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Biomedical subjects

Hiroyuki Yaoita

Publications and source records attributed to Hiroyuki Yaoita.

At least 19 recordsLinked to original sources
PubMed2006

Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol.

OBJECTIVE: Infarct size (IS) reduction by ischemic preconditioning (IPC) has been assessed in the heart in which coronary stenosis (CS)-induced chronic ischemia was not present. The aim of this study is to assess whether and how IS reduction by IPC is modified in the heart in which CS has occurred, and how further therapeutics, if any, modify it. METHODS: We assessed the IS produced by a 30-minute acute coronary occlusion and a 24-hour reperfusion (COR) in rat hearts in which CS had developed for 1-12 weeks. Modifications of IS by IPC and the mitochondrial KATP channel (mitoKATP) opener and blocker, and the effects of daily beta-blocker treatment with carvedilol on them, were also assessed. Myocardial protein kinase C (PKC)-epsilon activities in the risk areas were measured by Western blotting. RESULTS: One to 4 weeks after CS induction, myocardial PKC-epsilon was activated in the risk area of CS even without IPC, but such CS-induced PKC activation as well as that by IPC was attenuated 8-12 weeks after CS. The IS reductions by the mitoKATP opener as well as by IPC were attenuated 8-12 and 4-12 weeks after CS, respectively. Daily carvedilol treatment after inducing CS restored the malfunctioning PKC-mitoKATP signal cascade and the attenuated IPC and mitoKATP effect on IS. CONCLUSION: CS activates the PKC-mitoKATP signal cascade, mimicking the IPC effect, whereas this cardioprotective effect is attenuated late after CS via their downregulation. Restoration of these changes may be a novel mechanism for cardioprotection by carvedilol in the CS-induced ischemic heart.

Adrenergic beta-Antagonists↗
PubMed2006

Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats.

BACKGROUND: It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. METHODS AND RESULTS: Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. CONCLUSIONS: Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to beta adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments.

Actin Cytoskeleton↗
PubMed2006

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis.

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.

Aged↗
PubMed2006

[Heart failure in the elderly].

Heart failure (HF) is a major disease of the elderly. Since their symptoms of HF are generally light, on admission of the hospitals HF is sometimes in an advanced stage. Therefore, preventive medicine for those with the risk factors of HF is needed as a future strategy of cardiac gerontology. The routine assessment of the HF severity may be performed noninvasively by Nohria's profiles rather than other invasive methods. HF is worsened by the interaction with the co-morbidity factors, such as renal dysfunction and anemia. The interaction between HF and kidney disease (and anemia) is called 'cardiorenal (anemia) syndrome.' Recurrent hospitalization due to HF is common, and the period of hospitalization tends to be long in this syndrome. One of the hopeful therapeutic agents is carperitide, a recombinant human atrial natriuretic peptide. In cardiorenal syndrome, much lower initial doses of carperitide, such as 0.0125 microg/kg/min is recommended for treatment of HF in order to avoid possible worsening of renal dysfunction. In cardiorenal anemia syndrome, supplement of iron, careful blood transfusion in severe cases, administration of recombinant human erythropoietin, should be performed if indicated. However, the possibility of anemia unrelated to HF, such as due to gastrointestinal carcinoma, is also considered in the elderly. In such cases, finding a decrease of serum ferritin preceding that of hemoglobin may contribute to a differential diagnosis of anemia in elderly HF patients. Thus, the therapies considering several features of HF in elderly will contribute to improving quality of life and outcome.

Aged↗
PubMed2005

Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary stenosis and coronary occlusion.

OBJECTIVES: The aim of the study was to assess whether and how the high-cholesterol diet (HCD)-related worsening of heart failure differs between coronary stenosis (CS)-induced myocardial ischemia and coronary occlusion-induced myocardial infarction (MI). BACKGROUND: An HCD, a risk factor for coronary artery disease, also worsens ischemic heart failure. Although accelerated coronary plaque formation may be a cause of this, other mechanism(s), such as its effects through the coronary microcirculation, remain to be clarified. METHODS: In rats fed a normal chow diet or HCD, CS or MI was created surgically, and we assessed left ventricular (LV) function by echocardiography and myocardial inflammation by histopathology. In the CS groups, CS severity by histopathology, myocardial perfusion by microspheres, myocardial protein kinase C (PKC) translocation by Western blotting, and myocardial endothelial nitric oxide (NO) function were also investigated by the in vitro myocardial oxygen consumption method. RESULTS: Coronary stenosis impaired myocardial endothelial NO function and reduced coronary flow reserve, evoking myocardial ischemia, as shown by PKC- activation, myocardial inflammation, fibrosis, cardiac dysfunction, and remodeling. By itself, HCD greatly augmented such CS-induced myocardial abnormalities without modulating the CS severity. Such detrimental effects of HCD were ameliorated by supplying a cofactor of endothelial NO synthase-tetrahydrobiopterin. In contrast, MI-induced heart failure was not aggravated by HCD. CONCLUSIONS: The CS-induced ischemic myocardium seems to be more susceptible to the pro-inflammatory effect of HCD than infarcted myocardium, leading to aggravation of LV dysfunction and remodeling via modification of the coronary circulation downstream of the epicardial CS site, partly through impairment of endothelial NO.

Animals↗
PubMed2005

Different therapeutic responses to treadmill exercise of heart failure due to ischemia and infarction in rats.

OBJECTIVE: The effects of exercise, a therapeutic tool in ischemic heart disease (IHD), may differ in ischemic and infarcted hearts. METHODS AND RESULTS: To assess this, we created coronary stenosis (CS), which reduced coronary flow reserve (CFR), or coronary occlusion to induce myocardial infarction (MI) in rats, and subjected them to treadmill exercise for either 5 (5-min Ex) or 15 min/day (15-min Ex) for 12 weeks. Left ventricular (LV) diameters were increased and ejection fractions decreased by echocardiography, and myocardial nitric oxide (NO) activity, measured by the in vitro MVO2 method, was reduced in both CS and MI rats compared with the sham. In CS rats, myocardial wall thickening fractions were not affected at 5 min of exercise, whereas they were reduced at 15 min of exercise, suggesting exercise-induced ischemia. Despite no changes in CS severity, the 5-min Ex increased CFR, ameliorated myocardial NO activity, attenuated left ventricular (LV) dysfunction and remodeling, reduced serum brain natriuretic peptide (BNP) levels, and improved survival, whereas the 15-min Ex aggravated LV dysfunction and remodeling. In contrast, neither of the exercise protocols improved these parameters in MI rats. CONCLUSIONS: Therapeutic responses to exercise differed in ischemic and infarcted hearts, partly via circulatory modulation downstream of the epicardial CS in relation to exercise-induced ischemia. When employing exercise for IHD, the causes of IHD, as well as the exercise protocols, need to be considered to achieve optimal effects.

Animals↗
PubMed2005

Alterations of alpha-adrenergic modulations of coronary microvascular tone in dogs with heart failure.

BACKGROUND: It remains unclear whether coronary microvascular response to alpha-adrenergic activation alters in chronic heart failure (CHF). METHODS AND RESULTS: We investigated the alpha-adrenergic receptor-mediated effects on coronary pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure model. The dogs studied were male (29 of 31) and the drugs were given intracoronary. The slope of CPFR during long diastole was evaluated as an index of coronary vascular resistance, during alpha1- or alpha2-adrenergic stimulation or inhibition under anesthesia in the baseline and failing state after 3 weeks of rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in the failing state from the baseline state. Neither alpha1 nor alpha2 stimulation changed the slope of CPFR in the baseline state. However, in the failing state, alpha1 stimulation decreased the slope of CPFR by 23 +/- 5% (P < .05), whereas alpha2 stimulation increased it by 73 +/- 10% (P < .05), which was nearly abolished by pretreatment with NG-nitro-L-arginine methyl ester. CONCLUSION: Alpha2-mediated vasodilatory action, presumably via endothelium-derived nitric oxide release, would be enhanced in the coronary microvascular bed, which may antagonize enhanced alpha1-induced vasoconstriction in CHF.

Adrenergic alpha-Agonists↗
PubMed2005

A case of recurrent chest pain with reversible left ventricular dysfunction and ST segment elevation on electrocardiogram.

There is a syndrome consisting of acute infarction-like symptoms and ECG findings, and transient left ventricular apical ballooning without epicardial coronary artery obstruction. A 67-year-old female admitted to our hospital because of severe anterior chest pain was diagnosed as having this syndrome. Since stenotic, spastic, or occlusive sites were not found in epicardial coronary arteries by emergency cardiac catheterization, we speculated coronary microvasculature involvement in the pathophysiology of the event. Four weeks later in a drug-free condition, there was no significant epicardial coronary vasospasm by intracoronary acetylcholine administration (IC-ACh). The average peak flow velocity (APFV) of the left coronary artery (LCA) was measured using the Doppler flow wire method. Under maximal dilatation of the epicardial LCA by intracoronary nitroglycerin administration, IC-ACh was again performed taking into consideration that the change in APFV in response to IC-ACh reflects a coronary microvascular response to it. In the nonischemic control subjects, basal APFV increased to 296+/-29% (n = 24) of the basal value after IC-ACh. In this patient, although IC-ACh did not cause vasospasm in epicardial LCA, APFV was decreased to 54% of its basal value. After administration of a Ca antagonist and KATP opener, she had no chest symptoms and was discharged from the hospital. In 2003, she forgot to take her medication for 3 days and then experienced a sudden recurrence of the same type of attack. She started her medication again and her symptoms disappeared. Three weeks later, she underwent an assessment of the coronary microvascular response to ACh with medicine. Her APFV after ACh increased to 177% of the basal value.

Acetylcholine↗
PubMed2005

Noninvasive myocardial endothelial intervention in the persistence of coronary stenosis: a concept of myocardial endothelial nitric oxide activator through heart failure research on clinical demand.

Protection of ischemic myocardium has been attempted by a variety of pharmaceutical and non-pharmaceutical methods. When the coronary intervention is not indicated by some reasons in patients with ischemic heart failure, medical treatments are expected to offer cardioprotection against the persistence of stenotic/occlusive lesions of the epicardial coronary artery. The pharmaceuticals such as the angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta blocker, Ca antagonist, ATP-sensitive K channel opener and statin, or non-pharmaceutical approaches such as physical exercise, cardiac resynchronization, ventricular assist devices, and preconditioning upon ischemic insults appear to improve myocardial endothelial nitric oxide (NO) synthase (eNOS) function. Such eNOS activation contributes to amelioration of the cardiac dysfunction and remodeling induced by myocardial ischemia. Therefore, based on clinical evidence and basic research on clinical demand, we postulate a concept of 'myocardial endothelial NO activator' from the standpoint of mechanistic insights beyond the class-effects of each pharmaceutical category and each non-pharmaceutical intervention. In addition to such continuous eNOS activation for treating chronic ischemic heart failure, rapid eNOS activation in the setting of acute ischemic events upon chronic myocardial ischemia by new strategies such as postconditioning seems to be also essential for developing further effective anti-heart-failure therapies.

Cardiovascular Agents↗
PubMed2005

Low serum ferritin levels as a clue to colonic cancer detection in two patients with coronary artery disease: a case report.

We diagnosed colonic cancer using low serum ferritin levels as a clue in two patients with cardiac or cardiopulmonary disease. In the course of the follow-up, the serum ferritin levels decreased to less than 18 ng/mL without significant appearance of iron-deficiency anemia. One patient showed positive immunological fecal occult blood test results whereas the other not. Both patients rejected further colonoscopy because of their concern for stress in relation to their cardiac or cardiopulmonary diseases, but instead agreed to positron emission computed tomography (PET) using a F-18 deoxyglucose at their own expense. In both patients, PET documented abnormal tracer accumulation in the colon. From the results of PET imaging, they eventually agreed to colonoscopy. A colonic adenocarcinoma was detected at the site of the positive PET finding in each patient. Both patients underwent curative resection of the cancer. The detection of the levels of serum ferritin may be available for the screening colonic cancer in patients declining colonoscopic examination.

Adenocarcinoma↗
PubMed2005

Scintigraphic assessment of the effects of bone marrow-derived mononuclear cell transplantation combined with off-pump coronary artery bypass surgery in patients with ischemic heart disease.

UNLABELLED: Myocardial SPECT may be useful for assessment of the therapeutic effects and the mechanisms of cardiac regeneration medicine. We aimed to assess first the feasibility and the short-term safety of autologous bone marrow-derived mononuclear cell transplantation (BMCT) into the ischemic myocardium in patients who undergo off-pump coronary artery bypass surgery (OPCAB). In addition, we aimed to assess our hypothesis that the BMCT may help ameliorate myocardial perfusion in patients with ischemic heart disease (IHD) using myocardial perfusion scintigraphy. METHODS: We performed BMCT in 10 patients with IHD during OPCAB. Cells for BMCT were collected by intraoperative bone marrow aspiration or by preoperative cellular apheresis after pretreatment with granulocyte colony-stimulating factor. After OPCAB was performed in all graftable ischemic areas, a total of 3.4 +/- 1.2 x 10(9) mononuclear cells, including 5.2 +/- 1.6 x 10(6) CD34-positive (CD34(+)) cells, were injected into ungraftable ischemic myocardial areas. Dipyridamole-stress and resting (99m)Tc myocardial SPECT was performed before and 1 mo after the procedures. RESULTS: BMCT was performed safely in all patients. Compared with before treatment, myocardial (99m)Tc tracer uptake on the dipyridamole-stress image increased similarly in BMCT- and OPCAB-treated areas, whereas tracer accumulation at rest did not change in all myocardial areas. The improvement of myocardial perfusion was not correlated with the total number of mononuclear cells transplanted. However, it was positively correlated with the number of transplanted CD34(+) cells: (99m)Tc tracer uptake after/before BMCT (ratio) = 1.091 x (CD34(+) cell number [x10(6)])(0.074) (r(2) = 0.48, P < 0.05), although new development of coronary vessels was not documented cineangiographically. Myocardial histopathology in 2 of 3 autopsy cases revealed coronary angiogenesis in the areas corresponding to the sites of BMCT. CONCLUSION: The present study demonstrates the feasibility of BMCT combined with OPCAB. This therapy improves myocardial perfusion possibly via CD34-related development of coronary microvessels.

Adult↗
PubMed2004

Effects of antioxidants on coronary microvascular spasm induced by epicardial coronary artery endothelial injury in pigs.

OBJECTIVES: The effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury. METHODS: Balloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n = 12) and in pigs treated with oral ASC (3 g/day) (ASC group, n = 12) and ASC (3 g/day) plus GSH (1 g/day) (ASC + GSH group, n = 12). RESULTS: In the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18 +/- 17% to a decrease of 100% (that is, zero flow, 8 weeks, P < 0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC + GSH group, blood flow response to ACh was altered to a decrease of 45 +/- 17% (8 weeks, P < 0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4 +/- 12.5 signal intensities, P < 0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56 +/- 17%, P < 0.01 compared with the endothelial injury group). CONCLUSIONS: Chronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.

6-Ketoprostaglandin F1 alpha↗
PubMed2004

Altered effects of angiotensin ii type 1 and type 2 receptor blockers on cardiac norepinephrine release and inotropic responses during cardiac sympathetic nerve stimulation in aorto-caval shunt rats.

BACKGROUND: Inhibition of the sympathetic nervous and renin - angiotensin systems has become an important strategy in the treatment of chronic heart failure. However, direct evidence of how inhibition of the renin - angiotensin system alters sympathetic activity in a diseased heart is lacking. METHODS AND RESULTS: Four weeks after abdominal aorto-caval (AV) shunting or sham operation in rats, the hearts were retrogradely perfused in vivo and the left ventricles contracted isovolumetrically at 300 beats/min. Sympathetic nerve stimulation (SNS) was performed in the baseline state and repeated with an infusion of the angiotensin II (A-II) type 1 receptor (AT(1)-R) blocker, losartan, the A-II type 2 receptor (AT(2)-R) blocker, PD123319, or A-II. Norepinephrine (NE) overflow and left ventricular (LV) inotropic responses during baseline SNS were lower in the AV shunt rats. Losartan did not change the NE overflow or the LV inotropic responses to SNS in the sham rats, but did increase them in the AV shunt rats. PD123319 changed neither parameter in the sham rats, but decreased both in the AV shunt rats. A-II enhanced the NE overflow but attenuated the LV inotropic responses to SNS in the sham rats, but attenuated both in the AV shunt rats. CONCLUSIONS: The effects of A-II via the AT(1)-R and AT(2)-R on the adrenergic drive in the heart were altered significantly in volume overload hypertrophy induced by AV shunting.

Angiotensin II↗
PubMed2004

Transient improvement of left ventricular function after peripheral blood stem cell transplantation in a patient with myelodysplastic syndrome and dilated cardiomyopathy.

A patient who had myelodysplastic syndrome (MDS) and dilated cardiomyopathy (DCM) had a transient improvement of cardiac function after peripheral blood stem cell transplantation (PBSCT). When he was admitted to hospital for PBSCT, a chest X ray showed cardiomegaly, and Tc-99m quantitative gated single photon emission computed tomography (QGS) showed increases in left ventricular (LV) volumes and a decrease in LV ejection fraction (LVEF). A coronary angiogram showed no evidence of coronary artery disease. Left ventriculography showed similar findings as QGS, and the findings from a myocardial biopsy were compatible with DCM. Three months after a successful allo-PBSCT with his brother as the donor, the cardiomegaly had been attenuated, the LV volumes decreased and LVEF increased on the QGS images. However, 10 months later, his cardiac function had deteriorated. The changes in cardiac function did not correlate with the hematological changes, such as the hemoglobin level.

Adult↗
PubMed2003

Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker.

It is not known how the angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) attenuate heart failure (HF) in viable ischemic hearts. To assess HF in a rat coronary stenosis (CS) model, we administered vehicle and quinapril or candesartan (or both) orally for 12 wk. Compared with the sham group, the vehicle group showed impaired myocardial perfusion, impaired coronary endothelial nitric oxide (NO) function in vitro, exhausted myocardial mitochondrial respiration, larger left ventricular (LV) dimensions and lower ejection fraction, lower LV rate of pressure development over time (dP/dt), lower slopes of LV end-systolic pressure-dimension relations (ESPDRs), and increased myocardial fibrosis. Treatment with quinapril or candesartan ameliorated these parameters without modifying the epicardial CS severity. Moreover, their combination maintained similar myocardial perfusion, despite a trend toward lower blood pressure, and showed distinctive neurohumoral modulation, normalized mitochondrial respiration, and increased ESPDR slopes. Thus improved myocardial blood flow and coronary flow reserve by quinapril or candesartan are the key to alleviate CS-induced HF, and their combination may have a therapeutic significance partly through ameliorated mitochondrial respiration and improved LV systolic function.

Anesthesia↗