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The significance of microvessels within atherosclerotic plaques is not yet fully clarified. Associated with plaque vulnerability. The aim of this study is to examine tissue characteristics of plaque with microvessels detected by optical coherence tomography (OCT) by use of a commercially available color-coded intravascular ultrasound (IVUS) and coronary angioscopy (CAS). The subjects examined comprised of 44 patients with stable angina pectoris who underwent percutaneous coronary intervention. Microvessels were defined as a tiny tubule with a diameter of 50-300 µm detected over three or more frames in OCT. We compared the total volume of microvessels with tissue component such as fibrotic, lipidic, necrotic, and calcified volume and the number of yellow plaque. In IVUS analysis, % necrotic volume and % lipidic volume were significantly correlated and % fibrotic volume was inversely significantly correlated with the total volume of microvessel (r = 0.485, p = 0.0009; r = 0.401, p = 0.007; r = - 0.432, p = 0.003, respectively). The number of plaque with an angioscopic yellow grade of two or more was significantly correlated with the total volume of microvessel (r = 0.461, p = 0.002). The greater the luminal volume of microvessels, the more the percent content of necrotic/lipidic tissue volume within plaque and the more the number of yellow plaques. These data suggested that microvessels within coronary plaque might be related to plaque vulnerability.

Background and Aims: Macrophage accumulation in arteriosclerotic plaque of coronary arteries is involved in plaque destabilization. Atherosclerosis has been known to be progressive in patients with type 2 diabetes mellitus (DM). This study compared the features of 3-dimensional (3D) spatial distribution of macrophage accumulation within coronary artery wall between acute coronary syndrome (ACS) patients with DM (n = 20) and those without (non-DM, n = 20) by using intravascular ultrasound (IVUS) and optical coherence tomography (OCT)., Methods: The OCT-derived macrophage accumulation was measured within the proximal left anterior-descending artery. This measurement was performed for the whole vessel segment of interest, higher shear stress region (flow divider side) and lower shear stress region (the opposite side)., Results: Normalized macrophage accumulation per unit length of the whole segment of interest was significantly larger in ACS patients with DM than without. In non-DM patients, macrophage density per IVUS-derived plaque volume was significantly higher in high shear stress region compared to low shear stress region, however, there was no significant difference between the two regions in DM patients. The macrophage density in the low shear stress region was significantly higher in the DM group than in the non-DM group. A multivariate analysis showed that the presence of DM was a major determinant for macrophage distribution., Conclusions: Macrophage accumulation was more abundant and homogeneous within coronary arterial wall in DM patients with ACS compared to non-DM patients, suggesting that plaque destabilization may occur more widely throughout coronary wall in DM patients.

Drug-coated balloon angioplasty (DCBA) has been recognized for its utility in preventing in-stent re-restenosis (ISR); however, imaging of the neointima immediately after treatment and during follow-up has only been described in a few case reports. This study aimed to determine the efficacy and mechanism of the DCBA using imaging studies both immediately after the DCBA and during the follow-up period. We enrolled 15 consecutive patients who underwent DCBA for in-stent restenosis (ISR). The in-stent neointimal volume was evaluated using optical coherence tomography (OCT), and the in-stent yellow grade was assessed using coronary angioscopy (CAS) immediately after DCBA and during the median follow-up period of 9 (8-15) months. The neointimal volume was significantly reduced from 77.1 ± 36.2 mm 3 at baseline to 60.2 ± 23.9 mm 3 immediately after DCBA (p = 0.0012 vs. baseline) and to 46.7 ± 21.9 mm 3 during the follow-up (p = 0.0002 vs. post DCBA). The yellow grade of the residual plaques at the ISR lesion, which indicated plaque vulnerability, was significantly decreased in the follow-up CAG (from baseline: 1.79 ± 1.03, during the follow-up: 0.76 ± 0.82; p < 0.0001). These data suggest that DCBA may inhibit neointimal formation and provide angioscopic intimal stabilization for ISR lesions.

Low wall shear stress (WSS) is associated with plaque formation. However, the relationship between WSS and coronary plaque vulnerability remains unclear. Therefore, this study aimed to clarify the in vivo relationship between luminal WSS derived from three-dimensional (3D) computed tomography (CT) and plaque vulnerability within the coronary artery. Forty-three consecutive patients with ischemic heart disease and coronary stenotic lesions were enrolled and underwent coronary angiography and color-coded intravascular ultrasonography (iMap™) followed by multi-slice coronary CT angiography. CT-derived high-risk plaque was defined by specific CT characteristics, including low CT intensity (< 30 HU) and positive remodeling. The Student's t test, Mann-Whitney U test, χ 2 test, repeated measures analysis of variance, and logistic and multiple regression were used for statistical analyses. CT-derived high-risk plaque (n = 15) had higher values of maximum and average shear stress than CT-derived stable plaque (474 ± 453 vs. 158 ± 138 Pa, p = 0.018; 4.2 ± 3.1 vs. 1.6 ± 1.2 Pa, p = 0.007, respectively). Compared with patients with CT-derived stable plaque, those with CT-derived high-risk plaque had a higher prevalence of necrotic and lipidic characteristics (44 ± 13 vs. 31 ± 11%, p = 0.001) based on iMap™. Multivariate logistic regression analysis showed that the average WSS and necrotic plus lipidic content were independent determinants of CT-derived high-risk plaque (average WSS: odds ratio 2.996, p = 0.014; necrotic plus lipidic content: odds ratio 1.306, p = 0.036). Our findings suggested that CT-derived high-risk plaque may coexist with high shear stress on the plaque surface.

Diminishing yellow color, evaluated by coronary angioscopy, is associated with plaque stabilization and regression. Our aim was to assess the effect of aggressive lipid-lowering therapy with rosuvastatin on plaque regression and instability. Thirty-seven patients with stable angina or silent myocardial ischemia who planned to undergo elective percutaneous coronary intervention and had angioscopic yellow plaques of grade 2 or more were randomized to high-dose (group H, 20 mg/day, n = 18) or low-dose (group L, 2.5 mg/day, n = 19) rosuvastatin therapy for 48 weeks. Yellow plaque was graded on a 4-point scale of 0 (white) to 3 (bright yellow) by angioscopy, and plaque volume was determined by intravascular ultrasound for plaques with a length of 5 to 15 mm. Color and volume were assessed at baseline and after 48 weeks by the investigators blinded to the rosuvastatin dosage, and were compared between the 2 dosing groups. The level of low-density lipoprotein-cholesterol decreased from 130.3 ± 25.5 mg/dl to 61.7 ± 16.5 mg/dl (-50 ± 19%: high intensity) in group H (p <0.001) and from 130.9 ± 28.5 mg/dl to 89.7 ± 29.0 mg/dl (-30 ± 22%: moderate intensity) in group L (mean ± SD, p <0.001). The average color grade of yellow plaques decreased from 2.0 to 1.5 in group H (p <0.001) and from 2.0 to 1.6 in group L (p <0.001) after 48 weeks. Plaque volume decreased significantly in group H but not in group L. The percent change in plaque volume was significantly larger in group H than in group L (p = 0.005). In conclusion, both high-dose and low-dose rosuvastatin increased plaque stability. However, high-dose rosuvastatin was more effective than low-dose rosuvastatin in inducing plaque volume regression. Clinical Trial Registration No: UMIN-CTR, UMIN000003276., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Although the plaque characteristics have been recognized in patients with acute myocardial infarction (AMI), the plaque spatial distribution is not well clarified. Using color-mapping intravascular ultrasound (iMAP-IVUS), we examined culprit lesions to clarify plaque morphology, composition and spatial distribution of the sites of potential vulnerability., Methods: Sixty-eight culprit lesions in 64 consecutive AMI patients who underwent angiography and IVUS examinations before intervention were analyzed. Plaque morphology and composition were quantified with iMAP-IVUS. The spatial distribution of the sites of potential vulnerability was assessed with longitudinal reconstruction of the consecutive IVUS images. The plaque characteristics were also compared between ruptured and non-ruptured lesions, and between totally occlusive (TO) and non-TO lesions., Results: The sites with maximum necrotic area (maxNA), maximum plaque burden (maxPB) and most severely narrowed (minimal luminal area, MLA) were recognized vulnerability. In the majority of cases, maxNA sites were proximal to the maxPB sites, and MLA sites were distal to the maxNA and maxPB sites. Ruptures usually occurred close to maxNA sites and proximal to maxPB and MLA sites. The average distance from the site of rupture to the maxNA site was 0.33 ± 4.04 mm. Ruptured lesions showed significant vessel remodeling, greater plaque volume, and greater lipidic volume compared to those of non-ruptured lesions. Both the length and plaque burden (PB) of TO lesions were greater than those of non-TO lesions., Conclusions: Instead of overlapping on maxPB sites, most maxNA sites are proximal to the maxPB sites and are the sites most likely to rupture. Plaque morphology and composition play critical roles in plaque rupture and coronary occlusion.

This study aimed to clarify the relationships between arterial remodeling patterns and plaque volume regression or stabilization. The TOGETHAR trial is a prospective open-label trial designed to assess coronary plaque regression and stabilization with multiple plaque imaging modalities following 52 weeks of pitavastatin treatment (2 mg/day). Coronary plaques were observed in 46 patients with both angioscopy and intravascular ultrasound at baseline and after 52 weeks of drug treatment. We divided these patients into three groups according to their remodeling indices (RI). Group P consisted of patients with a baseline RI >1.05, Group M of patients with a baseline RI of 0.95-1.05, and Group N of patients with a baseline RI <0.95 and then evaluated differences in coronary plaque volume changes and yellow grade among the three groups. In the positive remodeling group, whose remodeling index (RI) exceeded 1.05 at baseline, RI and percent atheroma volume (PAV) were significantly reduced (RI 1.14 ± 0.07 to 1.05 ± 0.10, p = 0.010, PAV 47.3 ± 8.3 to 45.3 ± 7.3 mm(3), p = 0.048). There was no relationship between baseline RI and the change in yellow grade of plaque. RI increased without significant change of PAV or a decrease in lumen volume in group N, with RI below 0.95 at baseline. Plaques with positive remodeling were more likely to have plaque volume regression by pitavastatin than those without in patients with coronary artery disease. Moreover, plaques with positive and negative remodeling were changed into those with intermediate remodeling by pitavastatin. Pitavastatin might induce not only plaque regression or stabilization, but also conformational normalization of vessel structure.

Objectives: To examine serial change in the residual plaque behind the sirolimus-eluting stent (SES) using coronary angioscopy in patients with SES implantation and to identify its baseline determinants., Background: Previous coronary angioscopic studies have demonstrated that SES enhances the yellow grade of residual plaque during follow-up period., Methods: A total of 42 patients with stable angina pectoris or silent ischemic heart disease, who had a successful SES implantation were examined by coronary angioscopy both at the baseline (SES implantation) and the follow-up period (9-14 month follow-up). The patients were divided into three groups as: worsened group (WS: yellow color grade of coronary plaque at the follow-up period was worsened compared to the baseline period, n=15), no change group (NP: no change compared to the baseline, n=16), and improved group (IP: improved compared to the baseline, n=11). Then, the determinants of the nominal change of yellow color grade were examined by multiple regression analysis., Results: The low-density lipoprotein cholesterol (LDL-C) level in IP group at the follow-up was significantly decreased compared to baseline (from 120.0±29.8mg/dl to 74.3±16.7mg/dl, p=0.0005), and was the lowest among three groups (WS: 103.5±16.4mg/dl, NC: 105.7±18.7mg/dl, and IP: 74.3±16.7mg/dl). Multiple regression analysis revealed that family history, statin administration, baseline serum creatinine, baseline 'in-stent' thrombus, and follow-up LDL-C were significant determinants to the nominal change of yellow color grade after the SES implantation (p<0.0001)., Conclusions: Serial change in tissue characteristics within residual plaque under SES is determined by several factors, especially LDL-C level as well as statin administration. Adequate management of LDL-C by statins might be crucial for stabilizing residual plaque after SES implantation., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Background: The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl)., Methods: In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group)., Results: In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm(3)) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm(3)). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c., Conclusions: Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease., Trial Registration: ClinicalTrials.gov, Identifier NCT00329160.

Background: The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) trial showed that intensive statin therapy could induce significant coronary plaque regression in acute coronary syndrome (ACS). We evaluated the impact of metabolic syndrome (MetS) and its components on coronary plaque regression in the JAPAN-ACS patients., Methods and Results: Serial intravascular ultrasound measurements over 8-12 months were performed in 242 ACS patients receiving pitavastatin or atorvastatin. Patients were divided into groups according to the presence of MetS or the number of MetS components. Although the percent change in plaque volume (%PV) was not significantly different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was significantly associated with an increasing number of MetS components (component 0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69; components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The percent change in body mass index (%BMI) significantly correlated with %PV (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017). In addition, %BMI was an independent predictor of plaque regression after adjustment for the changes of low- and high-density lipoprotein cholesterol, triglycerides and HbA(1c)., Conclusions: The clustering of MetS components, but not the presence of MetS itself, could attenuate coronary plaque regression during intensive statin therapy in ACS patients. Therefore, to achieve a greater degree of plaque regression, it is necessary to treat to each MetS component and use lifestyle modification.

Objective: The Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering therapy with a statin resulted in a significant regression of coronary atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived protein with anti-atherogenic properties. Here, we investigated the association between adiponectin levels and the change in the plaque volume in ACS patients., Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and 12 months after the PCI. The percent change in the plaque volume (%PV) in a non-culprit coronary artery segment was evaluated. The serum adiponectin and lipid parameters were measured both at baseline and at the follow-up., Results: At baseline, adiponectin was correlated positively with HDL-cholesterol and negatively correlated with triglyceride, but no correlation was observed with the PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in adiponectin was also associated with an increase of HDL-cholesterol and decrease of triglyceride, however, no significant correlation was observed with the %PV. A significantly higher incidence of major adverse cardiac events (MACE) was observed in patients with hypo-adiponectinemia at baseline. A multiple logistic regression analysis identified adiponectin as a significant independent predictor of MACE., Conclusion: Adiponectin levels measured after PCI could serve as a marker of MACE in patients with ACS., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of the present study was to assess the relationship between shear stress distribution and coronary plaque rupture by means of a new color-mapping program of shear stress with 3-dimensional intravascular ultrasound (IVUS)., Background: Various in-vitro studies have demonstrated that shear stress of the vascular lumen is one of the important determinants of coronary plaque vulnerability. However, the in-vivo relationship between shear stress and plaque rupture is still unclear., Methods: In the present study, 3-dimensional IVUS was used to obtain spatial information on luminal geometry from 20 patients with acute coronary syndrome having a distinct ulcerative lesion. These 3-dimensional contours for each lumen were first reconstructed into mesh polygons, and then analyzed by means of a program for calculating the fluid dynamics. The flow was considered to be a constant laminar one. Then, colorized mappings of the distribution of the streamline, blood pressure, and shear stress were performed. The original luminal contour for each ruptured lesion was obtained by smoothing and extrapolation., Results: All patients had a coronary plaque rupture in the proximal or top portion of the plaque hill. In the color mapping, localized elevation of blood pressure and shear stress could be observed on each plaque surface. The shear stress concentration was frequently correlated with the plaque rupture site (kappa = 0.79)., Conclusions: Although the absolute value of shear stress is not sufficient to directly provoke mechanical destruction of the fibrous cap, localized high shear stress might be a trigger of fibrous cap rupture.

To establish the relationship between the cross-sectional geometry of the post-deployment stent and the degree of in-stent neointimal hyperplasia (INH), intravascular ultrasound (IVUS) was used to examine cross-sections of the coronary arteries from 23 patients with coronary stents 6 months after implantation. Stent cross-sectional area (Sa) and stent perimeter (Sp) from 200 stent cross-sections, and the stent radius (Sr) and thickness of INH (Id) of 2,880 radial axes, were measured, and the mean degree of roundness (Rd) of stent cross-section was calculated for each stent as Rd=4piSa/Sp2. The degree of deformity (Df) of the stent cross-section was also calculated by comparing it with a hypothetical circle (the area of this hypothetical circle was equal to the Sa): Df=Sr/R, where R is the radius of the hypothetical circle. The area of INH was significantly larger in the Rd<0.87 group (n=84) than in the Rd> or =0.87 group (n=116) (3.83+/-1.26 vs 3.16+/-1.32 mm2, p<0.0005). There were significant differences in the thickness of INH among the 3 groups classified by the value of Df (Df<0.95: n=425, 0.21+/-0.12mm; 0.95< or =Df<1.05: n=2008, 0.29+/-0.15mm; Df> or =1.05: n=447, 0.34+/-0.15mm, overall p<0.0001). These data suggest that in-stent neointimal proliferation is more likely to occur in stented coronary arteries with a more oval than rounded cross-section, and particularly within the more pronounced and curved portion of the oval.

To examine the responses of coronary conduit and resistance arteries to the continuous i.v. administration of nitroglycerin in 15 patients with atypical chest pain, we measured coronary blood flow velocity in the left anterior descending coronary artery using a Doppler guide wire and the lumen diameter and cross-sectional area by quantitative coronary angiography. Systolic flow, diastolic flow, total coronary flow, and coronary vascular resistance were calculated. Stepwise increases in dose of nitroglycerin resulted in significant dose-dependent decrease in mean aortic pressure (p < 0.01) and increase in lumen diameter (p < 0.05). After nitroglycerin administration of 0.5 microg/kg/min, systolic flow decreased significantly by 89.9+/-15.7% (p < 0.01), and diastolic flow increased significantly by 74.2+/-37.1% (p < 0.05). Total coronary flow did not change significantly with the various doses of nitroglycerin. However, coronary vascular resistance decreased significantly at concentrations greater than 0.5 microg/kg/min nitroglycerin. Continuous nitroglycerin infusion did not reduce either diastolic or total coronary blood flow despite a significant reduction in coronary perfusion pressure. These results indicate that subendocardial blood flow might be maintained during continuous i.v. infusion of nitroglycerin within the clinical dose range.

The purpose of the study was to compare four intravascular ultrasound (IVUS) machines in vitro for their image representation of coronary arterial walls. There has been considerable variability among reported studies on the accuracy of morphometric measurements of coronary arteries by IVUS. This variability may be caused in part by the difference in the IVUS system used. A total of 24 formalin-fixed coronary arteries were imaged in saline at 37 degrees with four different IVUS systems. The images were interpreted independently and compared with histology. Each system had benefits and limitations: System 1 overestimated the lumen area and had difficulty in identifying the media; System 2 underestimated the media area, but had a lower positive bias for lumen area; System 3 overestimated the lumen area but more clearly identified tissue characteristics such as internal elastic membrane and the echolucent media zone which improved the likelihood of observing a three-layer appearance; and System 4 showed less distinct separation of the arterial components and had poor correlations with histology for media measurements. The ability to make accurate morphometric measurements from IVUS images depends on the clarity of the separation of plaque and media. Among the four systems studied, there is significant variability in the appearance of the ultrasound images and the accuracy of morphometric measurements. These system differences should be considered when comparing IVUS studies performed by different groups.

We assessed the effect of dobutamine on left ventricoarterial coupling during acute regional ischemia. Using a conductance catheter, we analyzed the end-systolic pressure-volume relation (ESPVR) in anesthetized dogs. We calculated the slope of ESPVR (Ees), the slope of the end-systolic pressure-stroke volume relation (Ea), (Ea/Ees) and the ratio (work efficiency) of external work to pressure-volume area at base-line during ischemia induced by occlusion of the left anterior descending coronary artery and during low-dose (1-3 micrograms.min-1.kg-1) and high-dose (4-10 micrograms.min-1.kg-1)dobutamine infusions with ischemia. ESPVR shifted to the right without a change in Ees during ischemia. Dobutamine caused dose-dependent increases in Ees but did not affect the intercept of ESPVR. During ischemia, Ea/Ees increased and work efficiency decreased. Low-dose dobutamine was associated with a return in control for Ea/Ees and work efficiency. High-dose dobutamine increased Ees and Ea but produced no further increase in Ea/Ees or work efficiency. Low-dose dobutamine would appear to be the preferable regimen to achieve the optimal ventriculoarterial coupling in acute regional ischemia associated with mismatched ventriculoarterial coupling and depressed left ventricular work efficiency.

Intravascular ultrasound imaging was performed in vitro on six histologically normal and 104 minimally diseased arteries in patients aged 13 to 83 years. This study tested the hypothesis that normal coronary arteries produce a three-layer image that corresponds to the histologic layers of intima, media, and adventitia. The results showed a very good correlation between area of the echolucent ultrasound layer with the media and the inner echogenic layer with intimal area. In addition, a three-layer appearance was consistently seen when the internal elastic membrane was present with or without intimal hyperplasia. If the internal elastic membrane was absent, a three-layer appearance was still seen if the collagen content of the media was low. However, a two-layer appearance was observed when there was absence of the internal elastic membrane as well as a high collagen content of the media.

The response of the coronary artery to a small dose (0.01 mg) of ergonovine was observed in nine patients without variant angina and in 10 patients with variant angina. Coronary angiograms were obtained before and after small and larger (routinely used) doses of ergonovine. With the larger dose, all 10 patients with variant angina had total or subtotal spastic occlusion accompanied by angina and ECG changes. Excluding the site of spastic occlusion produced by the larger dose of ergonovine, diameters of proximal, middle, and distal segments in each major coronary artery were measured before and after a small dose of ergonovine. The mean percentage of change in diameter (diameter before - diameter after a small dose of ergonovine)/diameter before a small dose of ergonovine X 100% in patients without variant angina was not significantly different from that in patients with variant angina (5.2 +/- 9.5% vs 7.0 +/- 11.9%, respectively). However, in patients with variant angina, a small dose of ergonovine produced a percentage of change in diameter of 39.8 +/- 15.3% at the site of spastic occlusion included by a larger dose of ergonovine, compared with that of 7.0 +/- 11.9% in the remaining non-spastic coronary arteries (p less than 0.05). These results indicate that patients with variant angina have local segments which respond differently to ergonovine from the remaining segments of coronary arteries. Clinically, this observation might be helpful in determining the angiographic positivity to ergonovine.

In dogs anesthetized with pentobarbital, the anterior descending coronary artery (LAD) was partially occluded to reduce LAD flow to about half of the original flow (partial occlusion). Myocardial pH (MpH) was measured by the use of a micro glass pH electrode. MpH decreased from 7.5-7.63 to 6.82-6.86 30 min after partial occlusion of the LAD. Nipradilol (0.3 mg/kg) was injected intravenously 30 min after partial occlusion, which continued for a further 60 min after nipradilol injection. Nipradilol decreased blood pressure and heart rate, and significantly increased myocardial pH which had been decreased by partial occlusion, within 60 min after injection. Nipradilol-induced restoration of the myocardial [H+] (calculated from the pH data), that had been increased by partial occlusion, was 48.5%. Bradycardia induced by nipradilol was not a determinant factor in the pH effect of nipradilol, because even in the paced heart, nipradilol restored the myocardial [H+] that had been increased by partial occlusion. These results indicate that nipradilol attenuates ischemia-induced myocardial acidosis, suggesting the favorable effect of nipradilol on ischemic myocardium. The favorable effect of nipradilol may be due to the beta-adrenoceptor antagonistic effect rather than the vasodilating effect.