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RationaleAdverse remodeling leads to heart failure after myocardial infarction (MI), with important impact on morbidity and mortality. New therapeutic approaches are needed to further improve and broaden heart failure therapy. We established a minimally invasive, reproducible pericardial irrigation model in swine, as a translational model to study the impact of temperature on adverse cardiac remodeling and its molecular mechanisms after MI.ObjectiveChronic heart failure remains a leading cause of death in western industrialized countries, with a tremendous economic impact on the health care system. Previously, many studies have investigated mechanisms to reduce infarct size after ischemia/reperfusion injury, including therapeutic hypothermia. Nonetheless, the molecular mechanisms of adverse remodeling after MI remain poorly understood. By deciphering the latter, new therapeutic strategies can be developed to not only reduce rehospitalization of heart failure patients but also reduce or prevent adverse remodeling in the first place.Methods and ResultsAfter 90 min of MI, a 12Fr dual lumen dialysis catheter was place into the pericardium via minimal invasive, sub-xiphoidal percutaneous puncture. We performed pericardial irrigation with cold or warm saline for 60 min in 25 female farm pigs after ischemia and reperfusion. After one week of survival the heart was harvested for further studies. After cold pericardial irrigation we observed a significant decrease of systemic body temperature measured with a rectal probe in the cold group, reflecting that the heart was chilled throughout its entire thickness. The temperature remained stable in the control group during the procedure. We did not see any difference in arrhythmia or hemodynamic stability between both groups.ConclusionWe established a minimally invasive, reproducible and translational model of pericardial irrigation in swine. This method enables the investigation of mechanisms involved in myocardial adverse remodeling after ischemia/reperfusion injury in the future.

The adult human heart has an exceptional ability to alter its phenotype to adapt to changes in environmental demand. This response involves metabolic, mechanical, electrical, and structural alterations, and is known as cardiac plasticity. Understanding the drivers of cardiac plasticity is essential for development of therapeutic agents. This is particularly important in contemporary cardiology, which uses treatments with peripheral effects (e.g., on kidneys, adrenal glands). This review focuses on the effects of different hemodynamic loads on myocardial phenotype. We examine mechanical scenarios of pressure- and volume overload, from the initial insult, to compensated, and ultimately decompensated stage. We discuss how different hemodynamic conditions occur and are underlined by distinct phenotypic and molecular changes. We complete the review by exploring how current basic cardiac research should leverage available cardiac models to study mechanical load in its different presentations.

Rationale: Adverse remodeling leads to heart failure after myocardial infarction (MI), with important impact on morbidity and mortality. New therapeutic approaches are needed to further improve and broaden heart failure therapy. We established a minimally invasive, reproducible pericardial irrigation model in swine, as a translational model to study the impact of temperature on adverse cardiac remodeling and its molecular mechanisms after MI. Objective: Chronic heart failure remains a leading cause of death in western industrialized countries, with a tremendous economic impact on the health care system. Previously, many studies have investigated mechanisms to reduce infarct size after ischemia/reperfusion injury, including therapeutic hypothermia. Nonetheless, the molecular mechanisms of adverse remodeling after MI remain poorly understood. By deciphering the latter, new therapeutic strategies can be developed to not only reduce rehospitalization of heart failure patients but also reduce or prevent adverse remodeling in the first place. Methods and Results: After 90 min of MI, a 12Fr dual lumen dialysis catheter was place into the pericardium via minimal invasive, sub-xiphoidal percutaneous puncture. We performed pericardial irrigation with cold or warm saline for 60 min in 25 female farm pigs after ischemia and reperfusion. After one week of survival the heart was harvested for further studies. After cold pericardial irrigation we observed a significant decrease of systemic body temperature measured with a rectal probe in the cold group, reflecting that the heart was chilled throughout its entire thickness. The temperature remained stable in the control group during the procedure. We did not see any difference in arrhythmia or hemodynamic stability between both groups. Conclusion: We established a minimally invasive, reproducible and translational model of pericardial irrigation in swine. This method enables the investigation of mechanisms involved in myocardial adverse remodeling after ischemia/reperfusion injury in the future. [ABSTRACT FROM AUTHOR]

The adult human heart has an exceptional ability to alter its phenotype to adapt to changes in environmental demand. This response involves metabolic, mechanical, electrical, and structural alterations, and is known as cardiac plasticity. Understanding the drivers of cardiac plasticity is essential for development of therapeutic agents. This is particularly important in contemporary cardiology, which uses treatments with peripheral effects (e.g., on kidneys, adrenal glands). This review focuses on the effects of different hemodynamic loads on myocardial phenotype. We examine mechanical scenarios of pressure- and volume overload, from the initial insult, to compensated, and ultimately decompensated stage. We discuss how different hemodynamic conditions occur and are underlined by distinct phenotypic and molecular changes. We complete the review by exploring how current basic cardiac research should leverage available cardiac models to study mechanical load in its different presentations. [ABSTRACT FROM AUTHOR]

Anatomical evidence in several species shows highly heterogeneous fat distribution in the atrial and ventricular myocardium. Atrial appendages have fat deposits, and more so on the posterior left atrium. Although such fat distributions are considered normal, fatty infiltration is regarded arrhythmogenic, and various cardiac pathophysiological conditions show excess myocardial fat deposits, especially in the epicardium. Hypotheses have been presented for the physiological and pathophysiological roles of epicardial fat, however this issue is poorly understood. Therefore, this mini-review will focus on epicardial fat distribution and the (patho)-physiological implications of this distribution. Potential molecular mechanisms that may drive structural and electrical myocardial remodeling attendant to fatty infiltration of the heart are also reviewed.

Anatomical evidence in several species shows highly heterogeneous fat distribution in the atrial and ventricular myocardium. Atrial appendages have fat deposits, and more so on the posterior left atrium. Although such fat distributions are considered normal, fatty infiltration is regarded arrhythmogenic, and various cardiac pathophysiological conditions show excess myocardial fat deposits, especially in the epicardium. Hypotheses have been presented for the physiological and pathophysiological roles of epicardial fat, however this issue is poorly understood. Therefore, this mini-review will focus on epicardial fat distribution and the (patho)-physiological implications of this distribution. Potential molecular mechanisms that may drive structural and electrical myocardial remodeling attendant to fatty infiltration of the heart are also reviewed. [ABSTRACT FROM AUTHOR]