Objective: The aim of this study was to investigate how the enhanced nitric oxide (NO) production by intra-coronary infusion of L-arginine acts in myocardial stunning in dogs by focusing on the involvement of peroxynitrite, a reaction product of NO and superoxide G anion. Methods and Results: Dogs were divided into six groups; a control non-treated group (CON, n59), and, and SOD alone (SOD, n56) treated groups. L-NAME, or L-or D-arginine was continuously infused into the left anterior descending coronary artery (LAD) starting just prior to reperfusion, whereas SOD was intravenously injected before occlusion. During 120 min of reperfusion after 15 min occlusion of LAD, myocardial contractile function in the ischemic region gradually recovered and reached approximately 70% of the preischemic level in CON, D-ARG and SOD, but it remained dyskinetic (246%) in L-ARG. On the other hand, it was improved in L-NAME (90%). Tissue malondialdehyde was elevated ( p,0.005) after reperfusion, and myocardial NO metabolites measured by an intratissue-microdialyzer increased (approximately 150%, p,0.05) in the ischemic region during reperfusion in L-ARG but not in the CON, L-NAME, D-ARG or SOD groups. In the L-ARG1SOD group, L-arginine-induced contractile dysfunction and elevation of malondialdehyde were prevented, but the increase in NO metabolites remained. These results suggest that L-arginine aggravated myocardial stunning through oxidative stress and the cytotoxicity was caused by NO derivatives but not by NO itself. The formation of nitrotyrosine, a footprint of peroxynitrite, was immunohistochemically confirmed in the ischemic region of L-ARG. Conclusions: Our results demonstrate for the first time in vivo that NO has a detrimental role in myocardial stunning through the production of peroxynitrite.

Atherosclerosis is a dise ase characterized by inflammation in the arterial wall. Atherogenesis is dependent on the innate immune response involving activation of Toll-like receptors (TLRs) and the expression of inflammatory proteins, those may lead to acute coronary syndrome (ACS). We investigated the expression level of TLR-4 in ACS, as compared with TLR-2 and patients with stable angina. Fifty-eight consecutive patients who underwent primary percutaneous coronary intervention (PCI, n = 29) because of ACS and elective PCI (n = 29) because of stable angina using a filter-device distal protection device system were prospectively analyzed. mRNA levels of TLR-2 and TLR-4 in debris containing various inflammatory tissues entrapped in the filter device were altogether analyzed using real-time PCR. There were no significant differences in age, sex distribution, between stable angina and ACS groups. TLR-4 expression levels were higher in patients with ACS than in patients with stable angina. TLR-4 might play a more important role than TLR-2 in atherogenesis, especially in ACS.

Background and objective: To clarify the clinical features of coronary artery spasm (CAS) with no significant coronary stenosis in patients with suspected acute coronary syndrome (ACS) in real practice. Methods: This is a retrospective observational study of patients with suspected ACS (n = 645) based on symptoms, electrocardiographic changes, and/or positive cardiac biomarkers and vasospastic angina (VSA, n = 90). ACS patients were divided into two groups: (1) organic ACS (n = 515), culprit lesion ≥75% coronary stenosis with/without thrombosis; (2) spastic ACS (n = 70), coronary stenosis <75%, either with positive acetylcholine (ACh) test (n = 51) or without ACh test but verified spontaneous spasm (n = 19). The study compared clinical characteristics among organic ACS, spastic ACS, and VSA. Results: One hundred and thirty suspected ACS patients had a coronary organic stenosis <75% (130/645, 20%). Seventy of those patients (70/130, 54%) were confirmed to have CAS, and these accounted for 11% of all ACS patients (70/645). The rate of cigarette smoking was highest in the spastic ACS. No spastic ACS patients died during their hospital stay or after discharge, whereas acute myocardial infarction occurred in 19%, aborted sudden cardiac death in 6%, multivessel spasm was provoked in 78%, and diffuse spasm was more frequently provoked than in the VSA group (82% vs. 62%). Conclusions: CAS is not a rare cause of ACS. Although the prognosis of spastic ACS is good, there are occasional critical cases. An initial differential diagnosis including an ACh test is thus important to decide the treatment strategy of ACS.

Summary:We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal antiinflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.

Fulminant type 1 diabetes is recognized as a novel subtype of type 1 diabetes, which is a non-autoimmune disorder characterized by a sudden onset, several days duration of diabetic symptoms, the absence of islet-related autoantibodies, exhausted beta-cell function, and elevated pancreatic enzymes in the serum [1,2]. Although, the precise mechanisms by which beta-cell destruction occurs in fulminant type 1 diabetes are still unknown, an abrupt onset accompanied by flu-like symptoms, infiltration of lymphocytes and macrophages to pancreata and the presence of enterovirus-capsid protein in affected pancreata [3] abstract. This report presents the case of a 47-year-old female patient with fulminant type 1 diabetes mellitus and myocarditis. Following a high fever, nausea, vomiting and diarrhea, diabetic ketoacidosis occurred and she was transferred to the hospital. The plasma glucose level was 63.6mmol/L and HbA1c was 7.0%. C-peptide was undetectable in her plasma. Blood gas analysis showed a pH of 6.99. Antibodies to glutamic acid decarboxylase nor insulinoma associated antigen-2 were not detected. She was diagnosed to have fulminant type 1 diabetes mellitus. Her electrocardiogram showed diffuse ST-segment elevations on the second day of admission, along with a positive troponin test. However coronary angiography revealed neither occlusion nor stenosis of the cardiac arteries. An endomyocardial biopsy revealed hypertrophic cardiomyocytes with a disarrangement of myofibers and the focal accumulation of mononuclear cells in the stroma, thus suggesting myocarditis or mild myocarditic change. Viruses are an important cause of myocarditis and the preceding flulike symptoms indicate the association of viral infection with myocarditis in this case. The mechanisms by which fulminant type 1 diabetes mellitus occurs is still uncertain, but the presence of islet injury accompanied by myocardial inflammation in the current case suggested that a viral infection accounted for the onset of this type of diabetes.