The New 3D Printed Left Atrial Appendage Closure with a Novel Holdfast Device: A Pre-Clinical Feasibility Animal Study.

INTRODUCTION: Many patients undergoing cardiac surgery have risk factors for both atrial fibrillation (AF) and stroke. The left atrial appendage (LAA) is the primary site for thrombi formation. The most severe complication of emboli derived from LAA is stroke, which is associated with a 12-month mortality rate of 38% and a 12-month recurrence rate of 17%. The most common form of treatment for atrial fibrillation and stroke prevention is the pharmacological therapy with anticoagulants. Nonetheless this form of therapy is associated with high risk of major bleeding. Therefore LAA occlusion devices should be tested for their ability to reduce future cerebral ischemic events in patients with high-risk of haemorrhage. AIM: The aim of this study was to evaluate the safety and feasibility of a novel left atrial appendage exclusion device with a minimally invasive introducer in a swine model. MATERIALS AND METHODS: A completely novel LAA device, which is composed of two tubes connected together using a specially created bail, was designed using finite element modelling (FEM) to obtain an optimal support force of 36 N at the closure line. The monolithic form of the occluder was obtained by using additive manufacturing of granular PA2200 powder with the technology of selective laser sintering (SLS). Fifteen swine were included in the feasibility tests, with 10 animals undergoing fourteen days of follow-up and 5 animals undergoing long-term observation of 3 months. For one animal, the follow-up was further prolonged to 6 months. The device was placed via minithoracotomy. After the observation period, all of the animals were euthanized, and their hearts were tested for LAA closure and local inflammatory and tissue response. RESULTS: After the defined observation period, all fifteen hearts were explanted. In all cases the full closure of the LAA was achieved. The macroscopic and microscopic evaluation of the explanted hearts showed that all devices were securely integrated in the surrounding tissues. No pericarditis or macroscopic signs of inflammation at the site of the device were found. All pigs were in good condition with normal weight gain and no other clinical symptoms. CONCLUSION: This novel 3D printed left atrial appendage closure technique with a novel holdfast device was proven to be safe and feasible in all pigs. A benign healing process without inflammation and damage to the surrounding structures or evidence of new thrombi formation was observed. Moreover, the uncomplicated survival and full LAA exclusion in all animals demonstrate the efficacy of this novel and relatively cheap device. Further clinical evaluation and implementation studies should be performed to introduce this new technology into clinical practice.

Studies of the effect of grasshopper abdominal secretion on wound healing with the use of murine model.

ETHNOPHARMACOLOGICAL RELEVANCE: Grasshopper, belonging to Chorthippus sp., is a widespread insect inhabiting Polish territory. According to folk knowledge and folk tales, the grasshopper abdominal secretion was used by villagers of Central and South-West Poland as a natural drug accelerating the wound healing process. AIM OF THE STUDY: In the reported study the hypothesis about beneficial properties of grasshopper abdominal secretion on hard to heal wounds was verified. MATERIALS AND METHODS: The study was carried out with the use of a murine model (mice C57BL/6). In order to verify the beneficial properties of grasshopper abdominal secretion, the wounds of 8mm in diameter were formed on one side of each tested mouse. The influence of ethanolic extract of insects' secretion on healing process was evaluated in comparison to ethanolic solution of allantoin and 30% aqueous solution of ethanol (medium). The observation was carried out over a 14 day period. Finally the statistical analysis (ANOVA) was carried out to highlight the differences in wound healing rate between applied preparations. Moreover, qualitative composition of grasshoppers' secretion was studied with the use of GC/MS technique. RESULTS: During the first three days of observation, wounds treated with allantoin were healed with higher efficiency in comparison to ethanol and insect secretion preparations. The trend of healing changed from the 4th day of observation. Wounds treated with grasshoppers' abdominal secretion were closuring faster than wounds treated with allantoin or ethanol. In this part of observation, in the case of allantoin and ethanol application, the wound healing efficiency was similar. Since the 9th day of experiment the measurement of wounds size was problematic, due to crust formation. Finally at the 14th day of the study, wounds were totally healed. Morphological study enabled to observe all the phases of healing. In the 5th and 8th day, the infiltration of neutrophils and mononuclear cells in dermis was observed, which is characteristic for inflammatory phase of wound healing. On the 8th day of experiments, granulation of the tissue was clearly observed in the tested groups. Reepithelialization phase was observed from the 5th to 14th day, when the wound was totally healed. The analytical approach enabled to identify 38 compounds of hydrophobic or hydrophilic character. Among them, 6 amino acids, 14 organic acids and their derivatives, one sterol, 4 hydrocarbons, 5 carbohydrates, 2 inorganic acids, 4 alcohols, one diamine and one nucleoside were identified. CONCLUSION: The obtained results enabled to recognize the composition of grasshopper abdominal secretion. Some of the identified compounds possess therapeutic properties described in the literature. The performed in vivo study proved that application of insects secretion accelerates the healing process. The obtained results positively verified the scientific hypothesis based on ethnopharmacological premises about the beneficial properties of grasshopper abdominal secretion on wound healing process.