Search PubMed⌕ Search

Biomedical subjects

D M Mirvis

Publications and source records attributed to D M Mirvis.

At least 91 records · Page 5Linked to original sources
PubMed1987

Propranolol pharmacodynamic modeling using unbound and total concentrations in healthy volunteers.

In an attempt to evaluate the propranolol (P) concentration-effect relationship, percentage reduction in exercise heart rate was modeled as a function of unbound and total P concentrations using the linear, Emax, and sigmoid Emax models. Nine volunteers underwent repeated treadmill exercise tests over 48 hr during a control period, after receiving 160 mg of P orally and again after receiving 160 mg once daily for 7 days. Beta blockade was assessed as the percentage reduction in exercise heart rate compared to control. Total serum P concentrations were determined by HPLC and unbound fractions by equilibrium dialysis. Using nonlinear least-squares regression, the Emax model was best in describing the concentration-effect relationship in each subject. Mean parameters for combined single dose and steady state were Emax 33.6 +/- 4.5% and EC50 18.2 +/- 15.6 ng/ml for total P and Emax 33.5 +/- 4.3% and EC50 1.66 +/- 1.56 for unbound P. Model fits were not significantly better for unbound versus total P and EC50 values showed similar intersubject variability. The observed unbound EC50 values are consistent with reported receptor dissociation constants. Therefore the large intersubject variability in EC50 could not be accounted for by variability in P protein binding.

Adult↗
PubMed1987

Determination of cardiac equivalent generator properties using a numerical expansion method.

The ability of the Karhounen-Loeve (K-L) numerical expansion technique to quantitate cardiac dipolarity was assessed using data recorded from fifteen isolated perfused rabbit hearts. Potentials during the QRS complex, registered from thirty-two surface electrodes, were processed to yield percent dipolarity by a potential equation fit as well as by the K-L expansion. A total of 1174 data points was evaluated. The difference in values computed by the two methods equalled 1.02 +/- 6.99% (mean +/- 1 standard deviation); this difference, although small, was statistically significant (P less than 0.01). The correlation coefficient between the two sets of results equalled 0.53 (P less than 0.001). Thus, experimental support is given to the use of the K-L method to assess field dipolarity. Because ranges of differences were high and predictive accuracy of the regression was limited, the K-L expansion may be used with caution to detect directional shifts in equivalent cardiac generator properties.

Animals↗
PubMed1987

Termination of ventricular bigeminy by conversion to concealed forms.

Ventricular bigeminy may be either overt or concealed. In this study, we attempted to determine the frequency with which the overt form converted to the concealed variety. Ambulatory electrocardiographic recordings from 25 patients with greater than 40 episodes of monomorphic ventricular bigeminy were examined. A statistically significant (P less than 0.01, binomial distribution) predominance of odd or even number of sinus beats between the end of a bigeminal episode and the next ventricular premature beat was considered to be evidence for conversion of overt to concealed bigeminy. In 14 of the 25 cases, the number of episodes of bigeminy followed by odd numbers of sinus beats was beyond these statistical bounds. In 74 episodes in 9 patients, progressive prolongation of the coupling interval during bigeminy occurred before termination. These data demonstrate the high prevalence of concealment as a mode of termination of bigeminy. In a small number of episodes, this occurs in a pattern suggestive of progressive delay of conduction in or around an arrhythmogenic locus.

Cardiac Complexes, Premature↗
PubMed1987

Detection of experimental right ventricular infarction by isopotential body surface mapping during sinus rhythm and during ectopic ventricular pacing.

Electrocardiographic (ECG) effects of experimental, isolated right ventricular infarction were studied in 10 dogs during sinus rhythm as well as during ectopic right and left ventricular pacing. Infarction was produced by injecting latex into the right coronary artery and ECG consequences were examined by body surface isopotential mapping methods using an 84 electrode torso array. During sinus rhythm, subtraction of preinfarction from postinfarction maps demonstrated that right ventricular necrosis produced abnormal negative potentials over the right hemithorax during the early, middle and late portions of the QRS complex. These patterns corresponded to loss of R waves and deepening of preexistent or development of new Q and S waves in waveforms from this region. Patterns during ectopic ventricular stimulation were compared with mean maps derived from 13 control dogs. Both left and right ventricular pacing after right ventricular infarction resulted in a right-sided abnormal minimum, similar in location to that observed during sinus rhythm, throughout the QRS complex. Thus, right ventricular necrosis does produce QRS complex changes over the right torso that are analogous to those produced by left ventricular infarction, and the dominant pattern of an abnormal right-sided minimum was present regardless of the ventricular activation pattern. This latter finding suggests that the region of right ventricular necrosis provided a supplementary path for current to reenter the heart regardless of the current source, so that an overlying electrode would record negative voltage with all activation patterns.

Animals↗
PubMed1987

Prognostic value of the pressure-volume ratio in patients with coronary artery disease.

To determine if the peak-systolic pressure/end-systolic volume ratio [PSP/ESV], a load-insensitive index of left ventricular function, predicted perioperative mortality and long-term survival after coronary artery bypass surgery or medical treatment, 4,829 patients with coronary artery disease were studied retrospectively. Cardiac volumes, ejection fraction, and PSP/ESV ratio were computed using standard methods, and follow-up was performed using annual questionnaires. PSP/ESV ratio values were not significantly different (p = .09) between those who died during hospitalization (n = 101) after coronary surgery and those who were discharged. Long-term follow-up in surgically treated patients demonstrated a 97% 3-year and 93% 5-year survival for those with PSP/ESV over 2.292. These were significantly greater (p = .0026) in value in patients with PSP/ESV less than 1.237 (3-year and 5-year survival of 92 and 79.2%, respectively). In the medical group, survival rate for those with PSP/ESV over 2.292 at 5 years was 89.3%, while for those with PSP/ESV less than 1.237 it was 52.5% (p less than .001). Multivariate analysis, however, showed ejection fraction to be a more significant predictor of survival in both the groups compared with PSP/ESV ratio. Thus, PSP/ESV ratio does predict long-term survival in coronary disease patients treated either surgically or medically. Ejection fraction was nevertheless a more powerful predictor of outcome.

Adult↗
PubMed1987

Alterations in transmural blood flow and body surface ST segment abnormalities produced by ischemia in the circumflex and left anterior descending coronary arterial beds of the dog.

Previous studies have documented a quantitative relation between alterations in transmural myocardial blood flow and body surface electrocardiographic distributions during rapid atrial pacing after chronic occlusion of the left circumflex coronary artery (LCx). Because other studies have described functional differences between the left anterior descending (LAD) and the LCx perfusion beds, we tested the hypothesis that these two territories exhibit quantitative differences in their responses to demand-dependent myocardial ischemia. To do so, 25 sedated dogs were studied 3 weeks after implantation of an ameroid constrictor around the proximal LCx (15 dogs, group I) or the LAD (group II). Oxygen demand was increased by rapid atrial pacing at rates of 90 to 210 beats/min, myocardial blood flow was measured by serial injections of radiolabeled microspheres, and the electrocardiographic consequences were evaluated by isopotential body surface mapping. Endocardial flows and the endocardial/epicardial flow ratio fell to significantly lower levels during atrial pacing in the ischemic LAD bed than in the LCx perfusion zone. Electrocardiographic patterns indicative of subendocardial ischemia also developed with lesser abnormalities in endocardial/epicardial ratios as determined by logistic regression models, in the LAD than in the LCx bed. Thus the LAD bed is more susceptible to ischemia than the LCx region because of differences in collateral blood flow patterns. In addition, the intensity of the surface electrocardiographic potentials during ischemia was significantly greater, as measured by linear regression, after LAD than after LCx obstruction. These data thus demonstrate significant differences between the two cardiac regions as electrocardiographic potential sources during ischemia.

Animals↗
PubMed1986

Determination of the spatial and intensity properties of atrial repolarization potentials in the dog.

Body surface electrical potentials generated by atrial repolarization (Ta wave) normally extend from the P wave into or through the QRS complex. Thus, the Ta wave is partially obscured by the QRS complex and, conversely, the QRS complex is composed of atrial recovery as well as ventricular depolarization forces. To better study the spatial patterns and magnitudes of the Ta wave, transient atrioventricular (AV) block was induced in 15 dogs by atrial pacing using surgically implanted left or right atrial electrodes. ECG potentials were registered from 84 torso electrodes, and cycles with normal and with blocked AV conduction were segregated. In blocked cycles, the duration of the Ta wave measured 248.0 +/- 25.3 msec with right and 256.0 +/- 38.4 msec with left atrial stimulation. In all cases, the Ta wave extended into the QRS and, in 75% of cases, it extended into the S-T segment. Peak Ta magnitudes, measuring 50.7 +/- 17.9 and 51.8 +/- 21.7 uV RMS with right and left atrial stimulation, respectively, occurred during the P-R segment in all cases. The effect of Ta wave superposition on the QRS complex was assessed by subtraction of patterns in cycles with blocked AV conduction from those with intact AV conduction. Differences between directly recorded QRS waveforms and those computed by subtraction of the Ta wave were small; correlation coefficients exceeded 0.96 and differences in instantaneous RMS potential were less than 6%. Thus, the atrial recovery waveform does extend into the QRS and into the S-T segment in most cases, but the effect of this superposition of Ta on QRS waveforms is quantitatively small.

Animals↗
PubMed1986

R and S wave changes produced by experimental nontransmural and transmural myocardial infarction.

Electrocardiographic R and S wave changes occur after transmural myocardial infarction. It was the purpose of this study to define the spatial characteristics of these changes and their pathologic determinants after nontransmural as well as transmural necrosis. Twenty-six dogs were studied after occlusion of the left circumflex coronary artery for 60 to 240 minutes, followed by reperfusion. Electrocardiographic potentials were recorded before and 1 week after infarction using an 84 electrode array to compute maximal and root-mean-square R and S wave voltages. Infarct size was quantitated by computer-aided evaluation of heart slices stained by triphenyltetrazolium chloride. R and S wave amplitudes after infarction varied widely from one torso site to another in a pattern generally consistent with the inferoposterior location of the infarcted zones. Although changes in peak R and S wave potentials did not significantly correlate with infarct size, differences in pre- and postocclusion root-mean-square R and S wave amplitudes did, with correlation coefficients of -0.79 and -0.63, respectively. Root-mean-square values increased for small lesions and decreased for larger ones. These data indicate that nontransmural as well as transmural infarction can produce R and S wave changes that are dependent on overall lesion size and the specific lead studied. Such changes may represent useful methods to quantitate lesion size.

Animals↗
PubMed1986

Regional blood flow correlates of ST segment depression in tachycardia-induced myocardial ischemia.

Tachycardia produces subendocardial ischemia and ST segment abnormalities after coronary obstruction. To determine whether a quantitative relationship exists between these ST shifts and transmural blood flow, 19 dogs were studied. Coronary obstruction was produced by ameroid constriction of the left circumflex artery, and tachycardia was generated by atrial pacing at 90 to 210 beats/min. ST shifts were studied by body surface isopotential mapping with an 84-electrode torso grid, and blood flow was quantitated by serial radiolabeled microsphere injections. Isopotential maps at each paced rate, 40 msec into the ST segment, were classified as normal or ischemic based on spatial patterns of voltages. Pacing after 3 weeks of ameroid constriction reduced endocardial/epicardial flow ratios in 11 dogs from 1.16 +/- 0.22 at rest to 0.41 +/- 0.18 at 210 beats/min. Abnormal ST depression developed in these dogs at a rate of 184.0 +/- 16.5 beats/min. Endocardial/epicardial ratios with ST depression (0.45 +/- 0.15) were lower than at those without ST depression (1.05 +/- 0.19; p less than .01). Logistic regression analysis demonstrated that ST depression corresponded to an endocardial/epicardial ratio of 0.67 or less (p less than .01). With this model, 95.5% of data sets were correctly classified. Neither heart rate nor perfusion bed size were significant independent predictors of an ischemic electrocardiographic response. The magnitude of abnormal ST segment shift was significantly correlated (r = .87) with the transmural flow ratio. Thus development of electrocardiographic changes indicative of ischemia corresponds to a predictable degree of flow redistribution and the magnitude of the ST shift is correlated with the intensity of the flow abnormality.

Animals↗
PubMed1985

Natural history of left anterior descending coronary artery obstruction: significance of location of stenoses in medically treated patients.

We examined the prognostic significance of an obstructive lesion in the proximal left anterior descending (LAD) coronary artery. Five-year or longer follow-up data were examined from 311 patients with greater than 70% obstruction of the LAD treated without surgery. Mortality was compared in subsets with lesions proximal to and distal to the first septal perforating artery. Survival curves were worse in patients with proximal than with distal LAD disease (p less than 0.05); lesion location remained a significant determinant of survival when ejection fraction, age, and sex were controlled using a Cox regression model. However, when patient subsets were examined, survival with proximal LAD disease was worse than with distal obstruction only in the presence of an associated right coronary artery lesion and an ejection fraction of less than 40% (p less than 0.01). Patients with proximal LAD plus right coronary lesions had a 5-year mortality rate (34.08 +/- 8.9%) that was not significantly (p greater than 0.05) different from that of a group of 66 patients with greater than 50% narrowing of the left main coronary artery (24.02 +/- 4.3%). Thus, proximal LAD disease is more significant than is a distal lesion only in the presence of right coronary obstruction. This two-vessel combination results in a mortality rate as high as that associated with left main coronary artery obstruction.

Cardiac Catheterization↗
PubMed1985

Frequency content of the electrocardiogram. Spatial features and effects of myocardial infarction.

The frequency content of electrocardiographic signals has been used to define amplifier characteristics and, more recently, to detect myocardial pathology. It was the purpose of this study to evaluate the differences in frequency content of ECG signals recorded from different volume conductor surface sites and to determine the effects of coronary ligation on these spatial features. To do so, 15 isolated perfused rabbit hearts, enclosed within a precisely machined sphere, were studied; ten were examined prior to and 15 minutes after ligation of the anterior descending coronary artery. ECG signals, recorded from 32 surface electrodes, were subjected to Fourier analysis. Prior to occlusion, the frequency content of the different electrode signals varied widely, with a greater variance between electrodes than between hearts (p less than 0.01). This variation was related to a reproducible spatial effect, with records over the basal left ventricle having higher frequency components than waves from other sites. After litigation, ECG records from electrodes over electrodes over ischemic areas showed augmented R-wave amplitude and ST-segment elevation. This was associated with a spatial shift of the control high frequency peak to a site overlying the ischemic lesion. Thus the frequency content of ECG is spatially variable and hence lead-dependent, and this spatial variability is directly affected by acute myocardial infarction.

Animals↗
PubMed1985

Ability of standard ECG parameters to detect the body surface isopotential abnormalities of pacing induced myocardial ischemia in the dog.

The ability of parameters derived from standard, scalar ECG leads to predict abnormal body surface isopotential distributions was tested in 25 dogs. Atrial pacing to rates of 170 beats per minute or greater, two weeks after implantation of an ameroid constrictor on the left circumflex coronary artery, resulted in abnormal isopotential patterns due to subendocardial ischemia. A total of 96 scalar ECG variables (potential and slope measurements at 20, 40, 60 and 80 msec into the ST-segment in each of 12 leads) were computed. Ability of each variable and potential-slope pairs to distinguish normal from ischemic map forms was tested using discriminant function analysis and simple classification procedures. Results demonstrated that accuracy of prediction was lead-dependent, and time-dependent, with different sensitivities, specificities and boundary values in different leads and at different instants during the ST-segment. These new concepts may have direct relevance to the selection of clinical exercise ECG diagnostic criteria.

Animals↗
PubMed1985

Effects of tachycardia with normal and ectopic ventricular activation on S-T segment potential and patterns in the dog.

Tachycardia induced by atrial pacing in the dog increases the intensity of potentials recorded on the body surface during the ST-T interval. The effects of tachycardia caused by ectopic right or left ventricular stimulation on ventricular recovery potentials were studied in 30 dogs. Rate was increased in a stopwise manner from 90 to 250 beats per minute by atrial pacing (ten dogs), or by left atrial-right ventricular sequential pacing (ten dogs), or by left atrial-left ventricular sequential pacing (ten dogs). ECG effects were determined by construction of body surface isopotential maps from voltages registered from 84 torso electrodes using a P-R segment baseline. Ectopic stimulation intensified the repolarization maximum and shifted its location to correspond with sites of epicardial stimulation. These findings reflect a reduced cancellation of transventricular differences in recovery times, with earliest recovery occurring at earliest activated sites. Increasing rate with any one activation pattern linearly increased potential extrema magnitudes without further changes of spatial features. This singular response to tachycardia regardless of activation sequence is consistent with an increase in the apparent moment of a repolarization dipole without alteration of its orientation.

Animals↗
PubMed1985

Effects of experimental myocardial infarction on the ST segment response to tachycardia.

Prior studies have shown that tachycardia results in ST segment depression in dogs with chronic, gradual coronary occlusion. This response was compared with that produced by acute, total occlusion of the left anterior descending artery. Ten dogs served as controls; in another 10 dogs, an ameroid constrictor was implanted about the left anterior descending artery. This artery was acutely ligated in a third set of 10 animals, and in a final set of 10, the distal left anterior descending coronary vasculature was embolized by latex injection. Tachycardia was produced by atrial pacing from rates of 90 to 250 beats/min using implanted atrial electrodes. Electrocardiographic signals registered from 84 torso electrodes were used to construct body surface isopotential maps during the ST segment. In normal dogs, pacing increased repolarization potentials without shifts in spatial features. New and abnormal anterior negativity, correlating with significant ST depression, appeared at rates of 170 beats/min or faster in dogs with ameroid constriction. However, in both groups with acute occlusion that produced transmural myocardial infarction, tachycardia resulted in increases in anterior ST elevation and reciprocal ST depression. Specific findings demonstrated the lead dependency of the response to tachycardia and the greater than normal increase in potential magnitudes after infarction than in control cases. The similarity of the response with acute occlusion and with embolization suggested that the response to tachycardia after infarction was not dependent on coronary collateral function but may represent a direct electrophysiologic effect of rate. Thus, these acute occlusion models simulate exercise-induced ST segment elevation as it may be seen clinically.

Animals↗