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OBJECTIVE: This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (ICa,L) in Guinea pig ventricular cardiomyocytes. METHODS: Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated ICa,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes. RESULTS: Light pulses activated ICa,L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered ICa,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. CONCLUSION: OEPC-mediated activation of ICa,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of ICa,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices. SIGNIFICANCE: Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.
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Background: Surgical interventions can cause severe fluid imbalances in patients undergoing cardiac surgery, affecting length of hospital stay and survival. Therefore, appropriate management of daily fluid goals is a key element of postoperative intensive care in these patients. Because fluid balance is influenced by a complex interplay of patient-, surgery- and intensive care unit (ICU)-specific factors, fluid prediction is difficult and often inaccurate. Methods: A novel system theory based digital model for cumulative fluid balance (CFB) prediction is presented using recorded patient fluid data as the sole parameter source by applying the concept of a transfer function. Using a retrospective dataset of n = 618 cardiac intensive care patients, patient-individual models were created and evaluated. RMSE analyses and error calculations were performed for reasonable combinations of model estimation periods and clinically relevant prediction horizons for CFB. Results: Our models have shown that a clinically relevant time horizon for CFB prediction with the combination of 48 h estimation time and 8-16 h prediction time achieves high accuracy. With an 8-h prediction time, nearly 50% of CFB predictions are within ±0.5 L, and 77% are still within the clinically acceptable range of ±1.0 L. Conclusion: Our study has provided a promising proof of principle and may form the basis for further efforts in the development of computational models for fluid prediction that do not require large datasets for training and validation, as is the case with machine learning or AI-based models. The adaptive transfer function approach allows estimation of CFB course on a dynamically changing patient fluid balance system by simulating the response to the current fluid management regime, providing a useful digital tool for clinicians in daily intensive care.
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BACKGROUND: Peripheral nerve injuries affect over 2% of trauma patients and can lead to severe functional impairment and permanent disability. Autologous nerve transplantation is still the gold standard in the reconstruction of nerve defects. For small defects, conduits can be considered for bridging. Lately, the combined use of conduits and electrical stimulation has gained attention in the treatment of peripheral nerve injury. This review aimed to present the currently available data on this topic. METHODS: PubMed, Embase, Medline and the Cochrane Library were searched for studies on electrical stimulation through nerve conduits for nerve defects in in vivo studies. RESULTS: Fifteen studies fit the inclusion criteria. All of them reported on the application of nerve conduits combined with stimulation for sciatic nerve gaps in rats. Functional, electrophysiological and histological evaluations showed improved nerve regeneration after electrical stimulation. High variation was observed in the treatment protocols. CONCLUSION: Electrically stimulated conduits could improve peripheral nerve regeneration in rat models. The combined application of nerve guidance conduits and electrical stimulation shows promising results and should be further evaluated under standardized conditions.
