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Biomedical subjects

C H Owen

Publications and source records attributed to C H Owen.

17 recordsLinked to original sources

The effects of ventricular pacing on left ventricular geometry, function, myocardial oxygen consumption, and efficiency of contraction in conscious dogs.

The effects of ventricular pacing on left ventricular (LV) dynamic geometry, function, and myocardial oxygen consumption (MVO2) were measured in 12 conscious dogs using sonomicrometry, micromanometry, ultrasonic flow probes, and oximetry catheters during right atrial (A-) and right ventricular (V-) pacing at 150 beats/min. Systolic function was quantified using slopes (MW) and volume-intercepts (VW) of linear relationships between end-diastolic volume (EDV) and stroke work (SW) for data obtained during vena caval occlusion. V-pacing shifted SW-EDV relationships downward (MW decreased from 97 +/- 21 to 81 +/- 21 Kerg/mL) and to the right (VW increased from 14 +/- 11 to 20 +/- 12 mL) in comparison with A-pacing (P < 0.02). These functional changes correlated with altered contractile geometry manifest as early shortening in the septal free wall relative to anterior-posterior dimension (increased minor axis mid-wall eccentricity at end-diastole and begin-ejection). Steady-state LV power output decreased from 802 +/- 213 mW during A-pacing to 514 +/- 170 mW during V-pacing (P < 0.05), while MVO2 remained relatively unchanged during V-pacing (10 +/- 3 mL O2/min vs 11 +/- 3 mL O2/min during A-pacing, P = NS). As a result, overall LV efficiency decreased from 0.24 +/- 0.08 during A-pacing to 0.16 +/- 0.06 during V-pacing (P < 0.05). These data illustrate the impact of V-pacing on dynamic LV geometry and function, including impaired LV work output at all physiological levels of preload. Most importantly, the relationship between LV work output and MVO2 is depressed during V-pacing, emphasizing the interaction between LV mechanics and pump efficiency in intact subjects. As a result, measures taken to restore normal contractile geometry might improve LV efficiency and performance when V-pacing is necessary.

Animals↗

Ventricular and myocardial efficiencies during acute aortic regurgitation in conscious dogs.

BACKGROUND: Alterations in cardiac efficiency may signal pathologic stresses and energetic adaptation during aortic regurgitation (AR). METHODS AND RESULTS: LV systolic function, left coronary blood flow, and AVO2 difference were measured in conscious dogs to assess LV and contractile efficiencies at baseline, 1 day (n=10), 1 week (n=10), and 3 weeks (n=8) of AR. LV systolic function was assessed by the preload recruitable stroke work relationship. Total LV Efficiency (TEFF=SWxHeart Rate/MVO2) and contractile efficiency (CEFF=1/the slope of the MVO2 -pressure-volume area relationship) and steady-state potential energy (PVA-SWxHR), mechanical coupling efficiency (MCE=SWxHR/PVA) were calculated. LV systolic function decreased by 17% at 1 day (P<.05) and by 24% at 3 weeks (P<.05). CEFF decreased from 58+/-8% to 38+/-10% (P<.05) at 1 day, normalized at 1 week, and decreased to 28+/-14% at 3 weeks (P<.05). TEFF was not altered at 1 day and 1 week but decreased by 3 weeks (P<.05). MCE trended downward from baseline of 47+/-5%, reaching significance at 3 weeks (34+/-6%, P<.05). CONCLUSIONS: CEFF decreases acutely, indicating diminished economy of myocardial contraction. CEFF normalizes at 1 week, suggesting adequate compensation. TEFF is not altered in early AR. By 3 weeks, LV systolic dysfunction is accompanied by depressed TEFF, mechanical coupling, and CEFF signaling the onset of decompensated AR. Thus, volume overload of acute AR resulted in early compensation at the expense of myocardial efficiency with subsequent global dysfunction characterized by depressed LV systolic mechanics, mechanical, coupling, and contractile efficiencies.

Acute Disease↗

Alignment of electron tomographic series by correlation without the use of gold particles.

Electron tomography requires that a tilt series of micrographs be aligned and that the orientation of the tilt axis be known. This has been done conveniently with gold markers applied to the surface of a specimen to provide easily accessible information on the orientation of each tilt projection. Where gold markers are absent, another approach to alignment must be used. A method is presented here for aligning tilt projections without the use of markers, utilizing correlation methods. The technique is iterative, drawing principally on the work of Dengler [Ultramicroscopy 30 (1989) 337], and consists of computing a low resolution back projection image from which computed tomographic projections can be generated. These in turn serve as reference images for the next alignment of the tomographic series. An initial alignment must be made before the first back projection, and this is done following the method of Guckenberger [Ultramicroscopy 9 (1982) 167] for translational alignment and by common lines analysis [Liu et al., Ultramicroscopy 58 (1995) 393] for identification of the tilt axis. Four tomographic series of a biological nature were aligned and analyzed, and the method has proven to be both accurate and reproducible for the data presented here.

Animals↗

Mechanical determinants of myocardial oxygen consumption in conscious dogs.

A new practical descriptor of metabolic to mechanical myocardial energy transfer (MET), termed the virtual work model, was evaluated in 32 conscious dogs and in 8 isolated canine hearts. An index of total mechanical energy expenditure (TME) was calculated as the sum of external energy (stroke work) and an internal energy index of heat (left ventricular end-diastolic volume times left ventricular mean ejection pressure). Physiological comparison of TME (x-axis) and myocardial oxygen consumption (MVO2; y-axis) yielded highly linear MET relationships (mean r = 0.93 +/- 0.07), with an average slope of 0.86 +/- 0.39 (SD) and a y-intercept of 9.1 +/- 6.4 mW/ml myocardium. The linear MVO2-TME relationship did not vary under steady-state vs. dynamic vena caval occlusion, increased heart rate, increased afterload, or increased inotropic state with calcium infusion. Compared with five other indexes of myocardial energetics, the virtual work model of MET was the most linear, the most practical in not requiring determination of the end-systolic pressure-volume relationship, and the most accurate predictor of MVO2 under normal and altered hemodynamic conditions.

Animals↗

Revascularization of the internal mammary artery after coronary artery bypass grafting.

Symptomatic anterior myocardial ischemia as a result of stenosis at the origin of the left internal mammary artery developed in a patient who underwent prior coronary artery bypass grafting using the left internal mammary artery as a conduit. Successful revascularization of the left anterior descending coronary artery was achieved using a reversed saphenous vein bypass graft from the left common carotid artery to the proximal internal mammary artery. This approach provided myocardial revascularization and avoided reoperative median sternotomy.

Aged↗

Coronary artery bypass grafting in patients with dialysis-dependent renal failure.

Few data exist regarding functional results and long-term survival after coronary bypass in patients on dialysis. Therefore, a retrospective analysis was performed of 21 consecutive patients with dialysis-dependent renal failure who were undergoing coronary artery bypass grafting. Preoperatively, all but 1 patient had associated comorbid illnesses, 15 patients (71%) had class IV angina, and 16 patients (76%) had either left main or three-vessel disease. There were two perioperative deaths (9%), and complications occurred in 10 of the 21 patients (48%). All 19 hospital survivors showed symptomatic improvement with improved overall functional status (mean Karnofsky score increased from 37% +/- 16% preoperatively to 69% +/- 9% at hospital discharge or death; p < 0.001). Actuarial survival rates were 84% +/- 8% and 45% +/- 13% at 1 and 2 years, respectively. Therefore, coronary bypass grafting may be performed in dialysis patients with increased but acceptable morbidity and mortality, with excellent symptomatic relief, and with improved functional status. However, limited long-term survival suggests that the relative costs and benefits of surgical revascularization need further examination in this patient population.

Adult↗

Influence of hyperbaric oxygen on left ventricular contractility, total coronary blood flow, and myocardial oxygen consumption in the conscious dog.

It is known that hyperbaric oxygenation (HBO) decreases total coronary blood flow (TCBF) and cardiac output (CO). To determine whether this is related to an alteration in myocardial contractility, 10 chronically instrumented conscious dogs were studied during pharmacologic autonomic blockade. Left ventricular (LV) volume was measured with ultrasonic transducers, LV transmural pressure with micromanometers, TCBF with Doppler-flow probes, and coronary AVO2 difference (A-CSO2) was calculated from direct LV and coronary sinus (CS) sampling. To evaluate the effect of increased oxygenation, data were obtained during resting control conditions and during dynamic vena caval occlusions (VCO), at 1 atmosphere of pressure, while breathing air (1 bar/0.21); at 3 atmospheres, breathing compressed air (3 bar/0.21), and at 3 atmospheres breathing 100% oxygen (3 bar/1.0). Because of autonomic blockade, heart rate (HR) was not statistically different in the three conditions. With increasing oxygenation, arterial oxygen tension (PaO2) increased from 85 +/- 5 mmHg (mean +/- SD) at 1 bar/0.21, to 1374 +/- 201 mmHg at 3 bar/1.0 whereas arterial carbon dioxide tension (PaCO2) and pH values were not statistically different. Arterial oxygen content (AO2 content) and CSO2 content increased significantly (both P < 0.05) with increasing PaO2. LV stroke volume (SV), CO, coronary blood flow, and myocardial oxygen consumption (MVO2) were all significantly reduced (P < 0.05) with increasing levels of oxygenation. Intrinsic myocardial function, as measured by the stroke-work/end-diastolic volume relationship was unchanged from 1 bar/0.21 to 3 bar/0.21, and to 3 bar/1.0 (P < 0.20). Thus, the diminished TCBF, CO, and MVO2 associated with HBO do not seem to be associated with a primary alteration in myocardial contractility, but rather may result from a physiologic autoregulation of the myocardium to increasing levels of PaO2.

Animals↗

The effects of local ventricular pacing on recovery from regional myocardial ischemia.

After surgical revascularization of ischemic myocardium, temporary ventricular pacing is often used, yet no data exist to indicate whether pacing ischemic versus nonischemic myocardium affects myocardial recovery. Therefore, chronically instrumented conscious dogs were studied with segment length transducers in the left anterior descending (LAD) distribution, left ventricular and pericardial micromanometers, pneumatic occluders on the LAD and venae cavae, and bipolar ventricular pacing wires, one pair in the LAD zone and one pair in the nonischemic (LCX) zone. Six dogs underwent a total of twelve 15-min LAD occlusions, each followed by 48 hr of reperfusion. Just after reperfusion, either the LAD or LCX zone was paced at 150 bpm for 45 min. LAD versus LCX pacing decreased regional stroke work (6 +/- 5 versus 19 +/- 5 kerg.cm-2) and produced contractile asynchrony. Myocardial contractile function was assessed using preload recruitable work area (PRWA), the area under the regional stroke work versus end-diastolic length relationship. Relative to LCX pacing, LAD pacing significantly delayed the recovery of PRWA after 4 hr of reperfusion (54 +/- 9 versus 83 +/- 9% control PRWA, P < 0.05). Perhaps by increased contractile asynchrony despite the decreased regional stroke work, ventricular pacing of ischemically injured myocardium delays functional recovery and should be avoided in clinical settings where the ventricular pacing site may be chosen.

Animals↗

Regional geometry and function during myocardial ischemia and recovery.

To define the effects of altered left ventricular (LV) geometry on regional myocardial function during ischemia and recovery, regional and global LV geometry and transmural pressure (P) were measured in seven conscious dogs with sonomicrometry and micromanometry. Data were obtained at steady state and during rapid vena caval occlusion (VCO) under control conditions, after 15 min of left anterior descending occlusion, and after 1, 4, and 24 hr of reperfusion. Regional midwall minor axis (MA) Lagrangian strain (epsilon) and stress (sigma) were calculated from measured MA segment length (L), MA midwall radius, and wall thickness. Unstressed regional geometry was quantified using L0, the value of L at P = 0 during maximal VCO. Conventional (SWL) and normalized (SW sigma epsilon) regional MA stroke work were calculated for each cardiac cycle as the area of P vs L and sigma vs epsilon relationships, respectively. Regional Frank-Starling mechanisms corrected for changes in unstressed LV geometry were quantified as the slope (M sigma epsilon) of the linear end diastolic epsilon vs SW sigma epsilon relationship for data obtained during VCO (mean r = 0.98). M sigma epsilon returned to baseline levels within 1 h of reperfusion (P = 0.314 vs control). In contrast, 15 min of ischemia increased L0 by 15.2 +/- 2.5% (P < 0.05), which remained increased 5.7 +/- 1.7% above control values after 1 hr of reperfusion (P < 0.05). Both steady-state SWL and SW sigma epsilon decreased with ischemia and slowly returned towards baseline, remaining 28.7 +/- 7.5% and 26.4 +/- 6.3% below control values after 1 hr of reperfusion (both P < 0.05). Therefore, late functional recovery from reversible ischemic injury is primarily correlated with reversal of changes in regional geometry, specifically the reversal of diastolic creep. As a result, adequate quantification of postischemic regional myocardial performance requires characterization of changes in regional geometry as well as indicators of Frank-Starling mechanisms.

Animals↗

Physiology of cardiac tamponade and paradoxical pulse in conscious dogs.

The physiological mechanism of paradoxical pulse in cardiac tamponade remains controversial. In eight conscious dogs with intact pericardia, ultrasonic dimension transducers assessed biventricular geometry and volumes, while micromanometers measured right ventricular (RV), left ventricular (LV), pleural, and pericardial pressures. With normal inspiration, peak LV pressure fell by 7.7 +/- 1.3 mmHg at control and by 20.3 +/- 3.7 mmHg during tamponade (P < 0.001), consistent with the development of paradoxical pulse. At peak inspiration during tamponade, RV filling increased, the interventricular septum shifted leftward, transeptal pressure became negative, and LV septal arc length (l theta) became smaller than its respective unpreloaded value at maximal vena caval occlusion (l(o)). Analysis of stroke work (SW)-end-diastolic volume (EDV) and end-systolic pressure-volume coordinates at peak inspiration during tamponade revealed that end-systolic pressure was 19.1 +/- 10.2 mmHg below the baseline end-systolic pressure-volume curve (P < 0.01), and SW was 24.2 +/- 8.8% below the baseline SW-EDV curve (P < 0.01), indicating transient inspiratory LV dysfunction. It is proposed that inspiratory leftward interventricular septal shifting at low LV EDV during tamponade completely unloads the septum (l theta < l o), eliminates the septal contribution to global LV SW, results in transient inspiratory LV dysfunction, and contributes to the phenomenon of paradoxical pulse.

Animals↗

Effects of the left ventricular assist device on right ventricular function.

Right ventricular failure is a leading cause of death in patients who require the left ventricular assist device. Previous reports suggested right ventricular functional deterioration during left ventricular assist but lacked a method by which right ventricular function could be quantified adequately. This study examined the effects of left ventricular volume unloading on right ventricular systolic function by means of the stroke work/end-diastolic volume relationship, a load-insensitive index of myocardial performance. In 12 anesthetized open-chested dogs, right ventricular and left ventricular pressures were measured with micromanometers while ultrasonic dimension transducers measured left and right ventricular orthogonal diameters. Left ventricular unloading was accomplished with left atrial-to-femoral artery bypass with a centrifugal pump. Data were recorded during transient vena caval occlusion in the control state and with maximal left ventricular unloading by full support by the left ventricular assist device. Modified ellipsoidal geometry was used to calculate simultaneous biventricular volumes, and linear regression analysis of right ventricular stroke work versus end-diastolic volume was used to quantify right ventricular systolic function. Average slope and x intercept of this relationship under control conditions were 2.2 +/- 0.3 X 10(4) erg/ml and 10.7 +/- 5.0 ml, respectively. During full support by the left ventricular assist device (mean flow rate, 2.4 +/- 0.3 L/min), left ventricular end-diastolic volume decreased by 31% (p less than 0.01), left ventricular septal-free wall diameter decreased by 7% (p less than 0.001), and rate of rise of right ventricular peak positive pressure declined by 13% (p less than 0.05). The corresponding slope and x intercept of the right ventricular stroke work/end-diastolic volume relationship during full unloading of left ventricular assist device were 2.3 +/- 0.3 X 0.3 X 10(4) erg/ml and 14.3 +/- 4.8 ml, respectively; these values were not significantly different from control values (p greater than 0.5). Additionally, analysis of right ventricular end-diastolic pressure-volume relationships suggested improved right ventricular chamber compliance, although the effects were small and did not reach statistical significance (p = 0.10). These data imply that marked alterations in biventricular geometry accompanying left ventricular volume unloading by the left ventricular assist device in a normal heart do not significantly alter right ventricular performance characteristics.

Animals↗

Image analysis of helical objects: the Brandeis Helical Package.

Although the fundamental steps in Fourier-based image analysis of electron micrographs of helical structures have not changed significantly since the techniques were developed 30 years ago, there have been developments which aid both the analysis itself and the interpretation of results. Increases in computational resources have allowed the automation of many of the repetitive steps in image processing. We describe here a set of computer programs which have been developed at Brandeis University over the past 10 or more years. These programs, referred to as the Brandeis Helical Package, are designed to operate independently of each other with a simple and more uniform protocol for the flow of information between them. The programs are now easier to understand and to use and therefore represent a good tool for the analysis of helical structures.

Actins↗

Arterial windkessel parameter estimation: a new time-domain method.

We developed and validated a new, more accurate, and easily applied method for calculating the parameters of the three-element Windkessel to quantitate arterial properties and to investigate ventriculoarterial coupling. This method is based on integrating the governing differential equation of the three-element Windkessel and solving for arterial compliance. It accounts for the interaction between characteristic impedance and compliance, an important phenomenon that has been ignored by previously implemented methods. The new integral method was compared with four previously published methods as well as a new independent linear least-squares analysis, using ascending aortic micromanometric and volumetric flow measurements from eight dogs. The parameters calculated by the new integral method were found to be significantly different from those obtained by the previous methods but did not differ significantly from maximum likelihood estimators obtained by a linear least-squares approach. To assess the accuracy of parameter estimation, pressure and flow waveforms were reconstructed in the time domain by numerically solving the governing differential equation of the three-element Windkessel model. Standard deviations of reconstructed waveforms from the experimental ensemble-averaged waveforms, which solely reflect the relative accuracy of the Windkessel parameters given by the various methods, were calculated. The new integral method invariably yielded the smallest error. These results demonstrate the improved accuracy of our new integral method in estimating arterial parameters of the three-element Windkessel.

Animals↗

Actin crosslinking protein EF-1a of Dictyostelium discoideum has a unique bonding rule that allows square-packed bundles.

The elongation factor 1a (EF-1a) of Dictyostelium discoideum is an actin crosslinking protein that gives rise to a unique kind of actin bundle. Purified actin and EF-1a were allowed to form bundles and then were characterized by electron microscopy, computed diffraction analysis, and modeling. In these bundles crosslinked actin filaments are rotated by 90 degrees relative to each other, whereas other known crosslinking proteins require filaments to be unrotated. Bundles of actin EF-1a would tend to exclude other actin bundling proteins. EF-1a can thus regulate the state of the actin cytoskeleton as well as regulate protein synthesis.

Actins↗

Assessment of the Frank-Starling relationship by two-dimensional echocardiography.

The Frank-Starling relationship between left ventricular stroke work and end-diastolic minor-axis cross-sectional area was evaluated as a load-insensitive measure of inotropic state by two-dimensional echocardiography in 10 conscious dogs. Stroke work was calculated as the product of systolic change in cross-sectional area and either (1) beat-to-beat mean arterial pressure or (2) initial systolic blood pressure. Both Frank-Starling relationships were highly linear during preload variation (mean r = 0.96), sensitive to the inotropic state (slope increase with calcium 51% +/- 43% and 62% +/- 53%, respectively), and insensitive to afterload (r < 0.4, slope or x intercept versus afterload). Thus the Frank-Starling relationships derived from two-dimensional echocardiographic images and peripheral arterial pressure may be a useful and practical means of assessing inotropic state with minimally invasive measurements.

Animals↗