Koji Ohmori

Quantitative assessment of myocardial perfusion during graded coronary stenosis by real-time myocardial contrast echo refilling curves.

OBJECTIVES The present study examined the ability of real-time myocardial contrast echocardiography (MCE) to delineate abnormalities produced by graded coronary stenoses and to correlate signal intensity (SI) parameters derived from destruction/refilling curves with regional myocardial blood flow (MBF) and contractile function. BACKGROUND Recent technological advances have enabled myocardial opacification by MCE to be achieved during real-time imaging. METHODS In eight open-chest dogs, we created LAD occlusion and graded stenoses that were either flow-limiting at rest (FLS) or reduced adenosine hyperemia (non-flow-limiting at rest = NFLS). Myocardial contrast echo used Optison infusion and low-energy real-time power pulse inversion imaging. High-energy FLASH frames destroyed bubbles every 15 cardiac cycles. Myocardial SI-versus-time plots were fitted to a one-exponential function to obtain the rate of SI rise (b) and peak SI in the last frame. RESULTS Dyssynergy was not observed during any NFLS, but perfusion abnormalities were. Visual detection of decreased opacification was possible with severe NFLS and FLS. b demonstrated a significant reduction with severe NFLS and near significant with moderate NFLS; peak SI did not. All exponential parameters were significantly decreased with FL stenosis and occlusion. The MBF ratio in LAD/LCx beds (fluorescent microspheres) correlated with b (r = 0.79) and the product of the peak SI and b (r = 0.80). CONCLUSIONS In an open-chest dog model, parameters derived from microbubble refilling of the imaging field by real-time MCE correlate well with myocardial blood flow and can identify coronary stenosis.

Assessment of Coronary Stenosis Severity and Transmural Perfusion Gradient by Myocardial Contrast Echocardiography Comparison of Gray-Scale B-Mode With Power Doppler Imaging

BackgroundThe present study (1) compared the ability of power Doppler imaging with that of gray-scale B-mode tissue imaging to opacify the myocardium and detect coronary stenosis by myocardial contrast echocardiography and (2) compared the response of video intensity (VI) to variable pulsing intervals for each modality. Methods and ResultsFour grades of left anterior descending coronary artery (LAD) stenoses were created in 9 open-chest dogs. Stenoses reduced resting LAD flow by 25%, 50%, 75%, and 100% of baseline by flow probe. Myocardial contrast echocardiography was performed during varying ECG gated pulsing intervals (PIs) from 1:1 to 1:10. By gray-scale imaging, background-subtracted LAD bed VI was less than baseline VI at all PIs for the 100% reduced-flow state but not for any other flow state or interval. By power Doppler imaging, LAD bed VI was less than baseline VI at all intervals for 75% and 100% reduced-flow states but only 1:1 and 1:2 for 25% and 50% reduced-flow states, respectively. Correlation of VI and myocardial blood flow (determined by use of fluorescent microspheres) ratios from stenosed versus normal beds was stronger by power Doppler imaging. A transmural opacification gradient with stenosis was visualized and measured by power Doppler imaging, but it was insignificant by gray-scale imaging. The ratio of endocardial/epicardial flow determined by use of fluorescent microspheres was correlated with VI by power Doppler imaging at all PIs. ConclusionsPower Doppler imaging has advantages compared with gray-scale imaging in opacifying the myocardium and in detecting coronary stenosis and altered transmural distribution of myocardial perfusion from peak VI. Because VI differences from baseline at long PI vary for mild versus severe (75% and 100%, respectively) reduced-flow states, power Doppler imaging may provide a method to quantify coronary stenoses.

Evaluation of dynamic changes in microvascular flow during ischemia-reperfusion by myocardial contrast echocardiography

BACKGROUND Dynamic changes of myocardial blood flow have been observed after reperfusion of an occluded coronary artery. MCE performed by intracoronary contrast injection can provide an estimate of microvascular flow. We hypothesized that MCE performed using intravenous infusion of a new generation contrast agent and electrocardiogram-gated harmonic imaging would be able to assess serial changes of microvascular perfusion. OBJECTIVE To study the potential of myocardial contrast echocardiography (MCE) to assess serial changes of microvascular flow during ischemia-reperfusion. METHODS Sixteen dogs underwent 90 or 180 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Regional blood flow (RBF) was measured with fluorescent microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180 min during reperfusion. At the same time points, MCE was performed with intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Background-subtracted videointensity measured from MCE and RBF obtained from fluorescent microspheres were calculated for the risk area and for a control area, and were expressed as the ratio of the two areas. RESULTS After initial hyperemia, a progressive reduction in flow was observed during reperfusion. MCE correctly detected the time course of changes in flow during occlusion-reperfusion. Videointensity ratio significantly correlated with RBF data (r=0.79; p < 0.0001). CONCLUSIONS The progressive reduction in blood flow occurring within the postischemic microcirculation was accurately detected by MCE. This approach has potential application in the evaluation and management of postischemic reperfusion in humans.

Antioxidant Effect of a New Calcium Antagonist, Azelnidipine, in Cultured Human Arterial Endothelial Cells

Azelnidipine is a novel dihydropyridine-type calcium antagonist with long-acting anti-hypertensive action and a low reported incidence of tachycardia. We aimed to evaluate its antioxidant activity in cultured human arterial endothelial cells under oxidative stress. Endothelial cells were exposed to 1 mM H2O2 and treated with 100 μM α-tocopherol, 1 nM, 10 nM or 100 nM azelnidipine, 100 nM nifedipine or 100 nM amlodipine. After 3 h, the cell number and level of lipid peroxidation were evaluated by measuring the total protein and 8-iso-PGF2α concentrations, respectively. The total protein concentration was similar with each treatment. Inhibition of 8-iso-PGF2α was greatest with 10 nM azelnidipine (compared with the other drugs); the difference between 10 nM and 100 nM azelnidipine was not significant. We conclude that azelnidipine has a potent antioxidative effect that could be of significant clinical benefit when combined with its long-lasting anti-hypertensive action and low incidence of tachycardia.

Quantitative Assessment of Myocardial Perfusion During Graded Coronary Artery Stenoses by Intravenous Myocardial Contrast Echocardiography

OBJECTIVES The purpose of this study was to examine whether coronary stenoses of variable severity could be quantitatively assessed by analysis of myocardial perfusion as determined by intravenous (IV) myocardial contrast echocardiography. BACKGROUND Recently, new contrast agents and imaging technology have been developed that may enable improved assessment of myocardial perfusion by IV contrast injection. METHODS Variable obstruction of the left anterior descending (LAD) coronary artery in dogs was produced by a screw occluder. Coronary artery flow was measured with a transit time flowmeter during baseline, pharmacological vasodilation, a non-flow-limiting stenosis at rest in conjunction with vasodilation, a flow-limiting stenosis, and total occlusion. Myocardial contrast echocardiography was performed after IV injection of the contrast agent NC 100100. Time-intensity curves were obtained off-line for the LAD risk area and the adjacent left circumflex (LCx) territory, and peak background-subtracted video intensity was determined. Fluorescent microspheres were injected at each intervention for determination of regional myocardial blood flow. RESULTS During non-flow-limiting stenosis, flow limiting stenosis and total occlusion, LAD/LCx ratios of peak myocardial videointensity and blood flow decreased proportionately. Both LAD/LCx ratios of video intensity and blood flow identified the non-flow-limiting and the flow-limiting stenoses as well as total occlusion of the LAD artery. A significant correlation between LAD/LCx video intensity and blood flow ratios was observed (r = 0.83, p < 0.0001). CONCLUSIONS The degree of blood flow mismatch between ischemic and normal myocardial regions during graded coronary stenoses can be estimated in the dog by quantitative assessment of myocardial perfusion produced by IV myocardial contrast echocardiography.

Assessment of Myocardial Postreperfusion Viability by Intravenous Myocardial Contrast Echocardiography: Analysis of the Intensity and Texture of Opacification

BackgroundAlthough defects on intracoronary myocardial contrast echocardiography (MCE) indicate loss of viability after reperfusion, opacified segments may also exhibit persistent dyssynergy. Therefore, we related the intensity and texture of opacification produced by an intravenous contrast agent to histological findings to determine the characteristics of necrotic tissue by postreperfusion MCE. Methods and ResultsMCE was performed by intravenous injection of 0.15 mL/kg QW7437 in 14 dogs who underwent 3-hour coronary occlusion followed by 3-hour reperfusion. At baseline and 3 hours after reperfusion, midventricular short-axis images were digitized and segmented. Infarction fraction (IF) for each segment was determined by triphenyltetrazolium chloride stain. Of 224 segments, 140 showed no or small infarction and served as a control group. Of 84 segments with significant infarction (IF>30%), 52 exhibited a defect on MCE, and 32 exhibited no defect. Echo texture was quantified by computing entropy based on the co-occurrence matrix analysis of gray-level pairs within each segment. Three hours after reperfusion, average and maximal entropies in the infarct segments without opacification defects were significantly higher than control levels. Histologically, the degree of intracapillary erythrocyte stasis was less in this group than in the infarcted segments with MCE defects with similar magnitude of tissue injuries. ConclusionsOpacification defects by MCE may be present or absent in myocardium with histologically confirmed infarction. The texture of MCE from opacified but infarcted myocardium differed significantly from control segments and may assist in determination of segmental viability after reperfusion.

Influence of the angiotensin II receptor antagonist losartan on diuretic-induced metabolic effects in elderly hypertensive patients: comparison with a calcium channel blocker.

OBJECTIVE Diuretic therapy frequently induces undesirable biochemical changes and side effects. We compared metabolic effects of a low-dose diuretic (D) given in combination with an angiotensin II receptor antagonist, losartan (L), with those resulting from a diuretic given in combination with a calcium channel blocker, slow-release nifedipine (N). MATERIAL AND METHODS Thirty-seven elderly patients with mild to moderate hypertension (mean age: 71 +/- 3 years) were treated with either L+D (n = 18) or N+D (n = 19) for 1 year. Diuretic therapy included low-dose trichlormethiazide or low-dose furosemide in numbers of patients that were similar between L+D and N+D groups. Blood pressure, serum electrolytes, uric acid, blood glucose, renal function and lipid parameters were measured at baseline, 6 months and 1 year. RESULTS Effective blood pressure control was observed in both groups at 6 months, and with further improvement at 1 year. Serum potassium was significantly decreased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but not in the L+D group. Serum uric acid was significantly increased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but had minimally decreased at 1 year in the L+D group (p < 0.1). Blood glucose, renal function and lipid parameters did not change in either group. CONCLUSION The combination of losartan and low-dose diuretics effectively treated hypertension in elderly patients while minimizing the metabolic consequences of diuretic therapy. Larger trials will be necessary to confirm this finding.

Visualization of intramyocardial vasculature by contrast echocardiography

Contrast echocardiography has been applied since 1968, when the injection of agitated saline was observed to produce dense ultrasonic reflectances within cavities of the heart and great vessels [1, 2]. However, although intravenous contrast injections opacified the right-sided chambers, left-sided cardiac chambers were not affected due to filtering of the contrast by the lungs. The recognition that the disappearance of the contrast in the lungs was related to the propensity of very small microbubbles to dissolve in blood has led to the development of superior ultrasonic contrast agents with prolonged persistence times. These agents have proven capable of transiting the microcirculation of lungs and myocardium. In addition, instrumentation advances such as harmonic imaging have resulted in amplified signals from contrast compared with those from tissue [4, 5]. These advances have enabled myocardial opacification and vascular structure visualization.