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So far, application of MC-2DE for detection and delineation of regional perfusion defects involved primarily intracoronary or aortic root injection of the contrast agent, a procedure which can serve as a diagnostic adjunct in the catheterization laboratory. Thus, a left main coronary artery administration of sonicated renografin, during an LAD or left circumflex coronary artery occlusion, significantly enhances myocardial echo intensities in normal zones of a 2DE left ventricular short axis cross section, while the perfusion deficient risk zone remains essentially unenhanced. To evaluate the magnitude of risk zone residual perfusion (e.g. from collaterals), corresponding regional myocardial echo contrast appearance-disappearance dynamics might be studied with computerized MC-2DE videodensitometry. But for such MC-2DE study of an acutely ischemic zone to be effective, supplemental echo contrast would probably have to be injected distal to the coronary artery occlusion (e.g. via the center lumen of an intracoronary balloon catheter). It is uncertain how well a collateral blood supply from normal to ischemic myocardium, or an antegrade delivery via a severely stenosed coronary artery, can be quantitated with a microbubble-containing echo contrast agent.

Two dimensional echocardiographic analysis of global and regional left ventricular function was applied in seven closed chest dogs to study the effects of nitroprusslde In ischemic heart failure. Simultaneous hemodynamic and two dimensional echocardiographic measurements were obtained sequentially: (1) in the control period, (2) after proximal occlusion of the left anterior descending coronary artery, (3) after volume loading, which increased left ventricular end-diastollc pressure to 30.3 ± 9.1 mm Hg (mean ± siandard deviation), (4) during nltroprusside infusion at 33.8 ± 29.4 jug/min and (5) after discontinuation of infusion of nitroprusside. A Simpson reconstruction using five echocardiographic short axis cross sections was used for assessment of left ventricular volumes. Regional function in short axis cross sections at different levels of the left ventricle was expressed as sectional systolic fractional area of change. Furthermore, each short axis section was subdivided into eight 45 ° segments and segmental fractional area change was automatically calculated by computer. Nitroprusside reduced global end-diastolic and end-systolic volumes (p

The consequences of sublingual and intravenous nitroglycerin treatment after acute coronary occlusion were studied in 18 closed chest dogs. Intravenous (0.1 mg/min) or sublingual (0.4 mg/15 min) nitroglycerin therapy was instituted 1 hour after occlusion and the effects were observed over a period of 2 hours. Hemodynamics and global and regional cardiac function were measured in both the coronary occluded and nonoccluded segments of the left ventricle before and during coronary occlusion, and after administration of nitroglycerin. A similar nine dog control series was used to establish the significance of the measured effects of nitroglycerin. Intravenous nitroglycerin therapy after 1 hour of occlusion resulted in a marked increase in heart rate (37 ± 12 [mean ± standard error of the mean] percent), reduction of systolic blood pressure (9 ± 3 percent), decrease in left ventricular end-diastolic and end-systolic volumes (32 ± 5 percent and 34 ± 5 percent), increase in coronary sinus flow (64 ± 24 percent) and decrease in left ventricular stroke work (29 ± 8 percent). Sublingually administered nitroglycerin produced similar trends but much less pronounced effects. However, intravenous or sublingual administration of nitroglycerin provided no improvement or caused further deterioration in ischemic region lactate extraction and potassium loss. The left ventricular ejection fraction, which was severely depressed after 1 hour of occlusion, changed minimally after administration of nitroglycerin, and there was no evidence of any correction of regional left ventricular akinesia or dyskinesia. Whereas mean systemic vascular resistance changed minimally as a result of nitroglycerin therapy, it increased 19 ± 8 percent during a corresponding period of an untreated coronary occlusion series suggesting that nitroglycerin prevented an anticipated increase. Postocclusion S-T segment elevation in the electrocardiogram persisted after treatment. Our data corroborated that nitroglycerin reduced left ventricular volumes and increased coronary sinus flow; however, these improvements were accompanied by persisting metabolic and mechanical derangements in the ischemic region.

Two-dimensional echocardiography during agitated saline contrast injections into the left ventricle was applied in eight closed chest dogs to examine the degree of mitral valve regurgitation encountered with pacing from two sites: 1) at the right ventricular apex and 2) within the coronary sinus at the base of the left ventricle. Pacing was at a rate of 10 beats/min above the sinus rate, and ranged from 60 to 120 beats/min. Hemodynamic variables were monitored, and data on global and regional left ventricular function were derived from a series of short- and long-axis cross-sectional echographic images. The degree of valvular regurgitation was assessed independently by two observers, and systolic appearance of echo contrast in the left atrium was graded as 0 to +4. Although no mitral regurgitation was noted in sinus rhythm, regurgitation was severe with right ventricular apical pacing (3.2 +/- 0.7, mean +/- standard deviation) and relatively mild (0.9 +/- 0.7) with basal pacing (p less than 0.01 and 0.05, respectively). Relative to sinus rhythm, thermodilution stroke volume was significantly (p less than 0.05) depressed by both apical and basal pacing (from 32.6 +/- 14.6 to 25.0 +/- 7.9 and 26.0 +/- 7.6 cc, respectively), but there was no significant difference between the two pacing sites. Mapping of regional function at six levels of the left ventricle revealed significant heterogeneities, with maximal dysfunction noted in the vicinity of the pacing site. It is concluded that significant differences in mitral regurgitation exist depending on the site of pacing, with apical pacing causing severe regurgitation and abnormal regional contraction near the pacing site.

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.

In the present model study on the closed mitral valve, tensile force in the chordae tendineae is related to transvalvular pressure using a mathematical model of mechanics of the closed mitral valve. Circumferential stress as well as bending stress in the valve leaflets were neglected. Without precisely knowing the mechanical properties of the leaflet material, geometry of the leaflets was estimated by applying Laplace's law, which relates leaflet stress to leaflet curvature. Independent of shape of the mitral valve orifice, under all circumstances tensile force in the chordae tendineae was calculated to be equal or greater than half the force exerted on the mitral valve orifice by the transvalvular pressure.

Experimental coronary occlusions were carried out in 12 closed-chest dogs to investigate the functional anatomic characteristics of the mitral valve complex during acute myocardial ischemia. Two-dimensional echocardiography was used to assess left ventricular function, the mitral valve complex, and left atrial size. Presence of mitral regurgitation was assessed by left ventricular contrast echocardiography. Thirty-seven coronary occlusions of up to 10 min in duration were carried out in proximal or distal locations in the left anterior descending and the left circumflex coronary arteries. Mitral regurgitation, which was mild in severity as judged by a small rise in pulmonary artery wedge pressures, was observed in 15 of 37 brief coronary occlusion experiments. Mitral valve prolapse was noted in all 15 experiments, as well as in four additional studies in which mitral regurgitation was not seen. The development of experimental mitral valve prolapse was explained by measurements that demonstrated a relative displacement of the papillary muscle tips toward the mitral orifice. We conclude that mitral valve prolapse is a common sequela of short-term coronary occlusion and is often associated with mild mitral regurgitation. Relative displacement of ischemic papillary muscles toward the mitral orifice appears to be a likely mechanism of acute ischemic mitral valve prolapse.

Myocardial contrast two-dimensional echocardiography was used in 21 closed chest dogs to assess its ability to delineate the extent of underperfused acutely ischemic myocardium. An agitated saline-Renografin echocardiographic contrast agent was injected into the left main coronary artery after left anterior descending coronary artery occlusion, and the size of the contrast echo-free area characterizing the perfusion defect was outlined in short-axis cross sections of the left ventricle. In 13 dogs, monastral blue dye was injected after 45 minutes of coronary artery occlusion and before sacrifice to provide anatomic delineation of underperfused zones in equivalent sections. Perfusion defects assessed by contrast two-dimensional echocardiography correlated well with those delineated by monastral blue dye (r = 0.91). Contrast echocardiographic study was also performed in eight other dogs at 5 hours of occlusion, after which infarct size was measured with triphenyl-tetrazolium-chloride. Contrast echocardiographic outline of the perfusion deficiency correlated but slightly overestimated the extent of necrosis (r = 0.88). It is concluded that contrast two-dimensional echocardiography can detect and outline the underperfused “risk area” during acute coronary artery occlusion, and may also permit assessment of the extent of myocardial infarction.

Two computer-aided videodensitometric methods that may be used in conjunction with two-dimensional contrast echocardiography were examined to quantify the time course of echographic opacification in the myocardium after experimental injections of contrast agents (hand-agitated Renografin-saline and sonicated sorbitol 70% solutions) into the left main coronary artery. Echographic studies of myocardial cross sections were digitized with an image processing computer using a 128 X 128 resolution matrix. Both stop frame and continuous cycle modes of acquisition were performed. A set of computer programs was developed to extract and analyze time-intensity curves from the digitized images. These included cardiac outline delineation, segmental division, regional intensity computation and exponential curve analysis. The stop frame method was applied to experimental studies in 17 closed chest dogs during control states and after coronary occlusions. Significant differences were found in the decay half-lives of echo intensity between normal (24 +/- 8 seconds) and acutely ischemic (293 +/- 165 seconds; p less than 0.001) myocardium for the Renografin-saline solution. Interobserver reproducibility of the measured half-lives was r = 0.91 and standard error of the estimate = 5 seconds. The continuous cycle method of analysis was examined in five closed chest dogs (with up to six injections per dog), applying the sonicated sorbitol 70% solution in only the control state. The mean half-life was 4.2 +/- 1.1 seconds. These computer-based videodensitometric methods might be applied to a wide variety of experimental studies in two-dimensional contrast echocardiography that attempt to quantify myocardial perfusion and function.

A computer algorithm was developed and applied to measure brightness decay rates of myocardial contrast opacification observed with two-dimensional echocardiography (2DE). An agitated mixture of diatrizoate meglumine and saline (Renografin-saline) was injected into the left main coronary artery of 17 closed-chest dogs during the control state as well as after placement of an intracoronary plug to induce 85% stenosis in the left anterior descending coronary artery (LAD) in five dogs. In 12 dogs, injections were also performed distally to complete intracoronary balloon occlusion of the LAD. For each injection, up to 35 electrocardiographic-gated, end-diastolic 2DE frames were digitized into an image-processing computer that determined mean pixel brightness of each of 12 myocardial segments per 2DE short-axis cross-section. Time-activity curves for each segment were generated, and contrast decay half-life (t 1/2) was calculated. Mean t 1/2 for control-state injections was found to be 24.1 +/- 7.7 sec, as opposed to 293.8 +/- 164.5 sec after complete coronary occlusion (p less than .001). In the five dogs in which 85% LAD stenosis was induced, prolongation of contrast t 1/2 from 18.3 +/- 8.9 sec during control to 44.3 +/- 21.0 sec (p less than .001) after plug insertion occurred in myocardial segments subserved by the stenosed vessel. No significant change occurred in segments that were not supplied by the stenosed vessel (21.9 +/- 9.1 sec during control vs 24.9 +/- 11.6 after plug insertion into the LAD). A reproducibility study of injection-to-injection t 1/2 in the control state indicated a correlation coefficient of r = .84 and a standard error of the estimate (SEE) equal to 5.86 sec, while interobserver t 1/2 reproducibility was r = .91 and SEE = 5.21 sec. The t 1/2 measurement derived by computer analysis of myocardial contrast 2DE may serve as an index for characterization of regional myocardial blood flow and may be applicable to evaluate interventions that alter perfusion.

The relation between experimental coronary stenosis and myocardial contrast echo disappearance rate ("washout") was investigated in anesthetized closed chest dogs. Of 13 dogs, 8 had serial contrast echographic studies with two successive degrees of coronary stenosis (50 and 70%) produced by threading stenotic plugs into the proximal left circumflex coronary artery. Studies were repeated with complete coronary occlusion achieved by inflation of an intracoronary balloon immediately proximal to the plugs. Myocardial contrast echograms were recorded in short-axis cross sections of the left ventricle after intracoronary injection of 2 ml hand-agitated saline-Renografin solution through a catheter placed in the coronary artery. An echo contrast washout index (t 1/2) was measured by digital processing computer analysis of successive end-diastolic images obtained by two-dimensional echocardiography during myocardial contrast agent injection. The injection to injection correlation coefficient of these t 1/2 measurements was satisfactory (r = 0.87, standard error of estimate 4.8 seconds). Involved segment t 1/2 measurements were found to be significantly altered by intracoronary stenosis and occlusion, ranging from 23 +/- 6 seconds (mean +/- standard deviation) in the control state, 29 +/- 9 and 44 +/- 10 seconds for 50 and 70% stenosis, respectively, and 104 +/- 35 seconds for total occlusion. It was concluded that myocardial contrast two-dimensional echocardiographic measurement of t 1/2 appears to be a useful index of the degree of coronary stenosis.

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.

The adequacy of two-dimensional echocardiography during right atrial pacing for the detection and characterization of coronary artery stenosis was examined in 10 closed chest dogs. Pacing at successively higher rates up to 210 beats/min was carried out in the control state and again during a 70% left anterior descending coronary artery stenosis induced with intracoronary plugs. Left ventricular short-axis echographic cross sections were obtained at several levels of the left ventricle. After computer-aided standardized subdivision, contractile function of the global section and its subsegments was characterized by computed systolic fractional area change percent and wall thickening percent. Ventricular segments supplied from the site of the 70% coronary stenosis were delineated in a low papillary level cross section by a myocardial contrast echographic technique, and these segments demonstrated significant dysfunction during pacing at 150 to 210 beats/min. Echographic observation of the involved segments immediately after pacing revealed a maximal depression of function 5 seconds after pacing, equivalent to dysfunction at peak pacing, with function returning to control levels within about 2 minutes. Both maximal pacing and early postpacing studies facilitated satisfactory discrimination of ischemic from normally perfused myocardial segments. These experiments show that right atrial pacing study with quantitative two-dimensional echocardiography may serve to detect and assess a coronary stenosis associated with minor or no cardiac dysfunction in the rest state.

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.

Two-dimensional echocardiography was applied experimentally in a closed chest dog model with intact pericardium to determine the location, magnitude and extent of contractile response during pacing from discrete ventricular sites. Mid ventricular short-axis tomographic images obtained during regular sinus rhythm and subsequent premature ventricular beats provided comparative measurements of global and segmental systolic changes of cross-sectional luminal areas and myocardial wall thickness. Computer-assisted standardized analysis of segmental systolic fractional area change and wall thickening was used to map left ventricular contraction during normal rhythm and premature beats of 70% coupling interval, induced alternately from anterior and lateral aspects of the mid-left ventricular short-axis cross-sectional plane. A characteristic pattern consisting of early systolic contraction and wall thickening was followed by paradoxical motion and wall thinning in late systole in segments corresponding to the region of direct electrical stimulation. Statistical analysis of segment by segment function indicated a maximal amount of premature beat contractile derangement at the site of the stimuli. Pacing from a right ventricular wall site in the midventricular plane caused a similar premature beat response at the anterior aspect of the interventricular septum. It is concluded that two-dimensional echographic analysis of segmental ventricular function can identify the location of electrical stimuli, and thus might non-invasively characterize regional patterns of contraction associated with ectopic foci during arrhythmias.

The effects and reliability of a simple method of contrast two-dimensional echocardiographic delineation of myocardium after intracoronary injections were evaluated in closed-chest dogs. Multiple injections of an agitated saline-Renografin (meglumine diatrizoate) mixture (3:2 ratio, 2-ml bolus) into the left main coronary artery as well as at different sites of the left anterior descending and circumflex coronary arteries were studied in several short-axis and long-axis cross sections of the left ventricle. These contrast injections opacified specific regions of left ventricular myocardium depending on the site of injection. Contrast injection into the left main coronary artery provided a clear, echo-free outline (negative contrast) of underperfused myocardium distal to the coronary occlusion. Reproducibility studies of the extent of involved zones measured in echocardiographic cross sections indicated high intra- and interobserver correlation coefficients (r = 0.97 and 0.97). The effects of the intracoronary injection of contrast material appeared minor and brief. ECG ST-T changes lasted 49.4 +/- 36.7 seconds, aortic systolic pressure was reduced by 7.6 +/- 4.4% for 18.9 +/- 4.8 seconds, and the peak rate of left ventricular pressure rise decreased by 14.3 +/- 2.6%, but returned to control levels within 19.4 +/- 6.1 seconds. The zone of left ventricular asynergy after coronary occlusions was also delineated by cross-sectional echocardiography and corresponded to the contrast-outlined underperfused zone (negative contrast). This new intracoronary echocardiographic technique has only minor hemodynamic consequences and provides reliable quantitation of underperfused and dysfunctioning zones after experimental coronary occlusions. Further investigation and validation of this method may provide useful characterization of the extent and severity of myocardial ischemia and infarction.

This study examined whether an occlusive thrombus within a coronary artery can be lysed by streptokinase retroperfusion into the associated regional coronary vein. Experimental coronary artery thrombosis was induced in 15 closed chest dogs by placing a small copper coil at a proximal site of the left anterior descending coronary artery. Total thrombotic obstruction of this artery was verified within 10 to 60 minutes (38.0 +/- 15.8, mean +/- standard deviation) and streptokinase was administered within 94.0 +/- 17.4 minutes from coil insertion at an average rate of 42 IU/kg per minute by one of three modes: 1) intermittent 10 minute direct coronary venous retroinfusion (five dogs); 2) continuous infusion into the pumping circuit of synchronized phased retroperfusion of the great cardiac vein with arterial blood (five dogs); and 3) for comparison, streptokinase administered intravenously (five dogs). The intracoronary thrombus was fully lysed and anterograde reperfusion established within 51.0 +/- 18.7 minutes by intermittent streptokinase retroinfusion, and in 50.0 +/- 6.1 minutes by streptokinase supplemented synchronized retroperfusion (50.5 +/- 13.2 minutes for pooled retrograde coronary venous delivery). Lysis was also induced by systemic streptokinase, but the time to lysis was significantly longer and more variable (131.6 +/- 60.6 minutes) than with retrograde administration (p less than 0.01). The retroperfusion modality appears the preferable technique because it provides early thrombolysis and, at the same time, improves cardiac function and maintains myocardial viability of the jeopardized ischemic zone pending achievement of full reflow. Thus, streptokinase retroperfusion, if promptly instituted, may be a useful complemental nonsurgical treatment of evolving acute myocardial infarction after thrombotic coronary artery occlusion.

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.

Two-dimensional echocardiography was applied in 10 closed-chest dogs to evaluate, in several left ventricular (LV) short-axis cross sections and subsegments, the regional contractile response to right atrial pacing. Compared with sinus rhythm (81 +/- 10 beats/min), which exhibited a moderate 7.2 +/- 12.0% (mean +/- standard deviation) base-to-apex increment in function, this gradient was significantly augmented to 34 +/- 12% by pacing at a heart rate of 180 beats/min. Measurements of wall thickening and perimeter shortening exhibited similar trends. Differences also were observed in subsegments of individual cross sections: in sinus rhythm the base-to-apex difference in function was relatively minor in the anterior and lateral aspects of the left ventricle (-9.1 +/- 18% and -1.9 +/- 19%), whereas a significant increase was noted in posterior and midseptal zones (18 +/- 17% and 22 +/- 30%). In response to pacing, the anterior and lateral wall base-to-apex gradients were significantly augmented (25 +/- 8% and 35 +/- 34%), but there was no further change in the posterior or septal regions. In conclusion, apical regions of the canine left ventricle responded to right atrial pacing with significant augmentation of contractile function, whereas more basal levels showed little response. Circumferentially, response to atrial pacing was most pronounced in the anterior and lateral segments.

Contrast echocardiography has achieved importance in the diagnosis of cardiac shunt lesions. The technique provides information about flow patterns and serves as an adjunct to identifying communications that may be too small to image, even with high resolution real time scanning. This report reviews clinical applications and experiences in the use of standard, peripherally injected echocardiographic contrast agents for the detection of atrial septal defect, ventricular septal defect and patent ductus arteriosus. The importance and development of transpulmonary contrast agents capable of crossing the pulmonary capillary bed to opacify the left ventricle are reviewed and experience with a variety of experimental

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.

l -dopa was administered to 20 dogs in cardiogenic shock. Beneficial effects were noted three to five minutes after infusion began, but more significant effects were observed within 15 minutes, reaching a maximum 45 to 60 minutes after infusion. The principal changes observed were: (1) a significant increase in coronary flow, (2) a significant rise in left ventricular dp dt max , and (3) a decrease in total peripheral vascular resistance. Aortic and mesenteric flows increased significantly. Renal flow did not improve throughout the l -dopa infusion. l -dopa benefits were probably due to a stimulation of the beta-receptors.

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion. These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.

Venoarterial pulsatile partial bypass and intraaortic balloon counterpulse techniques produce (1) diastolic augmentation of aortic pressure which improves perfusion of the myocardium, and (2) a sink in presystolic and systolic pressures which lowers the workload of the left ventricle. Both techniques are effective in reversing the shock state in dogs and in man. Regional hemodynamic studies performed before, during and after counterpulsation explain benefits and drawbacks of each technique.

Two-dimensional echocardiographic measurements of regional left ventricular end-diastolic wall thickness and systolic wall thickening were studied during coronary artery occlusion and early after reperfusion and compared with measurements of regional myocardial infarct size. In 25 closed chest anesthetized dogs with left anterior descending coronary artery occlusion followed by reperfusion, the occlusion period was 3 minutes in group I (n = 4), 20 minutes in group II (n = 4), 60 minutes in group III (n = 5) and 180 minutes in group IV (n = 12). Infarct size in groups III and IV was quantitated using the triphenyltetrazolium chloride technique. After coronary occlusion, wall thickening was replaced by thinning in the center of the ischemic region at the midpapillary echographic short-axis section, and no improvement in function occurred up to 60 minutes after reperfusion, except in group I. Ischemic zone enddiastolic wall thickness did not change significantly from control to the end of the coronary occlusion period, except Group IV. At 60 minutes after reperfusion, enddiastolic wall thickness increased only slightly in groups I and II (by 7.2 and 0.24%, respectively), but a marked increase was observed in groups III and IV (by 41 and 50%, respectively). The percent change in ischemic zone end-diastolic wall thickness from before reperfusion to 60 minutes after reperfusion correlated well with the amount of myocardial necrosis in corresponding segments (r = 0.936, standard error of estimate = 11.4%); an increase in segmental end-diastolic wall thickness of more than 25% was generally associated with 20% or more segmental necrosis. It is concluded that significantly increased regional end-diastolic wall thickness early after reperfusion is associated with irreversibly damaged myocardium, and this might be used as an index of myocardial salvage.

Regional myocardial echo contrast appearance-disappearance after intracoronary contrast agent injection was examined with computerized two-dimensional contrast echocardiography in eight open chest dogs during successive variation of the coronary blood supply. A new sonication method applied to dextrose 50% produced an echo contrast agent with a microbubble size of 12 ± 6 μ (mean ± standard deviation), and 1 cc of this agent was injected into a coronary artery during the echocar-diographic study of the left ventricle. Left anterior descending or circumflex coronary artery flow, measured by electromagnetic flowmeter, was successively reduced up to 90% with an extravascular hydraulic occluder, or else increased 40 to 60% through intravenous dipyridamole infusion (7 to 10 μg/kg per min). The corresponding myocardial echo time-intensity curves were analyzed for each of 12 segments of a midventricular short-axis cross section.Several potential indexes of myocardial perfusion were derived: peak echo contrast intensity, time from echo contrast appearance to peak intensity, half-life of echo contrast decay phase (T½ and total duration of contrast appearance-disappearance. Except for peak intensity, all of these indexes provided significant (p < 0.05) differentiation between control coronary flow (66 ± 17 nil/min) and greater than 50% flow reductions (26 ± 6 nil/min) or hyperemia (115 ± 17 ml/min). Half-life values were 5.2 ± 0.3 seconds for the control state, 9 ± 2 seconds for the reduced coronary flow and 2 ± 2 seconds for dipyridamole hyperemia. Compared with an echo contrast-delineated circumferential extent of 5.6 ±1.4 myocardial segments subserved from the site of the coronary occluder, greater than 50% flow reduction significantly decreased contrast disappearance T½ in 3.7 ± 1.7 segments versus decreased systolic wall thickening in 6.6 ±1.4 segments. T½ for the central ischemic zone correlated moderately with coronary flow (r = 0.56, p < 0.05).It is concluded that myocardial contrast two-dimensional echocardiography, using small microbubbles as the agent, can identify a primary perfusion defect and may permit characterization of myocardial blood supply.

We studied the use of digital angiography for the quantification of regional myocardial perfusion in the dog using selective left coronary arterial injection of radiographic contrast material as a flow dilution indicator. We developed algorithms for generating time-intensity curves from regions of interest over the proximal coronary artery and the myocardium and for densitometric error correction by subtraction of the intensity curve over a small lead blocker before logarithmic transformation. The resultant myocardial time-density curves were analyzed for time from injection to peak concentration (TPC) and for exponential washout rate (k). A linear correlation was found between absolute coronary arterial blood flow and both k (slope = 0.13, r = .85) and 1/TPC (slope = 0.18, r = .85). Reproducibility of TPC and k for repeated studies was 11% and 16%. Induced hyperemia significantly improved the sensitivity to stenosis by increasing the average difference in TPC and k between regions served by normal and stenotic coronary arteries to 65% and 80%, respectively. By combining selective coronary arterial injection with the left lateral x-ray projection it was possible to avoid most overlap of regional perfusion beds in the dog. This study suggests that contrast dilution measurements made during digital coronary angiography provide a means for assessing the hemodynamic significance of stenoses and the efficacy of therapeutic interventions.

Mathematical modeling is a common approach to study the mechanics of the wall of the left ventricle. In designing such a model generally symplifying assumptions are proposed on left ventricular geometry, myocardial tissue properties and stress or strain distribution across the wall. Common assumptions on geometry are a spherical (6, 8), a cylindrical (2) or ellipsoidal (7,10,12) shape of the left ventricle. Generally myocardial tissue is considered to be isotropic despite its obviously anisotropic properties. We developed a cylindrical, thick-walled model (1,2) which differs from other models by considering anisotropy of myocardial tissue and torsion of the left ventricle. Torsion reflects rotation of the apex with respect to the base around the long axis of the left ventricle, and is associated with shear deformation of the outer surface (epicardium) of the left ventricle when using a cylindrical coordinate system.

An edge detection algorithm used in conjunction with digitized two-dimensional echocardiograms was applied to validate computerized two-dimensional echocardiographic (2DE) quantitation of cross-sectional areas of canine left ventricular chambers. Images were enhanced by space-time smoothing and dynamic range expansion, after which automatic edge detection was performed by convolving a Laplacian operator with the enhanced image. In an in vitro study of 29 myocardial slabs, computer-derived 2DE measurements of short-axis sections of the left ventricle were compared with manually derived 2DE data and validated against direct measurements of intraluminal areas of myocardial slabs. Correlations of both manually and computer-derived 2D echocardiograms vs direct measurements were equally satisfactory (r = .95 for both). Computer-derived measurements of perimeters tended to underestimate actual perimeters of the endocardial outlines of left ventricular sections. In 13 closed-chest anesthetized dogs, manually and computer-derived left ventricular short-axis areas measured by 2DE techniques showed a good correlation at both end-diastole (r = .91) and end-systole (r = .92). Left ventricular volumes reconstructed from 2DE images were compared with angiographically determined volumes. The computer-enhanced 2DE method correlated against angiography, with r = .93 for end-diastolic and r = .93 for end-systolic volumes. Left ventricular volume correlations between manually and computer-derived 2D echocardiograms were satisfactory, with r = .87 for end-diastole and r = .87 for end systole. We conclude that computerized enhancement and edge detection of 2D echocardiograms obtained in dogs provided accurate analysis of actual left ventricular cross-sectional areas and left ventricular volumes.

Coronary venous injections of sonicated Renografin-76 were performed in seven closed chest dogs during two-dimensional echocardiography to study the ability of this new technique to opacify regional myocardium before and after occlusion of the left anterior descending coronary artery. The balloon of a 4F double lumen catheter was inflated in the great cardiac vein for each contrast injection to prevent backflow through the coronary sinus into the right atrium. Retrograde injections before coronary artery occlusion generally resulted in patchy myocardial contrast uptake. Injections after coronary occlusion always resulted in confluent and transmural myocardial opacification which occupied 42.8 +/- 8.6% (range 26 to 54) (mean +/- standard deviation) of the myocardial circumference. Retrograde opacification always extended into adjacent myocardium beyond the ischemic zone, which was assessed in echocardiograms with antegrade contrast injections into the left main coronary artery and which measured 30 +/- 6.3% of the ventricular circumference. Shunting from the coronary venous system to cardiac chambers was evaluated in a parasternal four chamber view and was graded on a scale of 0 to 4+. Contrast appearance was equally intense in the right atrium and right ventricle (3.5 +/- 0.6+, range 2+ to 4+), less intense in the left ventricular cavity (1.5 +/- 0.6+, range 1+ to 3+) and absent in the left atrium. Postmortem anatomic validation with retrograde great cardiac vein injections of indocyanine green corroborated and in vivo contrast appearance in chambers. Retrograde coronary venous contrast echocardiography appears capable of providing in vivo information about the extent and location of myocardial zones that can be reached by retrograde infusions of therapeutic agents and about the ability of these agents to reach ischemic myocardium. In addition, this new method allows for in vivo evaluation of shunts between coronary veins and cardiac chambers, which may influence the efficacy of retrograde interventions.

Prostaglandin E1was administered by means of coronary venous synchronized retroperfusion and the effectiveness of the combined (prostaglandin-retroperfusion) system was examined during acute myocardial Ischemia in 10 closed chest anesthetized dogs. Such treatment was administered between 30 minutes and 3 hours after occlusion of the proximal left anterior descending coronary artery. An equivalent series of 10 dogs with arterial blood retroperfusion alone and 9 untreated dogs served as control subjects. Standardized two-dimensional echocardiographic measurements of global and regional left ventricular function were performed in five short-axis cross sections. The global low left ventricular section and its profoundly ischemic anterolateral region exhibited distinctly improved systolic fractional area changes as a result of the prostaglandin E1retroperfusion treatment between 30 minutes and 3 hours after occlusion (22.9 ± 1.5to41.2 ± 4.0% and 1.8 ± 3.6 to 29.4 ± 5.6%, respectively). In contrast, further deterioration in function was noted during an untreated equivalent coronary occlusion period (16.3 ± 2.7 to 10.0 ± 3.3% and 12.6 ± 6.1 to 4.1 ± 6.9%). Although arterial blood retroperfusion alone provided distinct benefits in the ischemic region of a midpapillary echo section (from 13.4 ± 3.9 to 32.1 ± 10.4%, p < 0.05), no improvements were observed in profoundly jeopardized segments at the low left ventricular level (5.6 ± 6.0 to 0.9 ± 5.7%).Triphenyltetrazolium chloride delineation of infarction revealed significant myocardial salvage with prostaglandin E, retroperfusion as compared with findings in untreated control dogs (3.7% ± 1.3% of the left ventricle versus 9.3 ± 1.9%, p < 0.05). The respective ratios of necrosis to glycogen-depleted ischemic zones in a mid-left ventricular slab were 19.5 ± 6.4% versus 47.1 ± 8.9 (p < 0.05).It is concluded that retrograde prostaglandin E, administration may further enhance the effectiveness of synchronized coronary venous retroperfusion treatment of jeopardized acutely ischemic myocardium.

Although characteristic alterations in myocardial performance in response to regional ischemia were first described by Tennant and Wiggers in 1935 [1], it was not until recently that these experimental findings were defined in detail by means of sophisticated noninvasive measurements. Regional left ventricular dysfunction can be demonstrated within a few cardiac beats after an acute coronary obstruction, and a characteristic sequence of segmental contractile derangements is seen during myocardial infarction. The advent of invasive ventriculography for studies of global and regional cardiac function [2–6], and the more recent nuclear procedures, contributed significantly to the understanding of mechanical consequences of myocardial ischemia. The problem with these techniques is that they do not lend themselves for bedside and sequential evaluation of cardiac performance. M-mode echocardiography has been used for detecting abnormal wall motion in patients with coronary artery disease [7–9], but it also is not satisfactory because of the ‘ice pick’ view which limits imaging of the left ventricle.

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.

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.

Two experimental series of closed chest dogs were compared: Group A (five dogs with 7 days of continuous occlusion of the proximal left anterior descending coronary artery); and Group B (six dogs with 7 days of reperfusion after 3 hours of acute occlusion of the same artery). Hemodynamic measurements, ventricular wall motion, coronary sinus blood flow and regional metabolism in both coronary occluded and nonoccluded segments of the left ventricle were measured sequentially. The infarct size was characterized by detailed histopathologic analysis. In the control dogs (Group A), mechanical and metabolic function remained severely depressed after 7 days of occlusion, and mean infarct size was 31.6 percent. In Group B, significant mechanical and metabolic dysfunction developed during 3 hours of occlusion and did not improve during the 1st hour of reperfusion. However, after 7 days of reperfusion, function returned to near preocclusion level. Mean infarct size was 14.2 percent, but in two of the six dogs infarct size was 43 percent and 23 percent, respectively. The study confirmed the unstable character of the early phase of reperfusion, attributed to cell swelling, edema and hemorrhages that resulted in inadequate coronary reflow, arrhythmias and functional derangements. Prolonged reperfusion for 7 days reduced mean infarct size and improved cardiac function.

Focal necrosis (microinfarcts) and regional lactate derangements were observed in closed chest dogs in the nonoccluded (remote) posterior segments of the left and right ventricles after acute occlusion of the proximal left anterior descending coronary artery. Focal infarcts in the remote areas were observed in five of the six dogs with 7 days of occlusion of the left anterior descending artery and in six of seven dogs with 7 days of reperfusion after 3 hours of occlusion. There was a good correlation between the finding of microinfarcts and myocardial lactate derangements in the corresponding remote myocardium. No significant lactate derangements or microinfarcts were found in sham experiments. These findings suggest that ischemia of the remote myocardium frequently accompanies an acute coronary occlusion and may result in irreversible focal lesions.

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 regional metabolic function was assessed simultaneously in 34 closed chest dogs during a preocclusion control period and 3 hours of intracoronary balloon occlusion of the proximal left anterior descending artery. The data indicate immediate alteration in hemodynamic measurements with many fluctuations in the 3 hour occlusion period. No specific hemodynamic pattern was evident. When the mean data were analyzed, occlusion was found to cause early increases in left ventricular end-diastolic pressure (43 percent) and systemic vascular resistance (21 percent), and decreases in peak systolic pressure (5 percent), maximal rate of rise of left ventricular pressure (dP/dt) (20 percent), cardiac output (19 percent), stroke work (26 percent) and coronary sinus blood flow (19 percent). Regional metabolic measurements showed significantly different metabolic function in the occluded and nonoccluded zones of the left ventricle. Lactate balance decreased to near production levels, and a substantial potassium loss occurred in the occluded zone shortly after occlusion; lactate and potassium balances later fluctuated, but usually remained depressed. Abnormal lactate metabolism and potassium efflux were often observed in the nonoccluded zone. A 6 to 8 percent increase in oxygen extraction was noted in both segments. Progressive alterations in hemodynamic and metabolic function of the heart after coronary occlusion are not uniform and exhibit dynamic fluctuations. Although a direct relation was noted between the degree of metabolic dysfunction and hemodynamic change, individual experiments often revealed a distinct metabolic-mechanical dissociation.

After almost 25 years of extensive experimentation there appears to be confusion about the actual clinical performance of available mechanical systems for treatment of cardiogenic shock. Because shock continues to have an 80 to 90 percent mortality rate, we consider it urgent that a multidisciplinary assessment be made of clinical benefits and drawbacks of circulatory assist techniques. The most attractive assist technique is counterpulsation, which provides,, in each cardiac cycle, left ventricular unloading and augmentation of the myocardial perfusion potentia1.l Such a dual assist concept represents an idea:l approach to the treatment of cardiac pump failure because it may reverse the vicious cycle that tends to perpetuate the shock state. Among the growing number of counterpulsation systems developed to date are: (1) femoral arterialarterial counterpulsationl; (2) venoarterial pulsatile phased bypassz; (3) intraaortic balloon pumping3T4; (4) ascending aorta synchronized pulsation5; (5) aortic root balloon pum!ping6; (6) unidirectional intraaortic balloon pumping7; (7) external pressure cardiac assists; (8) body acceleration synchronized with the heartg; and (9) implanted dynamic aortic patch for extended ae.sistance.lO Partial effects of counterpulsation, particularly unloading of the left ventricle, may be achieved with (10) transarterial closed chest left ventricular bypass,ll and (11) left atrium-to-aorta bypass.12 Although most of the physiologic data on the effectiveness of these systems were derived from animal experimentation, the ultimate test of effectiveness is its application to man. Results of 2 techniqu.es that have recently been popularized, intraaortic balloon and external pressure counterpulsation, are now available for evaluation. Clinical results of balloon counterpulsation: Recent reports of 2 major studies13y14 provided statistical data on this technique in patients with