Peng, Lillian T

Objective The aim of the study was to compare vaginal wound healing after exosome injection in a porcine mesh exposure model with (1) single versus multiple dose regimens and (2) acute versus subacute exposure. Methods Six 80-kg Yorkshire-crossed swine each had 2 polypropylene meshes implanted to create the vaginal mesh exposure model. Animals were divided into 3 groups based on number and timing of exosome injection: (1) single purified exosome product (PEP) injection (acute-single), (2) weekly PEP injections (acute-weekly, 4 total injections), and (3) delayed single injection (subacute-single). Acute and subacute injections occurred 1 and 8 weeks after mesh implantation, respectively. EdU, a thymidine analog, was given twice weekly after the first injection to track tissue regeneration. Euthanasia and tissue analysis occurred 4 weeks after the first injection. ImageJ was used to quantify epithelial thickness, cellular proliferation, and capillary density. Statistical analysis was performed using analysis of variance and post hoc Tukey test. Results Acute-single PEP injection tissues mirrored pilot study results, validating replication of protocol. Within the acute groups, weekly dosing resulted in 1.5× higher epithelial thickness (nonsignificant), 1.8× higher epithelial proliferation ( P < 0.05), and 1.5× higher regenerated capillary density ( P < 0.05) compared with single injection. Regarding chronicity of the exposure, the subacute group showed 1.7× higher epithelial proliferation (nonsignificant) and similar capillary density and epithelial thickness as compared with the acute group. Conclusions Exosome redosing resulted in significantly greater epithelial proliferation with significantly higher regenerated capillary density, leading to a trend toward thicker epithelium. Subacute exposure exhibited similar regeneration to acute exposure despite a delayed injection timeline. These results contribute to a growing body of preclinical research demonstrating utility of exosomes in pelvic floor disorders.

Abstract Background Left ventricular outflow tract (LVOT) obstruction is an important determinant of the management of hypertrophic cardiomyopathy (HCM). With a nationwide shortage of amyl nitrite in 2019, we implemented a ‘repetitive squat-to-stand’ manoeuvre to provoke LVOT obstruction during echocardiography. Case summary A 64-year-old female was referred with symptomatic HCM refractory to pharmacologic therapy. Transthoracic echocardiography showed minor LVOT obstruction with conventional imaging at rest and during Valsalva manoeuvre, but severe obstruction was confirmed with the repetitive squat-to-stand manoeuvre. Alcohol septal ablation via the first septal perforator was performed with subsequent resolution of symptoms. Discussion Due to the dynamic nature of LVOT obstruction, a series of provocative manoeuvres including Valsalva manoeuvre, inhalation of amyl nitrite, and exercise are often necessary to maximally augment ventricular obstruction. The recent unavailability of amyl nitrite during a nationwide shortage prompted the implementation of a protocol of repetitive squat-to-stand manoeuvre in our echocardiography laboratory. Rising from the squatting position decreases preload and afterload, both of which augment dynamic LVOT obstruction. Repetition of squatting and standing appears to enhance the sensitivity of the manoeuvre, particularly when exertional symptoms are reproduced. In this case, repetitive squat-to-stand manoeuvre led to the identification of severe LVOT obstruction which may not have been diagnosed otherwise, alteration of treatment to septal reduction therapy, and subsequent resolution of symptoms.