Evaluation of changes in skeletal muscle blood flow in the dog with contrast ultrasonography.

Intraoperative methods to assess skeletal muscle blood flow or muscle-flap perfusion during vascular reconstructive surgery are limited. At present, techniques enable only anatomic identification of the degree of patency of large vessels. We report here the first use of ultrasonography to assess dynamic changes in skeletal muscle perfusion. Baseline blood flow in the adductor muscle group of the hindlimbs of seven dogs was measured with an electromagnetic flow probe and with contrast ultrasound using the contrast agent Albunex. Blood flow was manipulated in each dog pharmacologically with random administration of intraarterial injections of Neo-Synephrine and papaverine. After each change in blood flow detected by electromagnetic flow probe, flow also was assessed qualitatively by four independent observers who graded video-recorded contrast enhancement in the muscle group on a 0 to 4 scale. Videodensitometry also was used to generate time versus intensity curves in the adductor muscle region of interest. Peak pixel intensity was determined during each flow condition. A total of 21 flow measurements were made with each assessment scheme (electromagnetic flow probe, video enhancement, videodensitometry) for each condition (7 control, 7 papaverine, 7 Neo-Synephrine). Changes in blood flow assessed by video enhancement scores and changes in peak pixel intensity correlated with changes measured by electromagnetic flow probe (r = 0.84 and 0.66, respectively). We conclude that contrast ultrasound may be used to detect changes in skeletal muscle perfusion intraoperatively. Measures of muscle perfused by visual inspection of contrast enhancement and videodensitometric data were in agreement with direct measurements of changes in skeletal muscle blood flow.

The relationship between immediate outcome after cardiac surgery, homogeneous cardioplegia delivery, and ejection fraction.

BACKGROUND: Optimal myocardial protection during cardiac surgery with ischemic arrest is predicated on among other variables, homogeneous cardioplegia distribution. Contrast echocardiography has been shown to provide information regarding the intramyocardial distribution of cardioplegia solution. To test the hypothesis that information regarding cardioplegia distribution derived from contrast echocardiography may be associated with immediate clinical outcome after cardiac surgery, data from 21 patients were examined retrospectively. METHODS: Contrast-enhanced cardioplegia distribution patterns of the left ventricle short axis view obtained with transesophageal echocardiography were examined off-line by four observers blinded to clinical outcome. Contrast effect was scored for eight equally divided myocardial segments (0 = no contrast, 1 = nonuniform contrast, 2 = uniform contrast, 3 = excessive contrast). The scores were then averaged between segments and between observers to generate an antegrade, a retrograde, and a combined global contrast score for each patient. RESULTS: Seventeen patients were separated from bypass without difficulty (group A) and 4 patients required sustained inotropic therapy or an intra-aortic balloon pump to facilitate separation from bypass (group B). As would be expected, group A patients had a higher average preoperative ejection fraction than did group B patients (60 percent +/- 14 vs 31 percent +/- 7, p < 0.01). In group A, however, for 4 of 17 patients (23 percent), low preoperative ejection fraction was not predictive of postoperative exogenous circulatory support requirements. Group A patients also had significantly higher antegrade (1.6 vs 1.2, p < 0.02), retrograde (1.7 vs 1.1, p < 0.02), and combined global contrast scores (1.7 vs 1.1, p < 0.01) than did group B patients. All patients with low preoperative ejection fraction and low intraoperative contrast scores required exogenous support to separate from cardiopulmonary bypass. CONCLUSION: Contrast echocardiography makes possible an evaluation of the intensity and distribution of contrast-enhanced cardioplegia delivery and we believe the efficacy of intraoperative myocardial protection. Although low preoperative ejection fraction is a known predictor of poor immediate postoperative outcome following cardiac surgery, not all patients with low preoperative ejection fractions require inotropic support postoperatively. Our results suggest that monitoring cardioplegia distribution with contrast echocardiography may offer insight for better patient stratification based on intraoperative myocardial protection in patients with low ejection fraction. We believe a more extensive evaluation of this relationship should be pursued in a prospective manner.

Intraoperative perfusion echocardiography.

The ability to assess perfusion intraoperatively should enable end-organ evaluation of the effects of therapeutic choices and provide a basis for understanding the mechanisms of disease. Several experimental techniques for assessment of tissue perfusion are being evaluated; contrast echocardiography appears to be adaptable to the perioperative setting because of its portability and relatively modest cost. With further improvements in commercial ultrasound imaging devices and ultrasonic contrast agents, intraoperative contrast echocardiography may prove to be a technique for quantitation of tissue perfusion. Contrast echocardiography is currently being used intraoperatively to assess cardioplegia distribution, coronary bypass graft patency, and coronary artery collateral vessel distribution. In addition, relative change in renal blood flow can be assessed during renal transplant surgery. With continued advancement of ultrasound technology providing linear (or known) acoustic signal response and wider dynamic range for detection of small and large concentrations of contrast agents, tissue blood flow may soon be evaluated with even greater precision.

Pitfalls in quantitative contrast echocardiography: the steps to quantitation of perfusion.

Current methods used clinically to assess myocardial perfusion are invasive and expensive. As the technology of ultrasound imaging improves, CE may provide a relatively inexpensive, noninvasive means of quantitating myocardial perfusion. Issues regarding stability of microbubble contrast agents must be studied more closely under physiologic conditions. As such, encapsulated microbubbles may provide more stability under physiologic pressures than free gas microbubbles. Introducing high concentrations of contrast, either by hyperconcentrating the contrast agent or by increasing the injection rate, may provide greater stability under physiologic conditions. Further, before quantitative statement of tissue perfusion can be made, the relationship between tracer concentration and system response must be established. Further, a "linear" postprocessing ultrasound setting does not eliminate this requirement as data must still undergo nonlinear transformation during log compression and time-gain compensation. Additionally, issues regarding "electronic thresholding" must be explored more extensively in vivo. Commercial ultrasound scanners, in their present form, may not offer adequate sensitivity for absolute quantitative studies. Further development of modified ultrasound systems may provide sufficient sensitivity for quantitative perfusion imaging. CE offers a potentially powerful tool in the clinical management of patients with ischemic heart disease. Conventional coronary angiography provides information on the size of a lesion, but accompanying tissue perfusion distal to the lesion cannot be determined. Doppler ultrasonography determines velocity of blood flow in large vessels but does not offer the potential to quantitate tissue perfusion. Clearly, CE has a place in the future of diagnostic imaging. The recent work of Ito et al. demonstrated the qualitative potential of CE in the identification of "areas at risk" in patients who had undergone thrombolysis or percutaneous transluminal coronary angioplasty after an acute myocardial infarction. With further improvement in the ultrasound imaging techniques and microbubble stability, CE may offer an inexpensive, noninvasive means of assessing myocardial perfusion.

Assessment of renal blood flow with contrast ultrasonography.

Sonicated albumin microspheres, a digitalizing ultrasound system, and a mathematical model for flow were used to determine whether blood flow in the canine kidney could be assessed with contrast ultrasound. Albunex ultrasound contrast microspheres were injected into the aorta while ultrasound images of the kidney and aorta were recorded simultaneously. Ultrasound data were obtained during contrast injections at 93 different renal blood flow rates in nine dogs. Contrast dose was calibrated to ultrasound system response for both aortic and renal images. A linear relationship between microbubble concentration used and pixel intensity was established (r = 0.89 for aortic images and r = 0.91 for renal images). Renal blood flow was manipulated from baseline by means of a hydraulic renal artery occluder and by intravenous dopamine or fenoldopam infusion. Blood flow calculated with contrast ultrasonography was compared with direct measurement obtained with an electromagnetic flow probe at each flow rate. Direct measurement correlated with rates calculated with contrast ultrasonography (r = 0.84, 95% confidence limits from 0.75 to 0.90). Overall, calculations tended to overestimate absolute flow measurements, and overestimation of flow tended to be greater during pharmacologically manipulated flow rates. We conclude the changes and trends in renal blood flow can be serially assessed in vivo with contrast ultrasonography, but technical limitations of present commercial ultrasounds systems preclude absolute quantification at this time.

Myocardial distribution of cardioplegic solution after retrograde delivery in patients undergoing cardiac surgical procedures.

The myocardial distribution of both antegrade and retrograde cardioplegia for cardiac surgical intervention, after induction of cardioplegia via the aortic root, was directly assessed and compared in 19 patients by means of contrast echocardiography. Two-dimensional transesophageal echocardiographic images of the short axis of the left ventricle at the level of the papillary muscles were obtained after sonicated Renografin-76 microbubbles were injected into an aortic root and/or transatrial coronary sinus catheter during delivery of cardioplegic solution. Segmental distribution of cardioplegic solution was immediately noted in the myocardium at the time of contrast injections. In 11 of 18 patients (61%) cardioplegic solution was dispersed to all left ventricular myocardial segments after antegrade delivery. In 17 of 19 patients (90%) retrogradely delivered cardioplegic solution (after antegrade induction of cardioplegia in 18 of the 19 patients) was dispersed to all the left ventricular myocardial segments, including the septum. In 2 of the patients, initial lack of retrograde distribution of cardioplegic solution was remedied when the coronary sinus catheter was repositioned and contrast cardioplegic solution was reinjected. Imaging of the right ventricle was possible in only 4 of the 19 patients and revealed that after retrograde delivery, cardioplegic solution had been at least partially distributed to the right ventricle as well. We performed off-line videodensitometric analysis in 9 patients after retrograde delivery of cardioplegic solution. Mean peak pixel-intensity ratio of flow from the endocardium to the epicardium in the left ventricular free wall was 1.46 +/- 0.27, and mean peak pixel-intensity ratio of flow from the left to the right intraventricular septal endocardium was 1.39 +/- 0.33 (p < or = 0.05).

In vitro calculation of flow by use of contrast ultrasonography.

Contrast echocardiography has been used for qualitative assessment of cardiac function, and its potential for quantitative assessment of blood flow is being explored. With the development of an ultrasound contrast agent capable of passage through the microcirculation, a mathematical model based on classic dye dilution theory, and a digital ultrasound acquisition system, absolute quantitation of myocardial perfusion may be feasible. This study validates the mathematical model in a simple in vitro tube system. Flow was delivered at variable rates through an in vitro tube system while a longitudinal section was imaged with a modified commercial ultrasound scanner. Albunex contrast agent was injected, and videointensity data were captured and analyzed off line. Time-intensity curves were generated, and flow was calculated by use of a mathematical model derived from classic dye dilution mathematics. For 39 different flow rates, ranging for 9.2 to 110 ml/seconds, a correlation coefficient of r = 0.928 (p < 0.001) with a slope of 0.97 was calculated. We conclude that (1) contrast ultrasonography is capable of quantitative determination of flow in an in vitro system, and (2) a mathematical model based on dye dilution theory can be used to calculate flow with accuracy and precision.

The influence of intravenous Albunex injections on pulmonary arterial pressure, gas exchange, and left ventricular peak intensity.

Contrast ultrasonography may be used to assess regional tissue perfusion. The purpose of this study was to evaluate the safety and efficacy of a new, commercially prepared ultrasound contrast agent (Albunex) in dogs. The injections were administered from peripheral intravenous (IV), right atrial (RA), and pulmonary artery (PA) sites. Acute pulmonary hemodynamic and gas exchange effects of low-dose (0.5, 1.0, 2.0 ml) Phase I injections, and high-dose (2.0, 5.0, 10, 20 ml) Phase II injections of Albunex were evaluated in nine dogs. Immediately before and after each injection, pulmonary artery pressure (PAP) and oxygen tension (PO2) were determined. In addition, left ventricular cavity opacification was assessed visually and by videodensitometric off-line analysis. Visual assessment was performed by four blinded observers who graded on a scale of 0 to 3 (0 = no contrast enhancement of the left ventricular (LV) cavity; 1 = weak or suboptimal contrast enhancement; 2 = optimal or excellent contrast enhancement; and 3 = attenuation of the ultrasound signal following a contrast injection). Peak pixel intensity was also determined with videodensitometric analysis. Results showed that significant changes in PAP or PO2 were not noted after Albunex injections, regardless of injection site or dose range. The average change in PAP after Albunex injection was 1.0 mm Hg +/- 1.2 mm Hg (NS), and the average change in PO2 after Albunex injections was 6.2 mm Hg +/- 6.7 mm Hg (NS). The left ventricular cavity peak pixel intensity was dependent on both injection site (PA = RA > IV) and dose range (2.0 = 1.0 > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of retrograde cardioplegia distribution using contrast echocardiography.

Retrograde cardioplegia has gained popularity in coronary and noncoronary cardiac operations. We have used contrast echocardiography in the open-chest canine model to compare the distribution of cardioplegia delivered antegrade in the aortic root versus retrograde through the coronary sinus, and to determine the effect of coronary occlusion on that delivery. With no coronary occlusion, antegrade cardioplegia was distributed to the entire left ventricle and septum whereas retrograde cardioplegia was distributed to the left ventricular free wall but had inconsistent delivery to the septum. Acute occlusion of the left circumflex coronary artery resulted in 57.06% +/- 9.52% of the left ventricle not being perfused by antegrade cardioplegia and occlusion of both the left circumflex and anterior descending coronary arteries caused a 65.46% +/- 18.5% reduction in perfusion by antegrade cardioplegia. Acute coronary occlusion had no effect on retrograde cardioplegia distribution. We conclude that retrograde cardioplegia is less homogeneous than antegrade cardioplegia in the intact coronary circulation but that retrograde cardioplegia preserves cardioplegia distal to acutely occluded coronary arteries. Furthermore, contrast echocardiography is a useful method of assessing myocardial perfusion and may have useful clinical applications.

Assessment of myocardial perfusion during CABG surgery with two-dimensional transesophageal contrast echocardiography.

No reliable, quantifiable index of tissue perfusion is currently available to assess the efforts of coronary artery bypass graft (CABG) surgery. We used two-dimensional transesophageal contrast echocardiography with sonicated Renografin-76 microbubbles to determine the distribution of myocardial blood flow during coronary artery bypass graft surgery in 15 patients. Sonicated Renografin-76 contrast agent was injected into the aortic root of all patients after institution of cardiopulmonary bypass and application of the aortic occlusive clamp. Eight patients had contrast agent injected directly into the free proximal end of the vein-CABG anastomosis. All patients again received aortic root injections during reperfusion after anastomosis of the proximal aortovein and distal coronary artery. Echocardiographic images of the left ventricle short axis at the level of the papillary muscles were obtained in real time and analyzed retrospectively from videotape. Injection of contrast provided information about the magnitude and geometric distribution of coronary artery-vein bypass run-off and enabled identification of poorly perfused myocardial regions. When predicted myocardial perfusion patterns, based on preoperative evaluation of epicardial vessel distribution derived from coronary angiography, were compared to actual perfusion patterns assessed with intraoperative echocardiography, contrast regional myocardial perfusion patterns were predicted 84% of the time (71-97%, 95% confidence limit). Regional myocardial perfusion deficits detected after coronary bypass grafting were associated with regional wall motion abnormalities detected after separation from cardiopulmonary bypass. Our technique makes possible on-line visualization of changes in regional blood flow in the heart before, during, and after CABG.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of renal blood flow by contrast ultrasonography: preliminary results.

Contrast ultrasonography, employing tracers behaving like red blood cells, is a promising technique to study regional blood flow distribution. Aim of this note is to quantitate renal blood flow in the dog using contrast ultrasonography. Mathematical formulae derived from the classical dye-dilution theory are applied. Ten different renal blood flow levels (ranging from 16 to 125 ml/min) were obtained by means of mechanical (stenosis and reperfusion) and pharmacological interventions (iv infusion of adrenaline, noradrenaline and fenoldopam). Renal blood flow was measured by electromagnetic flow-meter and contemporary calculated by contrast ultrasonography. The correlation coefficient between measured and calculated flow was 0.92 (p less than 0.01). Contrast ultrasonography is a technique capable of measuring renal blood flow at a wide range of different flow levels.