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C Cerutti

Publications and source records attributed to C Cerutti.

At least 19 recordsLinked to original sources
PubMed2005

Identification and characterization of two genes (MIP-1beta, VE-CADHERIN) implicated in acute rejection in human heart transplantation: use of murine models in tandem with cDNA arrays.

BACKGROUND: Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. METHODS AND RESULTS: Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1beta (MIP-1beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. CONCLUSIONS: We have demonstrated that the upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection.

Animals↗
PubMed2001

Time versus frequency domain techniques for assessing baroreflex sensitivity.

BACKGROUND: Newer techniques to evaluate baroreflex sensitivity (BRS) are based on the analysis of blood pressure (BP) and heart rate (HR) time series in the time or frequency domain. These novel approaches are steadily gaining popularity, since they do not require injection of vasoactive substances, nor do they rely on a complex experimental set-up. AIM: This review outlines and compares some basic features of the latest methods to assess spontaneous baroreflex function. RESULTS: Modern techniques for the estimation of spontaneous BRS are based on a variety of signal processing schemes and derive information on the baroreflex function from different perspectives. Thus factors such as respiration and other non-stationary agents may have different influences on the estimates provided by each of these approaches. Notwithstanding such individual specificity, however, it has been observed that in several physiological and pathophysiological conditions these techniques often provide comparable information on BRS changes over time, particularly when the estimates are averaged over time windows of a few minutes. CONCLUSIONS: Due to the general agreement in the pattern of BRS among most modern methods, it seems reasonable to employ the most validated of these techniques, for which data obtained in several studies are already available.

Animals↗
PubMed2001

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↗
PubMed2001

Renal elimination of amikacin and the aging process.

OBJECTIVE: Although amikacin is primarily eliminated via glomerular filtration, drug concentrations are not consistently predicted in all patients. To better describe the relationship between amikacin clearance and both age and renal function, we used a new heuristic approach involving statistical analysis of dependence. DESIGN AND SETTING: Retrospective pharmacokinetic study using data from seven centres in France. PARTICIPANTS: 634 patients with sepsis aged between 18 and 98 years of age who received intravenous amikacin. METHODS: Clearance of amikacin was modelled using the NonParametric EM algorithm for a two-compartment model (NPEM2) with intravenous infusion. RESULTS: A total of 2499 serum amikacin determinations was available for analysis. The relationship between the clearance of amikacin and age was weak. Interestingly, the Z method, which filters data based on dependence criteria, selected data that were best fitted by a polynomial function (r = 0.90; p < 0.001). This representation of the polynomial function was similar to a previously proposed theoretical model describing covariations between the clearance of amikacin and age. However, the polynomial function applied to only 33% of the patients that were selected by the Z method. The correlation between the clearance of amikacin and renal function was also relatively low (r = 0.39). The Z method exhibited a continuous and strong dependence pattern between the clearance of amikacin and age for 49% of the patients. CONCLUSIONS: The Z methodology, which filters data using dependence criteria, confirms that age, renal function and amikacin clearance are strongly related, but only in less than half of a large sample of patients with sepsis without renal pathology. These results suggest that other variables should be taken into account in order to improve the description of the behaviour of amikacin. The Z methodology improved the classical description of relationships between variables, and should be applied to better select pertinent variables in pharmacokinetic studies.

Adult↗
PubMed2001

Limits of clinical tests to screen autonomic function in diabetes type 1.

OBJECTIVES: A precocious detection of cardiac autonomic dysfunction is of major clinical interest that could lead to a more intensive supervision of diabetic patients. However, classical clinical exploration of cardiac autonomic function is not easy to undertake in a reproducible way. Thus, respective interests of autonomic nervous parameters provided by both clinical tests and computerized analysis of resting blood pressure were checked in type 1 diabetic patients without orthostatic hypotension and microalbuminuria. MATERIAL AND METHODS: Thirteen diabetic subjects matched for age and gender to thirteen healthy subjects volunteered to participate to the study. From clinical tests (standing up, deep breathing, Valsalva maneuver, handgrip test), autonomic function was scored according to Ewing's methodology. Analysis of resting beat to beat blood pressure provided autonomic indices of the cardiac function (spectral analysis or Z analysis). RESULTS: 5 of the 13 diabetic patients exhibited a pathological score (more than one pathological response) suggesting the presence of cardiovascular autonomic dysfunction. The most discriminative test was the deep breathing test. However, spectral indices of BP recordings and baro-reflex sensitivity (BRS) of these 5 subjects were similar to those of healthy subjects and of remaining diabetic subjects. CONCLUSION: Alteration in Ewing's score given by clinical tests may not reflect an alteration of cardiac autonomic function in asymptomatic type 1 diabetic patients, because spectral indices of sympathetic and parasympathetic (including BRS) function were within normal range. Our results strongly suggest to confront results provided by both methodologies before concluding to an autonomic cardiac impairment in asymptomatic diabetic patients.

Adult↗
PubMed2000

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↗
PubMed1999

In vivo efficacy of mefloquine for the treatment of Falciparum malaria in Brazil.

Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.

Adolescent↗
PubMed1999

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↗
PubMed1998

Short-term haemodynamic variability in the conscious areflexic rat.

1. Simultaneous measurements of arterial pressure and cardiac output (n = 8), mesenteric blood flow (n = 7) or hindquarters (n = 8) blood flow were performed during 1 h periods in conscious rats, before and after acute pharmacological blockade of the autonomic, renin-angiotensin and vasopressin systems. In the latter condition (areflexic state), arterial pressure was maintained with a continuous infusion of noradrenaline. 2. In the areflexic state, spontaneous fluctuations in arterial pressure were markedly exaggerated, especially depressor episodes. At the onset of these falls in arterial pressure, there was an abrupt and transient decrease in stroke volume and cardiac output. Systemic vasodilatation then developed while cardiac output returned to normal. Regional vasodilatations were also delayed from the onset of the falls in arterial pressure and were usually large enough to maintain blood flow. 3. Both time and frequency domain analyses confirmed that changes in systemic and regional vascular conductances lagged by about 1 s behind arterial pressure changes. 4. These results indicate that, in the absence of neurohumoral influences, autoregulatory-like mechanisms become dominant in the control of systemic and regional circulations and contribute to exaggeration of the spontaneous short-term variability of arterial pressure.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Mechanisms of spontaneous baroreflex impairment in lyon hypertensive rats.

This experiment aimed at 1) comparing the spontaneous baroreflex sensitivity (SBRS) in Lyon genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats and 2) assessing some aspects of the mechanisms of its impairment in LH rats. Baroreflex was studied in control animals after an early chronic converting enzyme inhibition with perindopril and after a 4-wk infusion of ANG II in perindopril-treated rats. The SBRS was determined with a previously validated method, using statistical dependence between blood pressure (BP) and heart rate values recorded in freely moving animals. LH rats exhibited high BP, cardiac hypertrophy, and decreased SBRS (LH, 1.3 +/- 0.2; LN, 2.5 +/- 0.4; LL, 2.2 +/- 0.4 beats . min-1 . mmHg-1). Perindopril prevented the development of hypertension and cardiac hypertrophy and normalized SBRS. BP rose in LH and LL rats after ANG II infusion, but only LH rats, which developed a cardiac hypertrophy, had an impaired SBRS (LH, 1.1 +/- 0.2; LN, 2.5 +/- 0.2; LL, 2.8 +/- 0.3 beats . min-1 . mmHg-1). This impairment was partially reversed by an acute ANG II blockade with losartan. These results demonstrate that high BP does not account for the decreased SBRS in LH rats. SBRS impairment could result either from cardiac hypertrophy or from the direct effect of ANG II on the baroreflex loop.

Angiotensin II↗
PubMed1997

Atovaquone and proguanil for the treatment of malaria in Brazil.

The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.

Adolescent↗
PubMed1996

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↗
PubMed1995

Hemodynamic analysis of arterial pressure oscillations in conscious rats.

This study examined the contribution of rhythmic fluctuations of regional blood flow and vascular conductance to the genesis of low- (LF, 0.27-0.74 Hz) and high- (HF, 0.76-5 Hz) frequency oscillations of arterial pressure. In conscious 15-week-old male intact (n = 11), guanethidine-sympathectomized (n = 8) and chronically sinoaortic denervated (n = 7) rats, arterial pressure and regional blood flow velocities (pulsed Doppler probes) were simultaneously recorded. Indices of subdiaphragmatic aortic, hindquarters and superior mesenteric conductances were calculated on a beat-to-beat basis over a 60-min period. Spectral power was calculated in the LF and HF bands using a fast Fourier transform algorithm. Transfer function analysis was also performed to calculate coherence and phase between arterial pressure and regional flows and conductances. In the LF band, spectral power of arterial pressure was decreased by approx. 85% in sympathectomized and approx. 54% in sinoaortic denervated rats. In the HF band, spectral power did not differ between the groups. In the three groups of rats, relations between arterial pressure and blood flow were characterized by a significant coherence in the HF band with little or no phase delay (synchronous oscillations). Relations between arterial pressure and vascular conductance were characterized in intact rats by a significant coherence in the LF band and a phase delay tending to pi radians (opposite oscillations), whereas in both sympathectomized and sinoaortic denervated rats, coherence did not reach significance. It is concluded that LF oscillations of arterial pressure are mostly secondary to rhythmic fluctuations in the vasomotor sympathetic tone in several regional circulations. Part of these oscillations originate from the synchronizing influence of the baroreceptor reflex. The study also suggests that the respiratory (HF) oscillations of arterial pressure involve fluctuations in cardiac output of purely mechanical origin.

Animals↗
PubMed1995

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↗
PubMed1995

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↗