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Aim Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. Methods This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. Results Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. Conclusions This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

Aim: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. Methods: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9–12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL. Results: In DM patients, the monotherapy group (n = 13) and the DLLT group (n = 12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: −2.77 ± 3.47% vs. −0.77 ± 2.51%, P = 0.11; non-DM: −2.01 ± 3.36% vs. −0.08 ± 2.66%, P = 0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r = 0.52, P = 0.008). Conclusions: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/). Identifier: KICS (UMIN000015397).

In patients with suspected coronary artery disease (CAD), coexisting extracardiac abnormalities have a major impact on the patient management. This study aimed to evaluate the image quality of whole-body computed tomography (CT) immediately after the coronary computed tomography angiography (CTA) and investigate the incidence of extracardiac findings in patients with suspected CAD. We enrolled 450 patients undergoing whole-body CT at 100 kVp and model-based iterative reconstruction immediately after the coronary CTA (Group A) and retrospectively reviewed 144 control patients who underwent conventional contrast-enhanced CT (120 kVp) with filtered back projection (Group B). We compared the signal-to-noise ratio (SNR) of the aorta and liver and radiation dose between the two groups. Then, we evaluated the prevalence of extracardiac findings in Group A. Compared with Group B, Group A demonstrated significantly higher aorta and liver SNR and lower radiation dose. In Group A, whole-body CT revealed 229 coexisting lesions in 165 patients, including 32 and 106 cases of oncologic and vascular diseases, respectively. Additional whole-body CT after coronary CTA may provide adequate image quality. Using additional whole-body CT, 36% of patients with suspected CAD had clinically relevant coexisting findings, including malignancy.

To compare the objective and subjective image qualities between single-energy computed tomography (CT) at 70 kVp and virtual monoenergetic imaging (VMI) of dual-source dual-energy CT for CT angiography with 180 mgI/kg.Total 63 patients scanned with 180 mgI/kg were randomly divided into two groups: Group A (32 patients) underwent CT angiography at 70-kVp, and Group B (31 patients) underwent dual-energy CT. VMI sets were generated at 10-keV increments between 40 and 100 keV. We calculated aortic attenuation, contrast-to-noise-ratio (CNR), signal-to-noise-ratio, figure of merit of CNR, and effective dose for each protocol. Three radiologists scored overall image quality and various arteries' visibility using a four-point scale. Quantitative and qualitative comparisons between 70 kVp and VMI with the highest CNR were performed with the two-tailed t test or Kruskal-Wallis test.The 40-keV images offered the highest CNR among VMIs. Aortic attenuation at 70 kVp was significantly lower than that at 40 keV (p0.001). However, the signal-to-noise-ratio, CNR, and figure of merit of CNR were significantly higher at 70 kVp than those at 40-keV (p0.001, p0.05, and p0.05, respectively). The effective dose of each group was almost equal. The qualitative visibility scores for various arteries, except the ascending and upper-abdominal aorta, were also better at 70 kVp than those at 40 keV.Aortic attenuation at 70 kVp with 180 mg I/kg was lower than that of VMI at 40 keV, and the objective and subjective image qualities were higher at 70 kVp than those at 40 keV.

Background and aims Although dual low-density lipoprotein cholesterol (LDL-C)-lowering therapy (DLLT) with statin-ezetimibe combination showed clinical benefit in patients with acute coronary syndrome (ACS) confirming "the lower, the better," the underlying mechanisms of DLLT are still unknown. Methods PRECISE-IVUS trial evaluated the effects of DLLT on IVUS-derived coronary atherosclerosis and lipid profile, compared with atorvastatin monotherapy, quantifying the coronary plaque response in 100 ACS patients. We explored the potential predictors of plaque regression. Results Lower total cholesterol, LDL-C, triglyceride, remnant-like particles cholesterol, and stronger reduction of small dense LDL-C and cholesterol absorption markers were observed in patients with plaque regression compared to those with progression. Multivariate analysis revealed that achieved LDL-C was the strongest predictor for coronary plaque regression (95% CI: 0.944–1.000, p = 0.05), followed by age (95% CI: 0.994–1.096, p = 0.09). Conclusions Incremental LDL-C lowering by DLLT was associated with stronger coronary plaque regression, reconfirming that lowering LDL-C to levels below previous targets provided additional clinical benefit.

Background Although the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy. Purpose The Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD. Methods The study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70 mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis. Conclusion PRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population.

Background Acute myocardial infarction (AMI) is mainly characterized by the rupture of lipid-rich vulnerable atherosclerotic plaque. The matrix metalloproteinases (MMPs) have been shown to play a critical role in inflammatory processes underlying plaque rupture. Some reports suggested statins inhibit the increased MMP levels after AMI. However, there are a few comparison studies between the different dosages of the same statin and circulating levels of MMPs. Purpose This study will preliminarily investigate the potential effects of appropriate or low dose of rosuvastatin on circulating MMPs levels in AMI patients. Moreover, we will also obtain plasma from patients while undergoing diagnostic angiography to determine differences in various cardiac sites and peripheral vessels. Methods This study is a multicenter, open-label, randomized, parallel-group study to be conducted to compare the appropriate or low dose of rosuvastatin in the effect on serum levels of inflammatory markers in AMI patients. The eligible patients undergoing percutaneous coronary intervention (PCI) will be randomly assigned to receive either appropriate or low-dose rosuvastatin daily using a web-based randomization software within 24 h after PCI. The low-dose group will be treated with rosuvastatin 2.5 mg once daily with a follow-up. The appropriate-dose group will begin treatment with rosuvastatin 5 mg once daily, and the dose of rosuvastatin will be titrated to 10 mg within 4 weeks. During administration of the study treatment, subjects will undergo laboratory testing including MMPs and be monitored for the occurrence of adverse events up to 24 weeks. The primary endpoint will be the change rate of MMPs at 24 weeks after administration. Conclusions INVITATION will compare the appropriate or low dose of rosuvastatin in the effects on serum levels of inflammatory markers including MMPs in AMI patients. This study will provide significant information on rosuvastatin as an anti-inflammatory agent for AMI.

Background The CHADS 2 score has mainly been used to predict the likelihood of cerebrovascular accidents in patients with atrial fibrillation. However, increasing attention is being paid to this scoring system for risk stratification of patients with coronary artery disease. We investigated the value of the CHADS 2 score in predicting cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation. Methods and Results This was a multicenter, observational cohort study. The subjects had been admitted to one of the participating institutions with coronary artery disease requiring percutaneous coronary intervention. We calculated the CHADS 2 scores for 7082 patients (mean age, 69.7 years; males, 71.9%) without clinical evidence of atrial fibrillation. Subjects were subdivided into low‐ (0–1), intermediate‐ (2–3), and high‐score (4–6) groups and followed for 1 year. The end point was a composite of cardiovascular/cerebrovascular death, nonfatal myocardial infarction, and ischemic stroke at 1‐year follow‐up. Rates of triple‐vessel/left main trunk disease correlated positively with CHADS 2 score categories. CHADS 2 scores among single, double, and triple‐vessel/left main trunk groups were 2 (1–2), 2 (1–3), and 2 (2–3), respectively (P

The purpose of this study was to evaluate the noise and image quality of images reconstructed with a knowledge-based iterative model reconstruction (knowledge-based IMR) in ultra-low dose cardiac computed tomography (CT).We performed submillisievert radiation dose coronary CT angiography on 43 patients. We also performed a phantom study to evaluate the influence of object size with the automatic exposure control phantom. We reconstructed clinical and phantom studies with filtered back projection (FBP), hybrid iterative reconstruction (hybrid IR), and knowledge-based IMR. We measured effective dose of patients and compared CT number, image noise, and contrast noise ratio in ascending aorta of each reconstruction technique. We compared the relationship between image noise and body mass index for the clinical study, and object size for phantom study.The mean effective dose was 0.98 ± 0.25 mSv. The image noise of knowledge-based IMR images was significantly lower than those of FBP and hybrid IR images (knowledge-based IMR: 19.4 ± 2.8; FBP: 126.7 ± 35.0; hybrid IR: 48.8 ± 12.8, respectively) (P .01). The contrast noise ratio of knowledge-based IMR images was significantly higher than those of FBP and hybrid IR images (knowledge-based IMR: 29.1 ± 5.4; FBP: 4.6 ± 1.3; hybrid IR: 13.1 ± 3.5, respectively) (P .01). There were moderate correlations between image noise and body mass index in FBP (r = 0.57, P .01) and hybrid IR techniques (r = 0.42, P .01); however, these correlations were weak in knowledge-based IMR (r = 0.27, P .01).Compared to FBP and hybrid IR, the knowledge-based IMR offers significant noise reduction and improvement in image quality in submillisievert radiation dose cardiac CT.

We compared the fixed injection rate protocol (P2) with the fixed injection duration protocol (P1) for coronary CT angiography using the test bolus technique. We randomly assigned 100 patients to one of two protocols. In P1, they received 0.7 mL/kg Iohexol-350 in an injection duration of 9 s, and we selected a delay of 3 s after peak enhancement of test bolus scan. In P2, they received 0.7 mL/kg Iohexol-350 at an injection rate of 5 mL/s, and we selected a delay after peak enhancement of test bolus scan using the following formula: TID/2-2 s, where TID is the injection duration of full bolus. We compared attenuation values in the ascending aorta and coronary arteries and patient-to-patient enhancement variability at each segment. At all segments, CT attenuations of P2 were significantly greater than those of P1 (ascending aorta 400 ± 64 vs. 368 ± 60, P = 0.01; left main trunk 399 ± 67 vs. 369 ± 55, P = 0.02; proximal-RCA 393 ± 66 vs. 363 ± 56, P = 0.01). There was no significant difference in patient-to-patient enhancement variability at all segments between the two groups (P > 0.05). P2 yielded superior vessel enhancement and comparable patient-to-patient enhancement variability compared with P1 in thin patients.

Clinical outcomes of percutaneous coronary intervention (PCI) at hospital with or without onsite cardiac surgery backup Tomonori Akasaka , Seiji Hokimoto ⁎, Shuichi Oshima , Koichi Nakao , Kazuteru Fujimoto , Yuji Miyao , Hideki Shimomura , Ryusuke Tsunoda , Toyoki Hirose , Ichiro Kajiwara , Toshiyuki Matsumura , Natsuki Nakamura , Nobuyasu Yamamoto , Shunichi Koide , Hideki Oka , Yasuhiro Morikami , Naritsugu Sakaino , Koichi Kaikita , Sunao Nakamura , Kunihiko Matsui , Hisao Ogawa , on behalf of, Kumamoto Intervention Conference Study (KICS) Investigators

Background Randomized trials have established statins as an agent for prevention of coronary heart disease (CHD). The purpose of this study was to assess the hypothesis that standard-dose statin therapy has a beneficial effect in normocholesterolemic diabetic patients with CHD. Methods and results A prospective, randomized, open, blinded-endpoint trial was conducted from 2002 to 2004 at 55 hospitals in Japan to evaluate the effect of statins on subsequent cardiovascular events. A total number of 1,016 CHD patients (301 patients with type 2 diabetes mellitus [DM] and 715 non-DM patients) with serum total cholesterol levels of 180-240 mg/dl were randomly divided into non-statin and statin treatments. Clinical parameters were comparable between DM and non-DM groups. Serum low-density lipoprotein (LDL)-cholesterol levels were equally decreased after statin treatment in the 2 groups. Statin treatment improved prognosis in both the DM and non-DM groups; however, the number needed to treat (NNT) and relative risk reduction (RRR) were remarkable especially in the DM group (NNT=8, RRR=67%) compared with the non-DM group (NNT=30, RRR=24%). Conclusions Standard-dose statin therapy provides incremental clinical benefits in DM patients with normal cholesterol levels compared with non-DM patients. The data suggest that DM patients may enjoy the pleiotropic effects of statins, independent of the LDL-cholesterol lowering effects of these agents.

Background Based on the 2011 American College of Cardiology/American Heart Association percutaneous coronary intervention (PCI) guideline, it is recommended that PCI should be performed at hospital with onsite cardiac surgery. But, data suggest that there is no significant difference in clinical outcomes following primary or elective PCI between the two groups. We examined the impact of with or without onsite cardiac surgery on clinical outcomes following PCI for acute coronary syndrome (ACS). Methods and results From August 2008 to March 2011, subjects ( n = 3241) were enrolled from the Kumamoto Intervention Conference Study (KICS). Patients were assigned to two groups treated in hospitals with ( n = 2764) or without ( n = 477) onsite cardiac surgery. Clinical events were followed up for 12 months. Primary endpoint was in-hospital death, cardiovascular death, myocardial infarction, and stroke. And we monitored in-hospital events, non-cardiovascular deaths, bleeding complications, revascularizations, and emergent coronary artery bypass grafting (CABG). There was no overall significant difference in primary endpoint between hospitals with and without onsite cardiac surgery [ACS, 7.6% vs. 8.0%, p = 0.737; ST-segment elevation myocardial infarction (STEMI), 10.4% vs. 7.5%, p = 0.200]. There was also no significant difference when events in primary endpoint were considered separately. In other events, revascularization was more frequently seen in hospitals with onsite surgery (ACS, 20.0% vs. 13.0%, p p = 0.009). We performed propensity score matching analysis to correct for the disparate patient numbers between the two groups, and there was also no significant difference for primary endpoint (ACS, 8.6% vs. 7.5%, p = 0.547; STEMI, 11.2% vs. 7.5%, p = 0.210). Conclusions There is no significant difference in clinical outcomes following PCI for ACS between hospitals with and without onsite cardiac surgery backup in Japan.

The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants.This study included 5,801 consecutive patients (males, 4,160; age, 69.7±11.1 years, mean±SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mild-to-moderate CKD (30≤eGFR60, n=1,956) and severe CKD (eGFR30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31-0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively).In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events.

Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy. We hypothesized that early use of statins would decrease cardiovascular events, including heart failure in patients with acute myocardial infarction (AMI). To examine the effect of statins in Japanese patients with AMI, a prospective, randomized, open-label trial was conducted in 486 patients with normal total cholesterol levels. Patients were randomly assigned to receive any available statin (n = 241) within 96 hours of AMI onset or no statin (n = 245) and were followed for up to 24 months. The primary end point was a composite of cardiovascular death, nonfatal AMI, recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke. Event rate for the primary end point was lower in the statin group than in the nonstatin group (6.1% vs 11.4%, p = 0.0433). The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia (p = 0.0154 and 0.0264, respectively). In conclusion, early lipid-lowering therapy with statins decreases recurrent cardiovascular events, in particular, congestive heart failure.

To evaluate the radiation dose and image quality of 100 kVp cardiac CT, and the effects of display setting optimization. We randomly assigned 100 patients undergoing cardiac CT to one of following two protocols. Fifty patients underwent our conventional protocol with 120 kVp, and the other 50 patients underwent our low radiation dose protocol with 100 kVp. We compared effective dose (ED); CT number, image noise, and contrast noise ratio (CNR) of ascending aorta at 120 and 100 kVp protocol. We also performed quantitative analysis and qualitative analysis for bitmap image of 120, 100 kVp, and display preset optimization for 100 kVp images. The estimated ED was 48 % lower with the 100 kVp protocol than the 120 kVp protocol (2.8 vs. 5.5 mSv, p0.01). There is no significant difference in the CNR between 100 and 120 kVp protocol (18.5 ± 3.6 vs. 18.6 ± 3.8, p = 0.84). Display preset optimization significantly improved image quality of 100 kVp cardiac CT, and there is no significant difference in qualitative analysis and quantitative analysis between 100 kVp scan with optimized display preset and 120 kVp scan (p0.05). The 100 kVp scanning with optimized display preset offers almost same image quality at cardiac CT of thin adults under 48 % decreased radiation dose.

To evaluate the effect on image quality of a low contrast and radiation dose protocol for cardiac computed tomography (CT) using a low tube voltage, the hybrid-iterative reconstruction algorithm, and a 256-row CT scanner. Before clinical study, we performed phantom experiments to evaluate the hybrid iterative reconstruction technique. We randomly assigned 68 patients undergoing cardiac CT to one of two protocols; 33 were scanned with our conventional 120 kVp protocol, the contrast material (370 mgI/kg body weight) was delivered over 15 s. The other 35 patients underwent scanning at a tube voltage of 80 kVp; the contrast dose, reduced by 50 % (185 mgI/kg), was delivered at the same fractional dose (24.7 mgI/kg/s). The 80 kVp images were post-processed with the 60 % hybrid-iterative reconstruction technique. We evaluated the effective dose (ED), image noise, mean attenuation, and contrast-to-noise ratio (CNR) of each protocol. The hybrid-iterative reconstruction technique offers almost same spatial resolution and noise-power-spectrum curve as compared with filtered back projection reconstruction. There were no decrease in spatial resolution and no shift of spatial frequency in noise power spectrum. The average ED was 74 % lower with the 80- than the 120 kVp protocol (1.4 vs 5.4 mSv). Dunnett's test showed that there were no significant differences in the image noise, mean attenuation, and CNR between hybrid-iterative-reconstructed 80 kVp scans and 120 kVp scans (28.6 ± 6.5 vs 25.3 ± 4.5, p = 0.18; 475.0 HU ± 87.0 vs 445.3 HU ± 67.7, p = 0.20; 17.1 HU ± 3.5 vs 17.8 HU ± 3.1, p = 0.53). The low kVp scan and hybrid-iterative reconstruction algorithm can dramatically decrease the radiation dose and contrast dose with adequate image quality at cardiac CT of thin adults using a 256-row CT scanner.

Objective: The aim was to examine differences in the vascular response to α adrenoceptor stimulation on both smooth muscle and endothelium among large arteries perfusing various organs. Methods: In ring preparations of coronary, carotid, iliac, mesenteric, and renal arteries from pigs (n=24), the magnitudes of contraction to noradrenaline (with β blocker), with or without endothelium, and endothelium dependent relaxation to noradrenaline (with α1 and β blocker) were compared in vitro. Results: In both endothelium-intact and denuded groups, the contractions to noradrenaline were significantly smaller in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. The presence of endothelium significantly suppressed the contractions in coronary and carotid arteries, but did not affect the contractions in iliac, mesenteric, and renal arteries. The endothelium dependent relaxations to noradrenaline, which were abolished by LNMMA, were more prominent in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. Conclusions: The contractions via α adrenoceptors were small, and endothelium dependent relaxations via α2 adrenoceptors were large, in the coronary and carotid arteries, which perfuse the vital organs (heart and brain), as compared with those in iliac, mesenteric, and renal arteries. These results suggest that in the state of activation of the sympathetic nervous system, arterial tone in response to α adrenoceptor stimulation may be regulated not only by α adrenoceptors on vascular smooth muscle but also by those on endothelium, through release of endothelium derived relaxing factor (EDRF) via α2 adrenoceptors. Cardiovascular Research 1993; 27 :779-784

To examine the constrictor response of the infarct-related stenotic coronary artery in comparison with that of noninfarct-related stenotic arteries, acetylcholine in maximal doses of 100 μg for the left and 50 μg for the right coronary artery was injected into the 16 infarct-related coronary arteries of 16 patients with previous myocardial infarction (group 1) and into 19 stenotic coronary arteries of 16 patients with stable angina without myocardial infarction (group 2). Acetylcholine's effects on lumen diameter and area were quantitatively analyzed at the stenotic segment and its proximal segment without significant stenosis.Acetylcholine decreased lumen diameter and area at the stenotic segments from 0.72 ± 0.18 to 0.18 ± 0.33 mm and from 0.45 ± 0.22 to 0.10 ± 0.22 mm2, respectively, in group 1 (both p < 0.01) and from 0.75 ± 0.22 to 0.49 ± 0.30 mm and 0.48 ± 0.29 to 0.26 ± 0.23 mm2, respectively, in group 2 (both p < 0.01). Acetylcholine decreased the diameter and area at the proximal segment from 2.71 ± 0.75 to 2.38 ± 0.6 mm and from 6.18 ± 3.4 to 4.71 ± 2.23 mm2, respectively, in group 1 (both p < 0.01) and from 2.31 ± 0.67 to 1.95 ± 0.59 mm and from 4.5 ± 2.97 to 3.22 ± 1.96 mm2, respectively, in group 2 (both p < 0.01). The changes in diameter and area at the stenotic segment in group 1 were significantly greater than those in group 2 (both p < 0.01); there were no significant differences between groups in the changes at the proximal segment. Total or subtotal occlusion of the stenotic artery was induced in 11 (69%) patients in group 1 compared with 4 (21%) patients in group 2 (p < 0.01 group 1 vs. group 2).It is concluded that the constrictor response to acetylcholine of the stenotic segment of the infarct-related coronary artery is enhanced as compared with that of noninfarct-related arteries.

Study objective — The aim was to investigate the relationship between vascular aging and endothelial regulation of the vascular tone by various agonists in isolated pig coronary arteries. Experimental materials and design — Coronary artery rings from young (4-6 month old) and aged (3-4 years old) Yorkshire pigs were studied under isometric tension by organ chamber experiments. Cumulative concentration-response curves were obtained for vasorelaxing agents including noradrenaline (with β blocker), substance P, bradykinin, and glyceryl trinitrate in rings precontracted with prostaglandin F2α (PGF2α). The degree of atherosclerosis of the coronary arteries was examined by light microscopy after the pharmacological experiments. Measurements and main results — In the presence of propranolol (3 × 10−6M), noradrenaline (10−8−10−5 M) caused endothelium dependent relaxation. The maximum relaxation was significantly greater in the young [45.4(SEM 2.5)% of the magnitude of precontraction induced by PGF2α] than in the aged group \[26.9(3.0)%\] (p

Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity.The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups.In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events.

BACKGROUND This study was designed to examine the hemodynamic, renal, and hormonal effects of brain natriuretic peptide (BNP) infusion in patients with congestive heart failure (CHF) and in control subjects. METHODS AND RESULTS We infused synthetic human BNP at a rate of 0.1 micrograms/kg/min. BNP infusion decreased pulmonary capillary wedge pressure (control, from 5 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01; CHF, from 21 +/- 3 to 14 +/- 4 mm Hg, p less than 0.05) and systemic vascular resistance (control, from 1,264 +/- 75 to 934 +/- 52 dyne.sec.cm-5; CHF, from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5; p less than 0.01, respectively) and increased stroke volume index (control, from 49.9 +/- 2.7 to 51.5 +/- 2.3 ml/m2, p = NS; CHF, from 25.6 +/- 3.8 to 32.0 +/- 3.9 ml/m2, p less than 0.01). BNP infusion significantly increased urine volume (control, from 2.3 +/- 0.7 to 7.5 +/- 1.9 ml/min; CHF, from 0.8 +/- 0.2 to 5.3 +/- 1.0 ml/min; p less than 0.01, respectively), excretion of sodium (control, from 79.2 +/- 21.6 to 332.8 +/- 70.9 microEq/min; CHF, from 77.4 +/- 20.8 to 753.5 +/- 108.0 microEq/min; p less than 0.01, respectively), and excretion of chloride (control, from 72.5 +/- 18.4 to 256.0 +/- 43.3 microEq/min; CHF, from 74.0 +/- 19.6 to 708.8 +/- 103.3 microEq/min; p less than 0.01, respectively). Urinary excretion of sodium and of chloride in response to BNP infusion was higher in patients with CHF than in control subjects (p less than 0.01, respectively). BNP infusion increased the levels of plasma atrial natriuretic peptide (control, from 65 +/- 11 to 84 +/- 14 pg/ml; CHF, from 262 +/- 65 to 301 +/- 62 pg/ml; p less than 0.05, respectively) and decreased plasma aldosterone concentrations in both groups (control, from 43.3 +/- 12.1 to 27.3 +/- 7.1 pg/ml; CHF, from 91.1 +/- 34.3 to 66.3 +/- 27.2 pg/ml; p less than 0.05, respectively). CONCLUSIONS We conclude that BNP infusion improves left ventricular function in patients with CHF by vasodilation and prominent natriuretic action.

To study the effects of magnesium (Mg2+) on human coronary arteries and to compare those effects with those of diltiazem and nitroglycerin, we measured the tension of ring segments from isolated human coronary arteries obtained at autopsy within 5 hours after death. Precontracted segments with 3 x 10(-6) M prostaglandin F2 alpha were studied after adding cumulative concentrations of these agents (1.0-8.0 mM, 10(-9)-10(-5) M, and 10(-10)-10(-6) M, respectively). Mg2+ significantly inhibited the tonic contraction compared with the time-matched controls at 1.0 and 2.0 mM (48.7 +/- 5.6% vs. 88.6 +/- 2.2%, p less than 0.01, 36.2 +/- 6.1% vs. 78.9 +/- 3.0%, p less than 0.01, respectively). 1.0 and 2.0 mM Mg2+ did not suppress, but actually increased, the amplitude of periodic contraction, but 8.0 mM Mg2+ reduced the amplitude compared with the controls (6.6 +/- 5.2% vs. 73.3 +/- 10.7%, p less than 0.01). Diltiazem at a concentration of 10(-5) M moderately inhibited the tonic contraction, and reduced the amplitude of periodic contraction almost completely. Nitroglycerin reduced the tonic contraction almost completely at a concentration of 10(-6) M but did not reduce the amplitude of periodic contraction at any concentration. We conclude that 1.0 and 2.0 mM Mg2+ inhibits the tonic contraction and that 8.0 mM Mg2+ inhibits the periodic as well as the tonic contraction of isolated human coronary arteries. Diltiazem inhibits the periodic contraction, whereas nitroglycerin suppresses tonic contraction without affecting the periodic contraction.

Constriction of epicardial coronary arteries induces severe flow reduction causing myocardial ischaemia in patients with vasospastic angina. Whether such constriction is inherent in coronary arteries in general was determined by perfusing isolated epicardial coronary segments of humans and pigs at a constant perfusion pressure. Mean flow reduction after perfusion with potassium chloride (60 mmol.litre-1), acetylcholine (10(-9)-10(-5) mol.litre-1), and histamine (10(-8)-10(-4) mol.litre-1) was not different between humans and pigs. Prostaglandin F2 alpha (PGF2 alpha; 3 X 10(-6) mol.litre-1) decreased the flow more substantially in humans (by 74(9)%) than in pigs (by 6(1)%) (p less than 0.01). A pronounced flow reduction to 0 ml.min-1 was observed in eight of 17 human coronary arteries after potassium chloride, histamine, or PGF2 alpha perfusion but in none of the pigs. Histological examination of the coronary arteries showed no atherosclerotic lesions in the pigs but various lesions in humans, ranging from intimal thickening to 96% luminal stenosis in cross sectional area. Flow reduction after PGF2 alpha was significantly greater in human coronary arteries with stenoses greater than 50% (94(4)%) than in those with stenoses less than 25% (55(14)%) (p less than 0.05). Complete cessation of flow was observed more often in the stenotic arteries (greater than 50% stenosis) than in others (p less than 0.05). A substantial reduction in flow, which may cause myocardial ischaemia in vivo, was not seen in normal pig coronary arteries even after strong vasoconstrictor stimuli but was present in human coronary arteries with atherosclerosis.