H.L. Wyatt

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 ventrides that were fixed in formalin and immnersed 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 with M-mode echo and angiography. Thus, short-axis area analysis with cross-sectional echocardiography is well-suited for quantifying left ventricular volumes in dogs.

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 peritneters, 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.

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.

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.

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.

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 pressure 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.

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.

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.

Two-dimensional echocardiographic quantitation of left ventricular volumes and ejection fraction. Importance of accounting for dyssynergy in short-axis reconstruction models.

Two-dimensional echocardiography (2DE) was used to measure left ventricular (LV) enddiastolic volume (EDV), end-systolic volume (ESV) and LV ejection fraction (EF). Thirty closed-chest dogs were studied in the control state and, of these, 11 were restudied 1 hour after proximal left anterior descending coronary artery (LAD) occlusion. Two basic left ventricular volume reconstruction models were used, using 2DE-derived LV long-axis length (L) and short-axis cross-sectional areas (A): (1) Simpsons rule with five short-axis areas and (2) a simplified formula (LVV = 5/6 AL) using a single short-axis area, at either the mitral valve (MV) or mid-papillary muscle (MP) level.In the control state, correlations of 2DE against cineventriculography were satisfactory regardless of the reconstruction procedure, but Simpsons rule gave the highest correlation coefficients. With segmental LV dyssynergy distal to the LAD occlusion, correlations for EDV, ESV and EF were good with the comprehensive Simpsons reconstruction (r = 0.89, 0.86 and 0.92, respectively) as well as with the 5/6 AL formula using the MP level area (r= 0.82, 0.87, and 0.92, respectively). However, there was no significant correlation for ESV and EF when the MV short-axis area was used. Thus, in the presence of significant regional asymmetry, satisfactory 2DE quantitation of LV volumes may be obtained with the simplified model 5/6 AL, but the single cross-section being used must adequately reflect the deranged LV geometry. This formula appears particularly suited for clinical 2DE studies in the presence of regional dysfunction, including beat-to-beat or sequential assessment of spontaneous events and evaluation of the effects of interventions.

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 < 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 Asg/kg/min); LVEDP did not change but cardiac output decreased significantly. LAD artery flow improved markedly and lactate production shifted to extraction (P < 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.