Yasuo Kudoh

Inability of Metoprolol to Achieve a Sustained Limitation of Infarct Size 24 h After Coronary Artery Embolization in the Closed Chest Dog

Studies were undertaken to ascertain whether metoprolol, a beta 1-selective adrenergic blocking agent, could offer a limitation of myocardial injury throughout a 24-h period of coronary embolization in the dog. Regional myocardial ischaemia was induced through the use of a bead embolization technique which did not require thoracotomy. In order to delineate the zone at risk of infarction (hypoperfused area), radioactive microspheres (141Ce) were administered intraventricularly immediately after embolization. In the drug-treated group (n = 8) metoprolol administration was initiated by an intravenous bolus injection (0.3 mg X kg-1). This was followed by a continuous infusion (0.003 mg X kg-1 X min-1) during the 24-h experimental period. In the control group (n = 8) saline was administered throughout the 24-h period. Electrocardiographic activity was monitored throughout the experiment and this confirmed the negative chronotropic and antiarrhythmic properties of metoprolol. After 24 h, the hearts were excised and transverse myocardial sections (3 mm) prepared. Areas of necrosis were visualized by tetrazolium staining and risk zones were defined by microsphere autoradiography. In the control and metoprolol-treated groups, 73.3 +/- 7.7% and 68.2 +/- 6.1% of the risk zone became necrotic, respectively. There was no significant difference between these groups.

Long-Term Effects of Oral L-Carnitine Supplementation on Anemia in Chronic Hemodialysis

Background: The therapeutic role of L-carnitine (LC) on the anemia of chronic hemodialized patients is still controversial. In order to clarify the long-term effects of LC administration on renal anemia, an open, observational 12-month study was performed. Methods: Twenty stable outpatients undergoing hemodialysis were administered LC 900 mg p.o. daily for 12 months. The recombinant human erythropoietin (rHuEPO) dose was adjusted monthly when necessary to maintain the target hemoglobin (Hb) levels. Results: The free LC level increased, while the acyl/free LC ratio decreased significantly 3 months after administration and was then maintained until the end of the study. There was no difference in Hb levels and the erythropoietin resistance index (ERI) during the study period. However, it was observed that ERI decreased significantly in 7 out of 18 patients (responders) 5 months after LC administration and was maintained thereafter (almost 40% reduction of the rHuEPO dose). The acyl/free carnitine ratio at baseline was the most contributing factor distinguishing responders from nonresponders. Conclusion: Although the beneficial effect of LC supplementation on renal anemia was not observed in all patients, at least 40% of the patients (responders) showed a significant improvement in ERI after long-term LC administration.

The Effects of Oral L-Carnitine Supplementation on Physical Capacity and Lipid Metabolism in Chronic Hemodialysis Patients

Background: It is well known that the physical activity in chronic hemodialysis patients decreases compared to that in normal subjects. In order to investigate the effects of L-carnitine on physical capacity and lipid metabolism, a cardiopulmonary exercise test using a bicycle ergometer was performed before and after 3 months of oral L-carnitine supplementation under double-blind conditions. Methods and Results: A total of 20 stable outpatients undergoing hemodialysis treatment were randomly divided into 2 groups: controls receiving placebo and patients receiving 900 mg L-carnitine p.o. daily. The levels of free and acyl carnitine increased significantly from 22.9 ± 7.3 to 149.9 ± 51.8 μmol/l and from 16.0 ± 2.8 to 100.3 ± 50.2 μmol/l, respectively, in the L-carnitine group; however, there was no significant change in other plasma lipid profiles. The exercise time was decreased and the heart rate at the anaerobic threshold was increased in the control group 3 months after the study period, but there were no such changes observed in the L-carnitine group. The minute ventilation/CO2 output slope increased significantly from 38.9 ± 7.8 to 43.8 ± 11.8 in the L-carnitine group. It has been speculated that a shift in the energy source occurs from carbohydrate to lipid, in terms of an increase of oxygen demand. Conclusion:L-Carnitine supplementation might have some beneficial effects on the physical capacity of chronic hemodialysis patients due to the improvement of the lipid metabolism in the muscle.

Mechanism of the depressor effect of recombinant human erythropoietin in anemic patients undergoing chronic hemodialysis.

慢性血液透析患者で, recombinant human erythropoietin (EPO) 長期投与による腎性貧血改善時に有意な降圧を示す例を経験し, その降圧機序を心エコー図による心血行動態と各種血管作動性内分泌因子の面から, 非降圧群と対比検討した. ヘマトクリット (Ht) 値23.5%以下の慢性血液透析患者28例に, Ht値25-30%を維持すべく12か月間EPOを投与. EPO投与前・後に血圧, 心拍数, 体重, 末梢血液, 心エコー図と血漿のノルアドレナリン (pNA) 濃度, レニン活性 (PRA), アンジオテンシンII (A-II) 濃度, 心房性ナトリウム利尿ペプチド (ANP) 濃度を測定した. そして, これら所見をEPO投与後血圧が有意に低下した降圧群と, 然らざる非降圧群の2群に分けて比較検討した. EPO投与後, 4例で有意な血圧低下を認め, 24例では降圧を認めなかった. 赤血球数, ヘモグロビン濃度, Ht値は両群いずれも有意に上昇したが, これらの改善度に差異は認めなかった. また, 心拍数, 体重は両群で不変であった. 心エコー図による左房径, 左室拡張末期径, 左室収縮末期径, 左室駆出分画 (EF) では, EPO投与3か月後の非降圧群で左室拡張末期径が有意に低下した以外, 全て不変であった. しかし, 降圧群は非降圧群に比して, EPO投与前のEFが有意に高値で, 投与後の1回拍出量 (SV), 心拍出量 (CO) の減少も持続し, COの変化率も大なる傾向を示した. さらに, SV, COの変化度と収縮期血圧の変化度の間には, 降圧群でのみ有意な正相関を認めた. 全末梢血管抵抗はEPO投与3か月後, 非降圧群で有意に上昇したが, 両群間には差異を認めなかった. 他方, pNA, PRA, A-II, ANPにはいずれにも両群間で差異を認めなかった.以上の成績より, EPO長期投与時の降圧群は非降圧群に比し, 貧血改善時の心拍出量の低下がより顕著で, これが降圧機序の一部をなすと考えられた.