Anatomical location, sex, and age influence murine arterial circumferential cyclic strain before and during dobutamine infusion

Abstract

Background One of the primary biomechanical factors influencing arterial health is their deformation across the cardiac cycle, or cyclic strain, which is often associated with arterial stiffness. Deleterious changes in the cardiovascular system, e.g., increased arterial stiffness, can remain undetected until the system is challenged, such as under a cardiac stressor like dobutamine. Purpose To quantify cyclic strain in mice at different locations along the arterial tree prior to and during dobutamine infusion, while evaluating the effects of sex and age. Study Type Control/cohort study. Animal Model Twenty C57BL/6 mice; male, female; ∼12 and 24 weeks of age; n = 5 per group. Field Strength/Sequence 7T; CINE MRI with 12 frames, velocity compensation, and prospective cardiac gating. Assessment Prior to and during the infusion of dobutamine, Green–Lagrange circumferential cyclic strain was calculated from perimeter measurements derived from CINE data acquired at the carotid artery, suprarenal and infrarenal abdominal aorta, and iliac artery. Statistical Tests Analysis of variance (ANOVA) followed by post‐hoc tests was used to evaluate the influence of dobutamine, anatomical location, sex, and age. Results Heart rates did not differ between groups prior to or during dobutamine infusion ( P = 0.87 and P = 0.08, respectively). Dobutamine increased cyclic strain in each group. Within a group, increases in strain were similar across arteries. At the suprarenal aorta, strain was reduced in older mice at baseline (young 27.6 > mature 19.3%, P = 0.01) and during dobutamine infusion (young 53.0 > mature 36.2%, P = 0.005). In the infrarenal aorta, the response (dobutamine – baseline) was reduced in older mice (young 21.9 > mature 13.5%, P = 0.04). Data Conclusion Dobutamine infusion increases circumferential cyclic strain throughout the arterial tree of mice. This effect is quantifiable using CINE MRI. The results demonstrate that strain prior to and during dobutamine is influenced by anatomical location, sex, and age. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:69–80.

Assessing structural and functional response of murine vasculature to acute β-adrenergic stimulation in vivo during hypothermic and hyperthermic conditions

“…To our knowledge, these data are the first to empirically quantify the spatially and temporally resolved response of arterial vasculature to a pharmacological stressor at different core body temperatures. The response to dobutamine, as measured by changes in vessel area, was diminished during hypothermic conditions while the response during hyperthermic conditions mimicked normothermia [22].…”

“…A dobutamine dosage of 40 μg/kg of body weight (Hospira, Inc., Lake Forest, IL) was prescribed at an infusion rate of 2 μL/min (Cole Parmer, Vernon Hills, IL) and pre-mixed assuming an average murine body weight of 25 g (actual mean and SEM of animals was 26.4±0.7 g). Prior to imaging, a tail vein catheter was placed using a 30 gauge needle, connected to an ~5 cm length of PE10 tubing prefilled with saline, followed by the dobutamine solution [22]. Mice were anesthetized with 1.25–2% isoflurane in 1 L/min of oxygen [24].…”

“…The CINE images were analyzed for vessel cross-sectional area and circumferential cyclic strain using an in-house semi-automated process previously described [19,21,22]. Circumferential cyclic strain is a measurement of the repetitive mechanical deformation of the vessel wall as it expands and constricts with the cardiac cycle.…”

“…Previous work by Crouch et al showed that under hypothermic conditions (35 °C) the average area was significantly smaller in the infrarenal aorta and femoral artery by −12% and −72%, respectively, and larger for hyperthermic conditions (38 °C) by 1.3 and 6.0%, respectively, compared to normothermic conditions (37 °C) [20]. While cross-sectional area tended to increase with temperature, with larger changes occurring inferiorly, previous work in well-controlled and nearly identical conditions, Castle et al showed that cross-sectional area at normothermic conditions decreased with the administration of dobutamine for the carotid, suprarenal and infrarenal aorta, and iliac artery by −19%, −16%, −14%, and −12%, respectively, with larger changes occurring superiorly in the body [22]. For either increases in core temperature or dobutamine administration, the end-diastolic/minimum areas experienced larger changes than the peak-systolic/maximum areas, resulting in changes in maximum cyclic strain.…”

“…For either increases in core temperature or dobutamine administration, the end-diastolic/minimum areas experienced larger changes than the peak-systolic/maximum areas, resulting in changes in maximum cyclic strain. Temperature’s effect on strain varied by location with a general overall decrease in strain from 35 to 38 °C [19,20], whereas dobutamine caused an increase in maximum cyclic strain for all vessels [22]. Combining these two cardiac stressors is of interest because of the differential response of core vasculature to changing temperature or administration of dobutamine alone.…”