Background: To elaborate the impact of new haemostatic agents we developed an instrument for the pressure-controlled induction of blunt liver injuries in a porcine animal model. Materials and Methods: A dilutional coagulopathy of 80% of animal blood volume was induced in 9 anaesthetized pigs. Animals were randomly assigned to be injured with a force of 112 Newton (N) (n = 1), 224 ± 19 N (n = 4) or 355 ± 35 N (n = 4). The impact of injury was measured by blood loss, survival time and coagulation parameters. Liver histology was obtained to evaluate the degree of liver injury. Results: The profound haemodilution resulted in a significant alteration of all coagulation parameters. After inflicting the injury with 355 ± 35 N, both the survival time (30 ± 9 min; p = 0.006) and blood loss (68 ± 16 ml min–1, p = 0.002) were significantly different as compared to injuries with 224 ± 19 N (survival time: 76 ± 20 min, blood loss: 23 ± 4 ml min–1). In contrast, an injury with 112 N led to an insignificant blood loss of only 239 ml. Conclusion: We developed a pressure-controlled clamp that allows for the induction of blunt liver traumas with highly reproducible injuries with a positive correlation with blood loss and survival.
Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca2+ channels (S-Bay K8644/verapamil) and Na+ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
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