[Show abstract][Hide abstract] ABSTRACT: Pulse wave velocity (PWV), a measure of arterial stiffness, has been demonstrated to be an independent predictor of adverse cardiovascular outcomes. This can be derived non-invasively using cardiovascular magnetic resonance (CMR). Changes in PWV during exercise may reveal further information on vascular pathology. However, most known CMR methods for quantifying PWV are currently unsuitable for exercise stress testing.
A velocity-sensitive real-time acquisition and evaluation (RACE) pulse sequence was adapted to provide interleaved acquisition of two locations in the descending aorta (at the level of the pulmonary artery bifurcation and above the renal arteries) at 7.8 ms temporal resolution. An automated method was used to calculate the foot-to-foot transit time of the velocity pulse wave. The RACE method was validated against a standard gated phase contrast (STD) method in flexible tube phantoms using a pulsatile flow pump. The method was applied in 50 healthy volunteers (28 males) aged 22–75 years using a MR-compatible cycle ergometer to achieve moderate work rate (38 ± 22 W, with a 31 ± 12 bpm increase in heart rate) in the supine position. Central pulse pressures were estimated using a MR-compatible brachial device. Scan-rescan reproducibility was evaluated in nine volunteers.
Phantom PWV was 22 m/s (STD) vs. 26 ± 5 m/s (RACE) for a butyl rubber tube, and 5.5 vs. 6.1 ± 0.3 m/s for a latex rubber tube. In healthy volunteers PWV increased with age at both rest (R 2 = 0.31 p < 0.001) and exercise (R 2 = 0.40, p < 0.001). PWV was significantly increased at exercise relative to rest (0.71 ± 2.2 m/s, p = 0.04). Scan-rescan reproducibility at rest was −0.21 ± 0.68 m/s (n = 9).
This study demonstrates the validity of CMR in the evaluation of PWV during exercise in healthy subjects. The results support the feasibility of using this method in evaluating of patients with systemic aortic disease.
Journal of Cardiovascular Magnetic Resonance 12/2015; 17(1). DOI:10.1186/s12968-015-0191-4 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
A jet injector is a device that can be used to deliver liquid drugs through the skin using a fluid jet, without the use of a needle. Most jet injectors are designed and used for the delivery of inviscid liquids, and are not optimized for the delivery of viscous drug compounds. To better understand the requirements for delivering viscous drugs, we have developed a mathematical model of the electro-mechanics of a moving-coil actuated jet injector as it delivers viscous fluids.
The model builds upon previous work by incorporating the nonlinear electrical properties of the motor, compliant elements of the mechanical piston and ampoule system, and the effect of viscosity on injector characteristics. The model has been validated by monitoring the movement of the piston tip and measurements of the jet force.
The results of the model indicate that jet speed is diminished with increasing fluid viscosity, but overshoot and ringing in the jet speed is unaffected. However, a stiffer ampoule and piston will allow for better control of the jet speed profile during an injection, and reduce ringing.
We identified that the piston friction coefficient, the compliance of the injector components, and the viscous properties of the fluid are important determinants of performance when jet injecting viscous fluids.
By expanding upon previous jet injector models, this work has provided informative simulations of jet injector characteristics and performance. The model can be used to guide the design of future jet injectors for viscous fluids.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Transdermal delivery of drugs has a number of advantages in comparison to other routes of administration. The mechanical properties of skin, however, impose a barrier to administration and so most compounds are administered using hypodermic needles and syringes. In order to overcome some of the issues associated with the use of needles, a variety of non-needle devices based on jet injection technology has been developed. Areas covered: Jet injection has been used primarily for vaccine administration but has also been used to deliver macromolecules such as hormones, monoclonal antibodies and nucleic acids. A critical component in the more recent success of jet injection technology has been the active control of pressure applied to the drug during the time course of injection. Expert opinion: Jet injection systems that are electronically controllable and reversible offer significant advantages over conventional injection systems. These devices can consistently create the high pressures and jet speeds necessary to penetrate tissue and then transition smoothly to a lower jet speed for delivery of the remainder of the desired dose. It seems likely that in the future this work will result in smart drug delivery systems incorporated into personal medical devices and medical robots for in-home disease management and healthcare.
Expert Opinion on Drug Delivery 05/2015; 12(10):1-12. DOI:10.1517/17425247.2015.1049531 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated systemic blood pressure, and the attendant development of pathologic left ventricular (LV) hypertrophy, ultimately culminates in heart failure and death. In clinical studies, a reduction of myocardial efficiency has been implicated in systemic hypertensive-hypertrophy. However, it is uncertain whether reduced efficiency correlates with LV wall thickness. Hence, we performed experiments on isolated working hearts of spontaneously hypertensive rats (SHRs)-a widely-used experimental model of human hypertensive-hypertrophy. We contrasted their mechanoenergetic performance with that of Wistar controls at two ages: Adult (9 months) and Aged (post-18 months). The use of animal hearts allowed us to perform experiments over a wide range of afterloads. We found that mechanoenergetic performance (coronary and aortic flows, work output and oxygen consumption) declined with age. The peak efficiency of the Adult SHR was essentially similar to that of Control, but that for the Aged SHR was lower, compared with that of age-matched Wistar rats. All variables, including peak efficiency, obtained from the failing Aged SHR hearts (which also developed right ventricular hypertrophy), were greatly reduced. Our data reveal that peak efficiency of the Aged SHR, upon transitioning from compensated hypertrophy to failure, diminishes sharply, arising from compromised flows-both aortic and coronary. We further show that the reduction of myocardial efficiency in hypertensive-hypertrophy does not correlate with LV wall thickness, but instead is inversely correlated with whole-heart mass. The latter relation may serve as a prognostic and diagnostic tool in the clinical setting.Hypertension Research advance online publication, 19 March 2015; doi:10.1038/hr.2015.37.
Hypertension Research 03/2015; 38(8). DOI:10.1038/hr.2015.37 · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca2+ cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced.
[Show abstract][Hide abstract] ABSTRACT: Determining heat losses in power transfer components operating at high frequencies for implantable inductive power transfer systems is important for assessing whether the heat dissipated by the component is acceptable for implantation and medical use. However, this is a challenge at high frequencies and voltages due to limitations in electronic instrumentation. Calorimetric methods of power measurement are immune to the effects of high frequencies and voltages; hence, the measurement is independent of the electrical characteristics of the system. Calorimeters have been widely used to measure the losses of high power electrical components (>50 W), however it is more difficult to perform on low power components. This paper presents a novel power measurement method for components dissipating anywhere between 0.2 W and 1 W of power based on a heat balance calorimeter that uses a Peltier device as a balance sensor. The proposed balance calorimeter has a single test accuracy of ±0.042 W. The experimental results revealed that there was up to 35% difference between the power measurements obtained with electrical methods and the proposed calorimeter.
[Show abstract][Hide abstract] ABSTRACT: An integrated instrument is being developed to study live cardiac trabeculae, which is capable of stimulating the muscle under controlled conditions while measuring the heat production, force, and sarcomere length distribution. To improve the accuracy of estimation of stress, strain, and volumetric heat production, the geometry of the muscle must be known. A spectral domain optical coherence tomography system (SD-OCT) has been constructed and calibrated to image the trabecula mounted inside the instrument. This system was mounted above the muscle chamber and a series of equally-spaced cross-sectional images were obtained. These were processed using a workflow developed to extract cross-sectional area and volume. The initial results have demonstrated the feasibility of using OCT to capture the overall geometry of cardiac trabecula mounted in the instrument. Further work will be directed to improve the image quality for larger samples and apply meshing algorithms to the acquired data.
[Show abstract][Hide abstract] ABSTRACT: We present a scaling model for electrically-actuated needle free jet injectors, establishing the relationship between injection volume and motor size. Using an analytical electromagnetic model for the motor, we derive an optimal motor design, and show that this design is approximately scale-invariant. To illustrate the utility of this model, we then describe the design of a motor for use with 300μL disposable injection ampoules with a mass of just 300g, including a light-weight support structure. Experimental verification of the motor performance shows close agreement to model predictions, with a peak force of 1000 N/kg and a 150 m/s water jet delivered.
[Show abstract][Hide abstract] ABSTRACT: Vascularized biological tissue has been shown to increase in stiffness with increased perfusion pressure. The interaction between blood in the vasculature and other tissue components can be modeled with a poroelastic, biphasic approach. The ability of this model to reproduce the pressure-driven stiffening behavior exhibited by some tissues depends on the choice of the mechanical constitutive relation, defined by the Helmholtz free energy density of the skeleton. We analyzed the behavior of a number of isotropic poroelastic constitutive relations by applying a swelling pressure, followed by homogeneous uniaxial or simple-shear deformation. Our results demonstrate that a strain-stiffening constitutive relation is required for a material to show pressure-driven stiffening, and that the strain-stiffening terms must be volume-dependent.
[Show abstract][Hide abstract] ABSTRACT: Diabetes induces numerous electrical, ionic and biochemical defects in the heart. A general feature of diabetic myocardium is its low rate of activity, commonly characterised by prolonged twitch duration. This diabetes-induced mechanical change, however, seems to have no effect on contractile performance (i.e., force production) at the tissue level. Hence, we hypothesise that diabetes has no effect on either myocardial work output or heat production and, consequently, the dependence of myocardial efficiency on afterload of diabetic tissue is the same as that of healthy tissue.
We used isolated left ventricular trabeculae (streptozotocin-induced diabetes versus control) as our experimental tissue preparations. We measured a number of indices of mechanical (stress production, twitch duration, extent of shortening, shortening velocity, shortening power, stiffness, and work output) and energetic (heat production, change of enthalpy, and efficiency) performance. We calculated efficiency as the ratio of work output to change of enthalpy (the sum of work and heat).
Consistent with literature results, we showed that peak twitch stress of diabetic tissue was normal despite suffering prolonged duration. We report, for the first time, the effect of diabetes on mechanoenergetic performance. We found that the indices of performance listed above were unaffected by diabetes. Hence, since neither work output nor change of enthalpy was affected, the efficiency-afterload relation of diabetic tissue was unaffected, as hypothesised.
Diabetes prolongs twitch duration without having an effect on work output or heat production, and hence efficiency, of isolated ventricular trabeculae. Collectively, our results, arising from isolated trabeculae, reconcile the discrepancy between the mechanical performance of the whole heart and its tissues.
[Show abstract][Hide abstract] ABSTRACT: It is generally recognized that increased consumption of polyunsaturated fatty acids, fish oil (FO) in particular, is beneficial to cardiac and cardiovascular health, whereas equivalent consumption of saturated fats is deleterious. In this study, we explore this divergence, adopting a limited purview: The effect of dietary fatty acids on the mechanoenergetics of the isolated heart per se. Mechanical indices of interest include left-ventricular (LV) developed pressure, stroke work, cardiac output, coronary perfusion, and LV power. The principal energetic index is whole-heart oxygen consumption, which we subdivide into its active and basal moieties. The primary mechanoenergetic index of interest is cardiac efficiency, the ratio of work performance to metabolic energy expenditure. Wistar rats were divided into three Diet groups and fed, ad libitum, reference (REF), fish oil-supplemented (FO), or saturated fatty acid-supplemented (SFA) food for 6 weeks. At the end of the dietary period, hearts were excised, mounted in a working-heart rig, and their mechanoenergetic performance quantified over a range of preloads and afterloads. Analyses of Variance revealed no difference in any of the individual mechanoenergetic indices among the three Diet groups. In particular, we found no effect of prior dietary supplementation with either saturated or unsaturated fatty acids on the global efficiency of the heart.
[Show abstract][Hide abstract] ABSTRACT: Numerous epidemiological studies, supported by clinical and experimental findings, have suggested beneficial effects of dietary fish- or fish oil- supplementation on cardiovascular health. One such experimental study showed a profound (100%) increase in myocardial efficiency (i.e., the ratio of work output to metabolic energy input) of the isolated whole-heart, achieved by a corresponding decrease in the rate of myocardial oxygen consumption. However, a number of other investigations have returned null results on the latter energetic index. Such conflicting findings have motivated us to undertake a re-examination. To that effect, we investigated the effects of dietary fatty acid supplementation on myocardial mechano energetics, with our primary focus on cardiac efficiency. We used both isolated hearts and isolated left ventricular trabeculae of rats fed with one of three distinct diets: Reference (REF), Fish Oil-supplemented (FO) or Saturated Fat-supplemented (SFA). For all three groups, and at both spatial levels, we supplied 10 mM glucose as the exogenous metabolic substrate. In the working-heart experiments, we found no difference in the average mechanical efficiency among the three dietary groups: 14.8 ± 1.1% (REF), 13.9 ± 0.6% (FO) and 13.6 ± 0.7% (SFA). Likewise, we observed no difference in peak mechanical efficiency of LV trabeculae: 13.3 ± 1.4%, 11.2 ± 2.2% and 12.5 ± 1.5% among the REF, FO and SFA groups, respectively. We conclude that there is no effect of a period of pre-exposure to a diet supplemented with either fish oil or saturated fatty-acids on the efficiency of the myocardium at either spatial level: tissue or whole-heart.
The Journal of Physiology 02/2014; 592(8). DOI:10.1113/jphysiol.2013.269977 · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes is known to alter the energy metabolism of the heart. Thus, it may be expected to affect the efficiency of contraction (i.e., the ratio of mechanical work output to metabolic energy input). The literature on the subject is conflicting. The majority of studies have reported a reduction of myocardial efficiency of the diabetic heart, yet a number of studies have returned a null effect. We propose that these discrepant findings can be reconciled by examining the dependence of myocardial efficiency on afterload.
We performed experiments on streptozotocin (STZ)-induced diabetic rats (7-8 weeks post-induction), subjecting their (isolated) hearts to a wide range of afterloads (40 mmHg to maximal, where aortic flow approached zero). We measured work output and oxygen consumption, and their suitably scaled ratio (i.e., myocardial efficiency).
We found that myocardial efficiency is a complex function of afterload: its value peaks in the mid-range and decreases on either side. Diabetes reduced the maximal afterload to which the hearts could pump (105 mmHg versus 150 mmHg). Thus, at high afterloads (for example, 90 mmHg), the efficiency of the STZ heart was lower than that of the healthy heart (10.4% versus 14.5%) due to its decreased work output. Diabetes also reduced the afterload at which peak efficiency occurred (optimal afterload: 63 mmHg versus 83 mmHg). Despite these negative effects, the peak value of myocardial efficiency (14.7%) was unaffected by diabetes.
Diabetes reduces the ability of the heart to pump at high afterloads and, consequently, reduces the afterload at which peak efficiency occurs. However, the peak efficiency of the isolated working rat heart remains unaffected by STZ-induced diabetes.