Serum basic fibroblast growth factor levels in exercise-induced myocardial ischemia more likely a marker of endothelial dysfunction than a marker of ischemia?

Increased levels and activity of fibroblast growth factor (FGF) have been documented in a variety of diseases, including ischemia. Both acute coronary syndromes and exercise are situations that stimulate FGF release. Since experimental studies have demonstrated that FGFs are involved in myocardial preconditioning, it has been suggested that cardiac and circulating FGFs may play a cardioprotective role in ischemic diseases. However, the profile of basic FGF (bFGF) release during transient myocardial ischemia remains uncertain. We sought to determine whether circulating bFGF might be changed in patients with demonstrated coronary artery disease and evidence of ischemia in exercise scintigraphy (Isch +; n = 21). Serum from 22 age-matched patients with no coronary artery disease and no isotopic ischemia (Isch-) were used as controls. Three blood samples were obtained to determine bFGF at different times: baseline (bFGF-A); maximal exercise (bFGF-B), and isotopic redistribution (bFGF-C). An enzyme-linked immunoassay specific for bFGF was used (limit of detection, 1.0 pg/ml). Circulating bFGF was increased at maximal exercise in both Isch + and control patients. However, serum levels of bFGF were elevated up to more than two-fold in Isch-patients compared to Isch+ patients (8.67 +/- 2.10 pg/ml in Isch+ vs 17.83 +/- 2.97 pg/ml in Isch- patients; p<0.01). According to previous data, these findings suggest that bFGF serum levels could be considered more likely a marker of endothelial dysfunction occurring in patients with coronary artery disease, rather than a marker of acute ischemia. This situation could be different in the clinical setting of chronic myocardial ischemia.

[Yield of transthoracic echocardiography with high frequency transducer in the study of the anterior descending coronary artery]. / Rendimiento de la ecocardiografía transtorácica con sonda de alta frecuencia en el estudio de la descendente anterior.

INTRODUCTION AND OBJECTIVES: This study was performed to evaluate the feasibility and utility of a transthoracic high frequency transducer to detect and measure the left anterior descending coronary artery flow in patients with lesions in this artery or anterior myocardial infarction. MATERIALS AND METHODS: We studied 11 subjects with lesions greater than 75% and another 10 with anterior myocardial infarction. We compared the results with a control group of 18 subjects. An ATL HDI 5000 ultrasound unit with a 5-8 MHz transducer was used to identify the left anterior descending in the anterior interventricular sulcus from an apical four chamber window. We considered that left anterior descending was detected when a diastolic predominant flow pattern was obtained with pulse Doppler. RESULTS: Left anterior descending was detected in 37/39 of cases (94.4%). Patients with coronary lesions showed a decrease in the limit of significance in the diastolic/systolic peak velocity ratios: 2.5 (SD 0.7) vs 1.8 (SD 0.3) with a p = 0.024. Patients with anterior myocardial infarction obtained lower diastolic/systolic peak velocity ratios than controls: 2.5 (SD 0.7) vs 1.4 (SD 0.3) with a p = 0.001. CONCLUSIONS: Left anterior descending coronary artery flow can be assessed by transthoracic high frequency echocardiography in greater than 90% of the cases. Patients with coronary lesions and those with anterior myocardial infarction have a decreased diastolic/systolic peak velocity ratio.

Electromagnetic therapeutic angiogenesis: the next step.

Therapeutic angiogenesis, in the form of growth factor protein administration or gene therapy, is a new method of treatment for patients with severe coronary and peripheral artery disease not amenable to conventional methods of revascularization. Furthermore, a new experimental strategy increases endogenous angiogenesis in ischemic tissue to induce local 'angiogens' by means of electromagnetic stimulation. Further studies examining the molecular basis and clinical efficacy of electromagnetic angiogenesis are necessary.

Fibroblast growth factor cardioprotection against ischemia-reperfusion injury may involve K+ ATP channels.

We investigated whether the adenosine triphosphate (ATP)-sensitive K+ (K+ATP) channel that was implicated in the ischemic preconditioning (I-PC) phenomenon, has a role in the cardioprotective effects of fibroblast growth factors (FGFs). For this purpose, we administered glibenclamide, a specific K+ATP channel blocker, before acidic fibroblast growth factor (aFGF, FGF-1) treatment, in rat heart subjected to left ventricular ischemia for 20 minutes followed by reperfusion for 24 hours. Creatine kinase (CK) activity was analyzed in myocardial tissue to assess the degree of cardiac injury. FGF-1 treatment markedly maintains CK activity. This cardioprotective effect of FGF-1 was blocked by glibenclamide. As shown by ultrastructural data, Ca2+ overload and associated cardiomyocyte alterations shown in glibenclamide-treated rats were not observed in specimens from the FGF-1 group. These findings suggest that FGF serves as an effector in I-PC and support a clinical interest of these proteins for increasing myocardial ischemic tolerance.

Cardioprotection from ischemia by fibroblast growth factor: role of inducible nitric oxide synthase.

Growing evidence from both animal experiments and clinical observations indicates that fibroblast growth factor (FGF) plays a protective role in myocardial reperfusion injury. The molecular and cellular mechanisms that lead to this postischemic myocardial protection, however, remain largely unexplored. We studied the cardioprotective effects of human recombinant acidic fibroblast growth factor (aFGF, FGF-1) in a rat model of myocardial reperfusion injury, induced by 20 minutes of left coronary artery occlusion followed by 24 hours of reperfusion. Intravenous FGF-1 administration at the onset of heart reperfusion attenuated both the functional impairment and the histological changes of ischemia/reperfusion injury. FGF-1 increases more than twice the left ventricular contractile function (p <0.005) compared to vehicle-treated rats. As shown by histology, myocardial tissue is better preserved with FGF-1 treatment. The infarct size, normalized for the area at risk, was significantly smaller in the FGF-1 group (p <0.01) than in the vehicle group. Furthermore, FGF-1 administration resulted in expression of inducible nitric oxide synthase (iNOS) in the area at risk. Since increased expression of iNOS could potentiate cardioprotection against myocardial reperfusion injury, our findings support a new non-mitogenic role for FGF and add a clinical interest for this protein in increasing myocardial ischemic tolerance.

[Study of active myocardial damage in children with suspected myocarditis using antimyosin monoclonal antibodies (AMMoAb-111In)]. / Estudio evolutivo del daño miocárdica activo en niños con sospecha de miocarditis mediante anticuerpos monoclonales antimiosina (AbMoAM-111In).

BACKGROUND: The study with monoclonal antimyosin antibody-111In has proved to be useful in the detection of the myocardial damage present in different processes. There is active myocardial damage and specific antimyosin uptake in myocarditis, as both experimental and clinical trials have shown. In experimental models the evolution of myocardial damage has been studied, where a parallelism between the histological changes of the myocardial damage and the evolution on the antimyosin uptake has been found. In clinical myocarditis it is difficult to do an histological follow up of the inflammatory process, and therefore the evolution of myocardial damage present in myocarditis is unknown. The antimyosin antibody images allow a non-invasive study of this evolution. OBJECTIVES: a) to study with monoclonal antimyosin antibody-111In, the myocardial damage present regarding the disease evolution in children with suspected clinical diagnosis of myocarditis; b) to evaluate the evolution of the active myocardial damage reflected on the changes on the monoclonal antimyosin antibody-111In uptake. METHODS: A study with monoclonal antimyosin antibody-111In was carried out on 43 children, 16 males and 27 females with a median age of 39 months (SD 48 m; range: 2-167) with suspected diagnosis of acute myocarditis defined as the presence of congestive cardiac failure or severe ventricular arrhythmia with less than 12 months of evolution. The image evaluation was done visually and through the heart to lung ratio. Twenty of these patients were also followed up with antimyosin antibody scan for a period of 19 +/- 9 months, and 3.8 +/- 1.7 studies were performed on them in this time. RESULTS: The prevalence of positive myocardial uptake was 83.72%. There is a negative correlation (r = -0.352; p < 0.02) between the evolution time of the process and the heart to lung ratio: patients studied before two months, have a higher heart to lung ratio and greater prevalence of positive studies than those studied later (heart to lung ratio 2.09 vs 1.74; p = 0.013; 90% vs 69.2%). Of the patients followed up with antimyosin antibody scans, 6 showed a clinical relapse which increased their heart to lung ratio. The other 14 showed an progressive decrease of the heart to lung ratio reaching normality in 14 +/- 6 months. CONCLUSIONS: a) the uptake intensity of monoclonal antimyosin antibody-111In, as a reflection of the myocardial damage, depends on the disease evolution time, as in the first two months is when the major damage happens; b) the uptake intensity slowly decreases, tending to normality around the 14th month, although this evolution may be altered by the appearance of relapses.

Serum levels of basic fibroblast growth factor in acute myocardial infarction.

As it has been reported that basic fibroblast growth factor (bFGF) is a circulating peptide and bFGF gene expression is increased after myocardial ischemia, this study was designed to investigate the serum levels of bFGF in patients with acute myocardial infarction (AMI). Using a bFGF enzyme-linked immunoassay, bFGF levels were determined in venous blood of 15 patients with AMI on admission, at 10 days, and 30 days after infarction, and of 15 age-matched healthy volunteers who were used as controls. bFGF serum levels on admission were similar to normal values (7.48 +/- 2.3 vs 8.14 +/- 2.9 pg/ml). However, they significantly increased (16.82 +/- 3.4 pg/ml; p <0.05) 10 days after the onset of AMI, and at 30 days they returned to baseline (7.07 +/- 2.9 pg/ml). The increased bFGF levels at the second week post AMI suggest that bFGF plays an important role in mediating the development of coronary collateral circulation after myocardial ischemia in humans.

[Doppler echocardiography in hypertrophic myocardiopathy]. / Ecocardiografía-Doppler en la miocardiopatía hipertrófica.

Hypertrophic cardiomiopathy is a peculiar process with different anatomical and functional abnormalities which are present in different degrees in each case. Echocardiography and Doppler techniques have contributed definitively to the knowledge of this process and these procedures are choices for establishing the diagnosis of hypertrophic cardiomyopathy and to evaluate the clinical and morphological diversity of this process consisting of a spectrum of abnormalities with a variable presence in each case. Disproportionate septal hypertrophy is the most frecuent finding but the hypertrophy can involve other segments and different patterns can be present; concentric hypertrophy, apical, involving right ventricle, inverted asymetric, etc. Anterior mitral valve motion can be produced by the interrelation between anatomic factors of the valve, geometry of the outflow tract and physical forces produced by flow changes. Doppler echocardiography allows us to evaluate subaortic obstruction, to define its site, to demonstrate and measure the degree of mitral regurgitation and to carry out intraoperative studies. In hypertrophy cardiomyopathy the pattern of delayed relaxation is the most frequent but patients with severe obstruction and mitral regurgitation can pseudonormalize this pattern and even show restrictive patterns.

[Diagnostic methods in angina pectoris. The Angina Pectoris Study Group of the Ischemic Cardiopathy Section and Coronary Units of the Spanish Society of Cardiology]. / Métodos diagnósticos en la angina de pecho. Grupo de Estudio de Angina de Pecho de la Sección de Cardioplatía Isquémica y Unidades Coronarias de la Sociedad Espanola de Cardilogía.

Diagnosis and risk stratification in angina pectoris is supported on clinical evaluation, rest electrocardiogram, exercise stress test and coronary angiography. Use and timing application of that diagnostic methods depend on coronary artery disease prevalence and on clinical situation. This review describe diagnostic and prognostic value of the tests in angina pectoris.

[Hypertrophic obstructive myocardiopathy complicated by severe mitral insufficiency secondary to rupture of the chordae tendineae]. / Miocardiopatía hipertrófica obstructiva complicada con insuficiencia mitral severa secundaria a rotura de cuerdas tendinosas.

A case of suddenly increasing dyspnea in a patient with hypertrophic obstructive cardiomyopathy is reported. Transesophageal echocardiography showed severe mitral regurgitation secondary to ruptured chordae tendineae. Mitral valve replacement was done, correcting both mitral regurgitation and subaortic gradient. Utility of transesophageal echocardiography in diagnosis and therapeutic options are discussed.

[A sinus of Valsalva aneurysm ruptured into the right atrium secondary to aortic endocarditis. The usefulness of transthoracic and transesophageal echocardiography]. / Aneurisma de seno de Valsalva roto en aurícula derecha secundario a endocarditis aórtica. Utilidad de la ecocardiografía transtorácica y transesofágica.

We present a case of a sinus of Valsalva aneurysm ruptured into right atrium secondary to aortic endocarditis. Early surgical procedure was indicated bases on transthoracic echocardiography. This technique demonstrated a abscess image enlarged into the right atrium and color Doppler showed a turbulent flow from aortic valve to right atrium. Cardiac surgery was performed with transesophageal echocardiography monitoring. This technique allowed anatomical and functional aortic valve evaluation and the abscess location and extension. This case shows the value of transthoracic and transesophageal color Doppler echocardiography in the diagnosis and management of patients with complications secondary to infective endocarditis.

[Rupture of the intraventricular septum and free wall of the left ventricle secondary to non-penetrating thoracic injury. Doppler echocardiography diagnosis]. / Rotura de septo interventricular y pared libre de ventrículo izquierdo secundaria a traumatismo torácico no penetrante. Diagnóstico por ecocardiografía Doppler.

The heart is often injured in the setting of blunt chest trauma with a broad spectrum of cardiac lesions. We present a twenty-nine years old man with interventricular septal and rupture and left ventricular free wall rupture following chest trauma. Doppler echocardiography was essential in the diagnostic and therapeutic procedure. We concluded that Doppler-echocardiography must be performed in all patients with suspicion of cardiac affectation after blunt chest trauma.