Abstract
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.
Highlights
We recently reported beneficial effects of hypothermia in a novel swine ischemia-reperfusion model (Marek-Iannucci et al, 2019)
The focus of our study is to investigate the influence of Therapeutic hypothermia (TH) on myocardial remodeling on a molecular basis, with the goal of inhibiting the adverse effects of remodeling after myocardial infarction (MI) and preventing chronic heart failure
By using echocardiography our group published a significant increase in E, a reduced E/E and left atrial pressure (LAP) in the cold group compared to the warm, suggesting improved diastolic function, when using this technique (Marek-Iannucci et al, 2019)
Summary
We recently reported beneficial effects of hypothermia in a novel swine ischemia-reperfusion model (Marek-Iannucci et al, 2019). Methods used in the clinical setting include retrograde cold perfusion through the coronary sinus, endovascular cooling with special catheters, intraperitoneal cooling systems, cold saline infusions and topical cooling with cooling pads or blankets (Erlinge et al, 2014; Herring et al, 2014; Nichol et al, 2015; Kloner et al, 2017) This leads us in two possible directions regarding future studies: First, the right technique regarding TH application, implementable in the clinical setting has not been found yet (Herring et al, 2014). This model can be used for various other studies requiring direct application of substances or stimulation of the myocardium
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