Myocardial infarction (MI) is a life-threatening condition that leads to loss of viable heart tissue. The best way to treat acute MI and limit the infarct size is to re-open the occluded coronary artery and restore the supply of oxygenated and nutrient-rich blood, but reperfusion can cause additional damage. Autophagy is an intracellular process that recycles damaged cytoplasmic components (molecules and organelles) by loading them into autophagosomes and degrading them in autolysosomes. Autophagy is increased in in vivo animal models of permanent ischemia and ischemia/reperfusion but by different molecular mechanisms. While autophagy is protective during permanent ischemia, it is detrimental during ischemia/reperfusion. Its modulation is being investigated as a potential target to reduce reperfusion injury. This review provides a synopsis of the current knowledge about autophagy, summarizes findings specifically in permanent ischemia and ischemia/reperfusion, and briefly discusses the potential implication of experimental findings.
To investigate the local, downstream, and systemic effects of 2 different paclitaxel-coated balloons.
Preclinical study in healthy peripheral arteries of a swine model, with randomized allocation of the distribution of the devices: the test paclitaxel-coated balloon (PCB) (LuminorⓇ), a control PCB (IN.PACTⓇ), and a plain angioplasty balloon (OceanusⓇ), considering single (1×) and overlapping (3×) doses with simple blind histologic analysis.
Twenty animals underwent balloon angioplasty at 1× or 3× doses in the external and internal branches of both femoral arteries and were followed-up for 28 days. Postprocedural and follow-up angiography were carried out. Comprehensive necropsy and histology were used to evaluate the local, downstream and systemic effects.
Angioplasty was successfully carried out in all animals. Significant protocol deviations appeared in 3 arteries (treated with Oceanus®) without clinical relevance. Those samples were excluded from the analysis. All the animals survived the follow-up period without major clinical issues. Local signs of drug toxicity were less marked with Luminor® than IN.PACT® at 1× dose, including endothelial loss (P = .0828), intima/media inflammation (P = .0004), transmural medial smooth muscle cell (SMC) loss (P = .0016), wall thickness loss (P = .0141), presence of fibrin in the vascular wall (P = .0054), and adventitial inflammation (P = .0080). A similar pattern was observed at the 3× dose for endothelial loss (P = .0011), intima/media inflammation (P < .0001), circumferential SMC loss (P = .0004), medial SMC replacement with proteoglycans (P = .0014), fibrin (P = .0034), and collagen content (P = .0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (P = .006). No systemic effects of toxicity were detected in any of the samples analyzed.
Luminor® showed better healing pattern (lower inflammation, and endothelial and muscular loss) than IN.PACT® balloon. The effect was evident at single and triple doses. The prevalence of downstream lesions, albeit low, was higher with the triple dose of IN.PACT® compared with Luminor®.
Pericardial fluid (PF) contains cells, proteins, and inflammatory mediators, such as cytokines, chemokines, growth factors, and matrix metalloproteinases. To date, we lack an adequate understanding of the inflammatory response that acute injury elicits in the pericardial space.
To characterize the inflammatory profile in the pericardial space acutely after ischemia/reperfusion.
Pigs were used to establish a percutaneous ischemia/reperfusion injury model. PF was removed from pigs at different time points postanesthesia or postischemia/reperfusion. Flow cytometry was used to characterize the immune cell composition of PF, while multiplex analysis was performed on the acellular portion of PF to determine the concentration of inflammatory mediators. There was a minimum of 3 pigs per group.
While native PF mainly comprises macrophages, we show that neutrophils are the predominant inflammatory cell type in the pericardial space after injury. The combination of acute ischemia/reperfusion (IR) and repeatedly accessing the pericardial space significantly increases the concentration of interleukin-1 beta (IL-1β) and interleukin-1 receptor antagonist (IL-1ra). IR significantly increases the pericardial concentration of TGFβ1 but not TGFβ2. We observed that repeated manipulation of the pericardial space can also drive a robust pro-inflammatory response, resulting in a significant increase in immune cells and the accumulation of potent inflammatory mediators in the pericardial space.
In the present study, we show that both IR and surgical manipulation can drive robust inflammatory processes in the pericardial space, consisting of an increase in inflammatory cytokines and alteration in the number and composition of immune cells.

