Narine Muselimyan

Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity

Plastics have revolutionized medical device technology, transformed hematological care, and facilitated modern cardiology procedures. Despite these advances, studies have shown that phthalate chemicals migrate out of plastic products and that these chemicals are bioactive. Recent epidemiological and research studies have suggested that phthalate exposure adversely affects cardiovascular function. Our objective was to assess the safety and biocompatibility of phthalate chemicals and resolve the impact on cardiovascular and autonomic physiology. Adult mice were implanted with radiofrequency transmitters to monitor heart rate variability, blood pressure, and autonomic regulation in response to di-2-ethylhexyl-phthalate (DEHP) exposure. DEHP-treated animals displayed a decrease in heart rate variability (-17% SD of normal beat-to-beat intervals and -36% high-frequency power) and an exaggerated mean arterial pressure response to ganglionic blockade (31.5% via chlorisondamine). In response to a conditioned stressor, DEHP-treated animals displayed enhanced cardiovascular reactivity (-56% SD major axis Poincarè plot) and prolonged blood pressure recovery. Alterations in cardiac gene expression of endothelin-1, angiotensin-converting enzyme, and nitric oxide synthase may partly explain these cardiovascular alterations. This is the first study to show an association between phthalate chemicals that are used in medical devices with alterations in autonomic regulation, heart rate variability, and cardiovascular reactivity. Because changes in autonomic balance often precede clinical manifestations of hypertension, atherosclerosis, and conduction abnormalities, future studies are warranted to assess the downstream impact of plastic chemical exposure on end-organ function in sensitive patient populations. This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices.NEW & NOTEWORTHY Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing.

Seeing the Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach

Background Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures. Objective To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions. Methods Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated and unablated spectra to each pixel was then displayed. Results of spectral unmixing were compared to lesion pathology. Results RF ablation caused significant changes in the tissue autofluorescence profile. The magnitude of these spectral changes in human left atrium was relatively small (< 10% of peak fluorescence value), yet highly significant. Spectral unmixing of hyperspectral datasets enabled high spatial resolution, in-situ delineation of radiofrequency lesion boundaries without the need for exogenous markers. Lesion dimensions derived from hyperspectral imaging approach strongly correlated with histological outcomes. Presence of blood within the myocardium decreased the amplitude of the autofluorescence spectra while having minimal effect on their overall shapes. As a result, the ability of hyperspectral imaging to delineate ablation lesions in vivo was not affected. Conclusions Hyperspectral imaging greatly increases the contrast between ablated and unablated tissue enabling visualization of viability gaps at clinically relevant locations. Data supports the possibility for developing percutaneous hyperspectral catheters for high-resolution ablation guidance.

Lesion detection for cardiac ablation from auto-fluorescence hyperspectral images

Direct visualization of the ablated region in the left atrium during radiofrequency ablation (RFA) surgery for treating atrial fibrillation (AF) can improve therapy success rates. Our visualization approach is auto-fluorescence hyperspectral imaging (aHSI), which constructs each hypercube containing 31 auto-fluorescence images of the tissue. We wish to use the spectral information to characterize ablated lesions as being successful or not. In this paper, we reshaped one hypercube to a 2D matrix. Each row (sample) in the matrix represents a pixel in the spatial dimension, and the matrix has 31 columns corresponding to 31 spectral features. Then, we applied k-means clustering to detect ablated regions without a priori knowledge about the lesion. We introduced an accuracy index to evaluate the results of k-means by comparing with the reference truth images quantitatively. To speed-up the detection process, we implemented a grouping procedure to decrease the number of features. The 31 features were divided into four contiguous disjoint groups. In each group, the summation of values yielded a new feature. By the same evaluation method, we found the best 4-feature groups to adequately detect the lesions from all possible combinations. The average accuracy for detection by k-means (k=10) using 31 features was about 74% of reference truth images. And, for using the best grouped 4 features, it was about 95% of that using 31 features. The time cost of 4-feature clustering is about 41% of the 31-feature clustering. We expect that the reduction of time for both acquisition and processing will make possible intraoperative real-time display of ablation status.

Anatomical and Optical Properties of Atrial Tissue: Search for a Suitable Animal Model.

The purpose of this study was to evaluate structural and optical properties of atrial tissue from common animal models and to compare it with human atria. We aimed to do this in a format that will be useful for development of better ablation tools and/or new means for visualizing atrial lesions. Human atrial tissue from clinically relevant age group was compared and contrasted with atrial tissue of large animal models commonly available for research purposes. These included pigs, sheep, dogs and cows. The presented data include area measurements of smooth atrial surface available for ablation and estimates of thickness of collagen and muscle for five different species. We also described methods to quantify presence of collagen and overall thickness of atrial wall. Provided information enables placement of atrial lesions to locations with clinically relevant atrial wall thickness and macroscopic structure ultimately helping investigators to develop better ablation and imaging tools. It also highlights the impact of collagen thickness on optical measurements and lesion visualization.