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1.
Comput Biol Med ; 34(5): 371-88, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15145710

ABSTRACT

A computer program is described for beat-to-beat analysis of cardiovascular parameters from high-fidelity pressure and flow waveforms. The Hemodynamic Estimation and Analysis Research Tool (HEART) is a post-processing analysis software package developed in Matlab that enables scientists and clinicians to document, load, view, calibrate, and analyze experimental data that have been digitally saved in ascii or binary format. Analysis routines include traditional hemodynamic parameter estimates as well as more sophisticated analyses such as lumped arterial model parameter estimation and vascular impedance frequency spectra. Cardiovascular parameter values of all analyzed beats can be viewed and statistically analyzed. An attractive feature of the HEART program is the ability to analyze data with visual quality assurance throughout the process, thus establishing a framework toward which Good Laboratory Practice (GLP) compliance can be obtained. Additionally, the development of HEART on the Matlab platform provides users with the flexibility to adapt or create study specific analysis files according to their specific needs.


Subject(s)
Myocardial Contraction , Software , Algorithms , Calibration , Guideline Adherence , Hemodynamics , Humans
2.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 3773-6, 2004.
Article in English | MEDLINE | ID: mdl-17271116

ABSTRACT

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. An artificial vasculature device (AVD) that may better facilitate myocardial recovery than VAD by controlling the afterload seen by the ejecting heart is being developed. The AVD concept is to enable any user-defined input impedance (IM) with resistance (R) and compliance (C) components. In this study, a pulse duplicator was used to test the efficacy of the AVD concept for two control strategies in an adult mock circulation: (1) R-C in series and (2) 2-element Windkessel (R-C in parallel) using instantaneous impedance position control (IIPC) to maintain a desired value or profile of R and C. In vitro experiments were performed and the resulting cardiovascular pressures, volumes, flows, and the afterload (R and C) seen by the LV during ejection for simulated cardiac failure were recorded and analyzed. Our results indicate that setting the AVD to lower IM reduced LV volume and pressure, restored LV stroke volume, and increased coronary flow. The IIPC control algorithms are better suited to maintain any instantaneous IM or an IM profile, but are susceptible to measurement noise.

3.
J Invest Surg ; 15(2): 91-9, 2002.
Article in English | MEDLINE | ID: mdl-12028619

ABSTRACT

In dynamic myoplasty, dysfunctional muscle is assisted or replaced with skeletal muscle from a donor site. Electrical stimulation is commonly used to train and animate the skeletal muscle to perform its new task. Due to simultaneous tetanic contractions of the entire myoplasty, muscles are deprived of perfusion and fatigue rapidly, causing long-term problems such as excessive scarring and muscle ischemia. Sequential stimulation contracts part of the muscle while other parts rest, thus significantly improving blood perfusion. However, the muscle still fatigues. In this article, we report a test of the feasibility of using closed-loop control to economize the contractions of the sequentially stimulated myoplasty. A simple stimulation algorithm was developed and tested on a sequentially stimulated neo-sphincter designed from a canine gracilis muscle. Pressure generated in the lumen of the myoplasty neo-sphincter was used as feedback to regulate the stimulation signal via three control parameters, thereby optimizing the performance of the myoplasty. Additionally, we investigated and compared the efficiency of amplitude and frequency modulation techniques. Closed-loop feedback enabled us to maintain target pressures within 10% deviation using amplitude modulation and optimized control parameters (correction frequency = 4 Hz, correction threshold = 4%, and transition time = 0.3 s). The large-scale stimulation/feedback setup was unfit for chronic experimentation, but can be used as a blueprint for a small-scale version to unveil the theoretical benefits of closed-loop control in chronic experimentation.


Subject(s)
Electric Stimulation Therapy , Muscle Contraction , Muscle, Skeletal/physiology , Muscle, Skeletal/transplantation , Algorithms , Animals , Dogs , Feedback/physiology , Muscle Fatigue , Muscle, Skeletal/innervation , Pressure , Urethra , Urinary Incontinence/surgery
4.
Oncogene ; 20(25): 3226-34, 2001 May 31.
Article in English | MEDLINE | ID: mdl-11423972

ABSTRACT

Avian leukosis virus induces lymphoma in chickens after proviral integration within the c-Myc gene, and subsequent expansion of Myc-overexpressing lymphocytes within transformed bursal follicles. The clonal expansion of these follicles allowed us to examine how Myc influences cell differentiation, growth, and apoptosis in lymphoid progenitors soon after the onset of Myc overexpression. Immunohistochemical analysis of developmental markers established that Myc overexpression consistently blocks lymphocyte differentiation at a late embryonic stage. Myc-transformed follicles also grow much more rapidly than normal follicles. This rapid growth is not mediated by suppression of apoptosis, as normal and Myc-transformed follicles showed similar rates of cell death by TUNEL immunohistochemical analysis of cells undergoing DNA degradation. Measurements of DNA synthesis and mitotic index showed modest effects of Myc to increase lymphocyte proliferation, as normal lymphocytes already divide rapidly. The major mechanism mediating rapid growth of transformed follicles instead involved failure of myc-overexpressing lymphocytes to emigrate from transformed follicles, while normal lymphocytes actively emigrate after hatching, as measured by BrdU pulse-chase labeling and immunohistochemical measurements. This failure to undergo the normal program of differentiation and subsequent bursal retention of lymphocytes accounts for most of the growth of transformed follicles, while Myc-induced proliferation makes a smaller contribution.


Subject(s)
B-Lymphocytes/cytology , Bursa of Fabricius/cytology , Cell Transformation, Viral , Genes, myc , Lymphoma/etiology , Animals , Avian Leukosis Virus , Cell Differentiation , Cell Movement , Chick Embryo , Lymphoma/genetics
5.
Biomed Sci Instrum ; 37: 313-8, 2001.
Article in English | MEDLINE | ID: mdl-11347409

ABSTRACT

Aside from the traditional diagnostic tools used to assess cardiac performance, such as blood pressure and cardiac output, cardiac source parameters can also be used as an indication of overall cardiac health. The cardiac source parameters under investigation are myocardial visco-elastic properties. The objective of this study is to model the left ventricle using electrical circuits, then use these models to estimate the cardiac source parameters. Two electrical models of the left ventricle have been developed, using a resistor (R) to model viscous losses, a capacitor (C) to represent inverse elastance, and a time-varying pressure source, which models the left ventricular pressure during an isovolumic beat. One model uses a single resistor and the other uses the two elements (R and C) in parallel. The differential equations describing these models have been derived, and a minimization procedure was used to adjust values of R and C in the differential equations until a good agreement between experimental and calculated left ventricular pressure was reached. Preliminary results indicate that the model including a parallel combination of R and C provides a better fit between experimental and calculated pressures. It is hoped that these parameters may one day provide clinicians with yet another diagnostic tool to help discover the source of cardiac disorders.


Subject(s)
Models, Cardiovascular , Models, Theoretical , Ventricular Function, Left , Animals , Elasticity , Female , Swine , Viscosity
6.
Cancer Res ; 61(7): 3151-6, 2001 Apr 01.
Article in English | MEDLINE | ID: mdl-11306501

ABSTRACT

The Bin1 gene encodes a c-Myc-interacting adapter protein with tumor suppressor and cell death properties. In this study, we offer evidence that Bin1 participates in a mechanism through which c-Myc activates programmed cell death in transformed primary chick or rat cells. Antisense or dominant inhibitory Bin1 genes did not affect the ability of c-Myc to drive proliferation or transformation, but they did reduce the susceptibility of cells to c-Myc-induced apoptosis. Protein-protein interaction was implicated, suggesting that Bin1 mediates a death or death sensitization signal from c-Myc. Our findings offer direct support for the "dual signal" model of Myc apoptotic function, based on interactions with a binding protein. Loss of Bin1 in human tumors may promote malignant progression in part by helping to stanch the death penalty associated with c-Myc activation.


Subject(s)
Apoptosis/physiology , Carrier Proteins/physiology , Cell Transformation, Neoplastic , Nuclear Proteins/physiology , Proto-Oncogene Proteins c-myc/physiology , Tumor Suppressor Proteins , Adaptor Proteins, Signal Transducing , Animals , Carrier Proteins/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Chick Embryo , Epithelial Cells/pathology , Epithelial Cells/physiology , Fibroblasts/pathology , Gene Expression Regulation , Genes, myc/genetics , Genes, myc/physiology , Humans , Kidney/pathology , Kidney/physiology , Nuclear Proteins/genetics , Proto-Oncogene Proteins c-myc/biosynthesis , Proto-Oncogene Proteins c-myc/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction , Transgenes
7.
Aviat Space Environ Med ; 72(1): 1-7, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11194987

ABSTRACT

The role of physiological elastance (Ep) in maximizing external work (EW) transfer is not well understood and has not been investigated during microgravity and increased acceleration conditions. By better understanding this relationship, cardiovascular control mechanisms for meeting metabolic demands during normal gravity and altered acceleration stresses may be elucidated. Therefore, the objectives of this study were to determine the effect of Ep in maximizing EW of the left ventricle and to investigate this relationship during altered acceleration states. Ventricular and arterial parameters were estimated using established lumped parameter models from isolated beats of experimental data. These data were obtained during parabolic flight (0 and approximately 2 Gz) and centrifuge runs (approximately 1 to approximately 4 Gz) where acceleration was used to drive the cardiovascular system into a wide range of physiologic operating and coupling conditions. Parameter estimates at each Gz level were used in a series of computer simulations in which Ep was varied over a wide range to find the point of maximum EW for that coupling condition. Cardiac output and mean arterial pressure were maintained throughout the simulation process by adjusting heart rate. Results of the simulation showed that as arterial elastance decreased from its initially estimated (physiologic) value, external work increased slightly and as elastance increased, external work decreased. In particular, we found that the arterial elastance was set at a point near that which would produce maximal external work. In addition, it was found that altered Gz states may affect the Ep-EW relationship.


Subject(s)
Gravitation , Ventricular Function, Left , Animals , Arteries/physiology , Cardiac Output , Computer Simulation , Heart Rate , Hemodynamics , Male , Papio/physiology , Vascular Resistance
8.
Comp Med ; 51(6): 513-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11924813

ABSTRACT

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.


Subject(s)
Anesthetics, Intravenous/pharmacology , Baroreflex/drug effects , Blood Pressure/drug effects , Echocardiography, Transesophageal/veterinary , Ketamine/pharmacology , Macaca mulatta/physiology , Ventricular Function, Left/drug effects , Anesthetics, Intravenous/administration & dosage , Animals , Heart Rate/drug effects , Infusions, Intravenous , Injections, Intravenous , Ketamine/administration & dosage , Male
9.
ASAIO J ; 46(5): 563-8, 2000.
Article in English | MEDLINE | ID: mdl-11016507

ABSTRACT

The objective was to determine whether a previously developed technique for biological aortic valves could predict flow through a mechanical valve. An electrical analog model of the aortic valve that includes compliance, resistance, and inertance parameters, and corresponding second order differential equations was used to predict flow given a pressure gradient, as previously reported. Simulated pressures and flow were recorded by using a pulse duplicator system. The heart rate was varied from 60 to 180 bpm, and the stroke volume was varied from 22 to 67 cc. Resistance, inertance, and compliance parameters of the governing differential equation were estimated by using a least-squares fit to the measured flow at 120 bpm and 50 cc stroke volume. By using these parameter estimates, flow was calculated for other heart rates and stroke volumes. To achieve a better flow prediction, a nonlinear filter (third order polynomial range calibration equation) was applied to the output of the linear model (flow). The mean error, full-scale error, and spectral error in magnitude and phase between measured and predicted flow were compared. Error in mean flow ranged from 3% at medium flow rates to 90% at low flow rates. The maximum and minimum full scale errors were 12% and 5%, respectively. Error in the harmonics of measured and calculated flow ranged from 0% to 55%. Larger errors were usually present at the higher harmonics. The agreement between measured and calculated flow was better at normal and high flows but rather poor at low flows. The nonlinear filter (range calibration equation) was unable to account for the discrepancies between the measured and calculated flow over all flow ranges. It seems that this linear model and nonlinear filter have limited application, and an alternate nonlinear approach may produce better results.


Subject(s)
Aortic Valve/physiology , Heart Valve Prosthesis , Aortic Valve/surgery , Heart Rate , Humans , Pressure , Stroke Volume
10.
Comp Med ; 50(3): 303-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10894497

ABSTRACT

BACKGROUND AND PURPOSE: Cardiac and arterial responses to prescribed doses of propofol and etomidate in rhesus monkeys were compared. METHODS: Intravenously administered induction doses of propofol (2 mg/kg of body weight) or etomidate (1 mg/kg) followed by continuous intravenous infusions of propofol (200 microg/kg/min) or etomidate (100 microg/kg/min) were administered. Left ventricular and right atrial access catheters were implanted for long-term use, along with a transit-time flow probe on the ascending aorta, and pericardial electrocardiogram leads. A dual sensor 3-F micromanometer was used to measure left ventricular pressure and aortic pressure, and an active redirectional transit-time probe measured aortic flow. Noordergraaf's four-element model was used to estimate total peripheral resistance and systemic arterial compliance. RESULTS: Significant (P < 0.01) decreases in mean arterial pressure, heart rate, and myocardial contractility were accompanied by an increase in systemic arterial compliance associated with propofol and etomidate. Only minimal changes in left ventricular diastolic pressure, cardiac output, stroke volume, and total peripheral resistance were found for both drugs. The changes associated with propofol are comparable to results in human beings, whereas the changes associated with etomidate did not agree with results of published human studies. CONCLUSION: The significant cardiovascular alterations associated with both agents were attributed to reductions in heart rate, although the possibility exists that negative inotropic effects may have had a role.


Subject(s)
Anesthetics, Intravenous/adverse effects , Cardiovascular System/drug effects , Etomidate/adverse effects , Propofol/adverse effects , Animals , Aorta/drug effects , Blood Pressure/drug effects , Heart Rate/drug effects , Kinetics , Macaca mulatta , Male , Myocardial Contraction/drug effects , Ventricular Function, Left/drug effects
11.
Eur J Cardiothorac Surg ; 16 Suppl 1: S83-7, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10536956

ABSTRACT

OBJECTIVE: Flow probes have been introduced as a non-invasive means of anastomotic quality assessment in off-pump coronary artery bypass graft (CABG). Flow waveform morphology cannot reliably be assessed visually unless severe anastomotic stenosis is present ( > 90%). We applied spectral analysis techniques to determine whether the frequency content of graft flow can improve the surgeon's ability to detect anastomotic errors. METHODS: Forty-six mammary to left anterior descending artery (LAD) anastomoses were created in mongrel dogs during off-pump CABG surgery. Graft flow was measured using transit-time flow probes with the LAD closed, and the mammary graft patent and with varying degrees of stenosis. The degree of anastomotic stenosis was created by an artificial stitch and verified by random postoperative angiography. Spectral analysis of the graft flow waveforms was performed. Differences in the magnitude and phase components of the graft flow for the first five harmonics were determined for the varying anastomosis test conditions. Differences were determined using analysis of variance and least square means techniques. RESULTS: The magnitude of the fundamental (zeroth) harmonic was statistically different in the internal mammary artery (IMA) with 0-25% stenosis compared to IMA with 50-75% stenosis (P < 0.01 ). Further, the magnitude of the first, second, and fourth harmonics were statistically different in IMA with 0-25% compared to IMA with 75% (P < 0.01). The phase of the first harmonic was statistically different in IMA with 25% stenosis than IMA with 50% stenosis (P < 0.01 ). No differences in interaction between the LAD and IMA for all ranges of stenosis were detected (P > 0.50). CONCLUSION: Spectral analysis of graft flow waveforms may be beneficial in detecting lesser degrees of anastomotic stenosis (i.e. < 90%) compared to traditional visual assessment of mean graft flow and/or graft flow waveform morphology.


Subject(s)
Coronary Angiography , Coronary Artery Bypass/methods , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/prevention & control , Signal Processing, Computer-Assisted , Anastomosis, Surgical/adverse effects , Animals , Coronary Artery Bypass/adverse effects , Coronary Vessels/physiopathology , Disease Models, Animal , Dogs , Graft Occlusion, Vascular/etiology , Regional Blood Flow , Rheology , Sensitivity and Specificity , Vascular Patency/physiology
12.
Ann Biomed Eng ; 27(4): 486-97, 1999.
Article in English | MEDLINE | ID: mdl-10468233

ABSTRACT

Numerous parameter estimation techniques exist for characterizing the arterial system using electrical circuit analogs. These techniques are often limited by requiring steady-state beat conditions and can be computationally expensive. Therefore, a new method was developed to estimate arterial parameters during steady and transient beat conditions. A four-element electrical analog circuit was used to model the arterial system. The input impedance equations for this model were derived and reduced to their real and imaginary components. Next, the physiological input impedance was calculated by computing fast Fourier transforms of physiological aortic pressure (AoP) and aortic flow. The approach was to reduce the error between the calculated model impedance and the physiological arterial impedance using a Jacobian matrix technique which iteratively adjusted arterial parameter values. This technique also included algorithms for estimating physiological arterial parameters for nonsteady physiological AoP beats. The method was insensitive to initial parameter estimates and to small errors in the physiological impedance coefficients. When the estimation technique was applied to in vivo data containing steady and transient beats it reliably estimated Windkessel arterial parameters under a wide range of physiological conditions. Further, this method appears to be more computationally efficient compared to time-domain approaches.


Subject(s)
Arteries/physiology , Gravitation , Models, Cardiovascular , Pulsatile Flow/physiology , Animals , Electric Impedance , Fourier Analysis , Hemodynamics/physiology , Monte Carlo Method , Primates , Sensitivity and Specificity
13.
Eur J Cardiothorac Surg ; 16(1): 88-93, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10456409

ABSTRACT

OBJECTIVE: The intra-operative assessment of the quality of anastomosis in minimally invasive coronary artery bypass surgery (CABG) is critical. Recent investigations demonstrated that flow probes used intra-operatively to assess anastomotic errors may give the surgeon a false sense of confidence as only severely stenotic anastomoses (>90%) could be reliably detected. We developed a neural network system using graft flow data and assessed its potential to improve anastomotic error detection. METHODS: Mammary to LAD grafts (n = 46) were constructed in mongrel dogs off-pump. Continuous beat-to-beat graft flow was recorded using transit-time flow probes. Various degrees of anastomotic stenoses (0-100%) were created by an additional suture. The degree of anastomotic stenosis was confirmed by postoperative angiography. A learning vector quantization neural network was created using heart rate, mean aortic pressure, mean systolic, maximum systolic, minimum systolic, mean diastolic, maximum diastolic, minimum diastolic, and mean graft flows. In addition, a spectral analysis of the flow waveforms was performed and the magnitude and phase of the first five harmonics were used to further develop the neural network. RESULTS: The neural network pattern recognition system was 94% accurate in detecting any stenosis >50%. To validate the model, a testing set was used with 20% of the data values, and the accuracy remained at 100% above chance alone. CONCLUSION: Pattern recognition of transit-time flow probe tracings using neural network systems can detect anastomotic errors significantly better than the surgeon's visual assessment, thereby improving the clinical outcome of minimally invasive CABG.


Subject(s)
Coronary Artery Bypass/methods , Anastomosis, Surgical , Animals , Dogs , Fourier Analysis , Humans , Intraoperative Period , Minimally Invasive Surgical Procedures , Neural Networks, Computer , Predictive Value of Tests , ROC Curve , Regional Blood Flow , Treatment Outcome
14.
ASAIO J ; 45(4): 334-8, 1999.
Article in English | MEDLINE | ID: mdl-10445741

ABSTRACT

An in vitro pulsatile pump flow system that is capable of producing physiologic pressures and flows in a mock circulatory system tuned to reproduce the first nine harmonics of the input impedance of a rhesus monkey was developed and tested. The system was created as a research tool for evaluating cardiovascular function and for the design, testing, and evaluation of electrical-mechanical cardiovascular models and chronically implanted sensors. The system possesses a computerized user interface for controlling a linear displacement pulsatile pump in a controlled flow loop format to emulate in vivo cardiovascular characteristics. Evaluation of the pump system consisted of comparing its aortic pressure and flow profiles with in vivo rhesus hemodynamic waveforms in the time and frequency domains. Comparison of aortic pressure and flow data between the pump system and in vivo data showed good agreement in the time and frequency domains, however, the pump system produced a larger pulse pressure. The pump system can be used for comparing cardiovascular parameters with predicted cardiovascular model values and for evaluating such items as vascular grafts, heart valves, biomaterials, and sensors. This article describes the development and evaluation of this feedback controlled cardiovascular dynamics simulation modeling system.


Subject(s)
Hemodynamics , Models, Cardiovascular , Animals , Compliance , Computer Simulation , Electric Impedance , Macaca mulatta , Vascular Resistance
15.
Ann Thorac Surg ; 67(5): 1470-2, 1999 May.
Article in English | MEDLINE | ID: mdl-10355434

ABSTRACT

We assessed the acute cardiovascular changes of partial left ventriculectomy (PLV) in a patient with idiopathic dilated cardiomyopathy (IDCM) without mitral regurgitation. Acutely, PLV reduced left ventricular (LV) end-diastolic dimension and volume while increasing LV ejection fraction and cardiac output due to increased HR and SV. Substantial increases in LV filling pressure, possibly due to high LV end-systolic and diastolic elastances, were of concern clinically and the mechanism(s) of change remain unclear. However, one year follow-up showed remarkable improvements in NYHA and VO2 max while maintaining reduced LV volume, increased LVEF, and trivial MR.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/surgery , Heart Ventricles/surgery , Ventricular Function, Left , Female , Humans , Middle Aged , Oxygen Consumption , Stroke Volume
16.
ASAIO J ; 45(3): 204-10, 1999.
Article in English | MEDLINE | ID: mdl-10360724

ABSTRACT

The objective was to develop a technique for calculating continuous, beat-to-beat aortic flow (AoF) using only left ventricular pressure (LVP) and aortic pressure (AoP). An electric analog model of the aortic valve was developed that includes resistance (R), inertance (L), and compliance (C) parameters, and resulting second order differential equations were derived. Aortic flow, AoP, and LVP recorded in eight subjects during a 5 day period and during lower body negative pressure (LBNP) were used to validate the model. Resistance, L, and C were estimated using a least-squares fit to the measured AoF on day 0 and during 0 mm Hg LBNP. For days 1-4, AoF was calculated using measured values of AoP and LVP and the R, L, and C values from day 0. Similarly, for LBNP, AoF was calculated using measured values of AoP and LVP, and the R, L, and C values from 0 mm Hg LBNP. The calculated and measured AoF were compared. Differences in cardiac output between the calculated and measured flows were less than 13.1+/-17% across days and under minor altered physiologic conditions (LBNP). Waveform morphology for the calculated AoF also agreed well with the measured AoF. Spectral analysis showed differences in magnitude and phase between measured and calculated aortic flow for the first five harmonics across days, less than 20+/-6% and 25+/-14 degrees, respectively. Preliminary evaluation indicates that our model works well for calculating flow through a biologic valve using LVP and AoP. We speculate that it may perform better for a mechanical valve, and if so it may be possible to develop an instrumented mechanical valve capable of continuous LVP, AOP, and AoF measurements.


Subject(s)
Aorta/physiology , Aortic Valve/physiology , Blood Pressure/physiology , Models, Cardiovascular , Pulsatile Flow/physiology , Animals , Blood Flow Velocity/physiology , Macaca mulatta , Male , Monte Carlo Method
17.
J Cell Physiol ; 179(3): 287-96, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10228947

ABSTRACT

In the companion article, we reported that the local phosphate (Pi) concentration triggers apoptosis in epiphyseal chondrocytes. The goal of the current investigation was to evaluate the apoptotic process in relationship to the energy status of cells in the growth plate. For these studies, we used sections of the adolescent growth plate, as well as cells isolated from the tissue. We found that there was a maturation-dependent loss of mitochondrial function in growth plate chondrocytes and these cells generated energy by glycolysis. Since treatment with the uncoupler 2,4-dinitrophenol as well as the site-specific inhibitors antimycin A and rotenone failed to elicit a further increase in the activity of the glycolytic pathway, we concluded that oxidative metabolism was minimum in these cells. Flow cytometric studies of growth plate cells and confocal microscopy of growth plate sections using the mitochondrial probes Rh123 and DiOC6(3) provided unequivocal evidence that there was loss of mitochondrial membrane potential in hypertrophic cells. Furthermore, the intrinsic fluorescence of the flavoprotein lipoamide dehydrogenase complex of the electron transport chain revealed that the mitochondria were in an oxidized state. Finally, we assessed Bcl-2 expression in these cells. Although immunohistochemical and Western blot analysis showed that the chick cells contained a low level of the anti-apoptotic protein Bcl-2, reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that transcripts were present in chondrocytes. Based on these observations, we suggest that terminally differentiated chondrocytes undergo a maturation-dependent loss of mitochondrial function. In concert with the low expression of Bcl-2, they become sensitive to signals for programmed cell death. We hypothesize that Pi triggers apoptosis in these energy-compromised cells by promoting a mitochondrial membrane transition, thereby inducing the death process.


Subject(s)
Apoptosis/physiology , Chondrocytes/cytology , Growth Plate/cytology , Growth Plate/metabolism , Mitochondria/metabolism , Adenosine Triphosphate/metabolism , Animals , Carbocyanines , Cell Membrane Permeability/drug effects , Cell Membrane Permeability/physiology , Cellular Senescence/physiology , Chickens , Dinitrophenols/pharmacology , Electron Transport/drug effects , Electron Transport/physiology , Fibroblasts/cytology , Fibroblasts/metabolism , Flow Cytometry , Fluorescent Dyes , Gene Expression/physiology , Glucose/metabolism , Intracellular Membranes/metabolism , Lactic Acid/metabolism , NAD/metabolism , Oxidation-Reduction , Phosphates/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Uncoupling Agents/pharmacology
18.
J Gravit Physiol ; 6(2): 1-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-11543080

ABSTRACT

We measured central venous pressure (CVP), plasma volume (PV), urine volume rate (UVR), and circulating hormones (renin activity (PRA), vasopressin (AVP), atrial natriuretic peptide (ANP), and cortisol) before and after acute volume infusion (Dextran-40) to test the hypotheses that head-down tilt bedrest (HDT) caused (1) a resetting of the CVP operating point and (2) attenuated urine excretion. Six rhesus monkeys underwent two experimental conditions (HDT and control, each of 48 hour duration) with each condition separated by nine days of ambulatory activities to produce a cross-over counterbalance design. One test condition was continuous exposure to 10 degrees HDT and the second test condition was a control, defined as approximately 12-14 hours per day of 80 degrees head-up tilt and 10-12 hours prone. Following 48 hours of exposure to either test condition, 20-minute continuous infusion of Dextran-40 was administered. CVP in HDT was lower than the control condition. Similar elevations in CVP occurred 30 min post-infusion in both test conditions, and returned to pre-infusion baseline levels between 22 and 46 h post-infusion in both treatments. The UVR response during infusion was attenuated by HDT despite similar elevation in CVP. Elevation in ANP and reduction in PRA at the end of infusion were greater in Control compared to HDT. No differences between control and HDT were detected for AVP and cortisol responses to infusion. Since CVP returned to its pre-infusion levels following volume loading in HDT and control conditions, it appeared that the lower CVP may reflect a new operating point about which vascular volume is regulated. Further, attenuated ANP and PRA responses during vascular volume loading may contribute to depressed UVR in low gravity exposure.


Subject(s)
Central Venous Pressure/physiology , Dextrans/pharmacology , Plasma Substitutes/pharmacology , Plasma Volume/drug effects , Plasma Volume/physiology , Weightlessness Simulation , Animals , Arginine Vasopressin/blood , Arginine Vasopressin/metabolism , Atrial Natriuretic Factor/blood , Atrial Natriuretic Factor/metabolism , Central Venous Pressure/drug effects , Fluid Therapy , Head-Down Tilt , Hydrocortisone/blood , Hydrocortisone/metabolism , Macaca mulatta , Male , Renin/blood , Renin/metabolism , Urine
19.
Acta Virol ; 43(2-3): 133-5, 1999.
Article in English | MEDLINE | ID: mdl-10696433

ABSTRACT

Strains of Marek's disease virus (MDV), a herpesvirus, have been shown to augment the development of lymphoid leukosis induced by retroviruses, the avian leukosis virus (ALV) or the reticuloendotheliosis virus. In this study we explored the possibility that the ability to augment lymphoid leukosis may be correlated with the ability of different strains of MDV to block apoptosis. Subclones of the ALV-transformed B cell line, DT40, which was free of MDV DNA were infected with either R2/23 strain of MDV-1, SB1 strain of MDV-2, or turkey herpes virus (HVT), a MDV-3. We found that most of the normal DT40 cells and DT40 cells infected with the R2/23 became apoptotic when cultured in serum-reduced medium. By contrast, the frequency of apoptotic cells was greatly reduced in the DT40-SB1 and DT40-HVT subclones. These findings suggest that because the SB-1 strain persists in the ALV-infected cells, it may augment lymphoid leukosis by inhibiting apoptosis and providing a survival advantage to the B cells which have a deregulated myc proto-oncogene.


Subject(s)
Apoptosis , B-Lymphocytes/cytology , B-Lymphocytes/virology , Herpesvirus 2, Gallid/physiology , Animals , Avian Leukosis Virus/physiology , Cell Line, Transformed , Chickens , Culture Media
20.
J Card Surg ; 14(2): 152-6, 1999.
Article in English | MEDLINE | ID: mdl-10709831

ABSTRACT

Partial left ventriculectomy (PLV) has been introduced as an alternative surgical therapy for patients with end-stage dilated cardiomyopathy. The physiological benefits of PLV are relatively unknown. Therefore, the objective of this study was to determine the acute effects of PLV by measuring cardiac function before and after PLV. Aortic and left ventricular pressures and aortic flow were measured in eight patients. Continuous, beat-to-beat data were recorded and compared pre-PLV and post-PLV with and without inferior vena cava (IVC) occlusions. PLV increased cardiac output (0.93+/-0.5, p = 0.01) as a result of increased stroke volume (5.12+/-4.24, p = 0.06) and heart rate (14.5+/-8.44, p = 0.02). Contractility (+/- dP/dt, 240.33+/-74.28, p = 0.001) and external work (650.8+/-320.4, p = 0.01) were also improved. Left ventricular end-diastolic elastance (0.15+/-0.14, p = 0.10) nearly doubled after PLV. Our results indicated an improved cardiac function as measured by increased cardiac output, stroke volume, ejection fraction (EF), and contractility.


Subject(s)
Cardiac Surgical Procedures , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/surgery , Heart Ventricles/surgery , Hemodynamics , Cardiac Output , Heart Rate , Humans , Intraoperative Period , Postoperative Period , Stroke Volume
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