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Rationale: Myocardial vulnerability to ischemia/reperfusion (I/R) injury is strictly regulated by energy substrate metabolism. Branched chain amino acids (BCAA), consisting of valine, leucine and isoleucine, are a group of essential amino acids that are highly oxidized in the heart. Elevated levels of BCAA have been implicated in the development of cardiovascular diseases; however, the role of BCAA in I/R process is not fully understood. The present study aims to determine how BCAA influence myocardial energy substrate metabolism and to further clarify the pathophysiological significance during cardiac I/R injury. Methods: Parameters of glucose and fatty acid metabolism were measured by seahorse metabolic flux analyzer in adult mouse cardiac myocytes with or without BCAA incubation. Chronic accumulation of BCAA was induced in mice receiving oral BCAA administration. A genetic mouse model with defective BCAA catabolism was also utilized. Mice were subjected to MI/R and the injury was assessed extensively at the whole-heart, cardiomyocyte, and molecular levels. Results: We confirmed that chronic accumulation of BCAA enhanced glycolysis and fatty acid oxidation (FAO) but suppressed glucose oxidation in adult mouse ventricular cardiomyocytes. Oral gavage of BCAA enhanced FAO in cardiac tissues, exacerbated lipid peroxidation toxicity and worsened myocardial vulnerability to I/R injury. Etomoxir, a specific inhibitor of FAO, rescued the deleterious effects of BCAA on I/R injury. Mechanistically, valine, leucine and their corresponding branched chain α-keto acid (BCKA) derivatives, but not isoleucine and its BCKA derivative, transcriptionally upregulated peroxisome proliferation-activated receptor alpha (PPAR-α). BCAA/BCKA induced PPAR-α upregulation through the general control nonderepresible-2 (GCN2)/ activating transcription factor-6 (ATF6) pathway. Finally, in a genetic mouse model with BCAA catabolic defects, chronic accumulation of BCAA increased FAO in myocardial tissues and sensitized the heart to I/R injury, which could be reversed by adenovirus-mediated PPAR-α silencing. Conclusions: We identify BCAA as an important nutrition regulator of myocardial fatty acid metabolism through transcriptional upregulation of PPAR-α. Chronic accumulation of BCAA, caused by either dietary or genetic factors, renders the heart vulnerable to I/R injury via exacerbating lipid peroxidation toxicity. These data support the notion that BCAA lowering methods might be potentially effective cardioprotective strategies, especially among patients with diseases characterized by elevated levels of BCAA, such as obesity and diabetes.

Summary Aims: Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. Methods: We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade

Summary Aims: Angiotensin receptor blockers (ARBs) exert favorable effects on the vascular system, which are not directly related to hypertension lowering function. The no-reflow phenomenon determines the prognosis in patients after acute myocardial infarction (AMI). Early ARB treatment has many beneficial effects on the prognosis after AMI. In this study, we tested the hypothesis that ARB treatment before admission would have beneficial effects on the development of the no-reflow phenomenon after infarction. Methods: We investigated 276 consecutive patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) flow grade

Objectives To evaluate the initial and long-term clinical outcomes of patients with unprotected left main (ULM) stenosis undergoing percutaneous coronary intervention (PCI) with drug eluting stents (DES) at XiJing Hospital Centre in real world patient population. Methods After excluding acute ST-segment elevation myocardial infarction and bailout stenting, 798 patients treated for ULM disease with DES from January 2003 to December 2011 at XiJing Hospital were enrolled. The clinical outcomes of ULM treated with DES were evaluated by major adverse cardiac events (MACE) and stent thrombosis (ST) during in-hospital period and after long-term follow-up respectively. MACE was defined as cardiac death, non-fatal myocardial infarction (MI) and clinically driven target lesion revascularisation (TLR). ST was evaluated in accordance with the Academic Research Consortium (ARC) definitions. Results The mean age of study population was 62±10 years, 649 (81%) patients were male, 199 (25%) patients were diabetic, and the mean ejection fraction was 54%±11%. 71 (9%) patients had an ostial and 27 (3%) had a shaft lesion (nondistal subgroup), 700 (88%) patients had a bifurcation lesion (distal subgroup). In distal subgroup, 416 (59%) patients were treated with 1 stent (1-stent subgroup) and 284 (41%) were treated with 2 stent (2-stent subgroup). Among 2-stent subgroup, 74 (11%) patients were treated with crush (crush subgroup), 86 (12%) were treated with culotte (culotte subgroup), 43 (6%) were treated with kissing (kissing subgroup) and 81 (12%) were treated with T stenting (T subgroup). Angiographic and clinical successes of PCI were obtained in all patients. During the in-hospital period, MACE occurred in 7 (0.8%) patients including 5 (0.6%) cardiac deaths and 2 (0.2%) MIs. one patient had definite (died) and four patients had probable stent thrombosis (1 had a MI and 3 died). During the long-term follow-up duration of 27±20 months, MACE occurred in 176 (22%) patients including 25 (3%) cardiac deaths, 16 (2%) MIs and 135 (17%) TLRs. six patients had probable (died) and 12 patients had possible stent thrombosis (2 had MI and 10 died). There were no significant differences in in-hospital MACE rates between nondistal and distal subgroup, between 1-stent and 2-stent subgroup and among different 2-stent technique subgroups. After long-term follow-up, the TLR rate was significantly higher in distal subgroup than in nondistal subgroup (18% vs 9%, p Conclusions Treatment of ULM with DES is feasible and safe with good in-hospital and acceptable long-term clinical results. Compared with ostial and shaft lesion, distal bifurcation lesion is associated with a worse long-term TLR rate. 1-stent technique had a better long-term MACE rate than 2-stent technique when distal bifurcation lesion was treated, whereas different 2-stent techniques had similar clinical outcomes.