Assessment of quantitative methods for 2-dimensional echocardiography.

Several 2-dimensional echocardiographic (2-DE) methods were tested in vitro for accuracy of linear and cross-sectional measurements and in vivo for left ventricular (LV) volume reconstruction. With 2-DE instrument settings at low and high gains and with precise in vitro calibrations, we studied myocardial slice thickness (3.0 to 10.0 mm). The 2-DE myocardial thickness was measured by leading-trailing, trailing-leading, and leading-leading methods. Regression analysis of 2-DE versus direct measurements yielded excellent correlations for all 3 methods (r greater than 0.985), with interobserver variability less than 3%. Accuracy of measurement was satisfactory only for the leading-leading method (3 and 6% error at low and high gains, respectively); other methods substantially over- or underestimated thickness. Thin myocardial slices (less than 1 mm thick) were applied to cylinders and fixed in formalin to produce precise cavity areas (1.8 to 7.0 cm2). Regression analysis of 2-DE versus actual cavity area gave high correlations (r greater than 0.970), and low interobserver variability (less than 4%) for the inner edge and leading edge methods, but the leading edge method was the most accurate (1.3 to 2.5% error). In vivo LV volumes in 7 anesthetized dogs were compared with 2-DE and cineangiography. Good correlations (r = 0.92) were obtained, but the inner edge method underestimated angiographic volume, whereas the leading edge method reduced the magnitude of underestimation. Thus, the leading edge method for 2-DE is most accurate not only for linear and cross-sectional measurements of the myocardium, but also for application to in vivo LV volumes.

Early changes in regional and global left ventricular function induced by graded reductions in regional coronary perfusion.

To determine the sequence of changes in segmental myocardial function, regional lactate metabolism and global left ventricular function induced by mild regional ischemia, blood flow in the left anterior descending coronary artery of 10 dogs was reduced by 10 percent decrements with use of a screw clamp. At each level of flow, segmental mechanical function and regional metabolism were assessed, the former with use of a mercury-in-Silastic length gauge and the latter with transmyocardial lactate balance measurements obtained with sampling from the anterior interventricular vein. Coronary arterial flow at the onset of regional lactate production was 48 +/- 4 percent (mean +/- standard error of the mean) of the control value. The onset of segmental mechanical dysfunction coincided with the onset of lactate production. Epicardial S-T segment abnormalities over the ischemic zone usually could not be detected until coronary flow was further reduced. After the onset of regional ischemia there was a linear correlation between coronary arterial flow and regional lactate production. At the onset of mild regional ischemia, defined as the onset of regional lactate production, no significant or directionally consistent changes were noted in standard measurements of global left ventricular performance, including heart rate, mean aortic pressure, left ventricular end-diastolic pressure, cardiac output, stroke volume, stroke work and peak positive dP/dt (maximal rate of rise of pressure). However, peak negative dP/dt (maximal rate of pressure decrease) decreased from 99 +/- 2 to 89 +/- 3 percent of the control value (P less than 0.0005) coincident with the onset of ischemia. It is hypothesized that dyssynchronous wall motion in the ischemic zone during isometric relaxation accounts for this decrease in peak negative dP/dt.

Effect of graded reductions in regional coronary perfusion on regional and total cardiac function.

This study examines the effects of graded reduction in regional coronary perfusion and changes in arterial oxygen concentration upon regional myocardial function and left ventricular function. In 14 open chest dogs, the distal left anterior descending coronary artery was cannulated and perfused at different pressures with blood equilibrated with either 21 or 95 percent oxygen, and regional function in the perfused myocardial segment was determined by use of the pressure-length loop. The mass of perfused left ventricular myocardium was determined by injection of sodium fluorescein at a constant pressure of 100 mm Hg. Regional function decreased minimally as coronary perfusion pressure and flow were reduced to 50 to 65 mm Hg and 25 to 55 ml/min per 100 g, respectively. When pressure and flow were reduced below these critical ranges, regional function decreased sharply. Changes in left ventricular function were comparable but of lesser magnitude. The relations between regional function or left ventricular function and coronary perfusion were not affected by changing arterial oxygen concentration, except at the low range of coronary perfusion pressures (22 plus or minus 6 mm Hg), at which pressure regional function was significantly lower (P less than 0.025) in the experiments with 95 percent oxygen. Thus, the sensitivity of myocardial performance to a decrease in effective coronary perfusion pressure and flow is remarkably dependent upon whether pressure and flow are above a critical level.

Functional abnormalities in nonoccluded regions of myocardium after experimental coronary occlusion.

The performance characteristics of both ischemic and "adjacent" and "remote" nonischemic myocardium were studied in open chest dogs by three mercury-in-Silastic length gauges sutured to the anterior surface of the left ventricle before and after occlusion of the distal left anterior descending coronary artery. The adjacent gauge was separated from the ischemic segment by one large nonoccluded diagonal branch of the left anterior descending artery. Remote myocardium was separated from the ischemic area by two such branches. At the time of occlusion epicardial S-T segment elevation appeared in the ischemic region but not in the adjacent or remote regions. Immediately after occlusion, typical changes of ischemic dysfunction appeared. Late systolic lengthening, depression of systolic shortening and increased diastolic compliance occurred consistently and simultaneously in ischemic and adjacent regions and inconsistently in the remote region. Five minutes after occlusion, fiber shortening was depressed to 21, 58 and 67 percent of control values in ischemic, adjacent and remote regions, respectively. Heart rate did not change, and mean arterial pressure decreased slightly. These changes persisted over time. In 11 of these dogs, end-diastolic pressure was maintained constant 20 minutes after occlusion. Systolic shortening was depressed to 40 and 74 percent of control values in the ischemic and adjacent regions, respectively. In six dogs, end-diastolic pressure was varied form 5 to 20 mm Hg by rapid volume loading during the control state and 30 minutes after occlusion. Systolic shortening in ischemic, adjacent and remote regions was depressed to 20, 40 and 65 percent of control values, respectively. The severity of all functional alterations after coronary occlusion was directly related to proximity to the ischemic region. These results indicate that depression of left ventricular function after coronary occlusion may be partially related to previously unrecognized depression of function in apparently "nonischemic" myocardium.

Influences of physical conditioning and deconditioning on coronary vasculature of dogs.

To investigate the effects of physical conditioning and deconditioning on the coronary vasculature, eight dogs were exercised by treadmill running. Five dogs were deconditioned by confinement in cages following the conditioning period. A technique was developed and validated for measuring circumflex coronary artery diameter from magnified projections of standardized coronary angiograms. Myocardial capillary density, perimeter, and basement membrane thickness were determined from electron microscopy of serial ventricular septal biopsy samples. Physical conditioning caused a small but statistically significant increase in cross-sectional area of the circumflex artery. Although physical conditioning caused no statistically significant changes in the myocardial capillaries, trends were apparent for increases in density and perimeter of myocardial capillaries and a decrease in basement membrane thickness. Physical deconditioning caused statistically significant reductions in cross-sectional area of the circumflex artery and in myocardial capillary density but little change in perimeter or basement membrane thickness of myocardial capillaries. The results suggest that physical conditioning may be associated with an improvement in coronary vascular capacity which may regress rapidly with deconditioning.

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.

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.

Clinical evaluation of left ventricular function using the cardiac helical fiber model: an echocardiographic study.

The cardiac helical fiber concept was introduced in 1969 and was shown mathematically to provide better approximations of normal ejection fractions compared with the conventional circumferential fiber model. The clinical applicability of this concept was evaluated noninvasively by M-mode and two-dimensional echocardiography in 55 subjects: 10 with aortic insufficiency, 10 with congestive cardiomyopathy, eight with hypertension, eight who were long-distance runners, 12 who were active and seven who were sedentary normals. Comparison of myocardial shortening by the circumferential and helical fiber models showed that the former discriminated only two groups of subjects, while endocardial and epicardial helical shortening discriminated three and four groups, respectively. Regression analyses suggest that more than 90% (r2 = 0.92) of variation in ejection fraction may be accounted for by variation in endocardial shortening, and that more than 75% (r2 = 0.77) of variation in observed endocardial shortening may be accounted for by variation in epicardial contraction. The study demonstrates that the helical fiber length concept may be useful for the noninvasive evaluation of left ventricular function in man.

Quantitation of regional cardiac function by two-dimensional echocardiography. I. Patterns of contraction in the normal left ventricle.

Regional differences in wall motion and wall thickening were quantitated in the normal left ventricle using two-dimensional echocardiography (2-D echo). Using a computer-aided system, the left ventricle was subdivided in a standardized manner into 40 segments of five 2-D echo short-axis cross sections from the mitral valve level to the low left ventricle or apex. Measurements of sectional and segmental cavity areas, muscle areas and endocardial as well as epicardial perimeters, allowed assessment of contractile function using such indexes as endocardial systolic fractional area change (FAC), wall thickening (WTh), and circumferential fiber shortening (shortening). In 50 normal anesthetized, closed-chest dogs (including 10 studies in the conscious state) and in 32 normal humans, left ventricular contractile function increased significantly from base to apex. Thus, in anesthetized dogs, sectional FAC, WTh and shortening increased from left ventricular base to apex as follows: 39.4 +/- 5.1% to 61.6 +/- 7.2%, 20.5 +/- 6.6% to 46.7 +/- 11.5% and 22.7 +/- 3.4% to 35.4 +/- 5.9%, respectively. Similar trends were noted in conscious dogs. In man, sectional FAC, WTh and shortening also increased from the mitral valve to the low left ventricular level: 38.8 +/- 3.3% to 60.7 +/- 4.5%, 23.9 +/- 5.6% to 28.9 +/- 7.6% and 21.4 +/- 5.0% to 30.6 +/- 5.6%, respectively. Detailed segmental analysis in individual cross sections also revealed regional differences in contraction. Generally, contraction was most vigorous in posterior regions of the left ventricle. The septal regions exhibited lowest contraction at the base, but also the greatest increase from base to apex, both in the canine and human. Lateral regions did not show significant changes along the length of the left ventricle. Diastolic wall thickness also varied. We conclude that contraction in the normal left ventricle cannot be assumed to be uniform or symmetrical. These normal regional differences in function should be taken into account when evaluating altered physiologic states and in studying effects of therapeutic interventions.

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.

Post-extrasystolic potentiation of ischemic myocardium by atrial stimulation.

The response of acutely ischemic myocardium to post-extrasystolic potentiation (PESP) was evaluated in 11 mongrel dogs. Mercury-in-silastic length gauges were sutured to the epicardial surface of the left ventricle; left ventricular pressure was determined via an apical large-bore catheter-transducer system and controlled by volume manipulation. The anterior descending coronary artery was then ligated, and single premature atrial contractions were introduced via an external stimulator. Thirty minutes after occlusion, shortening during ejection had decreased an average of 81 +/- 8 per cent, from 1.30 +/- 0.29 to 0.32 +/- 0.05 mm. PESP initially induced a marked restoration toward normal segmental contraction as systolic shortening increased significantly to 1.14 +/- 0.23 mm. Additionally, paradoxic systolic expansion, when present, reverted to a normal pattern of contraction during PESP. Responsiveness to PESP deteriorated progressively with time over 3 hours following occlusion until the muscle became essentially totally unresponsive to this stimulus. It is concluded that a single premature atrial beat may be used to induce PESP and provides an effective stimulus for contractile reserve of acutely dysfunctional ischemic myocardium. Loss of responsiveness to PESP may represent the progression to nonviability following acute ischemia.

Contrasting influences of alterations in ventricular preload and afterload upon systemic hemodynamics, function, and metabolism of ischemic myocardium.

This study of anesthetized, open-chest dogs compares the effects of primary increases in left ventricular preload and afterload upon global and regional myocardial function and metabolism in the presence of a left anterior descending coronary artery stenosis (LAD). When LAD flow was reduced to 40-50% of control, regional systolic shortening declined by 20 to 25% and regional lactate extraction changed to production. In seven control dogs the mechanical abnormalities persisted during the 30 min of observation, but lactate production was reduced spontaneously. In ten dogs, increases in left ventricular end-diastolic pressure (LVEDP) during dextran infusion were associated with increases in cardiac output and regional systolic shortening; however, regional lactate production also increased (P less than 0.05) despite an augmentation in LAD flow. In seven dogs mean arterial pressure increased by an average of 32 mm Hg during angiotensin infusion (0.2 to 0.4 mug/kg/min); LVEDP did not change but cardiac output decreased significantly. LAD artery flow improved markedly and lactate production shifted to extraction (P less than 0.05) while systolic shortening remained unchanged. When angiotensin was discontinued, lactate extraction worsened again. Thus, in the presence of a severe coronary stenosis, a primary increase in preload improves cardiac output but at the expense of aggravated ischemia. In contrast, a primary increase in afterload reduces cardiac output but may improve perfusion and lactate uptake of the ischemic myocardium.

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.

Myocardial reperfusion in acute experimental ischemia. Beneficial effects of prior treatment with steroids.

To test the hypothesis that prior steroid administration may enhance the mechanical and metabolic response to myocardial reperfusion, regional myocardial function (Hg-in-silastic length gauges), transmyocardial lactate balance and K+ difference were measured in 12 control and 13 treated (30 mg/kg methyl-prednisolone, 30 to 60 min postocclusion) dogs. At three hours of ischemia, systolic shortening in the ischemic segment was greater in treated dogs (40.6% vs. 12%, P less than 0.05), while both lactate balance and K+ arteriovenous difference became positive. Lactate balance and K+ difference remained negative in the untreated animals. After three hours of occlusion and one hour of reperfusion, recovery of shortening was significantly greater in the treated animals (75.9 vs. 31.6%, P less than 0.05). In addition, while lactate balance remained negative among the control dogs, it further improved in the treated dogs. Thus, steroid administration during experimental coronary occlusion impedes the progression of ischemia and is additive to reperfusion in reversing ischemic dysfunction.

Noninvasive analysis of regional myocardial wall motion: cardiokymography.

The validity of a new noninvasive device, the cardiokymograph, was assessed as to its ability to detect regional myocardial wall motion by direct comparison of the analog tracing with that of an epicardial length gauge in 11 open-chest dogs. The correlation of the two methods was excellent both during control conditions and following changes induced by acute coronary occlusion. The average difference between the methods in timing of various cardiac events was only 6.2 +/- 1.9 ms at rest and 6.8 +/- 1.5 ms following ischemia (P = NS). Relative amplitude ratio correlations, determined for the four portions of the cardiac cyele (isovolumic systole, ejection, isovolumic relaxation, and diastole), were also excellent. The average correlation of the kymograph to the length gauge was r = 0.896 +/- 0.018 at rest (K = 0.977 LG + 0.033) and r = 0.932 +/- 0.013 following occlusion (K = 1.071 LG + 0.101). Thus, the cardiokymograph is a sensitive and accurate noninvasive method for detection of regional ischemic dysfunction and produces an analog tracing essentially identical to that of the epicardial length gauge.

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.

Hemodynamic and metabolic effects of sodium nitroprusside on the performance and metabolism of regional ischemic myocardium;.

To assess the effects of sodium nitroprusside (5-10 mug/min) on total and regional cardiac performance, energetics, and lactate metabolism during acute ischemia, studies were performed in 21 open-chest dogs. For studies of regional function and metabolism, length gauges were sutured to the epicardial surface and an epicardial vein adjacent to the artery to be occluded was cannulated. Following occlusion of the left anterior descending coronary artery, cardiac output, mean arterial pressure, epicardial vein blood flow, and systolic shortening of the ischemic segment decreased significantly, In the blood samples from the ischemic zone, but not in those from the coronary sinus, lactate extraction shifted to production. In seven control dogs these alterations persisted throughout the experiment. In 14 animals treated with nitroprusside, cardiac output increased while peripheral resistance and mean arterial pressure decreased. Systolic shortening in the ischemic segment increased from 1.10 +/- 0.24 (SEM) to 1.77 +/- 0.30 mm (P less than 0.005). In eight dogs, regional venous outflow increased from 1.9 +/- 0.1 to 3.0 +/- 0.4 ml/min despite a slight reduction in mean arterial pressure. Concomitantly, regional negative lactate balance was reduced from -61.0 +/- 20.0 to -23.2 +/- 5.7% (P less than 0.05). These results indicate that nitroprusside significantly improves both total cardiac performance and the mechanical performance of regional ischemic myocardium. Moreover, this improvement in mechanical function occurred concomitantly with apparent increase in regional perfusion and reduction in lactate production, suggesting that nitroprusside simultaneously alleviates ischemia.

Functional significance of regional ischemic contraction abnormalities.

To evaluate the progression of segment function following induction of ischemia, the left anterior descending coronary artery was ligated (eight dogs) or cannulated and perfused at various pressures via a bypass-oxygenator (six dogs). Mercury-in-silastic length gauges were sutured to the anterior left ventricle, and pressure was recorded by a catheter-tipped transducer. Segment function was determined from the area of the pressure-length loop by plotting instantaneous left ventricular pressure against segment length and by evaluation of the degree of systolic shortening. Segment function decreased linearly as flow in the left anterior descending artery was decreased in a stepwise fashion by reduction in perfusion pressures from 100 to 20 mm Hg. With both left anterior descending coronary artery ligation and stepwise flow reduction, the pressure-length loop invariably showed four clearly identifiable morphologic patterns which relate conceptually to the specific left ventricular contraction patterns: dyssynchrony, hypokinesis, akinesis, and paradoxic systolic expansion. Re-oxygenation following occlusion invariably revealed return to a normal pattern in reverse order. This study demonstrates that a consistent and predictable progression of segmental contraction abnormalities occurs with ischemia.