Isquemia miocárdica: conceptos básicos, diagnóstico e implicaciones clínicas. Tercera parte / Myocardial ischemia: basic concepts, diagnosis and clinical implications. Part three

Resumen El término «cardiopatía isquémica¼ se refiere a la disfunción del ventrículo izquierdo secundaria a infarto del miocardio, miocardio isquémico viable o enfermedad coronaria severa documentada por arteriografía coronaria, la cual tiene un pobre pronóstico, con una supervivencia del 45% a 5 años. El tratamiento de la cardiopatía isquémica involucra la estimación de la viabilidad en el miocardio afectado para determinar si la revascularización puede generar una remodelación positiva que mejore la función del ventrículo izquierdo. Existen cuatro modalidades básicas usadas en la práctica clínica para calcular la viabilidad miocárdica: tomografía de emisión simple de positrones, tomografía por emisión de positrones, ecocardiograma estrés y resonancia magnética cardiaca. Hoy en día hay estudios que demuestran que la terapia médica mejora la función del ventrículo izquierdo en la cardiopatía isquémica, independiente de la presencia o no de viabilidad o de la revascularización miocárdica; por tanto es posible que otros factores como la cantidad de remodelado, los volúmenes del ventrículo izquierdo, la insuficiencia mitral y la fracción de eyección puedan afectar también los desenlaces. Se requiere definir de manera clara los estadios del remodelado ventricular izquierdo en los cuales la presencia de viabilidad es benéfica y las etapas en las que el remodelado es reversible con la revascularización miocárdica. En cuanto a los métodos para determinar la viabilidad, la resonancia magnética parece dar más respuestas al respecto, ya que puede aportar información adicional relacionada con dimensiones del ventrículo izquierdo, fracción de eyección, fibrosis miocárdica y anormalidades valvulares.

Abstract The term myocardial ischemia refers to a left ventricular dysfunction secondary to a myocardial infarction, viable ischemic myocardium or sever coronary disease documented by means of a coronary angiography, which has a poor prognosis, with five-year survival rate of 45%. Management of myocardial ischemia involves estimating viability of the affected myocardium in order to determine whether revascularization can generate a positive remodelling that improves left ventricle functioning. Four different basic modalities are used in clinical practice to assess myocardial viability: single-photon emission computed tomography, positron emission tomography, stress echocardiogram and cardiac magnetic resonance. Nowadays there are studies that have shown medical therapy improves left ventricle function in ischemic heart disease, regardless of the presence or not of the viability or the myocardial revascularization; therefore, it is possible that other factors such as the amount of remodelling, the left ventricle volumes, mitral insufficiency and ejection fraction could also afffect the outcomes. A clear definition of the left ventricle remodelling states where the presence of viability is beneficial and the stages where the remodelling is reversible with myocardial revascularization is required. With regards to methods for assessing viability, magnetic resonance seems to provide more answers, as it can give additional information related to the dimensions of the left ventricle, ejection fraction, myocardial fibrosis and valvular abnormalities.

Isquemia miocárdica: conceptos básicos, diagnóstico e implicaciones clínicas. Segunda parte / Myocardial ischemia: basic concepts, diagnosis and clinical implications. Part two

Resumen La isquemia miocárdica puede ser irreversible o reversible dependiendo de diferentes factores moleculares y fisiológicos. En la isquemia miocárdica irreversible se presentan tres tipos de muerte celular a nivel miocárdico: la necrosis, la apoptosis y la autofagia; mientras en la isquemia reversible la restauración de la función de los miocitos está determinada por factores como el restablecimiento temprano del flujo sanguíneo coronario y fenómenos de pre y posacondicionamiento isquémico. Conceptos como el miocardio aturdido (disfunción mecánica temporal luego de una lesión isquémica pero con flujo sanguíneo normal en ausencia de cualquier lesión irreversible) y el miocardio hibernante (región miocárdica viable, sin contractilidad) son formas quiescentes de la función cardiaca y explican un poco la capacidad del miocardio de restablecer su funcionamiento normal luego de un episodio de isquemia.

Abstract Myocardial ischemia can be irreversible or reversible depending on multiple molecular and physiological factors. In irreversible myocardial ischemia there are three types of cell death on a myocardial level: necrosis, apoptosis and autophagy; whereas in reversible ischemia the restoration of the myocytes is determined by factors such as early recovery of coronary blood flow and pre- and postischemic conditioning phenomena. Concepts such as stunned myocardium (temporary mechanical dysfunction following an ischemic episode but with normal blood flow and without irreversible damage) and hibernating myocardium (viable myocardial region without contractility) are quiescent forms of the cardiac function and explain the ability of the myocardium to resume its normal functioning after an ischemic episode.

Impact of drug intervention on cardiomyopathy in STZ-induced type 1 diabetic rats / 中国综合临床

Objective To investigate the pathological changes of myocardium in diabetic rats and the effect of aspirin, perindopril, prednisone on the pathological changes of myocardium in type 1 diabetic rats. Methods Thirty SD rats were randomly divided into the following groups: ( 1 ) diabetes mellitus (DM)group ( n = 20): treated with intraperitoneal injection of streptozocin (STZ) 60 mg/kg at one time, diluted in sodium citrate buffer. (2) normal control group (n = 10): intraperitoneal injection of sodium citrate buffer. The blood glucose and the weight were measured regularly for 8 weeks. The 20 diabetic model rats were randomly divided into four groups (n = 5 individually), from the 4th day, the rats were given normal saline dissolved aspirin, perindopril, prednisone gavage respectively, and the normal control group and diabetic group were given an equal volume of saline daily gavage. After 8 weeks, the pathological changes in the cardiac muscle tissue were observed under light microscope and electron microscope. Results Three days after the injection of STZ, the blood glucose in the DM group was higher than 16. 7 mmol/L,20 rats were all modeling successfully. The model rats suffered from polydipsia, polyphagia, polyuria and weight loss significantly. HE staining showed diabetic myocardial cell swell, hypertrophy, degeneration and significant nuclear enlargement; the myocardial fiber fractured,dissolved, contraction wavy and disorganized fibre infiltrated by inflammatory cells. Under electron microscope, diabetic myocardial muscle fibers arranged irregularly, fractured and dissolved; the glycogen between the muscle fiber accumulated, mitochondria swelled, most of the ridges in mitochondria were not clear, cell plate widened. Compared with the diabetic group, the above-mentioned pathological changes reduced in the drug intervention group,and the changes in perindopril group was most significant. Conclusion Injection of STZ 60 mg/kg could successfully induce diabetic in rats and held stable blood glucose level. After 8 weeks, diabetes could cause servere damages in myocardium in the rats, but aspirin, perindopril, prednisone could reduce the cardiomyopathy in diabetic rats,in which perindopril had more positive effect.

Effects of active immunization with Na/Ca exchanger ?1 repetitive peptides on cardiac structure and function in rats / 中国免疫学杂志

Objective:To observe the effects of active immunization with a synthesized repetitive peptides in the extracellular loops of Na/Ca exchanger(NCX)?1 on cardiac structure and function in rats.Methods:A repetitive peptide of 124 HNFTAGDLGPSTIVGSAAFNMF145 was synthesized,which was in line with the extracellular loops of Na/Ca exchanger(NCX)?1.Healthly male Wistar rats of 2 month age were immunized actively with the synthesized peptide as antigen repeated for 12 weeks.The control group was given Freund's adjuvant only.Specific antibodies were detected by ELISA.The cardiac function was observed by Langendorff isolated heart-perfusing assay and the hearts were prepared for routine histological evaluation.Results:All rats immunized with the peptide developed highly positive autoimmunities,indicated by the antibody titers.After 12 weeks of peptide inoculation,the cardiac functioning indexes including LVSP-LVDP,+dp/dtmax and -dp/dtmax increased much more significantly in immunized group than in control.Histological evaluation showed that the myofilaments of the control group arranged regularly and densely with better continuity,whereas the myofilaments of the immunized group were lined with disorder.Some of those were ruptured.The interstitial lymphocyte infiltration was observed.Conclusion:The results indicate that long term immunization with the synthesized repeatitive peptide in line with the extracellular parts of Na/Ca exchanger(NCX)?1 can enhance both systolic and diastolic function of rat heart,but it can also induce injury in the heart structure.This may relate with an increase of myocardial oxygen consumption owing to a long time and continued excitement of membrane ion transporters as well as their active effect in heart contraction to a larger extent.