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Published on: August 1, 2018
Central Artery Hemodynamics in Angiotensin II-Induced Hypertension and Effects of Anesthesia
S E Hopper1, D Weiss2, N Mikush3
1Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Insights
This study developed a method to estimate awake cardiovascular conditions in mice from anesthetized data. This revealed hypertension-induced vascular stiffness and altered hemodynamics, crucial for understanding cardiovascular disease.
Area of Science:
- Cardiovascular Physiology
- Biomedical Engineering
- Animal Models in Hypertension Research
Background:
- Systemic hypertension is a major risk factor for cardiovascular, neurovascular, and renovascular diseases.
- Central artery stiffness is a key factor in hypertension, linking vascular mechanics and hemodynamics.
- Mice are vital models for hypertension research, but hemodynamic data is typically collected under anesthesia.
Purpose of the Study:
- To develop and validate an experimental-computational workflow to estimate awake cardiovascular conditions from anesthetized data in mice.
- To quantify the effects of chronic angiotensin II-induced hypertension on cardiovascular hemodynamics and vascular properties in awake wild-type mice.
Main Methods:
- Developed a novel experimental-computational workflow to bridge anesthetized and awake physiological states.
- Utilized chronic angiotensin II infusion to induce hypertension in wild-type mice.
- Compared hemodynamic and vascular property changes between hypertensive and normotensive groups under simulated awake conditions.
Main Results:
- Anesthesia significantly impacted hemodynamics, particularly in angiotensin II-infused mice, leading to unexpected results when comparing anesthetized data.
- Awake simulations revealed that angiotensin II infusion increased in vivo vascular stiffness in the descending thoracic and suprarenal abdominal aorta.
- Hypertension led to increased pulse pressure in the distal aorta and characterized regionally varying vascular remodeling effects.
Conclusions:
- The developed workflow accurately estimates in vivo cardiovascular conditions, overcoming anesthesia-induced artifacts.
- Chronic angiotensin II infusion causes significant vascular remodeling and altered hemodynamics in mice, consistent with hypertension pathophysiology.
- This approach enables a better characterization of hypertension's impact on vascular structure, properties, and hemodynamics in a mouse model.
Abstract:
Systemic hypertension is a strong risk factor for cardiovascular, neurovascular, and renovascular diseases. Central artery stiffness is both an initiator and indicator of hypertension, thus revealing a critical relationship between the wall mechanics and hemodynamics. Mice have emerged as a critical animal model for studying effects of hypertension and much has been learned. Regardless of the specific mouse model, data on changes in cardiac function and hemodynamics are necessarily measured under anesthesia. Here, we present a new experimental-computational workflow to estimate awake cardiovascular conditions from anesthetized data, which was then used to quantify effects of chronic angiotensin II-induced hypertension relative to normotension in wild-type mice. We found that isoflurane anesthesia had a greater impact on depressing hemodynamics in angiotensin II-infused mice than in controls, which led to unexpected results when comparing anesthetized results between the two groups of mice. Through comparison of the awake simulations, however, in vivo relevant effects of angiotensin II-infusion on global and regional vascular structure, properties, and hemodynamics were found to be qualitatively consistent with expectations. Specifically, we found an increased in vivo vascular stiffness in the descending thoracic aorta and suprarenal abdominal aorta, leading to increases in pulse pressure in the distal aorta. These insights allow characterization of the impact of regionally varying vascular remodeling on hemodynamics and mouse-to-mouse variations due to induced hypertension.
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