Electrophysiologic observations during the spontaneous initiation of ischemia-induced ventricular fibrillation

Electrophysiologic features of spontaneous, ischemia-induced ventricular fibrillation were studied in 17 dogs using multiple endocardial bipoles positioned in normal and ischemic zones and at the border of ischemic myocardium. All dogs showed ventricular tachyarrhythmias prior to the initiation of ventricular fibrillation. The heart rate prior to the fatal arrhythmia in the ventricular fibrillation dogs was significantly faster than that of nonventricular fibrillation dogs. There was no difference in the coupling intervals of the initial premature complex between episodic and sustained ventricular arrhythmia in most dogs. However, shorter coupling intervals initiated sustained arrhythmia in some dogs. Sites of initiation of arrhythmia were mostly in the ischemic zone. Furthermore, diastolic electrical activity was consistently observed in the ischemic zone during fatal arrhythmia in dogs showing diastolic activity. Cycle length during the fatal arrhythmia prior to ventricular fibrillation gradually shortened, whereas cycle length of episodic ventricular tachycardia remained approximately 200 msec followed by lengthening prior to restoration of sinus rhythm. The disparity of local activation (time differences between the earliest and latest onset of the activation in the five recording sites) increased during the fatal arrhythmia. Examples of progressive intraventricular block (Wenckebach-like) between the border and the center of ischemic myocardium leading to ventricular fibrillation and resynchronization of this disparity leading to the termination of ventricular tachycardia are shown. The recording of continuous electrical activity using bipolar electrodes with an interelectrode distance of 1 mm suggests a smaller reentrant pathway during fatal arrhythmia. Our observations confirm the importance of endocardial recordings within ischemic myocardium, and adds new insight into the events leading to both episodic and sustained ventricular tachycardia/fibrillation.     

Observations on the relationship between digital heat loss and systemic hemodynamics in patients with heart disease

A concomitant study of finger heat discharge and systemic hemodynamics was undertaken in a series of 19 patients (mean age 54 years) suffering from various forms of heart disease. Finger heat discharge, as measured by calorimetry, was found to correlate significantly with mean circulation time (?0.760), cardiac index (+0.649), systemic vascular resistance (?0.615), stroke work index (+0.649), mean pulmonary artery pressure (?0.596), mean pulmonary capillary wedge pressure (?0.554), stroke index (+0.541), appearance time (?0.502) and mean right atrial pressure (?0.453). There was no significant correlation between finger heat discharge and mean arterial blood pressure, LV $\text{dp}\text{dt}{}_{\max }$, and heart rate. An effect of heart failure on finger heat discharge was found. When evidence of forward failure and also possibly backward failure was found, mean finger heat discharge was significantly diminished. When both forward and backward failure were present together, mean finger heat discharge fell still further.     

Comparison of clinical signs and hemodynamic state in the early hours of transmural myocardial infarction

The initial PCW, Killip-Scheidt classification, presence of third heart sound, and mortality were compared in 90 patients presenting with acute transmural myocardial infarction. Clinical and hemodynamic assessment was performed within 12 hours (time to clinical classification = 4.7 ± 2.7 hours (mean ± SD), time to hemodynamic assessment = 5.8 ± 2.4) of the sentinel event. A poor correlation was observed between early Killip-Scheidt clinical classification and early hemodynamic state when measured as percent correct classification (66%) or as a Kappa statistic (36% for the total population, 9% for nonsurvivors). Increased initial LVFP (>18 mm Hg) was associated with increased mortality (p < 0.01) and early clinical classification was not. Addition of third heart sound information did not alter this observation.     

Intracoronary thrombolysis in evolving myocardial infarction

After experimental studies in dogs confirmed the feasibility and safety of rapid intracoronary thrombolysis by local infusion of Thrombolysin (streptokinase and plasmin), intracoronary thrombolysis was attempted in 20 patients with evolving myocardial infarction who were hospitalized within 3 hours from the onset of symptoms during the day and within 2 hours at night. Thrombolysin was infused in the immediate vicinity of the site of coronary occlusion using a 0.85 mm outer diameter catheter advanced through the lumen of the Judkins catheter. Reperfusion was achieved in four patients after an average of 43 minutes of Thrombolysin infusion at a rate of 2000 IU/min and in 15 patients after an average of 21 minutes of Thrombolysin infusion at a rate of 4000 IU/min. The failure to open the artery in one patient may have been caused by our inability to advance the infusion catheter close to the site of occlusion. Rethrombosis occurred in one patient 8 days after reperfusion and 2 days after discontinuation of anticoagulants because of a history of chronic alcoholism. Wall motion and perfusion studies showed improvement following reperfjsion. Patency of the artery was achieved an average of 4 hours after the onset of symptoms. The need for earlier reperfusion is emphasized.     

Electrophysiologic effects of bretylium on canine ventricular muscle during acute ischemia and reperfusion

Electrophysiologic effects of bretylium were assessed on a recently developed animal model for analysis of conduction of premature impulses and excitation threshold. Bretylium was administered intravenously 10 mg/kg over 10 minutes followed by 2 mg/min of infusion immediately after coronary ligation. Conduction of the premature impulse was recorded in the epicardial and endocardial sites both in the base-to-apex and apex-to-base directions, in the normal, in the center, and across the border of ischemic myocardium. Compared to the control group of animals, bretylium did not cause any significant change in the conduction characteristics in the ischemic myocardium; however, it delayed the conduction of premature impulses in the normal myocardium. Thus the disparity in conduction times between the normal and the ischemic myocardium was lessened by bretylium. Further, conduction of impulses from normal tissue across the border of ischemia was also delayed. Bretylium also decreased the excitability threshold in the ischemic myocardium, although the normal myocardial excitation threshold was unaffected. These unique effects of bretylium on conduction and excitability in the normal, in the center, and across the border of ischemic myocardium, when a therapeutic dosage of the drug is used, further validate its antiarrhythmic potential and offer an insight into its mechanism of action in the setting of acute myocardial ischemia.     

The electrophysiologic effects of intravenous lidocaine in the Wolff-Parkinson-White syndrome

Twelve patients with the Wolff-Parkinson-White syndrome underwent electrophysiologic study, before and after the bolus intravenous administration of lidocaine, 1 mg./kg. There was no significant increase in the effective refractory period of the anterograde AV node pathway, the anterograde or retrograde accessory pathway, or the atrial or ventricular muscle; intravenous bolus administration of lidocaine is unlikely to terminate the re-entry tachycardias, or decrease the rate of the ventricular response in atrial fibrillation, in the WPW syndrome. There was no significant increase in the anterograde or retrograde AV conduction times; bolus administration of lidocaine is unlikely to decrease the rates of the re-entry tachycardias. In addition, lidocaine failed to alter significantly features related to tachycardia initiation. Except in isolated, unpredictable cases, intravenous bolus administration of lidocaine is not likely to be of benefit in the supreventricular tachyarrhythmias of the WPW syndrome.     

Electrophysiologic studies in survivors of late cardiac arrest after myocardial infarction

Nine patients resuscitated from life-threatening ventricular arrhythmias (VA) within 3 months of an acute myocardial infarction (AMI) underwent electrophysiologic studies (EPS) with clinical follow-up for at least 12 months. Neither reinfarction, drug therapy, nor electrolyte imbalance was a precipitating factor. VA was induced by ventricular pacing in six of nine patients. Five patients were prescribed empiric drug therapy, while the four other patients had repeated EPS to select optimal drug therapy. One patient remained unstable and died of VA in the hospital. No patient was discharged and successfully maintained on a drug known to prevent induction of VA, yet only two patients (25%) had a further recurrence of VA, one fatal. Our findings suggested that either drug therapy that is determined empirically or found not to suppress the induction of VA during EPS can be associated with a successful outcome in some of these patients, or the natural history of VA after myocardial infarction is that they are self-limiting in the absence of a new ischemic event.     

The precordial ECG belt for obtaining rapid reproducible precordial leads

A new, stretchable precordial ECC belt is described. It represents an excellent method for obtaining reproducible, accurate precordial ECGs and is especially useful in women and individuals with abnormal chest configurations.     

Electrophysiologic and hemodynamic actions of diltiazem: Disparate temporal effects shown by experimental dose-response studies

Diltiazem (DT), a potent slow channel blocker, has been found to be clinically useful for treatment of coronary vasospasm, hypertension, and tachyarrhythmias. Nevertheless, only limited data are available on the hemodynamic and electrophysiologic effects of DT. Atrial, His, right ventricular apex, aortic, and Swan-Ganz thermodilution catheters were used in 10 anesthetized dogs, and recordings were made during control period and after each of four infusions of DT (0.01, 0.02, 0.04, and 0.08 mg/kg/min) each lasting 30 minutes. Results showed that heart rate, pulmonary capillary wedge pressure, stroke volume, and HV interval did not change significantly. However, two dogs had second-degree AV block and a third had escape junctional rhythm during DT 0.08 mg/kg/min. Mean aortic pressure (AP¯), corrected sinus node (SN) recovery time, and systemic vascular resistance (SVR) were significantly reduced, whereas AH interval, AV functional and effective refractory periods were prolonged by DT. AV nodal refractory periods and AH interval were the only parameters significantly affected at DT 0.02 mg/kg/min. SN recovery time was significantly shortened at DT 0.04 mg/kg/min, whereasAP¯ and SVR fell significantly at DT 0.08 mg/kg/min. DT had significant electrophysiologic effects at low doses, whereas hemodynamics were significantly altered only at high doses. Further, major electrophysiologic effects were on the AV node with lesser effects on SN function. Therefore, at a dose when antiarrhythmic effects are evident, the safety of diltiazem is corroborated by lack of adverse hemodynamic effects.     

Effects of intravenous verapamil on hemodynamics in patients with heart disease.

The hemodynamic effects of intravenous verapamil (10 mg.) were evaluated in 13 patients with coronary artery disease and in seven patients with rheumatic valvular disease during cardiac catheterization. The peak effects were apparent at 3 to 5 minutes after injection and lasted about 10 minutes. The mean arterial pressure fell from 97.8 +/- 3.4 to 85.9 +/- 2.7 mm. Hg (-12%; p less than 0.01) accompanied by a significant decrease (-21%, p less than 0.001) in systemic vascular resistance (from 1435 +/- 80 to 1131 +/- 82 dynes-sex.-cm.-5) with an increase in left ventricular end-diastolic pressure (from 11.0 +/- 0.9 to 15.0 +/- 1.0 mm. Hg; +36%, p less than 0.01) and a reduction in LV dp/dt max (from 1343 +/- 152 to 1007 +/- 102 mm. Hg/sex.; -25%, p less than 0.05). The changes in heart rate (from 75.7 +/- 3.0 to 80.2 +/- 2.8 beats/min.), cardiac index (from 3.17 +/- 0.15 to 3.61 +/- 0.17 L./min./M.2), left ventricular minute work (from 3.63 +/- 0.28 to 3.31 +/- 0.23 Kg.-m./min./M.2) and mean pulmonary artery pressures (from 15.7 +/- 1.0 to 18.1 +/- 0.8 mm. Hg) were not statistically significant. The intrinsic negative inotropic action of verapamil is, therefore, minimized by its effect on afterload so that cardiac index is not reduced by the drug in patients with cardiac disease.     

Computer enhancement of direct and venous-injected left ventricular contrast angiography

Following peripheral venous injection of radiopaque contrast material, a new on-line automatic computer image enhancement technique was employed to delineate the left ventricular (LV) endocardial silhouette in 10 dogs and 8 patients. This technique employs a very fast analog-to-digital conversion system capable of digitizing video frames on-line. By averaging into digital image memory the first 30 video frames and then subtracting each incoming frame from this memory, most of the background is eliminated, leaving only the contrast-filled ventricle. Since the technique employs conventional fluoroscopic exposure rates rather than cineangiography, there is marked reduction in xray exposure. An in vitro study using the Rando whole body phantom demonstrated that a 5 mm object with 2% contrast could be imaged within the complex chest anatomy with an incident exposure rate of only 30 mR/sec, using digital subtraction followed by contrast enhancement. In vivo studies were performed to assess the relative accuracy of ventricular border definition using this new technique by comparison to the unenhanced images in eight patients. The difference in planmetered area of the two cardiac silhouettes was 13 ± 4 mm² (mean difference ± 3.4%). In four patients both direct and peripheral venous LV angiograms were obtained. There was a small (2% to 7%) systematic difference between calculated end-diastolic and end-systolic LV volume, with peripheral venous volumes invariably being smaller. Differences in calculated ejection fraction (EF) were of smaller magnitude; the maximum absolute difference in EF was 2%. We conclude that this technique is applicable to angiographic studies involving either cardiac or peripheral vascular injection of contrast material, and allows high quality images to be obtained at approximately seven-fold reduction in radiation dose (5 mA, 65 to 85 kv).     

Atrioventricular node reentry: Intravenous verapamil as a method of defining multiple electrophysiologic types

Fourteen patients with recurrent supraventricular tachycardia (SVT) underwent electrophysiological evaluation. Each patient was shown to have reentry confined to the region of the atrioventricular (AV) node. Verapamil, 0.075 to 0.15 mg/kg was administered intravenously to each patient during a stable episode of SVT, resulting in termination in each instance. There was more than one mechanism for termination of SVT. Nine patients showed termination by anterograde AV node block preceded by an increase in conduction time in the anterograde limb of the tachycardia circuit (Ae-H intervals) with no change in the conduction time in the retrograde limb (H-Ae intervals). Three patients showed termination by block in the retrograde limb of the circuit preceded by increases in both Ae-H and H-Ae intervals. An additional example of termination by spontaneous ventricular premature complexes and usurpation by sinus rhythm were also seen. Common features were that verapamil had significant effects on anterograde and retrograde conduction and refractoriness in the AV node. It prolonged the refractory periods of both fast and slow pathways in patients with dual anterograde AV node pathways, and observable effects on retrograde conduction and refractoriness were seen even in patients with constant ventriculoatrial conduction times during incremental ventricular pacing in a control study. However, three distinct groups of patients were identified on the basis of their response to ventricular pacing in a control study and upon verapamil effects recorded during their SVT. An explanation for these latter findings may be that there is a normal variation in the retrograde response of parts of the AV node to ventricular pacing, and a variability in some of the patients' responses to verapamil.     

Improved assessment of inferior segmental wall motion by the addition of a 70-degree left anterior oblique view in multiple gated equilibrium scintigraphy

Conventional anterior and 45-degree left anierior oblique (LAO) views are limited in the evaluation of inferior segmental wall motion by multiple gated equilibrium cardiac blood pool scintigraphy. This study evaluated the addition of a 70-degree LAO view by comparing scintigraphic and contrast ventriculography in 25 patients, of whom 17 demonstrated abnormal inferior wall motion. Abnormal inferior wall motion was correctly identified in only 10 of 17 patients in the anterior view, but in 16 of 17 patients in the 70-degree LAO view. The number of assessable inferior segments was improved from 58% in the anterior view to 98% in the 70-degree LAO view. When the inferior segments could be visualized in the anterior view, inferior wall motion was accurately assessed. The addition of the 70-degree LAO view aids in the multiple gated equilibrium scintigraphic detection of inferior wall motion abnormalities with a minor loss in specificity.     

Intracoronary thrombolysis in acute myocardial infarction: Experimental background and clinical experience

Occlusive intracoronary (IC) thrombosis was produced experimentally in dogs by placement of a copper coil. The thrombus was consistently lysed by application of Thrombolysin (streptokinase and plasminogen) at the site of occlusion, 1 to 6 hours after thrombosis. Thrombolysin has no toxic effect on the coronary artery wall or the myocardium. Reperfusion after 30 to 60 minutes of occlusion frequently resulted in ventricular fibrillation, but gradual reperfusion reduced the probability of ventricular fibrillation. Intramyocardial bleeding was noted after reperfusion in areas of advanced necrosis and was shown to be the consequence, rather than the cause, of necrosis. The reperfused myocardium remained hypocontractile, but in contrast to the occlusion period, its mechanical function could be enhanced by inotropic stimulation. After experimental studies confirmed the feasibility and safety of IC thrombolysis, the technique was applied within 3 hours of onset of pain in 29 patients with evolving acute myocardial infarction (AMI) and showing ST elevations without pathologic Q waves. Nitroglycerin (NTG), 0.1 mg, was injected into the occluded coronary artery to rule out spasm; NTG failed to open the occluded artery. A special, very flexible, radiopaque No. 2 French catheter was advanced through the angiography catheter to the site of occlusion. Thrombolysin was infused at a rate of 4000 to 6000 IU/min until patency was achieved, followed by 2000 IU/min for 60 minutes. Lysis of clot was achieved in 27 of 29 patients. The single death (unrelated to the procedure) occurred subsequently in a patient in whom the artery was not reopened. After successful thrombolysis, 12 patients underwent elective coronary bypass surgery because of multiple stenoses. The need for early reperfusion is emphasized for effective IC thrombolysis therapy in evolving AMI.     

Peripheral hemodynamics in anephric patients with hypertension

Peripheral hemodynamics were examined in a group of four anephric patients with hypertension and the results were compared with a group of 10 normal subjects. Measurements of systemic hemodynamics in these anephric patients showed increased arterial blood pressure and a modest increase in cardiac index. Renin blood levels were negligible. Mean forearm blood flow was significantly higher in the anephric patients. This was probably a reflection of the increased arterial blood pressure since mean forearm vascular resistance was within normal limits. Mean forearm venous capacitance was also within normal limits.Oscillometric examination showed markedly increased pulsation amplitudes proximally in the limbs of anephric patients, while at the wrist, elbow, fingers, and toes pulsation amplitudes were either normal or diminished.Skin blood flow, as reflected in both fingers and toes, was significantly diminished in anephric patients while skin temperature was normal. While this may indicate normal capillary blood flow in anephric hypertension, constriction at the precapillary network level, as seen by the increased resistance occurring in the skin, is present. Changes in the 1 and 10 minute reactive hyperemia and 30 pound/30 second active hyperemia reactions showed that in anephric patients a greater time period of increased levels of flow was obtained in all three reactions.These data suggest that the difference seen between anephric and normal subjects in their peripheral vasculature in part result from the hypertension, severe anemia, and other factors which may be present.