Optimization of resting tension for wire myography in male rat pulmonary arteries.

Wire myography to test vasomotor functions of blood vessels ex-vivo are well-established for the systemic circulation, however, there is no consensus on protocols for pulmonary arteries. We created a standardized wire myography protocol for healthy rat PAs and validated this in a pulmonary hypertension (PH) model. Vessels stretched to higher initial tensions (5.0, 7.5 and 10.0 mN) exhibited a uniform response to phenylephrine, a larger dynamic range, and lower EC50 values. The endothelium-mediated relaxation showed that moderate tensions (7.5 and 10.0 mN) produced robust responses with higher maximum relaxation and lower EC50 values. For endothelium independent responses, the higher initial tension groups had lower and more consistent EC50 values than the lower initial tension groups. Pulmonary arteries from rats with PH were more responsive to vasoactive drugs when subjected to a higher initial tension. Notably, vessels in the PH group subjected to 15.0 mN exhibited high dynamic ranges in contractile and relaxation responses without tearing. Lastly, we observed attenuated cholinergic responses in these vessels-consistent with endothelial dysfunction in PH. Therefore, a moderate initial tension of 7.5-10.0 mN is optimal for healthy rat pulmonary arteries and a higher initial tension of 15.0 mN is optimal for pulmonary arteries from animals with PH.

Home Respiratory Care: Design of a Prototype for Continuous Measurement at the Nasal Septum.

Chronic respiratory diseases have been on the rise, especially due to COVID-19, extreme air pollution, and other external circumstances. Millions of people around the world suffer from progressive lung diseases and require supplemental oxygen therapy to maintain blood oxygen (SpO2) levels above 90% to prevent hypoxic episodes that can lead to further organ damage. Today, these chronic episodes are more prevalent in aging populations suffering from Chronic Obstructive Pulmonary Disorder (COPD). Existing SpO2 measurement equipment, designed to assist with treating COPD at home, are suboptimal as they cannot measure SpO2 levels continuously, meaning supplemental oxygen devices are unable to adjust oxygen flow rates to the patient's needs. These discrepancies can result in hypoxic episodes of blood oxygen levels below 90%. Following this need, our team demonstrates preliminary results of the novel placement of a SpO2 sensor in the nasal septum to allow for comfortable and sustained SpO2 measurement. This will improve the experience of home-respiratory care with continuously obtained data from a novel location.

Restoring Blood Pressure in Hypertensive Mice Fails to Fully Reverse Vascular Stiffness.

BACKGROUND: Hypertension is a well-established driver of vascular remodeling and stiffening. The goal of this study was to evaluate whether restoring normal blood pressure (BP) fully restores vascular stiffness toward that of normotensive controls. METHODS: C57Bl6/J male mice received angiotensin II (angII; 1 µg/kg/min) via infusion pump for 8 weeks (hypertension group: HH), angII for 4 weeks (hypertension group: H4), angII for 4 weeks followed by 4 weeks of recovery (reversal group: HN), or sham treatment (normotensive group: NN). BP, heart rate, and pulse wave velocity (PWV) were measured longitudinally. At the end of the study period, aortas were harvested for testing of vasoreactivity, passive mechanical properties, and vessel structure. RESULTS: The HH group exhibited a sustained increase in BP and PWV over the 8-week period (p < 0.01). In the HN group, BP and PWV increased during the 4-week angII infusion, and, though BP was restored during the 4-week recovery, PWV exhibited only partial restoration (p < 0.05). Heart rate was similar in all cohorts. Compared to NN controls, both HH and HN groups had significantly increased wall thickness (p < 0.05 HH vs. NN, p < 0.01 HN vs. NN), mucosal extracellular matrix accumulation (p < 0.0001 HH vs. NN, p < 0.05 HN vs. NN), and intralamellar distance (p < 0.001 HH vs. NN, p < 0.01 HN vs. NN). Both intact and decellularized vessels were noted to have significantly higher passive stiffness in the HH and H4 cohorts than in NN controls (p < 0.0001). However, in the HN cohort, intact vessels were only modestly stiffer than those of NN controls, and decellularized HN vessels were identical to those from the NN controls. Compared to NN controls, the HH and HN cohorts exhibited significantly diminished phenylephrine-induced contraction (p < 0.0001) and endothelium-dependent vasodilation (p < 0.05). CONCLUSION: Hypertension causes a significant increase in in vivo aortic stiffness that is only partially reversible after BP normalization. Although hypertension does lead to matrix stiffening, restoration of BP restores matrix mechanics to levels similar to those of normotensive controls. Nevertheless, endothelial and vascular smooth muscle cell dysfunction persist after restoration of normotension. This dysfunction is, in part, responsible for augmented PWV after restoration of BP.

Commonly used mouse strains have distinct vascular properties.

Mice are the most common animal model to investigate human disease and explore physiology. Mice are practical, cost efficient, and easily used for genetic manipulations. Although variability in cardiac structure and function among mouse strains is well noted, the effect of mouse strain on vascular stiffness indices is not known. Here, we compared mouse strain-dependent differences in key vascular stiffness indices among frequently used inbred mouse strains-C57Bl/6J, 129S, and Bl6/129S. In young healthy animals, baseline blood pressure and heart rate were identical in all strains, and independent of gender. However, both active in vivo and passive ex vivo vascular stiffness indices exhibited distinct differences. Specifically, both male and female 129S animals demonstrated the highest tensile stiffness, were least responsive to acetylcholine-induced vasorelaxation, and showed the lowest pulse wave velocity (PWV), an index of in vivo stiffness. C57Bl/6J mice demonstrated the highest PWV, lowest tensile stiffness, and the highest response to acetylcholine-induced vasorelaxation. Interestingly, within each strain, female mice had more compliant aortas. C57Bl/6J mice had thinner vessel walls with fewer layers, whereas 129S mice had the thickest walls with the most layers. Values in the Bl6/129S mixed background mice fell between C57Bl/6J and 129S mice. In conclusion, we show that underlying vascular properties of different inbred wild-type mouse strains are distinct, despite superficial similarities in blood pressure. For each genetic modification, care should be taken to identify proper controls, and conclusions might need to be verified in more than one strain to minimize the risk of false positive studies.