松本 鉄也

The renin-angiotensin system regulates the vascular fibrinolytic balance. In the human forearm vasculature, angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) increase the release of t-PA through endogenous bradykinin. We tested the hypothesis that ACE inhibition and sex modulate the endogenous coronary release of tissue plasminogen activator (t-PA) in hypertensive patients. Seventy-three patients underwent diagnostic coronary angiography and had normal coronary angiograms. Thirty-three patients (21 men and 12 women) were treated with imidapril (5 mg/day) for 4 weeks (ACE-I group), and 40 (23 men and 17 women) were not treated with ACE-I (non-ACE-I group). All of the women were postmenopausal. Coronary blood flow in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Net coronary t-PA release was determined as (coronary sinus-aorta gradient of t-PA)X(coronary blood flow)X[(100-hematocrit)/100]. Age, arterial pressure, heart rate, lipid levels, coronary flow, and the plasma level of t-PA at either aorta or coronary sinus were comparable among the 4 groups. In women, net t-PA release in the ACE-I group was significantly higher than that in the other groups (P<0.05; man non-ACE-I group: 1.4 +/- 2.6 ng/mL; woman non-ACE-I group: 1.4 +/- 3.1 ng/mL; man ACE-I group: -1.8 +/- 2.8 ng/mL; woman ACE-I group: 14.8 +/- 3.6 ng/mL). Correction for smoking status gave similar results. There was a significant negative correlation between serum ACE activity and coronary t-PA release in women (r=-0.38; P<0.05) but not in men. ACE inhibition increases coronary release of t-PA in women but not in men. (Hypertension. 2010;56:364-368.)

Echocardiographic studies have suggested an association between diastolic dysfunction and exercise intolerance. The aim of this study was to examine the relationship between exercise capacity and left ventricular (LV) function during stress myocardial scintigraphy, and to investigate whether or not this relationship is caused by ischemia during exercise. The studied patients underwent technetium-99m sestamibi quantitative gated SPECT, including treadmill exercise. Myocardial stress images were acquired 30 min after the first tracer injection (370 MBq) during maximal exercise. Three hours later, the second tracer (740 MBq) was injected, and resting images were acquired 30 min after this injection. The presence of ischemia was determined by tracer accumulation. From the same data source, LV diastolic parameters [first third filling fraction (1/3FF), first third filling rate (1/3FR), peak filling rate (PFR) and time to PFR (TPF)], and systolic parameters [ejection fraction (EF), peak ejection rate (PER), time to PER (TPE) and first third ejection fraction (1/3EF)] were analyzed. Subjects with exercise inability (< 6 METs) were excluded. In 45 patients, diastolic parameters 1/3FF, 1/3FR, PFR and TPF correlated significantly with exercise duration (r = 0.32*, 0.37*, 0.37* and -0.40(#), respectively; *p < 0.05, (#) p < 0.01), but systolic parameters EF, PER, TPE and 1/3EF did not. At rest, 1/3FF, PFR and PER were significantly increased, suggesting functional deterioration during exercise. Even after 3 h, 1/3FR, PFR and TPF still correlated significantly with exercise duration (r = 0.29*, 0.36* and -0.30*, respectively; *p < 0.05). Such findings were observed even when the 10 patients who exhibited ischemia during exercise were excluded (1/3FR: r = 0.34*; PFR: r = 0.37*; TPF: r = -0.36*; *p < 0.05, n = 35). Our findings suggested that LV diastolic dysfunction, not systolic dysfunction, is associated with limited exercise capacity independent of the occurrence of ischemia.

The aim of this study was to determine the impact of pitavastatin on low-density lipoprotein cholesterol (LDL-C) and lectin-like oxidized LDL receptor-1 (LOX-1) in patients with hypercholesterolemia. Twenty-five hypercholesterolemic patients (8 male, 17 female; age 66 +/- 13, 21-80 years) who had not received anti-dyslipidemic agents and had LDL-C levels of more than 160 mg/dL were examined. Biochemical factors were measured at baseline and after treatment with pitavastatin (2 mg/day) for 6 months. Serum levels of LOX-1 with apolipoprotein B-100 particle ligand and a soluble form of LOX-1 (sLOX-1) were measured by ELISA. All subjects completed the study with no adverse side effects. Total-C (268 +/- 26 vs. 176 +/- 17 mg/dL), LDL-C (182 +/- 21 vs. 96 +/- 14 mg/dL), and LOX-1 ligand (867 +/- 452 vs. 435 +/- 262 ng/mL) were reduced with pitavastatin treatment (P < 0.0001 for each). Significant decreases in triacylglycerols were noted (P < 0.0001), but there were no changes in high-density lipoprotein cholesterol. After 6 months, there were no significant changes in high-sensitivity CRP or soluble LOX-1. At baseline, there were no significant correlations between LOX-1 ligand and either LDL-C or sLOX-1. The decrease in LOX-1 ligand was not correlated with the decrease in LDL-C, but was correlated with the decrease in sLOX-1 (r = 0.47, P < 0.05). In conclusion, pitavastatin therapy had beneficial effects on markers of oxidative stress in hypercholesterolemic subjects. Serum levels of LOX-1 ligand may be a useful biomarker of the pleiotropic effects of statins.

心室細動(ventricular fibrillation;VF)を発生後に自動体外式除細動器(automated external defibrillator;AED)より救命された重症心疾患例が下肢血行障害を合併し下肢を切断したが、心臓リハビリテーションを工夫して施行したことによって家庭に退院できるまでの日常生活動作(activities of daily living;ADL)が獲得できた2症例を報告する。症例1:74歳、男性。心筋虚血による心室細動(VF)に対して、体育館に設置してあった自動体外式除細動器(AED)が使用された。心不全に対して大動脈バルーンパンピング(IABP)が使用された。下肢の血行障害を生じて、右下腿切断を施行された。下腿装具を装着し、心臓リハビリテーションを実施しADLが向上した。致死性不整脈の再発はなく、家庭復帰した。症例2:16歳、男性。心筋炎によると考えられるVFの発作を繰り返した。初回のVFに対して、学校に設置してあったAEDが使用された。心不全に対して経皮的心肺補助装置(PCPS)が使用された。下腿の血行障害による壊死を生じたため、下腿切断を施行された。下腿装具を作製し、心臓リハビリテーションを行った。VFを繰り返したため植込み型除細動器(implantable cardioverter defibrillator;ICD)を植え込み、その後も心臓リハビリテーションを行い、家庭復帰と復学が可能となった。(著者抄録)

A 49-year-old female cardiomyopathic patient with heart, hepatic, and renal failure and lactic acidosis was transferred to the intensive care unit without a unifying diagnosis. She was of short stature ( 145 cm tall), had difficulty in hearing, a past history of complete atrioventricular block, and had received a permanent pacemaker. She had been diagnosed and treated as dilated cardiomyopathy by her primary doctor. Treatment in the intensive care unit for 21 days including plasma exchange, continuous hemodiafiltration, artificial ventilation, and administration of catecholamine, carperitide, and a large amount of coenzyme Q10 ( 210 mg/day) improved the symptoms. Genetic analysis using mitochondrial DNA from leukocytes and sternocleidomastoid muscle revealed a 3243A>G mutation in the mitochondrial tRNA(Leu (UUR)) gene, which is related to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes ( MELAS). The patient recovered through intensive care and could be discharged from hospital without any sequelae. This case was mitochondrial cardiomyopathy diagnosed from the symptoms of multiple organ dysfunction syndrome. Cardiomyopathy due to the mutation of mitochondrial DNA is not a common disease. However, it should be considered as a possible cause of heart failure. (C) 2007 Elsevier Ireland Ltd. All rights reserved.