Interaction of Radio Frequency and LAMBDA-DNA.

With the prevalence of wireless radio frequency (RF) devices, interest is growing to more fully understand the effect of RF on biological tissue. This research explores how ?DNA interacts with RF energy. By sweeping a radio frequency range from 1 GHz to 8.5 GHz we hope to observe if specific frequencies show significantly elevated RF energy-?DNA interaction (e.g. either absorbed and/or reflected). Our procedure is as follows: 1) Set up RF equipment (horn antennas and network analyzer), 2) vary frequency from 1- 8.5GHz at a RF power level of 0 dBm, 3) vary same frequency sweep with buffer in the cell culture wells, and next with DNA and buffer in the cell-culture wells, and 4) the frequency sweep was repeated 100 times with a duration of 1.0 second per sweep. The results indicate regions of RF- ?DNA interaction around 3 and 3.5 GHz.

Decay of postextrasystolic potentiation in the left and right ventricles of intact canine hearts.

Intracellular regulation of myocardial Ca2+ has long been of interest to physiologists. The force-interval relationship provides a phenomenological approach that permits insight into aspects of calcium regulation. The response to an extrasystole is a potentiation in contractile force and the recovery in contractile force is described by the recirculation fraction (RF). The RF provides a gross estimation of calcium uptake by sarcoplasmic reticulum (SR), leading to myocardial relaxation. The current study focused on the relationship of right (RV) and left ventricular (LV) RF in canines under several contractile states. Anesthetized canines (n = 5) were catheterized for RV and LV pressure measurements. dP/dt(max) for the RV and LV was calculated for three baseline beats, one extrasystole and the first five postextrasystolic beats. The relationship between the LV dP/dt(max) and RV dP/dt(max) for all of the mentioned beats was then examined. Contractility was increased with calcium chloride and extrasystoles were delivered. Once cardiac function returned to a baseline level, contractility was reduced by increasing the concentration of isoflurane and the evaluation repeated. All ventricular contractions were controlled by RA pacing to maintain intrinsic conduction. A strong linear relationship between RV and LV dP/dt(max) (r = 0.94 +/- .06) existed for most canine's contractile states. These results build on findings in isolated hearts and demonstrate that biventricular response to extrasystoles and subsequent contractile recovery is both linear and correlated, suggesting that intracellular calcium regulation in a given heart across contractile state is static.

Assessment of dsigma*/dt (max), a load independent index of contractility, in the canine.

The search for a load-independent index of myocardial contractility has been a focus for nearly 100 years. Nearly all of the parameters developed have yielded insight into cardiac function but their clinical utility has been limited. A new index, dsigma*/dt (max), has been proposed to be useful in the clinic. This parameter is expressed as the maximum time rate of change of the pressure normalized circumferential wall stress (sigma* = sigma ( theta )/P, where sigma ( theta ) is circumferential wall stress and P is pressure) for a thick walled sphere model of the left ventricle (LV). This definition for a contractility index renders dsigma*/dt (max) dependent only on LV wall volume (V (m)) and maximum time rate of change of the ventricular volume, dV/dt (max). The index dsigma*/dt (max) has been studied in patients with echocardiogram-derived volume, but up until this point its characteristics in canines have remained unknown. Validating this index in the canine will allow for a more intensive and wide-range investigation of the index that is not available with humans. The purpose of this study was to validate dsigma*/dt (max) as a load-independent measure of contractility in the canine heart with the hope that it was a noninvasive assessment of contractile function. To assess the load independence of dsigma*/dt (max), the index was estimated over a range of preloads (end diastolic volume, EDV) during a vena caval occlusion (VCO). The study was conducted in five canines under various pacing modes [right atrial (RA), right ventricular (RV), left ventricular (LV), and biventricular (BV)] at rates of 90 or 100, and 160 bpm. The animals' ventricular volume measurements were assessed by conductance catheter, calibrated with echocardiography. A 50 Hz filter was applied to the volume signal before differentiation to obtain dV/dt (max). Echocardiography was used to calculate left ventricle mass and V (m). In eight of ten cases, dsigma*/dt (max) was significantly correlated with decreasing EDV (p < 0.05). There was also a significant correlation between dsigma*/dt (max) and dP/dt (max). With a strong correlation between the values of dsigma*/dt (max), dP/dt (max), and EDV in all five subjects, dsigma*/dt (max) is not load independent in the canine heart when preload is altered by a VCO. Further evaluation of this index is required to delineate the situations where dsigma*/dt (max) can be accurately applied.

The effect of heart rate, preload, and afterload on the viscoelastic properties of the swine myocardium.

Experiments were performed to test the hypothesis that viscoelastic properties of the swine myocardium are independent of heart rate (HR), preload (PL), and afterload (AL). Left ventricular pressure and aortic flow (AoF) waveforms were recorded in 13 swine. At different paced heart rates, an inferior vena caval occlusion (IVC) was used to reduce PL, then the IVC was released and simultaneously the aorta was clamped to increase AL. Equivalent left ventricular pressure waveform pairs consisting of an ejecting waveform (denoted as LVP) and isovolumic waveform (denoted as hydromotive pressure, HMP) were selected according to specified criteria resulting in 371 equivalent waveform pairs. From the selected waveform pairs and corresponding aortic flow waveforms, the viscoelastic properties (k and epsilon1) were estimated by HMP = LVP + epsilon1 V(EJ) + k x LVP x AoF. Here epsilon1 is the parallel elastance, k is the myocardial friction, and V(EJ) is the integral of AoF over ejection. Next, using k, epsilon1, LVP, and AoF waveforms, HMP was estimated using the equation above. To validate the model, the measured HMP and model-calculated HMP were compared for 371 matched waveform pairs (R2 = 0.97, SEE = 3.7 mmHg). The viscoelastic parameters (k and epsilon1) did not exhibit any clear or predictable dependence on HR, PL, and AL.

Left ventricular and myocardial perfusion responses to volume unloading and afterload reduction in a computer simulation.

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. In a few cases, patients have been successfully weaned from these devices after myocardial recovery. To promote myocardial recovery and alleviate the demand for donor organs, we are developing an artificial vasculature device (AVD) that is designed to allow the heart to fill to its normal volume but eject against a lower afterload. Using this approach, the heart ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which has been programmed to produce any desired afterload condition defined by an input impedance profile. During diastole, the AVD returns this SV to the aorta, providing counterpulsation. Dynamic computer models of each of the assist devices (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model of the cardiovascular system. Computer simulations of these assist techniques were conducted to predict physiologic responses. Hemodynamic parameters, ventricular pressure-volume loops, and vascular impedance characteristics were calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a range of clinical cardiac conditions (normal, failing, and recovering left ventricle). These simulation results indicate that the AVD may provide better coronary perfusion, as well as lower vascular resistance and elastance seen by the native heart during ejection compared with continuous and pulsatile VAD. Our working hypothesis is that by controlling afterload using the AVD approach, ventricular cannulation can be eliminated, myocardial perfusion improved, myocardial compliance and resistance restored, and effective weaning protocols developed that promote myocardial recovery.

Integrated data acquisition system for medical device testing and physiology research in compliance with good laboratory practices.

In seeking approval from the US Food and Drug Administration (FDA) for clinical trial evaluation of an experimental medical device, a sponsor is required to submit experimental findings and support documentation to demonstrate device safety and efficacy that are in compliance with Good Laboratory Practices (GLP). The objective of this project was to develop an integrated data acquisition (DAQ) system and documentation strategy for monitoring and recording physiological data when testing medical devices in accordance with GLP guidelines mandated by the FDA. Data aquisition systems were developed as stand-alone instrumentation racks containing transducer amplifiers and signal processors, analog-to-digital converters for data storage, visual display and graphical user-interfaces, power conditioners, and test measurement devices. Engineering standard operating procedures (SOP) were developed to provide a written step-by-step process for calibrating, validating, and certifying each individual instrumentation unit and the integrated DAQ system. Engineering staff received GLP and SOP training and then completed the calibration, validation, and certification process for the individual instrumentation components and integrated DAQ system. Eight integrated DAQ systems have been successfully developed that were inspected by regulatory affairs consultants and determined to meet GLP guidelines. Two of these DAQ systems were used to support 40 of the pre-clinical animal studies evaluating the AbiCor artificial heart (ABIOMED, Danvers, MA). Based in part on these pre-clinical animal data, the AbioCor clinical trials began in July 2001. The process of developing integrated DAQ systems, SOP, and the validation and certification methods used to ensure GLP compliance are presented in this article.

Hemodynamic and pressure-volume responses to continuous and pulsatile ventricular assist in an adult mock circulation.

This study investigated the hemodynamic and left ventricular (LV) pressure-volume loop responses to continuous versus pulsatile assist techniques at 50% and 100% bypass flow rates during simulated ventricular pathophysiologic states (normal, failing, recovery) with Starling response behavior in an adult mock circulation. The rationale for this approach was the desire to conduct a preliminary investigation in a well controlled environment that cannot be as easily produced in an animal model or clinical setting. Continuous and pulsatile flow ventricular assist devices (VADs) were connected to ventricular apical and aortic root return cannulae. The mock circulation was instrumented with a pressure-volume conductance catheter for simultaneous measurement of aortic root pressure and LV pressure and volume; a left atrial pressure catheter; a distal aortic pressure catheter; and aortic root, aortic distal, VAD output, and coronary flow probes. Filling pressures (mean left atrial and LV end diastolic) were reduced with each assist technique; continuous assist reduced filling pressures by 50% more than pulsatile. This reduction, however, was at the expense of a higher mean distal aortic pressure and lower diastolic to systolic coronary artery flow ratio. At full bypass flow (100%) for both assist devices, there was a pronounced effect on hemodynamic parameters, whereas the lesser bypass flow (50%) had only a slight influence. Hemodynamic responses to continuous and pulsatile assist during simulated heart failure differed from normal and recovery states. These findings suggest the potential for differences in endocardial perfusion between assist techniques that may warrant further investigation in an in vivo model, the need for controlling the amount of bypass flow, and the importance in considering the choice of in vivo model.

Characterization of an adult mock circulation for testing cardiac support devices.

A need exists for a mock circulation that behaves in a physiologic manner for testing cardiac devices in normal and pathologic states. To address this need, an integrated mock cardiovascular system consisting of an atrium, ventricle, and systemic and coronary vasculature was developed specifically for testing ventricular assist devices (VADs). This test configuration enables atrial or ventricular apex inflow and aortic outflow cannulation connections. The objective of this study was to assess the ability of the mock ventricle to mimic the Frank-Starling response of normal, heart failure, and cardiac recovery conditions. The pressure-volume relationship of the mock ventricle was evaluated by varying ventricular volume over a wide range via atrial (preload) and aortic (afterload) occlusions. The input impedance of the mock vasculature was calculated using aortic pressure and flow measurements and also was used to estimate resistance, compliance, and inertial mechanical properties of the circulatory system. Results demonstrated that the mock ventricle pressure-volume loops and the end diastolic and end systolic pressure-volume relationships are representative of the Starling characteristics of the natural heart for each of the test conditions. The mock vasculature can be configured to mimic the input impedance and mechanical properties of native vasculature in the normal state. Although mock circulation testing systems cannot replace in vivo models, this configuration should be well suited for developing experimental protocols, testing device feedback control algorithms, investigating flow profiles, and training surgical staff on the operational procedures of cardiovascular devices.

Bed rest affects ventricular and arterial elastances in monkeys: implications for humans.

METHODS: Experimental data were obtained from five chronically instrumented rhesus monkeys exposed to 96 h of 10 degrees head-down bed rest (HDBR) and another 96 h of 80 degrees upright control separated by 9 d of ambulatory recovery in a counter-balanced, crossover experiment design to test the hypotheses that: 1) headward and footward fluid shifts would increase systemic arterial (Eart) and left ventricular end-systolic (Ees) elastances; and 2) changes in Eart and Ees would be related in magnitude and direction. Ees and Eart were calculated from measurements taken during five observation periods for initial 2-h and 4-d exposures to HDBR that produced headward volume shifts, and acute exposure to graded levels of lower body negative pressure (LBNP) designed to produce orthostatic volume shifts. RESULTS: There was no effect of HDBR on Ees and Eart for any observation period (initial 2-h, 4-d, or LBNP). Eart increased in a similar pattern during the 4-d exposure to both control and HDBR. Ees increased with increasing LBNP levels for both control and HDBR while Eart remained unchanged. CONCLUSION: Our data are consistent with the notion that elevated Eart may represent an adaptation to physical inactivity that is associated with cardiovascular deconditioning.