Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Summary

Background and objectives

Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.

Design, setting, participants, & measurements

STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method.

Results

In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%).

Conclusions

Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.     

Heart Rate Recovery in the First Minute at the Six-Minute Walk Test in Patients with Heart Failure

Background

Heart rate recovery at one minute of rest (HRR₁) is a predictor of mortality in heart failure (HF), but its prognosis has not been assessed at six-minute walk test (6MWT) in these patients.

Objective

This study aimed to determine the HRR₁ at 6MWT in patients with HF and its correlation with six-minute walk distance (6MWD).

Methods

Cross-sectional, controlled protocol with 161 individuals, 126 patients with stable systolic HF, allocated into 2 groups (G1 and G2) receiving or not β-blocker and 35 volunteers in control group (G3) had HRR₁ recorded at the 6MWT.

Results

HRR₁ and 6MWD were significantly different in the 3 groups. Mean values of HRR₁ and 6MWD were: HRR₁ = 12 ± 14 beat/min G1; 18 ± 16 beat/min G2 and 21 ± 13 beat/min G3; 6MWD = 423 ± 102 m G1; 396 ± 101m G2 and 484 ± 96 m G3 (p < 0.05). Results showed a correlation between HRR₁ and 6MWD in G1(r = 0.3; p = 0.04) and in G3(r = 0.4; p= 0.03), but not in G2 (r= 0.12; p= 0.48).

Conclusion

HRR₁ response was attenuated in patients using βB and showed correlation with 6MWD, reflecting better exercise tolerance. HRR₁ after 6MWT seems to represent an alternative when treadmill tests could not be tolerated.     

Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury

Background:

Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells.

Methods:

The effect of bucillamine was studied in a rat model of liver ischaemia–reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM).

Results:

The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 ± 511.79 vs. 932 ± 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 ± 16.86 vs. 181.11 ± 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001).

Conclusion:

Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.     

Acute Effects of Continuous Positive Air way Pressure on Pulse Pressure in Chronic Heart Failure

Background

Patients with heart failure (HF) have left ventricular dysfunction and reduced mean arterial pressure (MAP). Increased adrenergic drive causes vasoconstriction and vessel resistance maintaining MAP, while increasing peripheral vascular resistance and conduit vessel stiffness. Increased pulse pressure (PP) reflects a complex interaction of the heart with the arterial and venous systems. Increased PP is an important risk marker in patients with chronic HF (CHF). Non-invasive ventilation (NIV) has been used for acute decompensated HF, to improve congestion and ventilation through both respiratory and hemodynamic effects. However, none of these studies have reported the effect of NIV on PP.

Objective

The objective of this study was to determine the acute effects of NIV with CPAP on PP in outpatients with CHF.

Methods

Following a double-blind, randomized, cross-over, and placebo-controlled protocol, twenty three patients with CHF (17 males; 60 ± 11 years; BMI 29 ± 5 kg/cm², NYHA class II, III) underwent CPAP via nasal mask for 30 min in a recumbent position. Mask pressure was 6 cmH₂O, whereas placebo was fixed at 0-1 cmH₂O. PP and other non invasive hemodynamics variables were assessed before, during and after placebo and CPAP mode.

Results

CPAP decreased resting heart rate (Pre: 72 ± 9; vs. Post 5 min: 67 ± 10 bpm; p < 0.01) and MAP (CPAP: 87 ± 11; vs. control 96 ± 11 mmHg; p < 0.05 post 5 min). CPAP decreased PP (CPAP: 47 ± 20 pre to 38 ± 19 mmHg post; vs. control: 42 ± 12 mmHg, pre to 41 ± 18 post p < 0.05 post 5 min).

Conclusion

NIV with CPAP decreased pulse pressure in patients with stable CHF. Future clinical trials should investigate whether this effect is associated with improved clinical outcome.     

Is the protection against ischemia induced by red wine linked to its antioxidant capacity?

OBJECTIVE:

To establish whether the total antioxidant capacity of nonalcoholic extracts of three Argentine red wines (RWE) is correlated with their protection against ischemia-reperfusion injury.

ANIMALS AND METHODS:

The antioxidant properties of three RWE were determined using different free radical-generating systems. To examine the effects of these RWE during a 20 min global ischemic period followed by 30 min of reperfusion, isolated rat hearts received 50 μg/mL of RWE 1 (cabernet-sauvignon), RWE 2 (malbec) or RWE 3 (a commercial mixture of cabernet-sauvignon, malbec and merlot) 10 min before and after ischemia. Left ventricular developed pressure (LVDP), maximal velocity of rise of left ventricular pressure (+dP/dt_max) and left ventricular end-diastolic pressure (LVEDP) were used to assess contractility and diastolic function.

RESULTS:

All RWE inhibited lipid peroxidation induced by the Cl₄C/NADPH system in a similar proportion (42±4%, 47±9% and 43±14% for RWE 1, RWE 2 and RWE 3, respectively). The scavenging activity of superoxide anion and 2,2-diphenyl-1-picryl-hydrazyl radical was about the same with the three RWE. In hearts without RWE treatment, LVDP and +dP/dt_max were 61±4% and 62±5%, respectively, at the end of the reperfusion period. Infusion of RWE 1 and RWE 2 significantly improved postischemic recovery (LVDP and +dP/dt_max were 102±4% and 101±4% for RWE 1 and 92±5% and 91±5% for RWE 2, respectively) and attenuated the increase of LVEDP. RWE 3 did not improve either systolic or diastolic dysfunction.

CONCLUSION:

These data show that although the three non-alcoholic RWE exhibit a similar total antioxidant capacity, only two of them protect the heart against myocardial stunning, suggesting that the protective effect is not primarily linked to the anti-oxidant properties of the extracts.     

Impact of the prolonged slow expiratory maneuver on respiratory mechanics in wheezing infants

OBJECTIVE:

To evaluate changes in respiratory mechanics and tidal volume (V_T) in wheezing infants in spontaneous ventilation after performing the technique known as the prolonged, slow expiratory (PSE) maneuver.

METHODS:

We included infants with a history of recurrent wheezing and who had had no exacerbations in the previous 15 days. For the assessment of the pulmonary function, the infants were sedated and placed in the supine position, and a face mask was used and connected to a pneumotachograph. The variables of tidal breathing (V_T and RR) as well as those of respiratory mechanics-respiratory system compliance (Crs), respiratory system resistance (Rrs), and the respiratory system time constant (prs)-were measured before and after three consecutive PSE maneuvers.

RESULTS:

We evaluated 18 infants. The mean age was 32 ± 11 weeks. After PSE, there was a significant increase in V_T (79.3 ± 15.6 mL vs. 85.7 ± 17.2 mL; p = 0.009) and a significant decrease in RR (40.6 ± 6.9 breaths/min vs. 38.8 ± 0,9 breaths/min; p = 0.042). However, no significant differences were found in the variables of respiratory mechanics (Crs: 11.0 ± 3.1 mL/cmH₂O vs. 11.3 ± 2.7 mL/cmH₂O; Rrs: 29.9 ± 6.2 cmH₂O • mL⁻¹ • s⁻¹ vs. 30.8 ± 7.1 cmH₂O • mL⁻¹ • s⁻¹; and prs: 0.32 ± 0.11 s vs. 0.34 ±0.12 s; p > 0.05 for all).

CONCLUSIONS:

This respiratory therapy technique is able to induce significant changes in V_T and RR in infants with recurrent wheezing, even in the absence of exacerbations. The fact that the variables related to respiratory mechanics remained unchanged indicates that the technique is safe to apply in this group of patients. Studies involving symptomatic infants are needed in order to quantify the functional effects of the technique.     

Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats

Objective

We hypothesized that pretreatment with sivelestat therapy could attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat model.

Methods

The neutrophil elastase inhibitor was administered intraperitoneally 30 min before and at the initiation of ventilation. The rats were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV) early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid (BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI scores were investigated.

Results

The ratio of wet-to-dry weight, BALF neutrophil and protein, tissue MDA and VILI scores were significantly increased in the VILI group compared to the sham group [3.85±0.32 vs. 9.05±1.02, P<0.001; (0.89±0.93)×10⁴ vs. (7.67±1.41)×10⁴ cells/mL, P<0.001; 2.34±0.47 vs. 23.01±3.96 mg/mL, P<0.001; 14.43±1.01 vs. 36.56±5.45 nmol/mg protein, P<0.001; 3.78±0.67 vs. 7.00±1.41, P<0.001]. This increase was attenuated in the early sivelestat group compared with the sivelestat group [wet-to-dry ratio: 6.76±2.01 vs. 7.39±0.32, P=0.032; BALF neutrophil: (5.56±1.13)×10⁴ vs. (3.89±1.05)×10⁴ cells/mL, P=0.021; BALF protein: 15.57±2.32 vs. 18.38±2.00 mg/mL, P=0.024; tissue MDA: 29.16±3.01 vs. 26.31±2.58, P=0.049; VILI scores: 6.33±1.41 vs. 5.00±0.50, P=0.024].

Conclusions

Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.     

Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

Background

Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear.

Objective

The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats.

Methods

Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia.

Results

Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO_x) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO_x concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups.

Conclusion

Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.     

Cardiac I123-MIBG Correlates Better than Ejection Fraction with Symptoms Severity in Systolic Heart Failure

Background

The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood.

Objective

Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment.

Methods

Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to ¹²³I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed.

Results

According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex.

Conclusion

This study showed that cardiac ¹²³I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.     

Sex-Specific Equations to Estimate Maximum Oxygen Uptake in Cycle Ergometry

Background

Aerobic fitness, assessed by measuring VO₂max in maximum cardiopulmonary exercise testing (CPX) or by estimating VO₂max through the use of equations in exercise testing, is a predictor of mortality. However, the error resulting from this estimate in a given individual can be high, affecting clinical decisions.

Objective

To determine the error of estimate of VO₂max in cycle ergometry in a population attending clinical exercise testing laboratories, and to propose sex-specific equations to minimize that error.

Methods

This study assessed 1715 adults (18 to 91 years, 68% men) undertaking maximum CPX in a lower limbs cycle ergometer (LLCE) with ramp protocol. The percentage error (E%) between measured VO₂max and that estimated from the modified ACSM equation (Lang et al. MSSE, 1992) was calculated. Then, estimation equations were developed: 1) for all the population tested (C-GENERAL); and 2) separately by sex (C-MEN and C-WOMEN).

Results

Measured VO₂max was higher in men than in WOMEN: -29.4 ± 10.5 and 24.2 ± 9.2 mL.(kg.min)^-1 (p < 0.01). The equations for estimating VO₂max [in mL.(kg.min)^-1] were: C-GENERAL = [final workload (W)/body weight (kg)] x 10.483 + 7; C-MEN = [final workload (W)/body weight (kg)] x 10.791 + 7; and C-WOMEN = [final workload (W)/body weight (kg)] x 9.820 + 7. The E% for MEN was: -3.4 ± 13.4% (modified ACSM); 1.2 ± 13.2% (C-GENERAL); and -0.9 ± 13.4% (C-MEN) (p < 0.01). For WOMEN: -14.7 ± 17.4% (modified ACSM); -6.3 ± 16.5% (C-GENERAL); and -1.7 ± 16.2% (C-WOMEN) (p < 0.01).

Conclusion

The error of estimate of VO₂max by use of sex-specific equations was reduced, but not eliminated, in exercise tests on LLCE.     

Removal and Rebound Kinetics of Cystatin C in High-Flux Hemodialysis and Hemodiafiltration

Background and objectives

Cystatin C is a 13.3 kD middle molecule of similar size to β₂-microglobulin and a marker of GFR in CKD. This study aimed to determine cystatin C kinetics in hemodialysis to understand whether blood concentrations may predict residual renal function and middle-molecule clearance.

Design, setting, participants, & measurements

Cystatin C removal and rebound kinetics were studied in 24 patients on high-flux hemodialysis or hemodiafiltration. To determine whether cystatin C concentrations are predictable, an iterative two-pool mathematical model was applied.

Results

Cystatin C was cleared effectively, although less than β₂-microglobulin (reduction ratios±SD are 39%±11 and 51%±11). Cystatin C rebounded to 95%±5% of predialysis concentration by 12 hours postdialysis. The two-pool kinetic model showed excellent goodness of fit. Modeled extracellular cystatin C pool volume is smaller than that predicted, comprising 25.5%±9.2 of total body water. Iterated parameters, including nonrenal clearance, showed wide interindividual variation. Modeled nonrenal clearance was substantially higher than renal clearance in this population at 25.1±6.6 ml/min per 1.73 m² body surface area.

Conclusions

Plasma cystatin C levels may be used to measure middle-molecule clearance. Levels rebound substantially postdialysis and plateau in the interdialytic period. At low GFR, nonrenal clearance predominates over renal clearance, and its interindividual variation will limit use of cystatin C to predict residual renal function in advanced kidney disease.     

Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease

Background

Human tissue kallikrein (hK1) is a key enzyme in the kallikrein–kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear.

Objective

To evaluate hK1-specific amidase activity in the urine of CAD patients

Methods

Sixty-five individuals (18–75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffé’s method. Urinary hK1-specific amidase activity was expressed as µM/(min · mg creatinine) to correct for differences in urine flow rates.

Results

Urinary hK1-specific amidase activity levels were similar between CAD [0.146 µM/(min ·mg creatinine)] and non-CAD [0.189 µM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 µM/(min . mg creatinine)] and HF patients [0.104 µM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity.

Conclusion

CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease.     

Capnography improves detection of apnea during procedural sedation for percutaneous transhepatic cholangiodrainage

BACKGROUND:

Capnography provides noninvasive monitoring of ventilation and can enable early recognition of altered respiration patterns and apnea.

OBJECTIVE:

To compare the detection of apnea and the prediction of oxygen desaturation and hypoxemia using capnography versus clinical surveillance during procedural sedation for percutaneous transhepatic cholangiodrainage (PTCD).

METHODS:

Twenty consecutive patients scheduled for PTCD were included in the study. All patients were sedated during the procedure using midazolam and propofol. Aside from standard monitoring, additional capnographic monitoring was used and analyzed by an independent observer.

RESULTS:

The mean (± SD) cumulative duration of apnea demonstrated by capnography was significantly longer than the mean cumulative duration of clinically detected apnea (207.5±348.8 s versus 8.2±17.9 s; P=0.015). The overall number of detected episodes of apnea was also significantly different (113 versus seven; P=0.012). There were 15 events of oxygen desaturation (decrease in oxygen saturation [SaO₂] ≥5%), which were predicted in eight of 15 cases by capnography and in one of 15 cases by clinical observation. There were three events of hypoxemia (SaO₂ <90%) that were predicted in three of three cases by capnography and in one of three cases by clinical observation.

CONCLUSION:

Capnographic monitoring was superior to clinical surveillance in the detection of apnea and in the prediction of oxygen desaturation during procedural sedation for PTCD.     

Age-related changes in gap junctional protein of the rat heart

OBJECTIVE:

Connexin 43 (Cx43), a membrane protein involved in the control of cell-to-cell communication, is thought to play a role in physiological processes such as tissue homeostasis, growth regulation and development. The aim of the present study was to investigate the change of Cx43 expression in aged myocardium.

METHODS AND RESULTS:

Sixteen male Sprague-Dawley rats (adult: 10 weeks old, n=8; aged: two years old, n=8) were used in the present study. In an isolated rat heart Langendorff model, hearts were perfused for 10 min with a modified Krebs-Henseleit bicarbonate buffer. Contractile functions were measured and all hearts were stained with anti-Cx43 antibody for fluorescence microscopic examinations. There were no significant differences observed in heart rate (234±8.2 beats/min versus 231±15.6 beats/min), left ventricular developed pressure (112.5±6.3 mmHg versus 107.2±2.5 mmHg), first derivative of the left ventricular pressure (1450.4±165.1 mmHg/s versus 1384.6±95.4 mmHg/s) and coronary flow (17.4±0.7 mL/min versus 21.3±1.8 mL/min) between adult and aged rats, respectively. However, significant differences were observed in left ventricular weight (adult versus aged; 0.639±0.108 g versus 1.124±0.257 g, P=0.04) and in fluorescence examinations where there was reduced distribution of Cx43 in aged myocardium compared with adult myocardium.

CONCLUSIONS:

These results demonstrated that the role of Cx43 may be more important than previously reported, and that this protein is partially responsible for the maintenance of cellular structure in myocardial development.     

Evaluation of a novel method of teaching endobronchial ultrasound: Physician- versus respiratory therapist-proctored simulation training

BACKGROUND:

Computer endobronchial ultrasound (EBUS) simulators have been demonstrated to improve trainee procedural skills before attempting to perform EBUS procedures on patients.

OBJECTIVE:

To compare EBUS performance following training with computer simulation proctored by EBUS-trained respiratory therapists versus the same simulation training proctored by an interventional respirologist.

METHODS:

The present analysis was a prospective study of respiratory medicine trainees learning EBUS. Two cohorts of trainees were evaluated using a previously validated method using simulated cases with performance metrics measured by the simulator. Group 1 underwent EBUS training by performing 15 procedures on an EBUS simulator (n=4) proctored by an interventional respirologist. Group 2 received identical training proctored by a respiratory therapist with special training in EBUS (n=10).

RESULTS:

No significant differences between group 1 and group 2 were apparent for the primary outcome measures of total procedure time (15.15±1.34 min versus 14.78±2.88 min; P=0.816), the percentage of lymph nodes successfully identified (88.8±5.4 versus 80.91±8.9; P=0.092) or the percentage of successful biopsies (100.0±0.0 versus 98.75±3.95; P=0.549). The learning curves were similar between groups, and did not show an obvious plateau after 19 simulated procedures in either group.

DISCUSSION:

Acquisition of basic EBUS technical skills can be achieved using computer EBUS simulation proctored by specially trained respiratory therapists or by an interventional respirologist. There appeared to be no significant advantage to having an interventional respirologist proctor the computer EBUS simulation.     

Effects of AT1 receptor antagonist therapy in patients with severe heart failure pretreated with angiotensin-converting enzyme inhibitors

BACKGROUND:

The efficacy of angiotensin-converting enzyme (ACE) inhibitors is well documented in the treatment of chronic severe heart failure. Because pharmacological mechanisms of angiotensin II type 1 (AT1) receptor antagonists differ from the effects of ACE inhibitors, an additional positive effect can be expected by combining these drugs.

METHODS:

Sixty patients (mean age 68.3±10.0 years) with severe chronic heart failure receiving long term medication with digitalis, diuretics, ACE inhibitors and in part beta-blockers (68.3%) were randomly assigned after clinical recompensation to three groups: additional therapy with eprosartan (477.5±143.7 mg/day), telmisartan (65.9±17.7 mg/day) and control group according to a prospective study design. Hemodynamic measurements by impedance cardiography were performed before and during the observation period (9.6±3.4 days).

RESULTS:

Additional sartan treatment resulted in an improvement in cardiac output from 2.32±0.69 L/min to 3.12±1.24 L/min (P=0.003) in the eprosartan group and from 2.24±0.59 L/min to 2.76±0.91 L/min (P=0.001) in the telmisartan group; cardiac output in the control group did not increase. Furthermore, a significant decrease in total peripheral resistance was observed during treatment with eprosartan (23%, P=0.002) and telmisartan (18%, P=0.002). In the subgroup receiving combined therapy with beta-blockers, ACE inhibitors and AT1 antagonists, a significant increase in cardiac output was also observed.

CONCLUSIONS:

The additional treatment with AT1 receptor antagonists resulted in an increase in the cardiac output and a decrease in the peripheral resistance. This beneficial effect may be due to the additional property of sartans to block the interaction of locally and non-ACE-generated angiotensin II with their respective vascular and myocardial AT1 receptors.     

Oxygen desaturation in healthy subjects undergoing the incremental shuttle walk test

OBJECTIVE:

To determine the probability of oxygen desaturation in healthy individuals undergoing the incremental shuttle walk test (ISWT).

METHODS:

We enrolled 83 healthy subjects: 55 males (including 1 smoker) and 28 females. We determined pre-ISWT FEV₁, FEV₆, HR and SpO₂, as well as post-ISWT HR and SpO₂.

RESULTS:

Mean values overall were as follows: age, 35.05 ± 12.53 years; body mass index, 24.30 ± 3.47 kg/m²; resting HR, 75.12 ± 12.48 bpm; resting SpO₂, 97.96 ± 1.02%; FEV₁, 3.75 ± 0.81 L; FEV₆, 4.45 ± 0.87 L; FEV₁/FEV₆ ratio, 0.83 ± 0.08 (no restriction or obstruction); incremental shuttle walk distance, 958.30 ± 146.32 m; post-ISWT HR, 162.41 ± 18.24 bpm; and post-ISWT SpO₂, 96.27 ± 2.21%. In 11 subjects, post-ISWT SpO₂ was higher than was pre-ISWT SpO₂. In 17 subjects, there was a 4% decrease in SpO₂ after the ISWT. There were no statistically significant differences between the groups with and without post-ISWT oxygen desaturation in terms of age, gender, FEV₁, FEV₆, FEV₁/FEV₆, pre-ISWT SpO₂, incremental shuttle walk distance, HR, or percentage of maximal HR. In the individuals with post-ISWT oxygen desaturation, the body mass index was higher (p = 0.01) and post-ISWT SpO₂ was lower (p = 0.0001).

CONCLUSIONS:

Healthy individuals can present oxygen desaturation after the ISWT. Using the ISWT to predict subtle respiratory abnormalities can be misleading. In healthy subjects, oxygen desaturation is common after the ISWT, as it is during any intense physical activity.     

Sleep-disordered breathing in patients with cystic fibrosis

Objective:

To test the hypothesis that disease severity in patients with cystic fibrosis (CF) is correlated with an increased risk of sleep apnea.

Methods:

A total of 34 CF patients underwent clinical and functional evaluation, as well as portable polysomnography, spirometry, and determination of IL-1β levels.

Results:

Mean apnea-hypopnea index (AHI), SpO₂ on room air, and Epworth Sleepiness Scale score were 4.8 ± 2.6, 95.9 ± 1.9%, and 7.6 ± 3.8 points, respectively. Of the 34 patients, 19 were well-nourished, 6 were at nutritional risk, and 9 were malnourished. In the multivariate model to predict the AHI, the following variables remained significant: nutritional status (β = −0.386; p = 0.014); SpO₂ (β = −0.453; p = 0.005), and the Epworth Sleepiness Scale score (β = 0.429; p = 0.006). The model explained 51% of the variation in the AHI.

Conclusions:

The major determinants of sleep apnea were nutritional status, SpO₂, and daytime sleepiness. This knowledge not only provides an opportunity to define the clinical risk of having sleep apnea but also creates an avenue for the treatment and prevention of the disease.     

The Microvasculature in Chronic Kidney Disease

Summary

Background and objectives

Individuals with chronic kidney disease (CKD) stages 3 to 5 have an increased risk of cardiac and other vascular disease. Here we examined the association of CKD 3 to 5 with small vessel caliber.

Design, setting, participants, & measurements

This was a cross-sectional observational study of 126 patients with CKD stages 3 to 5 (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and 126 age- and gender-matched hospital patients with CKD 1 or 2. Retinal vessel diameters were measured from digital fundus images by a trained grader using a computer-assisted method and summarized as the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).

Results

Patients with CKD 3 to 5 had a smaller mean CRAE and CRVE than hospital controls (139.4 ± 17.8 μm versus 148.5 ± 16.0 μm, P < 0.001; and 205.0 ± 30.7 μm versus 217.4 ± 25.8 μm, respectively; P = 0.001). CRAE and CRVE decreased progressively with each stage of renal failure CKD1–2 to 5 (P for trend = 0.08 and 0.04, respectively). CKD and hypertension were independent determinants of arteriolar narrowing after adjusting for age, gender, diabetes, dyslipidemia, and smoking history. Patients with CKD 5 and diabetes had a larger mean CRAE and CRVE than nondiabetics (141.4 ± 14.9 μm versus 132.9 ± 14.2 μm; 211.1 ± 34.4 μm versus 194.8 ± 23.8 μm).

Conclusions

The microvasculature is narrowed in patients with reduced eGFR.