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We constructed and surgically implanted 114 chronic bipolar epicardial plunge electrodes for programmed left ventricular stimulation in closed chest dogs; 88 electrodes could be analyzed in animals surviving infarct surgery. Electrode plunges were constructed of silver wire, with conduction strands of silver-plated copper wire, in medical grade silicone tubing. Electrodes were implanted epicardially through left thoracotomy and secured with prolene. Wires exited the fifth intercostal space and were tunneled subcutaneously and secured at the dorsal aspect of the neck. Baseline thresholds (mA) were recorded at a paced cycle length of 300 ms and pulse duration of 1 ms. At least 5 days after implantation, under light Nembutal sedation, thresholds were reassessed before programmed stimulation. Each lead was tested repeatedly over 5-177 (mean 28) days. The number of leads decreased with time due to animal attrition from ventricular arrhythmias. Mean pacing threshold at implantation was 0.25 mA. Mean and median threshold values reached plateau after 1 week and showed little change thereafter for the duration of the study. More than 50% of the leads maintained thresholds less than 1.5 mA through the entire study. In animals that survived, 86% of the electrodes remained useful for the duration of the protocol. These data support the use of this electrode system as effective and reliable for chronic electrophysiologic studies in dogs.

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16–18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments.