Phenylephrine-modulated cardiopulmonary blood flow measured with use of X-ray digital subtraction angiography

Introduction: Cardiopulmonary blood flow is an important indicator of organ function. Limitations in measuring blood flow in live rodents suggest that rapid physiological changes may be overlooked. For instance, relative measurements limit imaging to whole organs or large sections without adequately visualizing vasculature. Additionally, current methods use small samples and invasive techniques that often require killing animals, limiting sampling speed, or both. A recently developed high spatial- and temporal-resolution X-ray digital subtraction angiography (DSA) system visualizes vasculature and measures blood flow in rodents. This study was the first to use this system to measure changes in cardiopulmonary blood flow in rats after administering the vasoconstrictor phenylephrine.

Methods: Cardiopulmonary blood flow and vascular anatomy were assessed in 11 rats before, during, and after recovery from phenylephrine. After acquiring DSA images at 12 time points, a calibrated non-parametric deconvolution technique using singular value decomposition (SVD) was applied to calculate quantitative aortic blood flow in absolute metrics (mL/min). Trans-pulmonary transit time was calculated as the time interval between maximum signal enhancement in the pulmonary trunk and aorta. Pulmonary blood volume was calculated based on the central volume principle. Statistical analysis compared differences in trans-pulmonary blood volume and pressure, and aortic diameter using paired t-tests on baseline, peak, and late-recovery time points.

Results: Phenylephrine had dramatic qualitative and quantitative effects on vascular anatomy and blood flow. Major vessels distended significantly (aorta, ~1.2-times baseline) and mean arterial blood pressure increased ~2 times. Pulmonary blood volume, flow, pressure, and aortic diameter were not significantly different between baseline and late recovery, but differences were significant between baseline and peak, as well as peak and recovery time points.

Discussion: The DSA system with calibrated SVD technique acquired blood flow measurements every 30s with a high level of regional specificity, thus providing a new option for in vivo functional assessment in small animals.