Can contrast echocardiography elucidate myocardial physiology?
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Biomedical subjects
Publications and source records attributed to S Meerbaum.
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The efficacy of coronary venous retroinfusion of superoxide dismutase and catalase was studied in anesthetized closed chest dogs with 90-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion. In group A, superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) were administered by a 30-min continuous right atrial infusion beginning 15 min before reperfusion and supplemented by a bolus injection of superoxide dismutase (2.5 mg/kg) and catalase (2.5 mg/kg) through the great cardiac vein immediately before reperfusion. The treatment in group B was similar to that in group A, except that the bolus injection was into the right atrium. In the control group (group C), saline was administered in the same manner as in group A. Infarct size, expressed as a percentage of the risk area, was significantly smaller in group A (11.3 +/- 8.9%) than in groups B (31.3 +/- 21.1%) and C (43.0 +/- 16.9%; p less than 0.05). Regional function of the ischemic zone measured by two-dimensional echocardiography exhibited significantly (p less than 0.05) greater recovery after 3-h reperfusion in group A (30.3 +/- 8.4%) versus groups B (12.5 +/- 13.7%) and C (12.1 +/- 11.7%). Moreover, there were significantly fewer postreperfusion ventricular arrhythmias in group A as compared with groups B and C. The results of this study indicate that coronary venous retroinfusion is an effective method for delivery of superoxide dismutase and catalase.
1. The present study was undertaken to determine noninvasively the sequential changes in left ventricular (LV) size, wall thickness and regional contractile function occurring during 3 h of proximal left anterior descending coronary artery occlusion (CAO), and their modification by reperfusion (REP) over a 7-day period. 2. Twenty, closed-chest, anesthetized dogs underwent CAO for 3 h and were reperfused for 7 days. Hemodynamics (aortic, LV pressure, LV dP/dt) and regional LV function were measured sequentially during CAO and reperfusion. The animals were killed at 7 days and infarct size was measured using the triphenyl-tetrazolium-chloride technique. Regional function (systolic fractional area change, FAC) was measured in 40 LV segments of 5 two-dimensional echo short-axis planes (8 segments per section). 3. At three hours of CAO, 14 dogs developed extensive areas of akinesis or dyskinesis in more than 6 segments (Group I, large risk area), whereas 6 dogs developed akinesis or dyskinesis in 6 segments or less (Group II, small risk area). Four dogs died between 12 and 48 h after REP in Group I and none of Group II died. Recovery of regional function after REP was significantly different between Groups I and II: in hypokinetic segments, FAC improved from 16.7 +/- 0.9% (mean +/- SEM) at 3 h of CAO to 25.4 +/- 3.2% at 24 h and to 34.9 +/- 2.0% at 7 days (66.3 +/- 3.4% of baseline) after REP in Group I; in Group II, FAC increased from 16.6 +/- 1.5% at 3 h of CAO to 48.5 +/- 7.4% at 24 h and to 52.4 +/- 1.6% (92.7 +/- 2.8% of baseline) at 7 days after REP. In akinetic/dyskinetic segments, FAC increased from -9.2 +/- 2.4% at 3 h of CAO to 8.2 +/- 2.6% at 72 h and to 8.3 +/- 3.2% (15.1 +/- 5.8% of baseline) at 7 days of REP in Group I; in Group II, FAC rose significantly from -7.6 +/- 1.6% at 3 h of CAO to 39.9 +/- 7.3% at 24 h and to 50.8 +/- 4.3% (89.2 +/- 4.9% of baseline) at 7 days after REP. There was a significant inverse correlation between the magnitude of compensatory hyperkinesis in the nonischemic wall and the extent of hypokinesis at 60 min (r = -0.82, P less than 0.001), but this correlation was less significant at 24 h (r = -0.64, P less than 0.01), 72 h (r = -0.53, P less than 0.02), and 7 days (r = -0.50, P less than 0.05) after REP.(ABSTRACT TRUNCATED AT 400 WORDS)
The delivery and distribution of retroinfusate premixed with radionuclide microspheres (15 microns) in the coronary venous system of canine hearts was studied in in vitro and in vivo experiments. Results showed that about 51-85% of the retroinfusate was shunted directly by vessels greater than 15 microns in diameter to the right heart in cases of isolated heart study, while the remaining 21-42% passed through intramyocardial capillaries with obvious nutritional effects. In the closed-chest experiments, 95% of the retroinfusate was bypassed to the right heart; less than 5% went through the intramyocardial microcirculation system. Intramyocardial distribution pattern of the retroinfusate indicated a predominant supply to the left ventricular free wall. There was a preferential distribution of the retroinfusate to the ischemic area with a subendo subepi blood flow ratio of up to 1.79 +/- 0.21 post-LAD occlusion.
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The effects of synchronized coronary venous retroperfusion of arterial blood on myocardial washout were studied with digital subtraction angiography in 10 closed chest dogs during balloon occlusion of the proximal left anterior descending coronary artery. The center lumen of the intracoronary balloon catheter was used for sequential injections of 1 ml (meglumine diatrizoate) Renografin-76, and contrast washout rate was determined by videodensitometry in myocardial regions subserved by the left anterior descending coronary artery. Before coronary artery occlusion, washout rate was 22.4 +/- 2.7 min-1 (mean +/- SEM). Five minutes after occlusion, and immediately before synchronized retroperfusion, washout rate dropped sharply to 2.0 +/- 0.7 min-1. Twenty-five minutes after occlusion, with 50 ml/min synchronized retroperfusion treatment applied for 5 minutes, washout rate was 5.0 +/- 1.5 min-1. Thus, synchronized retroperfusion significantly (p less than 0.05) accelerated contrast disappearance over that during presynchronized retroperfusion ischemia. To determine the effects of synchronized retroperfusion on retrograde delivery to the ischemic myocardium, monastral blue dye was retroinfused through the system into the great cardiac vein before the dog was killed. Transverse heart slices were then studied by light microscopy, and regional intravascular dye content was scored from 0 to 3 (0 = no dye, 3 = maximal dye). After great cardiac vein synchronized retroperfusion, blue dye content in capillaries of ischemic anterior and nonischemic posterior aspects of the left ventricle was 2.3 +/- 0.5 versus 0.7 +/- 0.3, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of intracoronary infusion (50 ml/min) of arterial blood, oxygenated or unoxygenated Fluosol, or Plasmalyte A on hemodynamics, electrocardiogram, regional myocardial function, and lactate metabolism were studied in six closed-chest dogs during 2 min occlusions of the left anterior descending coronary artery followed by 10 min of reperfusion. Normal hemodynamics were maintained with infusion of arterial blood and oxygenated Fluosol, whereas unoxygenated Fluosol and Plasmalyte A resulted in hemodynamic deterioration similar to that noted with no treatment. Ischemic zone systolic fractional area change, an index of systolic function measured by two-dimensional echocardiography, remained normal during the occlusion supplemented with intracoronary arterial blood (49 +/- 7%), was moderately hypokinetic with oxygenated Fluosol (31 +/- 10%), and became severely hypokinetic with unoxygenated Fluosol (14 +/- 14%), with Plasmalyte A (2 +/- 13%), and in the absence of treatment (5 +/- 9%). Only infusion of arterial blood resulted in no ST segment elevation or lactate production. Thus intracoronary infusion of arterial blood during brief coronary occlusion maintained normal myocardial function and aerobic metabolism. Infusion of oxygenated Fluosol resulted in amelioration of the decline in regional function after coronary occlusion, but not complete protection.
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A commercial two-dimensional echo unit, modified to permit digital acquisition (2.2 MHz) of echo signals prior to time-gain-compensation (TGC), was ratiometrically calibrated. Simulating the TGC in software, we demonstrated improvements in image quality as compared to conventional video methods. A path-dependent attenuation correction (PDAC) algorithm, utilizing the gray level image statistics to assign one of three attenuation coefficients (for chest, myocardium or blood) to each image pixel, was then developed. Using it on left ventricular (LV) short axis images obtained in nine healthy closed chest dogs, we demonstrated that the backscatter intensity at end diastole (ED) was 2.0 +/- 0.5 dB (mean +/- SEM) higher (p less than 0.01) than at end systole (ES), in circumferential segments of the myocardium oriented anteriorly and posteriorly, relative to the transducer. In seven of the dogs, subsequently occluded for one hour in the anterior descending branch of the left coronary artery (LAD), this normal phasic myocardial backscatter (PMB) variation decreased or was reversed in ischemic segments, relative to preocclusion values, suggesting utility of the method for sequential study of myocardial ischemia and its treatment.
Two-dimensional echocardiography (2DE) was performed in nine dogs with three hour proximal occlusion of the left anterior descending coronary artery and seven day reperfusion for sequentially mapping systolic functions (Seg-FAC%: percent segmental fractional area change) and diastolic functions (Seg-VLAC: mean velocity of segmental luminal area change) of eight segments in a mid-papillary left ventricular short-axis cross-section. The corresponding segment functions on 2DE to the most profoundly affected segment were evaluated by triphenyl-tetrazolium-chloride staining seven days post reperfusion, and categorized in two groups in terms percent mural necrosis (N%): N% greater than or equal to 40% in group A and N% less than 40% in group B, respectively. Seg-FAC% showed a significant difference between the two groups seven days post reperfusion (13.4 +/- 9.4% in group A, 53.3 +/- 7.7% in group B), while Seg-VLAC showed significant differences in the groups at three hours post occlusion (-1.6 +/- 2.1 cm2/sec in group A and 3.2 +/- 2.6 cm2/sec in group B) and seven days post reperfusion (0.48 +/- 4.7 cm2/sec in group A and 7.5 +/- 2.4 cm2/sec in group B). At seven days post reperfusion, Seg-VLAC correlated negatively with N% (r = -0.94), while Seg-FAC% did not with N% (r = -0.58). It was concluded that Seg-VLAC, after three hours' occlusion, predicts the recovery of the regional left ventricular function seven days after reperfusion; and Seg-VLAC, seven days after reperfusion can estimate the regional transmurality of necrosis thereafter.
Contrast echocardiographic assessment of blood flow within the myocardium requires standardization of contrast agents and echo image analysis. Sonicated contrast solutions containing small and relatively stable microbubble ultrasound reflectors were injected into coronary arteries of five dogs, and a newly developed computer assisted densitometric analysis of myocardial echo intensity decay was examined. The sonicated solutions included sorbitol 70%, dextrose 70%, and dextrose 50%, and myocardial contrast echo data were analyzed by applying an exponential decay index (T-1/2) to the digitized time intensity curves obtained with videodensitometric techniques. In 30 intracoronary injections selected for further analysis, sonicated sorbitol 70% demonstrated the most physiologic myocardial transit time with the smallest variability (6.0 +/- 2.0 seconds). Sonicated dextrose 70% and dextrose 50% solutions exhibited significantly prolonged and more variable transit times (11.4 +/- 4.0 seconds and 13.9 +/- 5.0 seconds). The results of this study suggest that appropriate echo contrast solutions with small microbubble diameters are critical to satisfactory echocardiographic assessment of myocardial blood flow, and that objective analysis of contrast two-dimensional echocardiographic images can be achieved with computer-assisted videodensity algorithms featuring standardized echo analysis of the time intensity data.
Renewed efforts are under way to apply clinically oriented coronary venous retroperfusion methods for treatment of myocardium jeopardized by major coronary artery obstructions. Based upon improved understanding of criteria for retroperfusion effectiveness and safety, improved arterial blood retroperfusion and pharmacologic agent retroinfusion techniques have been demonstrated to provide significant myocardial infarct salvage and enhance cardiac function. The retrograde systems also have a potential for prompt lysis of an acute coronary artery thrombus and for treatment of refractory arrhythmias. Retroperfusion may constitute an effective protective support when used in conjunction with new aggressive interventions, maintaining jeopardized myocardial viability and function pending permanent reversal of a severe coronary flow insufficiency or emergency revascularization in evolving acute infarction. Clinical applications are anticipated in the setting of unstable angina and arrhythmias, as circulatory assist during complex coronary angioplasty and thrombolytic procedures, and as adjunct support of cardiac surgery.
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.
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.
To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.
Coronary bypass surgery performed after more than 3 or 4 hours of coronary occlusion may results in serious derangements of cardiac metabolic, contractile, and electrical functions, and lead to extensive myocardial infarction, as well as to an unacceptable mortality. If the operation can be performed within the first 1 to 2 hours of acute coronary occlusion, hospital mortality rate is acceptably low. Although the average infarct size was usually reduced by reperfusion after 3 hours of experimental occlusion, in about 30 percent of cases there appeared to be no salvage of jeopardized myocardium.
We have attempted to summarize the current controversies regarding risk factors and preventive measures for control of arteriosclerosis and coronary heart disease. Recognizing that the genesis and development of the disease process are extremely complex and the basic knowledge is limited, it is not likely that conclusive answers to questions will be forthcoming soon which will provide more effective preventive or therapeutic measures. It might be desirable to institute educational and control program aimed at curtailing, at a young age, known AS risk factors such as heavy smoking, particularly if the family history indicates severe risk. Few will question the normal approaches to the treatment of complications of coronary heart disease by control of hypertension, elevated cholesterol, and smoking. However, great caution must be exercised when trying to institute large scale modifications in prevailing life patterns, particularly when based on indefinite risk factor studies and in the face of potentially profound and frequently unknown consequences. The unknowns of atherosclerotic heart disease risk factors, coupled with uncertainties and even doubts about protracted and expensive population studies, lead us to propose an emphasis on alternate selective approaches. We strongly believe that fundamental to progress in the field of arteriosclerosis is an amplification of preventive research efforts with stronger attention focused upon influencing the atherosclerotic processes within the arterial wall. But, more immediately, we urge systematic gathering and careful evaluation of patient data in particular population subsets which exhibit and accelerated mode of arteriosclerosis. Comparative studies of patients, particularly twins, families, and ethnic populations with redilection to early or accelerated arteriosclerosis may be extremely rewarding. Our repeated review of the enormous literature suggests that worldwide collaboration is needed to perfect more meaningful protocols as well as to correlate and critically evaluate existing data provided by population studies of this insidious disease process which represents an evermounting burden to society.
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