Reproducibility and variability of digital thermal monitoring of vascular reactivity.

BACKGROUND: Previous studies demonstrated that digital thermal monitoring (DTM) of vascular reactivity, a new test for vascular function assessment, is well correlated with Framingham Risk Score, coronary calcium score and CT angiography. This study evaluates the variability and reproducibility of DTM measurements. We hypothesized that DTM is reproducible, and its variability falls within the accepted range of clinical diagnostic tests. METHOD: A fully automated DTM device (VENDYS, Endothelix Inc., Houston, TX, USA) was used for repeated measurement of vascular function in 18 healthy volunteers (age 35 ± 4 years, 74% men) after 24 h. All subjects underwent overnight fasting, and the test was preceded by 30-min rest in a supine position inside a dimmed room with temperature 22-24°C. The measurements were obtained during and after a 2-min supra systolic arm-cuff occlusion-induced reactive hyperaemia procedure. As a part of this study, the Doppler ultrasound hyperaemic, low-frequency, blood velocity of radial artery and a fingertip DTM of vascular function were compared simultaneously. Postcuff deflation temperature rebound and area under the curve, DTM indices of vascular function, were studied. RESULTS: Temperature rebound area under the curve correlated closely with Doppler hyperaemic, low-frequency, blood velocity (r = 0·97, P = 0·0001). Day-to-day intra-subject variability was 6·2% for baseline temperature, 8·7% for mean blood pressure and 11·4% for heart rate. The coefficient of repeatability of temperature rebound and area under the curve were 2·4% and 2·8%. CONCLUSION: In a controlled environment, the repeatability of DTM is excellent. DTM can be used as a reproducible and operator-independent test for non-invasive measurement of vascular function.

Sensitivity of digital thermal monitoring parameters to reactive hyperemia.

Both structural and functional evaluations of the endothelium exist in order to diagnose cardiovascular disease (CVD) in its asymptomatic stages. Vascular reactivity, a functional evaluation of the endothelium in response to factors such as occlusion, cold, and stress, in addition to plasma markers, is the most widely accepted test and has been found to be a better predictor of the health of the endothelium than structural assessment tools such as coronary calcium scores or carotid intima-media thickness. Among the vascular reactivity assessment techniques available, digital thermal monitoring (DTM) is a noninvasive technique that measures the recovery of fingertip temperature after 2-5 min of brachial occlusion. On release of occlusion, the finger temperature responds to the amount of blood flow rate overshoot referred to as reactive hyperemia (RH), which has been shown to correlate with vascular health. Recent clinical trials have confirmed the potential importance of DTM as an early stage predictor of CVD. Numerical simulations of a finger were carried out to establish the relationship between DTM and RH. The model finger consisted of essential components including bone, tissue, major blood vessels (macrovasculature), skin, and microvasculature. The macrovasculature was represented by a pair of arteries and veins, while the microvasculature was represented by a porous medium. The time-dependent Navier-Stokes and energy equations were numerically solved to describe the temperature distribution in and around the finger. The blood flow waveform postocclusion, an input to the numerical model, was modeled as an instantaneous overshoot in flow rate (RH) followed by an exponential decay back to baseline flow rate. Simulation results were similar to clinically measured fingertip temperature profiles in terms of basic shape, temperature variations, and time delays at time scales associated with both heat conduction and blood perfusion. The DTM parameters currently in clinical use were evaluated and their sensitivity to RH was established. Among the parameters presented, temperature rebound (TR) was shown to have the best correlation with the level of RH with good sensitivity for the range of flow rates studied. It was shown that both TR and the equilibrium start temperature (representing the baseline flow rate) are necessary to identify the amount of RH and, thus, to establish criteria for predicting the state of specific patient's cardiovascular health.

Flow visualization techniques in a mock ventricle supported by a nonpulsatile left ventricular assist device.

Little is known about flow patterns in ventricles supported by continuous flow left ventricular assist devices (LVADs), and valuable information can be obtained with simple flow visualization experiments. We describe the application of several experimental techniques for the in vitro study of ventricular flow patterns (e.g., unsteadiness, vortical motions, stagnation regions) in the presence of a continuous flow LVAD. We used dye streaks, particle paths, and hydrogen bubble techniques to visualize fluid flow in an idealized, static, transparent mock ventricle attached to a Jarvik 2000 continuous flow LVAD. We recorded ventricular flow behavior at various pump speeds while independently adjusting pump flow (by varying the afterload) to emulate in vivo pump flow at various phases of the cardiac cycle. Changes in ventricular flow behavior at different pump flow rates may be of clinical relevance, because continuous flow pumps are extremely sensitive to inflow and outflow pressures and instantaneous pump flow varies significantly at different points throughout the cardiac cycle. Further work is needed to quantitatively compare the flow behavior of different continuous flow devices in a pulsatile ventricular model.

Assessment of fetal canine cardiac myocyte survival in a dual-side flow bioreactor with modeled hypoxia/reperfusion injury.

The present study introduces a new experimental model of hypoxia/reperfusion injury using a newly developed bioreactor system. The injury is introduced and kept localized via fluid dynamic manipulation. Using low Reynolds number fluid flow, regions of the culture can be injured while maintaining physiological conditions in the remaining culture. This approach enables both normal and injured cells within the same monolayer to be investigated side-by-side. The current study evaluated the ability of the model to induce localized reperfusion injury in a monolayer of fetal canine cardiomyocytes (FCCs). Significant apoptosis was found in the hypoxia/reperfusion-injured but not normal-flow regions of the myocyte cultures. The model holds the potential to help elucidate the fundamental mechanisms of hypoxic/reperfusion insults in myocardium.

Model of the mass transport to the surface of animal cells cultured in a rotating bioreactor operated in micro gravity.

A mathematical model is used to investigate the transport of dissolved oxygen from the bulk fluid to the surface of aggregates of animal cells cultured in a rotating bioreactor. These aggregates move through different regions of the bioreactor with a local flow field and concentration distribution that vary with time. The time variation of the Sherwood number and the surface concentration for a range of parameters typical of a cell science experiment executed in the Rotating Wall Perfused Vessel (RWPV) bioreactor in space are investigated. The Reynolds numbers experienced by the aggregate are generally low (Re < 1) and the Peclet numbers range from O(1) to O(100). Comparison of the results from the numerical solution of the mathematical model with those from a quasi-steady model, using a steady-state correlation for mass transport on a sphere, indicate that the quasi-steady assumption is not a good model to compute the instantaneous Sherwood number. This indicates a significant history effect in the Sherwood number response to the variations of acceleration of the aggregates in the bioreactor. A high resistance to the mass transport from the bulk fluid to the surface of the aggregate exists for the bioreactor operated in micro gravity. The difference between the surface concentration and the free stream concentration was as high as 30% for aggregates larger than 3 mm. Diffusion reduces the variations of the free stream concentration resulting in a nearly constant value for the concentration at the surface of the aggregates.

RWPV bioreactor mass transport: earth-based and in microgravity.

Mass transport and mixing of perfused scalar quantities in the NASA Rotating Wall Perfused Vessel bioreactor are studied using numerical models of the flow field and scalar concentration field. Operating conditions typical of both microgravity and ground-based cell cultures are studied to determine the expected vessel performance for both flight and ground-based control experiments. Results are presented for the transport of oxygen with cell densities and consumption rates typical of colon cancer cells cultured in the RWPV. The transport and mixing characteristics are first investigated with a step change in the perfusion inlet concentration by computing the time histories of the time to exceed 10% inlet concentration. The effects of a uniform cell utilization rate are then investigated with time histories of the outlet concentration, volume average concentration, and volume fraction starved. It is found that the operating conditions used in microgravity produce results that are quite different then those for ground-based conditions. Mixing times for microgravity conditions are significantly shorter than those for ground-based operation. Increasing the differential rotation rates (microgravity) increases the mixing and transport, while increasing the mean rotation rate (ground-based) suppresses both. Increasing perfusion rates enhances mass transport for both microgravity and ground-based cases, however, for the present range of operating conditions, above 5-10 cc/min there are diminishing returns as much of the inlet fluid is transported directly to the perfusion exit. The results show that exit concentration is not a good indicator of the concentration distributions in the vessel. In microgravity conditions, the NASA RWPV bioreactor with the viscous pump has been shown to provide an environment that is well mixed. Even when operated near the theoretical minimum perfusion rates, only a small fraction of the volume provides less than the required oxygen levels.