Beneficial effects of direct call to emergency medical services in acute myocardial infarction.

OBJECTIVES: We investigated the impact of an emergency medical services call on the management of acute myocardial infarction, considering time intervals for intervention and revascularization procedures. METHODS: Data were prospectively collected from January 2001 to October 2002 from 531 patients hospitalized for myocardial infarction with ST segment elevation and a pre-hospital delay of less than 24 h. RESULTS: Only 26% of patients called the emergency medical services at the onset of symptoms (n=140). Other patients (n=391, 74%) called another medical contact. Baseline characteristics and cardiovascular history were similar in the two groups, except for the percutaneous coronary intervention history (10% in the emergency medical services group versus 4% in the other medical contact group, P<0.05). Time intervals from the onset of symptoms of myocardial infarction to call or to medical intervention, as well as the time interval from medical intervention to hospital admission were significantly shorter in the emergency medical services group. The early reperfusion rate was also significantly greater in the emergency medical services group (77%) compared with the other medical contact group (64%), mainly because of a greater incidence of primary percutaneous coronary intervention (36 versus 26%, P<0.03, respectively). Multivariate analysis adjusted for sex and age showed that less than three medical care providers [odds ratio (OR) 5.042, P<0.001], percutaneous coronary intervention history (OR 2.462, P<0.05), as well as rhythmic disorders (OR 2.105, P<0.05) and complete atrioventricular block (OR 2.757, P<0.05) were independent predictors of emergency medical services care. CONCLUSION: This study demonstrated that a call to the emergency medical services is underutilized by patients with symptoms of myocardial infarction, and documented the beneficial effects of an emergency medical services call by reducing pre-hospital delays and increasing early revascularization therapies.

Analysis of myosin heavy chain functionality in the heart.

Comparison of mammalian cardiac alpha- and beta-myosin heavy chain isoforms reveals 93% identity. To date, genetic methodologies have effected only minor switches in the mammalian cardiac myosin isoforms. Using cardiac-specific transgenesis, we have now obtained major myosin isoform shifts and/or replacements. Clusters of non-identical amino acids are found in functionally important regions, i.e. the surface loops 1 and 2, suggesting that these structures may regulate isoform-specific characteristics. Loop 1 alters filament sliding velocity, whereas Loop 2 modulates actin-activated ATPase rate in Dictyostelium myosin, but this remains untested in mammalian cardiac myosins. Alpha --> beta isoform switches were engineered into mouse hearts via transgenesis. To assess the structural basis of isoform diversity, chimeric myosins in which the sequences of either Loop 1+Loop 2 or Loop 2 of alpha-myosin were exchanged for those of beta-myosin were expressed in vivo. 2-fold differences in filament sliding velocity and ATPase activity were found between the two isoforms. Filament sliding velocity of the Loop 1+Loop 2 chimera and the ATPase activities of both loop chimeras were not significantly different compared with alpha-myosin. In mouse cardiac isoforms, myosin functionality does not depend on Loop 1 or Loop 2 sequences and must lie partially in other non-homologous residues.

Modelos animales genéticamente modificados en investigación cardiovascular / Genetically Modified Animal Models in Cardiovascular Research

Es un principio básico de la medicina clínica y molecular que la función de las células y los órganos se basa en elementos proteicos específicos. Puesto que la función de las células y en último término de los órganos depende de los polipéptidos que se encuentran presentes, no es sorprendente que cuando se altera la función se produzcan cambios en el contenido de proteínas. En el corazón existen numerosos ejemplos en los que cambios en las proteínas contráctiles se correlacionan con alteraciones funcionales, tanto durante el desarrollo normal como durante el desarrollo de numerosas patologías. De la misma manera, diversas enfermedades cardíacas congénitas se caracterizan por determinados cambios en las proteínas motoras. Para comprender esta relación, y para establecer modelos en los que los procesos patogénicos puedan ser estudiados longitudinalmente, es necesario dirigir el corazón para que sintetice de manera estable la proteína candidata, en ausencia de otros cambios pleiotrópicos. Posteriormente, se puede determinar si la presencia de la proteína causa directa o indirectamente los efectos con el objetivo de definir potenciales dianas terapéuticas. Mediante la manipulación controlada de la dotación proteica del corazón, se puede establecer el mecanismo y la función de diferentes proteínas mutadas o isoformas proteicas. La reconstrucción génica y la transgénesis en el ratón proporcionan herramientas para modificar el genoma de los mamíferos y la dotación proteica motora del corazón. Dirigiendo la expresión de una proteína modificada por ingeniería genética directamente al corazón, es posible remodelar de manera efectiva el perfil proteico cardíaco y estudiar las consecuencias de una única manipulación genética a nivel molecular, bioquímico, citológico y fisiológico, tanto en condiciones normales como bajo estímulos de estrés (AU)