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Cardioprotective Strategies (cardioprotective + strategy)
Selected AbstractsVagal Afferent Stimulation as a Cardioprotective Strategy?ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2005Introducing the Concept The effect of vagal afferent signaling on cardioinhibition has been well known for over 130 years. Both experimental and clinical studies have demonstrated not only the potential adverse effect of unrestrained sympathoexcitation in high risk patients with ischemic heart disease but the potential for cardioprotection by programmed vagal activity. The vasodepressor and negative chronotropic effects of efferent vagal stimulation has been a cause for concern. However it is becoming clear that favorable shifts towards increased cardiac vagal modulation can be achieved by vagal afferent nerve stimulation. This phasic effect appears to operate though central medullary pathways. Thus by engaging vagal afferent fibers in humans there is the possibility that one can exploit the benefits of central cardioinhibition without adversely affecting heart rate, respiration or hemodynamics. This commentary explores the background and rationale for considering vagal afferent stimulation as a plausible cardioprotective strategy. [source] Human Heart Cytosolic Reductases and Anthracycline CardiotoxicityIUBMB LIFE, Issue 1 2001Alvaro Mordente Abstract Anthracyclines are a class of antitumor drugs widely used for the treatment of a variety of malignancy, including leukemias, lymphomas, sarcomas, and carcinomas. Different mechanisms have been proposed for anthracycline antitumor effects including freeradical generation, DNA intercalation/binding, activation of signaling pathways, inhibition of topoisomerase II and apoptosis. A life-threatening form of cardiomyopathy hampers the clinical use of anthracyclines. According to the prevailing hypothesis, anthracyclines injure the heart by generating damaging free radicals through iron-catalyzed redox cycling. Although the "iron and freeradical hypothesis" can explain some aspects of anthracycline acute toxicity, it is nonetheless disappointing when referred to chronic cardiomyopathy. An alternative hypothesis implicates C-13 alcohol metabolites of anthracyclines as mediators of myocardial contractile dysfunction ("metabolite hypothesis"). Hydroxy metabolites are formed upon two-electron reduction of the C-13 carbonyl group in the side chain of anthracyclines by cytosolic NADPH-dependent reductases. Anthracycline alcohol metabolites can affect myocardial energy metabolism, ionic gradients, and Ca 2+ movements, ultimately impairing cardiac contraction and relaxation. In addition, alcohol metabolites can impair cardiac intracellular iron handling and homeostasis, by delocalizing iron from the [4Fe-4S] cluster of cytoplasmic aconitase. Chronic cardiotoxicity induced by C-13 alcohol metabolite might be primed by oxidative stress generated by anthracycline redox cycling ("unifying hypothesis"). Putative cardioprotective strategies should be aimed at decreasing C-13 alcohol metabolite production by means of efficient inhibitors of anthracycline reductases, as short-chain coenzyme Q analogs and chalcones that compete with anthracyclines for the enzyme active site, or by developing novel anthracyclines less susceptible to reductive metabolism. [source] Segmental Differences of Impaired Diastolic Relaxation Following Cardiopulmonary Bypass Surgery in Children: A Tissue Doppler StudyARTIFICIAL ORGANS, Issue 11 2009Linda B. Pauliks Abstract Impaired myocardial relaxation is an important aftereffect of cardiopulmonary bypass (CPB). Infants with their immature calcium metabolism may be particularly vulnerable. However, it has been difficult to quantitate diastolic dysfunction clinically. This study used tissue Doppler to measure regional diastolic myocardial velocities in 31 pediatric patients undergoing open heart surgery. Color tissue Doppler images were acquired in the operating room before and 8 and 24 h post CPB surgery. Early (E) and atrial (A) diastolic velocities were determined. Long axis motion was assessed from apical views near the mitral and tricuspid rings and radial wall motion from the parasternal view. The study included 31 children aged 3.6 ± 4.4 years (6 days to 16 years), with a mean weight of 14.7 ± 13.7 kg and body surface area of 0.59 ± 0.35 m2. Tissue Doppler analysis of regional wall motion revealed abnormal left ventricle (LV) and right ventricle (RV) diastolic relaxation in the early postoperative phase after CPB. Initially, all segments were significantly altered, but by 24 h, regional differences became apparent: LV radial wall motion was recovered, while longitudinal fibers in LV and RV appeared to be less resilient. RV myocardial mechanics were most abnormal. Tissue Doppler analysis may deepen our understanding of myocardial recovery and offers a sensitive tool to compare different cardioprotective strategies. [source] Preconditioning and postconditioning: new strategies for cardioprotectionDIABETES OBESITY & METABOLISM, Issue 6 2008D. J. Hausenloy Despite optimal therapy, the morbidity and mortality of coronary heart disease (CHD) remains significant, particularly in patients with diabetes or the metabolic syndrome. New strategies for cardioprotection are therefore required to improve the clinical outcomes in patients with CHD. Ischaemic preconditioning (IPC) as a cardioprotective strategy has not fulfilled it clinical potential, primarily because of the need to intervene before the index ischaemic event, which is impossible to predict in patients presenting with an acute myocardial infarction (AMI). However, emerging studies suggest that IPC-induced protection is mediated in part by signalling transduction pathways recruited at time of myocardial reperfusion, creating the possibility of harnessing its cardioprotective potential by intervening at time of reperfusion. In this regard, the recently described phenomenon of ischaemic postconditioning (IPost) has attracted great interest, particularly as it represents an intervention, which can be applied at time of myocardial reperfusion for patients presenting with an AMI. Interestingly, the signal transduction pathways, which underlie its protection, are similar to those recruited by IPC, creating a potential common cardioprotective pathway, which can be recruited at time of myocardial reperfusion, through the use of appropriate pharmacological agents given as adjuvant therapy to current myocardial reperfusion strategies such as thrombolysis and primary percutaneous coronary intervention for patients presenting with an AMI. This article provides a brief overview of IPC and IPost and describes the common signal transduction pathway they both appear to recruit at time of myocardial reperfusion, the pharmacological manipulation of which has the potential to generate new strategies for cardioprotection. [source] Vagal Afferent Stimulation as a Cardioprotective Strategy?ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2005Introducing the Concept The effect of vagal afferent signaling on cardioinhibition has been well known for over 130 years. Both experimental and clinical studies have demonstrated not only the potential adverse effect of unrestrained sympathoexcitation in high risk patients with ischemic heart disease but the potential for cardioprotection by programmed vagal activity. The vasodepressor and negative chronotropic effects of efferent vagal stimulation has been a cause for concern. However it is becoming clear that favorable shifts towards increased cardiac vagal modulation can be achieved by vagal afferent nerve stimulation. This phasic effect appears to operate though central medullary pathways. Thus by engaging vagal afferent fibers in humans there is the possibility that one can exploit the benefits of central cardioinhibition without adversely affecting heart rate, respiration or hemodynamics. This commentary explores the background and rationale for considering vagal afferent stimulation as a plausible cardioprotective strategy. [source] | ||||||||||