Cardiotoxicity of Oncologic Treatments Edited by Manuela Fiuza doc

CARDIOTOXICITY OF ONCOLOGIC TREATMENTS Edited by Manuela Fiuza Cardiotoxicity of Oncologic Treatments Edited by Manuela Fiuza Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Sasa Leporic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.org Cardiotoxicity of Oncologic Treatments, Edited by Manuela Fiuza p. cm. ISBN 978-953-51-0273-1 Contents Preface VII Chapter 1 Cardiovascular Pathophysiology Produced by Natural Toxins and Their Possible Therapeutic Implications 1 Robert Frangež, Marjana Grandič and Milka Vrecl Chapter 2 Role of Nitric Oxide in Isoproterenol-Induced Myocardial Infarction 17 Victoria Chagoya de Sánchez, Lucía Yañez-Maldonado, Susana Vidrio-Gómez, Lidia Martínez, Jorge Suárez, Alberto Aranda-Fraustro, Juan Carlos Torres and Gabriela Velasco-Loyden Chapter 3 Cardiac Complications of Cancer Treatment 33 Beata Mlot and Piotr Rzepecki Chapter 4 Neuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity 65 David Goukassian, James P. Morgan and Xinhua Yan Chapter 5 Doxorubicin-Induced Oxidative Injury of Cardiomyocytes – Do We Have Right Strategies for Prevention? 89 Vukosava Milic Torres and Viktorija Dragojevic Simic Chapter 6 Trastuzumab and Cardiotoxicity 131 M. Fiuza and A. Magalhães Chapter 7 Early Detection and Prediction of Cardiotoxicity – Biomarker and Echocardiographic Evaluation 153 Elena Kinova and Assen Goudev Preface Many drugs, including those used in cancer patient treatments can cause injuries to human heart. As number of cured cancer patients continues to increase, the issue of cardiotoxicity is currently being subject of intensive research, since it can harmly influence long-term health condition of patients. This book reviews this subject over seven chapters which are briefly described below. In Chapter 1 the authors address the issue of cardiac damage caused by natural toxins. This compressive review focuses on toxins affecting heart physiology through modulation of the ionic channels in plasma membrane, describing most of the toxins affecting heart function, their targets in the heart tissue, mode of action and the most important clinical effects of envenomation. Chapter 2 revisits the issue of nitric acid as a protective mechanism involved in the recovery of myocardial ischaemia. The results of this study clearly show the action of NO in isoproterenol-induced myocardial infarction and suggest the importance to assess the role of NO in pre infarction and early post infarction stages in patients. It is possible that the therapeutic modulation of NO release might prevent the cytotoxic actions of the excessive NO release which facilitate the recovery of the patient at the post infarction stage. Chapter 3 reviews in depth the problem of cardiotoxicity of cancer therapy. The authors review different most used drugs and their potential mechanisms responsible for cardiac injury and major cardiac manifestations. Authors also revised the issue of cardiac involvement in patients undergoing mediastinal radiotherapy. Chapter 4 addresses the issue of Neureregulin1-Erb signaling in Doxorubicin-induced cardiotoxicity. In this chapter authors review several studies, from basic and clinical findings regarding the potential cardioprotective role of neureregulin in prevention and promising therapeutic approach to prevent or reverse myocardial dysfunction of doxorubicin-induced cardiotoxicity. In Chapter 5 authors deal with cardiotoxicity related to doxorubicin therapy. The mechanisms underlying cardiotoxicity of doxorubicin are complex. No single drug is able to prevent cardiotoxicity therefore, more clinical studies are needed to elucidate VIII Preface the mechanism and develop strategies in prevention against doxorubicin-induced cardiotoxicity. Chapter 6 deals with the question of trastuzumab cardiotoxicity in patients with breast cancer Her2+. The use of trastuzumab has changed the natural history of patients with HER-2 positive breast cancer, both in adjuvant and metastatic setting, and has become the standard of care for treatment of these patients. However, the occurrence of symptomatic and asymptomatic cardiac dysfunction is one of major concerns. Several methods are proposed to early identify at-risk patients. Chapter 7 reviews the issue of critical importance - the detection and prediction of early cardiotoxicity using biomarkers and echocardiographic techniques that can provide the diagnosis of myocardial injury in real time which is one of the main goals for both cardiologists and oncologists. Manuela Fiuza Echocardiography Laboratory of the Cardiology Department of University Hospital Santa Maria, Lisbon Medical University, Portugal [...]... important 26 Cardiotoxicity of Oncologic Treatments decrease on both isoforms Animals treated with L-.NAME showed a gradual diminution of eNOS activity (3, 24 h) After this time the activities of the isoforms reach normal values The increase in nitric oxide release during the pre infarction periods are the result of an increase in the activity of eNOS and iNOS and L-NAME decreased NO release by decreasing... address: Department of Medicine, University of California, San Diego, CA, USA * 18 Cardiotoxicity of Oncologic Treatments occurred at 12-24h after ISO administration MI lesion was defined by: 1) histological criteria looking for coagulative necrosis and fiber fragmentation, 2) physiological and biochemical criteria, 3) functionally by a continuous telemetric ECG recordings and 4) the increase of serum marker... Table 2 Effect of isoproterenol and L-NAME on serum levels of marker enzymes of myocardial damage at the time of infarction (12h) Values are average activity of the different enzymes in serum samples of the rats (n=5) ± standard error P value of the isoproterenol column represents a comparison with the control group without treatment and the P value of the ISO-NAME group is the significance of the L-NAME/ISO... geographus and consist of 10 to 30 amino acid residues Many of these peptides modulate the activity of different ion 10 Cardiotoxicity of Oncologic Treatments channels ω-conotoxin inhibits N-type voltage-dependent Ca2+ channels It decreases the magnitude of cardiac AP and possesses a negative inotropic effect (Nielsen, 2000) 4.9 Crotoxin Crotoxin (CTX) is derived from the venom of the South American... mediated by NO and might be critical for the MI development The main goal of this study is to investigate the role of NO in the development of MI using an inhibitor of its synthesis L-NAME (nitro-Larginine methyl ester) We examined the relative role of eNOS and iNOS on IM-induced pathological changes of histological, physiological, biochemical and molecular parameters as well as energy state of heart... 3 – 10 Anderson, of P-Q µg/kg i.p 2000; Su et interval, first al., 2003 degree of atrioventricular block, ventricular fibrilation Table 3 Natural cardiotoxic toxins from microbes: source, structure, receptors, mode of action, effects on heart and toxicity; i.g.- intra-gastric administration 6 Cardiotoxicity of Oncologic Treatments electrical activity is blocked leading to blockade of myocardium excitability... after 6-96 h of ISO treatment as a consequence of ion superoxide formation during the pre-infarction period And the nitric oxide (NO) generated throughout the experimental period The glutathione cycle, studied by the content of GSH and GSSG and the activities of GSH-peroxidase and GSH-reductase, was decreased during the three stages of ISO-induced cardiotoxicity Thus, confirming the importance of the oxidative... Ramsdell JS., Jensen DJ., Cooney JM & Miles CO Semisynthesis of S-desoxybrevetoxin-B2 and brevetoxin-B2, and assessment of their acute toxicities Chemical Research in Toxicology Vol 21, No 4, (Apr 2008), pp 944-950, 0893-228X 16 Cardiotoxicity of Oncologic Treatments Sepcić K., Berne S., Potrich C., Turk T., Maček P & Menestrina G Interaction of ostreolysin, a cytolytic protein from the edible mushroom... mechanical activity of the heart affecting pumping or leading even to cardiac arrest The aim of this chapter is to describe most of the toxins affecting heart function, their targets in the heart tissue, mode of action and the most important clinical effects of envenomation 2 Main molecular targets of the toxins in the heart 2.1 Sodium channels Voltage-gated sodium channels are an essential part of excitable... intraperitonealy (i.p.) to mice Although the mechanisms of the cardiotoxicity of YTX and homoyessotoxins are not well understood, some data from in vitro experiments, such as changes of intracellular calcium and cyclic AMP concentrations, alteration of cytoskeletal and adhesion molecules, caspases activation and opening of the permeability transition pore of mitochondria, support their cardiotoxic action . CARDIOTOXICITY OF ONCOLOGIC TREATMENTS Edited by Manuela Fiuza Cardiotoxicity of Oncologic Treatments Edited by Manuela Fiuza. and consist of 10 to 30 amino acid residues. Many of these peptides modulate the activity of different ion Cardiotoxicity of Oncologic Treatments