Biomedical subjects

B B Keller

Publications and source records attributed to B B Keller.

At least 19 recordsLinked to original sources

PubMed2002

Effects of mechanical interaction between two rabbit cardiac muscles connected in parallel.

The hypothesis that myocardium mechanical inhomogeneity produces a substantial effect on mechanical function was tested. Muscle inhomogeneity was studied in isolated papillary muscles or trabeculae excised from rabbit right ventricle and connected in a parallel duplex. Each muscle was placed in a separate perfusion bath. One end of each muscle was fastened to an individual force transducer and the other to the common lever of a servomotor. This arrangement allowed both muscles, being excited independently, to pull jointly a load applied to the lever. Separate electrodes for each perfusion bath allowed to stimulate muscles with a time delay. Tension developed in the individual muscles and their interaction were studied. Developed tension was critically dependent on the timing and sequence of excitation. Using mathematical modeling, patterns of tension distribution experimentally observed in parallel duplexes were simulated. These results suggest that changes both in Ca(2+) transients and in the time course of Ca(2+)-troponin complexion due to the duplexed muscles interaction offset the effect of mechanical inhomogeneity.

Animals↗

PubMed2001

Identification of the t-type calcium channel (Ca(v)3.1d) in developing mouse heart.

During cardiac development, there is a reciprocal relationship between cardiac morphogenesis and force production (contractility). In the early embryonic myocardium, the sarcoplasmic reticulum is poorly developed, and plasma membrane calcium (Ca(2+)) channels are critical for maintaining both contractility and excitability. In the present study, we identified the Ca(V)3.1d mRNA expressed in embryonic day 14 (E14) mouse heart. Ca(V)3.1d is a splice variant of the alpha1G, T-type Ca(2+) channel. Immunohistochemical localization showed expression of alpha1G Ca(2+) channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the alpha1G channels. Dihydropyridine-resistant inward Ba(2+) or Ca(2+) currents were present in all fetal ventricular myocytes tested. Regardless of charge carrier, inward current inactivated with sustained depolarization and mirrored steady-state inactivation voltage dependence of the alpha1G channel expressed in human embryonic kidney-293 cells. Ni(2+) blockade discriminates among T-type Ca(2+) channel isoforms and is a relatively selective blocker of T-type channels over other cardiac plasma membrane Ca(2+) handling proteins. We demonstrate that 100 micromol/L Ni(2+) partially blocked alpha1G currents under physiological external Ca(2+). We conclude that alpha1G T-type Ca(2+) channels are functional in midgestational fetal myocardium.

Animals↗

PubMed2001

Power spectrum analysis of heart rate and blood flow velocity variability measured in the umbilical and uterine arteries in early pregnancy: a comparative study.

OBJECTIVE: To compare power spectral derived variability parameters from the fetal side of the placental circulation with those from the maternal side of the placental circulation, during early pregnancy. METHODS: Doppler velocity waveforms were obtained from both the umbilical and the uterine arteries in a study group of 40 pregnant women between 10 and 14 (n = 25) and 15 and 20 (n = 15) weeks of gestation. The coefficient of variation of both the beat-to-beat heart rate variability and the blood flow velocity variability was determined. The ratio of the integrated low-frequency components (< 0.2 Hz) and the integrated high-frequency components (> 0.2 Hz) from normalized power spectrum analysis (LH-ratio) was established, to reflect sympathovagal balance. RESULTS: The coefficient of variation and LH-ratio of fetal heart rate variability constitute only a fraction of the same maternal heart rate variability parameters. Nevertheless a highly significant increase (P < 0.001) in LH-ratio was demonstrated with advancing gestational age. The coefficient of variation and LH-ratio of blood flow velocity variability were significantly lower in the fetal umbilical artery only in the 10-14-weeks' gestation group. Due to a decrease of the maternal uterine blood flow velocity variability parameters with advancing gestational age, statistically equal fetal and maternal values for coefficient of variation and LH-ratio were found in the 15-20 weeks' gestation group. CONCLUSIONS: The increase in LH-ratio of fetal heart rate variability indicates functional development of the fetal autonomic nervous system at 15-20 weeks' gestation. The umbilical blood flow velocity variability may be secondary to maternal uterine arterial flow variability rather than due to primary changes in fetal cardiovascular function.

Blood Flow Velocity↗

PubMed2001

[Contraction-relaxation dynamics and mechanical restitution in the developing myocardium of the chick embryo].

Parameters of the contraction-relaxation cycle and mechanical restitution (MR) were assessed in isolated ventricular preparations of 3- and 4-day chick embryos (EM) and posthatched (PH) chicks. Ryanodine reduced the relaxation rate in the EM but increased it in the PH chicks. It also suppressed a rest-induced potentiation and the MR in all the preparations. Low Na superfusion significantly suppressed the relaxation and decreased the rest potentiation in the myocardial preparations all ages. The findings substantiate existence of a sarcolemmal Ca pool which participates in regulation of twitch parameters and Ca outflux via the Na-Ca exchange.

Animals↗

PubMed2000

Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB.

We have evaluated several lumped parameter analog models for the early chick embryonic vascular system that may be used to infer loading characteristics of the developing heart. We measured dorsal aortic pressure and flow simultaneously with a servo-null pressure system and a pulsed Doppler velocimeter. Four different analog circuit models were chosen for comparisons. We formulated the time-domain differential equations specifying the relations between pressure and flow in the models, and then estimated the lumped parameters that produced the best fit. The MLAB mathematical modeling software was used for solving differential equations, and for minimizing the difference between model-predicted values and experimental data. The traditional three-element Windkessel model with an added inductance term was most often the best-fitting model. This is compatible with the previous study using a frequency-domain approach. The procedures developed for the current study are adaptable for the study of a variety of nonlinear models, and distributed parameter models for mammalian cardiovascular development with mechanically, pharmacologically, or genetically altered conditions.

Analog-Digital Conversion↗

PubMed2000

Maturation of end-systolic stress-strain relations in chick embryonic myocardium.

The embryonic myocardium increases functional performance geometrically during cardiac morphogenesis. We investigated developmental changes in the in vivo end-systolic stress-strain relations of embryonic chick myocardium in stage 17, 21, and 24 white Leghorn chick embryos (n = 10 for each stage). End-systolic stress-strain relations were linear in all developmental stages. End-systolic strain decreased from 0.50 +/- 0.02 to 0.31 +/- 0.01 (mean +/- SE, P < 0.05), while average end-systolic wall stress was similar at 3.29 +/- 0.34 to 4.19 +/- 0.43 mmHg (P = 0.14) from stage 17 to 24. Normalized end-systolic myocardial stiffness, a load-independent index of ventricular contractility, increased from 2.98 +/- 0.19 to 6.03 +/- 0.39 mmHg from stage 17 to 24 (P < 0.05). Zero-stress midwall volume increased from 0.024 +/- 0.002 to 0.124 +/- 0.004 microl from stage 17 to 24 (P < 0.05). These results suggest that the embryonic ventricle increases normalized ventricular "contractility" while maintaining average end-systolic wall stress over a relatively narrow range during cardiovascular morphogenesis.

Animals↗

PubMed2000

Right and left ventricular wall deformation patterns in normal and left heart hypoplasia chick embryos.

The vertebrate embryonic ventricle transforms from a smooth-walled single tube to trabeculated right ventricular (RV) and left ventricular (LV) chambers during cardiovascular morphogenesis. We hypothesized that ventricular contraction patterns change from globally isotropic to chamber-specific anisotropic patterns during normal morphogenesis and that these deformation patterns are influenced by experimentally altered mechanical load produced by chronic left atrial ligation (LAL). We measured epicardial RV and LV wall strains during normal development and left heart hypoplasia produced by LAL in Hamburger-Hamilton stage 21, 24, 27, and 31 chick embryos. Normal RV contracted isotropically until stage 24 and then contracted preferentially in the circumferential direction. Normal LV contracted isotropically at stage 21, preferentially in the longitudinal direction at stages 24 and 27, and then in the circumferential direction at stage 31. LAL altered both RV and LV strain patterns, accelerated the onset of preferential RV circumferential strain patterns, and abolished preferential LV longitudinal strain (P < 0.05 vs. normal). Mature patterns of anisotropic RV and LV deformation develop coincidentally with morphogenesis, and changes in these deformation patterns reflect altered cardiovascular function and/or morphogenesis.

Analysis of Variance↗

PubMed1999

Umbilical arterial blood flow in the mouse embryo during development and following acutely increased heart rate.

In anesthetized, pregnant ICR mice, we measured embryonic umbilical arterial velocity at baseline and during bipolar atrial or ventricular pacing. Pregnant mice were anesthetized with pentobarbital (60 mg/kg intraperitoneal) and ventilation was mechanically supported via a tracheotomy. Embryos were exposed through a mid-line laparotomy and regional hysterotomy. We recorded umbilical velocity using a 1-mm diameter piezoelectric crystal and 20-MHz, pulsed Doppler velocimeter at embryo day (ED) 10.5 (n = 8), 12.5 (n = 10), 13.5 (n = 27), 14.5 (n = 12), and 16.5 (n = 17). We then acutely altered embryonic heart rate in n = 8 ED 13.5 mouse embryos by bipolar atrial and ventricular pacing. Embryonic heart rate in this experimental preparation increased from 123+/-7 to 193+/-11 beats/min from ED 10.5 to 16.5 (p<0.05). Peak instantaneous average velocity increased from 21+/-2 to 55+/-6 mm/s from ED 10.5 to 16.6 (p<0.05), as did stroke volume and blood flow (p<0.05 for each). In contrast to human umbilical arterial velocity profiles, significant forward diastolic flow was not seen at these stages, suggesting higher placental resistance in mice versus humans at comparable developmental time points. As previously noted for the chick embryo, murine embryonic umbilical arterial velocity decreased after atrial pacing and disappeared after ventricular pacing. Thus, we can determine embryonic umbilical blood flow during the overlapping periods of murine cardiac and placental morphogenesis.

Animals↗

PubMed1999

Fetal heart rate and umbilical artery velocity variability in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVES: To examine the variability in fetal heart rate and absolute flow velocity, which are possible hemodynamic markers of cardiovascular homeostasis in pregnancies complicated by diabetes mellitus. METHODS: Doppler studies of umbilical artery velocity waveforms were performed at 12-21 weeks of gestation in 16 women with well-controlled type I (insulin-dependent) diabetes mellitus. From umbilical artery velocity waveforms of at least 13 s in duration, we determined absolute values and beat-to-beat variability for fetal heart rate and umbilical artery flow velocities and compared these findings with normal controls matched for gestational age. RESULTS: Fetuses of diabetic women displayed increased fetal heart rate variability and umbilical artery peak systolic velocity. Fetal heart rate, umbilical artery time-averaged velocity and variability in umbilical artery flow velocity were not essentially different between the two groups. CONCLUSION: Fetal heart rate variability and umbilical artery peak systolic velocity may be markers for fetal cardiovascular homeostasis in pregnancies complicated by insulin-dependent diabetes mellitus.

Adolescent↗

PubMed1999

Do heart rate and velocity variability derived from umbilical artery velocity waveforms change prior to clinical pregnancy-induced hypertension?

OBJECTIVE: To investigate the hypothesis that alterations in heart rate variability, peak systolic velocity variability and time-averaged velocity variability in the human umbilical artery may predict early signs of dysfunctional fetal-placental coupling in pregnancies that later develop pregnancy-induced hypertension. METHODS: Doppler flow velocity recordings from the umbilical artery were performed at 10-20 weeks of gestation in 12 nulliparous women who subsequently developed pregnancy-induced hypertension. From umbilical artery velocity waveforms of at least 12 s in duration we determined absolute values and beat-to-beat variability in fetal heart rate, peak systolic and time-averaged velocity and compared these findings with those in normal nulliparous pregnant women matched for gestational age. RESULTS: Absolute values for fetal heart rate, peak systolic and time-averaged velocity as well as beat-to-beat variability in fetal heart rate did not differ significantly between women later developing pregnancy-induced hypertension and normal controls. However, variability in peak systolic velocity and time-averaged velocity were decreased in women who subsequently developed pregnancy-induced hypertension. CONCLUSIONS: Whereas fetal heart rate variability was similar, umbilical artery flow velocity variability was reduced in women developing pregnancy-induced hypertension compared with controls. It is proposed from this study that variability of the umbilical artery flow velocity is associated with mechanical changes in the vascular bed of women who later develop pregnancy-induced hypertension.

Adult↗

PubMed1999

Assessment of fetal heart rate variability and velocity variability by Doppler velocimetry of the descending aorta at 10-20 weeks of gestation.

OBJECTIVES: Determination of gestational age-related modulations in fetal heart rate and descending aorta blood flow velocity in the early human fetus and comparison of aortic variability data with data obtained from the umbilical artery. It is hypothesized that these modulations present in the umbilical artery also occur in the descending aorta. METHODS: Doppler studies of descending aorta velocity waveforms were performed at 10-20 weeks in 55 normal pregnant women. In 24 of the 55 women, Doppler recordings from both the descending aorta and the umbilical artery were collected. Absolute values and variability of fetal heart rate, peak systolic and time-averaged velocities were determined from flow velocity waveforms of at least 18 s in duration. RESULTS: From 10 to 20 weeks of gestation, the descending aorta peak systolic and time-averaged velocities increased, whereas the fetal heart rate decreased. The descending aorta peak systolic variability also increased. However, the time-averaged velocity variability and fetal heart rate variability remained constant during the study period. In the subset of 24 women, the fetal heart rate variability and velocity variability data from the descending aorta and umbilical artery were not significantly different. CONCLUSIONS: Reproducible fetal heart rate and velocity variability data can be derived from the descending aorta and umbilical artery. The increase in heart rate variability observed in the umbilical artery was not seen in recordings obtained from the descending aorta. Different fetal activity states may be the underlying mechanism for these heart rate variability discrepancies.

Aorta, Thoracic↗

PubMed1999

End-systolic myocardial stiffness is a load-independent index of contractility in stage 24 chick embryonic heart.

Cardiac morphogenesis and function are interrelated during cardiovascular development. We evaluated the effects of acute alteration of loading condition to chick embryonic ventricular contractility using end-systolic myocardial stiffness based on the incremental elastic modulus concept. End-systolic stress-strain relations including geometric factor and end-systolic myocardial stiffness were determined from the simultaneous measurement of ventricular pressure and chamber dimension in the following four groups of stage 24 White Leghorn chick embryos: volume infusion (n = 9), conotruncal occlusion (n = 9), calcium suffusion (n = 10), and verapamil suffusion (n = 8). The end-systolic stress-strain relationship was linear in each embryo. There was no correlation between end-systolic myocardial stiffness and end-systolic stress. End-systolic myocardial stiffness increased with calcium suffusion (P < 0.05 vs. volume infusion). The geometric factor increased after verapamil suffusion (P < 0.05). End-systolic myocardial stiffness normalized by geometric factor was not changed by alteration of preload or afterload, increased after calcium suffusion, and decreased after verapamil administration (P < 0.05). These results suggest that normalized end-systolic myocardial stiffness is a load-independent index of ventricular contractility in the developing embryonic chick ventricle.

Animals↗

PubMed1998

Umbilical artery waveform analysis based on maximum, mean and mode velocity in early human pregnancy.

The objective of this study was to identify the best method for reconstructing blood-flow velocities from the early human umbilical artery to determine the physiological changes in fetal blood-flow velocity and heart rate. Pulsed Doppler recordings from the umbilical artery with a duration of approximately 7 s were made at 10-20 weeks of gestation. For reconstruction of the blood-flow velocity from the Doppler audio signal, the maximum (envelope), mean and mode frequency reconstruction methods were used. For the assessment of variability in blood-flow velocity and heart rate in the umbilical artery, the maximum velocity reconstruction method is preferred because it is relatively insensitive to noise, nonuniform insonation, and wall filter settings.

Adolescent↗

PubMed1998

Heart rate and flow velocity variability as determined from umbilical Doppler velocimetry at 10-20 weeks of gestation.

1. The aim of this study was to define from umbilical artery flow velocity waveforms absolute peak systolic and time-averaged velocity, fetal heart rate, fetal heart rate variability and flow velocity variability, and the relation between fetal heart rate and velocity variables in early pregnancy.2.A total of 108 women presenting with a normal pregnancy from 10 to 20 weeks of gestation consented to participate in a cross-sectional study design. Doppler ultrasound recordings were made from the free-floating loop of the umbilical cord.3. Umbilical artery peak systolic and time-averaged velocity increased at 10-20 weeks, whereas fetal heart rate decreased at 10-15 weeks of gestation and plateaued thereafter. Umbilical artery peak systolic velocity variability and fetal heart rate variability increased at 10-20 and 15-20 weeks respectively.4. The inverse relationship between umbilical artery flow velocity and fetal heart rate at 10-15 weeks of gestation suggests that the Frank-Starling mechanism regulates cardiovascular control as early as the late first and early second trimesters of pregnancy. A different underlying mechanism is suggested for the observed variability profiles in heart rate and umbilical artery peak systolic velocity. It is speculated that heart rate variability is mediated by maturation of the parasympathetic nervous system, whereas peak systolic velocity variability reflects the activation of a haemodynamic feedback mechanism.

Blood Flow Velocity↗

PubMed1998

Hemodynamic response to anesthesia in pregnant and nonpregnant ICR mice.

Mean arterial blood pressure (BP) and heart rate (HR) during and after recovery from anesthesia in pregnant and nonpregnant ICR mice were evaluated. Mice were evaluated during mechanical ventilation, from 15 to 60 min after induction of anesthesia. The anesthetic protocols were pentobarbital (80 mg/kg, given intraperitoneally [i.p.]); two low doses of ketamine and xylazine (90 mg/kg, 7.5 mg/kg, respectively, i.p., with a second dose given 20 min after the initial dose); and a single high dose of ketamine and xylazine (150 mg/kg, 12.5 mg/kg, respectively, i.p.). The BP was measured in the right carotid artery, using a fluid-filled catheter connected to a chamber containing a solid-state pressure transducer. Mechanical ventilation was performed via tracheotomy, using a normalized minute ventilation of 3.5 ml*min-1*g-1 for nonpregnant mice and 3.0 ml*min-1*g-1 for pregnant mice. Mean BP was lower and HR was higher in pregnant than in nonpregnant mice for each anesthetic protocol. Pentobarbital induced significantly greater tachycardia and hypotension than did the other protocols. The average BP and HR were similar between two low doses and a single high dose of ketamine and xylazine. During spontaneous breathing from 30 to 180 min after recovery from anesthesia by use of a single low dose, ketamine and xylazine induced similar HR profiles, but mean BP in pregnant mice recovered earlier than did that in nonpregnant mice. These results suggest that ketamine and xylazine induced adequate anesthesia for superficial surgical procedures in pregnant and nonpregnant mice while inducing small changes in HR and BP, and pregnancy resulted in a different hemodynamic reaction in response to ketamine and xylazine. These data will be useful for the design and interpretation of physiologic protocols using pregnant and nonpregnant genetically targeted mice.

Anesthesia↗

PubMed1998

[The role of intra- and extracellular calcium sources in the rhythmic inotropic regulation of isometric contractions in the chick embryo myocardium].

Isometric contractions and force-frequency relationships (FFR) were assessed in isolated ventricular preparations of 3- and 4-day chick embryos (EM) and posthatched (PH) chicks. Pacing protocols for the FFR assessment were applied in normal buffer, buffer with 50% and 25% of normal Na+ concentration, and in buffer with ryanodine. PH myocardium showed greater peak force and more prominent FFR than EM. 50% low Na+ superfusion induced positive inotropic effect and increase in the FFR in PH and EM. 25% low Na+ superfusion induced negative inotropic effect and suppressed FFR more prominent in EM. Ryanodine more suppressed FFR in PH myocardium. The observed age-dependent differences substantiate the fact that Na-Ca exchange plays a leading role in the FFR regulation in early embryonic myocardium and sarcoplasmic reticulum plays a leading role in PH myocardium.

Animals↗

PubMed1997

Characterization of passive embryonic myocardium by quasi-linear viscoelasticity theory.

The mechanical properties of embryonic cardiac tissue, an important link between form and function, are largely unknown. This study provides new information on the viscoelastic behavior of the stage-16 and stage-18 (21/2 and 3 d) chick ventricle. The cylindrical ventricles were removed from the embryo, arrested in diastole, and mounted between two small wires in a specially designed experimental workstation. After preconditioning, ramp-and-hold stress relaxation tests were performed at 10, 20 and 40% stretch. The resulting reduced relaxation functions were fit by graphical approach with a quasi-linear viscoelastic representation. All functions were highly linear with natural log time between 1 and 60 s; mean slopes were -0.051 to -0.067. Other mean values were: fast time constant tau 1, 0.037-0.052 s; slow time constant tau 2, 296-486 s; and final relaxation G([symbol: see text]), 0.38-0.59. These results agree closely with those of adult tissue. The differences in parameters were not significant either between stretch levels within stage or between stages at the same stretch level. An extrapolation/renormalization procedure increased agreement in slope between stretch levels but decreased agreement in G([symbol: see text]). Events occurring on the short time scale may represent extracellular fluid filtration while final relaxation may be a function of true tissue viscoelasticity. These results will provide a baseline for extension to later developmental stages in cases of both normal and altered growth.

Animals↗

PubMed1997

Passive stress-strain measurements in the stage-16 and stage-18 embryonic chick heart.

The first stress-strain measurements on embryonic cardiovascular tissue are described here, obtained from cyclic uniaxial loading of the primitive ventricle. An excised ventricular segment from Hamburger/Hamilton stage-16 or stage-18 chicks (2-1/2 and 3 days of a 21-day incubation period) was mounted longitudinally between two small wires in oxygenated Krebs-Henseleit cardioplegia solution. One wire was attached to an ultrasensitive force transducer and the other to a Huxley micromanipulator controlled by remote motor drive. A real-time video tracking system calculated three myocardial surface strains based on the positions of three surface markers while the heart was deformed in a triangular wave pattern. Force transducer output was filtered, digitally sampled, and stored with strains and time. Results were plotted as strain (longitudinal, circumferential, shear, and principal) versus time, stress versus time, and stress versus longitudinal strain. The stress-strain curves were nonlinear, even at low strain levels. The hysteresis loops were large; mean hysteresis energy as a proportion of total cycle stored strain energy was 36 percent (stage 16) and 41 percent (stage 18). We created a finite element model of the ventricle and fit the model behavior to the experimental behavior to determine parameters for a stage-18 pseudoelastic strain-energy function of exponential form. The calculated exponential parameter is significantly lower than that found in corresponding uniaxial studies of mature myocardium, possibly indicating the lower fiber content of the immature tissue. The results of this study are the first step in characterizing material properties for comparisons with later developmental stages and with impaired and altered myocardium. The long-term goal is to aid in identifying the biomechanical factors regulating growth and morphogenesis.

Animals↗