Taku Matsubara

Negative NO3− difference in human coronary circulation with severe atherosclerotic stenosis

To examine whether or not the levels of NOx (nitrite; NO2- and nitrate; NO3-) in coronary circulating blood reflect endothelial dysfunction due to coronary atherosclerosis, NOx levels in plasma obtained from ostium of left coronary artery and coronary sinus of patients who complained of chest pain were evaluated in relation to their coronary angiographic findings. Prior to the study, a HPLC-Griess system for NOx measurement was critically evaluated. This system has a detection limit of 0.1 microM of NO2- and NO3- by 10 microl of loading and was able to distinguish a difference of 0.1-0.2 microM of these substances. Heparin (1 U/10 microl) did not affect the detective and discriminative abilities. NO3- difference, calculated from sino-arterial difference of NO3-, was almost zero (-0.2 +/- 0.2 microM) in patients with either normal coronary arteries or mild organic coronary stenosis (< or = 20% narrowing), while a significant negative value (-5.9 +/- 1.7 microM) was obtained from patients with significant stenosis (> or = 70% narrowing) in the left coronary arteries. These results demonstrate reliable ability on the HPLC-Griess system in evaluating NO2- and NO3- in biological samples, and that the negative NO3- difference through coronary circulation may reflect endothelial dysfunction in the patients with coronary atherosclerosis with severe organic stenosis.

Balloon catheter with check valves for experimental relief of acute aortic regurgitation

To evaluate the ability of a newly designed balloon catheter with check valves to temporarily relieve hemodynamic deterioration in acute aortic regurgitation, we produced an experimental model of acute aortic regurgitation in closed-chest dogs using endomyocardial biopsy forceps. Aortic regurgitation was produced until an increase in aortic pulse pressure of over 50% was achieved. Left ventricular end-diastolic pressure rapidly increased after the production of aortic regurgitation. Immediately after the catheter began functioning, pulse pressure decreased from 133 +/- 1 to 78 +/- 5 mm Hg (mean +/- SEM) and left ventricular end-diastolic pressure also decreased from 26 +/- 1 to 13 +/- 1 mm Hg. These effects lasted as long as the catheter functioned. Although a mild (21 +/- 8 mm Hg) pressure gradient between the left ventricular peak systolic pressure and the aortic peak systolic pressure was observed when this catheter was used, forward stroke volume was no less than in the group in which the catheter had not been used. These findings suggest that the balloon catheter with check valves may effectively reduce aortic regurgitation.

Possible role of coronary artery spasm in unexplained syncope

Coronary spasm provocation by intracoronary methylergonovine was performed in 14 patients (8 men and 6 women, mean age 56 +/- 6 years) with syncope that remained unexplained despite neurologic and noninvasive cardiac evaluations. Electrophysiologic testing was also performed in 6 of 14 patients. No patient had structural heart disease or significant fixed stenosis of greater than or equal to 75% in the coronary arteries. Six patients had no history of chest pain even when they developed syncope. Serious arrhythmia was documented in 2 patients, cardiac standstill in 1 and complete atrioventricular block in the other. Coronary spasm was induced in 9 patients using the methylergonovine provocation test. Multivessel spasms were found in 3 patients. Coronary spasm was induced in the artery supplying the inferior wall in 7 of 9 patients with positive results. In 4 of 9 patients who had a positive result, there was no prior history of chest pain. In 1 patient, whose electrocardiogram was recorded during syncope, cardiac standstill was documented and cardiac standstill and syncope also occurred during the provocation test. Monomorphic ventricular tachycardia was not induced by the electrophysiologic study. These results suggest that coronary spasm is involved in unexplained syncope.

Coronary artery perforation with subepicardial hematoma.

Coronary artery perforation is a relatively rare complication in coronary angioplasty. We report the case of a 71-year-old male, who was salvaged by emergency surgery, for cardiogenic shock due to subepicardial hematoma associated with balloon angioplasty. Such a case has not yet previously been reported.

Association between coronary endothelial dysfunction and local inflammation of atherosclerotic coronary arteries

We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS — Ao) x 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = -0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = -0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction. (Mol Cell Biochem 249: 67–73, 2003)

Immediate effects of percutaneous transvenous mitral commissurotomy on pulmonary hemodynamics at rest and during exercise in mitral stenosis

Hemodynamics were evaluated during exercise in 33 patients with mitral stenosis who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC was performed using an Inoue balloon. Each patient underwent a supine ergometer exercise test before and on the day after PTMC. Ergometer work load was started at 20 W and increased in increments of 20 W at 3-minute intervals until terminated by the patients fatigue or shortness of breath. Mitral valve area increased by 0.8 +/- 0.4 cm2 (1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.001). Mean mitral pressure gradient decreased (12 +/- 5 to 6 +/- 2 mm Hg, p less than 0.001). Pulmonary arterial pressure significantly decreased and the cardiac index significantly increased both at rest and during exercise after PTMC. Before PTMC, the increases in pulmonary arterial pressure, total pulmonary resistance and pulmonary arteriolar resistance during exercise were greater in patients with a mitral valve area less than 1.0 cm2 than in patients with an area greater than or equal to 1.0 cm2. After PTMC, total pulmonary resistance still increased during exercise. However, pulmonary arteriolar resistance did not change during exercise in patients with a mitral valve area greater than or equal to 1.5 cm2, whereas it increased in patients with an area less than 1.5 cm2. An enlarged mitral valve area greater than or equal to 1.5 cm2, which may prevent pulmonary vasoconstriction and permits a greater increase in pulmonary blood flow during exercise, is considered a good result immediately after PTMC.

Decrease in plasma NOx concentration by isosorbide dinitrate, an organic nitrate ester.

It has been suggested that isosorbide dinitrate (ISDN)–induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential increase in plasma concentrations of NOx (NO2− and NO3−, stable end-products of NO) in venous blood than arterial blood. Plasma NOx was measured by high-performance liquid chromatography–Griess system with a sensitivity of 0.01 &mgr;M for NO2− and 0.1 &mgr;M for NO3−. Arterial and venous blood samples were obtained after coronary angiography from the aorta and right atrium of patients with or without ischemic heart disease. Nicardipine, a calcium channel blocker, was used as a non–NO-related arteriovasodilator. At 1 mg i.v., it did not cause any changes in NOx concentration in arterial and venous blood irrespective of hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2− and decreased NO3− in both arterial and venous blood, with concomitant venodilation. Further analysis revealed that plasma NO2− increased in the pulmonary circulation and this increase was preserved after nicardipine and ISDN, and that ISDN, but not nicardipine, increased plasma NO3− in the pulmonary circulation. The authors did not detect higher concentrations of NOx in venous blood relative to their level in arterial blood. Further studies are necessary to clarify the kinetics of NO and NO-related compounds in the whole body.

Clinical characteristics of hemodialysis patients with atrial fibrillation: The RAKUEN (Registry of atrial fibrillation in chronic kidney disease under hemodialysis from Niigata) study

BACKGROUND Clinical characteristics, management, and outcomes in hemodialysis patients with atrial fibrillation (AF) remain unclear. METHODS AND RESULTS We studied 423 Japanese patients undergoing maintenance hemodialysis (age 65.2±12.4 years, male 70%, mean duration of hemodialysis 139±124 months). AF was present in 19% (n=82) and was independently related to increased age (odds ratio 1.070, 95% confidence interval 1.043-1.098), longer hemodialysis duration (odds ratio 1.006, 95% confidence interval 1.004-1.008), and congestive heart failure (odds ratio 2.749, 95% confidence interval 1.546-4.891). During observations lasting a mean of 36 months, the incidences of all-cause death, cardiovascular death, and major bleeding, in particular gastrointestinal bleeding, were significantly higher in the AF (n=82) than the non-AF (n=341) patients (p<0.001, p=0.004, p=0.002, p=0.027, respectively), but the incidence of ischemic stroke/systemic embolism was similar in the AF and non-AF patients. AF was independently associated with all-cause death (hazard ratio 1.728, 95% confidence interval 1.123-2.660) and major bleeding (hazard ratio 1.984, 95% confidence interval 1.010-3.896). Warfarin was prescribed in 33% of the AF patients, but the rates of all-cause death, ischemic stroke, and major bleeding during the study period were not significantly different between warfarin (n=27) and non-warfarin (n=55) groups. CONCLUSIONS In our hemodialysis patients, AF was a common comorbidity and was independently associated with all-cause death and major bleeding, but not with increased risk of ischemic stroke.

Angioscopic study of the antithrombotic effect of a new selective thromboxane A2 synthetase inhibitor, CV-4151, on experimental arterial thrombi

Using fibreoptic angioscopy, the effectiveness of CV-4151 in suppressing the formation of arterial thrombi after balloon injury has been shown

Comparison of clinical outcomes of coronary artery stent implantation in patients with end-stage chronic kidney disease including hemodialysis for three everolimus eluting (EES) stent designs: Bioresorbable polymer-EES, platinum chromium-EES, and cobalt c

BACKGROUNDS New-generation bioresorbable polymer-everolimus eluting stents (BP-EES) are available. This study aimed to compare the clinical outcomes for BP-EES compared to more established stent designs, namely the platinum chromium-EES (PtCr-EES) and cobalt chrome-EES(CoCr-EES) in patients with the end-stage chronic kidney disease (CKD) including hemodialysis (HD). METHODS One-hundred-forty-one consecutive stents (BP-EES [n = 44], PtCr-EES [n = 45], and CoCr-EES [n = 52]) were implanted in 104 patients with CKD. All patients underwent a follow-up coronary angiography at 12 months after implantation. End-stage CKD was defined as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 , or the need for HD. The following outcome variables were compared among the three stent groups after implantation and the 12-month follow-up: target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac event (MACE). Minimal stent diameter (MSD) and %diameter-stenosis (%DS) were measured using quantitative coronary angiography. RESULTS The overall rate of TLR and MACE was 14.6% and 30.8%, respectively, with no incidence of ST. Immediately after implantation, the MSD (P = 0.22) and %DS (P = 0.42) were equivalent among the three groups. However, at the 12-month follow-up, a tendency towards higher TLR was observed for the BP-EES group (22.7%) compared with the PtCr-EES (8.8%) and CoCr-EES (9.6%) groups (P = 0.07). Late loss in lumen diameter was also significantly greater for the BP-EES (0.51 ± 0.64 mm) group than either the PtCr-EES (0.20 ± 0.61 mm) and CoCr-EES (0.25 ± 0.70 mm) groups (P = 0.03). CONCLUSIONS BP-EES might increase the risk of in-stent restenosis in patients with end-stage of CKD or the need for HD.