Background The inward rectifier potassium current, IK1, contributes to the terminal phase of repolarization of the action potential (AP), as well as the value and stability of the resting membrane potential. Regional variation in IK1 has been noted in the canine heart, but the biophysical properties have not been directly compared. We examined the properties and functional contribution of IK1 in isolated myocytes from ventricular, atrial and Purkinje tissue. Methods and Results APs were recorded from canine left ventricular midmyocardium, left atrial and Purkinje tissue. The terminal rate of repolarization of the AP in ventricle, but not in Purkinje, depended on changes in external K+ ([K+]o). Isolated ventricular myocytes had the greatest density of IK1 while atrial myocytes had the lowest. Furthermore, the outward component of IK1 in ventricular cells exhibited a prominent outward component and steep negative slope conductance, which was also enhanced in 10 mM [K+]o. In contrast, both Purkinje and atrial cells exhibited little outward IK1, even in the presence of 10 mM [K+]o, and both cell types showed more persistent current at positive potentials. Expression of Kir2.1 in the ventricle was 76.9-fold higher than that of atria and 5.8-fold higher than that of Purkinje, whereas the expression of Kir2.2 and Kir2.3 subunits was more evenly distributed in Purkinje and atria. Finally, AP clamp data showed distinct contributions of IK1 for each cell type. Conclusions IK1 and Kir2 subunit expression vary dramatically in regions of the canine heart and these regional differences in Kir2 expression likely underlie regional distinctions in IK1 characteristics, contributing to variations in repolarization in response to in [K+]o changes.

Background Developmental changes in the electrical characteristics of the ventricular myocardium are not well defined. This study examines the contribution of inwardly rectifying K+ current (IK1), transient outward K+ current (Ito), delayed rectifier K+ currents (IKr and IKs) and sodium channel current (INa) to repolarization in the canine neonate myocardium. Methods Single myocytes isolated from the left ventricle of 2-3 week old canine neonate hearts were studied using patch-clamp techniques. Results Neonate cells were ~6-fold smaller than those of adults (28.8±8.8 vs. 176±6.7 pF). IK1 was larger in neonate myocytes and displayed a substantial inward component and an outward component with negative slope conductance, peaking at −60 mV (4.13 pA/pF). IKr tail currents (at −40 mV), were small (<20 pA). IKs could not be detected, even after exposure to isoproterenol (100 nM). Ito was also absent in the neonate, consistent with the absence of a phase 1 in the action potential. Peak INa, late INa and ICa were smaller in the neonate compared with adult. KCND3, KCNIP2 and KCNQ1 mRNA expression was half, while KCNH2 was equal and KCNJ2 was greater in the neonate when compared with adults. Conclusions Two major repolarizing K+ currents (IKs and Ito) present in adult ventricular cells are absent in the 2 week old neonate. Peak and late INa are significantly smaller in the neonate. Our results suggest that the absence of these two currents in the neonate heart may increase the susceptibility to arrhythmias under certain long QT conditions.

Background Hepatitis C virus (HCV) is a leading cause of advanced liver disease and death. In the United States about 3.5 million people are living with HCV, but only 50% are aware of the infection, 16% are prescribed treatment, and only 9% achieve sustained viral response. The World Health Organization published an HCV elimination goal for 2030 that strives to achieve a 65% reduction in HCV-related deaths and 90% reduction in transmission. An important step toward this goal is micro-elimination at local hospitals by addressing care gaps in the HCV care cascade. Figure 1 Methods We created a retrospective cohort of patients who tested positive for HCV antibody (HCV Ab+) between 2016 and 2018 at Tufts Medical Center in Boston, Massachusetts. We assessed achievement of care cascade steps including HCV viral load (VL) testing, linkage to care, treatment initiation, and sustained viral response (SVR). We also assessed patient demographics, clinical factors and HCV risk factors. We used STATA/IC 14.1 to conduct bivariate analysis to identify factors associated with loss to follow-up across each care cascade step. Results A total of 24,308 HCV antibody tests were done during this timeframe, of which 5% (n=1,222) were HCV Ab+. After excluding duplicate tests, 1,041 unique patients with HCV Ab+ were included. This cohort had a mean age of 47 years and were 61% male, 66% white, 72% on public insurance, 12% HIV-positive, 13% HCV treatment-experienced. The most frequent HCV risk factor was injection drug use, occurring in 64% of patients. Of patients with HCV Ab+, 76% (n=791) were tested for an HCV VL, of which 50% (n=393) had detectable VL and 50% (n=398) had undetectable VL. Of the patients with a detectable VL, 58% (n=226) were linked with care. Following care linkage, 69% (n=155) initiated treatment, of which 90% (n=139) completed treatment, of which 97% (n=135) achieved SVR (Figure 1). Factors that were significantly associated with getting a VL test and linking to care included private insurance, HIV co-infection, absence of intravenous drug use and cirrhosis; however, these factors were not significantly associated with achieving subsequent steps. Conclusion Assessment of the HCV care cascade at our hospital allowed us to identify clear care gaps and areas needing improvement towards a local micro-elimination. Disclosures All Authors: No reported disclosures

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Ischemic heart disease is a common pro-arrhythmic condition characterized by hypoxia, acidosis, hyperkalemia and impaired Ca(2þ) handling. Here we investigated the ischemia responses to acute hypoxia and acidification in developing cardiomyocytes derived from neonatal rat hearts (rN-CM) or human induced pluripotent stem cells. L-type Ca(2þ) current (I Ca ) was measured