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Background: Coronary artery disease remains a leading cause of death worldwide. Bone mesenchymal stem cell–derived extracellular vesicles (EVs) have shown promise in the setting of myocardial ischemia. Furthermore, the properties of the EVs can be modified via preconditioning of progenitor cells. Previous research from our lab demonstrated a significant decrease in proinflammatory signaling following treatment with EVs derived from starvation preconditioning of human bone mesenchymal stem cells (MVM EVs) in a porcine model of chronic myocardial ischemia. However, rodent models have demonstrated that the use of EVs derived from hypoxia preconditioning of bone mesenchymal stem cells (HYP EVs) may have extended benefits compared to MVM EVs. This study evaluated the effect of HYP EVs on inflammation in a swine model of chronic myocardial ischemia. We hypothesized that HYP EVs would have a greater anti-inflammatory effect than MVM EVs or saline (CON). Methods: Yorkshire swine fed a standard diet underwent placement of an ameroid constrictor to the left circumflex artery. Two weeks later, the animals received intramyocardial injection of saline (CON; n = 6), starvation-derived EVs (MVM; n = 10), or hypoxia-derived EVs (HYP; n = 7). After 5 weeks, myocardial perfusion was assessed, and left ventricular myocardial tissue was harvested. Protein expression was measured using immunoblotting. Data were analyzed via the Kruskal-Wallis test or one-way analysis of variance based on the results of a Shapiro-Wilk test. Coronary perfusion was plotted against relative cytokine concentration and analyzed with the Spearman rank-sum test. Results: HYP EV treatment was associated with decreased expression of proinflammatory markers interleukin (IL)-6 (P = .03), Pro-IL-1ß (P = .01), IL-17 (P

Background: Coronary artery disease remains a leading cause of death worldwide. Bone mesenchymal stem cell-derived extracellular vesicles (EVs) have shown promise in the setting of myocardial ischemia. Furthermore, the properties of the EVs can be modified via preconditioning of progenitor cells. Previous research from our lab demonstrated a significant decrease in proinflammatory signaling following treatment with EVs derived from starvation preconditioning of human bone mesenchymal stem cells (MVM EVs) in a porcine model of chronic myocardial ischemia. However, rodent models have demonstrated that the use of EVs derived from hypoxia preconditioning of bone mesenchymal stem cells (HYP EVs) may have extended benefits compared to MVM EVs. This study evaluated the effect of HYP EVs on inflammation in a swine model of chronic myocardial ischemia. We hypothesized that HYP EVs would have a greater anti-inflammatory effect than MVM EVs or saline (CON)., Methods: Yorkshire swine fed a standard diet underwent placement of an ameroid constrictor to the left circumflex artery. Two weeks later, the animals received intramyocardial injection of saline (CON; n = 6), starvation-derived EVs (MVM; n = 10), or hypoxia-derived EVs (HYP; n = 7). After 5 weeks, myocardial perfusion was assessed, and left ventricular myocardial tissue was harvested. Protein expression was measured using immunoblotting. Data were analyzed via the Kruskal-Wallis test or one-way analysis of variance based on the results of a Shapiro-Wilk test. Coronary perfusion was plotted against relative cytokine concentration and analyzed with the Spearman rank-sum test., Results: HYP EV treatment was associated with decreased expression of proinflammatory markers interleukin (IL)-6 ( P  = .03), Pro-IL-1ß ( P  = .01), IL-17 ( P  < .01), and NOD-like receptor protein 3 (NLRP3; P  < .01) compared to CON. Ischemic tissue from the MVM group showed significantly decreased expression of pro-inflammatory markers NLRP3 ( P  < .01), IL-17 ( P  < .01), and HLA class II histocompatibility antigen ( P  < .01) compared to CON. The MVM group also had decreased expression of anti-inflammatory IL-10 ( P  = .01) compared to CON counterparts. There were no significant differences in expression of tumor necrosis factor-α, interferon-γ, IL-12, Toll-like receptor-2, and nuclear factor kappa-light-chain-enhancer of activated B cells in either group . There was no correlation between coronary perfusion and cytokine concentration in the MVM or HYP groups, either at rest or with pacing., Conclusions: HYP EVs and MVM EVs appear to result in relative decreases in the degree of inflammation in chronically ischemic swine myocardium, independent of coronary perfusion. It is possible that this observed decrease may partially explain the myocardial benefits seen with both HYP and MVM EV treatment., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Objectives. We aimed to assess the spontaneous healing of myocardial function after occlusion of a chronically stenosed coronary vessel in a porcine model. Design. Ischemia and infarction was produced by Ameroid constrictor placement and a subsequent ligation of the left circumflex artery. Cardiac MRI and 18FDG-PET were performed one and five weeks later. Ki67 staining was used to identify proliferating cells. Results. Restoration of perfusion defect was detected by MRI (p=0.0065), reduced systolic function of the lateral segment spontaneously recovered (p=0.03). There was also a suggestive raise in impaired ejection fraction (p=0.06). Left ventricular early diastolic filling and peak filling rate were substantially improved (p=0.039 and p=0.0078). Scar size reduced (p=0.03). On the 18FDG-PET, deranged metabolism was alleviated (p=0.03). Cardiomyocytes with positive Ki-67 staining were located principally in the non-infarcted myocardium as compared to the infarction or border areas (p=0.037). Conclusions. We demonstrated spontaneous functional healing of ischemic and infarcted left ventricle, suggesting border zone perfusion recovery. Scar reduction was detected. Different pattern of myocyte proliferation between infarction and non-ischemic myocardium was seen. [ABSTRACT FROM AUTHOR]

The purpose of this work was to develop a device which allows slow progressive banding of a great artery in infants within 4 to 5 weeks. Employed was the hygroscopic casein ameroid. When brought in contact with fluids, an ameroid cylinder expands characteristically. An early phase of fast expansion proceeds gradually to a phase of slow growth. Size, shape, and encasement of ameroid as well as temperature and type of surrounding fluid modify but do not alter the typical pattern of expansion. The developed constrictor (weight: 5.8 kg, length: 18 mm, diameter: 12 mm) includes a stainless steel socket containing an ameroid cylinder (length: 8.5 mm, diameter: 8 mm). The expanding ameroid pushes a piston with a concave extension (makrolon) a maximum of 2 mm against the artery, which is fixed to the metal housing by a teflon band (width: 4 mm, thickness: 0.5 mm). The band runs in 2 fitting grooves on the metal housing to which it is fixed by a metal ring with a precisely manufactured internal thread allowing exact tightening and loosening of the band around the artery. Utilization of inert materials like teflon, makrolon, and stainless steel warrents experimental and possibly clinical application of the developed small constrictor. [ABSTRACT FROM AUTHOR]