Ashish Singal

Erythrocyte aging as a mechanism of anemia and a biomarker of device thrombosis in continuous-flow left ventricular assist devices

BACKGROUND Blood trauma caused by continuous-flow left ventricular assist devices (CF-LVADs) has been associated with device thrombosis and anemia. Accurate in vivo quantification of erythrocyte turnover and its contribution to CF-LVAD complications have yet to be elucidated. METHODS We investigated the age (lifespan) of circulating erythrocytes in subjects with CF-LVAD. Erythrocyte lifespan is a quantitative indicator of in vivo erythrocyte turnover that can be accurately derived from measurement of the exhaled carbon monoxide (CO) level. Sixty non-smoking subjects were prospectively enrolled: 25 had a CF-LVAD without thrombosis; 10 had a CF-LVAD with thrombosis; and 25 were normal controls. End-tidal breath CO levels were measured and used to calculate erythrocyte lifespan. RESULTS The mean erythrocyte lifespan was significantly shorter in CF-LVAD subjects with (29.7 ± 14.9 days) compared to those without (65.0 ± 17.3 days) device thrombosis (p < 0.0001). The lifespans in these 2 groups were significantly shorter compared with normal controls (96.0 ± 24.9 days, both p < 0.0001). A receiver operator curve demonstrated high sensitivity-specificity for use of erythrocyte lifespan to detect device thrombosis (AUC = 0.94). In addition, all CF-LVAD subjects had low hemoglobin (11.8 ± 2.0 g/dl), and their anemia was normochromic normocytic with elevated mean reticulocyte counts. Erythrocyte lifespan correlated significantly with mean corpuscular hemoglobin concentration (r = 0.56, p = 0.0005) and red cell distribution width (r = -0.65, p < 0.001), but not with reticulocyte count (r = 0.27, p = 0.32). CONCLUSIONS Erythrocyte lifespan is substantially reduced in subjects with a CF-LVAD, which was more pronounced in the presence of device thrombosis. The etiology of anemia in CF-LVAD was primarily due to accelerated erythrocyte aging. Further studies are needed to determine whether erythrocyte lifespan could provide a practical means of detecting subtle pre-clinical thrombosis.

Effects of Ablation (Radio Frequency, Cryo, Microwave) on Physiologic Properties of the Human Vastus Lateralis

Objective: Ablative treatments can sometimes cause collateral injury to surrounding muscular tissue, with important clinical implications. In this study, we investigated the changes in muscle physiology of the human vastus lateralis when exposed to three different ablation modalities: radiofrequency ablation, cryoablation, and microwave ablation. Methods: We obtained fresh vastus lateralis tissue biopsy specimens from nine patients (age range: 29–73 years) who were undergoing in vitro contracture testing for malignant hyperthermia. Using leftover waste tissue, we prepared 46 muscle bundles that were utilized in tissue baths before and after ablation. Results: After ablation with all the three modalities, we noted dose-dependent sustained reductions in peak force (strength of contraction), as well as transient increases in baseline force (resting muscle tension). But, over the subsequent 3-h recovery period, peak force improved and the baseline force consistently recovered to below its preablation levels. Conclusion: The novel in vitro methodologies we developed to investigate changes in muscle physiology after ablation can be used to study a spectrum of ablation modalities and also to make head-to-head comparisons of different ablation modalities. Significance: As the role of ablative treatments continues to expand, our findings provide unique insights into the resulting changes in muscle physiology. These insights could enhance the safety and efficacy of ablations and help individuals design and develop novel medical devices.

Assessment of Ablative Therapies in Swine: Response of Respiratory Diaphragm to Varying Doses

Ablation is a common procedure for treating patients with cancer, cardiac arrhythmia, and other conditions, yet it can cause collateral injury to the respiratory diaphragm. Collateral injury can alter the diaphragm’s properties and/or lead to respiratory dysfunction. Thus, it is important to understand the diaphragm’s physiologic and biomechanical properties in response to ablation therapies, in order to better understand ablative modalities, minimize complications, and maximize the safety and efficacy of ablative procedures. In this study, we analyzed physiologic and biomechanical properties of swine respiratory diaphragm muscle bundles when exposed to 5 ablative modalities. To assess physiologic properties, we performed in vitro tissue bath studies and measured changes in peak force and baseline force. To assess biomechanical properties, we performed uniaxial stress tests, measuring force–displacement responses, stress–strain characteristics, and avulsion forces. After treating the muscle bundles with all 5 ablative modalities, we observed dose-dependent sustained reductions in peak force and transient increases in baseline force—but no consistent dose-dependent biomechanical responses. These data provide novel insights into the effects of various ablative modalities on the respiratory diaphragm, insights that could enable improvements in ablative techniques and therapies.

Design of Electromagnetic Coils and Temperature Regulation Circuits for Impeding Microbial Growth on Medical Device Surfaces

Microorganisms that form biofilm on surface of medical devices represent a major health risk for patients and an economic burden for the health care system [1]. Biofilms are conglomerates of bacterial colonies characterized by the production of an exo-polysaccharide matrix making it challenging to eradicate them by using chemical or antibiotic treatments [2]. More than 70% of biofilm-related infections are resistant to at least one drug, therefore, alternative forms of treatments have been investigated. Previously we have reported compelling new data showing the synergistic effects of electromagnetic fields (EMF) and elevated temperatures on the colonization and survival of pathogenic bacteria on medical device surfaces [3]. Here we report the design and development of prototypical EMF coils and temperature regulation circuits that are simple and cost effective for impeding microbial growth on medical device surfaces.Copyright

The Sub-Hemolytic Effect of Left Ventricular Assist Devices: Erythrocyte Survival as a Novel Biomarker of Device Thrombosis

The Sub-Hemolytic Effect of Left Ventricular Assist Devices: Erythrocyte Survival as a Novel Biomarker of Device Thrombosis Ziad Taimeh1, Ryan Koene1, Julie Furne2, Ashish Singal1, Peter Eckman3, Michael Levitt2, Marc Pritzker1; 1Lillehei Heart Institute, University of Minnesota School of Medicine, Minneapolis, MN; 2Minneapolis Veterans Affairs Hospital, Minneapolis, MN; 3Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, MN

Assessment of Reactive Hyperemia Using Peripheral Arterial Tonometry

Reactive hyperemia (RH) is characterized by temporary increase in blood flow, which occurs in a blood vessel following a brief period of ischemia. Following ischemia there is a shortage of oxygen bioavailability and a build-up of metabolic waste, which must be replenished to restore normal function [1]. An increased blood flow, an increased vessel diameter (cross-sectional area), and increased pulsatility are all characteristic normal physiological responses post ischemia. The vasodilation post ischemia is caused by release of nitric oxide into the blood stream [2]. Over time, the blood flow returns to baseline levels. Endothelial dysfunction (dysfunction of the inner lining of blood vessels), which is commonly associated with reduced nitric oxide levels in the blood stream, is a sign of cardiovascular disease and is a predictor of unsatisfactory clinical results. Peripheral Arterial Tonometry (PAT) signals from patient’s finger have been used in clinical settings to characterize cardiovascular performance, and have shown correlations to central pressures of the heart [3]. The noninvasive nature of PAT makes its applicability attractive as its clinical applications continue to advance. Therefore, PAT has a potential clinical application as a noninvasive metric, which can describe a patient’s endothelial function and overall cardiovascular health by measuring the reactive hyperemia response during a period of induced ischemia. Due to the ability of PAT to measure pulsatility of blood flow through digits, we hypothesize that reactive hyperemia responses can be measured non-invasively by recording PAT signals. Further, we hypothesize that there will be changes in reactive hyperemia responses shown through PAT signals when the length of ischemic time is altered. These results may have important clinical implications in terms of unravelling endothelial dysfunction and vascular elasticity.

Measurement of Biomechanical Properties of Tissues Under Uniaxial Stress

• Knowledge of biomechanical properties of tissues is necessary for credible description of their constitutive behavior in physiological conditions of normality and stress • A comprehensive and comparative understanding of tissue properties is of prime importance from the perspectives of device-tissue interactions • Moreover, ablation has become a common medical procedure, which alters both the structure and function of the ablated tissue; and in small percentage of cases, it can cause collateral damage of surrounding vital structures, which can have severe clinical implications • In order to maximize the efficacy of ablative procedures and minimize collateral damage, it is important to understand the biomechanical properties of all tissues that may be potentially affected by ablation • We have developed unique methodologies to assess the biomechanical properties of various tissues under uniaxial stress that include measurement of force-displacement graphs, stress-strain characteristics, calculations of avulsion forces, avulsion strains, energies associated with avulsions, and the elastic moduli of various tissue samples