Early restoration of blood flow to the ischemic myocardium not only saves myocardium but also induces reperfusion injury. While no specific therapy to reduce reperfusion injury has yet been established, recent laboratory studies have shown that G protein-coupled receptor (GPCR) agonists, insulin, and postconditioning can effectively prevent reperfusion injury in various experimental settings and animal species. The potential mechanisms underlying the cardioprotection initiated by these interventions may include activation of the reperfusion injury salvage kinase (RISK) pathway, inactivation of glycogen synthase kinase 3beta (GSK-3beta), and modulation of mitochondrial permeability transition pore (mPTP) opening. These encouraging laboratory findings may help us develop successful clinical strategies to salvage reperfused myocardium in patients with acute myocardial infarction.
Glycogen Synthase Kinase 3 ; metabolism ; Humans ; Mitochondrial Membrane Transport Proteins ; physiology ; Myocardial Infarction ; complications ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 micrometer and 4.0+/-1.7% in EGCG 10 micrometer, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 micrometer GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 micrometer HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.
Animals ; Anti-Arrhythmia Agents/pharmacology ; Antioxidants/*pharmacology ; Catechin/*analogs & derivatives/pharmacology ; Decanoic Acids/pharmacology ; Glyburide/pharmacology ; Heart/*drug effects/physiology/physiopathology ; Hemodynamics ; Humans ; Hydroxy Acids/pharmacology ; KATP Channels/*metabolism ; Male ; Mitochondria, Heart/*drug effects/metabolism ; Myocardial Infarction/*pathology ; Myocardial Ischemia/*pathology ; Potassium Channel Blockers/pharmacology ; Rats ; Rats, Wistar

BACKGROUNDLocally advanced non-small cell lung cancer with pulmonary artery invasion is very difficult to treat surgically. The aim of this study is to evaluate the feasibility and safety of pretreatment blocking of intrapericardial pulmonary artery in operation of lung cancer with pulmonary artery invasion.

METHODSPericardium was dissected and pretreatment blocking of intrapericardial pulmonary artery was used in patients, who were diagnosed as lung cancer with pulmonary artery invasion through either preoperative radiological examination or exploratory thoracotomy.

RESULTSTwenty-eight patients were enrolled, and eighteen of them received blocking of pulmonary artery during operation. All the tumors were resected completely. There was no heavy bleeding or pneumonectomy.

CONCLUSIONSThe use of pretreatment blocking of intrapericardial pulmonary artery can improve the safety of operation, achieve complete resection and decrease the application of pneumonectomy for lung cancer with pulmonary artery invasion.

BACKGROUND AND OBJECTIVES: We investigated whether 1 hour reperfusion is enough to assess cardiodynamics and infarct size in both regional ischemia (RI) and global ischemia (GI) in isolated rat heart models. MATERIALS AND METHODS: Hearts were randomly assigned to one of the following groups (each n=14): 1) Sham hearts for 1 hour; 2) Sham hearts for 2 hours; 3) 30 minutes RI followed by 1 hour reperfusion; 4) 30 minutes of RI followed by 2 hours reperfusion; 5) 30 minutes GI followed by 1 hour reperfusion; and 6) 30 minutes GI followed by 2 hours reperfusion. RESULTS: There were no significant differences in infarct size between 1 hour and 2 hours reperfusion in both RI and GI. Left ventricular developed pressure was significantly decreased at both 1 hour and 2 hours reperfusion in groups of RI and GI compared to baseline (p<0.01). Rate-pressure product and +dP/dtmax also significantly decreased compared to baseline level at both 1 hour and 2 hours reperfusion in groups of RI and GI (p<0.05). CONCLUSION: There was no significant difference in infarct size between 1 hour and 2 hours reperfusion in groups of RI and GI. Cardiodynamic variables measured at 1 hour and 2 hours reperfusion significantly decreased compared to baseline level. Our data suggests that reperfusion of 1 hour is sufficient to assess cardiodynamics in both regional and global ischemic isolated hearts model.
Animals ; Heart ; Ischemia ; Myocardial Infarction ; Myocardial Ischemia ; Myocardial Reperfusion ; Rats ; Reperfusion ; Salicylamides

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.
Central Nervous System ; Heart ; Immune System ; Ion Channels ; Mammary Glands, Human ; Metabolism ; Metallothionein ; Oxidation-Reduction ; Pancreas ; Prostate ; Protein Conformation ; Signal Transduction ; Zinc*

BACKGROUND AND OBJECTIVES: Information about the role of the stromal cell-derived factor-1α (SDF-1α)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the SDF-1α/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC. METHODS: Isolated rat hearts were divided into four groups. The control group was subjected to 30-min of regional ischemia and 2-hour of reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4 antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC group, n=11) and control group (AMD group, n=9). Hemodynamic changes with electrocardiography were monitored and infarct size was measured. The SDF-1α, lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate were measured. We also analyzed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation state expression. RESULTS: IPOC significantly reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC. IPOC significantly decreased LDH and CK, but these effects were reversed by AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects were blocked by AMD3100. CONCLUSION: Based on the results of this study, SDF-1α/CXCR4 signaling may be involved in IPOC cardioprotection and this signaling pathway couples to the ERK1/2 and Akt pathways.
Animals ; Creatine Kinase ; Electrocardiography ; Family Characteristics ; Heart* ; Hemodynamics ; Ischemia ; Ischemic Postconditioning* ; L-Lactate Dehydrogenase ; Phosphorylation ; Phosphotransferases ; Rats* ; Receptors, CXCR4 ; Reperfusion ; Reperfusion Injury