Apical Resection and Cryoinjury of Neonatal Mouse Heart.

Neonatal mouse hearts have a regenerative capacity similar to adult zebrafish. Different cardiac injury models have been established to investigate the regenerative capacity of neonatal mouse hearts, including ventricular amputation, cryoinjury, and ligation of a major coronary artery. While the ventricular resection model can be utilized to study how tissue forms and regenerates de novo, cryoinjury and coronary artery ligation are methods that might better mimic myocardial infarction by creating tissue damage and necrosis as opposed to the removal of healthy tissue in the ventricular amputation model. Here we describe methods of creating ventricular resection and cardiac cryoinjury in newborn mice.

Ventricular Cryoinjury as a Model to Study Heart Regeneration in Zebrafish.

Zebrafish have the capacity to regenerate most of its organs upon injury, including the heart. Due to its amenability for genetic manipulation, the zebrafish is an excellent model organism to study the cellular and molecular mechanisms promoting heart regeneration. Several cardiac injury models have been developed in zebrafish, including ventricular resection, genetic ablation, and ventricular cryoinjury. This chapter provides a detailed protocol of zebrafish ventricular cryoinjury and highlights factors and critical steps to be considered when performing this method.

A Genetic Cardiomyocyte Ablation Model for the Study of Heart Regeneration in Zebrafish.

Adult zebrafish possess an elevated cardiac regenerative capacity as compared with adult mammals. In the past two decades, zebrafish have provided a key model system for studying the cellular and molecular mechanisms of innate heart regeneration. The ease of genetic manipulation in zebrafish has enabled the establishment of a genetic ablation injury model in which over 60% of cardiomyocytes can be depleted, eliciting signs of heart failure. After this severe injury, adult zebrafish efficiently regenerate lost cardiomyocytes and reverse heart failure. In this chapter, we describe the methods for inducing genetic cardiomyocyte ablation in adult zebrafish, assessing cardiomyocyte proliferation, and histologically analyzing regeneration after injury.

Decoding an organ regeneration switch by dissecting cardiac regeneration enhancers.

Heart regeneration in regeneration-competent organisms can be accomplished through the remodeling of gene expression in response to cardiac injury. This dynamic transcriptional response relies on the activities of tissue regeneration enhancer elements (TREEs); however, the mechanisms underlying TREEs are poorly understood. We dissected a cardiac regeneration enhancer in zebrafish to elucidate the mechanisms governing spatiotemporal gene expression during heart regeneration. Cardiac lepb regeneration enhancer (cLEN) exhibits dynamic, regeneration-dependent activity in the heart. We found that multiple injury-activated regulatory elements are distributed throughout the enhancer region. This analysis also revealed that cardiac regeneration enhancers are not only activated by injury, but surprisingly, they are also actively repressed in the absence of injury. Our data identified a short (22 bp) DNA element containing a key repressive element. Comparative analysis across Danio species indicated that the repressive element is conserved in closely related species. The repression mechanism is not operational during embryogenesis and emerges when the heart begins to mature. Incorporating both activation and repression components into the mechanism of tissue regeneration constitutes a new paradigm that might be extrapolated to other regeneration scenarios.

Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration.

In zebrafish, the role of matrix metalloproteinases (MMPs) in the inflammatory phase of heart regeneration following cryoinjury remains poorly understood. Here, we demonstrated an increase in MMP enzymatic activity and elevated expression of mmp9 and mmp13 in the injured area (IA) of hearts from as early as 1 day post-cryoinjury (dpc). Treatment with the broad-spectrum MMP inhibitor, GM6001, during the first week after cryoinjury resulted in impaired heart regeneration, as indicated by the larger scar and reduced numbers of proliferating cardiomyocytes. GM6001 also significantly reduced the number of leukocytes to the IA at 0.5 dpc to 4 dpc. Specific inhibition of both MMP-9 and MMP-13 also resulted in impaired regeneration and leukocyte recruitment. However, chemokine rescue with recombinant CXCL8 and CCL2 restored the recruitment of macrophages and the cardiac regenerative capability in GM6001-treated fish. MMP-9 and MMP-13 cleaved zebrafish CXCL8 at the same site, and the truncated form was more chemotactic than the intact form. In contrast, CCL2 did not have an MMP-9 or MMP-13 cleavage site. Together, these data suggest that MMPs might play a key role in the inflammatory phase of heart regeneration in zebrafish, by mediating leukocyte recruitment via the activation of chemokines.

Dynamics of Zebrafish Heart Regeneration Using an HPLC-ESI-MS/MS Approach.

Failure to properly repair damaged due to myocardial infarction is a major cause of heart failure. In contrast with adult mammals, zebrafish hearts show remarkable regenerative capabilities after substantial damage. To characterize protein dynamics during heart regeneration, we employed an HPLC-ESI-MS/MS (mass spectrometry) approach. Myocardium tissues were taken from sham-operated fish and ventricle-resected sample at three different time points (2, 7, and 14 days); dynamics of protein expression were analyzed by an ion-current-based quantitative platform. More than 2000 protein groups were quantified in all 16 experiments. Two hundred and nine heart-regeneration-related protein groups were quantified and clustered into six time-course patterns. Functional analysis indicated that multiple molecular function and metabolic pathways were involved in heart regeneration. Interestingly, Ingenuity Pathway Analysis revealed that P53 signaling was inhibited during the heart regeneration, which was further verified by real-time quantitative polymerase chain reaction (Q-PCR). In summary, we applied systematic proteomics analysis on regenerating zebrafish heart, uncovered the dynamics of regenerative genes expression and regulatory pathways, and provided invaluable insight into design regenerative-based strategies in human hearts.

Calidad de vida del paciente con enfermedad cardiovascular que asiste al programa de rehabilitación cardiaca / Quality of life of patients with cardiovascular disease to attending cardiac rehabilitation / Qualidade de vida de pacientes com doença cardiovascular para atendimento reabilitação cardíaca

La enfermedad cardiovascular es un problema de salud pública en expansión, pues es la principal causa de muerte en el mundo y afecta las dimensiones físicas, sociales y emocionales de la calidad de vida del paciente. Por lo anterior, se hace necesario que el profesional de enfermería intervenga en la mejora de la calidad de vida, promoviendo la participación de los pacientes en los programas de rehabilitación cardiaca y aplicando herramientas útiles para la determinación de la calidad de vida, a fin de lograr una medición más comprensiva, integral y válida del estado de salud de los pacientes con enfermedades cardiovasculares y la efectividad de la atención ofrecida dentro del programa. El propósito de este artículo es proporcionar a los profesionales de enfermería fundamentos relacionados con la calidad de vida del paciente con enfermedad cardiovascular que asisten a programas de rehabilitación cardiaca y los instrumentosgenéricos o específicos que se pueden utilizar como herramientas útiles de valoración y seguimiento de la calidad de vida...

Cardiovascular disease has become a public health problem in expansion, being the leading cause of death worldwide and affecting the physical, social and emotional quality of life of patients. Therefore, it is necessary that the nurse involved in improving the quality of life, promoting the participation of patients in cardiac rehabilitation programs, using tools for determining the quality of life, thus achieving a more comprehensive measurement and valid health status of patients with cardiovascular disease and the effectiveness of care offered within the program. The purpose of this review paper is to provide research results to nurses foundation related to quality of life of patients with cardiovascular disease who attend cardiac rehabilitation programs and generic or specific instruments thatcan be used as tools assessment and monitoring of the quality of life...

Doença cardiovascular tornou-se um problema de saúde pública em expansão, sendo a principal causa de morte no mundo e que afetam a qualidade física, social e emocional da vida dos pacientes. Portanto, é necessário que a enfermeira envolvida na melhoria da qualidade de vida, promovendo a participação dos pacientes em programas de reabilitação cardíaca, o uso de ferramentas para determinar a qualidade de vida, alcançando assim uma medida mais abrangente e estado de saúde válido de pacientes com doença cardiovascular ea eficácia dos cuidados oferecidos dentro do programa. O objetivo deste artigo de revisão é fornecer resultados de pesquisa para enfermeiras fundação relacionados à qualidade de vida de pacientes com doenças cardiovasculares que freqüentam programas de reabilitação cardíaca e instrumentos genéricos ou específicos que podem ser usados como ferramentas de avaliação e monitoramento da qualidade de vida...

Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish.

The zebrafish heart has the capacity to regenerate after ventricular resection. Although this regeneration model has proved useful for the elucidation of certain regeneration mechanisms, it is based on the removal of heart tissue rather than its damage. Here, we characterize the cellular response and regenerative capacity of the zebrafish heart after cryoinjury, an alternative procedure that more closely models the pathophysiological process undergone by the human heart after myocardial infarction (MI). Localized damage was induced in 25% of the ventricle by cryocauterization (CC). During the first 24 hours post-injury, CC leads to cardiomyocyte death within the injured area and the near coronary vasculature. Cell death is followed by a rapid proliferative response in endocardium, epicardium and myocardium. During the first 3 weeks post-injury cell debris was cleared and the injured area replaced by a massive scar. The fibrotic tissue was subsequently degraded and replaced by cardiac tissue. Although animals survived CC, their hearts showed nonhomogeneous ventricular contraction and had a thickened ventricular wall, suggesting that regeneration is associated with processes resembling mammalian ventricular remodeling after acute MI. Our results provide the first evidence that, like mammalian hearts, teleost hearts undergo massive fibrosis after cardiac damage. Unlike mammals, however, the fish heart can progressively eliminate the scar and regenerate the lost myocardium, indicating that scar formation is compatible with myocardial regeneration and the existence of endogenous mechanisms of scar regression. This finding suggests that CC-induced damage in zebrafish could provide a valuable model for the study of the mechanisms of scar removal post-MI.

Rehabilitación cardíaca en España. Encuesta SORECAR / Cardiac Rehabilitation in Spain. SORECAR survey

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[Heart injuries]. / Raneniia serdtsa.

Operations were carried out on 32 patients with injuries to the heart and pericardium during a period of 14 years. The pericardium was injured in 7 patients. All fatal cases were brought to the clinic in the first 30 minutes after the accident. Seven patients died after operation. The late results were studied in 22 patients in follow-up periods of 12 months to 14 years. The results were excellent and good in 20 patients and satisfactory in 2 patients. Poor results were not encountered. The capacity for work was restored in 21 patients.

[Peace-time heart injuries]. / O reneniiakh serdtsa mirnogo vrenmeni.

Basing on the experience of treatment of 23 patients the authors emphasize the importance of rendering the correct urgent aid to patients with such injuries. Cases of injuries of "dangerous zones" of the heart are analyzed. Postoperative complications in such patients are described. The conclusion is made that the time is a decisive factor in decreasing the mortality rate of patients with heart injuries.

[Regeneration of the myocardium of fetuses and newborn rabbits]. / O regeneratsii miokarda plodiv i novorozhdennykh krolikov

The work is devoted to studies of regeneration of the myocardium in fetuses and newborns of rabbits after a mechanical trauma of the heart. It was established that in fetuses under natural conditions of the alive organism instead of the perished tissue of the myocardium during the period of 5-8 days there developed a wholesome transverse-striated musculature whose fibers contained glycogen and redox enzymes. In newborn rabbits the defect of the myocardium was replaced by a mature fibrous connective tissue, regeneration was accomplished at the expence of hyperplasia of intracellular ultrastructures. The loss by the heart muscular tissue of the capacity for complete regeneration takes place within the 24th day of the intrauterine development and the 1st day of life.