Release characteristics of enzymes used in the diagnosis of myocardial infarction.

Release characteristics of S-LD, S-LD1, S-ASAT, S-CK and S-CK-MB were studied in 47 consecutive AMI patients. In addition, previously obtained data for serum myoglobin (S-MYO) were compared. Serum was sampled at regular intervals after admission to the Coronary Care Unit (CCU). The release rate and half lives of the enzymes were calculated according to a one-compartment kinetic model. The time to peak values, the time of total release and the half lives were interrelated in the following order: MYO less than CK-MB less than CK less than ASAT less than LD1 less than LD which coincides with the wellknown appearance and disappearance rates in serum. The ratio between mean peak values and upper reference limits followed the reverse order. The finding that the release rate of enzymes and half-lives co-vary is hypothetically suggested to be attributed to differences in rate of membrane diffusion. There is indirect evidence that a slow indicator such as LD1 reflects infarct size better than fast indicators with rapid release and removal such as MYO or CK-MB. However, these fast markers have a better signal to noise ratio, whereby they probably reflect changes in the infarction process better.

Flow and pressure responses of coronary arteries and veins to vasodilating agents.

The response to a bolus injection of nitroglycerine, adenosine, nifedipine, and dipyridamole of the canine systemic as well as coronary artery and venous circulations was observed and contrasted. Particular attention was paid to the time of change of pressures and flows and to changes in oxygen extraction by the myocardium induced by the pharmacological agents. The dosages of vasodilators used were selected so that no significant change in aortic blood flow occurred. Nitroglycerine and adenosine caused a rapid and similar vasodilation in the coronary circulation. Oxygen extraction was not altered by nitroglycerine, but was decreased by adenosine. The onset time of the vasodilation produced by either nifedipine or dipyridamole was similar, but the time to peak action was much slower for dipyridamole. As well, the effect of dipyridamole on intramyocardial and left intraventricular pressures was more delayed than that following the injection of the other agents. Oxygen extraction was reduced by nifedipine and dipyridamole. These results indicate that pharmacological vasodilating agents can affect coronary arteries, coronary veins, and myocardial oxygen extraction differently.

QT interval variability on the body surface.

To assess the effects of measurement methodology on QT determinations and to define the spectrum of QT values, including interlead variability, on the body surface, we measured QT in each of 120 simultaneously-recorded, signal-averaged ECG leads in 10 normal subjects and 14 patients with QT prolongation (lead II QTc greater than 440). Two separate, but related, methods of QT measurement were utilized. Method A was a relatively conventional technique in which ST-T offset was defined as the time instant of return of the T wave to a P-P baseline, or as the point of U-on-T intersection. Method B was a more rigorous method, which defined ST-T offset in a similar manner, and in addition discarded from analysis all QT values from leads with monophasic ST-T waveform in which the QT values were greater than the longest QT from leads with definite U waves. Method B was utilized to minimize factitious prolongation of QT by inapparent U-on-T. By both methods the mean body surface QTc values were significantly greater (p less than 0.001) in the patient group (482 +/- 65 [S.D.] msec, method A; 447 +/- 43 msec, method B), than in the normal subject group (399 +/- 14 msec, method A; 396 +/- 12, method B). Interlead QTc variability (difference between the longest and shortest QT) was considerable with both methods and in both study groups. Expressed as percent of average body surface values, the mean interlead QTc variability in normal subjects averaged 22 percent with method A and 19 percent with method B; in the patient group, however, it averaged 32 percent with method A and only 18 percent with method B. In absolute terms, the mean variability in the patient group with method A (155 +/- 62 msec) was significantly greater (p less than 0.001) than that of the normal group (89 +/- 33 msec); with method B, interlead variability was the same (p = NS) in the normal (76 +/0 27 msec) and patient groups (80 +/- 44 msec). This latter finding suggests the possibility that the repolarization abnormality in patients with QT prolongation may occur relatively uniformly throughout the ventricular myocardium. Thus, measurement techniques are important in multiple-lead QT determinations. Although reduced by techniques designed to minimize factitious QT prolongation, interlead QT variation is considerable over the torso surface, in both normal subjects and patients with repolarization abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Galvanic element produced by defective electrode insulation--a possible cause of abnormal pulse generator inhibition.

In patients with pacemaker, abnormal inhibition with prolongation of pacing intervals may cause alarming clinical symptoms. A case is described in which high current threshold in relation to voltage threshold indicated probability of an insulation defect with current leakage. Electrograms from the electrode disclosed false signals, which had appeared after replacement of a pulse generator six months earlier. A sharp bend of the wire in the tricuspid area was shown by X-ray and was accentuated by movements of the valve. Experimentally it was demonstrated that similar potentials, sufficient to inhibit a pulse generator, can be obtained from an electrode with defective insulation. A galvanic element forms between the metals of the electrode tip and the non-insulated cable, and potential variations are elicited by movement of the wire.

Pacing threshold interval with decreasing and increasing output.

The study was made in 44 patients, of which 23 received a new endocardial electrode and 21 were investigated during pulse-generator replacement. Indication for pacemaker therapy was sino-atrial bradycardia in 12 patients and atrio-ventricular block in 32 patients. When the pacing threshold was determined with decreasing output it was found to be 0.6V/0.7 mA for new implantations and 2.0 V/2.0 mA with pulse generator replacement. When determined with increasing output the threshold was found to be an average 0.20 V/0.20 mA higher than when determined with decreasing output (threshold interval). The maximal difference observed was 0.70 V/0.55 mA. This threshold interval was of the same size irrespective of pacemaker indication and spontaneous activity and whether the electrode was newly implanted or not. Pacemaker ventricular block of Mobitz type I with Wenckebach periodicity was never observed.

Myocardial and non-myocardial release of myoglobin and creatine-kinase MB following cardiac operations with hypothermic potassium cardioplegia.

Serum time-activity curves for myoglobin, creatine-kinase (CK) and its isoenzyme MB were determined during and after coronary bypass surgery and aortic valve replacement. Hypothermic potassium cardioplegia was the method employed to initiate cardiac arrest. Cardiac myoglobin and CK-MB release rates were maximal 0.5 to 1.0 h post aortic cross-clamp release (PACR) with maximal concentrations at 1 and 4 h PACR respectively. The cardiac release ceased within 5 h PACR but was followed by a noncardiac release with maximal concentrations from 10 to 35 h PACR. The cardiac myoglobin release was significantly lower in the coronary bypass group, whereas no significant intergroup difference was observed for CK-MB. The cumulative CK-MB release corresponded roughly to about 5 g of myocardium.

Myoglobin and creatine kinase release in coronary care patients without acute myocardial infarction.

Fifty-nine consecutive coronary care patients, clinically evaluated as not having acute myocardial infarction (AMI) and with a duration of symptoms of less than 6 hours on admission, were studied. Serum myoglobin (MG) and creatine kinase (CK) were determined sequentially during the first 25 hours. Two groups are identified, one with a pattern of a serum MG peak followed by a CK peak and one without. Twenty-four patients had a serum MG peak of 137 plus or minus 33 micrograms x 1(-1) followed by a CK peak of 1.6 plus or minus 0.9 microkat x 1(-1). Values above th reference limits were found in 19 patients for MG and in 5 for CK. After the onset of symptoms, the peaks were observed at 5.3 plus or minus 2.8 (MG) and 12.7 plus or minus 5.3 (CK) hours. Compared to the group without MG and CK peaks, ECG alterations were more frequent in the group with peaks, 20/24 (84%) versus 15/35 (43%). The entire patient group had the same 2-year incidence of major coronary events as patients with AMI, but it tended to be higher in patients with MG/CK release.

Myoglobin and creatine kinase rates of release during acute myocardial infarction.

The release of cardiac enzymes as an index of infarct size (IS) development was studied in patients with acute myocardial infarction (AMI) treated at a coronary care unit. Serial determinations of serum myoglobin (MG) and creatine kinase (CK) were made on 34 consecutive patients with duration of symptoms less than 6 h at admission and with initial CK values below the upper reference limit. Computer-calculated CK-IS was determined on the basis of the log-normal algorithm. This was compared to discretely calculated CK and MG release. The correlation between computer- and discretely calculated cumulated CK release was 0.995 with a regression close to the line of equivalence. Computer-calculated CK rates of release showed a one-peak development, while, when discretely calculated, mostly three or four peaks were observed, as found also for MG rates of release. The occurrence of MG and CK peaks was related as indicated by a correlation coefficient of 0.75. The initial CK rate of release was slower when computer-calculated. In the group studied, CK release began about 3 h post onset of symptoms, at which time 56% had an MG value above the upper reference limit. The CK and MG releases were finished about 31 and 36 h post onset of symptoms, respectively, with MG peaks at 6, 11, 19, and 22 h with corresponding CK peaks delayed 2, 3, 3, and 9 h. The first MG and CK peaks represented between 30 and 40% of the total release while the following three peaks represented between 20 and 30% each. Cumulative MG release was correlated to the time of AMI development. No such correlation was found for CK. The results indicate that the development of AMI is a wavelike process not sufficiently described by the log-normal algorithm, on the basis of which, however, an index of total release might be obtained.