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Biomedical subjects

D E Lovelace

Publications and source records attributed to D E Lovelace.

11 recordsLinked to original sources

Secondary structure of detergent-solubilized phospholamban, a phosphorylatable, oligomeric protein of cardiac sarcoplasmic reticulum.

The structure of phospholamban, a 30-kDa oligomeric protein integral to cardiac sarcoplasmic reticulum, was probed using ultraviolet absorbance and circular dichroism spectroscopy. Purified phospholamban was examined in three detergents: octyl glucoside, n-dodecyloctaethylene glycol monoether (C12E8) and sodium dodecyl sulfate (SDS). Ultraviolet absorption spectra of phospholamban reflected its aromatic amino acid content: absorption peaks at 275-277 nm and 253, 259, 265 and 268 nm were attributed to phospholamban's one tyrosine and two phenylalanines, respectively. Phospholamban phosphorylated at serine 16 by the catalytic subunit of cAMP-dependent protein kinase exhibited no absorbance changes when examined in C12E8 or SDS. Circular dichroism spectroscopy at 250-190 nm demonstrated that phospholamban possesses a very high content of alpha-helix in all three detergents and is unusually resistant to denaturation. Dissociation of phospholamban subunits by boiling in SDS increased the helical content, suggesting that the highly ordered structure is not dependent upon oligomeric interactions. The purified COOH-terminal tryptic fragment of phospholamban, containing residues 26-52 and comprising the hydrophobic, putative membrane-spanning domain, also exhibited a circular dichroism spectrum characteristic of alpha-helix. Circular dichroism spectra of phosphorylated and dephosphorylated phospholamban were very similar, indicating that phosphorylation does not alter phospholamban secondary structure significantly. The results are consistent with a two-domain model of phospholamban in which each domain contains a helix and phosphorylation may act to rotate one domain relative to the other.

Adenosine Triphosphatases

An editing method for computer-assisted ambulatory ECG review systems.

Editing of computer-assisted ambulatory ECG reviews is critical for accuracy and quantification of the arrhythmias present. This may be time consuming for high arrhythmia content types or tapes with noise interference. A system that combines probit analysis and principle components transformation coupled with maximum likelihood decision theory, through identification of the complexes most subject to classification error in the initial review process and by correcting residual errors automatically, can decrease the number of complexes which need to be overread by a human editor. Probit analysis assigns a statistically derived value, a z value, to complexes classified as normal sinus or ventricular premature complexes. This permits the grouping of complexes for which the likelihood of being normal sinus or ventricular premature is high and a group which has a greater likelihood of being incorrectly classified. This latter group can be shown to the human editor for verification or correction of classification. The complexes undergo principle components transformation which describes the QRS by a set of derived components. When a classification is approved or changed by the human editor, the computer, utilizing maximum likelihood decision rules, moves ahead in the tape to correct the classification of the remaining unedited complexes on the basis of the similarity of their principle components profile to the edited ones. The system reduced total errors, false positive or false negative, to less than one percent in all of the high arrhythmia and noise content tapes used for this study.

Computers

Behavior of the terminal T wave during exercise in normal subjects, patients with symptomatic coronary artery disease and apparently healthy subjects with abnormal ST segment depression.

The Q-T interval and apex of T wave to end of T wave (aT-eT) interval were measured by computer in four age-matched study groups at rest and during exercise to determine whether: the behavior of the aT-eT interval differs in patients with myocardial ischemia when compared with normal subjects, and the behavior of the aT-eT interval differs in subjects with true positive and false positive ST segment responses. Group I consisted of 57 normal subjects. Group II consisted of 41 symptomatic patients with documented coronary artery disease. A group of apparently healthy subjects with asymptomatic ST segment depression during exercise was divided into two additional groups: Group III, those without coronary artery disease; and Group IV, those with coronary artery disease. Subjects were excluded from the study if they had left ventricular hypertrophy or an intraventricular conduction defect or were taking digitalis or type I antiarrhythmic agents. There were no significant differences in the aT-eT interval and aT-eT/Q-T ratio among the four study groups when compared at rest; however, during exercise at similar heart rates, the aT-eT interval was significantly shorter and the aT-eT/Q-T ratio significantly smaller in Groups II and IV, the subjects with coronary artery disease, than in Group I, the normal subjects. The aT-eT interval and aT-eT/Q-T ratio measurements in Group III did not differ from those in Group I at rest or during exercise. In conclusion, the aT-eT interval and aT-eT/Q-T ratio may reflect changes in myocardial repolarization in exercise-induced ischemia and may have potential for future clinical application.

Adrenergic beta-Antagonists

On-line analysis of intracellular electrophysiological data using a microcomputer system.

Automated analysis of intracellular action potentials from cardiac Purkinje fibers was implemented using a microcomputer system. A dual sampling rate was used during analog-to-digital conversion of action potentials recorded from stimulated fibers. The rapid phase of depolarization was sampled at 42.55 kHz. The repolarization and the diastolic phases were sampled at 1 kHz. The resting potential, action potential amplitude, conduction time, action potential duration measured at 50% and at 90% of repolarization, and the maximum upstroke velocity were obtained on-line. The digital form of the action potential was stored on cassette tape and a table containing the various measurements was assembled during the experiment. In unstimulated fibers, the time interval between consecutive action potentials was measured on-line along with the maximum diastolic potential, the action potential overshoot, and the slope of the diastolic depolarization.

Action Potentials

Relationship between changes in left ventricular bipolar electrograms and regional myocardial blood flow during acute coronary artery occlusion in the dog.

The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrograms, in open-chest dogs following acute coronary artery occlusion. We found that the degree of regional myocardial ischemia was related quantitatively to the reduction in amplitude recorded with bipolar electrograms in the subepicardium and subendocardium, and to the increase in duration of subepicardial electrograms. Other characteristics measured in electrograms did not relate to the degree of ischemia. Despite a comparable reduction in regional myocardial blood flow, subepicardial conduction delay exceeded that recorded in the subendocardium, which often exhibited accelerated conduction.

Acute Disease

Stroke volume calculated from the mitral valve echogram in patients with and without ventricular dyssynergy.

A formula was derived for calculating mitral valve stroke volume (MVSV) using the rate of mitral valve (MV) opening (DE slope on the MV echogram), the vertical disease between the mitral leaflet echoes early in diastole (EE), the electrocardiographic PR interval and heart rate. The formula was tested prospectively on 80 consecutive patients from whom 95 simultaneous MV echograms and either thermodilution (45) or Fick (50) cardiac outputs were obtained. Sixteen patients were normal; 54 had coronary artery disease; three had cardiomyopathy; and seven had nonrheumatic mitral regurgitation (MR). Linear regression for stroke volume was r = 0.90, SEE +/- 6, and for cardiac output r = 0.83, SEE +/- 0.5 liter for the 73 patients without MR. The presence or absence of ventricular dyssynergy did not alter statistical findings. MVSV consistently overestimated forward stroke volume for the seven patients with MR. This study shows that the MV echogram provides an accurate, widely applicable method for calculating MVSV.

Cardiac Catheterization

Myocardial blood flow as measured by fractional uptake of rubidium-84 and microspheres.

Under conditions of varying flow rates, total myocardial blood flow, measured by fractional uptake of rubidium-84, using a coincidence counting system, was compared with myocardial flow measured by microspheres (15 +/- 5 micrometer). The methods were compared, open-chested, in 47 dogs: 17 during control, ten following 5 min of ligation of left anterior descending coronary artery, five following i.v. isoproterenol, six following ligation and isoproterenol, and nine after ligation plus dipyridamole. Regional flows by Rb-84 and by either Ce-141 or Cr-51 microspheres were also compared for left ventricle, as well as for nonischemic posterior wall, which served as a reference area, and for anterior wall with ligation of left anterior descending artery in the same preparations. There were no significant differences in total or regional flow measured by the two methods, nor in the estimate of ischemic area size. The data indicate that measurement of myocardial blood flow by fractional uptake of a potassium analog is a reliable method in the presence of ischemia and drug intervention. It is suggested that the inequalities of extraction ratio that occur with differing flow rates do not invalidate fractional-uptake methods over the flow ranges examined.

Animals

Computer detection of premature ventricular complexes: a modified approach.

The accuracy of a data reduction system for arrhythmia detection in identifying premature ventricular complexes was evaluated in continuous tape records of 30 patients in a coronary care unit. Computer analysis was performed with a Honeywell 316 digital computer. Threshold values for dominant complexes were automatically determined and recognition of premature ventricular complexes was based on differences in QRS configuration, timing and T wave configuration from the dominant complexes. Verification of the computer accuracy in detecting premature ventricular complexes was made with visual beat by beat inspection using a two channel strip chart recorder with simultaneous recording of the electrocardiogram and computer signal. This procedure allowed for exact beat to beat correlation and, thus, absolute determination of false positive and false negative identification. From 0.5 to 6 continuous hours of monitoring per patient (average 3.5 hours) were analyzed for a total of 105 monitoring hours. The basic cardiac rhythms noted were normal sinus rhythm, sinue arrhythmia, sinus tachycardia, demand pacemaker rhythm, atrial fibrillation and atrioventricular (A-V) dissociation with junctional rhythm. Premature ventricular complexes were evident in 28 tapes (93 percent) including 12 (43% with multifocal premature ventricular complexes and 3 (11 percent) with ventricular tachycardia. The visual count of premature ventricular complexes totaled 7,921. Of these, 7,542 (95 percent) were properly classified by the computer. The total computer count was 8.717, representing a 13 percent false positive and 5 percent false negative identification rate. The false positive identifications of premature ventricular complexes occurred during periods of 10 seconds or more of continuous noise artifact and in the presence of atrial premature complexes conducted aberrantly. When these sections of tape were excluded, the computer had a less than 2 percent false negative and 3 percent false positive rate of identification of premature ventricular complexes.

Arrhythmias, Cardiac

Nonparoxysmal junctional tachycardia in acute myocardial infarction: computer-assisted detection.

Thirty consecutive patients with acture myocardial infarction had continuous magnetic tape recording of their stay in the coronary care unit. Analysis of the 24 hour tape recordings was implemented on a Honeywell model 316 digital computer. In the first 24 hours after admission to the coronary care unit, 12 of the 30 patients (40 percent) exhibited nonparoxysmal junctional tachycardia; in 5 the arrhythmia was not recognized by conventional monitoring techniques. For the subsequent 3 days, the incidence rate of the arrhythmia was 13 percent for the first 48 hours and 3 percent for 72 hours. Although the mortality rate in patients with nonparoxysmal junctional tachycardia was greater than in patients not demonstrating the arrhythmia (33 versus 6 percent), there was a greater percentage of patients with anterior infarction in the former group; therefore, mortality may have been related to site of infarction rather than being reflective of the arrhythmia or its associated pathophysiologic state. Of possible significance is the association of a greater degree of sinus arrhythmia with nonparoxysmal junctional tachycardia. The incidence of nonparoxysmal junctional tachycardia in this group of patients was greater than previously reported. It is possible that computer tape analysis may have provided more accurate recognition of the arrhythmia and, thus, more realistic incidence data. The association of nonparoxysmal junctional tachycardia with sinus arrhythmia could only have been recognized by computer technique. The computer system is not a diagnostic system but rather a tape review method.

Analog-Digital Conversion

An adaptive algorithm for noise rejection.

An adaptive algorithm for the rejection of noise artifact in 24-hour ambulatory electrocardiographic recordings is described. The algorithm is based on increased amplitude distortion or increased frequency of fluctuations associated with an episode of noise artifact. The results of application of the noise rejection algorithm on a high noise population of test tapes are discussed.

Arrhythmias, Cardiac

A two-dimensional clustering technique for identification of multiform ventricular complexes.

A computer algorithm for the identification of multiform ectopic ventricular complexes in 24-hour ambulatory electrocardiographic recordings is described. The clustering technique established regions, based on R-R interval and ST-segment slope, in a two-dimensional probability space based on the fit of each ventricular complex. The boundaries of any overlapping regions are analyzed using a Bayesian decision rule to minimize misclassification.

Arrhythmias, Cardiac