(E-174) Hemodynamic-Metabolic Coupling During Artery Occlusion studied by Broadband Near-Infrared Spectroscopy and Wavelet Transform Coherence

Introduction:: Cardiovascular disease (CVD) is the leading cause of death in the United States. Endothelial dysfunction (ED) is a major contributor to CVD development and progression. Repeated arm arterial occlusion, also known as ischemic preconditioning, involves exposing cells, blood vessels, or tissues to brief sublethal stress, has been shown to protect endothelial cells from ischemia and reperfusion injury, including CVD. This study aimed to investigate the effects of arterial occlusion on hemodynamic and metabolic coupling using a novel approach of broadband near-infrared spectroscopy (bbNIRS) combined with wavelet transform coherence (WTC) analysis. The goal of this study was to gain a better understanding of the physiology of metabolic-vascular coupling in oxygen-deficient environments, which may provide insight into the protective mechanisms of preconditioning against CVD.

Materials and Methods:: Methods
The participants came in for initial and follow-up appointments. During the experiment, the subjects laid down and relaxed their arms before an automatic arm cuff was placed on their forearm just distal to the elbow. A duplex Doppler Ultrasound machine was used to image the brachial artery in the same arm where the cuff was placed. A broadband near-infrared (bbNIRS) spectrometer was placed on the forearm muscle distal to the cuff and proximal to the wrist. The participants underwent a vascular occlusion protocol, which included a 5-min baseline, 5-min supra-systolic cuff occlusion (220 mmHg) to induce ischemia in the distal forearm tissue, and 3-min recovery. During the 13-min vascular occlusion, bbNIRS data were continuously acquired at a 0.67-Hz sampling rate. First, temporal changes in oxygenated (HbO), deoxygenated (Hb), and cytochrome C oxidase (CCO) concentrations were quantified. Then, a time-frequency analysis called wavelet transform coherence (WTC) was performed for both the HbO and CCO time series, which quantifies both the temporal and spectral characteristics of the coherence between the two signals. The frequency bands in the analysis covered three characteristic infra-slow oscillation bands: endogenic (E), neurogenic (N), and myogenic (M). Fig. 1 illustrates the relationship between these three frequencies and vascular layers, including endothelial cells, smooth muscle cells, and other surrounding components. WTC analysis is unique for non-stationary signal processing and enables the achievement of temporal coherence values. These coherence values are illustrated in a heat map, indicating both the coherence and phase differences.

Results, Conclusions, and Discussions::
Results
Our results revealed the temporal curves of HbO and Hb concentrations before, during, and after forearm occlusion. As expected, HbO and Hb concentrations decreased and increased, respectively, under arterial occlusion due to tissue ischemia, and thus insufficient oxygen delivery (Fig. 2). Next, as an example, Figure 3 shows a WTC-derived coherence map between HbO and CCO with a 5-min baseline, 5-min forearm occlusion, and 3-min recovery. This figure shows three distinct time-frequency features of vascular-metabolic coupling: in-phase coupling, decoupling, and anti-phase recoupling. Specifically, during the baseline and initial occlusion phase within 1-2 min, HbO and CCO were strongly in-phase coupled across three frequency bands (E/N/M). However, after the initial phase of occlusion, HbO and CCO were decoupled starting from the endogenic frequency and then spreading to the neurogenic band and then to the myogenic band. Consequently, within a short time (< 1 min), the two vascular and metabolic activities were recoupled with strong antiphase coherence during the later portion of the 5-min occlusion. This recoupling process lasted for 1 min or longer after the occlusion ceased.
Discussion
The results presented above facilitate our preliminary interpretations.
During the baseline and initial cuff stages, local vascular and metabolic activities were closely in-phase coupled, reflecting an equilibrium or balance between the supply and demand of oxygen.
The supply-demand balance was interrupted after the onset of the cuff, leading to a temporary disconnect between metabolic/mitochondrial activity and endothelial vascular supply.
After a short period of decoupling, metabolic-vascular coupling was rebuilt, starting from the endothelial layer and expanding to the smooth muscle layer of the vessels.
Conclusion
In conclusion, the novel approach of bbNIRS with WTC analysis provides a promising tool to investigate the underlying mechanisms of ischemic preconditioning and to gain insight into its protective mechanisms against CVD. This study sheds light on new perspectives of hemodynamic and metabolic signal coupling during arterial occlusion. Future studies with a larger sample size and a more diverse participant population (i.e. age, health status, racial/ethnic populations, etc.) are needed to validate and expand upon these findings in oxygen-deficient environments.



Acknowledgements : The authors would like to thank Dr. Brother's team for their generous collaboration efforts, and Dr. Sadra Shahdadian for his establishment of the coherence code and assistance.