this study demonstrated that (1) hypoxic-induced improvements in glucose tolerance in the 4 h following exposure can be attributed to improvements in peripheral insulin sensitivity (S( I)(2*) and (2) exercise and hypoxia have an additive effect on insulin sensitivity (S(I)(2*) in type 2 diabetic patients. Acute hypoxia may therefore improve short-term glycaemic control in individuals with type 2 diabetes. The application of these findings in the clinic will require further investigation.

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.

Introduction: Measurements of cyclic strain give insight into vessel wall properties, offer a better understanding of the pathogenesis of atherosclerosis, and can be used in quantifying loss of vessel compliance. Using dobutamine stimulation to increase heart rate and cardiac output provides a clinically relevant means to begin to understand alterations in cyclic strain during a vascular challenge which mimics some aspects of exercise. Similar work has been completed in murine models, but translating these methods to a species that is an order of magnitude larger allows for a better understanding of how these results could allometrically scale to the human condition. We hypothesize that using a pharmacological cardiovascular stimulant will cause cyclic strain shifts that vary between species. Materials and Methods: Cyclic strain was non-invasively quantified using MRI. Young rats and mice were anesthetized using isoflurane and imaged at 7T. 2D and 3D gradient echo data were used to plan ECG-gated acquisitions that included 12 CINE frames across the cardiac cycle, in the infrarenal aorta pre- and post- dobutamine infusion. Vessel strain was quantified in each CINE frame. Results: Baseline strain in rats was 17% and 16%, for males and females respectively (A, C). In mice, baseline strain was 22% in males and 18% in females (B, D). After infusion of dobutamine, strain in rats increased to 26% in males and 27% in females, while in mice strain increased to 36% in males and 32% in females. Conclusions: In conclusion, there are evident variations in cyclic strain under a cardiovascular challenge between species. With this insight, a clearer understanding of the biomechanical forces experienced by the vasculature in different species may lead to improved extrapolation from mouse to human in understanding the effects of atherosclerosis on vessel compliance and developing therapeutic approaches.

Background: Because of the importance of adrenoreceptors in regulating the cardiovascular (CV) system and the role of the CV system in thermoregulation, understanding the response to these two stressors is of interest. The purpose of this study was to assess changes of arterial geometry and function in vivo during thermal and β-adrenergic stress induced in mice and quantified by MRI. Methods: Male mice were anesthetized and imaged at 7T. Anatomical and functional data were acquired from the neck (carotid artery), torso (suprarenal and infrarenal aorta and iliac artery), and periphery (femoral artery). Intravenous dobutamine (tail vein catheter, 40 μg/kg/min, 0.12 mL/hr) was used as β-adrenergic stressor. Baseline and dobutamine data were acquired at minimally hypothermic (35°C) and minimally hyperthermic (38°C) core temperatures. Cross-sectional vessel area and maximum cyclic strain were measured across the cardiac cycle. Results: Vascular response varied by location and by core temperature. For minimally hypothermic conditions (35°C), average, maximum, and minimum areas decreased with dobutamine only at the suprarenal aorta (avg: −17.9%, max: −13.5%, min: −21.4%). For minimally hyperthermic conditions (38°C), vessel areas decreased between baseline and dobutamine at the carotid (avg: −19.6%, max: −15.5%, min: −19.3%) and suprarenal aorta (avg: −24.2%, max: −17.4%, min: −17.3%); whereas, only the minimum vessel area decreased for the iliac artery (min: −14.4%). Maximum cyclic strain increased between baseline and dobutamine at the iliac artery for both conditions and at the suprarenal aorta at hyperthermic conditions. Conclusion: At hypothermic conditions the vessel area response to dobutamine is diminished compared to hyperthermic conditions where the vessel area response mimics normothermic dobutamine conditions. The varied response emphasizes the need to monitor and control body temperature during medical conditions or treatments that may be accompanied by hypothermia, especially when vasoactive agents are used.

Dobutamine increases heart rate and cardiac output, similar to the effects the sympathetic nervous system has on the body during exercise. This makes dobutamine an excellent surrogate for exercise, and it is often administered during stress tests. The purpose of this study was to quantify changes in arterial strain using in vivo high frequency ultrasound in order to better understand the effects of dobutamine on vascular dynamics. Here, C57BL/6 mice were infused with 40 μg/min/kg of dobutamine at a flow rate of 0.002 mL/min via a tail vein catheter (n=3; 19 weeks old, 31 ± 2.0 g). Ultrasound images of the suprarenal aorta, infrarenal aorta, iliac arteries, and carotid artery were acquired before the infusion of dobutamine (baseline) and again after the heart rate had plateaued during the infusion using B- and M-Modes images in both short and long axis. These mice showed an average heart rate increase of 76±18.7 bpm roughly 20 minutes after the start of the dobutamine infusion. Green-Lagrangian circumferential cyclic strain, calculated from arterial diameters in systole (maximum, dashed) and diastole (minimum, solid), increased throughout the vasculature after infusion. The suprarenal aorta increased from 22.5±1.3% to 41.9±2.4%, while the infrarenal aorta increased from 21.2±2.5% to 38.0±1.7%. The iliac artery increased from 22.4±2.9% to 42.0±2.7%, and the carotid artery increased from 26.0±2.3% to 43.5±5.2%. The average strain for all four locations increased from 23.0±2.1% (A) to 41.4±2.4% (B), representing a 79.6% increase from baseline. These results suggest that high frequency ultrasound is capable of capturing rapid changes in vascular dynamics due to dobutamine infusion. The effects of dobutamine on these healthy vessels can be used as a baseline for future studies that investigate murine disease models including advanced atherosclerosis and abdominal aortic aneurysms.