Roberto V. Haendchen

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.

Two-dimensional echocardiographic contrast assessment of pacing-induced mitral regurgitation: relation to altered regional left ventricular function

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.

Hypothermic coronary venous phased retroperfusion: a closed-chest treatment of acute regional myocardial ischemia.

Hypothermic synchronized retroperfusion (HSRP) was applied in closed-chest dogs after acute coronary occlusion to determine whether this intervention can significantly retard the otherwise rapidly developing irreversible ischemic injury. The left anterior descending coronary artery (LAD) was occluded for 3 hours in 22 dogs and for 6 hours in 16 dogs. Starting 30 minutes after occlusion, HSRP was applied during maintained coronary occlusion in 21 dogs. The remaining dogs served as untreated controls. Arterial blood was cooled to 20 degrees C and retroperfused in diastole into the regional coronary veins. Hemodynamics, contrast cineangiography and two-dimensional echocardiography were measured sequentially. Glycogen-depleted ischemic areas and necrotic zones were delineated in transverse slices of the left ventricle. Untreated controls dogs further deteriorated; in contrast, HSRP between 30 minutes and 3- and 6-hour LAD occlusion significantly reduced the rate-pressure product (21.3 +/- 4.0% or 26.8 +/- 8.2%) and left ventricular end-diastolic pressure (39.5 +/- 9.5% or 51.4 +/- 7.7%) and increased ejection fraction (28 +/- 17% and 33 +/- 2.0%). HSRP caused no arrhythmias and led to much less necrosis of ischemic myocardium in the treated 3- or 6-hour occlusion series (7.4 +/- 2.7% or 28.9 +/- 12.6%) than in respective untreated controls (47.1 +/- 8.9% and 72.3 +/- 5.9%). Moderately hypothermic closed-chest phased retroperfusion appears to protect reversibly injured ischemic myocardium and improve cardiac function. Such treatment may be particularly suitable in the earliest stages of evolving myocardial infarction, when maintenance of myocardial viability is essential for preservation of jeopardized myocardium while awaiting coronary bypass revascularization or nonsurgical thrombolytic reperfusion.

Myocardial contrast two-dimensional echocardiography: comparison of contrast disappearance rates in normal and underperfused myocardium

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.

Effects of pressure-controlled intermittent coronary sinus occlusion on regional ischemic myocardial function

Pressure-controlled intermittent coronary sinus occlusion has been reported to reduce infarct size in dogs with coronary artery occlusion, possibly because of increased ischemic zone perfusion and washout of toxic metabolites. The influence of this intervention on regional myocardial function was investigated in open and closed chest dogs. In six open chest dogs with severe stenosis of the left anterior descending coronary artery and subsequent total occlusion, a 10 minute application of intermittent coronary sinus occlusion increased ischemic myocardial segment shortening from 5.5 +/- 1.2 to 8.2 +/- 2.6% (NS) and from -0.1 +/- 2.1 to 2.3 +/- 1.2% (NS), respectively. In eight closed chest anesthetized dogs, intermittent coronary sinus occlusion was applied for 2.5 hours between 30 minutes and 3 hours of intravascular balloon occlusion of the proximal left anterior descending coronary artery. Standardized two-dimensional echocardiographic measurements of left ventricular function were performed to derive systolic sectional and segmental fractional area changes in five short-axis cross sections of the left ventricle. Fractional area change in all the severely ischemic segments (less than 5% systolic wall thickening) was -4.0 +/- 4.7% at 30 minutes after occlusion, and increased with subsequent 60 and 150 minutes of treatment to 13.1 +/- 3.3 and 7.0 +/- 3.3%, respectively (p less than 0.05). At the most extensively involved low papillary muscle level of the ventricle, regional ischemic fractional area change was increased by intermittent coronary sinus occlusion between 30 and 180 minutes of coronary occlusion from -0.4 +/- 0.1 to 14.4 +/- 4% (p less than 0.05), whereas a further deterioration was noted in untreated dogs with coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrograde lysis of coronary artery thrombus by coronary venous streptokinase administration

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.

Coronary venous retroperfusion support during high risk angioplasty in patients with unstable angina: Preliminary experience

Synchronized coronary venous retroperfusion was used during coronary balloon angioplasty to support the ischemic myocardium of 20 patients with unstable angina and anatomy at high risk of a coronary event. Hemodynamics and left ventricular function were the major end points of the study. Coronary venous catheterization and retroperfusion were successfully performed in 15 patients. The target vessel was an unprotected left main artery in 2, left anterior descending artery in 10, left circumflex coronary artery in 1 and right coronary artery in 2 patients. A nonsupported balloon inflation (mean 44 +/- 13 s) was compared with a later retroperfusion-supported inflation (mean 145 +/- 21 s). Right anterior oblique left ventriculograms, aortic blood pressure, pulmonary artery pressure and thermodilution cardiac output were obtained before and during peak untreated and treated balloon inflations and on completion of angioplasty. All patients had either a baseline left ventricular ejection fraction less than 0.40 or greater than 40% of contracting myocardium estimated to be at risk for severe ischemia during angioplasty. The cardiac (liters/min per m2) and stroke work (g.m/m2) indexes decreased from mean baseline values of 2.5 +/- 0.52 and 52 +/- 15 to 1.7 +/- 0.47 and 27 +/- 12 (mean +/- SD), respectively, during nonsupported balloon inflations but decreased only to 2.1 +/- 0.52 (p less than 0.01 vs. nonsupported) and to 36 +/- 14 (p = 0.01 vs. nonsupported), respectively, during retroperfusion-supported inflations. Ejection fraction (n = 8) decreased from a baseline value of 55 +/- 13% to 27 +/- 7.3% during nonsupported inflations but only to 39 +/- 10% during retroperfusion-supported inflations (p = 0.01 vs. nonsupported). Regional wall motion (area change) in the ischemic (target) region was reduced from a baseline value of 49 +/- 17% to 11 +/- 16% during nonsupported inflations but only to 27 +/- 15% during retroperfusion-supported inflations (p less than 0.01 vs. nonsupported). All but two patients had a favorable hemodynamic response to retroperfusion. There were no serious adverse effects related to the procedures and no hospital deaths. It is concluded from this preliminary study that coronary venous retroperfusion appears to be safe, to provide hemodynamic support and to improve left ventricular function during angioplasty in patients with unstable angina and anatomy at high risk of a coronary event.

Percutaneous cooling of ischemic myocardium by hypothermic retroperfusion of autologous arterial blood: Effects on regional myocardial temperature distribution and infarct size

The effects of synchronized coronary venous retroperfusion of cooled autologous arterial blood on regional myocardial temperature distribution and infarct size were studied in open chest dogs with 3.5 h of left anterior descending coronary artery occlusion. After 30 min of occlusion, the dogs were randomly assigned to one of three groups: 1) untreated control group (n = 5), 2) normothermic retroperfusion group (infusion temperature 32 degrees C) (n = 7), and 3) hypothermic retroperfusion group (infusion temperature 15 degrees C) (n = 7). Regional myocardial temperatures were measured by using needle-tipped thermistors stabbed in the 1) anterior wall distal to the occlusion site, 2) anterior wall proximal to the occlusion site, 3) left lateral wall, 4) posterior wall, and 5) right ventricular free wall. Rectal and pulmonary artery temperatures were also measured. In the hypothermic retroperfusion group, the anterior wall temperature decreased rapidly by 5 degrees C at 15 min of retroperfusion (p less than 0.05 vs. normothermic retroperfusion or untreated control groups), whereas the temperature at other sites decreased with a linear trend over time. Myocardial temperatures in the ischemic area (distal anterior wall) were generally lower than those in the other sites during the first 60 min of hypothermic retroperfusion and the largest intramyocardial temperature difference (3.6 degrees C) was found at 15 min after retroperfusion. Infarct size expressed as a percent of the risk area was significantly smaller in the hypothermic retroperfusion group (6.2 +/- 3.3%) than in the control (64.9 +/- 14%) or normothermic retroperfusion groups (24.1 +/- 6.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Retrograde coronary venous contrast echocardiography: Assessment of shunting and delineation of regional myocardium in the normal and ischemic canine heart*

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.

Short-term synchronized retroperfusion before reperfusion reduces infarct size after prolonged ischemia in dogs.

BackgroundPrevious studies have demonstrated that synchronized coronary venous retroperfusion (SRP) can restore blood flow to the ischemic myocardium, resulting in infarct size reduction and improvement of the left ventricular function. Despite the nutritive blood flow achieved by SRP being relatively limited, SRP has been shown to improve washout of by-products from the ischemic myocardium. The aim of this study was to investigate whether short-term SRP immediately prior to reperfusion would attenuate the deteriorative phenomena following reperfusion. Methods and ResultsClosed-chest anesthetized dogs underwent 3 hours of left anterior descending coronary artery (LAD) occlusion. The dogs were then randomized into two groups: (1) control group (n=9), in which the occlusion was immediately followed by 3-hour reperfusion; or (2) SRP group (n=9), in which SRP was started 3 hours after occlusion and maintained for 30 minutes with sustained occlusion followed by 2.5-hour reperfusion with simultaneous discontinuation of SRP. There were no statistical differences between the groups in global hemodynamics and degree of ischemia measured by radiolabeled microspheres. Myocardial infarct size (triphenyltetrazolium method) expressed as percentage of risk area was significantly smaller in the SRP group (24±7%, mean+SEM) than in the control group (54±9%o). The extent of myocardial hemorrhage expressed as percentage of infarct size was also significantly reduced in the SRP group (3±2%) compared with the control group (24±6%). The increase in end-diastolic wall thickness in the ischemic area after reperfusion assessed by two-dimensional echocardiography was significantly less in the SRP group. Blood flow measurements after reperfusion demonstrated the occurrence of no-reflow phenomenon only in the control group. Histological examination revealed extensive myocardial hemorrhages only in the control group, which extended into the nonnecrotic myocardium in four of nine hearts and extensive contraction band necrosis compared with the SRP group. ConclusionsShort-term SRP prior to reperfusion can reduce infarct size, myocardial hemorrhage, wall swelling, and no-reflow phenomenon. The mechanism of this beneficial effect is not clear but might be due to gradual reperfusion and washout of by-products from the ischemic myocardium before fully oxygenated arterial blood reperfusion.