Eiji Toyota

Assessment of Coronary Arterial Thrombus by Optical Coherence Tomography

We analyzed optical coherence tomographic (OCT) characteristics of different types of coronary thrombi that had been confirmed at postmortem histologic examination. We examined 108 coronary arterial segments of 40 consecutive human cadavers. OCT images of red and white thrombi were obtained and the intensity property of these thrombi was analyzed. Red and white thrombi were found in 16 (17%) and 19 (18%) of the 108 arterial segments, respectively. Red thrombi were identified as high-backscattering protrusions inside the lumen of the artery, with signal-free shadowing in the OCT image. White thrombi were identified as low-backscattering projections in the OCT image. There were no significant differences in peak intensity of OCT signal between red and white thrombi (130+/-18 vs 145+/-34, p=0.12). However, the 1/2 attenuation width of the signal intensity curve, which was defined as the distance from peak intensity to its 1/2 intensity, was significantly different between red and white thrombi (324+/-50 vs 183+/- 42 microm, p<0.0001). A cut-off value of 250 microm in the 1/2 width of signal intensity attenuation can differentiate white from red thrombi with a sensitivity of 90% and specificity of 88%. We present the first detailed description of the characteristics of different types of coronary thrombi in OCT images. Optical coherence tomography may allow us not only to estimate plaque morphology but also to distinguish red from white thrombi.

Mitral annulus flattens in ischemic mitral regurgitation: geometric differences between inferior and anterior myocardial infarction: a real-time 3-dimensional echocardiographic study.

Background—New surgical strategies to restore the saddle shape of the mitral annulus are expected to increase annuloplasty effectiveness. Preoperative and postoperative configuration of the curved annulus, however, is difficult to quantify with 2-dimensional echocardiography. We sought to investigate the geometric deformity in the mitral annulus in ischemic mitral regurgitation (MR), comparing inferior and anterior myocardial infarction (MI) with the use of a custom quantitation software system with transthoracic 3-dimensional echocardiography. Methods and Results—We performed real-time 3-dimensional echocardiography in 23 patients with ischemic MR attributable to inferior MI or anterior MI and in 10 controls. Three-dimensional data were cropped into 18 radial planes, and we manually marked the annulus in mid systole. Three-dimensional annular images were reconstructed, and annular circumferences, areas, and heights were quantified. Annulus was significantly more dilated and flattened in ischemic MR than in controls and was further deformed in anterior MI as compared with inferior MI (control: circumference 9.9±0.7 cm, area 9.6±0.5 cm2, height 5.0±0.7 mm; inferior MI: circumference 11.5±1.2 cm [P<0.01 compared with control], area 11.4±2.0 cm2 [P<0.05 compared with control], height 3.5±1.6 mm [P<0.05 compared with control]; anterior MI: circumference 14.2±2.4 cm [P<0.0001 compared with control, P<0.05 compared with inferior MI], area 13.7±2.8 cm2 ]P<0.01 compared with control, P<0.05 compared with inferior MI], height 1.7±1.5 mm [P<0.0001 compared with control, P<0.05 compared with inferior MI]). Conclusions—Mitral annulus flattens in ischemic MR. Deformity of the mitral annulus was greater in anterior MI group than in the inferior MI group.

Effects of intraaortic balloon pumping on septal arterial blood flow velocity waveform during severe left main coronary artery stenosis

OBJECTIVES We sought to evaluate the effect of intraaortic balloon pumping on the phasic blood velocity waveform into myocardium with severe coronary artery stenosis. BACKGROUND In the presence of severe coronary artery stenosis, it is not clear whether intraaortic balloon pumping augments intramyocardial inflow during diastole or changes systolic retrograde blood flow from the myocardium to the extramural coronary arteries. METHODS Using anesthetized open chest dogs (n=7), we introduced severe stenosis in the left main coronary artery to reduce the poststenotic pressure to approximately 60 mm Hg (>90% diameter stenosis). Septal arterial blood flow velocities were measured with a 20-MHz, 80-channel ultrasound pulsed Doppler velocimeter. Left anterior descending arterial flow, aortic pressure and poststenotic distal coronary pressure were measured simultaneously. The diastolic anterograde flow integral and systolic retrograde flow integral were compared in the presence and absence of intraaortic balloon pumping. RESULTS Although intraaortic balloon pumping augmented diastolic aortic pressure, this pressure increase was not effectively transmitted through stenosis. Septal arterial diastolic flow velocity was not augmented, and left anterior descending arterial flow was unchanged during intraaortic balloon pumping. CONCLUSIONS In the presence of severe coronary artery stenosis, intraaortic balloon pumping failed to increase diastolic inflow in the myocardium and did not enhance systolic retrograde flow from the myocardium to the extramural coronary artery. Thus, the major effect of intraaortic balloon pumping on the ischemic heart with severe coronary artery stenosis may be achieved by reducing oxygen demand by systolic unloading.

Activator of G Protein Signaling 8 (AGS8) Is Required for Hypoxia-induced Apoptosis of Cardiomyocytes ROLE OF Gβγ AND CONNEXIN 43 (CX43)

Ischemic injury of the heart is associated with activation of multiple signal transduction systems including the heterotrimeric G-protein system. Here, we report a role of the ischemia-inducible regulator of Gβγ subunit, AGS8, in survival of cardiomyocytes under hypoxia. Cultured rat neonatal cardiomyocytes (NCM) were exposed to hypoxia or hypoxia/reoxygenation following transfection of AGS8siRNA or pcDNA::AGS8. Hypoxia-induced apoptosis of NCM was completely blocked by AGS8siRNA, whereas overexpression of AGS8 increased apoptosis. AGS8 formed complexes with G-proteins and channel protein connexin 43 (CX43), which regulates the permeability of small molecules under hypoxic stress. AGS8 initiated CX43 phosphorylation in a Gβγ-dependent manner by providing a scaffold composed of Gβγ and CX43. AGS8siRNA blocked internalization of CX43 following exposure of NCM to repetitive hypoxia; however it did not influence epidermal growth factor-mediated internalization of CX43. The decreased dye flux through CX43 that occurred with hypoxic stress was also prevented by AGS8siRNA. Interestingly, the Gβγ inhibitor Gallein mimicked the effect of AGS8 knockdown on both the CX43 internalization and the changes in cell permeability elicited by hypoxic stress. These data indicate that AGS8 is required for hypoxia-induced apoptosis of NCM, and that AGS8-Gβγ signal input increased the sensitivity of cells to hypoxic stress by influencing CX43 regulation and associated cell permeability. Under hypoxic stress, this unrecognized response program plays a critical role in the fate of NCM.

C-Reactive protein predicts severity, progression, and prognosis of asymptomatic aortic valve stenosis

BACKGROUND C-Reactive protein (CRP) has been shown to play a pivotal role in the pathogenesis of atherosclerosis progression. The aim of this study was to assess whether CRP predicts severity, progression, and prognosis of aortic valve stenosis (AS). METHODS One hundred and thirty-five patients with asymptomatic AS were studied. Patients were diagnosed as mild (n = 18, aortic valve area [AVA] > or =1.5 cm(2)), moderate (n = 57, AVA 1.0-1.49 cm(2)), or severe AS (n = 60, AVA <1.0 cm(2)) by Doppler echocardiography. Patients with serial (baseline and at 1 year) echocardiographic examination (n = 47) were grouped as either slow (n = 22, DeltaAVA <-0.15 cm(2)/y) or rapid progression group (n = 25, DeltaAVA > or =-0.15 cm(2)/y). In addition, long-term prognosis was compared between patients with low CRP (n = 68, CRP <0.15 mg/dL) and those with high CRP (n = 67, CRP > or =0.15 mg/dL). RESULTS Baseline CRP was significantly higher in patients with severe AS than in those with mild or moderate AS (mild AS 0.17 +/- 0.43, moderate AS 0.22 +/- 0.28, severe AS 0.53 +/- 0.66 mg/dL, P = .001). By multivariate logistic regression analysis, CRP was an independent predictor of severe AS (odds ratio 3.51, P = .015). Similarly, CRP was significantly higher in the rapid progression group than in the slow progression group (0.56 +/- 0.76 vs 0.19 +/- 0.25 mg/dL, P = .004). Furthermore, long-term survival was significantly lower in the high CRP group than in the low CRP group (log rank: P < .001). CONCLUSION C-Reactive protein predicts severity, progression, and prognosis in patients with asymptomatic AS.

Fibrin Clot Visualized by Optical Coherence Tomography

Optical coherence tomography (OCT) is a recently developed optical imaging technique that provides high-resolution (≈10 to 20 μm) cross-sectional images of vessels.1 It has been reported that OCT images of white and red thrombus were characterized as backscattering protrusions in the coronary lumen.2 However, OCT characteristics of fibrin clot composed of fibrin material and few blood cells have not been described. The coronary arteries of a 75-year-old man …

Role of NO and K ATP + channels in adenosine-induced vasodilation on in vivo canine subendocardial arterioles

Adenosine (Ado) plays an important role in regulation of coronary vascular tone with nitric oxide (NO) and ATP-sensitive K+ [Formula: see text]) channels. In vitro, it was reported that subendocardial (Endo) arterioles are more sensitive to Ado than subepicardial (Epi) arterioles. The purpose of this study was to observe enhanced vasodilation of Endo arterioles directly and to evaluate possible roles of [Formula: see text] channels and NO in the different responses of Endo and Epi arterioles to Ado-induced vasodilation. We evaluated dilation of Endo and Epi arterioles (<120 μm) of beating canine hearts ( n = 19) by Ado (20 and 50 μg ⋅ kg-1 ⋅ min-1ic) before and after [Formula: see text] channel blockade (glibenclamide; 200 μg/kg ic), inhibition of NO synthase [ N G-nitro-l-arginine methyl ester (l-NAME); 30 μg ⋅ kg-1 ⋅ min-1, 20 min ic], or glibenclamide +l-NAME using a novel needle-probe CCD intravital microscope. Ado induced dose-dependent vasodilation in both Epi and Endo arterioles, but vasodilation was greater in Endo arterioles, i.e., increase at 120 s (maximum dilation) after Ado (50 μg ⋅ kg-1 ⋅ min-1) was 17% in Endo and 13% in Epi arterioles ( P < 0.01). Endo arteriole dilation was attenuated by blockade of [Formula: see text]channels from 18% (Ado) to 9% (Ado+glibenclamide) increase ( P < 0.001) and by inhibition of NO synthase from 17% (Ado) to 9% (Ado+l-NAME) ( P < 0.005). Epi arteriole vasodilation was attenuated by blockade of[Formula: see text] channels from 15 to 9% ( P < 0.005) and inhibition of NO from 16 to 10% ( P < 0.005). Suppression of vascular response was additive (Endo, 14 to -1%; Epi, 12 to 3%) with glibenclamide +l-NAME. We conclude that 1) the degree of Ado-induced vasodilation was greater in Endo than in Epi arterioles, with higher sensitivity of smaller arterioles in both layers and 2) transmural difference of arteriolar sensitivity to adenosine was abolished or reversed by[Formula: see text] channel blockade and/or by NO synthase inhibition, indicating crucial involvement of[Formula: see text] and NO in transmural sensitivity difference.

Quantitative measurement of mitral valve coaptation in functional mitral regurgitation: In vivo experimental study by real-time three-dimensional echocardiography

BACKGROUND The degree of mitral valve (MV) coaptation should be an important parameter in the assessment of functional mitral regurgitation (MR). This study aimed to quantify the degree of MV coaptation in experimental models of functional MR caused by acute left ventricular (LV) pressure overload, using real-time three-dimensional (3D) echocardiography. METHODS AND RESULTS Using canine models, LV pressure overload was induced by staged ascending aortic banding. Echocardiographic examinations were performed before and during the aortic banding. By using a novel software system for 3D quantification (REALVIEW®), the annulus and leaflet were traced manually both at the onset of MV closure and at the maximum MV closure. The coaptation index was calculated by the following formula: [(3D tenting surface area at the onset of MV closure-3D tenting surface area at the maximum MV closure)/3D tenting surface area at the onset of MV closure] x 100. MR area gradually increased with the decrease in coaptation index during progressively exacerbated aortic banding. MR area was significantly correlated with the coaptation index. A coaptation index < 12 had a high sensitivity and specificity in the presence of significant MR. CONCLUSIONS The degree of MV coaptation can be quantified using 3D echocardiography. The coaptation index should be a useful parameter in the assessment of functional MR.

Effect of dietary control on plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans

Abstract It is of great interest and value to evaluate the systemic nitric oxide (NO) production rate in humans under various conditions. However, the currently available estimation methods are troublesome and time-consuming. We thus aimed at developing a simple method to estimate the basal systemic NO production rate in humans based on a steady-state analysis, i.e., a balance between the systemic NO production rate and the total nitrate elimination rate. Plasma nitrate concentrations of young healthy volunteers (n = 7 in group 1; n = 9 in group 2) were measured for 2 days. In group 1, all subjects had the same meals for 7 days prior to the plasma nitrate measurement. In group 2, all subjects were allowed free diets. The plasma nitrate concentrations were highly influenced by dietary nitrite/nitrate intake in both groups and reached the steady-state levels after 14-h fasting. Accordingly, the basal systemic NO production rates were estimated from the plasma nitrate concentrations after 14-h fasting (group 1, 630 ± 37 nmol min−1 = 0.78 ± 0.03 μmol kg−1 h−1; group 2, 597 ± 45 nmol min−1 = 0.66 ± 0.05 μmol kg−1 h−1, P = not significant vs group 1). These estimated values were comparable to the values obtained by other methods. In conclusion, the present estimation method with 14-h fasting using a single-compartment analysis was found to be a simple approach to quantitative evaluation and intra- and interindividual comparisons of the basal systemic NO production rates in humans.

Endothelium-derived nitric oxide enhances the effect of intraaortic balloon pumping on diastolic coronary flow

BACKGROUND High shear rate with pulsation is one of the major stimuli for the release of endothelium-derived nitric oxide leading to coronary arteriolar dilation. Intraaortic balloon pumping mechanically enhances shear rate and diastolic-to-systolic flow oscillation. We aimed to evaluate whether or not coronary blood flow augmentation during intraaortic balloon pumping is mediated by coronary arteriolar dilation through endothelium-derived nitric oxide release. METHODS Using a charge-coupled device intravital videomicroscope, we observed epicardial coronary arterioles (40 to 220 microm in diameter) in anesthetized open-chest dogs (n = 10) during 2:1 mode of intraaortic balloon pumping. Endothelium-derived nitric oxide-mediated vasodilatory effects of intraaortic balloon pumping were evaluated by comparing end-diastolic arteriolar diameters between the coupled beats of on and off intraaortic balloon pumping before and after intracoronary endothelium-derived nitric oxide synthesis inhibition with Nomega-nitro-L-arginine (L-NNA, 2 micromol/min) administration. RESULTS Intraaortic balloon pumping increased coronary arteriolar diameters and coronary blood flow by 11.4%+/-1.8% (p < 0.0001) and 33.4%+/-4.1% (p < 0.001), respectively. Vasodilation was greater in small arterioles (<110 microm; 15.4%+/-2.2%) than in large arterioles (> or =110 microm; 4.2%+/-1.2%, p < 0.0001). L-NNA attenuated the intraaortic balloon pumping-induced vasodilation and augmentation of coronary blood flow to 4.6%+/-1.0% (p < 0.001) and to 20.8%+/-2.1%, (p < 0.05), respectively. Attenuation of vasodilatory effect by L-NNA was observed mainly in small arterioles (from 15.4%+/-2.2% to 5.9%+/-1.2%). CONCLUSIONS Intraaortic balloon pumping augmented coronary blood flow by dilating coronary arterioles in diastole, more significantly in small arterioles than in large arterioles. Endothelium-derived nitric oxide inhibition markedly attenuated these effects. We conclude that, in a canine model, endothelium-derived nitric oxide contributes to mechanical enhancement of the coronary blood flow with diastolic arteriolar vasodilation during intraaortic balloon pumping.