The Langendorff mouse heart model is widely employed in studies of myocardial function and responses to injury (e.g. ischaemia). Nonetheless, marked variability exists in its preparation and functional properties. We examined the impact of early growth (8, 16, 20 and 24 weeks), sex, perfusion fluid [Ca 2+ ] and pacing rate on contractile function and responses to 20 min ischaemia followed by 45 min reperfusion. We also assessed the impact of strain, and tested the utility of the model in studying coronary function. Under normoxic conditions, hearts from 8-week-old male C57BL/6 mice (2 mm free perfusate [Ca 2+ ], 420 beats min -1 ) exhibited 145 ± 2 mmHg left ventricular developed pressure (LVDP). Force development declined by ∼15% (126 ± 5 mmHg) with a reduction in free [Ca 2+ ] to 1.35 mm, and by 25% (108 ± 3 mmHg) with increased pacing to 600 beats min -1 . While elevated heart rate failed to modify ischaemic outcome, the lower [Ca 2+ ] significantly improved contractile recovery (by >30%). We detected minimal sex-dependent differences in normoxic function between 8 and 24 weeks, although age modified contractile function in males (increased LVDP at 24 versus 8 weeks) but not females. Both male and female hearts exhibited age-related reductions in ischaemic tolerance, with a significant decline in recovery evident at 16 weeks in males and later, at 20-24 weeks, in females (versus recoveries in hearts at 8 weeks). Strain also modified tolerance to ischaemia, with similar responses in hearts from C57BL/6, 129/sv, Quackenbush Swiss and FVBN mice, but substantially greater tolerance in BALB/c hearts. In terms of vascular function, baseline coronary flow (20-25 ml min −1 g −1 ) was 50-60% of maximally dilated flows, and coronary reactive and functional hyperaemic responses were pronounced (up to 4-fold elevations in flow in hearts lacking ventricular balloons). These data indicate that attention to age (and sex) of mice will reduce variability in contractile function and ischaemic responses. Even small differences in perfusion fluid [Ca 2+ ] also significantly modify tolerance to ischaemia (whereas modest shifts in heart rate do not impact). Ischaemic responses are additionally strain dependent, with BALB/c hearts displaying greatest intrinsic tolerance. Finally, the model is applicable to the study of vascular reactivity, providing large responses and excellent reproducibility.

Background The opioid epidemic across the U.S. poses an array of public health concerns, especially HCV transmission. HCV is now widely curable, yet incident rates are increasing due to the opioid epidemic. Despite the established trajectory from oral prescription opioids (OPOs) to opioid use disorder (OUD), OUD to injection drug use (IDU), and IDU to hepatitis C virus (HCV), OPOs are not a defined risk factor (RF) for HCV infection. The objective of this study was to observe rates of HCV testing and Ab reactivity (HCVAb+) in patients receiving OPOs to substantiate them as a RF, ultimately contributing to HCV elimination. Methods Data from MedStar Health patients receiving OPOs from 1/2017 to 12/2018 were collected and analyzed using chi-squared or student t-tests and logistic regression for uni- or multi-variable analyses, respectively. Statistical significance was defined as P < .05; Epi Info and SAS v 9·4 were used for statistical analyses; IRB approval was received. Results There were 115 415 individuals prescribed OPOs over the study period. In this population, 8.6% (932) were HCVAb+ when tested and not previously diagnosed (10 900); 3.4% (3893) had an OUD diagnosis, 20.6% (803) of whom were HCV tested; 25.4% (361) of all HCVAb+ (1421) had an OUD diagnosis. OUD (ORadj 8.53 [7.22-10.07]) was an independent predictor of HCVAb+ in this population. Conclusions (1) In a large population prescribed oral opioids, HCVAb+ was 8.6%, higher than our previously published data (2.5%) and the US rate (1.7%); (2) only 20% of patients diagnosed with OUD were tested; and (3) only 25% of HCVAb+ patients were classified with OUD; this suggests underreporting of OUD in this population. Primary Care and Community Health Recommendations: (1) Re-testing for HCV in patients taking OPOs; (2) increased HCV testing among OUD patients; and (3) improved surveillance and reporting of OUD.

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Background & objectives Screening for hepatitis C virus is the first critical decision point for preventing morbidity and mortality from HCV cirrhosis and hepatocellular carcinoma and will ultimately contribute to global elimination of a curable disease. This study aims to portray the changes over time in HCV screening rates and the screened population characteristics following the 2020 implementation of an electronic health record (EHR) alert for universal screening in the outpatient setting in a large healthcare system in the US mid-Atlantic region. Methods Data was abstracted from the EHR on all outpatients from 1/1/2017 through 10/31/2021, including individual demographics and their HCV antibody (Ab) screening dates. For a limited period centered on the implementation of the HCV alert, mixed effects multivariable regression analyses were performed to compare the timeline and characteristics of those screened and un-screened. The final models included socio-demographic covariates of interest, time period (pre/post) and an interaction term between time period and sex. We also examined a model with time as a monthly variable to look at the potential impact of COVID-19 on screening for HCV. Results Absolute number of screens and screening rate increased by 103% and 62%, respectively, after adopting the universal EHR alert. Patients with Medicaid were more likely to be screened than private insurance (ORadj 1.10, 95% CI: 1.05, 1.15), while those with Medicare were less likely (ORadj 0.62, 95% CI: 0.62, 0.65); and Black (ORadj 1.59, 95% CI: 1.53, 1.64) race more than White. Conclusions Implementation of universal EHR alerts could prove to be a critical next step in HCV elimination. Those with Medicare and Medicaid insurance were not screened proportionately to the national prevalence of HCV in these populations. Our findings support increased screening and re-testing efforts for those at high risk of HCV.