Hospital volume and often also operator volume have documented impacts on the quality of care for aortic and aortocoronary bypass surgery, for percutaneous angioplasty and for radiofrequency ablation for arrhythmias, whereas data are less consistent for treatment of acute myocardial infarction. A review of this research is given. In the Nordic countries hospitals are small, and often the plateau of the learning curve cannot be reached. To discourage low-volume centers from embarking upon too complicated interventional or surgical procedures, the author suggests that a minimal number should be set for certain major procedures, both for hospitals and for physicians. 相似文献
Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl‐2 expression and downregulating Bax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91phox expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor‐dependent manner. 相似文献
Summary. Since calcium overload and increased in T-type calcium channel activity have been observed in the cardiomyopathic (CM) hamster, we hypothesized that mibefradil (Ro 40-5967), a new T- and L-type calcium channel blocker, may exert significant cardioprotection in the early phase of the disease. Young (30-day-old) CM hamsters of the UM-X7.1 subline were treated with mibefradil or verapamil for 4 to 6 weeks. Mibefradil doses were in the range of 0.5 to 8 mg/kg/day while verapamil was given at a dose of 5–10 mg/kg/day, both drugs being injected twice daily (sc and ip alternatively). At the end of the treatment period, myocardial and skeletal muscle (tongue) were harvested and processed for assessment of necrotic changes and calcification. In hearts from control CM hamsters, numerous necrotic and calcified foci were observed. These myocardial necrosis markers were not attenuated by mibefradil in the dose range studied whereas verapamil significantly reduced their severity. The dystrophic process in skeletal muscle (tongue) was not inhibited by mibefradil or verapamil. These results suggest that mechanisms other than inhibition of T- and L-type calcium channels are related to the cardioprotection observed in the presence of verapamil. A specific action on the sarcoplasmic reticulum (ryanodine-sensitive calcium channel) or the mitochondria may explain the efficacy of phenylalkylamines (verapamil) in this condition. 相似文献
Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynaud's phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases. 相似文献
Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.
Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.
Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients. 相似文献
Heat stress is known to confer protection against ischemia, but the mechanisms involved are yet to be elucidated. Opening
of ATP-sensitive potassium (KATP) channels has been demonstrated to be involved in other endogenous forms of cardioprotection, in particular“classic” ischemic
preconditioning and delayed preconditioning following treatment with the endotoxin derivative, monophosphoryl lipid A. We
therefore speculated that there may be a role for KATPchannels in delayed heat stress–induced cardioprotection. This hypothesis was investigated in an in vivo rabbit model of acute
myocardial infarction using two structurally dissimilar KATP channel blockers, glibenclamide and sodium 5-hydroxydecanoate. Sodium pentobarbitone–anesthetized rabbits were subjected
to either transient heat stress at 42 ± 0.2°C for 15 minutes or sham anesthesia. Twenty-four hours later, animals were reanesthetized
(“Hypnorm” and sodium pentobarbitone) and a midline sternotomy and pericardiotomy were performed. An anterolateral branch
of the circumflex coronary artery was occluded for 30 minutes and reperfused for 2 hours. The infarct-to-risk ratio was significantly
limited in vehicle-treated rabbits from 41.3 ± 4.0% in controls (n = 10) to 24.1 ± 5.0% (n = 9; P = 0.014 by one-factor ANOVA)
in heat-stressed hearts. This limitation in infarct size was abolished by 0.3 mg/kg iv glibenclamide or 5 mg/kg iv5-hydroxydecanoate
when administered 10 minutes prior to coronary occlusion (45.2 ± 6.4%; n = 9 and 41.5 ± 5.0%; n = 5, respectively.) The same
doses of glibenclamide and 5-hydroxydecanoate in sham-anesthetized hearts had no effect (42.3 ±5.1%; n = 10 and 51.9 ± 2.2%;
n = 6, respectively). The adequacy of the heat stress protocol was confirmed by Western blot analysis of the inducible 72-kD
heat stress protein. It is concluded, therefore, that KATP channels appear to play a role in the heat stress response. The underlying mechanisms involved are, however, unclear.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献