Physiologic Basis and Pathophysiologic Implications of the Diastolic Properties of the Cardiac Muscle

Although systole was for long considered the core of cardiac function, hemodynamic performance is evenly dependent on appropriate systolic and diastolic functions. The recognition that isolated diastolic dysfunction is the major culprit for approximately fifty percent of all heart failure cases imposes a deeper understanding of its underlying mechanisms so that better diagnostic and therapeutic strategies can be designed. Risk factors leading to diastolic dysfunction affect myocardial relaxation and/or its material properties by disrupting the homeostasis of cardiomyocytes as well as their relation with surrounding matrix and vascular structures. As a consequence, slower ventricular relaxation and higher myocardial stiffness may result in higher ventricular filling pressures and in the risk of hemodynamic decompensation. Thus, determining the mechanisms of diastolic function and their implications in the pathophysiology of heart failure with normal ejection fraction has become a prominent field in basic and clinical research

Efeitos Miocárdicos da Endotelina-1

A endotelina (ET)-1 foi identificada em 1988como sendo um peptídeo vasoconstrictorproduzido pelo endotélio vascular. Sabe-se,actualmente, que a nível cardiovascular a ET-1pode ser sintetizada não só pelo endotélio(vascular e endocárdico), mas também porcélulas miocárdicas.A activação dos receptores da ET-1 modulauma grande variedade de processos biológicosincluindo o tono e crescimento vasculares, bemcomo, a função contráctil miocárdica. Nosmamíferos, os seus efeitos são mediados pordois tipos de receptores, ETA e ETB. Osreceptores ETA promovem vasoconstrição,aumento do inotropismo e mitogénese. Poroutro lado, os receptores ETB induzemgeralmente vasodilatação (mediada pelalibertação do óxido nítrico e de prostaciclinas),inibição do crescimento e proliferação celular edepuração pulmonar da ET-1 circulante. Épossível ainda subdividir os receptores ETBBem: ETB1 de localização endotelial epromotores de vasodilatação e efeitosinotrópicos negativos, e em ETB2 delocalização muscular e promotores devasoconstrição e efeitos inotrópicos positivos.Vários estudos têm descrito elevados níveisplasmáticos e tecidulares cardíacos de ET-1 nainsuficiência cardíaca (IC) e fortes correlaçõespositivas entre os níveis de ET-1, odesenvolvimento de disfunção cardíaca eseveridade da IC. Este aspecto fez com que oantagonismo das acções da ET-1 se tornassenum alvo atraente sob o ponto de vistaterapêutico, tendo resultado na procuraincessante de antagonistas da ET (antagonistasdos receptores e inibidores das enzimas deconversão) pela indústria farmacêutica.O presente artigo constitui uma revisão acerca dos efeitos miocárdicos da ET-1 e dosmecanismos que lhes estão subjacentes.Endothelin (ET)-1 was originally identified in 1988 as a vasoconstrictor peptide produced by vascular endothelial cells. It is now known that ET-1 can be produced by vascular and endocardial endothelium and by myocardial cells. Activation of endothelin receptors modulates a wide variety of biological processes including vascular tone, growth and myocardial contractile function. In mammals, ET-1's effects are mediated through binding to two types of receptors, ET(A) and ET(B). ET(A) receptor activation elicits vasoconstriction, positive inotropism and mitogenesis, and acutely increases myocardial distensibility. ET(B) receptor stimulation generally promotes vasodilatation, mediated by release of nitric oxide and prostacyclins, growth-inhibitory effects and clearance of ET-1 from the circulation. ET(B) receptors can be further subdivided into ET(B1), located in endothelial cells and responsible for vasodilatation and negative inotropic effects, and ET(B2), located in smooth muscle and myocardial cells and responsible for vasoconstriction and positive inotropic effects. Increased levels of cardiac and circulating ET-1 have been linked to development of cardiac dysfunction and severity of heart failure. This has fueled research into the development of endothelin antagonists (ET receptor and converting enzyme inhibitors) in view of the potential benefits that might derive from their use in clinical practice. The present review will focus on current understanding of the mechanisms mediating the myocardial actions of ET-1

Inibidores da enzima de conversão da endotelina e sua aplicação na patologia cardiovascular.

A endotelina, um potente vasoconstrictordescrito em 1988 por Yanagisawa, contribuiupara normal regulação da funçãocardiovascular. No entanto, quando emdesequilíbrio, concorre para o processopatológico de várias doenças cardiovascularescomo sejam o enfarte do miocárdio, areestenose, a hipertensão pulmonar, ahipertensão arterial e até mesmo a doença deChagas. Têm sido desenvolvidos váriosesforços na tentativa de bloquear esta via. Osresultados obtidos com inibidores dosreceptores foram desanimadores, no entanto,tem-se verificado um interesse crescente nobloqueio da sua formação. Estão descritosinibidores selectivos e não selectivos daenzima de conversão da endotelina (ECE),estes últimos com a possibilidade da inibiçãoassociada da enzima de conversão daangiotensina e da endopeptidase neutralpermitindo o bloqueio simultâneo de váriasvias envolvidas na fisiopatologia destasdoenças.Nesta revisão são apresentados osdiferentes tipos de inibidores da ECE comreferência às características farmacológicas,dando particular ênfase à potencialidade dasua aplicação clínica nas diversas patologiascardiovasculares.Endothelin, a potent vasoconstrictor first described in 1988 by Yanagisawa, is an important regulator of cardiovascular function. Hyperactivation of the endothelin system has been implicated in the pathogenesis of various cardiovascular disorders including myocardial infarction, restenosis, hypertension, heart failure and Chagas cardiopathy. Various attempts have been made to suppress this axis. Although promising, the results of clinical trials on endothelin receptor antagonists have been disappointing. There is growing interest in blockade of endothelin formation. Several selective and non-selective endothelin-converting enzyme (ECE) inhibitors have been developed, the latter with the possibility of simultaneously blocking angiotensin-converting enzyme and neutral endopeptidase, combining inhibition more than one axis. This article reviews the different ECE inhibitors, with particular emphasis on their potential clinical application in cardiovascular disease

Cardiac venous arterialization in acute myocardial infarction: how great is the benefit?

Cardiac venous arterialization has been proposed as an alternative approach for myocardial revascularization in ischaemic heart disease. It is based on using the cardiac venous system to transport arterial blood from a systemic artery to infarcted myocardial areas. Our goal was to evaluate its benefit in reducing acute myocardial infarct size and its effects on cardiac performance. In a group of pigs, the left internal mammary artery was anastomosed to the left anterior descending vein; this vein was ligated proximally. The left anterior descending coronary artery was also occluded. Over 5 days, several diagnostic procedures were used to characterize and measure the extent of myocardial infarct, namely ECG, echocardiography, cardiac biomarkers and histopathology. Data were compared with those from a control group of pigs, which were submitted to ligation of only the left anterior descending coronary artery. In the experimental group, echocardiography revealed that the ejection fraction and thickness of the ventricular walls remained unchanged 4 days after surgery, in contrast to the major alterations in the control group. In fact, the ejection fraction in the control group decreased by 21% (P 0.2). This study reveals that selective cardiac venous arterialization can nourish the myocardium and is able to reduce infarct size by more than 50%, while protecting cardiac performance. We believe, therefore, that further investigation should be carried out into this technique in order for it to be considered as an option in coronary surgery

Operacionalização do heart team em Portugal

© 2013 Sociedade Portuguesa de Cardiologia Published by Elsevier España, S.L. All rights reserved.Whenever several therapeutic options exist, multidisciplinary decision-making is beneficial for the patient and for society at large. The main obstacles to the establishment of heart teams in Portugal are organizational and logistical. Implementing a heart team approach entails definition of the situations requiring multidisciplinary discussion, creation of clear lines of communication, written protocols and obtaining patient informed consent. The European Society of Cardiology guidelines define the clinical scenarios where intervention of the heart team is recommended.A decisão médica tomada em equipas multidisciplinares é uma mais-valia indiscutível para o doente e para a sociedade, particularmente quando existem várias opções terapêuticas. A falta de disponibilidade dos intervenientes, problemas logísticos e barreiras interdisciplinares são alguns dos obstáculos à operacionalização do Heart Team em Portugal. A operacionalização passa pela definição das situações que necessitam discussão multidisciplinar, a elaboração de protocolos escritos, a criação de vias de comunicação claras, a consignação das decisões tomadas e a informação fornecida ao doente. As situações, na doença coronária e na doença valvular, que requerem a intervenção do Heart Team estão definidas nas recomendações da Sociedade Europeia de Cardiologia.info:eu-repo/semantics/publishedVersio

Myocardial stretch-induced compliance is abrogated under ischemic conditions and restored by cGMP/PKG-related pathways

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI.Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure–volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats.Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading.Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia

ENDOVASCULAR ANEURYSM REPAIR FOR INTACT AND RUPTURED ABDOMINAL AORTIC ANEURYSMS: SHOULD WE EXPECT MORE COMPLICATIONS AFTER R-EVAR?

Introduction: Endovascular Aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) has been increasingly advocated due to short term benefits. Survival after discharge seems to be similar between EVAR for rAAA (r-EVAR) and for elective patients (el-EVAR). Still, due to higher anatomical complexity more graft-related complications may arise in r-EVAR patients. Methods: MEDLINE databases were searched to identify publications reporting on outcomes after r-EVAR and el-EVAR. Landmark EVAR randomized controlled trial results were used as comparison. Results: After-discharge outcomes (other than mortality), were reported in 5 studies including 509 r-EVAR patients. A direct comparison between r-EVAR and el-EVAR patients was found in 2 studies, including 2895 patients (256 r-EVAR and 2653 el-EVAR). Type I endoleak rates ranged from 5.4-21% in r- EVAR and from 4.4-10% el-EVAR. Rates of secondary intervention in r-EVAR ranged between 16.7-76% and in el-EVAR from 11-27.7%. Five year rate of complications after r-EVAR inside instructions for use were 8.8% and reinterventions were 16.7%. Conclusions: r-EVAR patients present higher rates of type I endoleaks and secondary interventions. However, when complying with IFU, aneurysm-related complications overlap to the el-EVAR patients. Surveillance strategies should be tailored according to the baseline anatomical complexity and early complications and not to the timing of repair