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Biomedical subjects

S Meerbaum

Publications and source records attributed to S Meerbaum.

At least 73 records · Page 4Linked to original sources

Divergent effects of inotropic stimulation on the ischemic and severely depressed reperfused myocardium.

Mechanical function remains depressed for hours and days after even brief periods of ischemia. To determine whether the depressed function of the reperfused myocardium could be improved y inotropic stimulation, we studied segmental function during ischemia and after reperfusion using mercury-in-Silastic length gauges in 15 dogs. During coronary artery occlusion, segmental function could not be improved by inotropic stimulation with dopamine. Release of occlusion after 30 minutes of ischemia resulted in only slight improvement in segmental function (systolic shortening at 20% of control). After reperfusion, segmental function could be markedly enhanced by inotropic stimulation. The response to inotropic stimulation was similar after reperfusion after 3 hours of ischemia if the myocardium remained viable (nine dogs). When the myocardium was necrotic (five dogs), there was no improvement after reperfusion, either spontaneously or in response to inotropic stimulation. If applicable to humans, these results suggest that intractable pump failure caused by extensive but reversible ischemia could be effectively treated by reperfusion and inotropic stimulation.

Animals↗

Two-dimensional echocardiographic assessment of left ventricular stroke volume: experimental correlation with thermodilution and cineangiography in normal and ischemic states.

Left ventricular stroke volumes derived by two-dimensional echocardiography (2D echo) were compared with thermodilution and cineangiography measurements in closed-chest dogs before andone hour after proximal LAD occlusion. Stroke volume was calculated from end-diastolic and end-systolic volumes reconstructed by two models: 1) Simpson's rule employing left ventricular length and five short-axis cross-sectional areas; 2) a simplified volume formula (V = 5/6 area . length), utilizing a single short-axis area at either the mitral valve or midpapillary muscle level. The comprehensive Simpson reconstruction yielded a good correlation of 2D echo stroke volume against thermodilution (r = 0.89) over a range of normal (N = 14) and ischemic (N = 8) states. The simplified formula provided a satisfactory correlation (r = .90, N = 22) when using the midpapillary cross-section, which encompassed the induced ischemic dys-synergy. In contrast, when using the mitral valve level cross-section above the site of ventricular asymmetry, there was no significant statistical correlation. Comparison of cineangiography with 2D echo volume reconstruction based on the simplified formula with the midpapillary muscle level section yielded good correlations for stroke volume (r = 0.87) and ejection fraction (r = 0.97). Intraobserver and interobserver variability of duplicate echo stroke volume measurements was 8% and 10%, respectively. We conclude that 2D echocardiography in dogs permits quantitation of left ventricular stroke volume in normal and ischemic states.

Animals↗

Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique.

Gross histochemical delineation of myocardium which has lost dehydrogenase enzyme activity has been shown to facilitate macroscopic recognition of necrotic myocardium. The present study was undertaken to assess the accuracy of the triphenyl tetrazolium chloride (TTC) technique for quantitating myocardial infarct size very early after coronary occlusion. In 16 closed-chest dogs the left anterior descending coronary artery was occluded with an intra-arterial balloon. Twelve dogs were killed 6 hours after occlusion, their hearts excised, cut from apex to base into 1 cm thick slices, and incubated in TTC. Whole-mount histologic sections of each slice were prepared. Myocardial infarct size was measured by planimetry of photographs of each gross slice and histologic section using classical criteria of necrosis. Myocardial infarct size determined in 54 slices by the TTC technique and histologically was similar (25 +/- 16% vs 27 +/- 16% of the left ventricular mass, mean +/- SD) with close correlation between the two methods (r = 0.91). Four dogs were killed 3 hours after occlusion and TTC stained and unstained myocardium was studied by electron microscopy. When the TTC technique identified necrosis so did electron microscopy. Areas identified by the TTC technique as non-necrotic were either normal or only ischemic by electron microscopy. Thus, using TTC, necrosis can be quantitated reliably 6, and even 3 hours after coronary occlusion, before histologic changes are clearly diagnostic. This technique represents a reliable, practical means for quantitation of recent infarction and for studying the evolution of ischemic injury in its early phase.

Acute Disease↗

Real time computerization of two-dimensional echocardiography.

A computerized system was developed for real time acquisition, enhanced processing, analysis, and display of cross-sectional images of the left ventricle derived by two-dimensional echocardiography (2DE). The new methodology couples a standard medical imaging computer system to the video output of any current 2DE unit, uses a 128 x 128 or 64 x 64 matrix window and stores the real time 30 frames/sec digitized images on a magnetic disk. Computerized beat-to-beat and frame-by-frame processing employs space-time smoothing the automatic detection of endocardial interfaces by standard threshold and second derivative techniques. Multiple views are displayed in real time with 256 levels of gray and color. The methodology was used to analyze and graphically display frame-by-frame changes throughout the cardiac cycle. In addition, regional wall motion and thickness were analyzed in 12 sectors of individual cross-sections using a standardized angular subdivision originating at the center of area and indexed by an external reference point. An algorithm was developed to correct cross-sectional interference definition from the commonly used trailing-to-leading edge to the more valid leading-to-leading outline technique. Computerized analysis of spatial and temporal variations of cardiac contraction were demonstrated in several clinical and experimental applications, including bicycle exercise testing, investigation of acute myocardial infarction, and assessment of interventions. Initial evaluation indicates that the new real time computerized digital acquisition and data analysis represents a major advances toward quantitation of left ventricular function using 2DE.

Animals↗

Characterization of left ventricular mechanical function during arrhythmias with two dimensional echocardiography. I. Premature ventricular contractions.

Two dimensional echocardiography was applied experimentally in the closed chest dog to quantitate left ventricular function during and immediately after single premature ventricular contractions induced through threshold stimulation at the apex. Coupling intervals were varied over a range from 35 to 85 percent of the R-R interval during normal sinus rhythm (920 to 980 ms). The quality of tomographic echocardiographic images during premature as well as postextrasystolic beats was found to be satisfactory for quantitating short axis section areas at end-diastole and end-systole. A systolic fractional area change was computed from two dimensional echocardiographic measurements to characterize mid ventricular cardiac function, which correlated significantly with peak left ventricular pressure and maximal first derivative of left ventricular pressure (dP/dt). Marked shortening of coupling intervals reduced fractional shortening during premature systole and enhanced the degree of potentiation during the postextrasystolic beat. By contrast, premature beats with relatively long coupling intervals caused less reduction in contraction and only minor postextrasystolic potentiation. Systolic shortening of left ventricular length as well as transverse diameters were studied in a two dimensional echocardiographic long axis cross section. During long coupling intervals contraction was normal except for distinct regional systolic outward "bulging" in the apical region. In contrast, short coupling intervals were associated with a more significant generalized derangement of ventricular wall motion during systole. It is concluded that the two dimensional echocardiographic method can be used to portray and quantitate global as well as regional left ventricular function during disturbances of cardiac rhythm.

Animals↗

Quantitative two dimensional echocardiography during bicycle exercise in normal subjects.

A quantitative two dimensional echocardiographic study was conducted in 10 normal subjects performing bicycle exercise in a supine position. Standardized two dimensional echocardiographic short axis and apical views of the left ventricle were analyzed to derive left ventricular sectional areas and length. Over a range of exercise heart rates from 108 to 152 beats/min, satisfactory two dimensional echocardiographic views and measurements were obtained for quantitative assessment of sectional and global left ventricular function. Variability of left ventricular short axis area measurements ranged from 2.9 to 8.3 percent. Left ventricular volume reconstruction employed a simplified formula (volume = 5/6 area X length) with a single papillary muscle level short axis area and left ventricular length. Changes in left ventricular function from rest to exercise quantitated by two dimensional echocardiography indicated a significant reduction in end-systolic volume (from 28.1 +/- 5.6 to 20.8 +/- 4.3 cc/m2, p less than 0.001) and increased left ventricular ejection fraction (from 63.4 +/- 6.3 to 72.1 +/- 5.7 percent, p less than 0.001). The change in end-diastolic volume was not significant. It is concluded that standardized two dimensional echocardiographic study during supine bicycle exercise in normal subjects provides good reproducibility of measurement of sectional and global left ventricular function. Quantitative two dimensional echocardiographic exercise study of global as well as segmental left ventricular performance in patients may be feasible using standardized procedure and analysis.

Adolescent↗

A closed chest animal model for the study of reversible ischemia.

An experimental methodology consisting of partial coronary occlusions, pacing-induced myocardial ischemia and photokymography-aided fluoroscopic study of segmental left ventricular motion, was verified in 14 closed chest dogs. A partial intracoronary occluder device was found suitable for single or multiple coronary arterial stenosis, and remained patent up to 10 h with 10/cm3 heparin administration. With 38% proximal left circumflex coronary artery stenosis, pacing up to 220 beats/min produced no significant regional or global left ventricular dysfunction. In contrast, a 68.5% stenosis which was not associated with dysfunction in the resting state produced significant derangements of segmental motions at a pacing rate of 150 beats/min. Photokymography probes placed at several segments of the left ventricular epicardial and endocardial interface delineated by fluoroscopy or ventriculography allowed monitoring of regional contractions in both pacing-induced ischemic and remote nonischemic zones. The methodology is considered ready for further applications in experimental studies of ischemic states and treatments, simulating clinically meaningful coronary stenosis in the animal without requiring prior thoracotomy and pericardiotomy for implanting occluders.

Animals↗

Experimental evaluation of the extent of myocardial dyssynergy and infarct size by two-dimensional echocardiography.

The extent of left ventricular (LV) dyssynergy was assessed noninvasively in 19 dogs with two-dimensional echocardiographic short-axis sections during myocardial ischemia and infarction. After coronary occlusion, two-dimensional echocardiography uniformly indicated an increase in LV end-diastolic volume and a decrease in LV ejection fraction. Two-dimensional echocardiographic measurements of dyssynergy were evaluated and compared in three subgroups against (1) the extent of LV dyssynergy determined by force-gauge mapping during 10 coronary occlusions of 30-60 minutes' duration in eight open-chest dogs, (2) infarct size delineated by nitroblue tetrazolium (NBT) staining of left ventricular slabs after 48 hours of left anterior descending coronary artery (LAD) occlusion in five closed-chest dogs, and (3) NBT infarct size after 3-hour LAD occlusion followed by 45 hours of reperfusion in six closed-chest dogs. Linear regression analysis of results from these three comparisons gave good correlations (r = 0.89) for groups 1 and 2; in group 2, the extent of dyssynergy by two-dimensional echocardiography was consistently greater than infarct size by NBT. In group 3, the correlation was poor (r = 0.39). These results suggest that an adequate estimate for the extent of LV dyssynergy or infarct size may be obtained with two-dimensional echocardiography during myocardial ischemia or infarction, but not in the presence of coronary reflow, which causes an acute discrepancy between myocardial viability and function.

Animals↗

Cross-sectional echocardiography. III. Analysis of mathematic models for quantifying volume of symmetric and asymmetric left ventricles.

Cross-sectional echocardiography was utilized for quantification of volume in 19 formalin-fixed left ventricles in the presence or absence of ventricular symmetry, defined by the ratio of septal-lateral to anterior-posterior diameter. In 10 symmetric ventricles this ratio was 1.23 +/- 0.06 (mean +/- SEM), whereas in nine asymmetric ventricles the ratio was 1.80 +/- 0.07. Area, diameter, and length measurements were obtained from short- and long-axis cross-sectional images of the left ventricle and volume was calculated by five mathematical models previously described. To evaluate the reliability of each model, echocardiographic left ventricular volume was compared by linear regression and percent error analyses to directly measured fluid volume. In symmetric ventricles, excellent correlations (r = 0.996 to 0.967) and reasonable mean percent errors (6% to 31%) were observed for all models. In asymmetric ventricles, models utilizing short-axis area or two short-axis diameters retained high correlation coefficients (r = 0.985 to 0.956) and similar mean percent errors, but standard formulas previously used with M-mode echo and angiography showed lower correlations (r = 0.886 to 0.873) and higher mean percent errors (52% to 54%). Thus, in the presence of ventricular asymmetry, analysis of short-axis areas or diameters with cross-sectional echocardiography is well suited for quantification of left ventricular volumes.

Cardiac Volume↗

Cross-sectional echocardiography. II. Analysis of mathematic models for quantifying volume of the formalin-fixed left ventricle.

Cross-sectional echocardiography was used to quantify volume in 21 canine left ventricles that were fixed in formalin and immersed in mineral oil. Area, length and diameter measurements were obtained from short- and long-axis cross-sectional images of the left ventricle and volume was calculated by seven mathematic models. Calculated volume was then compared, by linear regression and percent error analyses, with fluid volume of the left ventricle, obtained by filling the chamber with a known amount of fluid. Volumes ranged from 13-146 ml. Mathematic models using short-axis area and long-axis length gave higher correlation coefficients (r = 0.982 and r = 0.969) and lower mean errors (10-20%) than standard formulas previously used for M-mode echo and angiography. Thus, short-axis area analysis with cross-sectional echocardiography is well-suited for quantifying left ventricular volumes in dogs.

Animals↗

Cross-sectional echocardiography. I. Analysis of mathematic models for quantifying mass of the left ventricle in dogs.

Cross-sectional echocardiography was used to quantify left ventricular mass noninvasively in 21 dogs. Short- and long-axis cross-sectional images of the left ventricle were reproducibly traced at endocardial and epicardial borders during stop-motion video-tape replay. We used area, length and diameter measurements to calculate left ventricular mass by seven mathematic models, including the standard formulas used with M-mode echocardiography and cineangiography. Calculated mass was compared with excised weight of the left ventricle by regression and percent error analyses. Formulas using short-axis areas and long-axis length resulted in higher correlation coefficients (0.94--0.95) and lower mean errors (6--7%) than for standard formulas. Since short-axis areas account for regional left ventricular irregularities, noninvasive quantification of left ventricular mass by cross-sectional echocardiography in dogs is most accurate with formulas using short-axis areas.

Animals↗

Synchronized retroperfusion of coronary veins for circulatory support of jeopardized ischemic myocardium.

A retroperfusion system was developed that augments retrograde delivery of arterial blood into an acutely ischemic myocardial region during diastole and facilitates coronary venous drainage in systole. An electrocardiogram-synchronized, gas-actuated bladder pump propels retroperfusate through an autoinflatable balloon catheter whose tip is placed within the regional coronary vein that drains the ischemic myocardium. Experiments were performed in 26 closed chest dogs with 4 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery. An untreated control series consisted of 13 dogs; the remaining 13 dogs were treated with retroperfusion, which was initiated after the first hour of acute coronary occlusion. Synchronized retroperfusion resulted in a significant 37 +/- 10 per cent (mean +/- standard error of the mean) decrease in left ventricular end-diastolic pressure from 11 +/- 2 to 5 +/- 21 mm Hg, a 20 +/- 4 percent decrease in peak systolic pressure (140 +/- 7 to 110 +/- 6 mm Hg) and a 25 +/- 6 percent reduction in systemic vascular resistance (3,880 +/- 340 to 2,380 +/- 300 dynes sec cm-5). Ischemic region intracoronary S-T segment elevation decreased 40 +/- 15 percent, and potassium loss was reduced 92 +/- 22 percent. Partial pressure of oxygen measured distal to the coronary occlusion decreased 36 +/- 2 percent, suggesting oxygen delivery to and extraction by the jeopardized ischemic myocardium. Ventriculography in four dogs revealed an increase in left ventricular ejection fraction and reversal of ischemic segment dyskinesia by synchronized retroperfusion. A nitro-blue tetrazolium study of 10 excised hearts indicated that 3 hours of synchronized retroperfusion significantly reduced the size of ischemic injury to 3.3 +/- 2 percent of the left ventricle (versus 16.2 +/- 5 percent in the untreated control group). In addition, retroperfusion appeared to correct ischemic arrhythmias. The experimental data suggest that this treatment is capable of improving cardiac function and salvaging jeopardized myocardium. Clinical application is envisioned as a prompt temporary emergency support for acute and profound ischemic dysfunction not readily treatable by other interventions.

Animals↗

Derangements of myocardial metabolism preceding onset of ventricular fibrilliation after coronary occlusion.

To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.

Animals↗

Is early revascularization following acute coronary occlusion a safe and effective surgical procedure?

Coronary bypass surgery performed after more than 3 or 4 hours of coronary occlusion may results in serious derangements of cardiac metabolic, contractile, and electrical functions, and lead to extensive myocardial infarction, as well as to an unacceptable mortality. If the operation can be performed within the first 1 to 2 hours of acute coronary occlusion, hospital mortality rate is acceptably low. Although the average infarct size was usually reduced by reperfusion after 3 hours of experimental occlusion, in about 30 percent of cases there appeared to be no salvage of jeopardized myocardium.

Acute Disease↗

Do risk factor interventions prevent or reverse arteriosclerosis?

We have attempted to summarize the current controversies regarding risk factors and preventive measures for control of arteriosclerosis and coronary heart disease. Recognizing that the genesis and development of the disease process are extremely complex and the basic knowledge is limited, it is not likely that conclusive answers to questions will be forthcoming soon which will provide more effective preventive or therapeutic measures. It might be desirable to institute educational and control program aimed at curtailing, at a young age, known AS risk factors such as heavy smoking, particularly if the family history indicates severe risk. Few will question the normal approaches to the treatment of complications of coronary heart disease by control of hypertension, elevated cholesterol, and smoking. However, great caution must be exercised when trying to institute large scale modifications in prevailing life patterns, particularly when based on indefinite risk factor studies and in the face of potentially profound and frequently unknown consequences. The unknowns of atherosclerotic heart disease risk factors, coupled with uncertainties and even doubts about protracted and expensive population studies, lead us to propose an emphasis on alternate selective approaches. We strongly believe that fundamental to progress in the field of arteriosclerosis is an amplification of preventive research efforts with stronger attention focused upon influencing the atherosclerotic processes within the arterial wall. But, more immediately, we urge systematic gathering and careful evaluation of patient data in particular population subsets which exhibit and accelerated mode of arteriosclerosis. Comparative studies of patients, particularly twins, families, and ethnic populations with redilection to early or accelerated arteriosclerosis may be extremely rewarding. Our repeated review of the enormous literature suggests that worldwide collaboration is needed to perfect more meaningful protocols as well as to correlate and critically evaluate existing data provided by population studies of this insidious disease process which represents an evermounting burden to society.

Adult↗