Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous expression of connexin 43

Altered gap junctional coupling potentiates slow conduction and arrhythmias. To better understand how heterogeneous connexin expression affects conduction at the cellular scale, we investigated conduction in tissue consisting of two cardiomyocyte populations expressing different connexin levels. Conduction was mapped using microelectrode arrays in cultured strands of foetal murine ventricular myocytes with prede fi ned contents of connexin 43 knockout (Cx43KO) cells. Corresponding computer simulations were run in randomly generated two-dimensional tissues mimicking the cellular architecture of the strands. In the cultures, the relationship between conduction velocity (CV) and Cx43KO cell content was nonlinear. CV fi rst decreased signi fi cantly when Cx43KO content was increased from 0 to 50%. When the Cx43KO content was ≥ 60%, CV became comparabletothatin100%Cx43KOstrands.Co-culturingCx43KOandwild-typecellsalsoresultedinsigni fi cantly more heterogeneous conduction patterns and in frequent conduction blocks. The simulations replicated this behaviour of conduction. For Cx43KO contents of 10 – 50%, conduction was slowed due to wavefront meandering between Cx43KO cells. For Cx43KO contents ≥ 60%, clusters of remaining wild-type cells acted as electrical loads thatimpairedconduction.ForCx43KOcontentsof40 – 60%,conductionexhibitedfractal characteristics,wasprone to block, and was more sensitive to changes in ion currents compared to homogeneous tissue. In conclusion, conduction velocity and stability behave in a nonline ar manner when cardiomyocytes expressing different connexin amounts are combined. This behaviour results from heterogeneous current-to-load relationships at the cellular level. Such behaviour is likely to be arrhythmogenic in various clinical contexts in which gap junctional coupling is heterogeneous.

An insulin infusion advisory system based on autotuning nonlinear model-predictive control

This paper aims at the development and evaluation of a personalized insulin infusion advisory system (IIAS), able to provide real-time estimations of the appropriate insulin infusion rate for type 1 diabetes mellitus (T1DM) patients using continuous glucose monitors and insulin pumps. The system is based on a nonlinear model-predictive controller (NMPC) that uses a personalized glucose-insulin metabolism model, consisting of two compartmental models and a recurrent neural network. The model takes as input patient's information regarding meal intake, glucose measurements, and insulin infusion rates, and provides glucose predictions. The predictions are fed to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. An algorithm based on fuzzy logic has been developed for the on-line adaptation of the NMPC control parameters. The IIAS has been in silico evaluated using an appropriate simulation environment (UVa T1DM simulator). The IIAS was able to handle various meal profiles, fasting conditions, interpatient variability, intraday variation in physiological parameters, and errors in meal amount estimations.

Quantitative assessment of physiological and behavioural parameters in healthy dairy cows evoked by transcutaneous electrical nerve stimulation of the udder

The pain and distress associated with transcutaneous electrical nerve stimulation (TENS) of the udder was evaluated by treating 20 healthy dairy cows with an electrical udder stimulator. This generated a sequence of pulses (frequency: 160+/-10% impulses per second, duration 250 mus) and provided voltage ranges from 0 to 10 volts (+/-10%). Trials took place on three consecutive days, twice daily after morning and evening milking. Daily sessions were divided into two periods: (1) control (sham treatment) and (2) treatment (real treatment). Physiological (heart rate, respiratory rate, and plasma cortisol concentration) as well as ethological parameters (kicking, weight shifting, and looking backwards to udder) were defined as pain-indicating parameters and observed. Evaluation of data showed that only one parameter (kicking) was significantly increased during real treatment compared to sham treatment. It is concluded that the TENS therapy tested in this study can evoke changes in behaviour (increased kicking) consistent with an experience of pain in some cows.