Vasorelaxant Effect of a Baccharis trimera Infusion on Precontracted Rat Aortic Rings.

Baccharis trimera (Less.) DC is a South American plant that in folk medicine is considered to produce reduction in blood pressure. One aspect of this putative effect is the vasorelaxation. The aim of this work was to evaluate the ability of a B. trimera extract to relax rat aortic rings precontracted with noradrenaline. As the infusion is the usual way of intake of this plant, an infusion of B. trimera was prepared using 100 g of the plant (leaves) boiled in water, frozen and lyophilized. Working solutions were prepared using different concentrations of the dried extract diluted in Krebs Henseleit solution. It was proved that the infusion relaxed the aortic rings in a dose dependent manner 100 minutes after adding the exract to the bath. Considering as 100% the maximum contraction achieved with noradrenaline, a relaxation of 101.1 ± 2.3% was observed with the highest dose of the infusion used in these experiments (0.32 mg/mL). While in control rings relaxation was 12.9 ± 2.4%. In aortic rings denuded from endothelium the percentage of vasoralaxation did not show statistically significant differences when compared to intact rings. These data support the hypothesis of a vasorelaxant effect of this plant and constitutes the first approach to the scientific basis of a potential antihypertensive effect.

Heart rate variability during carbachol-induced REM sleep and cataplexy.

The nucleus pontis oralis (NPO) exerts an executive control over REM sleep. Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a single microinjection of carbachol (a cholinergic agonist) into the NPO produces either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA). In order to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings from chronically prepared cats during REMc, CA as well as during sleep and wakefulness. Subsequently, we performed statistical and spectral analyses of the HRV. The heart rate was greater during CA compared to REMc, NREM or REM sleep. Spectral analysis revealed that the low frequency band (LF) power was significantly higher during REM sleep in comparison to REMc and CA. Furthermore, we found that during CA there was a decrease in coupling between the RR intervals plot (tachogram) and respiratory activity. In contrast, compared to natural behavioral states, during REMc and CA there were no significant differences in the HRV based upon the standard deviation of normal RR intervals (SDNN) and the mean squared difference of successive intervals (rMSSD). In conclusion, there were differences in the HRV during naturally-occurring REM sleep compared to REMc. In addition, in spite of the same muscle atonia, the HRV was different during REMc and CA. Therefore, the neuronal network that controls the HRV during REM sleep can be dissociated from the one that generates the muscle atonia during this state.

Statistical, spectral and non-linear analysis of the heart rate variability during wakefulness and sleep.

As a first step in a program designed to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings on chronically-prepared cats during semi- restricted conditions. We found that the tachogram, i.e. the pattern of heart beat intervals (RR intervals) was deeply modified on passing from alert wakefulness through quiet wakefulness (QW) to sleep. While the tachogram showed a rhythmical pattern coupled with respiratory activity during non-REM sleep (NREM), it turned chaotic during REM sleep. Statistical analyses of the RR intervals showed that the mean duration increased during sleep. HRV measured by the standard deviation of normal RR intervals (SDNN) and by the square root of the mean squared difference of successive intervals (rMSSD) were larger during REM and NREM sleep than during QW. SD-1 (a marker of short- term variability) and SD-2 (a marker of long-term variability) measured by means of Poincaré plots increased during both REM and NREM sleep compared to QW. Furthermore, in the spectral analysis of RR intervals, the band of high frequency (HF) was larger in NREM and REM sleep in comparison to QW, whereas the band of low frequency (LF) was larger only during REM sleep in comparison to QW. The LF/HF ratio was larger during QW compared either with REM or NREM sleep. Finally, sample entropy analysis used as a measure of complexity, was higher during NREM in comparison to REM sleep. In conclusion, HRV parameters, including complexity, are deeply modified across behavioral states.

Right atrium cholinergic deficit in septic rats.

Heart rate variability (HRV) is mainly determined by the influence of both branches of the Autonomic Nervous System over the sinus node. Low HRV has been associated with a worse prognosis in patients with sepsis. The objective of this study was to explain the reduction in HRV during experimental sepsis in adult rats. We recorded the heart's electrical activity by telemetry in conscious unrestrained male rats before and 1day after the induction of peritonitis (N=39) or sham peritonitis (N=15). Then, we analyzed the chronotropic responsiveness of the isolated heart to the autonomic neurotransmitters and determined catecholamine concentrations in blood plasma and acetylcholine and choline concentrations in the right atrium. The surviving septic rats (N=33) had increased heart rate (HR) and diminished HRV. Despite the higher HR in situ, the spontaneous basal HR in septic and sham isolated hearts was the same. The isolated septic hearts showed acetylcholine hypersensitivity (log (IC50,M)=-7.2±0.2 vs. -6.0±0.4, P=0.025) and lower concentrations of choline in their right atriums (in nMol/mg protein: 0.6±0.1 vs. 1.6±0.6, P=0.013). Norepinephrine concentration in blood plasma from septic rats was higher (in ng/ml: 29.2±8.4 vs. 5.8±4.1, P=0.019). In conclusion, septic rats present a deregulation of the autonomic nervous system, not only sympathetic overexcitation but also parasympathetic dysfunction.

Exercise training slows down heart rate and improves deceleration and acceleration capacity in patients with heart failure.

Controlled physical training has been shown to be a valuable therapeutic addition to a pharmacological treatment in patients with chronic heart failure (CHF). It is speculated that repeated physical training can improve the autonomic modulation of the cardiovascular system in patients with CHF. The present study evaluates autonomic function in patients with CHF by means of heart rate variability and the phase-rectified signal averaging of heart rate that allows the quantification of the acceleration capacity and deceleration capacity. Two groups of patients with CHF treated with comparable pharmacological medications were enrolled into this study. One group entered a 24-week training program, whereas another group remained without it. After the completion of the study, there was a significant increase of mean RR interval, high- and low-frequency power of heart rate variability, and the magnitudes of deceleration capacity and acceleration capacity only in patients who underwent the cardiac rehabilitation program with controlled physical training.

Asymmetrical properties of heart rate variability in type 1 diabetes.

Heart rate variability related to heart rate decelerations and accelerations is reduced in patients with type 1 diabetes compared to healthy individuals both in resting 10-min and ambulatory 24-h ECGs.

Correlations between frequency-domain HRV indices and lagged Poincaré plot width in healthy and diabetic subjects.

The conventional Poincaré plot for heart rate variability (HRV) analysis is a scatterplot of successive (lag 1) pairs of RR intervals (intervals between heartbeats), and its width (SD1) is considered a measure of short-term variability. It has been shown that SD1 correlates better with HF than with LF (high- and low-frequency bands of the spectrum, respectively). Our aim was to assess how these correlations were affected when SD1 was obtained for longer lags. 10 min ECGs were used to construct Poincaré plots with lags of 1-10 heartbeats in two groups of subjects, one with normal HRV and the other with impaired HRV (control and diabetic groups respectively, N = 15 each). SD1 was quantified for these subjects and HRV spectral indices were estimated. The diabetic group had lower LF, HF and SD1 than the control group (p < 0.05). In both groups, SD1 tended to increase as the lag increased. In the control group, SD1 for lags 1 and 2 was highly correlated with HF (r(s) > 0.9), while SD1 for lags 4 correlated better with LF (r(s) 0.9) than with HF (0.65

Design, synthesis, and biological characterization of potential antiatherogenic nitric oxide releasing tocopherol analogs.

Synthesis and biological characterization of a series of alpha-tocopherol analogs with NO-releasing capacity are reported. The selected NO-donor moieties were nitrooxy and furoxan. All products were tested for their in vitro NO-releasing capacities, vasodilating properties, and antiplatelet activity. They were also capable of preventing LDL oxidation.

Short-term studies of heart rate variability: comparison of two methods for recording.

Heart rate variability (HRV) is often analysed using short-term studies. Our objective was to compare two of them in a group of diabetic patients (reduced HRV) and in a control group. From the same 10 min surface electrocardiogram (ECG) two recordings were obtained. In one of them the whole signal was acquired through an A/D converter (post-event method). In the other (real-time method), an interface between the electrocardiograph and a parallel port of a computer was used to perform real-time processing of the ECG signal. The R-R intervals were measured after a visual validation in the post-event method. In the real-time method, the stored R-R intervals were automatically filtered. For both methods HRV indexes were calculated using the same software. The values of mean R-R intervals for each subject were almost identical regardless of the method. Accordingly, we found a high correlation between HRV indexes obtained from both methods (all Spearman values > or = 0.9441 and P < 0.0001). In addition, we found similar P values in the comparisons between the diabetic and control groups. We conclude that both methods are suitable for HRV analysis. Therefore, the selection of method can be based on other considerations such as the capability to store the ECG of the post-event method or the speed of analysis and lower cost of the real-time one.

Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients.

PURPOSE: To determine whether measuring heart rate variability (HRV) in a group of septic patients without multiple organ dysfunction syndrome (MODS) made it possible to predict which of them would later develop this syndrome. MATERIAL AND METHODS: We studied 46 septic patients without MODS at the time of admission to an intensive care unit (ICU). During the first 24 hours of admission, a 10-minute electrocardiogram (ECG) was performed and 8 HRV indexes were calculated off-line. Eleven patients later developed MODS (MODS group) during their ICU stay, and 28 did not (non-MODS group). Seven patients were excluded. RESULTS: Although Acute Physiological and Chronic Health Evaluation (APACHE II) scores were similar for both groups, most HRV indices on admission were reduced significantly in the MODS group. Compared with a subset from the non-MODS group (control group, n = 11) paired by age, the MODS group had significantly lower low-frequency spectral components (LF, P =.0128) and mean squared successive differences of R-R intervals (rMSSD) (P =.0473) values. Multivariable logistic regression identified LF as the best predictor of MODS and received operating characteristic (ROC) curves established its cut-off point at 18 ms(2). Mortality rates were 63.6% for the MODS group and 0% for the non-MODS group (P <.0001). CONCLUSIONS: Reduction of HRV on ICU admission may be useful in identifying septic patients at risk for development of MODS.

Heart rate variability: short-term studies are as useful as holter to differentiate diabetic patients from healthy subjects.

BACKGROUND: The definitive incorporation of heart rate variability (HRV) as a clinical tool depends on the development of more confident techniques of measurement. The length of the studies is a critical issue. Whereas Holter studies allow the monitorization at different hours and activities, short-term recordings allow the control of environmental conditions. Recording length is also strongly related to the procedure of analysis; for instance, some time-domain indexes are strongly affected by the duration of the study. Meanwhile, spectral analyses require stationary conditions, only achieved in short-term studies. Our main goal was to determine if HRV indexes obtained from short-term analyses were as useful as those from Holter monitoring for diagnosis of reduced HRV in diabetes. METHODS: We studied two groups: one with impaired HRV (15 diabetic patients) and another with normal HRV (15 healthy subjects). HRV indexes obtained from 24-hour Holter recordings (SDNN, rMSSD, and the power of LF and HF bands), were correlated with analog indexes obtained from 10-minute digital acquired studies within each group. Besides, we compared the diabetic and control groups using the indexes obtained with both methodologies. RESULTS: The correlation was high (0.70

Action potential duration and contraction after rest at room temperature in guinea pig papillary muscle

Simultaneous recordings of action potential and isometric tension of right papillary muscles were performed. After regular stimulation at 1 Hz, pauses of 10 min were allowed. In the first beat after rest, we measured action potential duration at the 90 percent of the repolarization (APD90), maximal twitch tension (T), time to peak of contraction (TTP), and rate of development of tension (+dT/dt) and relaxation (-dT/dt). Values were normalized against pre-rest ones. No significative changes were observed after rest at 35 degrees Celsius. After rest at 25 degrees Celsius APD90 and TTP were prolonged but T was reduced. Post-rest+dT/dt were shower, dT/dt did not shown significative changes. Nifedipine 10 muM prevented post-rest APD90 tengthening, and produced a further reduction of mechanical response. Substitution of external Na+ by Li+ shortened APD90, increased T of either regular or post-rest beats and led to calcium overload signs. When pause were allowed during Na+ substitution, calcium overload signs were attenuated. We conclude that the combination of rest and room temperature diminished [Ca++]i mainly by Na+/Ca++ mechanism. The reduction of [Ca++]i in turn could delay the inactivation of iCa. As a consequence, longer APs were obtained, accompanied by weaker and slower mechanical responses. Changes in TTP and +dT/dt could suggest that post-rest contractions in room temperature, are dependent of extracellular Ca++ rather than a deplected RS.

Action potential duration and contraction after rest at room temperature in guinea pig papillary muscle

Simultaneous recordings of action potential and isometric tension of right papillary muscles were performed. After regular stimulation at 1 Hz, pauses of 10 min were allowed. In the first beat after rest, we measured action potential duration at the 90 percent of the repolarization (APD90), maximal twitch tension (T), time to peak of contraction (TTP), and rate of development of tension (+dT/dt) and relaxation (-dT/dt). Values were normalized against pre-rest ones. No significative changes were observed after rest at 35 degrees Celsius. After rest at 25 degrees Celsius APD90 and TTP were prolonged but T was reduced. Post-rest+dT/dt were shower, dT/dt did not shown significative changes. Nifedipine 10 muM prevented post-rest APD90 tengthening, and produced a further reduction of mechanical response. Substitution of external Na+ by Li+ shortened APD90, increased T of either regular or post-rest beats and led to calcium overload signs. When pause were allowed during Na+ substitution, calcium overload signs were attenuated. We conclude that the combination of rest and room temperature diminished [Ca++]i mainly by Na+/Ca++ mechanism. The reduction of [Ca++]i in turn could delay the inactivation of iCa. As a consequence, longer APs were obtained, accompanied by weaker and slower mechanical responses. Changes in TTP and +dT/dt could suggest that post-rest contractions in room temperature, are dependent of extracellular Ca++ rather than a deplected RS. (AU)