Regeneración miocárdica: el futuro al alcance de la mano / Myocardial regeneration: future at reach

En los últimos años hemos asistido a un interés creciente por eltratamiento de la insuficiencia cardíaca mediante el trasplante decélulas madre. Mientras que los estudios con células madre de músculo(mioblastos) se iniciaron hace mas de 10 años, la posibilidadde que las células madre de la médula ósea tengan un enorme potencialde diferenciación y proliferación han estimulado la investigacióncon otros tipos de células madre. Estos estudios experimentales handemostrado, en no pocas ocasiones, resultados contradictorios loque ha llevado a posturas enfrentadas en cuanto a la ética de iniciarestudios clínicos. Creemos que es adecuado tratar de ofrecer unavisión crítica sobre la utilización de las células madre en la insuficienciacardíaca. Quizá la pregunta mas difícil de contestar en estemomento es, si la realización de ensayos clínicos esta justificado ono a la luz de los conocimientos actuales o si por el contrario debemosadquirir un conocimiento mucho más preciso de la posibleeficacia de este tipo de tratamiento y de los mecanismos que justificandicha eficacia, antes de siquiera iniciar los estudios en humanos.En nuestra opinión existen suficientes evidencias que justifican eldesarrollo de ensayos clínicos a pesar de que, sin duda, existenmuchos interrogantes que debemos resolver mediante estudios experimentalesen animales

The last few years have witnessed a growing interest in regenerative therapy of the failing heart by cell transplantation. Initial studies with skeletal myoblasts were conducted more than 10 years ago. However, the potential of bone marrow derived cells has more recently led to a flurry of experimental studies generating overall positive but occasionally conflicting results. The ethics of initiating clinical trials with stem cells in patients with heart failure has been questioned. Although laboratory research attempts to overcome a number of questions surrounding the usefulness and safety of cell therapy, the accumulated body of evidence warrants implementation of clinical trials. The earliest of these have now documented the feasibility of cell therapy. It is now appropriate to conduct safety and efficacy studies which, if carefully done, should allow assessment of the extent to which this concept of regenerative therapy can be made a clinical reality (AU)

[Myocardial regeneration: future at reach]. / Regeneración miocárdica: el futuro al alcance de la mano.

The last few years have witnessed a growing interest in regenerative therapy of the failing heart by cell transplantation. Initial studies with skeletal myoblasts were conducted more than 10 years ago. However, the potential of bone marrow derived cells has more recently led to a flurry of experimental studies generating overall positive but occasionally conflicting results. The ethics of initiating clinical trials with stem cells in patients with heart failure has been questioned. Although laboratory research attempts to overcome a number of questions surrounding the usefulness and safety of cell therapy, the accumulated body of evidence warrants implementation of clinical trials. The earliest of these have now documented the feasibility of cell therapy. It is now appropriate to conduct safety and efficacy studies which, if carefully done, should allow assessment of the extent to which this concept of regenerative therapy can be made a clinical reality.

[Large false aortic aneurysm after 30 years of a coarctation repair]. / Falso aneurisma aórtico 30 años después de la corrección de una coartación: tratamiento quirúrgico bajo hipotermia profunda.

We report a case of a large false aortic aneurysm that had developed in a 43-year-old man who had had coarctation repair 30 years previously. The coarctation repair had been done by inserting an end-to-end Dacron tubular graft which was sutured with silk. The re-operation was successfully performed under deep hypothermic arrest and it was noted that there was complete separation of the graft from both ends and no sutures were visualised. The deep hypothermic technique has considerably improved the ease and safety of this operation. We attribute this complication to the reabsorption of the silk sutures. Patients after coarctectomy with graft material should have regular chest X-rays for life in order to detect false aneurysms.

Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in the arterial wall contributing to restenosis after vascular injury. Antioxidants have been proposed as inhibiting multiple proatherogenic events. We explore the effect of vitamins C and E on PAI-1 expression in an experimental model of angioplasty in hypercholesterolemic pigs. METHODS AND RESULTS: A total of 44 Yucatan minipigs were divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC), and a high-cholesterol plus vitamins C+E (HCV) group. Balloon injury was induced in the right internal iliac artery 4 weeks after initiation of either dietary regimen, and plasma and tissue samples were taken at different time periods to measure PAI-1 activity and vascular inhibitor expression. The cholesterol-rich diet induced an increased in vascular PAI-1 expression in the intima, media and adventitia which was markedly reduced in the HCV group. After injury, severe structural changes were observed in NC and HC animals associated with increased systemic PAI-1 activity (P<0.001) and local PAI-1 expression being more intense in HC group. Vitamins C and E significantly reduced plasma PAI-1 activity (P=0.018) and attenuated the inhibitor expression as compared with HC. CONCLUSIONS: This experimental study in a porcine model of hypercholesterolemia demonstrates that vitamins C and E reduce local and systemic PAI-1 induced after angioplasty as well as the hypercholesterolemia-induced vascular PAI-1.

¿Cuál o cuáles son los mecanismos de acción significativos de las estatinas? / Which is or what are the significant mechanisms of action of statins?

En la actualidad, las estatinas son los fármacos más empleados en el tratamiento de las dislipidemias. Además de la disminución de los niveles de colesterol LDL, las estatinas tienen otros efectos 'vasculares' y hemostáticos que permiten explicar mejor su probada eficacia clínica. En la presente revisión se describen los mecanismos de acción de las estatinas tratando de explicar mediante ellos no sólo la reducción de los niveles lipídicos, sino también la producción de los citados efectos vasculares y hemostáticos. La mejor comprensión de estos mecanismos permitirá, sin duda, un uso más racional de estos fármacos (AU)

Clandestine ischemia in patients with vasospastic angina.

BACKGROUND: Coronary vasospasms generally occur at rest, but can also be triggered by physical exercise. Anginal pain and ST-segment elevation may be seen during exercise-stress tests. ST-segment depression, due to nonocclusive vasospasms, has also been found to occur. When the result of a test is positive, scintigraphy usually reveals perfusion defects. True silent or clandestine ischemia (normal result of exercise test with perfusion defects) in these patients is very uncommon. OBJECTIVE: To stress the need for suspecting occurrence of coronary vasospasms in order to perform a proper diagnosis. METHODS: Eight patients with angina were selected for this study. They had negative results of exercise tests with perfusion defects detected by thallium-201 tomography, normal coronary arteries and vasospasms. Maximal exercise-stress tests with thallium-201 tomography were performed. Sizes of perfusion defects were quantified by examining polar maps. Coronary angiography and then an intracoronary ergonovine test were performed for each patient. RESULTS: Significant defects were seen in territory of the right coronary artery, the left anterior descending artery, or both. Lung:heart ratio was normal in every case. The coronary arteries were normal and vasospasms were elicited with ergonovine in all the patients. Correspondence between the location of perfusion defects and angiographic spasms was generally observed. After treatment with calcium antagonists and nitrates all of them improved and defects detected by thallium tomography were no longer found when tests were repeated. CONCLUSIONS: Some patients with vasospastic angina may have normal results of exercise-stress tests and reversible perfusion defects detectable by scintigraphy. This finding must lead one to perform coronary angiography without administration of nitroglycerine beforehand and an ergonovine test if the coronary arteries are normal.

[Myocardial perfusion reserve studied by single-photon emission-computed tomography with thallium-201 and a drug stress test with adenosine triphosphate in patients with cardiovascular risk factors]. / Estudio de la reserva de perfusión miocárdica mediante tomografía de emisión de fotón único con talio-201 y estrés farmacológico con adenosina trifosfato en pacientes con factores de riesgo cardiovascular.

INTRODUCTION AND OBJECTIVE: Recent studies have suggested that the evaluation of coronary reserve is a sensitive method in the early detection of vascular alterations before plaques exist, and certainly before clinical detection of atherosclerotic lesions. Single-photon emission-computed tomography (SPECT) with thallium-201 (201Tl) provides a noninvasive tool for evaluating myocardial perfusion reserve. The objective of this study was to measure the myocardial perfusion reserve in two groups of subjects, some with and some without cardiovascular risk factors and in a group of patients with coronary artery disease. METHODS: Seventy-four subjects, divided into three groups, were recruited to assess regional and global myocardial perfusion reserve. The control group consisted of 11 asymptomatic individuals without cardiovascular risk factors. The second group was composed of 49 patients with one or more risk factors. Finally, the third group included 14 patients with coronary artery disease. 201Tl-SPECT at rest and after pharmacological stress with a 7 minute adenosine triphosphate (ATP) infusion (140 micrograms/kg/min) was performed in all patients. ATP minus rest value subtraction was applied in order to obtain the stress data. Relative myocardial perfusion reserve indices were calculated as the ratio between stress and rest values. RESULTS: Global and regional myocardial perfusion reserves of the vascular territories were significantly lower in patients with cardiovascular risk factors than in control subjects (Global: 1.48 +/- 0.19 vs 1.81 +/- 0.08, LAD: 1.52 +/- 0.21 vs 1.85 +/- 0.09, CX: 1.45 +/- 0.2 vs 1.79 +/- 0.86, RCA: 1.47 +/- 0.2 vs 1.79 +/- 0.86) and higher than in patients with coronary artery disease (Global: 1.48 +/- 0.19 vs 1.31 +/- 0.14, LAD: 1.52 +/- 0.21 vs 1.35 +/- 0.15, CX: 1.45 +/- 0.2 vs 1.2 +/- 0.24). Univariate linear regression analysis in a group of 40 patients with high risk lipid profiles revealed a significant negative correlation between myocardial perfusion reserve and total cholesterol (r = -0.35; p = 0.01), LDL-cholesterol (r = -0.38; p = 0.036) and LDL/HDL ratio (r = -0.39; p = 0.029). CONCLUSION: Determination of myocardial perfusion reserve with 201Tl-SPECT allows the detection of abnormal vasodilatory response to intravenous ATP in patients with cardiovascular risk factors. These patients have higher reserves than patients with coronary disease, which might suggest an early phase of atherosclerosis.

[Growth factors and mitogenic activity in experimental hypercholesterolemia]. / Factores de crecimiento y actividad mitogénica en la hipercolesterolemia experimental.

INTRODUCTION: Hypercholesterolemia is associated with increased platelet reactivity and changes in megakaryopoiesis, which might influence the synthesis of growth factors in the megakaryocyte. MATERIAL AND METHODS: 20 miniature pigs were randomly assigned to received 18 weeks of either regular pig chow feed (control group, n = 10) or a high cholesterol diet (cholesterol group, n = 10). Platelet count, mean platelet volume, platelet distribution width and bleeding time were determined in both groups. Intraplatelet and serum mitogenic activity was quantified by Swiss 3T3 and vascular smooth muscle cells proliferation assays. Insulin-like growth factor I and platelet-derived growth factor (BB isoform) levels were quantified in platelet lysates and in serum in both groups. RESULTS: Hypercholesterolemia was associated to a significant decrease in mean platelet volume and bleeding time, but it did not affect the proliferative effect of serum and platelet lysates nor its growth factor content. CONCLUSIONS: Taken together, our results suggest that although hypercholesterolemia affects platelet reactivity, its atherosclerosis-promoting effects cannot be explained by a direct effect on vascular smooth muscle cell proliferation or by changes in serum or intraplatelet growth factor content.

Effect of hypercholesterolaemia on platelet growth factors.

Evidence from several sources suggests that important interactions occur between platelets and low-density lipoproteins. This study was undertaken to find out if diet-induced hypercholesterolaemia affects the growth factor content in circulating platelets. Minipigs were fed either normal diet supplemented with 2% cholesterol (n = 12) or normal diet alone (n = 12). After 4 months, mean platelet volume was significantly lower (P < 0.05) and monocyte count was significantly higher (P < 0.05) in the cholesterol group. Serum and intraplatelet levels of platelet-derived growth factor (BB homodimer) and transforming growth factor beta 1 were statistically unchanged after diet. Hypercholesterolaemia did not affect the proliferative effect of either serum or platelet lysates on porcine vascular smooth muscle cells and Swiss-3T3 cells in culture. A significant positive correlation between Swiss-3T3 and smooth muscle cell proliferation was present in both groups. These results suggest that the atherosclerosis-promoting effect of hypercholesterolaemia cannot be explained by its direct effect on smooth muscle cell proliferation or by changes in serum or intraplatelet concentrations of growth factors.

[Myocardiopathies (XI). Restrictive myocardiopathy: concept, classification, and clinical approach]. / Miocardiopatías (XI). Miocardiopatía restrictiva: concepto, clasificación y actitud clínica.

Currently, cardiomyopathies are defined as "heart muscle diseases of unknown etiology". Restrictive cardiomyopathy is the rarest type of this disease, and the only one with no uniformly accepted diagnostic criteria. Its importance lies primarily in properly distinguishing it from constrictive pericarditis because of the direct consequences of mistakenly treating a case of constrictive pericarditis as if it were inoperable. Restrictive cardiomyopathy must be considered within the broader spectrum of diastolic dysfunction. Diagnostic criteria used show a general consensus for the diagnosis of restrictive cardiomyopathy in patients with clinical signs of heart failure in the presence of a nondilated, nonhypertrophic left ventricle with preserved contractility but abnormal diastolic function. Characteristically, right and left ventricular filling pressures are elevated and a dip and plateau diastolic pressure pattern appears. Restrictive cardiomyopathy may be either idiopathic and thus be a true cardiomyopathy in the strict sense of the term or secondary to an infiltrative disease of the myocardium. In this article we review the clinical and hemodynamic features of this disease and the different imaging techniques used in patients to help differentiate restrictive cardiomyopathy from constrictive pericarditis. Finally we study some types of restrictive cardiomyopathies.

Diagnostic accuracy of predicting coronary artery disease related to patients' characteristics.

Patients' demographic and clinical characteristics may affect diagnostic accuracy of cardiologists. We asked a group of experienced cardiologists from three institutions to estimate the pretest probability of coronary artery disease in 257 patients referred for diagnostic coronary angiography and with no history of previous myocardial infarction nor valvular heart disease. Physicians pretest estimates were compared with the diagnostic findings of coronary angiography. We tested the influence of five variables on the accuracy of the pretest estimates: age, sex, chest pain characteristics, rest electrocardiogram and electrocardiographic exercise test result. Cardiologists tended to overestimate the presence of coronary artery disease and this tendency was particularly remarkable in the group of patients showing a negative exercise test. Pretest diagnostic accuracy was 0.72 when the test result was negative and 0.85 when the test result was positive (95% confidence interval of the difference 0.03 to 0.23; p < 0.001). The diagnosis of coronary artery disease was also more accurate for male than for female patients (0.81 vs 0.70; 95% confidence interval of the difference 0.02 to 0.21; p < 0.02). Characteristics of chest pain, age and rest electrocardiogram did not affect the level of pretest diagnostic accuracy. Cardiologists should be cognizant of correctly interpreting a negative exercise test and the clinical data of female patients; in both cases, they should move circumspect of the diagnosis of coronary artery disease.

[The threat syndrome of the anterior descending coronary artery]. / Síndrome de amenaza de la arteria coronaria descendente anterior.

Some patients with unstable angina develop a deep T-wave inversion in ECG leads V1 to V4. It has been suggested that this special ECG pattern is associated with a severe stenosis of the left anterior descending (LAD) coronary artery. We have studied 73 of this patients. All of them had an LAD involvement, nearly always as severe atherosclerotic plaque and in 5% of the cases due to non-atherosclerotic alterations (milking or spasm). Angioplasty was performed in 33% and bypass surgery in 61%. In both cases the immediate results were good (0% and 4% respectively in-hospital mortality) as well as the outcome (12% restenosis and 0% late mortality respectively). The ECG signs disappeared in the year after.

[Applications of nuclear magnetic resonance in the diagnosis of cardiopathies]. / Aplicaciones de la resonancia magnética nuclear en el diagnóstico de las cardiopatías.

Applications of nuclear magnetic resonance imaging in cardiovascular diagnosis. The role of magnetic resonance imaging in the evaluation of cardiovascular system is still evolving. Nevertheless, this technique is of great promise for cardiac patient management in the near future. Magnetic resonance imaging provides a high contrast between the blood pool and myocardial function that has been shown to be effective for the evaluation of a wide variety of anatomic abnormalities as well as to assess cardiac contractile function or myocardial perfusion. Moreover, magnetic resonance spectroscopy has provided a new research tool for the evaluation of myocardial metabolism. Such performances indicate the potential of magnetic resonance techniques to establish the link between myocardial function and metabolism. In this presentation we will review the current status of magnetic resonance imaging for the diagnosis and evaluation of a wide variety of cardiovascular diseases and discuss its future potential.

Unsuccessful pericardiocentesis for cardiac tamponade during angiocardiography with nonionic contrast material.

Cardiac tamponade secondary to ventricular wall perforation is one of the possible complications of right-sided as well as left-sided cardiac catheterization. Ventriculography was performed on a patient with obstructive cardiomyopathy using a nonionic contrast medium. During the procedure, the right ventricle was accidentally perforated and the patient developed cardiac tamponade. Pericardiocentesis was unsuccessful and surgical drainage was needed after the patient developed progressive hemodynamic deterioration. At surgery, pericardial thrombus was found. We consider the reason for failure of pericardiocentesis was rapid coagulation of the extravasated blood in connection with nonionic contrast material.

[Non-invasive study of myocardial ischemia. Alternatives to the conventional stress test]. / Estudio no invasivo de la isquemia miocárdica. Alternativas a la prueba de esfuerzo convencional.

Stress techniques for inducing myocardial ischemia in patients with coronary atherosclerosis have been widely studied. The most frequently used are those requiring physical effort, increasing their diagnostic efficiency with radioisotopes and echocardiographic monitoring. Patients unable to make physical exercise and with suspected ischemic heart disease may undergo nonexercise stress test. Transesophageal atrial stimulation and pharmacological stress tests with dipyridamol, dobutamine and adenosine are good alternatives, provided a strict methodology is used.