Koji Miyazaki

Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model

In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to increase blood pressure and prolong survival time. On the other hand, NOS inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we hypothesized that the beneficial effect of NOS inhibitor is attributable to the increased coronary perfusion pressure and that it outcompetes the coronary vasodilating effects of nitric oxide. To investigate the direct effect of NOS inhibitor on the regulation of coronary circulation and the induction of myocardial ischemia in HS, we used a canine model at a constant aortic pressure of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction of HS increased both systemic and coronary vascular resistances and further increased the serum catecholamine concentration at 10 min after L-NAME. In another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and freeze clamped (-190°C) by a specially developed sampling device after 10 min of HS. Transmurally distributed myocardial ischemia was visualized by the enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was significantly increased with L-NAME (n = 7). Chemical analysis revealed a decrease in the myocardial ATP concentration with L-NAME in the subendocardial ischemic region in HS. In conclusion, with the use of an aortic reservoir to keep the aortic pressure constant in HS, NOS blockade significantly worsened myocardial ischemia by decreasing coronary flow and augmenting the serum catecholamine concentration.

A case of fundus albipunctatus with a retinol dehydrogenase 5 gene mutation in a child

BACKGROUNDnWe examined a family with fundus albipunctatus in which mutation of the retinol dehydrogenase 5(RDH 5) gene was suspected to be the cause of this disease.nnnCASEnAn 8-year-old girl had diffuse multiple white dots in her fundus except for the macula. She had good central vision. The amplitude of her electroretinogram wave was low, but it recovered after three hours of dark adaptation. Dark adaptometry showed an elevated threshold for rod adaptation. No visual field loss was observed. A homozygous missense mutation was found in exon 5 of the RDH 5 gene that substituted histidine for arginine at codon 280(Arg 280 His). Her mother had a normal fundus but was heterozygous for the same mutation.nnnCONCLUSIONnA missense mutation of RDH 5(Arg 280 His) was found in a Japanese family with fundus albipunctatus.

Association between brachial-ankle pulse wave velocity and the ratio of l-arginine to asymmetric dimethylarginine in patients undergoing coronary angiography

BACKGROUNDnEndothelial dysfunction causes vasomotor dysregulation and vascular stiffening in addition to structural changes. By influencing NO synthesis, deficiency of l-arginine relative to asymmetric dimethylarginine (ADMA), which is an l-arginine derivative that acts as a competitive NO synthase inhibitor, may lead to the promotion of arterial stiffness. This study investigated the relationship between the l-arginine/ADMA ratio and brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness.nnnMETHODS AND RESULTSnThis cross-sectional study enrolled 74 patients (62 men, 12 women; mean age, 67±10 years) undergoing elective coronary angiography. A total of 54 (73%) patients had coronary artery disease. Serum l-arginine and ADMA were measured by high-performance liquid chromatography with fluorescence detection. The ratio of l-arginine to ADMA and the serum l-arginine level was associated with baPWV in univariate regression analysis (l-arginine/ADMA ratio: β=-0.323, p=0.005; l-arginine: β=-0.247, p=0.034). In addition, baPWV was related to blood hemoglobin concentration, hematocrit, brain natriuretic peptide level, symmetric dimethylarginine, renal function, blood pressure, and heart rate. In multivariate analysis, the l-arginine/ADMA ratio was a significant predictor of baPWV (β=-0.310, p<0.001). In subgroup analyses, the l-arginine/ADMA ratio was associated with baPWV in elderly patients (n=46, β=-0.359, p=0.004), and in younger patients (n=28, β=-0.412, p=0.006).nnnCONCLUSIONnA low l-arginine/ADMA ratio may be associated with high baPWV in patients undergoing coronary angiography.

A case of drug-induced interstitial pneumonia caused by repeated exposure to bepridil

The patient was a 78‐year‐old man. In August 2007, he underwent catheter ablation for atrial fibrillation after taking bepridil for 3 weeks. Soon after the ablation, he experienced frequent atrial extrasystoles and began taking bepridil again on the day he left the hospital. Six days after discharge, he was readmitted to our hospital with dyspnea and was diagnosed with acute heart failure. The patient had no recurrence of atrial fibrillation, so the administration of bepridil was stopped. His dyspnea was eased using standard therapy for heart failure and he was discharged from our hospital. In March 2011, he had a recurrence of atrial fibrillation and was readmitted to our hospital. The administration of bepridil was initiated to defibrillate the atrial fibrillation. Although bepridil stopped the atrial fibrillation by the third day, he presented with dyspnea and fever on the fourth day. A chest radiograph showed bilateral interstitial patterns that radiated from the pulmonary hilum. He was treated for acute heart failure and bacterial pneumonia, but this was ineffective. We suspected that the interstitial pneumonia was caused by bepridil. Corticosteroid therapy dramatically improved his symptoms. This was a rare case of acute drug‐induced interstitial pneumonia caused by repeated exposure to bepridil.