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Failure Progression (failure + progression)
Selected AbstractsOpposite effects of uracil and adenine nucleotides on the survival of murine cardiomyocytesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2008Alessia Mazzola Abstract We previously showed that the human heart expresses all known P2X and P2Y receptors activated by extra-cellular adenine or uracil nucleotides. Despite evidence that, both in humans and rodents, plasma levels of ATP and UTP markedly increase during myocardial infarction, the differential effects mediated by the various adenine- and uracil-preferring myocardial P2 receptors are still largely unknown. Here, we studied the effects of adenine and uracil nucleotides on murine HL-1 cardiomyocytes. RT-PCR analysis showed that HL-1 cardiomyocytes express all known P2X receptors (except for P2X2), as well as the P2Y2,4,6,14 subtypes. Exposure of cardiomyocytes to adenine nucleotides (ATP, ADP or BzATP) induced apoptosis and necrosis, as determined by flow-cytometry. Cell death was exacerbated by tumour necrosis factor (TNF)-,, a cytokine implicated in chronic heart failure progression. Conversely, uracil nucleotides (UTP, UDP and UDPglucose) had no effect ,per se', but fully counteracted the deleterious effects induced by adenine nucleotides and TNF-,, even if added to cardiomyocytes after beginning exposure to these cell death-inducing agents. Thus, exposure of cardiomyocytes to elevated concentrations of ATP or ADP in the presence of TNF-, contributes to cell death, an effect which is counteracted by uracil-preferring P2 receptors. Cardiomyocytes do not need to be ,primed' by uracil nucleotides to become insensitive to adenine nucleotides-induced death, suggesting the existence of a possible ,therapeutic' window for uracil nucleotides-mediated protection. Thus, release of UTP during cardiac ischaemia and in chronic heart failure may protect against myocardial damage, setting the basis for developing novel cardioprotective agents that specifically target uracil-preferring P2Y receptors. [source] Acute Myocardial Infarction Complicated by Early Onset of Heart Failure:JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2003Feasibility of Interhospital Transfer for Coronary Angioplasty., Safety Objective: The objective of this study is to assess the feasibility and safety of interhospital transfer (within up to 60 minutes) for primary/rescue coronary angioplasty of patients with myocardial infarction (AMI) complicated by an early onset of acute heart failure (AHF) admitted to a community hospital without PCI facilities. Design and patients: From the multicenter randomized PRAGUE-1 study, a subgroup of 66 patients with AMI complicated by AHF on the first presentation to the community hospital were retrospectively analyzed. Group A patients(n = 21)were treated on site in community hospitals using thrombolysis (streptokinase), group B patients(n = 20)were transported with thrombolytic infusion to a PCI center for coronary angioplasty, and group C patients(n = 25)were immediately transported to a PCI center for primary angioplasty without thrombolysis. Results: No patient died during transportation. One group B patient developed ventricular fibrillation during transfer. The time delay from the onset of chest pain to reperfusion was >142 minutes, and 253 and 251 minutes in groups A, B, and C, respectively. Hospital stay (16 vs 11 vs 10 days,P = NS) was shorter in the angioplasty groups. Transported patients (groups B, C) displayed a significant decrease in heart failure progression within the first 24 hours after treatment (48% vs 15% vs 8%,P < 0.05). The combined end point, i.e., mortality + nonfatal reinfarction (43% vs 25% vs 8%,P < 0.05), was significantly less frequent in the coronary angioplasty group. Conclusions: Interhospital transfer for coronary angioplasty of patients with AMI complicated by an early onset of AHF is feasible and safe. Transport for angioplasty may even reduce the risk of heart failure progression and improve clinical outcome compared to immediate thrombolysis in the nearest community hospital. (J Interven Cardiol 2003;16:201,208) [source] Protective role of ,-aminobutyric acid against chronic renal failure in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2006Sumiyo Sasaki The protective effect of ,-aminobutyric acid (GABA) against chronic renal failure (CRF) was investigated using a remnant kidney model with 5/6 nephrectomized rats. Nephrectomy led to renal dysfunction, which was evaluated via several parameters including serum urea nitrogen, creatinine (Cr) and Cr clearance. However, the administration of GABA ameliorated renal dysfunction, and a longer administration period of GABA increased its protective effect. In addition, nephrectomized control rats showed an elevation in the fractional excretion of sodium (FENa) with an increase in urinary sodium, while GABA led to a significant decline in FENa. Moreover, nephrectomy resulted in a decrease of serum albumin and an increase of urinary protein with a change in the urinary protein pattern, whereas the rats administered GABA showed improvement in these changes associated with CRF caused by nephrectomy. This suggests that GABA would inhibit the disease progression and have a protective role against CRF. As one of the risk factors for CRF progression, hypertension was also regulated by GABA. The results also indicate that GABA may play a protective role against CRF through improvement of the serum lipid profile, with reductions in triglyceride and total cholesterol. Furthermore, nephrectomy led to renal oxidative stress with a decrease in the activity of antioxidative enzymes and elevation of lipid peroxidation. The administration of GABA attenuated oxidative stress induced by nephrectomy through an increase in superoxide dismutase and catalase, and decrease in lipid peroxidation. The histopathological lesions, including glomerular, tubular and interstitial lesions, under nephrectomy were also improved by GABA with the inhibition of fibronectin expression. This study demonstrated that GABA attenuated renal dysfunction via regulation of blood pressure and lipid profile, and it also ameliorated the oxidative stress induced by nephrectomy, suggesting the promising potential of GABA in protecting against renal failure progression. [source] Prophylactic Implantation of Cardioverter Defibrillators in Idiopathic Nonischemic Cardiomyopathy for the Primary Prevention of Death: A Narrative ReviewCLINICAL CARDIOLOGY, Issue 5 2010Cihan Cevik MD, FESC Implantable cardioverter defibrillator (ICD) therapy reduces sudden cardiac death rates and reduces mortality in patients with ischemic heart disease and low ejection fractions. One-third of the deaths in patients with nonischemic cardiomyopathy are sudden. However, the efficacy of ICDs in the primary prevention of death in these patients is less clear. The most common cause of mortality in patients treated with ICDs is heart failure progression. ICD shocks can cause direct myocardial injury, fibrosis, inflammation, and adverse psychological outcomes, and these changes may contribute to the ventricular dysfunction in patients who already have a significantly depressed ejection fraction. We have reviewed the published randomized controlled trials and meta-analysis of prophylactic ICD therapy in the primary prevention of death in patients with nonischemic cardiomyopathy. The individual randomized controlled trials do not report a statistically significant reduction of mortality unless the ICD treatment is added to cardiac resynchronization therapy, but the meta-analysis did show a significant mortality reduction and favored ICD therapy in these patients. Medical management of many study participants was suboptimal, at least based on current guidelines. The patients with non-ischemic cardiomyopathy have good outcomes with medical therapy, and ICD therapy in this relatively low-risk population needs better selection criteria. Copyright © 2010 Wiley Periodicals, Inc. [source] | ||||||||||