Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) results in chronic right heart failure, which is associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. We investigated the changes in cardiac autonomic nervous activity in relation to disease severity in patients with PAH. In 48 patients with PAH (median World Health Organization class III, pulmonary artery pressure 52+/-14 mmHg, pulmonary vascular resistance 1,202+/-718 dyn x s x cm(-5), cardiac index 2.0+/-0.8 L x min(-1) x m(-2)) and 41 controls, cardiac autonomic nervous activity was evaluated by measurement of heart rate variability (HRV) and baroreflex sensitivity. All patients underwent cardiopulmonary exercise testing (peak oxygen uptake 13.2+/-5.1 mL x kg(-1) x min(-1), minute ventilation/carbon dioxide production slope 47+/-16). In patients with PAH, spectral power of HRV was reduced in the high-frequency (239+/-64 versus 563+/-167 ms2), low-frequency (245+/-58 versus 599+/-219 ms2) and very low-frequency bands (510+/-149 versus 1106+/-598 ms2; all p<0.05). Baroreflex sensitivity was also blunted (5.8+/-0.6 versus 13.9+/-1.2 ms x mmHg(-1); p<0.01). The reduction in high-frequency (r = 0.3, p = 0.04) and low-frequency (r = 0.33, p = 0.02) spectral power and baroreflex sensitivity (r = 0.46, p<0.01) was related to the reduction in peak oxygen uptake. Patients with PAH have a marked alteration in cardiac autonomic control that is related to exercise capacity and may, therefore, serve as an additional marker of disease severity.

Absorption of calcium measured by intubation and perfusion of the intact hyman small intestine.

Absorption of calcium was measured by direct intubation and perfusion of the small intestine in 10 volunteer normal adult subjects, two adults with celiac-sprue, and one with a parathyroid adenoma. A total of 60 studies were completed using one of two different levels, duodenojejunum or ileum. Solutions containing stable calcium, radiocalcium(47), and a nonabsorbable dilution-concentration marker, polyethylene glycol, were infused at a uniform rate via the proximal lumen of a triple-lumen polyvinyl tube. The mixed intraluminal contents were continuously sampled by siphonage from two distal sites, 10 and 60 cm below the point of infusion. Unidirectional flux rates, lumen to blood and blood to lumen, and net absorption of calcium for the 50 cm segment of small intestine between the two collection sites were calculated from the measured changes in concentration of stable calcium, calcium-47, and polyethylene glycol.Flux of calcium from lumen to blood in the duodenojejunum of normal subjects was appreciable even when the concentration of calcium in the perfusate was below that of extracellular fluid and, as the intraluminal concentration of calcium was increased through a range of 0.5-3.5 mumoles/ml, was positively correlated, ranging from 1.9 to 7.0 mumoles/min per 50 cm. Repeated studies of individual subjects demonstrated a consistent pattern of absorptive efficiency in each, but significant variability from person to person. Flux from lumen to blood in the ileal segment occurred at a much lower rate than that found in the proximal intestine, and there was not a significant dependence upon intraluminal calcium concentration. The opposite flux, from blood to lumen, was low both in the duodenojejunum and ileum (average 0.76 mumoles/min per 50 cm) and was independent of the intraluminal calcium concentration. Unidirectional flux, lumen to blood, from the duodenojejunum was not altered by parathyroid extract administered at the time of the infusion, but was accelerated in the subject with a parathyroid adenoma and markedly reduced in the two subjects with celiac-sprue.

Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension.

BACKGROUND: The continuous infusion of prostacyclin has been shown to improve exercise capacity and survival in patients with primary pulmonary hypertension (PPH). Inhalation of iloprost, a stable analog of prostacyclin, might be an alternative therapy for PPH, selectively acting on the pulmonary vascular bed through ventilation-matched alveolar deposition of the drug. We investigated the short-term effects of iloprost inhalation on exercise capacity and gas exchange in patients with PPH. METHODS AND RESULTS: In 11 patients with PPH, we performed 2 consecutive cardiopulmonary exercise tests before and after the inhalation of 17 microgram of iloprost. Patients had marked pulmonary hypertension (mean pulmonary artery pressure 65 mm Hg), and inhalation resulted in a decrease in pulmonary vascular resistance (1509 versus 1175 dyne. s(-1). cm(-5), P<0.05). Arterial blood gases remained unchanged (PaO(2) 69.3 versus 66.8 mm Hg; PaCO(2) 29.6 versus 28.8 mm Hg). Iloprost significantly (P<0.05) improved exercise duration (379 versus 438 seconds), peak oxygen uptake (12.8 versus 14.2 mL. kg(-1). min(-1)), VE-versus-V CO(2) slope (58 versus 51.4). CONCLUSIONS: The present data show that iloprost inhalation exerts pulmonary vasodilatation and improves symptoms and exercise capacity in patients with PPH. The data also suggest that iloprost inhalation is a suitable treatment for PPH. Whether these effects are maintained during long-term treatment and are paralleled by improvement in prognosis remains to be determined.

Impairment of ventilatory efficiency in heart failure: prognostic impact.

BACKGROUND: Impairment of ventilatory efficiency in congestive heart failure (CHF) correlates well with symptomatology and contributes importantly to dyspnea. METHODS AND RESULTS: We investigated 142 CHF patients (mean NYHA class, 2.6; mean maximum oxygen consumption [VO(2)max], 15.3 mL O(2) x kg(-1) x min(-1); mean left ventricular ejection fraction [LVEF], 27%). Patients were compared with 101 healthy control subjects. Cardiopulmonary exercise testing was performed, and ventilatory efficiency was defined as the slope of the linear relationship of V(CO(2)) and ventilation (VE). Results are presented in percent of age- and sex-adjusted mean values. Forty-four events (37 deaths and 7 instances of heart transplantation, cardiomyoplasty, or left ventricular assist device implantation) occurred. Among VO(2)max, NYHA class, LVEF, total lung capacity, and age, the most powerful predictor of event-free survival was the VE versus V(CO(2)) slope; patients with a slope 130% (54.7%; P<0.001). CONCLUSIONS: The VE versus V(CO(2)) slope is an excellent prognostic parameter. It is easier to obtain than parameters of maximal exercise capacity and is of higher prognostic importance than VO(2)max.

Current guidelines for the treatment of congestive heart failure.

Overt congestive heart failure (CHF) has a prevalence of 1% of the population. The predominant symptoms of patients with CHF are fatigue and dyspnoea. Fatigue is thought to result from changes in peripheral muscle metabolism secondary to decrease vasodilative capacity and physical inactivity. An increase of peripheral perfusion by vasodilator therapy and physical activity are therefore recommended. Beside overt decompensation, where dyspnoea results from acute pulmonary congestion due to backward failure, increased physiological dead space ventilation caused by pulmonary ventilation/perfusion mismatch accounts, to a large degree, for dyspnoea, and can be improved by vasodilator therapy. According to the pathophysiology of CHF, normalisation of loading conditions and myocardial inotropy are the parameters addressed by various pharmacological agents in order to alleviate symptoms and slow progression of the disease. Diuretics are rapidly acting and effective agents to improve congestion and decrease filling pressures. Digitalis improves haemodynamics and symptomatology by increasing inotropy and slowing resting heart rate in atrial fibrillation; however, prognostic effects have yet to be proved. The introduction of vasodilators has significantly improved the prognosis of the disease, and the administration of ACE inhibitors in particular has been shown to slow progression of CHF. This results in a substantial decrease in morbidity and mortality. The present article appraises the role of the currently used drugs in the treatment of CHF, considering effects on pathophysiology and clinical outcome and provides an approach to a differential drug regimen.

Relationship between impaired pulmonary diffusion and cardiopulmonary exercise capacity after heart transplantation.

STUDY OBJECTIVES: Diffusion impairment and reduced performance in cardiopulmonary exercise testing (CPX) have been found in patients after heart transplantation. The pathogenesis of these abnormalities is unclear. In particular, the contribution of pulmonary interstitial changes has not yet been verified. DESIGN: We analyzed pulmonary function tests, high-resolution CT (HRCT), echocardiography, left heart catheterization, and CPX in transplanted patients. PATIENTS: Forty long-term survivors were studied at a median of 47 months (range, 12 to 89 months) after heart transplantation. RESULTS: Diffusion was impaired in 40% (transfer factor for carbon monoxide) or 82.5% (carbon monoxide transfer coefficient) of the patients. Diffusion impairment was caused by a decreased diffusing capacity of the alveolar capillary membrane in 89% and/or by a decreased blood volume of the alveolar capillaries in 46% of cases. In five patients (12.5%), CT revealed interstitial lung changes. These patients did not have different values of diffusion capacity. Maximal oxygen uptake and ventilatory efficiency during exercise (minute ventilation/carbon dioxide output slope) were impaired in 92% and 46% of the cases, respectively. CONCLUSIONS: Our data show that the diffusion abnormalities are caused by an impaired diffusion status of the alveolar capillary membrane. Interstitial changes detectable in HRCT were found not to be involved in this process. The reduced performance in CPX in our long-term survivors is caused by pulmonary perfusion abnormalities and low tidal volume, which is due to the deconditioning of respiratory muscle, rather than by interstitial changes or diffusion abnormalities.

Ventilatory and diffusion abnormalities in long-term survivors after orthotopic heart transplantation.

OBJECTIVE: To investigate the long-term development of pulmonary diffusion abnormalities after orthotopic heart transplantation (oHT). DESIGN: Retrospective analysis of pulmonary function test results of different patient groups at different time intervals after oHT was performed. PATIENTS: This investigation included 642 patients who had undergone oHT for chronic heart failure. Patients were grouped according to the time elapsed after transplantation (group 1: n = 164; age, 47 +/- 14 years; days after oHT, 324 +/- 101; group 2: n = 100; age, 48 +/- 15 years; days after oHT, 723 +/- 104; group 3: n = 106; age, 52 +/- 12 years; days after oHT, 1,092 +/- 98; group 4: n = 84; age, 51 +/- 13 years; days after oHT, 1,442 +/- 99; group 5: n = 61; age, 50 +/- 14 years; days after oHT, 1,819 +/- 105; group 6: n = 101; age, 53 +/- 12 years; days after oHT, 2,463 +/- 303; and group 7: n = 26; age, 54 +/- 14 years; days after oHT, 3,478 +/- 246). In 56 (group 8) of the 642 patients, follow-up measurements were performed with tests before and at two time points after oHT (6.5 +/- 1.7 and 12.5 +/- 9.3 months). RESULTS: Of all patients, 39% showed restrictive and obstructive abnormalities with no differences between the groups. No significant differences in lung transfer factor for carbon monoxide (DLCO) were observed (61.2 vs 63.7 vs 65.5 vs 65.6 vs 64.5 vs 65.7 vs 67.6% predicted). Differences in transfer coefficient for carbon monoxide (Kco) were significant between group 1 and 4 (58.7 vs 64.1% predicted), and group 1 and 6 (58.7 vs 63.4% predicted). No differences occurred in the rate with which patients exhibited pathologic abnormalities for DLCO and KCO. After oHT, a marked reduction in diffusion capacity occurred in group 8. On follow-up, these measurements were only slightly restored in terms of the predicted DLCO percentage. No such improvement was observed in KCO or in the rate of pathologic changes for both DLCO and KCO. We conclude, therefore, that the impairment of diffusion does not improve even after a significant period has passed after the oHT. Whether this has any effect on symptoms and/or the prognosis for these patients is extremely unclear.

Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension.

STUDY OBJECTIVES: Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology that is characterized by a poor prognosis. This study was undertaken to investigate possible correlations between endothelin (ET)-1 and big ET-1 plasma levels and the severity of PPH. PATIENTS: Sixteen consecutive patients with PPH were included. INTERVENTIONS: Hemodynamics of patients with PPH were measured by right-heart catheterization, and a 6-min walk test was performed. MEASUREMENTS: Plasma levels of the biologically active peptide ET-1 and its precursor big ET-1 were determined in blood samples from the pulmonary artery, peripheral artery, and peripheral vein by radioimmunoassay. RESULTS: A strong correlation was shown between pulmonary vascular resistance, mean pulmonary artery pressure, cardiac output, cardiac index, 6-min walk data, and elevated plasma levels of big ET-1 as well as mature ET-1 plasma levels at all sites of blood sampling (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Levels of circulating ET-1 might become a prognostic marker for patients with PPH and serve as a tool for the selection of patients who may benefit from treatment with ET-receptor antagonists.

Acetylcholine but not sodium nitroprusside exerts vasodilation in pulmonary hypertension secondary to chronic congestive heart failure.

BACKGROUND: Reduced endothelium-dependent vasodilation contributes to the development of pulmonary hypertension in chronic congestive heart failure (CHF). We investigated pulmonary endothelium-dependent and independent vasodilation in patients with CHF. METHODS: We studied 42 patients with CHF (age 55 +/- 10, NYHA Classes II-III, left ventricular ejection fraction 27 +/- 10%, mean PAP 29 +/- 12 mmHg). The endothelial vasodilator capacity of pulmonary resistance vessels was assessed by the infusion of acetylcholine into a pulmonary artery branch while measuring the blood flow velocity with a Doppler flow wire. For comparison endothelium-independent vasodilation was measured with the response to sodium nitroprusside. The conductance vessel diameter (4.4 +/- 0.2 mm) was determined by intravascular ultrasound. Acetylcholine was administered at concentrations of 10(-6) to 10(-4) mol/l, sodium nitroprusside was administered at concentrations of 0.125 and 0.25 microg/kg per min. The effects on conductance vessel diameter were investigated in 12 patients by the measurement of diameter and flow velocity following the administration of acetylcholine and sodium nitroprusside. RESULTS: Acetylcholine markedly increased blood flow velocity (+39 +/- 7% at 10(-4) mol/l; p < .05). This correlated with the baseline PAP (r = 0.58; p < .05) and pulmonary vascular resistance (r = 0.58; p < .05). Sodium nitroprusside caused a small increase in the flow velocity (5 +/- 2% at 0.125, 12 +/- 4% at 0.25 microg/kg per minute; p < .05) that was accompanied by systemic vasodilation. The conductance vessel diameter was unchanged after acetylcholine was administered and was only marginally decreased after the administration of sodium nitroprusside. CONCLUSIONS: In CHF acetylcholine reveals preserved receptor-mediated endothelial vasodilation, that is positively correlated to pulmonary hypertension, and cannot be reproduced by sodium nitroprusside.

Protein-energy malnutrition in gastroenterology outpatients: increased risk in Crohn's disease.

A screening study was conducted to identify malnutrition in gastroenterology outpatients and to ascertain whether poor food intake is a contributing factor. A 48-hour recall method was used to collect dietary data from 154 patients (87 women and 67 men). Fourteen (16%) of the women and 8 (12%) of the men were classified as having protein-energy malnutrition (PEM) on the basis of abnormal anthropometric measurements or low serum albumin concentration. PEM was found in several diagnostic groups, but 9 of the 14 malnourished women had Crohn's disease. Protein undernutrition was more evident in women; calorie undernutrition was more evident in men. More women than men had low serum albumin levels. Low hemoglobin levels were particularly prevalent among patients with Crohn's disease. Many of the patients, especially women, had "inadequate" and "marginal" intakes of folate, vitamin A, thiamin, and calcium according to Nutrition Canada interpretive standards. The intake of iron was particularly poor among women: 59% of the intakes of female patients were classified as inadequate (less than 10 mg/day). Ten of the 14 female patients with PEM had inadequate iron intakes. Serum folates of less than 5 ng/ml were present in 72% of the women and 77% of the men. The data suggest that gastrointestinal outpatients are at high risk of malnutrition and that one of the factors contributing to the problem is inadequate food intake.

Protein-energy intake and malnutrition in Crohn's disease.

A detailed nutrient assessment was made of 23 male and 24 female patients with Crohn's disease who entered sequentially into an outpatient clinic. Assessment included 48-hour dietary recall, anthropometric measurements, and biochemical and hematological tests appropriate to characterize protein-energy malnutrition. Approximately 40% of patients had energy intakes equal to only two-thirds of the Recommended Dietary Allowance (RDA). Three men and five women had relative body weights less than 85% of standard, but body weight was not correlated with energy intake. Relative body weight was correlated with arm muscle circumference in both male and female patients and with triceps skinfold and total lymphocyte count in women. Although the mean protein intake was greater than 150% of the RDA, evidence of protein malnutrition included low arm muscle circumference in 14% of the men and 15% of the women, low serum albumin concentration in 13% of the women, and low total lymphocyte count in one-half of the patients. The Crohn's disease activity index was correlated significantly with serum albumin, energy intake, and duration of disease in men and with serum ferritin and hemoglobin concentration in women. Thus, a reduced relative body weight or reduced serum albumin was not uncommon in patients with Crohn's disease but did not necessarily occur in those with reduced intakes of protein and energy. However, a low relative body weight may indicate need for further nutritional assessment.

Nutritional status of gastroenterology outpatients: comparison of inflammatory bowel disease with functional disorders.

Dietary intakes of two groups of gastrointestinal patients, one group with inflammatory bowel disease (IBD)--Crohn's disease or chronic ulcerative colitis--and the other with functional disorders (FD)--irritable bowel syndrome, nonulcer dyspepsia, or gastroesophageal reflux disease, were assessed by means of 48-hour recalls. The relationships between dietary intake and anthropometric and biochemical measurements were examined. The IBD group had lower mean serum albumin and hemoglobin levels (p less than .05); however, FD patients had less adequate diets. The mean energy intake of women with FD was significantly lower than that of women with IBD (p less than .05) and was associated with inadequate or marginal intakes of many nutrients. Comparison of nutrient intakes between the IBD and FD groups revealed a significantly lower mean intake of folate, ascorbic acid, and vitamin A for women with FD than for women with IBD (p less than .05). In general, women had poorer diets and a higher prevalence of abnormal biochemical parameters than men. One notable feature of the dietary pattern of the women was that they consumed less meat than the general population consumed. Increasing meat consumption would improve the intake of many nutrients, including protein and iron. The results of this study suggest that more attention should be given to the adequacy of dietary intakes of gastrointestinal patients in general and of women in particular.

Cost reduction in cardiac surgery.

OBJECTIVE: To reduce surgical waiting lists at the University of Alberta Hospitals. A cost reduction program was initiated, allowing more cases to be performed on the same budget. Reducing the cost of delivering health care services has become necessary as demands upon the system increase. METHODS: Data were retrospectively gathered on patients having open heart surgery at the University of Alberta Hospitals between March 1, 1991 and February 29, 1992. Group 1 were patients operated on before the start of the cost reduction program (September 1, 1991) and group 2 were those operated on after. Student's t test and logistic regression were use to compare population characteristics and to correlate dependent variables. RESULTS: Demographic features and severity indices were not different. Operating time decreased from 4.5 +/- 1.5 to 4 +/- 1 h, P < 0.002. Preoperative, intensive care unit (ICU) and postoperative ward length of stay were reduced (P < 0.002). Total length of stay went from 19.3 +/- 22.7 to 13.8 +/- 10.7 days, P < 0.001. Operating room, nursing and x-ray costs decreased, P < 0.002. Hospital costs declined from $14,182 +/- 16,464 to $10,710 +/- 7,332, P < 0.001. Multiple regression showed hospital stay, ICU, operating room time, severity of illness and age to be significant determinants of cost, P < 0.03 for each. Waiting time and number of patients on the waiting list declined significantly as surgical lists increased. Mortality and rate of readmission following discharge were not different between the two groups. CONCLUSIONS: Substantial cost savings can be made by changing practice patterns, without adverse consequences. ICU and hospital length of stay are the most important cost determinants.

Assessing appropriateness of treatment: a case study of transplantation in older patients with congestive heart failure.

OBJECTIVE: To evaluate the appropriateness of transplantation therapy for older patients with congestive heart failure (CHF). DATA SOURCES: Comparative review of contemporary survival and quality of life data of CHF patients treated medically versus by transplantation. DATA SYNTHESIS: Approximately 300,000 Canadians have CHF and the incidence is increasing as the population ages; suitable donor allografts are found for about 300 CHF patients each year. Overall survival among cardiac allograft recipients, with a mean age of 48 years, is approximately 80% at two years. However, risk from all causes appears higher, and survival lower (range 40 to 78%), for transplant patients 55 years of age and older. Among medically treated patients, with mean age over 60 years, survival is inversely related to level of functional disability, averaging more than 90% at two years for patients with mild limitation and decreasing to 75% and 40% for patients with moderate and severe symptoms, respectively. Perceived quality of life is low in all CHF patients, but is significantly improved by intense out-patient care and education, irrespective of medical or transplant allocation. CONCLUSIONS: Among adults with CHF, the greatest benefit of transplantation is enhanced survival in younger severely disabled patients. However, noncardiac risks are substantial, particularly for older recipients. The great discrepancy between donor and candidate availability prohibits transplantation from being a life expanding therapy for the whole CHF population. When physicians are, simultaneously, patients' and society's advocates a utilitarian decision model using the totality of efficacy data, including degree of efficacy and population effectiveness, may assist determination of the most appropriate therapy.

Can practice patterns and outcomes be successfully altered? Examples from cardiovascular medicine. The Clinical Quality Improvement Network (CQIN) Investigators.

OBJECTIVE: To offer an attributive opinion of recent improvements in acute myocardial infarction (AMI) practice patterns and patient outcomes in the culture of an active health care research program. DATA SOURCES: Review of original clinical data from five sequential, consecutively enrolled, AMI patient cohorts at the University of Alberta Hospitals from 1987-93. DATA SYNTHESIS: Early cohorts had low use of trial-proven efficacious therapies for AMI, particularly among high risk older and female patients. Over time, there were continuous and marked increases in the use of efficacious therapies and decreased use of nonefficacious therapies, with a parallel decrease in mortality among high risk patients. CONCLUSIONS: In a large tertiary care hospital between 1987 and 1993 the use of evidence-based AMI therapy and survival in high risk patients significantly increased. The continuity and large size of these improvements in AMI practice patterns, compared with similar populations reported in the contemporary literature, suggest it is unlikely they were due to chance. Rather, intercurrent repeated measurement and reporting of key health care performance indicators, and initiation of explicit critical path AMI practice guidelines provide a more likely explanation. Future studies by a network of community and university investigators will test whether these findings are true for a broad AMI population and whether similar practice definition and improvement tools are effective for other cardiac problems, including the management of congestive heart failure.

Promoting physician-nurse collaboration throughout the organization.

For health care institutions embracing the total quality approach to management, interdisciplinary collaboration focused on the processes associated with patient care is vital. To attain a vision of effective physician-nurse collaboration, specific initiatives at all levels of the University of Alberta Hospitals have helped to transform the vision into current reality.

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin-treated rats.

AIM: Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo. METHODS: Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests. RESULTS: Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups. CONCLUSIONS: Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

Polysomnography underestimates altered cardiac autonomic control in patients with obstructive sleep apnea.

BACKGROUND: Repetitive nocturnal sympathetic activation during episodes of apnea and postapneic hyperventilation increases cardiovascular risk. The effects of hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea on sympathico-vagal balance have not been assessed yet. HYPOTHESIS: Hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea cause increased sympathetic activity when compared to normal respiration in nonREM stages 2­4. METHODS: A total of 34 patients were studied using in-laboratory polysomnography including continuous ECG recording. Absolute spectral power of heart rate variability in the very low (VLF), low (LF), and high frequency (HF) bands and low frequency to high frequency power ratio (LF/HF ratio) were analyzed during apnea, hypopnea, and during the pre- and post-phases of such respiratory episodes and compared to spectral powers during normal respiration in nonREM sleep 2­4. RESULTS: Patients with hypopnea and/or obstructive apnea showed higher power of VLF and the LF/HF ratio in intervals of hypopnea/apnea and in non-apneic, non-hypopneic intervals before and after hypopnea/apnea compared to normal respiration in nonREM stages 2­4. CONCLUSION: The effect of sleep-disordered breathing on alteration of autonomic tone in patients with hypopnea and obstructive apnea is more severe than estimated by conventional polysomnographic assessment of apnea and hypopnea. Patients with sleep apnea show a sympathetic overdrive not only during phases of hypopnea and obstructive apnea but also in non-apnea, non-hypopnea intervals before and after hypopnea, and obstructive apnea.