Kazuhito Yamashita

Angiotensin receptor blocker improves coronary flow velocity reserve in hypertensive patients: comparison with calcium channel blocker.

Large-scale clinical studies have indicated that angiotensin receptor blockers (ARBs) have beneficial effects against cardiovascular diseases. We designed this study to compare the effects of an ARB and a calcium channel blocker (CCB) on coronary flow velocity reserve (CFVR), a predictor of cardiovascular events, as estimated using transthoracic Doppler echocardiography. Sixteen hypertensive patients (63.1±9.6 years old; 10 males) were randomly allocated in a double-blind fashion to valsartan (n=8, 40–80 mg/day) or nifedipine (n=8, 20–40 mg/day) groups. Age- and gender-matched subjects without hypertension were enrolled as a control group (n=12). CFVR was calculated by dividing the adenosine triphosphate–induced hyperemic flow velocity by the basal flow velocity in the left anterior descending coronary artery. Baseline characteristics and reduction in systolic and diastolic blood pressure after 6 months were similar in both groups. CFVR in the valsartan group increased from 2.34±0.38 to 3.10±0.84 at 2 months (p<0.05), and to 3.04±1.09 at 6 months (p<0.01). Both values became comparable to that in the control group (2.81±0.60). CFVR in the valsartan group was significantly higher (p<0.001) than that in the nifedipine group, which was little changed at 6 months. This discrepancy was derived from the significant increase of hyperemic velocity in the valsartan group, from 36.6±17.3 cm/s to 41.1±12.7 cm/s at 2 months, and to 48.1±20.2 cm/s at 6 months. We concluded that the ARB valsartan not only reduced high blood pressure but improved CFVR in hypertensive patients. However, these effects were not seen with the CCB nifedipine.

Oxidized low-density lipoprotein-induced apoptosis is attenuated by insulin-activated phosphatidylinositol 3-kinase/Akt through p38 mitogen-activated protein kinase.

1. The aim of the present study was to investigate whether p38 mitogen‐activated protein kinase (p38 MAPK) is involved in oxidized low‐density lipoprotein (oxLDL)‐induced apoptosis of human umbilical vein endothelial cells (HUVECs). We also sought to determine whether this apoptosis is regulated by the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway.

Low-density Lipoprotein Apheresis Therapy With a Direct Hemoperfusion Column: A Japanese Multicenter Clinical Trial

Abstract:  Low‐density lipoprotein (LDL) apheresis has been applied to patients with familial hypercholesterolemia (FH) with coronary artery disease (CAD). To examine the efficacy and safety of a new type of LDL adsorption column (KLD01, Kaneka, Osaka, Japan), which deals with whole blood without separating plasma, the new system was evaluated in a multicenter trial. The present study included 33 FH patients with CAD (24 males, 9 females, 57 ± 13 years) who were treated five times with a mean interval of 2.12 ± 0.60 weeks between treatments. We studied the removal efficacies for serum LDL cholesterol, Lipoprotein(a) (Lp(a)) and triglyceride, the times for the preparation of the system and for treatment, symptoms, and the biochemical data. The scheduled treatments were completed by 31 patients. Serum levels of LDL cholesterol, Lp(a) and triglycerides were all significantly reduced with KLD01; 61.5 ± 6.2%, 72.4 ± 5.9% and 69.5 ± 9.7%, respectively. The times for both setting up the column system (26 ± 7 min) and treatment (138 ± 20 min) were shorter with KLD01 than conventional methods. Adverse reactions occurred in eight cases (17 episodes), but the patients fully recovered immediately after each apheresis therapy session. We conclude that the new type of LDL adsorption column, one that deals with whole blood, is a promising apheresis therapy for FH patients in view of its efficacy, reduced time for treatment, and safety.

Evaluation of Improved Coronary Flow Velocity Reserve Using Transthoracic Doppler Echocardiography After Single LDL Apheresis

Abstract:  The purpose of this study was to clarify whether coronary flow velocity reserve (CFVR), evaluated by adenosine 5′‐triphosphate‐induced hyperemia, is improved by single low‐density lipoprotein (LDL) apheresis. Lipid lowering therapy is known to improve endothelium‐dependent vasodilatation in forearm or coronary resistant vessels. However, few reports have studied the effect of acute LDL reduction on CFVR. Methods: Seven patients with familial hypercholesterolemia and significant coronary stenosis except in the left anterior descending artery (LAD) were enrolled in this study. Coronary flow velocity reserve was estimated before and after LDL apheresis using transthoracic Doppler echocardiography (TTDE), which detects the flow velocity at the distal site of the LAD. Although the averaged diastolic peak velocity (ADPV) during ATP‐induced hyperemia was similar before and after LDL apheresis, the ADPV at baseline decreased from 30.69 to 25.56 cm/s, resulting in an increased CFVR from 1.78 to 2.10 (P < 0.001). Plasma bradykinin and 6 keto PGF1α increased while fibrinogen and plasma viscosity decreased after apheresis. Single LDL apheresis improves CFVR according to TTDE analysis because of the decreasing ADPV at baseline, which is thought to be induced by epicardial coronary artery dilatation and improved microvessel function. This is the result of various factors, such as changes in plasma LDL cholesterol, bradykinin and PGI2 levels with LDL apheresis.

Increase in intracellular calcium ion in smooth muscle cells induced by low-density lipoprotein

It was investigated whether low-density lipoprotein (LDL) had effects on intracellular Ca2+ concentration in the smooth muscle cell (SMC). LDL promoted SMC proliferation and increased intracellular Ca2+ by a two-phase pattern, an initial peak and a following plateau. Each phase was suppressed by treatment with ryanodine or extracellular Ca(2+)-free buffer. This increase in intracellular Ca2+ was also suppressed by anti-LDL receptor antibody. Moreover, inositol triphosphate (IP3) was elevated with short-term LDL treatment. Since SMC proliferation is the most important event in atherosclerosis and LDL is one of the main risk factors, it was concluded that LDL might trigger SMC proliferation by increasing IP3 and intracellular Ca2+ through LDL receptor.

Eosinophilic Myocarditis Complicated by Acute Myocardial Infarction A Case Report

The authors report a patient with eosinophilic myocarditis who developed severe chest pain with marked elevation of the ST segment on the electrocardiogram, which led them to suspect the presence of acute myocardial infarction. Emergency coronary angiography showed numerous occlusions and stenoses at the distal right and left coronary arteries, especially affecting the latter, owing probably to thrombus. The angiographic findings in this case demonstrate the formation and obstruction of thrombus in the small coronary arteries in a patient in the acute necrotic stage of eosinophilic myocarditis, believed to be the first such case reported.

Detection of patency of internal mammary artery grafts to the left anterior descending artery by transthoracic Doppler echocardiography.

Background: To determine whether a coronary artery bypass graft (CABG) is patent, we examined the flow of the left internal mammary artery (LIMA) to the left anterior descending artery (LAD) by transthoracic Doppler echocardiography (TTDE). Patients and Methods: Eighty‐seven patients with CABG (LIMA to distal LAD) were enrolled in the study. The flows from each subject were analyzed by three criteria: mosaic flow at the anastomosis site, distal anterograde flow (ante flow), and proximal retrograde flow (retro flow). Results: On angiography, 79 grafts were patent and eight were not. TTDE study of 79 patent grafts demonstrated mosaic, ante, and retro flow in 63 (79.7%), 74 (93.7%), and 35 grafts (49.4%), respectively. The averaged diastolic peak velocity of ante flow was 26.3 ± 11.0 cm/sec, significantly higher than that (4.8 ± 7.1 cm/sec, P ≤ 0.0001) in eight patients without patent grafts. These eight patients had no mosaic or retro flow and only three had ante flow. The accuracies to predict patency were 81.6%, 90.8%, and 49.4% for mosaic, ante, and retro flows, respectively. Conclusions: The existence of mosaic, retro, or sufficient ante flows strongly indicated the patency of LIMA to the LAD. When symptoms are possible to be derived from the occlusion of CABG to LAD, TTDE is a promising method to examine whether a LIMA to LAD bypass is patent.

Intracoronary Administration of Isosorbide Dinitrate Induced Severely Slow Flow and Transient ST-Segment Elevation

Nitroglycerin is one of the most widely used drugs in the treatment of angina. However, nitroglycerin fails to relieve angina in patients with syndrome X who have microvessel dysfunction. Microvessel function is impaired in several diseases. In this article, the authors report that despite normal coronary angiograms at control, intracoronary administration of isosorbide dinitrate induced severe coronary slow flow and transient ST-segment elevation with mild chest pain in a patient with congestive heart failure. The authors speculated that functional stenosis and a delay in the dilatation of microvessels less than 100 µm in diameter because of their dysfunction resulted in a severely slow flow after intracoronary administration of isosorbide dinitrate.

Persistence of recruitable coronary collaterals in the absence of coronary vasospasm in a patient with variant angina.

Recruitable coronary collaterals may appear when spasm suddenly occludes the coronary artery. We report a patient with variant angina who had visible collateral vessels on a control coronary angiogram, despite the presence of normally appearing coronary arteries. These collaterals disappeared after intracoronary administration of nitroglycerin. These findings suggest that recruitable collateral vessels can remain patent long after spontaneous attacks of angina have resolved, and become visible when there is a pressure difference between two small coronary arteries.