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Biomedical subjects

M P Gustin

Publications and source records attributed to M P Gustin.

15 recordsLinked to original sources

Beat-to-beat stroke volume estimation from aortic pressure waveform in conscious rats: comparison of models.

Several methods for estimating stroke volume (SV) were tested in conscious, freely moving rats in which ascending aortic pressure and cardiac flow were simultaneously (beat-to-beat) recorded. We compared two pulse-contour models to two new statistical models including eight parameters extracted from the pressure waveform in a multiple linear regression. Global as well as individual statistical models gave higher correlation coefficients between estimated and measured SV (model 1, r = 0.97; model 2, r = 0.96) than pulse-contour models (model 1, r = 0.83; model 2, r = 0.91). The latter models as well as statistical model 1 used the pulsatile systolic area and thus could be applied to only 47 +/- 17% of the cardiac beats. In contrast, statistical model 2 used the pressure-increase characteristics and was therefore established for all of the cardiac beats. The global statistical model 2 applied to data sets independent of those used to establish the model gave reliable SV estimates: r = 0.54 +/- 0.07, a small bias between -8% to +10%, and a mean precision of 7%. This work demonstrated the limits of pulse-contour models to estimate SV in conscious, unrestrained rats. A multivariate statistical model using eight parameters easily extracted from the aortic waveform could be applied to all cardiac beats with good precision.

Animals↗

Mental stress-induced increase in blood pressure is not related to baroreflex sensitivity in middle-aged healthy men.

The baroreflex that acts to blunt blood pressure (BP) variations through opposite variations in heart rate should limit the BP increase produced by an emotional challenge. However, relations between baroreflex sensitivity and BP reactivity induced by a psychological stress in a large group of adults have never been firmly established. In 280 healthy men, rest (10 minutes) and stress (5 minutes) BP and heart rate were recorded beat to beat by a blood pressure monitor. The mental stress was elicited by a well-standardized computerized version of a word color conflict stress test (Stroop Color Test). Rest and stress baroreflex sensitivity was assessed by the cross-spectral analysis of BP and heart rate and by the sequence method. The stress-induced increase in systolic BP (22.4+/-0.1 mm Hg) was not correlated with resting baroreflex sensitivity but was slightly correlated (r=0.2, P<0.001) with BP variability assessed either by standard deviation or by mid-frequency band spectral power. Our results suggested that a centrally mediated sympathetic stimulation overcame cardiac autonomic regulation and emphasized the role of the sympathetic vasoconstriction in the pressure response at the onset of the stressing stimulation. During the sustained sympathoexcitatory phase, the cardiac baroreflex blunts BP variations but at a lower sensitivity.

Adolescent↗

Noninvasive exploration of cardiac autonomic neuropathy. Four reliable methods for diabetes?

OBJECTIVE: The purpose of this work was to assess relevant information that could be provided by various mathematical analyses of spontaneous blood pressure (BP) and heart rate (HR) variabilities in diabetic cardiovascular neuropathy. RESEARCH DESIGN AND METHODS: There were 10 healthy volunteers and 11 diabetic subjects included in the study. Diabetic patients were selected for nonsymptomatic orthostatic hypotension in an assessment of their cardiovascular autonomic impairment. Cardiac autonomic function was scored according to Ewing's methodology adapted to the use of a Finapres device. The spontaneous beat-to-beat BP and HR variabilities were then analyzed on a 1-h recording in supine subjects. The global variabilities were assessed by standard deviation, fractal dimension, and spectral power. The cardiac baroreflex function was estimated by cross-spectral sequences and Z analyses. RESULTS: In diabetic patients, Ewing's scores ranged from 1 to 4.5, confirming cardiovascular autonomic dysfunction. In these diabetic patients, global indices of variabilities were consistently lower than in healthy subjects. Furthermore, some of them (standard deviation and fractal dimension of HR, spectral power of systolic blood pressure and HR) were significantly correlated with the Ewing's scores. The Z methods and the spectral analysis found that the cardiac baroreflex was less effective in diabetic subjects. However, the baroreflex sensitivity could not be reliably assessed in all the patients. The sequence method pointed out a decreased number of baroreflex sequences in diabetic subjects that was correlated to the Ewing's score. CONCLUSIONS: Indices of HR spontaneous beat-to-beat variability are consistently related to the degree of cardiac autonomic dysfunction, according to Ewing's methodology. The Z method and spectral analysis confirmed that the cardiac baroreflex was impaired in diabetic patients. These methods might be clinically relevant for use in detecting incipient neuropathy in diabetic patients.

Adult↗

Beat-to-beat estimation of windkessel model parameters in conscious rats.

A windkessel model was applied on a beat-to-beat basis to evaluate the arterial mechanical characteristics in seven conscious rats. Ascending aortic arterial pressure (AP) and blood flow were recorded during steady-state in basal conditions, during infusions of isoprenaline, sodium nitroprusside, and phenylephrine, and after intravenous atenolol injection. For each cardiac cycle the exponential decay time constant (tau) was estimated from the aortic AP curve, peripheral resistances (R) were taken as the ratio of mean AP to cardiac output, and systemic arterial compliance (C) was calculated as tau/R. In all conditions, mean correlation coefficients of the exponential regression and approximately 70% of values in each rat were > 0.99, demonstrating the model validity. In all conditions tau and C exhibited a large spontaneous variability over time, and beat-to-beat correlations were high between tau and C (0.83 +/- 0.03). C was increased by sodium nitroprusside, decreased by isoprenaline, but not significantly decreased by phenylephrine [5.1 +/- 0.2, 3.2 +/- 0.3, and 3.9 +/- 0.2 microliters/mmHg, respectively, vs. 4.2 +/- 0.3 microliters/mmHg (baseline)]. In conclusion, the windkessel model enables tau and C to be reliably estimated in conscious rats during spontaneous and drug-induced hemodynamic variations.

Animals↗

Identification of spontaneous cardiac baroreflex episodes at different timescales in rats.

To study spontaneous cardiac baroreflex at different timescales, a new method has been developed that identifies such episodes. Mean arterial pressure (MAP) and heart rate (HR) were recorded beat to beat over 1 h in freely moving control (n = 10) and acutely (1 day before study, n = 7) and chronically (2 wk before study, n = 10) sinoaortic-denervated (SAD) 12- to 14-wk-old male Sprague-Dawley rats. These beat-to-beat time series were successively low-pass filtered seven times and resampled at different time intervals from 0.1 to 6.4 s, allowing different timescales to be scanned. With the use of the Z coefficient, the statistical relationship was estimated for the associations of inverse MAP and HR variations when these inverse MAP and HR variations occurred simultaneously or were time shifted. In control rats and for timescales > or = 0.4 s, the highest Z coefficient (0.38) was obtained when MAP variations preceded inverse HR variations by one sampling interval. The baroreflex origin of this link was demonstrated by its disappearance after acute SAD. In conclusion, this method enabled spontaneous baroreflex episodes to be identified for unusually long timescales without limiting the study to fast, linear, stationary, or oscillating phenomena.

Animals↗

Spontaneous cardiac baroreceptor reflex and regional circulations in conscious rats.

OBJECTIVE: To determine the relationships between the activity of the spontaneous cardiac baroreceptor reflex (BRX) and regional vascular dynamics in conscious unrestrained rats. DESIGN: Simultaneous beat-to-beat recordings of blood pressure and measurements of indices of mesenteric and hindquarters blood flows were performed in seven male normotensive conscious rats under baseline conditions during 1 h. METHODS: The relationships between systolic blood pressure (SBP) and heart rate were examined using a computerized method, giving the degree of statistical dependence between values of the two parameters with the Z coefficient. This analysis permitted detection of cardiac beats related to cardiac BRX activity. Z analysis was also applied to SBP and to mesenteric or hindquarters blood flow or vascular resistance. Time-series representations were used to describe the chronological patterns corresponding to BRX spontaneous activity. RESULTS: In these rats, which presented spontaneous BRX-like patterns manifested by the Z analysis, BRX was active during approximately 15% of the time. For 80% of these patterns, cardiac BRX acted to buffer falls in SBP. These depressor events were preceded by muscular vasodilations whereas vasodilations in the mesentery were delayed. Z analysis of these spontaneous haemodynamic patterns confirmed that muscular vasodilations were strongly associated with falls in SBP, whereas vasodilations lagged behind SBP by about seven beats and were not dependent on simultaneous SBP values. CONCLUSIONS: The Z method showed that spontaneous hindquarters vasodilations were associated with cardiac BRX patterns and that mesenteric vasodilations were not concomitant with falls in SBP and may be the consequence either of a delayed central response or of a local mechanism such as myogenic autoregulation.

Animals↗

A new non-invasive statistical method to assess the spontaneous cardiac baroreflex in humans.

1. A new method was developed to evaluate cardiac baroreflex sensitivity. The association of a high systolic blood pressure with a low heart rate or the converse is considered to be under the influence of cardiac baroreflex activity. This method is based on the determination of the statistical dependence between systolic blood pressure and heart rate values obtained non-invasively by a Finapres device. Our computerized analysis selects the associations with the highest statistical dependence. A 'Z-coefficient' quantifies the strength of the statistical dependence. The slope of the linear regression, computed on these selected associations, is used to estimate baroreflex sensitivity. 2. The present study was carried out in 11 healthy resting male subjects. The results obtained by the 'Z-coefficient' method were compared with those obtained by cross-spectrum analysis, which has already been validated in humans. Furthermore, the reproducibility of both methods was checked after 1 week. 3. The results obtained by the two methods were significantly correlated (r = 0.78 for the first and r = 0.76 for the second experiment, P < 0.01). When repeated after 1 week, the average results were not significantly different. Considering individual results, test-retest correlation coefficients were higher with the Z-analysis (r = 0.79, P < 0.01) than with the cross-spectrum analysis (r = 0.61, P < 0.05). 4. In conclusion, as the Z-method gives results similar to but more reproducible than the cross-spectrum method, it might be a powerful and reliable tool to assess baroreflex sensitivity in humans.

Adult↗

Assessment of spontaneous baroreflex sensitivity in rats a new method using the concept of statistical dependence.

A new method was developed to evaluate the cardiac baroreflex sensitivity (BRS) from spontaneous mean arterial pressure (MAP) and heart rate (HR) changes in conscious rats. It relies on the determination of the statistical dependence between MAP and HR values. In 13 control rats, 12 rats with a pharmacologically induced hypertension, and 7 rats with a chronic sinoaortic denervation (SAD), dependent (MAP, HR) couples related to the baroreflex activity were selected to determine the spontaneous BRS (Sp-BRS). In control and hypertensive rats, pharmacological BRS (Ph-BRS) was estimated using graded bolus intravenous doses of vasoactive drugs. Ph-BRS was significantly lower in hypertensive than in control rats. Sp-BRS was determined in 10 control and 10 hypertensive rats and was strongly correlated with Ph-BRS (r = 0.83, n = 20, P < 0.0001). Sp-BRS could be evaluated in six SAD rats and was profoundly decreased (-86%, P < 0.001) compared with control rats. In conclusion, this work validates the estimation of the cardiac BRS from spontaneous MAP and HR variations with use of (MAP, HR) couples of values that are statistically dependent.

Animals↗

[Comparison of three methods for the estimation of spontaneous cardiac baroreflex sensitivity in normotensive and hypertensive subjects].

This study aimed at comparing estimations of spontaneous cardiac baroreflex sensitivity (BRS) obtained with 3 different methods from continuous non-invasive blood pressure recordings in humans. A new method, allowing the quantification of the statistical dependence between values of 2 parameters (Z coefficient), was applied to beat-to-beat systolic blood pressure (SBP) and heart period (HP) values. SBP and HP values with positive Z coefficient and corresponding to baroreflex activity (SBP and HP values both lower or higher than the modal values) were submitted to a linear regression and the regression coefficient (Zgain) was taken as an index of BRS. Second, cross-spectral analysis of SBP and HP gave a BRS value (Csgain) computed as the average value of transfer function moduli for frequencies between 0.07 and 0.14 Hz, with coherence between SBP and HP greater than 0.5. The third method relies on the analysis of linear sequences (r > 0.97) containing at least 3 values of SBP and HP varying in the same direction. The average regression coefficient obtained from all selected SBP and HP sequences is the index of BRS (Seqgain). SBP and HR were recorded during 1 hour with a Finapres in 10 healthy male volunteers (NT), 23 to 32 year-old (SBP: 123 +/- 2 mmHg) and 10 recent and untreated hypertensive subjects (HT) (SBP: 152 +/- 6 mmHg). [table: see text] These results show that, in both groups, Zgain and Seqgain correlated with Csgain. No correlation was found between Zgain and Seqgain in healthy volunteers whereas the correlation was strong in hypertensives probably due to more heterogeneous SBP levels and BRS values in these subjects. This suggests that these methods are sensitive to different ways of response of the baroreflex.

Adult↗

Hemodynamic analysis of arterial pressure lability in sympathectomized rat.

Male Sprague-Dawley rats, treated with either saline (n = 14) or guanethidine (n = 12) from 1 to 13 wk of age, were instrumented for the measurement of mean arterial pressure (MAP) and indexes of regional blood flows (pulsed Doppler flow probes) in the subdiaphragmatic aorta, superior mesenteric artery, and distal aorta (hindquarters). Hemodynamic parameters were simultaneously recorded in the conscious rats on a beat-to-beat basis by a computer. Chronic sympathectomy did not change the MAP level but nearly doubled its spontaneous variability, mainly due to large decreases in MAP associated with regional vasodilations that were slightly delayed with respect to the onset of the decreases in pressure, especially in the aortic and mesenteric circulations. In the hindquarters vascular bed, the onset of vasodilations sometimes coincided with the onset of the decreases in MAP. During depressor episodes, blood flow varied little (aortic and mesenteric circulations) or even increased (hindquarters). This hemodynamic pattern was not affected by acute beta-adrenoceptor blockade. We conclude that chronic sympathectomy sensitizes the cardiovascular system to decreases in arterial pressure mainly by unmasking local autoregulatory responses of regional circulations. The sympathetic control of vascular tone overrides these responses and considerably limits the MAP variability.

Adrenergic beta-Antagonists↗

High blood pressure and metabolic disorders are associated in the Lyon hypertensive rat.

OBJECTIVE: A large population of F2 rats, obtained from a cross between male Lyon hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in order to assess the relationship between increased body weight, hyperlipidaemia and high blood pressure which characterize LH rats. METHODS: Mean arterial pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2 rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low-density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids, triglycerides, insulin and glucose were measured. RESULTS: In the F2 cohort it was observed that high MAP was a recessive trait that depends on several genes and was unrelated to body weight. The left ventricular weight, corrected for tibia length, was correlated with MAP. Plasma total and high-density lipoprotein-cholesterol and phospholipids concentrations were lower in the F1 rats than in the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP was related to total, high-density lipoprotein- and low-density lipoprotein-cholesterol. Plasma triglycerides, insulin and the insulin:glucose ratio, which were higher in the LH rats than in the LN rats, were also correlated with MAP in the F2 cohort. Using stepwise multiple regression analysis, MAP remained correlated with plasma total cholesterol, insulin and the insulin:glucose ratio, but not with triglycerides. CONCLUSIONS: Hypertension in LH rats is a recessive trait that is independent of body weight. In addition, the cosegregation of blood pressure with plasma cholesterol and, to a lesser degree, with insulin levels, which was observed in the present study provides the first direct evidence that these phenotypes are associated and are not due simply to genetic drift in the Lyon model.

Animals↗

Autonomic nervous system and cardiovascular variability in rats: a spectral analysis approach.

Mechanisms underlying systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) beat-to-beat variability were investigated using spectral analysis in conscious genetically normotensive (LN) and hypertensive (LH) adult rats from the Lyon strains. In LN rats, basal SBP, DBP, and HR spectra exhibited peaks in low (LF: 0.38-0.45 Hz) and high (HF: 1.04-1.13 Hz) frequencies. The LF peak of SBP, and even more of DBP, could be attributed to the influence of the sympathetic nervous system as it disappeared after destruction of the sympathetic nerves or a combined alpha- and beta-adrenoceptor blockade, whereas it was higher after blockade of the parasympathetic system. The HF peak of HR, linked to the respiratory rate, was abolished by the parasympathetic system blockade, whereas those of SBP and DBP were enhanced. In LH rats, which exhibit a lower sympathetic activity, the LF peaks of SBP and DBP were less distinct compared with LN controls. We conclude that the LF peak of DBP and the HF peak of HR are likely to represent useful estimates of the sympathetic vascular control and of the parasympathetic cardiac control, respectively.

Angiotensin Receptor Antagonists↗

Heterogeneous computer network for real-time hemodynamic signal processing.

A computer network is described that allows real-time processing, graphical monitoring and off-line analysis of blood pressure, nervous activity and Doppler signals recorded in conscious rats. Real-time processing is performed by an acquisition station using a powerful microprocessor, allowing extraction and storage of several characteristic parameters from each cardiac cycle and real-time graphical monitoring. The experimenter can thereby follow the time evolution of the hemodynamic parameters. Experimental data are sent through the local network to a workstation that ensures off-line processing such as chronograms, histograms and statistical analyses.

Animals↗

[The sympathetic and renin-angiotensin systems are complementary in blood pressure regulation].

The consequences of a chronic destruction of sympathetic nerves or of the blockade of the renin angiotensin system (RAS) on the blood pressure (BP) level and its spontaneous variability were studied using a computerized method which allows a continuous monitoring of BP in conscious unrestrained rats. Guanethidine, used to lesion the sympathetic fibres did not alter the BP level but significantly enhanced its variability. On the opposite, angiotensin converting enzyme inhibition decreased the BP level without changing its variability. It is concluded that both systems play a complementary role as the RAS determines the long-term BP level while the sympathetic nerves control its short-term variability in conscious animals.

Animals↗