Myocardial contrast echocardiography in acute myocardial infarction using aortic root injections of microbubbles in conjunction with harmonic imaging: potential application in the cardiac catheterization laboratory.

OBJECTIVES: The aim of this study was to evaluate myocardial contrast echocardiography using aortic root injections with harmonic imaging in experimental acute myocardial infarction to determine the potential of this approach in the cardiac catheterization laboratory. BACKGROUND: It would be desirable to have an adjunctive procedure that could evaluate myocardial perfusion at the time of cardiac catheterization in patients with acute myocardial infarction. A single injection of contrast medium in the aortic root would provide complete information on myocardial perfusion in a cross section of the heart. High quality images would provide on-line assessment of myocardial perfusion without recourse to image processing. These data could be very valuable for determining patient management. METHODS: Perfusion defects on myocardial contrast echocardiography were measured during coronary occlusion and reflow, using fundamental and harmonic imaging in both continuous and intermittent modes in nine open chest dogs. These defects were compared with risk area on technetium-99m autoradiography and infarct size on tissue staining. RESULTS: Whereas harmonic imaging increased myocardial video intensity by more than twofold (p < 0.001) compared with fundamental imaging after aortic root injection of contrast medium, intermittent imaging was not superior to continuous imaging. The improved signal to noise ratio of harmonic imaging allowed on-line definition of risk area (r = 0.98) and infarct size (r = 0.93) without recourse to off-line processing. Similar results could be obtained with fundamental imaging only after off-line processing. CONCLUSIONS: Aortic root injection of contrast medium coupled with harmonic imaging can be used to provide accurate on-line assessment of risk area and infarct size during acute myocardial infarction. These results have important implications for the catheterization laboratory.

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection.

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.

Deoxygenated blood minimizes adherence of sonicated albumin microbubbles during cardioplegic arrest and after blood reperfusion: experimental and clinical observations with myocardial contrast echocardiography.

Both administration of cardioplegic solution and blood reperfusion result in endothelial dysfunction. The transit rate of albumin microbubbles during myocardial contrast echocardiography may reflect endothelial injury. Accordingly, we performed myocardial contrast echocardiography in 12 dogs undergoing cardiopulmonary bypass and measured the myocardial transit rate of microbubbles injected into the aortic root during delivery of cardioplegic solutions containing arterial and venous blood and delivery of pure crystalloid cardioplegic solution. The myocardial transit rate of 99mTc-labeled red blood cells was measured and perfusates were sampled for biochemical analysis at each stage. The microbubble transit rate was markedly prolonged during delivery of crystalloid cardioplegic solution and improved significantly during infusion of blood cardioplegic solution (p < 0.001); venous compared with arterial blood in the solution resulted in a greater rate (p < 0.001). The microbubble transit rate did not correlate with pH, oxygen tension or carbon dioxide tension values, or K+ concentration. The red blood cell transit rate remained constant regardless of the cardioplegic perfusate infused. Myocardial contrast echocardiography was also performed in 12 patients undergoing coronary artery bypass who underwent sequential arterial and venous reperfusion after cardioplegic arrest. The microbubble transit rate was faster with venous than arterial blood reperfusion (p = 0.01), although this gain was diminished when arterial blood reperfusion preceded venous blood reperfusion (p = 0.05). Our results indicate that endothelial dysfunction after cardioplegic arrest may be ameliorated by reperfusion with venous rather than arterial blood.

Mechanism of myocardial dysfunction in the presence of chronic coronary stenosis and normal resting myocardial blood flow: clinical implications.

In chronic coronary artery disease, resting myocardial dysfunction can exist despite normal resting transmural myocardial blood flow (MBF). We hypothesized that this phenomenon occurs because of diminished endocardial MBF reserve. MBF (measured with radiolabeled microspheres) and wall thickening (WT) (measured with echocardiography) were assessed in 7 dogs after the development of severe left ventricular dysfunction caused by placement of ameroid constrictors on the left anterior descending (LAD) and left circumflex arteries and 3 weeks after selective bypass surgery to the LAD. Before surgery, the mean transmural MBF at rest and at peak dobutamine dose in the LAD bed were 1.1 +/- 0.5 and 3.0 +/- 1.5 mL/min per gram, respectively, and were not significantly changed after LAD bypass. The resting endocardial-to-epicardial MBF ratio (EER) was also normal before bypass (1.5 +/- 0.6) and remained unchanged after surgery. The prebypass EER at peak dobutamine dose, however, was markedly diminished in the LAD bed (0.7 +/- 0.3) and improved significantly (1.3 +/- 0.8, P <.01) after surgery. Resting WT in the LAD bed also improved to normal levels (36% +/- 4% versus 13% +/- 6%, P =.0001) and no longer demonstrated a biphasic response to dobutamine. In comparison, the nonbypassed left circumflex bed continued to show reduced resting WT (12% +/- 6%), a biphasic response to dobutamine, and abnormal EER during rest and dobutamine (0.7 +/- 0.3). We conclude that persistent myocardial dysfunction in the presence of normal resting transmural MBF can occur as a result of diminished endocardial MBF reserve, with transmural MBF reserve remaining normal.

Integrated backscatter and digital acquisition during myocardial contrast echocardiography: is there an advantage over conventional echocardiography for intracoronary injections?

This study was designed to answer the question of whether, despite their theoretic superiority, integrated backscatter imaging (IBS) and digital data acquisition (DA) offer any advantage over conventional echocardiography (CE) during quantitative myocardial contrast echocardiography. In vitro experiments were performed (1) to determine the microbubble concentration versus videointensity relationships for CE and IBS and (2) to define the relationship between flow through and microbubble transit rates for CE and IBS. These data were stored on videotape. In vivo experiments were performed whereby microbubbles were injected into the left anterior descending artery at different flow rates in 14 dogs and IBS and CE data were stored both in digital format and on videotape. Although the level of compression did not affect the microbubble concentration versus videointensity plots during IBS compared with CE, in practical terms the mean transit rate, peak intensity, and area under the curve were not affected by the level of compression for both forms of imaging as long as the postprocessing used for CE imaging was linear and the microbubble dose was small. In addition, although DA resulted in higher peak intensity and area under the curve compared with storage on videotape because of its broader dynamic range, the correlation between these measurements was excellent with both forms of image storage. We conclude that, although differences exist between CE and IBS and between Da and analog acquisition, these differences do not significantly affect the derivation of parameters from time-intensity plots during myocardial contrast echocardiography when contrast material is injected into a coronary artery.

Myocardial perfusion characteristics and hemodynamic profile of MRX-115, a venous echocardiographic contrast agent, during acute myocardial infarction.

We sought to determine whether MRX-115, a new venous echocardiographic contrast agent, could accurately assess risk area during coronary occlusion and infarct size after reperfusion by using novel imaging modalities meant to selectively enhance contrast signals. In 12 open-chest dogs, venous injections of 0.5 ml of MRX-115 were performed during baseline and coronary occlusion and after reperfusion in the presence of exogenous hyperemia. Ultrasound was transmitted at 2 MHz and received at both 2 MHz (fundamental) and 4 MHz (harmonic) frequencies during continuous and intermittent (end-systolic only) imaging. The risk area during coronary occlusion was compared with technetium autoradiography, and the infarct size after reperfusion was compared with postmortem tissue staining. MRX-115 produced no alterations in hemodynamic or pulmonary gas exchange at any stage. During continuous (both fundamental and harmonic) and intermittent fundamental imaging, measurements of perfusion defects were precluded in many dogs by either poor signal enhancement or posterior wall attenuation. By comparison, these measurements were possible during intermittent harmonic imaging in all dogs except one, which had a very small infarction during reflow. Correlation analysis between perfusion defect size on intermittent harmonic imaging and either autoradiographic risk area or postmortem infarct size gave r values of 0.83 and 0.92, respectively. We conclude that MRX-115 is hemodynamically well tolerated and, when imaging is performed after venous injection, can accurately assess regions of hypoperfusion when combined with intermittent harmonic imaging. These results are promising for the use of this approach in patients with acute myocardial infarction.

Distinguishing reverse transcriptase of an RNA tumor virus from other known DNA polymerases.

Assays are described that permit one to distinguish the reverse transcriptase of RNA tumor viruses from known normal cellular DNA-instructed DNA polymerases. Template responses of purified reverse transcriptase were compared with those of similar preparations of the DNA polymerase I of Escherichia coli and of calf-thymus polymerase. All three enzymes responded well to the synthetic duplexes poly(dT).poly(A), poly(U).poly(A), and poly(dT).poly(dA). Hence, these duplexes can detect, but cannot distinguish reverse, transcriptase from the known normal DNA polymerases. However, certain oligomer-homopolymer complexes serve as excellent distinguishing agents. The reverse transcriptase responds very well to (dT)(10).poly(A) and very poorly to (dT)(10).poly(dA), whereas both cellular DNA polymerases do not exhibit this behavior.Purified single-stranded RNA also serves as a diagnostic device, since only reverse transcriptase gives a detectable response. To be definitive, a positive response to RNA must be accompanied by a demonstration via molecular hybridization that the DNA product is complementary to the RNA and not to some minor DNA contaminant.

Determination of natural host taxonomy of RNA tumor viruses by molecular hybridization: application to RD-114, a candidate human virus.

The lysogenic bacteriophages and the RNA tumor viruses have in common the ability to add their genetic information to the genome of their host cells. The biological similarity extends further; data summarized here indicate that they both possess homology to the DNA of their uninfected indigenous hosts. Sharing of common sequences with normal host DNA has been established with avian, murine, feline, and primate oncornaviruses. This finding provides a method for determining the taxonomic position of the natural host of any new RNA tumor virus isolated. Application of this approach to RD-114 revealed extensive hybridization to normal cat DNA and little, if any, hybridization to human DNA. We conclude that the data assign a feline origin rather than a human origin to RD-114.

Changes in myocardial blood volume with graded coronary stenosis.

Vasodilation of microvessels distal to a stenosis results in an increase in myocardial blood volume (MBV). The purpose of this study was to examine the changes in MBV induced by graded coronary artery stenoses by using myocardial contrast echocardiography (MCE). Accordingly, 21 dogs underwent progressive stenosis of a coronary artery in a random order, the severity of which was judged by the pressure distal to it. Total myocardial blood flow (MBF) to the bed distal to the artery (both anterograde and collateral) was measured by injection of radiolabeled microspheres into the left atrium. In seven dogs, anterograde and total MBF were measured at each stenosis stage by injection of different microspheres into the left atrium and directly into the coronary artery, respectively. MBV was calculated by dividing MBF by the mean transit rate of microbubbles injected directly into the coronary artery during MCE. The perfusion bed size of the artery was also measured by MCE. Our major findings are as follows: 1) there is a nonlinear increase in MBV with increasing degrees of coronary stenosis until the coronary stenosis becomes critical; 2) at moderate levels of coronary stenosis, MBV remains constant despite ongoing autoregulation because of reduction in the size of the perfusion bed supplied by the stenotic vessel; and 3) after exhaustion of autoregulation, a decrease in MBV is noted with increasing levels of stenosis. We conclude that assessment of MBV provides insights into myocardial perfusion distal to a coronary stenosis above and beyond that provided by the measurement of MBF alone.

Coronary reserve abnormalities in the infarcted myocardium. Assessment of myocardial viability immediately versus late after reflow by contrast echocardiography.

BACKGROUND: The aim of this study was to determine whether myocardial contrast echocardiography (MCE) during exogenous vasodilation can accurately delineate infarct size, and hence the extent of myocardial viability, both immediately (15 minutes) and late (3 hours) after reperfusion when postreflow coronary hyperema is still present. METHODS AND RESULTS: Twenty-one open-chest anesthetized dogs underwent 3 to 6 hours of coronary occlusion followed by reperfusion. MCE was performed 15 minutes after reflow before and during infusion of 0.2 mg.kg-1.min-1 adenosine i.v.. In 12 dogs, infarct size was measured at this time. In the remaining 9 dogs, reperfusion was continued for 3 hours, when MCE was repeated before and after an infusion of 0.56 mg.kg-1.min-1 dipyridamole i.v. and infarct size was measured. In the absence of adenosine, MCE perfusion defect at 15 minutes underestimated infarct sizes at both 15 minutes and 3 hours, whereas in the presence of adenosine, the estimate of infarct size was more accurate. Similarly, in the absence of dipyridamole, although MCE perfusion defect underestimated infarct size (both measured 3 hours after reflow), in the presence of dipyridamole, the estimate of infarct size was more accurate. CONCLUSIONS: By unmasking abnormalities in flow reserve within the infarct bed, MCE in conjunction with coronary vasodilators can accurately predict infarct size both 15 minutes and 3 hours after reperfusion. Thus, MCE can be used for assessing the extent of myocardial viability both immediately and late after reperfusion when postreflow coronary hyperemia is still present.

Contractile versus microvascular reserve for the determination of the extent of myocardial salvage after reperfusion. The effect of residual coronary stenosis.

BACKGROUND: We hypothesized that microvascular reserve is a better indicator of the extent of viable myocardium postinfarction than contractile reserve, especially in the presence of a residual stenosis of the infarct-related artery. METHODS AND RESULTS: Fifteen dogs with various infarct sizes were studied after reperfusion. Contractile reserve, studied by use of dobutamine echocardiography, and microvascular reserve, studied by use of myocardial contrast echocardiography, were measured both before and after creation of a stenosis. In the absence of a stenosis, the relation between infarct size, expressed as percent of risk area, and wall thickening improved with increasing doses of dobutamine (r = .41, .71, and .90 for 5, 10, and 15 micrograms.kg-1.min-1, respectively; P < .01 for dobutamine 15 micrograms.kg-1.min-1). In the presence of a stenosis, however, the relation was poor for all doses of dobutamine (r = .22, .57, and .32 for 5, 10, and 15 micrograms.kg-1.min-1, respectively; P < .01 for 15 micrograms.kg-1.min-1 dobutamine in the absence of a stenosis). There was a fair correlation between infarct size and perfusion defect size on myocardial contrast echocardiography after reperfusion (r = .82), with the defect size underestimating infarct size by approximately 20%. This relationship improved (P < .01) during infusions of both adenosine (r = .99) and dobutamine (r = .94) in the absence of a stenosis. The correlations between infarct size and perfusion defect on myocardial contrast echocardiography also remained good in the presence of a stenosis (r = .95 and .81 for adenosine and dobutamine, respectively; P = NS compared with stenosis). CONCLUSIONS: Microvascular reserve is superior to contractile reserve for definition of the spatial topography of necrosis and hence the extent of viable myocardium within the infarct bed after reperfusion, particularly when a residual stenosis is present in the infarct-related artery.

A canine model of chronic ischemic cardiomyopathy: characterization of regional flow-function relations.

The controversy regarding the mechanism(s) of left ventricular (LV) dysfunction in chronic coronary artery disease is, in part, related to the lack of an appropriate animal model for this condition. We have developed such a model by placing Ameroid constrictors on proximal portions of coronary arteries in dogs who were euthanized (mean of 6 wk) after the development of severe global LV dysfunction noted on two-dimensional echocardiography. The LV end-systolic size nearly doubled (P < 0.001) over the observation period, and the percent change in LV size from end diastole to end systole decreased by >50% (P < 0.001). Regional dysfunction was noted in 23 of 24 myocardial beds analyzed within regions showing no gross evidence of infarction. In 10 of these beds, severe dysfunction was noted without a decrease in radiolabeled microsphere-derived myocardial blood flow (MBF). In 13 myocardial beds, decrease in function was associated with a decrease in MBF (P < 0.001), with close coupling noted between percent wall thickening and MBF. In the beds that exhibited an ultimate decrease in MBF, the decrease in function preceded the decrease in MBF. In conclusion, we describe chronic LV dysfunction in a canine model of multivessel stenosis that closely mimics chronic ischemic LV dysfunction in humans. Whereas regional function is severely reduced in this model, MBF is varied in different segments and at different times during the observation period. These results provide new insights regarding flow-function relations in chronic ischemic LV dysfunction.

Effects of radiofrequency catheter ablation on regional myocardial blood flow. Possible mechanism for late electrophysiological outcome.

BACKGROUND: We postulated that the late electrophysiological effects of radiofrequency (RF) ablation may be related to microvascular injury extending beyond the region of acute coagulation necrosis. METHODS AND RESULTS: Eighteen RF lesions created in the left anterior descending coronary artery (LAD) perfusion bed of seven open chest anesthetized dogs were studied. The ablation electrode and surrounding myocardium were imaged using high-resolution two-dimensional echocardiography at x 4 magnification. After 60 seconds of RF delivery, sonicated albumin microbubbles (mean size, 4.3 microns) were injected into the LAD to measure regional myocardial perfusion, and time-intensity plots were generated from simultaneously acquired two-dimensional echocardiography images. The regions with persistent contrast effect on two-dimensional echocardiography were larger than the pathological lesions (mean cross-sectional area, 48.3 +/- 6.3 versus 19.3 +/- 4.7 mm2, respectively; P < .0001). The mean contrast transit rate in the area corresponding to the pathological lesion was 25 +/- 12% of that in the normal myocardium, but it was also reduced beyond the lesion, being 48 +/- 27% and 82 +/- 28% of normal, respectively, in the 3-mm and 3- to 6-mm circumferential rims surrounding the pathological lesion (P < .05). Electron microscopy performed in two additional dogs with similar lesions demonstrated the presence of ultrastructural damage to the microvascular endothelium well beyond the pathological lesion edge. CONCLUSIONS: RF catheter ablation not only results in a marked reduction in blood flow within the acute pathological lesion but also causes reduced flow beyond the borders of the acute lesion because of microvascular endothelial cell injury. The progression or resolution of tissue injury within the region beyond the border of the pathological lesion may explain the late electrophysiological effects of RF ablation.

The presence of unique DNA sequences after viral induction of leukemia in mice. (RNA tumor virus-nucleic acid hybridization-insertion of viral DNA).

From previous studies, lymphocyte DNA from human leukemias and DNA from involved tissues of patients with Hodgkin's disease or Burkitt's lymphoma contain sequences that are absent from their normal counterparts. These sequences are related to those found in particulate elements associated with these neoplasias and possessing biochemical properties characteristic of RNA tumor viruses. Similar observations have been made of unique sequences related to those of the feline virus RD-114 and found in spontaneous mastocytomas in cats. Here we extend these results to the classical murine model of virus-induced leukemias. Splenic DNA from BALB/c mice with leukemia induced by Rauscher leukemia virus (RLV) possess some RLV-related sequences that do not exist in normal BALB/c DNA. Furthermore, these leukemia-specific sequences were absent in all other mouse strains examined, including AKR, a strain with a high incidence of spontaneous leukemia. The DNA of all noninfected mouse strains possesses considerable homology with the RLV genome. Temperature denaturation studies indicate, however, that although the RLV-related sequences found in all normal mice are similar to each other, they are not exactly homologous with RLV sequences. We conclude that RLV-induced leukemia in BALB/c results in the insertion of RLV sequences into cellular DNA that itself possesses only partial homology with the RLV genome.

Relation between regional function and coronary blood flow reserve in multivessel coronary artery stenosis.

In the setting of chronic coronary stenoses, percent wall thickening (%WT) both at rest and during catecholamine stimulation can be abnormal despite normal resting myocardial blood flow (MBF). We hypothesized that this phenomenon is related to abnormal MBF reserve. Accordingly, 15 dogs were studied between 7 and 10 days after placement of Ameroid constrictors around the proximal coronary arteries and their major branches, at a time when collateral development had not yet occurred. %WT and MBF were measured at rest, after 0.56 mg/kg of dipyridamole, and at incremental doses of dobutamine (5-40 microgram. kg(-1). min(-1)). Resting %WT and MBF were normal in all four sham dogs. Resting transmural MBF was normal in all segments in the 11 study dogs, despite reduced (-2 SD of normal) %WT (<30%) in 40 of 82 segments. MBF reserve was reduced (<3) in segments with reduced %WT, and a close coupling was noted between resting %WT and MBF reserve. All segments showed an increase in %WT with dobutamine up to a dose of 20 microgram. kg(-1). min(-1), above which those with abnormal endocardial MBF reserve showed a "biphasic" response. It is concluded that, in the presence of chronic coronary stenoses, abnormalities in resting %WT as well as inducible reduction in %WT during pharmacological stress are related to the degree of abnormal MBF reserve.

Reduction of femoral artery bleeding post catheterization using a collagen enhanced fibrin sealant.

As the number of cardiac catheterization procedures increases, so do associated complications and costs. This study suggests that the application of a new collagen enhanced fibrin sealant, Collaseal, may be used effectively to achieve rapid hemostasis at the arterial puncture site following femoral artery catheterization. Results in nine dogs anticoagulated with heparin (activated clotting time 396 +/- 107, mean +/- S.D.) revealed a statistically significant reduction in signs of gross bleeding in the sealant-treated groins as compared to control (2 versus 9, P = .0156). These results indicate that this commercially produced sealant might be used in human patients undergoing cardiac catheterization to decrease complications, lengths of stay, and costs.

Myocardial perfusion imaging in the setting of coronary artery stenosis and acute myocardial infarction using venous injection of a second-generation echocardiographic contrast agent.

BACKGROUND: We hypothesized that by producing excellent myocardial opacification, venous injection of FS-069 coupled with intermittent harmonic imaging (IHI) can be used to determine the presence and severity of coronary stenoses during hyperemia, the size of the risk area during coronary occlusion, and the extent of myocardial salvage after reperfusion. METHODS AND RESULTS: Twelve dogs were imaged both continuously and intermittently (every end systole) in the fundamental (2 MHz) and harmonic (transmit at 2 and receive at 4 MHz) modes. FS-069 (1 mL) was injected intravenously for all stages and modes of imaging. Myocardial video intensity was severalfold (P<.01) higher during IHI than all other modes of imaging. Perfusion defects were difficult to measure during continuous and intermittent fundamental imaging and during continuous harmonic imaging. In comparison, the defects were clearly demarcated during IHI. When this mode was used, the magnitude of perfusion mismatch during hyperemia in the presence of a coronary stenosis correlated closely with the magnitude of flow mismatch when radiolabeled microspheres were used (r=.94). The perfusion defect sizes during coronary occlusion and reperfusion also correlated closely with postmortem risk area (r=.89) and infarct size (r=.96), respectively. CONCLUSIONS: Venous injection of FS-069 coupled with IHI produces excellent myocardial opacification. This approach can be used to determine the severity of coronary stenoses during hyperemia, the size of the risk area during coronary occlusion, and the extent of myocardial salvage after reperfusion. This approach, therefore, holds promise in the clinical setting.

Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion. An experimental evaluation.

BACKGROUND: Although dobutamine echocardiography is being increasingly used to determine the presence of viable myocardium in patients who have undergone successful reperfusion therapy, the physiological basis for such a use has not been clearly defined. Because postischemic myocardium has contractile reserve, we hypothesized that the absolute degree of wall thickening induced by dobutamine during reflow would be directly related to the amount of myocardium that has escaped necrosis. METHODS AND RESULTS: Three groups of 12 dogs each were studied at baseline and during 2 to 6 hours of coronary artery occlusion and 15 minutes of reperfusion. In group 1 dogs, which did not receive dobutamine during any of these stages, percent wall thickening at these stages was 32 +/- 6%, -2 +/- 6%, and 5 +/- 6%, respectively, and there was no relation between infarct size and percent wall thickening during reflow (r = .20, P = .51). In group 2 dogs, which received 15 micrograms/kg per minute of dobutamine at all stages, wall thickening at these stages was 40 +/- 8%, 0 +/- 8%, and 19 +/- 10%, respectively, and a good inverse correlation was noted between infarct size and percent wall thickening during reflow (r = -.81, P = .001). In group 3 dogs, in which wall thickening during reflow was measured both before and during infusion of 15 micrograms/kg per minute of dobutamine, it was 5 +/- 8% and 18 +/- 14%, respectively, at these stages. Although the correlation between infarct size and percent wall thickening was poor in the absence of dobutamine (r = .36, P = .26), an excellent inverse correlation was noted between the two in the presence of dobutamine (r = -.93, P < .001). A fair inverse correlation was also noted between infarct size and the absolute change in wall thickening induced by dobutamine (r = -.72, P < .01). Maximal wall thickening was noted at a dobutamine dose of 15 micrograms/kg per minute, and lower doses did not elicit thickening in the presence of larger infarcts despite the presence of viable myocardium. CONCLUSIONS: When myocardial necrosis coexists with post-ischemic myocardial dysfunction and no residual coronary stenosis, the absolute degree of wall thickening during dobutamine can be used to determine the extent of myocardium that has escaped necrosis. The dose of dobutamine needed to elicit maximal thickening of the postischemic myocardium is related to the amount of myocardial necrosis.