Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction.

We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.

Evaluation of an immunoradiometric assay specific for the CK-MB isoenzyme for detection of acute myocardial infarction.

Clinical evaluation of patient's symptoms, electrocardiographic changes and increased serum enzyme levels, specifically creatine kinase (CK)-MB by electrophoresis, are established as the primary diagnostic indicators for myocardial infarction (MI). Two hundred fifteen patients were evaluated in this study. Of these patients, 102 were admitted to the coronary care unit and 113 were admitted to the emergency room and screened for possible MI. The immunoradiometric assay used in this study was a double antibody "sandwich" technique, which utilizes antibody to the M and B monomers of the CK isoenzymes. This assay is specific for the CK-MB isoenzyme, which is present in increased levels in MI. The intraassay coefficients of variation for 30 samples were 11.7% (mean 4.1 equivalent units [EU]/liter) and 8.4% (mean 15.4 EU/liter) and the interassay coefficients of variation for 30 samples were 11.1% (mean 2.6 EU/liter) and 8.1% (mean 13.6 EU/liter). The diagnostic sensitivity, specificity and accuracy in this study was 100%, respectively. The CK-MB by the immunoradiometric assay was found to be significantly more accurate than electrophoresis and, therefore, a reliable and also technically simpler replacement for electrophoresis.

Diagnosing myocardial infarction with a radioimmunoassay for the B-monomer of the creatine phosphokinase isoenzymes.

A diagnosis of myocardial infarction (MI) is usually established by the evaluation of clinical symptoms, electrocardiographic changes, and serum enzyme levels, specifically creatine phosphokinase, subunit MB (CK-MB), by electrophoresis. A total of 215 patients were evaluated in this study. One hundred two of them were admitted to the coronary care unit and 113 to the emergency room, where they were screened for possible MIs. The radioimmunoassay (RIA) used in this study determines levels of the CK-MB isoenzyme by detecting the B monomer, which also has 100% cross-reactivity with the CK-BB isoenzyme. The intra-assay coefficients of variability (CVs) for 30 samples were 22% (means = 7.0 ng/ml) and 11% (means = 47.3 ng/ml), and the interassay CVs for 30 samples were 17% (means = 7.1 ng/ml) and 9.2% (means = 49.3 ng/ml). Of the 215 patients evaluated, 21 had myocardial infarction by the criteria in the study. The diagnostic sensitivity, specificity, and accuracy were 100.0%, 92.8%, and 93.5% respectively. These values increased to 100.0%, 96.9%, and 97.2% when only coronary care unit patients were considered. The CK-MB RIA was found to be a reliable replacement for electrophoresis, but it was nonspecific in some patients.

Effects of lignocaine on bidirectional tachycardia and on digitalis-induced atrial tachycardia with block.

Most recent studies discussing tachycardias with alternating QRS polarity have referred to those known as torsade de pointes. This report, in contrast, deals with bidirectional tachycardia and the effects of lignocaine on 10 patients with this arrhythmia. Three of the patients also had digitalis-induced atrial tachycardia with block. In one patient, a single bolus of lignocaine was followed (five minutes later) by ventricular fibrillation, but the other nine patients received two boluses of 75 mg followed by a drip infusion of 3 mg/min. The drug terminated the episodes of atrial tachycardia with block and bidirectional tachycardia in all patients thus treated. Whereas the abolition of the bidirectional tachycardia was permanent in the seven patients with digitalis intoxication, it recurred after stopping the drip infusion in the two patients without digitalis toxicity. It is concluded that lignocaine can be useful in the treatment of digitalis-induced bidirectional tachycardia and atrial tachycardia with block. From this study no conclusions can be drawn, however, as to whether lignocaine is superior to other class I or class IV agents.

Left fascicular blocks during right-heart catheterization using the Swan-Ganz catheter.

During insertion of Swan-Ganz catheters, mechanical right bundle branch block occurred in association with left posterior fascicular block in two patients and with left anterior fascicular block in two. None of the four patients had acute myocardial infarction or acute (spontaneous or iatrogenic) pulmonary disease. In two cases, electrophysiologic studies demonstrated the coexistence of intra- and infra-Hisian conduction delays and blocks. Although the right bundle branch block may have resulted from injury to the central or peripheral right branch, the left fascicular blocks could not be explained by direct trauma to these left-sided structures. Our findings support the recent clinical and experimental reports that show that left fascicular block (as well as right bundle branch block) may be due to lesions involving the His bundle; presumably because of longitudinal dissociation of this structure affecting the transverse interconnections. In one patient, 2:1 intra-Hisian block may have coexisted with bradycardia-dependent (phase 4) right bundle branch block. More studies are required to determine the implications of catheter-induced conduction disturbances in other clinical settings, such as acute myocardial infarction.

Atropine-induced multilevel block in acute inferior myocardial infarction. A possible indication for prophylactic pacing.

The degree of A-V block increased after intravenous administration of atropine in 10 nondigitalized patients with acute inferior myocardial infarction who had narrow QRS complexes during periods of 1:1 A-V conduction. Short episodes of 3:1, 4:1 and 5:1 A-V block were seen to emerge: (a) in 6 patients, directly from Wenckebach periods; (b) in 3 patients, from alternating Wenckebach periods; and (c) in 1 patient, from a 3:2 Wenckebach period which led to a short-lived alternating Wenckebach period. Apparently, the predominance of the chronotropic effects on the sinus node over the dromotropic effects on the A-V node led to a tachycardia-dependent (more ischemic than vagal) process, exposing or producing multi- (two, three or four) level block involving the A-V node (and perhaps the His bundle). Subsequently, therapeutic pacing was instituted in 9/10 patients because they developed spontaneous symptomatic advanced A-V block. Therefore, it is possible that the early effects of atropine identified a narrowly-defined subset of patients in whom prophylactic pacing may be indicated. However, more studies are necessary to corroborate these assumptions.

Relationship between plasma levels of procainamide, suppression of premature ventricular complexes and prevention of recurrent ventricular tachycardia.

We compared the relationship between plasma levels of procainamide and suppression or prevention of various forms of ventricular arrhythmias in 18 patients, six of whom had premature ventricular complexes (PVCs) during acute myocardial infarction (AMI), six of whom had PVCs in the setting of stable chronic ischemic heart disease (CIHD), and six of whom had recurrent symptomatic ventricular tachycardia (VT) with chronic PVCs between episodes of VT. The mean plasma level of procainamide required for 85% suppression of PVCs in the AMI patients was 5.0 +/- 0.5 micrograms/ml, while that required for the CIHD patients was 9.3 +/- 0.7 micrograms/ml (p less than 0.05). The mean plasma level required for prevention of spontaneous episodes of symptomatic sustained tachycardia in the VT group was 9.1 +/- 3.4 micrograms/ml, while the mean level required for 85% suppression of PVCs in the same patients was 14.9 +/- 3.8 micrograms/ml (p less than 0.01). In the VT group, PVC frequency was decreased by a mean of only 36% (range 11-63%) at plasma levels of procainamide sufficient to prevent spontaneous VT. The relationship between plasma levels of procainamide and PVC suppression appears to be different in AMI and CIHD patients; furthermore, a high degree of PVC suppression is not a necessary endpoint of antiarrhythmic therapy when attempting to protect patients against recurrent symptomatic VT.