Marc A. Kates

Combination of dobutamine and myocardial contrast echocardiography to differentiate postischemic from infarcted myocardium

OBJECTIVES This study tested whether the combination of dobutamine echocardiography (DE) and myocardial contrast echocardiography (MCE) was superior to either technique alone in identifying postischemic myocardium and in differentiating it from necrotic myocardium. BACKGROUND Wall motion abnormalities at rest occur in postischemic myocardium in the presence of infarction, stunning or hibernation, alone or in combination. Various investigators have suggested that either DE or MCE can be used to identify the presence of myocardial viability. METHODS We studied a total of 53 mongrel dogs in an open chest model of coronary occlusion of various durations followed by reperfusion and dobutamine administration (10 microg/kg body weight per min). MCE with aortic root injections of Albunex (area under the curve) and DE (percent thickening fraction) were performed at the different stages. Postmortem triphenyltetrazolium chloride (TTC) staining was used to identify myocardial necrosis. RESULTS Thirteen dogs underwent brief (15 min) occlusions and developed no necrosis (Group I). Of 40 dogs that underwent prolonged (30 to 360 min) occlusions, 14 had no infarction (Group II), whereas 26 did (Group III: 12 papillary muscle, 7 subendocardial, 7 transmural). MCE (expressed as percent change from baseline) demonstrated changes that paralleled the blood flow changes observed by radiolabeled microspheres at all interventions (r = 0.67, p < 0.0001). Regional ventricular function improved with dobutamine administration in the ischemic region in all three groups. The sensitivity (88%) for detecting myocardial viability was superior when the two techniques were combined; however, a poor specificity (61%) was observed. CONCLUSIONS Contractile reserve and perfusion data are complementary when assessing regional wall motion abnormalities in postischemic myocardium. DE alone cannot differentiate postischemic from infarcted myocardium; simultaneous data on myocardial perfusion are required. The combination of DE and MCE is superior to either technique alone for identifying the absence of myocardial necrosis.

Potential clinical implications of abnormal myocardial perfusion patterns immediately after reperfusion in a canine model: A myocardial contrast echocardiography study

During myocardial infarction, lack of myocardial opacification after reperfusion has been associated with poor or no recovery of function. We have previously documented the presence of perfusion abnormalities after brief coronary occlusions without infarction and the absence of perfusion abnormalities after prolonged occlusions with infarction. To characterize myocardial perfusion patterns immediately after reperfusion, we studied 53 animals in two groups in a coronary occlusion-reperfusion model. Temporary occlusions (group 1, 15 minutes; group 2, 30 to 360 minutes) were performed, followed by reperfusion with and without dobutamine. Myocardial contrast echocardiography was performed with aortic root injections of sonicated 5% serum human albumin (Albunex) during each intervention. Group 1 dogs showed no evidence of myocardial infarction. In group 2, 26 of 40 dogs had infarctions. After reperfusion, no perfusion abnormalities were seen in 13 of 26 group 2 dogs with infarctions; perfusion abnormalities were identified after reperfusion in 2 of 13 group 1 and in 8 of 14 group 2 dogs without infarctions. In animals subjected to prolonged ischemia, the absence of perfusion abnormalities after reperfusion did not rule out the presence of necrosis. Similarly, in animals without infarction subjected to ischemia, the presence of a perfusion defect after reperfusion did not represent the presence of necrosis but an abnormal microvascular reserve. These results suggest that early after reperfusion, assessment of perfusion by myocardial contrast echocardiography has significant limitations in the evaluation of myocardial viability and salvage.

Identification of Perfusion Abnormalities Using FSO69, a Novel Contrast Agent, in Conscious Dogs

Recent advances in the production of echocardiographic contrast agents has resulted in the ability to delineate areas of hypoperfusion after coronary occlusions and stenoses following their intravenous injection. Most of these studies though have been done in open chest animals. This study was done to determine if we could assess myocardial perfusion following the intravenous administration of FSO69, a suspension of perfluoropropane filled albumin microspheres (3.6 μm average microbubble size, concentration 8 × 108), in spontaneously breathing closed chest dogs. Twenty‐seven mongrel dogs were instrumented on day 1. The chest was then closed and the dogs were restudied 3–7 days later, while spontaneously breathing. Homogeneous perfusion was observed in most dogs by all three independent and blinded observers. Perfusion abnormalities were likewise identified in most instances by all blinded reviewers on interventions designed to decrease regional blood flow. A good correlation between perfusion defect size between investigators was observed. In summary, our data suggest that FSO69 can be used to assess regional myocardial perfusion in spontaneously breathing dogs. These results support its use in humans.

Assessment of Renal Perfusion in a Canine Model Using FS069, A New Transpulmonary Echocontrast Agent

We have previously demonstrated the safety and efficacy of FS069, a new transpulmonary echocontrast agent, for myocardial opacification. To our knowledge, no information exists regarding the use of this agent for transcutaneous assessment of renal perfusion. We studied 14 mongrel dogs using intravenously administered FS069. Renal ultrasound imaging was performed with a Hewlett‐Packard Sonos 1500 using a 3.5‐MHz transducer. Renal blood flow (ReBF) was altered using renal artery occlusion in four dogs and dipyridamole (0.56 rag / kg IV) in ten dogs. Renal perfusion was quantitatively assessed before and after each intervention using background subtracted peak intensity. ReBF was assessed with radiolabeled microspheres in ten dogs. Renal opacification was observed in all 14 dogs at baseline. The intravenous contrast dose required to produce optimal renal opacification ranged from 0.3–0.7 cc. After renal artery occlusion, peak intensity was reduced from 5.4 ± 5.8 to 0.93 ± 1.1 units (r = 0.99, P < 0.008). As expected, blood pressure and ReBF dropped in all ten dogs after dipyridamole administration. Interestingly, peak intensity increased in all but one dog. An inverse correlation (r = ‐0.75, P = 0.02) was observed between ReBF and peak intensity (percent change from baseline). The inverse relation between ReBF and peak intensity observed suggests vasocon‐striction of the afferent arterioles in response to dipyridamole and a reduced clearance of the contrast. These findings are in agreement with previous data demonstrating decreased renal thallium clearance postdipyridamole administration. Our data document the feasibility to assess renal perfusion under various flow states after intravenous injection of FS069.