and there were lower incidences of ventricular fibrillation (0% v 47%) and ventricular tachycardia (30% v 80%). CONCLUSIONS--Rapid ventricular pacing "preconditions" the myocardium in a manner similar to that following short coronary artery occlusions. Short periods of ischaemia no matter how induced protect the heart against the arrhythmogenic effect of a prolonged coronary artery occlusion.     

Prediction of immediate ventricular arrhythmias after coronary artery ligation.

OBJECTIVES. Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability. BACKGROUND. Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG. METHODS. With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated. RESULTS. Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1 +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/- 2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex. CONCLUSIONS. Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation.     

Antiarrhythmic and myocardial metabolic effects of verapamil during coronary artery reperfusion

The accumulation of metabolic intermediates subsequent to impaired beta-oxidation of free fatty acids has been suggested to be a cause of cellular damage and ventricular arrhythmias in the ischemic heart. The effects of verapamil on ventricular arrhythmias and free fatty acids metabolism during coronary artery reperfusion in experimental dogs were evaluated over a period of 40 minutes and followed by reperfusion for 15 minutes. One tenth mg/kg/min of verapamil was administered for 5 minutes before occlusion and followed by an infusion of 0.01 mg/kg/min to the end of the experiment. Myocardial samples were obtained from both the non-ischemic and ischemic areas after coronary artery reperfusion and then ATP, free carnitine, long chain acyl carnitine and long chain acyl CoA were measured. In the control group, 3 dogs (27%) had ventricular fibrillation and 2 dogs (18%) had ventricular tachycardia during coronary occlusion. In addition, 2 dogs (25%) developed ventricular fibrillation after reperfusion. On the other hand, all 6 dogs treated with verapamil had neither ventricular fibrillation nor tachycardia during both coronary artery occlusion and reperfusion. ATP and free carnitine levels in the ischemic area were significantly higher in the verapamil group than in the control group (ATP: p less than 0.01, free carnitine: p less than 0.05), while long chain acyl carnitine levels in the ischemic area were significantly lower in the verapamil group than in the control group (p less than 0.01). However, there was no significant change in long chain acyl CoA levels between the control and verapamil groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Computer simulation of ventricular tachyarrhythmias during coronary artery ligation and release.

A computer (PDP-10) simulation model was constructed using rapid, simultaneous measurements of effective refractory period (ERP), ERP dispersion (RPD), premature ventricular beat (PVB) thresholds, and multi-directional conduction times during coronary artery ligations and release in the anesthetized dog. In addition, estimates of currents of injury between ischemic and non-ischemic electrodes were included based on published data from electromagnetic recordings in dogs. Propagated PVB's were inscribed by the model when criteria for excitation, dispersion, and conduction were met based on known electrophysiological characteristics of heart muscle. The model correctly predicts high vulnerability to arrhythmias at three to seven minutes of ligation, stabilization at 10 to 15 minutes of ligation, and decreased vulnerability by lidocaine during ischemia. There was no arrhythmia when ischemic thresholds were increased by the drug before significant RPD and conduction prolongation developed. Vulnerability to arrhythmias was also predicted by the model after release of short (five minute) and long (15 minute) ligation. Since (experimentally) arrhythmias occurred much more frequently after long ligations, additional yet unknown factors other than those considered in the model must be operative in the genesis of reperfusion arrhythmias. This conclusion is supported by the observations that high ischemic thresholds induced by lidocaine returned to normal slowly after ligation release, and despite this protective effect, experimentally, lidocaine failed to abolish reperfusion arrhythmias.     

Ventricular fibrillation resulting from ischemia at a site remote from previous myocardial infarction: A conscious canine model of sudden coronary death

In anesthetized dogs, a 30 gauge silver wire was inserted into the lumen of the left circumflex (LC) coronary artery and myocardial ischemic injury was produced by subsequent occlusion of the left anterior descending (LAD) coronary artery for 90 minutes followed by reperfusion through a critical stenosis. Four days after acute myocardial infarction, with the dog ambulatory, the intimai surface of the LC coronary artery was injured by applying a 150 μA anodal current. Coronary artery thrombosis and subsequent reduction in coronary artery blood flow were accompanied by S-T segment changes at 132 ± 65 minutes (mean ± standard deviation [SD]) with ventricular fibrillation (VF) occurring in 29 of 30 dogs (97% ) at 141 ± 60 minutes. Infarct mass in the LAD distribution was 15 ± 8% of total left ventricular mass with no histochemical evidence of irreversible ischemic injury in the LC coronary artery distribution. VF was preceded by the development of delayed electrical activity within the LC coronary artery distribution, and the development of ventricular arrhythmias accompanied by continuous local electrical activity within the subepicardial region of the distribution of the LC coronary artery. In 10 dogs with placement of a critical stenosis around the LAD coronary artery without earlier occlusion and reperfusion, LC intimal injury and subsequent thrombus formation resulted in only 2 deaths (20% ) from VF. Thus, acute myocardial ischemia at a site distant to a previous myocardial infarction enhances the likelihood of primary VF in the conscious dog. This model of sudden coronary death may simulate the clinical state in man and might serve as an appropriate model for the study of electrophysiologic mechanisms associated with the development of VF and for the evaluation of potential antifibrillatory drugs.     

R-wave amplitude responses to rapid atrial pacing: a marker for myocardial ischemia

Atrial pacing-induced changes in the sum of R-wave amplitude were measured in leads V5, X, Y, and Z at rates of 100 bpm (phase I), 150 bpm (phase II), and immediately after pacing (phase III) in 33 patients undergoing cardiac catheterization for evaluation of chest pain. Seventeen (51%) patients showed evidence of ischemia during atrial pacing (typical anginal pain and/or at least a 1 mm ST-segment depression) and 16 (49%) showed no evidence of ischemia. Mean R-wave amplitude changes from baseline in the ischemic patients were: phase I: -8% (p = not significant), phase II: +3% (p = not significant), and phase III: +13% (p less than 0.01); and in nonischemic patients: phase I: -11% (p less than 0.02), phase II: -18% (p less than 0.01), and phase III: +2% (p = not significant). These two distinct patterns of R-wave amplitude changes were highly sensitive (85%), specific (92%), and predictive (92%) for identifying patients with myocardial ischemia but did not correlate (p = not significant) with either the angiographically determined extent of coronary artery obstructive disease (CAD), resting left ventricular function, or the dynamic, atrial pacing-induced changes in left ventricular dimensions determined by M-mode and two-dimensional echocardiography. Thus, R-wave amplitude changes induced by atrial pacing can be used to identify patients with myocardial ischemia independent of coronary anatomy or resting left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Superoxide dismutase reduces reperfusion arrhythmias but fails to salvage regional function or myocardium at risk in conscious dogs

To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p less than 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6 +/- 5.8%, 37.4 +/- 6.4%, 28.3 +/- 5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations.