Biomedical subjects

R Colombo

Publications and source records attributed to R Colombo.

At least 19 recordsLinked to original sources

PubMed1999

Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.

BACKGROUND: Nocturnal Cheyne-Stokes respiration (CSR) occurs frequently in patients with chronic heart failure (CHF), and it may be associated with sympathetic activation. The aim of the present study was to evaluate whether CSR could affect prognosis in patients with CHF. METHODS AND RESULTS: Sixty-two CHF patients with left ventricular ejection fraction </=35%, in NYHA class II to III, underwent clinical evaluation, Doppler echocardiography, ergospirometry, phenylephrine test, Holter recording, and a sleep study to evaluate the occurrence of CSR, expressed as percentage of periodic breathing, and apnea/hypopnea index (AHI) (ie, the number of apneas and hypopneas per hour of recording). During a mean follow-up of 28+/-13 months, 15 patients died of cardiac causes. Nonsurvivors were in a higher NYHA functional class than survivors (P<0.001) and had a more depressed left ventricular ejection fraction (P<0.03), a shorter deceleration time of early filling (P<0. 05), larger left and right atria (P<0.05 and P<0.02, respectively) and a lower peak V(O2) (P<0.05). Nonsurvivors also spent a greater percentage of the night in periodic breathing (P<0.01) with a greater AHI (P<0.03) and showed lower values of diurnal baroreflex sensitivity (P<0.05) and of heart rate variability (sdNN: P<0.01). Multivariate analysis revealed the AHI (chi2, 10.4; P<0.01), followed by left atrial area (chi2, 5.7; P<0.01), as the only independent and additional predictors of subsequent cardiac death. Patients at very high risk for fatal outcome could be identified by an AHI >/=30/h and left atria >/=25 cm2. CONCLUSIONS: The AHI is a powerful independent predictor of poor prognosis in clinically stable patients with CHF. The presence of an AHI >/=30/h adds prognostic information compared with other clinical, echocardiographic, and autonomic data and identifies patients at very high risk for subsequent cardiac death.

Aged↗

PubMed1999

The assembly of Ni2+-actin: some peculiarities.

Nickel alters the organisation of highly dynamic cytoskeletal elements. In cultured cells Ni2+ causes microtubule aggregation and bundling as well as microfilament aggregation and redistribution. Here, we have analysed the effect(s) of Ni2+ on in vitro actin polymerisation. Using limited proteolysis by trypsin we have suggested that the regions around Arg-62 and Lys-68 change their conformation following Ni2+ binding to the single high-affinity site for divalent cations in the G-actin molecule. We have found that Ni2+ shortens the lag phase of actin polymerisation and increases the rate of assembly mainly because of an increased elongation rate. Ni2+ has no significant effect on the final plateau of actin polymerisation nor on the actin critical concentration. Electron microscopy revealed that actin filaments polymerised by 2 mM Ni2+ showed some tendency to lateral aggregation, being frequently formed by the cohesion of two or three filaments. Furthermore, they often appeared shorter than those of control as also confirmed by the larger amount of free filament ends as well as the faster depolymerisation rate than control.

Actins↗

PubMed1998

Effect of replacement of the tightly bound Ca2+ by Ba2+ on actin polymerization.

G-actin has a single tight-binding (high-affinity) site for divalent cations per mole of protein, whose occupancy is important for the stability of the molecule. Different tightly bound divalent cations differently influence the polymerization properties of actin. The tightly bound metal ion easily exchanges for free exogenous cations. Moreover, biochemical and structural evidence demonstrates that actin, in both the G- and F-forms, assumes different conformations depending on the metal ion bound with high affinity in the cleft between two main domains of the molecule. In this work, we used proteolytic susceptibility to detect possible local conformational alterations of the actin molecule following a brief incubation of Ca-G-actin with barium chloride and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. We found that substitution of Ba2+ for the tightly bound Ca2+ affects the regions around Arg-62 and Lys-68 in subdomain 2 of G-actin, as judged from inhibition of tryptic cleavage at these residues. Using the fluorescent chelator Quin-2, we observed that about 0.95 mol of Ba2+ is released per 1 mol of actin. We also examined the effect of replacement of the tightly bound Ca2+ by Ba2+ on actin polymerization. With respect to Ca-actin, Ba-actin shows an increased polymerization rate, mainly due to its enhanced nucleation and a higher critical concentration.

Actins↗

PubMed1998

Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon.

OBJECTIVE: The aims of this study were to determine the relationships between oscillations in systolic blood pressure and heart period at different breathing frequencies and to investigate the role of sympathetic contribution to this relationship. METHODS: Fourteen healthy volunteers underwent three randomized periods of controlled breathing at 6, 10 and 16 breaths/min. ECG (RR), respiratory signal (RESP) and systolic blood pressure (SBP) were continuously recorded. The component of RR and SBP oscillations related to respiration (RRResp and SBPResp) was defined by means of uni- and bivariate spectral analysis. The squared coherence (K2) and phase between RR and RESP, and RR and SBP (RR-SBP) were also assessed. When the K2 of RR-SBP in the respiratory band was > 0.5, we considered the phase and calculated the closed-loop gain between the two signals. Seven subjects were also studied after chronic metoprolol treatment. RESULTS: Although the mean values of RR and SBP did not differ between the three periods of breathing, the higher the respiratory rate, the smaller the RRResp and SBPResp. The phase was always negative (SBPResp changes preceded RRResp changes), thus suggesting a baroreflex link. The higher the respiratory rate, the lower the gain and phase. Pharmacological beta-adrenoceptor blockade increased the gain and shifted the phase, but the relationships found at baseline between the respiratory rate and both the gain and phase remained unchanged. CONCLUSIONS: The effect of breath rate on the relationship between heart rate and systolic pressure variabilities is a frequency-dependent phenomenon that is also independent of the sympathetic drive.

Adrenergic beta-Antagonists↗

PubMed1998

Effects of hydrophilic and lipophilic beta-blockers on heart rate variability and baroreflex sensitivity in normal subjects.

To evaluate the effect of a hydrophilic and a lipophilic beta-blocker on the autonomic nervous system, 20 normal subjects were studied under baseline conditions and 7 days after being randomly assigned to metoprolol (200 mg/day), nadolol (80 mg/day), and placebo. Under each condition, the time-domain parameters were analyzed by means of 24-hour ECG monitoring and the frequency-domain parameters by means of the autoregressive method using 10-minute ECGs during rest, controlled respiration, and after a head-up tilt test. The alpha index (the gain in the relationship between the RR period and systolic arterial pressure variability) was also calculated. Both nadolol and metoprolol significantly increased all of the time-domain parameters except the standard deviation of the RH intervals; they also modified the frequency-domain parameters. Both blunted the significant reduction in the high frequency (HF) component and alpha index during tilt. In normal subjects, hydrophilic and lipophilic beta-blockers similarly modify the time- and frequency-domain parameters that are particularly evident when high sympathetic tone is present (during daytime and tilt). The value of the alpha index was increased by both beta-blockers in the HF, but not in the low frequency band; this difference might be due to the fact that the former is a measure of the vagal component of the baroreflex control and the latter a measure of the sympathetic component. The effects of hydrophilic and lipophilic beta-blockers on the time- and frequency-domain parameters of heart rate variability are similar.

Adrenergic beta-Antagonists↗

PubMed1998

Different trends of changes in heart rate variability in patients with anterior and inferior acute myocardial infarction.

Modifications in heart rate variability (HRV) parameters occur after acute myocardial infarction. The aim of this study was to evaluate the trend of HRV change during the acute phase and the first month after myocardial infarction, and establish whether they were affected by the anterior or inferior location of the infarction. The time-domain HRV measures of 59 patients with a first uncomplicated acute myocardial infarction were computed from 24-hour ECG recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and the root mean square successive difference of NN intervals (RMSSD) were lower in the patients with anterior myocardial infarction. Although the parameters were similar in all of the patients at day 28, their behavior over time was different (P = 0.01): the SDNN in the patients with inferior myocardial infarction had decreased to the values found in anterior myocardial infarction patients by day 2 but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had diminished in both groups by day 2, but at day 10, had increased in the patients with anterior, but not in those with inferior myocardial infarction. These findings suggest that (1) in the very early phase of myocardial infarction, HRV is different in the two locations, (2) during the first hours of myocardial infarction patients with inferior location showed a greater vagal activity than patients with anterior location that became lower at day 10, and (3) the recovery of HRV is an early phenomenon in both groups, being already evident by the second week after myocardial infarction.

Case-Control Studies↗

PubMed1998

G-actin conformational change and polymerization induced by paraquat.

Paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride) is a broad-spectrum herbicide that is highly toxic to animals (including man), the major lesion being in the lung. In mammalian cells, paraquat causes deep alterations in the organization of the cytoskeleton, marked decreases in cytoskeletal protein synthesis, and alterations in cytoskeletal protein composition; therefore, the involvement of the cytoskeleton in cell injury by paraquat was suggested. We previously demonstrated that monomeric actin binds paraquat; moreover, prolonged actin exposure to paraquat, in depolymerizing medium, induces the formation of actin aggregates, which are built up by F-actin. In this work we have shown that the addition of paraquat to monomeric actin results in a strong quenching of Trp-79 and Trp-86 fluorescence. Trypsin digestion experiments demonstrated that the sequence 61-69 on actin subdomain 2 undergoes paraquat-dependent conformational changes. These paraquat-induced structural changes render actin unable to completely inhibit DNase I. By using intermolecular cross-linking to characterize oligomeric species formed during paraquat-induced actin assembly, we found that the herbicide causes the formation of actin oligomers characterized by subunit-subunit contacts like those occurring in oligomers induced by polymerizing salts (i.e., between subdomain 1 on one actin subunit and subdomain 4 on the adjacent subunit). Furthermore, the oligomerization of G-actin induced by paraquat is paralleled by ATP hydrolysis.

Actins↗

PubMed1998

Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors.

PURPOSE: The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study. MATERIALS AND METHODS: A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system, based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas. RESULTS: After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved. CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.

Administration, Intravesical↗

PubMed1997

Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure.

BACKGROUND: The precise mechanisms responsible for the sympathetic overactivity and blunted baroreflex control in chronic heart failure (CHF) remain obscure. Augmented peripheral chemosensitivity has recently been demonstrated in CHF. We evaluated the relation between peripheral chemoreflex sensitivity and autonomic activity in patients with CHF. METHODS AND RESULTS: We studied in 26 stable patients with CHF the peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalations of pure nitrogen), autonomic balance (spectral analysis of heart rate variability [HRV]), and baroreflex sensitivity (bolus phenylephrine method and alpha index). To determine whether transient inactivation of peripheral chemoreceptors might influence autonomic balance, 12 patients underwent a second study during which they breathed 100% O2. Peripheral chemosensitivity correlated inversely with HRV power within the low-frequency band (0.04 to 0.15 Hz) (r=-.52, P=.006) and inversely with baroreflex sensitivity (r=-.60, P=.005). When the patients were divided into two groups according to the chemosensitivity of age-matched normal controls (above and below mean+2 SDs of chemosensitivity of control subjects), those above the normal range revealed more impaired autonomic balance, ie, lower baroreflex sensitivity (1.4 +/- 1.3 versus 5.0 +/- 1.5 ms/mm Hg, P<.0001) and depressed values of low-frequency power (2.5 +/- 1.8 versus 4.1 +/- 0.8 ln ms2, P<.005) compared with those with normal chemosensitivity. Transient hyperoxia did not alter heart rate or systolic pressure but resulted in an increase in HRV and an improvement in baroreflex sensitivity. CONCLUSIONS: A link between increased peripheral chemosensitivity and impaired autonomic control, including baroreflex inhibition, is demonstrated. The clinical importance of this phenomenon warrants further investigation.

Aged↗

PubMed1997

Actin assembly by cadmium ions.

Cadmium is a highly toxic metal entering cells by a variety of mechanisms. Its toxic action is far from being completely understood, although specific interaction with the cellular calcium metabolism has been indicated. Metal ions that influence intracellular Ca2+ concentrations or compete with Ca2+ for protein binding sites may exert an effect on actin filaments, whose assembly and disassembly are both regulated by a number of calcium-dependent factors. Cadmium is such a metal. Much evidence demonstrates that cadmium interferes with the dynamics of actin filaments in various types of cells. Here we show that, at high (0.8-1.0 mM) concentrations, CdCl2 causes actin denaturation. At such Cd2+ concentrations, actin precipitates (really actin, as shown by SDS-PAGE, see Fig. 1B) in the form of irregular, disordered clots, clearly appreciable by electron microscopy. Denaturation seems to be reversible since, after Cd2+ removal by dialysis, the polymerizability of sedimented actin is restored almost completely. On the other hand, at concentrations ranging from 0.25 to 0.6 mM, CdCl2 is more effective as an actin polymerizing agent than both MgCl2 and CaCl2. The Cd-related increase in the actin assembly rate is ascribable to an enhanced nucleation rather than to an increased monomer addition to filament growing ends. The latter, in contrast, appears quite slow. Critical concentration measurements revealed that the extent of polymerization of both Mg- and Cd-assembled actin are very close (C(c) ranges from 0.25 to 0.5 microM), while Ca-polymerized actin shows a polymerization extent markedly lower (C(c) = 4.0 microM). By both the fluorescent Ca2+ chelator Quin-2 assay and limited proteolysis of actin by trypsin and alpha-chymotrypsin, the real substitution of G-actin-bound Ca2+ by Cd2+ has been appreciated. The increase in Quin-2 fluorescence after addition of excess CdCl2 indicates that, in our experimental conditions, Ca2+ tightly-bound to actin is partially (60-70%) replaced by Cd2+, forming Cd-actin. Electrophoretic patterns after limited proteolysis reveal that the trypsin cleavage sites in the segment 61-69 of the actin polypeptide chain are less accessible in Cd-actin than in Ca-actin, although the cation-dependent effect is less pronounced in Cd-actin than in Mg-actin. Our results are consistent with some of the consequences on microfilament organization observed in Cd2(+)-treated cells; however, considering the positive effect of Cd2+ on actin polymerization in solution we have noticed that this was never observed in vivo. A different indirect effect of Cd2+ on some cellular event(s) influencing cytoplasmic actin polymerization appears to be reasonable.

Actins↗

PubMed1997

Prolonged oxidative stress on actin.

Hydrogen peroxide, coming from polymorphonuclear leukocytes, causes severe oxidative injury on actin molecules with the disarrangement of cortical actin cytoskeleton followed by plasmalemma blebbing. In this paper we demonstrate that actin oxidation does not simply develop into denaturation, but oxidative injuries on actin are specific and related to the chemical characteristics of the oxidant. Experiments on purified actin in solution have shown that actin behavior to oxidation depends on (i) the amino acidic targets of the oxidant and (ii) on the structural plasticity of the actin molecule, which differently responds to different chemical modifications. Therefore, hydrogen peroxide (that presents a broad oxidative activity) affects actin dynamics by markedly inhibiting the assembly of actin monomers, by forcing the disassembly of actin polymers, and, moreover, by affecting the interaction between oxidant-stressed actin and DNase I. Diamide (a specific thiol oxidant), in contrast, mainly lowers the actin polymerization extent, while it slightly influences the polymerization rate and results uneffective on both F-actin disassembly and actin-related DNase I inhibition. Actin response to oxidative stresses likely depends on the "structural connectivity in actin," the property allowing it to finely modulate the actin filament architecture. The potential cellular relevance of the alterations in the interaction between oxidized actin and DNase I has been briefly discussed.

Actins↗

PubMed1997

Pathologic features and clinical outcome after anatomic radical prostatectomy by transcoccygeal approach.

OBJECTIVES: A nonrandomized prospective study was conducted aimed at verifying the clinical outcome and pathologic features of a group of patients submitted to transcoccygeal radical prostatectomy. METHODS: Radical transcoccygeal prostatectomy was performed at our institution in 26 patients after laparoscopic (24 cases) or open surgical (2 cases) pelvic lymphadenectomy. Eighteen patients were selected because they were considered to be at risk for nodal metastases on the basis of preoperative staging (prostate-specific antigen level of 20 ng/mL or greater and/or Gleason score greater than 5); the remaining 8 manifested incidental prostate carcinoma. RESULTS: Intraoperative complications included rectal injury in 1 patient (3.8%) and massive blood loss in another. Transitory leakage at the site of the urethrovesical anastomosis and urethrorectal fistula occurred postoperatively in 2 patients. The rate of positive surgical margins was 26.9%. The mean follow-up time is 27 months (range 3 to 39 months). Total urinary continence was obtained in 21 patients (80.8%); 5 patients (19.2%) still require urinary pads. Four patients (15.4%) have experienced tumor recurrence evidenced only by increased serum prostate-specific antigen levels. Local tumor recurrence with positive biopsy of the urethrovesical junction was diagnosed in 3 patients (11.5%), and 1 (3.8%) experienced systemic tumor recurrence. CONCLUSIONS: Radical transcoccygeal prostatectomy is a safe procedure for the surgical treatment of prostate cancer, both from a clinical and a pathologic point of view. Operative complication as well as pathologic features and clinical outcome reported in this series of patients must be related to selection criteria used in most cases. The exact role of radical transcoccygeal prostatectomy in the clinical setting has yet to be defined. According to these preliminary results, radical transcoccygeal prostatectomy should be further investigated in the treatment of incidental carcinoma after transurethral resection of the prostate or suprapubic prostatectomy and could become an elective indication in such cases.

Aged↗

PubMed1997

Paraquat induces actin assembly in depolymerizing conditions.

The molecular mechanism (or mechanisms) at the basis of paraquat (PQ) (a widely used herbicide) toxicity is far from being fully understood. Until now, two main points of view have emerged: 1) PQ-related cell injuries could be mediated by toxic oxygen free radicals coming from the metabolism of the herbicide by the microsomal enzyme system, and/or 2) PQ, by inducing mitochondrial swelling and breakage, could cause troubles in cell energy charge, then driving the cell to death. Recently, some of cytoskeletal structures (microtubules and microfilaments) have been proposed as further PQ cell targets. The microfilament system in particular seems to be markedly affected by the herbicide, but so far no direct evidence associates PQ to actin damage. In this study, experimental data are presented concerning the direct effect of PQ on actin dynamics in solution. We demonstrate that actin selectively binds PQ; moreover, PQ induces the formation of actin sopramolecular structures in depolymerizing medium (G-buffer). Furthermore, by the interactions with F-actin cross-linking proteins (alpha-actinin and filamin), FITC-phalloidin, and myosin subfragment 1 (S1), it is demonstrated that PQ-induced actin aggregates are undoubtedly built up by F-actin. Electron micrographs showed that PQ-induced actin polymers are very short and tend to aggregate one to another. This mutual cohesion leads to the steric blockage of polymer growing ends as suggested by nucleated actin polymerization assays. Sonication, by releasing F-actin fragments from short polymer aggregates, allows actin polymer ends to regain their growing ability.

Actinin↗

PubMed1997

Chemoreceptor dependence of very low frequency rhythms in advanced chronic heart failure.

Factors responsible for very low frequency oscillations (VLF; cycle > 30 s) in the cardiovascular system remain obscure. We tested the hypothesis that increased peripheral chemosensitivity is important in the pathogenesis of VLF oscillations in patients with chronic heart failure (CHF). Fourteen male patients with stable, moderate to severe CHF (age 60 +/- 1.1 yr, ejection fraction 23 +/- 11%) and reproducible VLF oscillations in heart rate underwent a protocol consisting of three consecutive 20-min phases during which they breathed air, hyperoxia (O2 via mask, 60% O2 concn), and air again. Autoregressive spectral analysis of R-R intervals, blood pressure, and respiration was used to quantify total oscillatory power (TP), VLF, low (0.04-0.15 Hz)- and high (0.15-0.40Hz)-frequency power, and the coherence between these signals. Peripheral chemosensitivity was studied by assessing the ventilatory response to hypoxia using transient inhalations of pure N2. Discrete VLF rhythms were seen in R-R intervals in all 14 patients, in blood pressure in 7 of 14, and in respiration in 8 of 14 patients. A significant coherence (> 0.5) between heart rate and systolic blood pressure within the VLF band with mean phase value of -140 degrees, suggesting an antibaroreflex relationship, was seen in six subjects. Transient hyperoxia abolished the VLF oscillations in most subjects (12 of 14 in R-R intervals) and decreased R-R variability power within the VLF band. This response significantly correlated with peripheral chemoreceptor sensitivity (r = 0.77, P = 0.014). This study suggests that in CHF, enhanced peripheral chemoreceptor activity may facilitate slow oscillations in the cardiorespiratory signals.

Aged↗

PubMed1997

Plasma mitomycin C concentrations determined by HPLC coupled to solid-phase extraction.

The aim of this study was to set up a method for quantification of plasma mitomycin C (MMC) concentrations during intravesical chemotherapy delivered in the presence of local bladder hyperthermia (HT). In comparison with existing methods, this assay, characterized by relative simplicity and efficiency, resulted in the facilitation of performance with nondedicated instrumentation or nonspecialized staff. Purification from plasma matrix was carried out by solid-phase extraction under vaccuum. The purified drug was then collected directly into the vials of the HPLC autosampler. Chromatographic analysis was performed on a reversed-phase C18 column with water:acetonitrile (85:15 by vol) as the mobile phase and the UV detector set at 365 nm. The use of porfiromycin as internal standard provided a method with good within-day precision (CV 6.0% at 5 micrograms/L, n = 6), linearity (0.5-50 micrograms/L), and specificity. The lower limit of detection (< or = 0.5 microgram/L) proved to be suitable for plasma pharmacokinetics monitoring in two tested patients treated with MMC + HT for superficial bladder cancer.

Antibiotics, Antineoplastic↗

PubMed1997

[The effects of chronic beta-blocker administration on respiratory sinus arrhythmia].

The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. In some studies in which an increased RSA was reported, central vagotonic activity has been proposed. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. Twenty normal subjects (mean age 28 +/- 2 years) were randomized to receive a hydrophilic (nadolol, N), a lipophilic (metoprolol, M) beta-blocker and placebo (PL). After 1 week of therapy a spectral analysis was made of the variability in heart rate and systolic blood pressure (SBP) while they controlled their breathing at 16 breaths/min for a period of 5 min. The high frequency component was calculated for the RR interval (HF-RR, RSA measure) and SBP (HF-SBP), and the squared coherence (K2) and phase functions (phi HF) were assessed between RR and SBP fluctuations in the respiratory band (RR-SBP); a negative phi HF means that RR changes follow SBP changes. The alpha HF (an index of the baroreflex gain) was also calculated. Both beta-blockers increased the mean RR interval (PL 808 +/- 21, N 1054 +/- 30, M 1031 +/- 27 ms; p < 0.0001), HF-RR (PL 6.3 +/- 0.3, N 7.1 +/- 0.3, M 7.2 +/- 0.3 ln-ms2; p = 0.002) and alpha HF (PL 13.6 +/- 1.5, N 21.9 +/- 2.8, M 24.5 +/- 3.6 ms/mmHg; p < 0.002), and both modified phi HF (PL -0.23 +/- 0.05, N -0.02 +/- 0.05, M -0.03 +/- 0.04 s; p < 0.0001). No difference was found between N and M. Chronic beta-adrenergic blockade enhanced RSA and baroreflex gain and reduced the phase between the RR interval and SBP oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.

Administration, Oral↗

PubMed1997

Effects of short-term treatment with the alpha 1-blocker alfuzosin on urodynamic pressure/flow parameters in patients with benign prostatic hyperplasia.

OBJECTIVE: The objective of this double-blind, placebo-controlled urodynamic pressure/flow study was to assess the efficacy of short-term treatment with the alpha 1-blocker alfuzosin in outflow obstruction of patients with symptomatic benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: Urodynamic pressure/flow parameters were assessed after 2 weeks of placebo run-in, 4 weeks of placebo (47 patients) or 2.5 mg t.i.d. alfuzosin treatment (47 patients), followed by an 8-week extension period with alfuzosin (single-blind). RESULTS AND CONCLUSION: Four weeks of alfuzosin treatment significantly increased maximum flow (+29.0%) and decreased detrusor pressure at maximum flow (-30.2%), detrusor opening pressure (-39.4%) and maximum detrusor pressure (-28.7%). Short-term alfuzosin treatment improved outflow conditions in BPH by reducing prostatic urethral obstruction.

Adrenergic alpha-Antagonists↗

PubMed1996

Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure.

Although in advanced chronic congestive heart failure (CHF) very low frequency (< 0.04 Hz, VLF) oscillations are prominent, the clinical importance and the physiologic basis of these rhythms have not been elucidated. To investigate the physiologic determinants of the VLF rhythms in RR interval variability, we studied 36 patients with stable, moderate to severe CHF (33 men, age: 58 +/- 8 years, ejection fraction 25 +/- 10%, peak oxygen consumption 18.1 +/- 4.6 ml/kg/min) and 12 age- and sex-matched controls using autoregressive spectral analysis of RR interval, blood pressure, and respiratory signals during controlled conditions. We quantified low frequency (LF) (0.04 to 0.15 Hz), high frequency (HF) (0.15 to 0.40 Hz), VLF, and total power (0 to 0.5 Hz), and calculated the coherence between systolic blood pressure and RR interval variability within each band. Peripheral chemosensitivity was assessed by the ventilatory response to hypoxia using transient inhalation of pure nitrogen. The influence of transient inactivation of peripheral chemoreceptors on the VLF rhythm was investigated by exposing 6 patients to hyperoxic (60% oxygen) conditions for 20 minutes. Twenty-three patients (64%) with CHF, but no controls, had a discrete VLF rhythm (0.019 +/- 0.008 Hz) in RR variability. The presence of VLF rhythm was not related to any difference in clinical parameters (etiology, New York Heart Association class, ejection fraction, oxygen uptake) but rather to a different pattern in RR interval and blood pressure variability: lower LF power (2.8 +/- 1.6 ms2 natural logarithm [ln]) compared either to patients without VLF (4.0 +/- 1.3 ms2 ln) or to controls (5.9 +/- 0.7 ms2 ln), higher percentage of power within VLF band (86.3 +/- 8.3% vs 77.5 +/- 7.9% and 61.5 +/- 14.1%) and a markedly impaired coherence between RR interval and systolic blood pressure variability within the LF band (0.26 +/- 0.10 vs 0.42 +/- 0.18 and 0.63 +/- 0.15, in patients with vs without VLF peak and controls, respectively). Patients with VLF had significantly increased hypoxic chemosensitivity, and hyperoxic conditions were able to decrease VLF power and abolish the VLF rhythm in 5 of 6 patients with CHF. Discrete VLF oscillations in RR variability are common in patients with advanced CHF and appear to be related to severely impaired autonomic regulation and suppression of baroreceptor function, with enhancement of hypoxic chemosensitivity. We hypothesize that this rhythm represents an enhanced chemoreflex harmonic oscillation in CHF patients, which may have application for arrhythmogenesis.

Autonomic Nervous System↗