Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains.

Optimal autophagic activity is crucial to maintain muscle integrity, with either reduced or excessive levels leading to specific myopathies. LGMD2H is a muscle dystrophy caused by mutations in the ubiquitin ligase TRIM32, whose function in muscles remains not fully understood. Here, we show that TRIM32 is required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models. Trim32 inhibition results in a defective autophagy response to muscle atrophy, associated with increased ROS and MuRF1 levels. The proautophagic function of TRIM32 relies on its ability to bind the autophagy proteins AMBRA1 and ULK1 and stimulate ULK1 activity via unanchored K63-linked polyubiquitin. LGMD2H-causative mutations impair TRIM32's ability to bind ULK1 and induce autophagy. Collectively, our study revealed a role for TRIM32 in the regulation of muscle autophagy in response to atrophic stimuli, uncovering a previously unidentified mechanism by which ubiquitin ligases activate autophagy regulators.

Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight.

This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Columbia Space Shuttle mission. Continuous blood pressure (BP), ECG, and respiratory frequency were collected in four astronauts on ground (baseline) and during flight at days 0-1, 6-7, and 12-13, both at rest and during moderate exercise (75 W) on a cycle ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI); low-frequency (LF) power and high-frequency (HF) power of systolic BP (SBP), diastolic BP (DBP), and R-R interval (RRI); the RRI LF/HF ratio; and the RRI root mean square of successive differences (RMSSD) index were also estimated. We found that, at rest, BRS increased in early flight phase, compared with baseline (means +/- SE: 18.3 +/- 3.4 vs. 10.4 +/- 1.2 ms/mmHg; P < 0.05), and it tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between preflight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (P < 0.05) compared with baseline, whereas LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. These findings demonstrate that heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.

Upgraded diagnostic value of Gen-Probe PACE 2 assay for detection of Chlamydia trachomatis infection.

In this study, we evaluate the performance of a nucleic acid amplification assay, COBAS AMPLICOR (Roche Molecular systems) (PCR), compared to non-amplified DNA probe assay PACE2 (Gen-Probe Inc.) for the detection of C. trachomatis in a total of 2,916 samples (2,114 females and 802 males) consecutively collected in two different clinical pathology laboratories, over a period of three years. In the females, the endocervical swabs showed a similar range of detection when using the two different methods: out of 1,581 females processed with PACE 2, 1.4% (2005), 0.9% (2006), 0.5% (2007), resulted positive for C. trachomatis; out of 533 females processed with PCR, 1.3% (2005), 1.5% (2006) and 1.2% (2007), resulted positive. However, in the male subjects we found an increased positivity of Chlamydia detection on urethral swabs by using PACE 2: 4.8% (2005), 1.9% (2006) and 2.9% (2007), compared to urine specimen processed by PCR: 1% (2005), 1.4% (2006) and 0% (2007). Even if PCR should be considered a most promising tool for routine diagnosis of Chlamydia infection, Gen Probe allowed us to better identify Chlamydia trachomatis (in 4.8% of urethral swabs compared to urine) leading to a hypothesis that extracellular EB forms of Chlamydia could be absent in urine in persistent infectious.

Blood pressure changes after high- and low-salt diets: are intermittent arm measures and beat-by-beat finger measures equivalent?

The assessment of sodium sensitivity requires to measure the difference in mean arterial pressure (MAP) at the end of sodium-loading (SLoad) and sodium-depletion (SDepl) maneuvers with an arm-cuff manometer. Aim of this study is to evaluate whether MAP measuring devices based on the volume-clamp method at the finger can also be used for assessing sodium sensitivity. Sixty-eight normotensive volunteers underwent SLoad and SDepl diets in random order. MAP was simultaneously measured at the end of each diet with arm (Spacelabs 90207) and finger (Portapres model-2) cuff devices. The sodium sensitivity was assessed as the difference in MAP at the end of SLoad and SDepl diets (ΔMAP), and as salt-sensitivity index (SSI; SSI = ΔMAP divided by the difference in urinary-sodium-excretion rate at the end of the diets). Discrepancies between finger and arm-cuff devices in ΔMAP or SSI were evaluated by Bland and Altman analysis. Even if discrepancies between devices had null-fixed bias, results showed a significant proportional bias and large limits of agreement (between -25 and 25 mm Hg for ΔMAP, between -196 and 180 mm Hg mol(-1) per day for SSI). The SSI distribution over the group was larger, flatter and less symmetric if derived from finger-cuff rather than arm-cuff devices, and this influenced substantially the identification of salt-sensitive individuals. Therefore, the response of MAP to SLoad/SDepl diets and consequently the assessment of the salt-sensitivity condition depends importantly on the measurement site, and brachial measures should be preferred for consistency with literature and normative data.

ICF-based approach to evaluating functionality in cardiac rehabilitation patients after heart surgery.

BACKGROUND: Heart surgery is a frequent reason for admission to in-patient cardiac rehabilitation programmes. ICF approach has never been used to evaluate cardiac patients after major heart surgery. AIM: The aim was to evaluate and measure functionality in cardiac patients who have undergone heart surgery, using for the first time the ICF-based approach and to assess whether such approach can be feasible and useful in cardiac rehabilitation. DESIGN: Observational study. SETTING: In-patients cardiac Rehabilitation Unit in Milan. POPULATION: Fifty consecutively admitted patients who had undergone heart surgery (34 males, 16 females; mean age 65.7±12.5 years). METHODS: We prepared a ICF-core set short enough to be feasible and practical. Patients were individually interviewed by different healthcare professionals (randomly selected from a group of two physicians, two physiotherapists and two psychologists) at the beginning (T1) and end of cardiac rehabilitation (T2) RESULTS: The sum of the scores of each ICF body function, body structure, activity and participation code significantly decreased between T1 and T2 (P<0.001). The environmental code scores significantly decreased in the case of facilitators between T1 and T2 (P=0.0051), but not in the case of barriers. There were significant correlations between the ICF body function scores and Barthel's index (ρ=0.381; P=0.006), NYHA class (ρ=0.404; P=0.004) and plasma Cr-P levels (r=0.31; P=0.03), between the ICF body structure codes and the Conley scale (ρ=0.306; P=0.02), and between the activity/participation codes and SpO2 (ρ=0.319; P=0.04). There were no correlations between the ICF environmental codes and clinical parameters. CONCLUSION: The ICF-based data provided functional information that was consistent with the patients' clinical course. CLINICAL REHABILITATION IMPACT: The core set used allowed to quantify important body functions and activities, including some areas that are generally insufficiently considered by healthcare professionals during cardiac rehabilitation, and document their improvement.

[B-mode sonography visualizing microemboli flow in the main cerebral arteries]. / Visualisation du passage de micro-emboles cérébraux par ultrasonographie en mode B-Flow.

In a patient with a mechanical prosthetic aortic valve admitted for transient amnesia, transcranial duplex Doppler and B-mode sonography visualized the transit of microemboli along the main cerebral arteries. Gaseous microemboli resulting from a cavitation phenomenon at valve closure were seen as high-intensity transient signals (HITS). To our knowledge, this is the first report of microemboli flow visualized in B-mode.

Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal.

Blood pressure variability includes rhythmic and nonrhythmic fluctuations that, with the use of spectral analysis, appear as clear peaks or broadband power, respectively. This review offers a concise and critical description of the spectral methods most commonly used (fast Fourier transform versus autoregressive modeling, time-varying versus broadband spectral analysis) and an evaluation of their advantages and disadvantages. It also provides insight into the problems that still affect the physiological and clinical interpretations of data provided by spectral analysis of blood pressure and heart rate variability. In particular, the assessment of blood pressure and heart rate spectra aimed at providing indexes of autonomic cardiovascular modulation is discussed. Evidence is given that multivariate models--which allow evaluation of the interactions between changes in blood pressure, heart rate, and other biological signals (such as respiratory activity) in the time or frequency domains--offer a more comprehensive approach to the assessment of cardiovascular regulation than that represented by the separate analysis of fluctuations in blood pressure or heart rate only.

Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing.

The accuracy of blood pressure values obtained by continuous noninvasive finger blood pressure recording via the FINAPRES device was evaluated by comparison with simultaneous intraarterial monitoring both at rest and during performance of tests known to induce fast and often marked changes in blood pressure. The comparison was performed in 24 normotensive or essential hypertensive subjects. The average discrepancy between finger and intra-arterial blood pressure recorded over a 30-minute rest period was 6.5 +/- 2.6 mm Hg and 5.4 +/- 2.9 mm Hg for systolic and diastolic blood pressure, respectively; a close between-method correspondence was also demonstrated by linear regression analysis. The beat-to-beat changes in finger systolic and diastolic blood pressure were on average similar to those measured intra-arterially during tests that induced a pressor or depressor response (hand-grip, cold pressor test, diving test, Valsalva maneuver, intravenous injections of phenylephrine and trinitroglycerine) as well as during tests that caused vasomotor changes without major variations in blood pressure (application of lower body negative pressure, passive leg raising). The average between-method discrepancy in the evaluation of blood pressure changes was never greater than 4.3 and 2.0 mm Hg for systolic and diastolic blood pressure, respectively; the corresponding standard deviations ranged between 4.6 and 1.6 mm Hg. Beat-to-beat computer analysis of blood pressure variability over the 30-minute rest period provided standard deviations almost identical when calculated by separate consideration of intra-arterial and finger blood pressure tracings (3.7 and 3.8 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Broadband spectral analysis of blood pressure and heart rate variability in very elderly subjects.

Systolic blood pressure (SBP) variability is increased and R-R interval variability is reduced in the elderly. Little is known, however, about how SBP and R-R interval variabilities change in the very elderly. More important, however, it is not known which frequency components of SBP and R-R interval variability are affected significantly. We addressed this issue in subjects older than 70 years by broadband spectral analysis, which allows all variability components from the lowest to the highest frequency to be considered. In 20 very elderly normotensive subjects (mean +/- SD age, 78.1 +/- 6.8 years) and 28 normotensive adult subjects (36.1 +/- 7.1 years), noninvasive finger blood pressure and R-R intervals were recorded continuously for 30 minutes in the supine position and 15 minutes in the upright position. SBP and R-R interval power spectral densities were computed over the entire frequency region between 0.005 Hz (0.007 Hz in the upright position) and 0.5 Hz. Overall SBP variability (SD) was greater and overall R-R interval variability was less in very old subjects than in adult subjects. All spectral R-R interval powers were reduced significantly in very elderly individuals. The spectral SBP powers were greater in the very elderly group than in the adult group only in the very-low-frequency range (<0.04 Hz). This was true in the supine and the standing positions. With subjects in the standing position, the shape of the broadband spectra differed in the very old and adult subjects because in the former group the increase in SBP and R-R interval power around 0.1 Hz that was seen in the latter was blunted. Therefore, in very elderly subjects a reduction in overall R-R interval variability is accounted for by a reduction in all of its frequency components. The accompanying increase in overall BP variability, however, results from a nonhomogeneous behavior of its frequency components, which consists of an increase in the very low frequency and a concomitant reduction in the higher frequency powers. The mechanisms responsible for these changes may be complex, but at least they may in part reflect the baroreflex impairment and autonomic dysfunction that characterize aging.

Continuous vs intermittent blood pressure measurements in estimating 24-hour average blood pressure.

In the past few years noninvasive automatic blood pressure (BP) recorders have been increasingly used to estimate patients' 24-hour BP more accurately than by one or few isolated measurements. However, these recorders only allow BP to be intermittently measured at intervals between 5 to 30 minutes, which means that the number of values collected over 24 hours (10 to 100) remains a tiny fraction of the thousands of values that occur during the same period. To determine whether this represents a limitation to this approach, BP was recorded intraarterially for 24 hours (Oxford method) in 20 ambulant hypertensive patients. A beat-to-beat analysis of the BP recording was provided by a computer, and the average 24-hour systolic, diastolic, and mean BP values were compared with those obtained by analyzing single BP waves of the same recording at intervals of 5, 10, 15, 30, and 60 minutes. In each subject the average 24-hour BP values obtained by the beat-to-beat analysis closely corresponded to those obtained by the analysis performed at 5-, 10-, 15-, or 30-minute intervals. In most subjects, this was the case also when the analysis was performed at 60-minute intervals. These findings demonstrate that intermittency of measurements does not limit the accurate assessment of true average BP. Indeed, accurate assessment can be achieved at intervals as much as 30 or 60 minutes apart.

Sympathectomy and cardiovascular spectral components in conscious normotensive rats.

We examined the extent to which sympathetic influences are reflected by spectral powers of blood pressure and pulse interval in specific frequency bands in spontaneously behaving Wistar-Kyoto rats subjected to continuous intraarterial blood pressure recording. The rats were pretreated with 6-hydroxydopamine (150 mg/kg twice in 1 week, n = 19) to produce chemical sympathectomy or received vehicle (n = 15). In the sympathectomized group, additional monitoring sessions were performed with rats under alpha-adrenergic receptor blockade with phenoxybenzamine (n = 8), beta-receptor blockade with propranolol (n = 7), or cholinergic receptor blockade with atropine (n = 8). Blood pressure signals were analyzed by a computer to calculate spectral powers (fast Fourier transform) in the low-frequency (0.025 to 0.1 Hz), mid-frequency (0.1 to 0.6 Hz), and high-frequency (0.8 to 3.0 Hz) bands. In sympathectomized rats, low-frequency power of blood pressure was 70% greater than in intact rats, whereas mid-frequency power was 60% smaller (P < .05 for both) and high-frequency power was unchanged. High-frequency power of pulse interval was also unchanged in sympathectomized rats, whereas low- and mid-frequency powers were reduced by approximately 50% (P < .05). No further alterations in spectral powers were observed by adding alpha- or beta-adrenergic blockade to sympathectomy, whereas adding cholinergic blockade caused a striking reduction in all pulse interval powers. Thus, mid-frequency blood pressure power depends on sympathetic but also to a substantial extent on nonsympathetic influences. Sympathetic influences do not contribute to low-frequency blood pressure power, having instead a restraining effect. The low- and mid-frequency pulse interval powers depend on both sympathetic and vagal influences. Thus, no blood pressure or pulse interval power in the mid- and low-frequency ranges can be regarded as a specific marker of sympathetic activity.

Beta-adrenergic blocking treatment and 24-hour baroreflex sensitivity in essential hypertensive patients.

We dynamically evaluated the effects of beta-blockade on the sensitivity of arterial baroreflex control of heart rate in 10 mild or moderate essential hypertensive patients in whom blood pressure was recorded intra-arterially for 24 hours in ambulatory conditions. Twenty-four-hour baroreflex sensitivity was assessed by both (1) a time-domain approach based on the calculation of the slope of the regression line between linearly related progressive increases in systolic blood pressure and pulse interval (+PI/+SBP sequences) and decreases in systolic blood pressure and pulse interval (-PI/-SBP sequences) and (2) a frequency-domain approach, ie, the ratio between the spectral powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha coefficient). Data were obtained before and after 1 month of administration of either acebutolol (n = 5) or labetalol (n = 5). Before treatment, the 24-hour average slopes of the +PI/+SBP and -PI/-SBP sequences were 4.36 +/- 0.32 and 4.05 +/- 0.27 ms/mm Hg, respectively, while the alpha coefficient was 7.78 +/- 0.7 ms/mm Hg. After beta-blockade, these values were increased by 25.3 +/- 6.8%, 25.0 +/- 8.0%, and 32.1 +/- 9.3%, respectively (P < .01 for all values). Thus, beta-blockers potentiate baroreflex sensitivity in daily life. Time-domain and frequency-domain methods yielded superimposable results in dynamically evaluating 24-hour baroreflex sensitivity and its changes after beta-blockade.

Spectral and sequence analysis of finger blood pressure variability. Comparison with analysis of intra-arterial recordings.

The aim of our study was to assess whether the Finapres device is able to accurately monitor not only average blood pressure values but also blood pressure variability. To examine this issue, we analyzed 30-minute recordings of finger and intra-arterial pressure simultaneously obtained at rest in 14 patients. We compared systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse interval (the reciprocal of heart rate), overall variability (standard deviation), and specific time-domain and frequency-domain components. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse interval spectral powers were computed by fast Fourier transform over three frequency bands: low frequency (0.025 to 0.07 Hz), midfrequency (0.07 to 0.14 Hz), and high frequency (0.14 to 0.35 Hz). The coherence, ie, the degree of association between blood pressure and pulse interval powers obtained by the two techniques, was also assessed. Standard deviations of diastolic blood pressure, mean arterial pressure, and pulse interval were similar when assessed from the two recordings, whereas standard deviation of systolic blood pressure was overestimated by analysis of finger pressure recordings. All powers of diastolic blood pressure and mean arterial pressure and high-frequency powers of systolic blood pressure estimated from analysis of finger blood pressure tracings were superimposable to those obtained by analyzing invasive recordings. Low-frequency and midfrequency powers of intra-arterial systolic blood pressure were significantly overestimated by the analysis of finger blood pressure tracings (+13.7 +/- 4.4 mm Hg2, P < .01, and +2.3 +/- 0.9 mm Hg2, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential spectral analysis of 24-hour blood pressure and pulse interval in humans.

Blood pressure and pulse interval are characterized not only by erratic variations but also by rhythmic fluctuations at low-, mid-, and high-frequency (0.025-0.07, 0.07-0.14, and 0.14-0.35 Hz, respectively). However, information on these phenomena has largely been derived from analysis of short-term recordings taken in standardized laboratory conditions. In seven normotensive and 10 untreated mild essential hypertensive subjects, power spectrum analysis was performed on the intra-arterial blood pressure and pulse interval signal collected over a 24-hour period using the fast Fourier transform algorithm and splitting the recording into contiguous segments of 256 beats. About 70% of the segments were suitable for the analysis; the segments excluded for a nonstationary signal amounted to only 30%. All powers were characterized by a high segment-to-segment variability, but in each subject the mid- and high-frequency powers of diastolic blood pressure and the mid-frequency power of systolic blood pressure were markedly reduced during the night as compared with the daytime period, whereas the opposite occurred for the low- and high-frequency powers of the pulse interval. Over the 24-hour period, mid- and high-frequency powers of blood pressure were positively correlated to each other, but both accounted for less than 25% of the 24-hour blood pressure variance. No difference between mean normalized power values of normotensive and hypertensive subjects was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial baroreflexes and blood pressure and heart rate variabilities in humans.

The factors responsible for 24-hour blood pressure and heart rate variabilities have never been clarified; however, studies performed in unanesthetized animals have shown an increase in blood pressure variability after sinoaortic denervation, and a negative relationship has been reported occasionally between blood pressure variability and baroreflex control of heart rate in humans. We have systematically investigated this issue in 82 ambulant hypertensive subjects using 24-hour intraarterial blood pressure recording (Oxford method) in which blood pressure and heart rate variabilities were measured by calculating the standard deviations of the values obtained throughout the 24 hours or during separate daytime and nighttime periods. Baroreflex sensitivity was assessed by the bradycardic or tachycardic responses to intravenous injections of phenylephrine or nitroglycerin and by the blood pressure response to changes in carotid transmural pressure obtained with a neck chamber. The sensitivity of the baroreceptor-heart rate reflex as assessed by the vasoactive drug technique showed a negative relationship with 24-hour blood pressure variability as well as with daytime and nighttime blood pressure variabilities measured separately (r = -0.28 to -0.50, p less than 0.05). These variabilities also correlated negatively with the sensitivity of the baroreceptor-blood pressure reflex as assessed by the neck chamber technique. By contrast, baroreflex sensitivity showed a positive correlation with heart rate variabilities (r = 0.32 to 0.47, p less than 0.05). The relationship between baroreflex sensitivity and blood pressure and heart rate variabilities was confirmed when the data were analyzed by multiple regression to adjust for blood pressure and age differences among the 82 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intra-arterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats in which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+PI/+SBP) or fell (-PI/-SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and -PI/-SBP sequences of 3 beats were found whereas the number of sequences of 4, 5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of +PI/+SBP (7.6 +/- 2.0 msec/mm Hg) and -PI/-SBP (6.4 +/- 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 +/- 4.7 and 62.6 +/- 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (-33.2% for +PI/+SBP and -31.7% for -PI/-SBP) and less steep in hypertensive subjects (-40.3 and -36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations in sensitivity due in part to hemodynamic, temporal, and behavioral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of blood pressure variability from 24-hour ambulatory finger blood pressure.

Portapres is a noninvasive, beat-to-beat finger blood pressure (BP) monitor that has been shown to accurately estimate 24-hour intra-arterial BP at normal and high BPs. However, no information is available on the ability of this device to accurately track ambulatory BP variability. In 20 ambulatory normotensive and hypertensive subjects, we measured 24-hour BP by Portapres and through a brachial artery catheter. BP and pulse interval variabilities were quantified by (1) the SDs of the mean values (overall variability) and (2) spectral power, computed either by fast Fourier transform and autoregressive modeling of segments of 120-second duration for spectral components from 0.025 to 0.50 Hz or in a very low frequency range (between 0.00003 and 0.01 Hz) by broadband spectral analysis. The 24-hour SD of systolic BP obtained from Portapres (24+/-2 mm Hg) was greater than that obtained intra-arterially (17+/-1 mm Hg, P<0.01), but the overestimation was less evident for diastolic (3+/-1 mm Hg, P<0.01) and mean (3+/-1 mm Hg, P<0.01) BP. The BP spectral power <0.15 Hz was also overestimated by Portapres more for systolic than for diastolic and mean BPs; similar findings were obtained by the fast Fourier transform, the autoregressive approach, and focusing on the broadband spectral analysis. BP spectral power >0.15 Hz obtained by the Portapres was similar during the day but lower during the night when compared with those obtained by intra-arterial recordings (P<0.01). No differences were observed between Portapres and intra-arterial recordings for any estimation of pulse interval variabilities. The overestimation of BP variability by Portapres remained constant over virtually the entire 24-hour recording period. Thus, although clinical studies are still needed to demonstrate the clinical relevance of finger BP variability, our study shows that Portapres can be used with little error to estimate 24-hour BP variabilities if diastolic and mean BPs are used. For systolic BP, the greater error can be minimized by using correction factors.

Potassium depletion and salt sensitivity in essential hypertension.

To evaluate the actual role of potassium depletion on blood pressure, 11 hypertensive patients were placed on a 10-day isocaloric diet providing a daily potassium intake of either 18 or 80 mmol, with each subject serving as his or her own control; the intake of sodium (220 mmol/day) and other minerals was kept constant. On day 11 each patient was also subjected to central volume expansion by water immersion associated with either normal or low potassium intake. After a 10-day period of low potassium intake, systolic blood pressure increased (P < 0.02) by 5 mm Hg, whereas serum potassium decreased (P < 0.001) by 0.9 mmol/L; no significant changes in urinary sodium and a marked increase in urinary calcium excretion (P < 0.001) were found during the 10-day low potassium intake. PRA (P < 0.02) and plasma aldosterone (P < 0.04) concentrations also decreased during low potassium intake in hypertensive patients. Even though an identical natriuretic response was found during the water immersion experiments with either high or low potassium in the whole hypertensive group, the evaluation of hypertensive subjects in relation to salt sensitivity enabled us to disclose pronounced differences in the natriuretic and calciuretic response. In fact, although an impaired natriuretic ability and moderate calcium loss were particularly found during water immersion in those hypertensive subjects exhibiting a lower salt sensitivity index, a predominant calcium depletion appeared to be the most important consequence of potassium depletion in the hypertensive subjects with a higher salt sensitivity index. By confirming that potassium depletion may exacerbate essential hypertension, our data also suggest that not only sodium restriction, but also potassium and calcium supplementation, could be particularly advisable in salt-sensitive hypertensive patients.

Oxidation products of polyamines induce mitochondrial uncoupling and cytochrome c release.

Spermine is shown to uncouple isolated mitochondria and to trigger the selective release of cytochrome c. Pargyline, an inhibitor of amine oxidase (AO), fully prevented these effects of spermine, which instead were potentiated by exogenous AO. Hydrogen peroxide, an oxidation product of spermine, mimicked the effects of spermine on mitochondria, while the addition of catalase prevented them. Spermidine and putrescine also caused mitochondrial uncoupling and triggered cytochrome c release, with a potency which correlated with the substrate preference of mitochondrial AO. Pargyline protected human lymphoma U937 cells against UVB-induced apoptosis, by reducing AO activity, mitochondrial uncoupling and cytochrome c release.

How to measure baroreflex sensitivity: from the cardiovascular laboratory to daily life.

Arterial baroreflex function in humans is commonly assessed through a number of laboratory tests based on quantification of the reflex responses in heart rate or blood pressure to external stimuli applied to the cardiovascular system. Evidence is available that these laboratory estimates of baroreflex sensitivity have both pathophysiological and clinical relevance. Indeed, a number of studies have shown that the sensitivity of the baroreceptor-heart rate reflex may have a prognostic value in myocardial infarction, heart failure and diabetic patients, where mortality seems to be inversely related to the sensitivity of cardiac baroreflex modulation. A deeper insight into the features of daily-life baroreflex cardiovascular control has been offered more recently by techniques based on computer analysis of spontaneous blood pressure and heart rate fluctuations. This innovative approach allows spontaneous baroreflex sensitivity to be assessed in real life conditions, with no need for external stimulation of the patient as required by the older laboratory techniques. This review will briefly survey the methods most widely used to assess baroreflex function in humans, in the laboratory and in daily life.