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.

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 hemorrhage after knee arthroplasty using cryo-based fibrin sealant.

The spray application of cryo-based fibrin sealant was evaluated for reducing hemorrhage in a complex, anticoagulated canine model of knee joint arthroplasty. Nine heparinized dogs underwent bilateral knee arthroplasty under tourniquet control with each animal having 3 mL of fibrin sealant sprayed onto one joint and the other joint serving as control. The fibrin sealant significantly reduced total and incremental bleeding as compared to the control side (P < .05). In addition, the hemostatic effectiveness of the fibrin sealant increased as bleeding propensity increased (P < .05). This study suggests that fibrin sealant may reduce bleeding from orthopedic joint replacement in human patients undergoing routine operations as well as those receiving forms of anticoagulation to reduce the incidence of deep venous thrombosis and pulmonary embolus.

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.

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.

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.

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.

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.

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.

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.

Seroma prevention in a rat mastectomy model: use of a light-activated fibrin sealant.

Seroma formation following mastectomy and axillary dissection remains a common and significant problem contributing to patient morbidity and health-care costs. Previous data have suggested that fibrin sealant (FS), a biological adhesive, is capable of controlling lymphatic leakage and assisting with skin graft adhesion. In this study, the use of an experimental, light-activated FS under development by CryoLife (CFS) was evaluated in a rat mastectomy model in order to reduce seroma formation. CFS is a premixed form of FS, containing an inactivator that is reversed in the presence of light, causing sealant to form. In this model, rats underwent mastectomy and extensive dissection of the axillary lymphovasculature. Next, 1 ml of saline or FS was applied to the operative site and the wound was closed. Three groups of animals were evaluated 5 days postoperatively by measuring the volume (in milliliters) of seroma able to be aspirated from the surgical site. The saline control group (N = 20) had a seroma volume (mean +/- standard deviation [SD]) of 4.2 +/- 2.9 ml, while a form of CFS containing human fibrinogen (80 to 100 mg per milliliter) and human thrombin (20 U per milliliter) (N = 20) had a significantly smaller seroma volume of 1.1 +/- 1.6 ml (p < 0.001 analysis of variance). University of Virginia (UVA) FS, containing human fibrinogen (20 mg per milliliter) and bovine thrombin (500 U per milliliter) (N = 20), had a seroma volume of 2.0 +/- 1.6 ml (p < 0.01, compared to control; p > 0.2, compared to CFS). Thus, this form of CFS significantly reduced seroma formation compared to saline control and also appeared to result in a smaller fluid accumulation than with UVA FS, although this trend was not statistically significant. These data suggest that the use of CFS may help to reduce seroma formation in humans.

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.

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.

Effect of fibrinogen and thrombin concentrations on mastectomy seroma prevention.

Seroma formation remains a significant clinical problem which increases morbidity and hospital costs in patients undergoing mastectomy operations. This study evaluated the effect of varying the concentrations of fibrinogen and thrombin in fibrin sealant on successfully preventing seroma formation in a rat model. After axillary dissection, control animals (Groups I and II) had 1 ml of either normal saline or thrombin (100 U/ml) applied to the axilla while treated animals (Groups III-VIII) had increasing concentrations of 0.5 ml of fibrinogen (25, 50, or 100 mg/ml) and 0.5 ml of thrombin (10 or 100 U/ml) applied. Seroma volumes (means +/- standard deviation) were measured on Postoperative Day 5. They were largest in Group I (3.1 +/- 1.9 ml, n = 13) and Group II (3.9 +/- 2.7 ml, n = 15) and then decreased from a high in Group III (2.5 +/- 2.4 ml, n = 15) using fibrinogen, 25 mg/ml, and thrombin, 10 mg/ml, to a low in Group VIII (0.8 +/- 1.0 ml, n = 15) using fibrinogen, 100 mg/ml, and thrombin, 100 U/ml. Analysis of variance revealed a statistically significant difference in the mean seroma fluid volumes between the groups (P = 0.0021), while Scheffe's comparison showed a specific significant difference (P = 0.028) between the thrombin control (Group II) and the highest concentration fibrin sealant (Group VIII). The difference in seroma volumes for all control animals (Groups I and II), 3.5 +/- 2.4 ml, and all treated animals (Groups III-VIII), 1.7 +/- 2.1 ml, was highly significant by unpaired t test. (P < 0.0001). Thus, fibrin sealant was useful in reducing seroma formation in this rat model with the highest concentration of fibrinogen and thrombin appearing most effective. These data may be useful in guiding future clinical trials in humans.

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.

Detection of coronary stenoses and quantification of the degree and spatial extent of blood flow mismatch during coronary hyperemia with myocardial contrast echocardiography.

BACKGROUND: We hypothesized that the degree and spatial extent of blood flow mismatch in beds supplied by stenoses that are not flow-limiting at rest can be quantified with myocardial contrast echocardiography (MCE) using left atrial (LA) and right atrial (RA) injections of contrast during pharmacologically induced coronary hyperemia. METHODS AND RESULTS: In 12 open-chest dogs, MCE was performed and myocardial blood flow (MBF) was measured by use of radiolabeled microspheres at baseline and during phenylephrine-induced coronary hyperemia. In the presence of this drug, stenoses were placed during different stages on the left anterior descending (LAD) and left circumflex (LCx) coronary arteries, and MCE and MBF assessments were performed. LA injections of 2 mL of 0.5 billion/mL microbubbles (mean diameter, 4.3 microns) were performed at each stage in all 12 dogs, and RA injections of 10 mL of 6 billion/mL microbubbles (mean diameter, 3.7 to 5.3 microns) were administered in 7 dogs. MCE images in which the contrast disparity between the LAD and LCx beds was maximal were digitally subtracted from precontrast images, and mean videointensities in these beds were measured after the dynamic range of gray-scale intensities was increased in the subtracted image and the image was color coded. The region showing hypoperfusion during LAD stenosis was planimetered and expressed as a percentage of the myocardial area in the short-axis slice. There was an excellent correlation between the LAD/LCx bed videointensity ratio and LAD/LCx bed MBF ratio (y = 0.5x + 0.44, r = .91, P < .001) during 57 LA injections. There was also an excellent correlation between the hypoperfused bed size on MCE during LA injection of contrast in the presence of LAD stenosis and the hypoperfused myocardium as determined by radiolabeled microspheres (y = 0.8x + 4.2, r = .90, P < .001, SEE = 2.4, n = 11). The anterior myocardium was opacified in 6 dogs receiving RA injections of contrast, and the hypoperfused area during LAD stenosis correlated closely with that determined by radiolabeled microspheres (y = 0.86x + 3.4, r = .93, P < .01). CONCLUSIONS: Coronary stenoses, which are not flow limiting at rest, can be detected and the degree and spatial extent of blood flow mismatch during pharmacologically induced coronary hyperemia can be quantified with MCE using LA and RA injections of contrast. Thus, it is possible that the severity of coronary stenoses and the quantum of myocardium in jeopardy could be quantified in the future with MCE using venous injection of contrast.

Reduction of femoral arterial bleeding post catheterization using percutaneous application of fibrin sealant.

The number of cardiac catheterizations performed yearly is growing with correspondingly increasing amounts of morbidity, complications, and hospital costs. This study suggests that fibrin sealant instillation via an arterial sheath at the completion of femoral catheterization may improve hemostasis. Results using fibrin sealant in 12 unheparinized dogs documented significant reductions (McNemar's exact test) versus control for groin ecchymoses (1 versus 8, P = .008) and radiolabeled hematoma formation (0 versus 7, P = .016). Also swelling was less in the fibrin sealant treated groins when compared to control groins (1 versus 6, P = .125), but failed to reach statistical significance. Results in eight heparinized dogs (activated clotting time 374 +/- 22, mean +/- SEM) revealed a statistically significant reduction in signs of gross bleeding in the fibrin sealant-treated groins (1 versus 8, P = .016). This method may contribute to reduced morbidity, complications, and length of hospitalization. It may also allow for earlier patient mobilization after cardiac catheterization.

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.

Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.

BACKGROUND: The purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. METHODS AND RESULTS: Based on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P < .001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y = 0.24x + 0.73, SEE = 0.36, r = .88, P < .001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. CONCLUSIONS: Myocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.