Background The optimal enzyme blend which maximizes human islets yield for transplantation remains to be determined. In this study, we evaluated 8 different enzyme combinations (ECs) in an attempt to improve islet yield. The ECs consisted of purified, intact, or truncated class 1 (C1) and class 2 (C2) collagenases from Clostridium histolyticum (Ch) as well as neutral protease (NP) from Bacillus thermoproteolyticus rokko (thermolysin) or Ch (ChNP). Methods We report the results of 249 human islet isolations, including 99 deceased donors (research n=57, clinical n=42) and 150 chronic pancreatitis pancreases. We prepared a new enzyme mixture (NEM) composed of intact C1 and C2 collagenases and ChNP instead of using thermolysin. The NEM was first tested in split pancreas (n=5) experiments and then used for islet autologous (n=21) and allogeneic transplantation (n=10). Islet isolation outcomes from 8 different Ecs were statistically compared using multivariate analysis. Results The NEM consistently achieved higher islet yields from pancreatitis (p<0.003) and deceased donor pancreases (p<0.001) than other standard ECs. Using the NEM, islet products met release criteria for transplantation from 8 of 10 consecutive pancreases, averaging 6510±2150 IEQ/g pancreas and 694,681±147,356 total IEQ/transplantation. In autologous isolation, the NEM yielded >200,000 IEQ from 19 of 21 pancreases (averaging 422,893±181,329 total IEQ and 5979±1469 IEQ/kg recipient body weight) regardless of the severity of fibrosis. Conclusions A new enzyme mixture composed of Clostridium histolyticum neutral protease with CIzyme high intact C1 collagenase recovers higher islet yield from deceased and pancreatitis pancreases while retaining islet quality and function.
Implantation of rotary blood pumps is an established treatment for end-stage heart failure. Anticoagulation is routinely used for reducing pump thrombosis, but this severe complication still occurs in 5-8% of patients. In 105 patients, the sound produced by the left ventricular assist device HeartWare HVAD was prospectively and sequentially recorded. The acoustic spectra calculated by runtime fast Fourier transformation were investigated. Results were compared with respect to patients without thrombotic complications (97 patients) and those with signs of pump thrombosis (8 patients). All eight pumps exchanged were opened and investigated. Thrombus formation was confirmed in all eight exchanged pumps. The existence of a sound peak with the threefold frequency of the pump speed correlated with the presence of thrombi inside the pump (p < 0.001). An increase in the sound amplitude of the rotary frequency of approximately 75% compared to previous measurements also denotes pump thrombosis. Analysis of the acoustic spectrum of the HVAD pump can be used as a reliable method to detect pump thrombosis. The appearance of third harmonics indicates the presence of thrombotic particles independently of previous baseline measurements. The goal of this study is to define and validate such a method.
Aims Haemodynamic load induces cardiac remodelling via mechano-transduction pathways, which can further trigger inflammatory responses. We hypothesized that particularly in an inflammatory disorder such as myocarditis, a therapeutic strategy is required which, in addition to providing adequate circulatory support, unloads the left ventricle, decreases cardiac wall stress, and mitigates inflammatory responses. Methods and results Axial flow pumps such as the Impella systems comply with these requirements. Here, we report a potential mode-of-action of prolonged Impella support (PROPELLA concept) in fulminant myocarditis, including a decrease in cardiac immune cell presence, and integrin α1, α5, α6, α10 and β6 expression during unloading. Conclusion PROPELLA may provide benefits beyond its primary function of mechanical circulatory support in the form of additional disease-altering effects, which may contribute to enhanced myocardial recovery/remission in patients with chronic fulminant myocarditis.
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