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Biomedical subjects

D E Lovelace

Publications and source records attributed to D E Lovelace.

At least 19 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↗

Echocardiographic detection of ischemic and infarcted myocardium.

The purpose of this study was to determine the potential of a clinically adaptable two-dimensional echocardiographic system using computer enhancement and a mathematically defined integrated backscatter ratio for the early detection of ischemic and infarcted myocardium. Fifteen dogs had two-dimensional echocardiograms recorded during either open chest coronary occlusion (n = 5), closed chest occlusion (n = 5), occlusion followed by reperfusion (n = 3) or sham coronary occlusion (n = 2). A serial increase in integrated backscatter ratio, representing differences in returned ultrasound intensities between a reference point and specific myocardial regions, was detected between 7 and 12 minutes of complete occlusion in 9 of 12 animals (p less than 0.05), and at minutes 18, 43 and 67 in the remaining 3 animals. Reperfusion after 20 minutes of occlusion in two studies resulted in normalization of the backscatter ratio. An increase in backscatter ratio was not detected when 5 minute occlusion periods were used or during the 5 hour sham occlusion studies. The computer enhancement techniques utilized in this study provided increased visual detail of intracardiac structures over that provided by routine two-dimensional echocardiograms; myocardial tissue was identifiable in what appeared to be echo-free segments; and boundaries that appeared as noncontiguous horizontal lines on the routine echocardiograms were identifiable as trabeculae. The results indicate that: 1) significant increases in backscatter from nonperfused myocardium are detectable echocardiographically within 12 minutes of coronary occlusion and temporal changes can be assessed in the canine model, and 2) the echocardiographic data acquisition and computer analysis system utilized provide a clinically adaptable approach to identify and map myocardial characteristics in human beings.

Animals↗

Computers and clinical arrhythmias.

Cardiac arrhythmias are ubiquitous in normal and abnormal hearts. These disorders may be life-threatening or benign, symptomatic or unrecognized. Arrhythmias may be the precursor of sudden death, a cause or effect of cardiac failure, a clinical reflection of acute or chronic disorders, or a manifestation of extracardiac conditions. Progress is being made toward unraveling the diagnostic and therapeutic problems involved in arrhythmogenesis. Many of the advances would not be possible, however, without the availability of computer technology. To preserve the proper balance and purposeful progression of computer usage, engineers and physicians have been exhorted not to work independently in this field. Both should learn some of the other's trade. The two disciplines need to come together to solve important problems with computers in cardiology. The intent of this article was to acquaint the practicing cardiologist with some of the extant and envisioned computer applications and some of the problems with both. We conclude that computer-based database management systems are necessary for sorting out the clinical factors of relevance for arrhythmogenesis, but computer database management systems are beset with problems that will require sophisticated solutions. The technology for detecting arrhythmias on routine electrocardiograms is quite good but human over-reading is still required, and the rationale for computer application in this setting is questionable. Systems for qualitative, continuous monitoring and review of extended time ECG recordings are adequate with proper noise rejection algorithms and editing capabilities. The systems are limited presently for clinical application to the recognition of ectopic rhythms and significant pauses. Attention should now be turned to the clinical goals for detection and quantification of arrhythmias. We should be asking the following questions: How quantitative do systems need to be? Are computers required for the detection of all arrhythmias? In all settings? Should we be focusing alternatively on those arrhythmias that are frequent and with clinical significance? The ultimate test of any technology is, after all, its use in advancing knowledge and patient care.

Arrhythmias, Cardiac↗

Computer quantitation of Q-T and terminal T wave (aT-eT) intervals during exercise: methodology and results in normal men.

Computer-quantitated measurements of the Q-T intervals, the Q-T/Q-Tc ratio (Q-T/corrected Q-T) and the terminal T wave (apex to end of T [aT-eT] interval) were evaluated in resting and exercise electrocardiograms of 130 normal men with a mean age of 40 years. Pseudo-orthogonal, bipolar X, Y and Z axis leads were recorded during treadmill exercise testing, and 25 consecutive QRS-T complexes from standing rest and three exercise stages were computer-averaged. The Q-T intervals, Q-T/Q-Tc ratio and aT-eT interval measurements were then computed in the X and Z axis leads only, because the Y lead proved to be too noisy for accurate interpretation. A correlation coefficient of 0.9830 resulted between measurements made manually from the plotted, composite QRS-T complexes and those made by computer. No significant differences , in the paired sense, were found between any of the measurements. Measurements made on the Z axis lead; however, the differences in the measurements remained constant across all stages of exercise. A Q-T/Q-Tc ratio of greater than 1.08, previously reported to be a reliable indicator of coronary disease, was observed in the majority of our normal subjects during exercise. Although the Q-T interval is substantially influenced by many factors, the aT-eT interval proved not to be age- or heart rate-dependent. It appears that the aT-eT interval can be measured with a high degree of reliability during exercise and it may prove to be a relatively specific indicator of repolarization alterations that occur with myocardial ischemia.

Adult↗

Effect of ethanol on electrogram changes and regional myocardial blood flow during acute myocardial ischaemia.

Acute occlusion of the left anterior descending coronary artery in dogs produced delayed conduction and diminished amplitude of bipolar electrograms recorded from ischaemic zones. Intravenous infusion of ethanol (1.2 g . kg-1), before coronary artery occlusion, delayed conduction and reduced the amplitude of electrograms recorded in normal myocardium, but attenuated ischaemia-induced electrogram changes produced by the subsequent occlusion. Ethanol (0.6 g . kg-1 iv) did not significantly alter activation of electrograms recorded from normal myocardium, but reduced ischaemia-induced electrogram changes and decreased the incidence of ventricular fibrillation elicited by rapid ventricular pacing from five of eight to one of eight dogs. Infusion of 10 or 30% (V/V) ethanol directly into a non-occluded coronary artery significantly increased conduction time and reduced electrogram amplitude recorded in the epicardium perfused by that coronary artery. These effects were more pronounced when ethanol was infused into an occluded coronary artery distal to the site of occlusion. Ethanol did not alter regional myocardial blood flow determined by labelled microspheres during ischaemia. Thus, despite a direct depressant effect on extracellular electrical activity recorded from normal and ischaemic myocardium, ethanol reduced the severity of ischaemia-induced electrogram alterations and decreased the incidence of ventricular fibrillation when given intravenously prior to coronary artery occlusion.

Acute Disease↗

Influence of secobarbital and alpha-chloralose, and of vagal and sympathetic interruption, on left ventricular activation after acute coronary artery occlusion in the dog.

The purpose of this study was to examine the effect of secobarbital vs. alpha-chloralose anesthesia, and of tonic autonomic influence, upon ischemia-induced subepicardial and subendocardial bipolar electrogram changes during acute coronary artery occlusion in the open-chest dog. We found that the degree of bipolar electrogram alterations for similar reductions of regional myocardial blood flow was less in dogs anesthetized with alpha-chloralose than in those anesthetized with secobarbital. We also noted greater electrogram change when the sympathetic system was unopposed by the vagus nerves. Finally, this study demonstrates the reproducibility of ischemia-induced changes in bipolar electrograms during serial, short term, acute coronary artery occlusions.

Animals↗

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↗