Effects of zoledronic acid and dexamethasone on early phases of socket healing after tooth extraction in rats: A preliminary macroscopic and microscopic quantitative study.

BACKGROUND: The exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is still unknown. The aim of this paper was to investigate the effects of zoledronic acid and dexamethasone on the early phases of socket healing in rats subjected to tooth extractions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into 2 groups: pharmacologically treated group (T, n=20) and non-pharmacologically treated group (C, n=10). T group rats received 0.1 mg/Kg of zoledronic acid (ZOL) and 1 mg/Kg of dexamethasone (DEX) three times a week for 10 consecutive weeks. C group rats were infused with vehicle. After 9 weeks from the first infusion, first maxillary molars were extracted in each of the rats. Quantitative macroscopic and microscopic analysis was performed to evaluate socket healing 8 days after extraction. RESULTS: Pharmacologically treated rats showed significant inhibition of bone remodeling. Connective tissue/alveolar bone ratio, osteoclast number and woven bone deposition were significantly reduced in group T compared to group C. Conversely, the proportion of necrotic bone was higher in group T compared to group C (0.8% and 0.3%, respectively. P=0.031). ZOL plus DEX do not cause gross effects on socket healing at a macroscopic level. CONCLUSIONS: Our findings confirmed that exposure to ZOL plus DEX impairs alveolar wound repair. Inhibition of osteoclastic resorption of socket walls after tooth extraction and the inability to dispose of the necrotic bone may be considered the initial steps of MRONJ onset.

Additional predictive value of nutritional status in the prognostic assessment of heart failure patients.

BACKGROUND AND AIMS: Nutritional status (NS) is not routinely assessed in HF. We sought to evaluate whether NS may be additive to a comprehensive pre-discharge evaluation based on a clinical score that includes BMI (MAGGIC) and on an index of functional capacity (six minute walking test, 6mWT) in HF patients. METHODS AND RESULTS: The CONUT (Controlling Nutritional Status) score (including serum albumin level, total cholesterol and lymphocyte count) was computed in 466 consecutive patients (mean age 61 ± 11 years, NYHA class 2.6 ± 0.6, LVEF 34 ± 11%, BMI 27.2 ± 4.5) who had pre-discharge MAGGIC and 6MWT. The endpoint was all-cause mortality. Mild or moderate undernourishment was present in 54% of patients with no differences across BMI strata. The 12-month event rate was 7.7%. Deceased patients had a more compromised NS (CONUT 2.8 ± 1.5 vs 1.7 ± 1.3, p < 0.0001), and a more advanced HF (MAGGIC 28.2 ± 6.0 vs 22.0 ± 6.6, p < 0.0001; 6MWT 311.1 ± 102.2 vs. 408.9 ± 95.9 m, p < 0.0001). The 12-month mortality rate varied from 4% for well-nourished to 11% for undernourished patients (p = 0.008). At univariate analysis, the CONUT was predictive for all-cause mortality with a Hazard Ratio of 1.701 [95% CI 1.363-2.122], p < 0.0001. Multivariable analysis showed that the CONUT significantly added to the combination of MAGGIC and 6MWT and improved predictive discrimination and risk classification (c-index 0.82 [95% CI 0.75-0.88], integrated discrimination improvement 0.028 [95% CI 0.015-0.081]). CONCLUSIONS: In HF patients assessment of NS, significantly improves prediction of 12-month mortality on top of the information provided by clinical evaluation and functional capacity and should be incorporated in the overall assessment of HF patients.

Diet, bite force and skull morphology in the generalist rodent morphotype.

For many vertebrate species, bite force plays an important functional role. Ecological characteristics of a species' niche, such as diet, are often associated with bite force. Previous evidence suggests a biomechanical trade-off between rodents specialized for gnawing, which feed mainly on seeds, and those specialized for chewing, which feed mainly on green vegetation. We tested the hypothesis that gnawers are stronger biters than chewers. We estimated bite force and measured skull and mandible shape and size in 63 genera of a major rodent radiation (the myomorph sigmodontines). Analysis of the influence of diet on bite force and morphology was made in a comparative framework. We then used phylogenetic path analysis to uncover the most probable causal relationships linking diet and bite force. Both granivores (gnawers) and herbivores (chewers) have a similar high bite force, leading us to reject the initial hypothesis. Path analysis reveals that bite force is more likely influenced by diet than the reverse causality. The absence of a trade-off between herbivores and granivores may be associated with the generalist nature of the myomorph condition seen in sigmodontine rodents. Both gnawing and chewing sigmodontines exhibit similar, intermediate phenotypes, at least compared to extreme gnawers (squirrels) and chewers (chinchillas). Only insectivorous rodents appear to be moving towards a different direction in the shape space, through some notable changes in morphology. In terms of diet, natural selection alters bite force through changes in size and shape, indicating that organisms adjust their bite force in tandem with changes in food items.

Clinical value of baroreflex sensitivity.

The arterial baroreflex is an important determinant of the neural regulation of the cardiovascular system. It has been recognised that baroreflex-mediated sympathoexcitation contributes to the development and progression of many cardiovascular disorders. Accordingly, the quantitative estimation of the arterial baroreceptor-heart rate reflex (baroreflex sensitivity, BRS), has been regarded as a synthetic index of neural regulation at the sinus atrial node. The evaluation of BRS has been shown to provide clinical and prognostic information in a variety of cardiovascular diseases, including myocardial infarction and heart failure that are reviewed in the present article.

Long-term time-course of nocturnal breathing disorders in heart failure patients.

Some important aspects of clinical manifestations of nocturnal breathing disorders in heart failure (HF) patients are still unknown. We questioned whether the severity of these disorders, first, is stable over time; secondly, shows any systematic trend; and, thirdly, can be predicted over time by a single baseline measurement. We studied 79 stable, optimally treated, moderate-to-severe HF patients who performed a monthly cardiorespiratory recording during 1-yr follow-up. According to their behaviour over time, nocturnal breathing disorders were classified as persistent, absent or occasional. During follow-up, clinically relevant breathing disorders were persistent in approximately 50% of the patients, absent in <20% and occasional in approximately 30%. Increasing/decreasing trends were rarely observed. The positive and negative predictive value of baseline measurement for persistent behaviour over time ranged, respectively, from 71% to 91% and from 91% to 95%, depending on different levels of severity of breathing disorders. A large portion of HF patients experience persistent clinically significant nocturnal breathing disorders over long periods of time. Breathing disorders occur irregularly in about one-third of the patients and are negligible in a minority of them. Rarely do they show a steady increase or decrease over time. A single baseline recording predicts a persistent behaviour with moderate-to-high accuracy.

Efficacy of Osteopathic Manipulative Treatment on postural control in Parkinsonian patients with Pisa syndrome: A pilot randomized placebo-controlled trial.

BACKGROUND: Pisa syndrome (PS) is a clinical condition frequently associated with Parkinson's disease (PD). It is characterized by a trunk lateral flexion higher than 10 degrees and reversible when lying. One pathophysiological hypothesis is the altered verticality perception, due to a somatosensory impairment. Osteopathic Manipulative Treatment (OMT) manages fascial-system alterations, linked to somatic dysfunctions. Fascial system showed to be implicated in proprioceptive sensibility. OBJECTIVE: The aim of the study was to assess OMT efficacy on postural control in PD-PS patients by stabilometry. METHODS: In this single-blinded trial we studied 24 PD-PS patients, 12 of whom were randomly assigned to receive a multidisciplinary physical therapy protocol (MIRT) and sham OMT, while the other 12 received four OMT plus MIRT, for one month. The primary endpoint was the eye closed sway area assessment after the intervention. Evaluation of trunk lateral flexion (TLF) with DIERS formetrics was also performed. RESULTS: At one month, the sway area of the OMT group significantly decreased compared to placebo (mean delta OMT - 326.00±491.24 mm2, p = 0.01). In the experimental group TLF showed a mean inclination reduction of 3.33 degrees after treatment (p = 0.044, mean d = 0.54). Moreover, a significant positive association between delta ECSA and delta TLF was observed (p = 0.04, r = 0.46). DISCUSSION: Among PD-PS patients, MIRT plus OMT showed preliminary evidence of postural control and TLF improvement, compared to the control group.

Effectiveness of Rotigotine plus intensive and goal-based rehabilitation versus Rotigotine alone in "de-novo" Parkinsonian subjects: a randomized controlled trial with 18-month follow-up.

BACKGROUND: Dopamine Replacement Therapy (DRT) represents the most effective treatment for Parkinson's disease (PD). Nevertheless, several symptoms are unresponsive to treatment and its long-term use leads to serious side effects. To optimize the pharmacological management of PD, dopamine-agonists are often prescribed to "de-novo" patients. Moreover, several studies have shown the effectiveness and the synergic effect of rehabilitation in treating PD. OBJECTIVE: To evaluate the synergism between DRT and rehabilitation in treating PD, by investigating the short and the long-term effectiveness of a multidisciplinary, intensive and goal-based rehabilitation treatment (MIRT) in a group of patients treated with Rotigotine. MATERIALS AND METHODS: In this multicenter, single blinded, parallel-group, 1:1 allocation ratio, randomized, non-inferiority trial, 36 "de-novo" PD patients were evaluated along 18 months: 17 were treated with Rotigotine plus MIRT; 19 were treated with Rotigotine alone (R). The primary outcome measure was the total score of Unified Parkinson's Disease Rating Scale (UPDRS). The secondary outcomes included the UPDRS sub-sections II and III (UPDRS II-III), the 6-Minute Walk Test (6MWT), the Timed Up and Go Test (TUG) and the amount of Rotigotine. Patients were evaluated at baseline (T0), 6 months (T1), 1 year (T2), and at 18 months (T3). RESULTS: No differences in UPDRS scores in the two groups (total score, III part and II part, p = 0.48, p = 0.90 and p = 0.40, respectively) were found in the time course. Conversely, a greater improvement in Rotigotine + MIRT group was observed for 6MWT (p < 0.0001) and TUG (p = 0.03). Along time, the dosage of Rotigotine was higher in patients who did not undergo MIRT, at all observation times following T0. CONCLUSIONS: Over the course of 18 months, the effectiveness of the combined treatment (Rotigotine + MIRT) on the patients' global clinical status, evaluated with total UPDRS, was not inferior to that of the pharmacological treatment with Rotigotine alone. Importantly, rehabilitation allowed patients to gain better motor performances with lower DRT dosage.

Correction to: Effectiveness of Rotigotine plus intensive and goal­based rehabilitation versus Rotigotine alone in "de­novo" Parkinsonian subjects: a randomized controlled trial with 18­month follow­up.

The original version of this article unfortunately contained a mistake. The funding information was incorrect. The corrected funding information is given below.

[Function recovery in patients with knee arthroplasty: role of proprioceptive rehabilitation]. / Il recupero funzionale del ginocchio artroprotesizzato: ruolo dell'allenamento propriocettivo.

This study evaluates the outcome of proprioceptive rehabilitation in 18 patients who underwent knee joint prosthetic replacement using the dynamic electronic plate Pro-kin_machine. The proprioceptive performance was determined by having the patients trace a set of three outlines (horizontal, vertical and circular) using the foot of the operated limb. The measures of outcome parameters were: 1) time taken to do the test; 2) score of accuracy of the test measured in percentage. Tests were performed on admission, half way through rehabilitation and on discharge. Each patient had 15 sittings of physiotherapy. Our results demonstrate a significant improvement of both parameters at the end of the treatment. After prosthetic knee joint replacement, not only is it important to re-establish mechanical stability but also dynamic stability. The latter can be achieved through active virtual taping by the stabilizer muscles. Prompt management of instability of the joint in the rehabilitation phase is extremely important in the re-activating of the control mechanisms that are compromised by the surgical operation.

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure.

OBJECTIVES: The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV). BACKGROUND: In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited. METHODS: Nineteen consecutive patients with moderate, stable CHF (age 54 +/- 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 +/- 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age +/- 3 years, same NYHA class, LVEF +/- 3%, pulmonary wedge pressure +/- 3 mm Hg, peak volume of oxygen +/- 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months. RESULTS: Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 +/- 0.4 vs. 1.8 +/- 0.5, p < 0.01), systolic and diastolic function (LVEF 23 +/- 7 vs. 28 +/- 9%, p < 0.01; pulmonary wedge pressure 17 +/- 8 vs. 14 +/- 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 +/- 5.1 vs. 3.6 +/- 3.0 cm2, p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 +/- 3.4 to 7.1 +/- 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 +/- 113 to 894 +/- 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 +/- 17 to 80 +/- 28 ms and from 12 +/- 7 to 18 +/- 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 +/- 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade. CONCLUSIONS: Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.

Assessing baroreflex sensitivity in post-myocardial infarction patients: comparison of spectral and phenylephrine techniques.

OBJECTIVES: This study sought to compare, in post-myocardial infarction patients, baroreflex sensitivity (BRS) measured by the phenylephrine method (Phe-BRS) with that estimated by the Robbe (Robbe-BRS) and Pagani (alpha-low frequency [LF] and alpha-high frequency [HF]) spectral techniques. BACKGROUND: BRS assessed by Phe-BRS has been shown to be of prognostic value in patients with a previous myocardial infarction, but the need for drug injection limits the use of this technique. Several noninvasive methods based on spectral analysis of systolic arterial pressure and heart period have been proposed, but their agreement with Phe-BRS has never been investigated in post-myocardial infarction patients. METHODS: The linear association and the agreement between each spectral measurement and Phe-BRS were assessed by correlation analysis and by computing the relative bias and the limits of agreement in 51 post-myocardial infarction patients. RESULTS: The correlation with Phe-BRS was r = 0.63 for Robbe-BRS, r = 0.62 for alpha-LF and r = 0.59 for alpha-HF. The relative bias was significant for alpha-LF (2.6 ms/mm Hg, p < 0.001) and alpha-HF (2.5 ms/mm Hg, p = 0.01) and not significant (-0.6 ms/mm Hg, p = 0.3) for Robbe-BRS. The normalized limits of agreement ranged from -98% to 95% for Robbe-BRS, from -67% to 126% for alpha-LF and from -108% to 143% for alpha-HF. When patients were classified according to left ventricular ejection fraction (LVEF, cutoff value 40%), the relative bias was higher in patients with a depressed LVEF, although statistical significance was high only for Robbe-BRS and was borderline for alpha-LF. The limits of agreement were similar in both groups of patients (p > 0.3). CONCLUSIONS: Despite a substantial linear association, the agreement between spectral measurements and Phe-BRS in post-myocardial infarction patients is weak because the difference can be as large as the BRS value being estimated. Phe-BRS is the measurement most associated with hemodynamic impairment. Because several factors within each method contribute to the overall difference, neither method can be defined as being better than the other in estimating baroreflex gain, nor can one be used as an alternative to the other. Ad hoc studies are needed to assess which method provides the most useful physiologic or pathophysiologic information or the most accurate prediction of prognosis.

Echo-Doppler mitral flow monitoring: an operative tool to evaluate day-to-day tolerance to and effectiveness of beta-adrenergic blocking agent therapy in patients with chronic heart failure.

OBJECTIVES: The goals of this study were: 1) to assess the predictive value of baseline mitral flow pattern (MFP) and its changes after loading manipulations as regards tolerance to and effectiveness of beta-adrenergic blocking agent treatment in patients with chronic heart failure (CHF); and 2) to analyze the prognostic implications of chronic MFP modifications after beta-blocker treatment. BACKGROUND: In patients with CHF, carvedilol therapy induces clinical and hemodynamic improvements. Individual management, clinical effectiveness and prognostic implications, however, remain unclear. The MFP changes induced by loading manipulations provide independent prognostic information. METHODS: Echo-Doppler was performed at baseline and after loading manipulations in 116 consecutive patients with CHF (left ventricular ejection fraction: 25 +/- 7%); 54 patients with a baseline restrictive MFP were given nitroprusside infusion; 62 patients with a baseline nonrestrictive MFP performed passive leg lifting. According to changes in MFP, we identified four groups: 17 with irreversible restrictive MFP (Irr-rMFP), 37 with reversible restrictive MFP (Rev-rMFP), 12 with unstable nonrestrictive MFP (Un-nrMFP) and 50 with stable nonrestrictive MFP (Sta-nrMFP). Carvedilol therapy (44 +/- 27 mg) was administered blind to results of loading maneuvers. After six months, MFP was reassessed and patients reclassified according to chronic MFP changes. During follow-up, tolerance to and effectiveness of treatment and major cardiac events (death, readmission and urgent transplantation) were considered. RESULTS: Changes of MFP after loading manipulations were more accurate than baseline MFP in predicting both tolerance to (p < 0.01) and effectiveness of (p < 0.05) carvedilol. After 26 +/- 14 months of follow-up, cardiac events had occurred in 23/102 patients (23%). The event rate in patients with chronic Irr-rMFP or Un-nrMFP was markedly higher than it was in those with Rev-rMFP or Sta-nrMFP. CONCLUSIONS: In our patients, tolerance to and effectiveness of carvedilol was predicted better by echo-Doppler MFP changes after loading manipulations than by baseline MFP. Chronic changes of MFP after therapy are strong predictors of major cardiac events.

Noninvasive measurement of blood pressure variability: accuracy of the Finometer monitor and comparison with the Finapres device.

To assess the accuracy of spectral indices of arterial pressure variability and baroreflex sensitivity obtained from beat-by-beat noninvasive blood pressure recordings by the Finometer device, we compared these measures with those obtained from intra-arterial recordings. The performance of the Finometer was also compared to the traditional Finapres device. In 19 cardiac disease patients, including myocardial infarction, heart failure and cardiac transplant, we estimated the power of systolic and diastolic pressures in the VLF (0.01-0.04 Hz), LF (0.04-0.15 Hz) and HF (0.15-0.45 Hz) bands and computed absolute and percentage errors relative to intra-arterial brachial pressure. We also computed the characteristic frequency of each band (i.e. the barycentric frequency of spectral components identified in the band). The variability of systolic pressure in the VLF and LF bands was markedly overestimated by both the Finometer and Finapres (p < 0.01), with percentage median errors of respectively 130% and 103% (Finometer), and 134% and 78% (Finapres). The HF power was substantially unchanged using the Finometer and reduced using the Finapres (-28%, p < 0.05). The limits of agreement between noninvasive and invasive spectral measurements were wide. Linear system analysis showed that most (>80%) of the power of noninvasive signals was linearly related to the power of the invasive signal. The characteristic frequency of each band was substantially preserved in both noninvasive signals. The results for diastolic pressure were similar, but the Finapres errors in the VLF and LF bands were lower. Baroreflex sensitivity was significantly underestimated by both devices (Finometer: -31%, Finapres: -24%). Despite previous studies having shown that brachial artery waveform reconstruction performed by the Finometer has improved the accuracy of blood pressure measurement compared to the Finapres device, measurement of blood pressure variability in cardiac disease patients provides worse results in most spectral parameters and a better accuracy only in the HF band of systolic pressure.

Leave-one-out prediction error of systolic arterial pressure time series under paced breathing.

In this paper, we consider systolic arterial pressure time series from healthy subjects and chronic heart failure patients, undergoing paced respiration, and show that different physiological states and pathological conditions may be characterized in terms of predictability of time series signals from the underlying biological system. We model time series by the regularized least-squares approach and quantify predictability by the leave-one-out error. We find that the entrainment mechanism connected to paced breath, that renders the arterial blood pressure signal more regular and thus more predictable, is less effective in patients, and this effect correlates with the seriousness of the heart failure. Using a Gaussian kernel, so that all orders of nonlinearity are taken into account, the leave-one-out error separates controls from patients (probability less than 10(-7)), and alive patients from patients for whom cardiac death occurred (probability less than 0.01).

Ontogenetic allometry in the foot size of Oligoryzomys flavescens (Waterhouse, 1837) (Rodentia, Sigmodontinae).

Ontogenetic allometry is the study of how the size or shape of certain structures changes over the course of an animal's development. In this study, using Huxley's formula of allometric growth (1932), we assessed the changes in the rate of growth of the feet size of the sigmodontine rodent Oligoryzomys flavescens during its ontogeny and compared differences between males and females. We find evidence of a change of polarity during the ontogenetic development of the species, with the presence of positive allometry during pregnancy and negative allometry in adulthood. Moreover, we note the presence of sexual dimorphism in the size of the feet, in which males of the species have a higher rate of growth than females. This growth pattern is positively related to escape from predators in childhood in both sexes and, in adulthood, provides a higher encounter rate of females by males, due to the larger displacement of the latter. We suggest that both the forces of natural selection and sexual selection have acted to shape the evolution of foot size in this species.

Crossover versus Stabilometric Platform for the Treatment of Balance Dysfunction in Parkinson's Disease: A Randomized Study.

Balance dysfunctions are a major challenge in the treatment of Parkinson's disease (PD). Previous studies have shown that rehabilitation can play a role in their treatment. In this study, we have compared the efficacy of two different devices for balance training: stabilometric platform and crossover. We have enrolled 60 PD patients randomly assigned to two groups. The first one (stabilometric group) performed a 4-week cycle of balance training, using the stabilometric platform, whereas the second one (crossover group) performed a 4-week cycle of balance training, using the crossover. The outcome measures used were Unified Parkinson's Disease Rating Scale (UPDRS) part II, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Six Minutes Walking Test (6MWT). Results showed that TUG, BBS, and UPDRS II improved in both groups. There was not difference in the efficacy of the two balance treatments. Patients in both groups improved also the meters walked in the 6MWT at the end of rehabilitation, but the improvement was better for patients performing crossover training. Our results show that the crossover and the stabilometric platform have the same effect on balance dysfunction of Parkinsonian patients, while crossover gets better results on the walking capacity.

Angiotensin II type 1 receptor blockade prevents cardiac remodeling in bradykinin B(2) receptor knockout mice.

Knockout mice (B(2)(-/-)) lacking the bradykinin (BK) B(2) receptor gene develop mild hypertension, cardiac hypertrophy, and myocardial damage. We hypothesized that these effects are due to the hypertrophying and damaging actions of angiotensin II (Ang II) in the absence of the balancing protection of BK. To verify this hypothesis, B(2)(-/-) or wild-type mice (B(2)(+/+)) were administered a nonpeptide antagonist of Ang II type 1 (AT(1)) receptors (A81988) from conception through 180 days of age. Untreated B(2)(+/+) and B(2)(-/-) served as controls. Blood pressure (BP) and heart rate were monitored with the use of tail-cuff plethysmography at regular intervals. Ventricular weights, diameters, wall thickness, chamber volume, and myocardial fibrosis were measured at 40 and 180 days. No differences were observed in BP, heart rate, and cardiac weight and dimensions between treated and untreated B(2)(+/+). The BP of AT(1) antagonist-treated B(2)(-/-) was reduced until 70 days; then, it increased to the levels found in untreated B(2)(-/-). AT(1) receptor blockade resulted in a reduction in left ventricular mass, chamber volume, and wall thickness and abrogated myocardial fibrosis in B(2)(-/-). These results indicate that Ang II is the major factor responsible for ventricular remodeling and myocardial damage in mice with disruption of BK B(2) receptor signaling. The interaction of Ang II and BK appears to be essential for the development of a normal heart.

Association between hemodynamic impairment and Cheyne-Stokes respiration and periodic breathing in chronic stable congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Irregular breathing occurs frequently in patients with congestive heart failure (CHF) both during daytime and nighttime. Many factors are involved in the genesis of these breathing abnormalities, but the role of the hemodynamic impairment remains controversial. This study investigated the relation between worsening ventricular function and the frequency of respiratory disorders in patients with mild to severe CHF. One hundred fifty patients with CHF (mean age 53 +/- 8 years, left ventricular (LV) ejection fraction 26 +/- 7, in New York Heart Association [NYHA] classes II to IV, and who underwent stable therapy for > or =2 weeks) were studied. Analysis of instantaneous lung volume signal and arterial oxygen saturation during awake daytime revealed a normal respiratory pattern in 63 patients, whereas 87 had a persistent alteration of breathing, with a typical Cheyne-Stokes respiration (CSR) in 42 and periodic breathing (PB [oscillation of tidal volumes without apnea]) in 45 patients. Patients with PB and CSR showed a more pronounced hemodynamic impairment with a significantly reduced cardiac index, an increased pulmonary arterial wedge pressure, and a longer lung-to-ear circulation time (LECT) compared with patients with normal respiratory patterns. In a logistic regression model that included all of the variables significantly associated with breathing disorders, cardiac index and LECT emerged as the major determinants of CSR. In those patients with LECT > or =30 seconds (upper quartile) and cardiac index < or =1.9 L/min/m2 (lower quartiles), the incidence of CSR was significantly higher (69%) than in patients with lower LECT and higher cardiac index (14%, p <0.001). In conclusion, abnormalities of breathing activity during daytime are significantly associated with a prolonged circulation time and a more severe impairment of systolic and diastolic LV indexes.

The development of hyperventilation in patients with chronic heart failure and Cheyne-Strokes respiration: a possible role of chronic hypoxia.

AIM: To analyze the relationship between daytime respiratory and cardiac function in patients with compensated chronic heart failure (CHF) with and without periodic breathing (PB) or Cheyne-Stokes respiration (CSR). PATIENTS: We studied 132 patients (female, 13%; mean age, 53+/-8 years; body mass index, 25.9+/-3.5 kg/m2; left ventricular ejection fraction <40%; 23% in New York Heart Association class I, 43% in class II, and 34% in class III-IV). METHODS: Measurement of pulmonary function and blood gases, hemodynamic evaluation, analysis of breathing profile, echocardiography, recording of ECG, beat-to-beat arterial oxygen saturation, and respiration during spontaneous breathing. RESULTS: Fifty-eight percent of patients showed PB or CSR. Patients with PB or CSR have greater cardiac function impairment. Mean values of lung volumes and PaO2 were similar in the three groups of patients considered. In contrast, patients with PB or CSR had an increased minute ventilation and reduced PaCO2 values. Interestingly, patients with PB or CSR had lower values of arterial content of O2 and systemic oxygen transport (SOT) than patients with a normal breathing pattern (SOT, 394+/-9.8, 347+/-9.6, 438+/-11 mL of O2/min/m2, respectively; analysis of variance p<0.001). Weak correlations were found among lung volumes, blood gases, and cardiac function parameters: ie, vital capacity was correlated inversely with pulmonary capillary wedge pressure (PCWP) (-0.25; p<0.05); PaCO2 with PCWP (r=0.26; p<0.05), lung-to-ear circulation time (LECT) (r=-0.4; p<0.05), SOT (r=-0.33; p<0.0001), and cardiac index (CI) (r=0.27; p=0.003). Multiple regression analyses showed that arterial PCO2 was significantly correlated with SOT, LECT, and CI (r=0.51; r2=0.26; p<0.000001); the correlation became stronger considering only CSR patients (r=0.64; r2=0.4; p<0.001). CONCLUSIONS: Our study shows that patients with daytime breathing disorders have chronic hypocapnia. A reduced SOT may be one of the stimuli determining increased minute ventilation in these patients.