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Cardiorespiratory function after correction of tetralogy of Fallot. Modifying effect of previous shunt operation.

Of 28 patients with total surgical correction of tetralogy of Fallot in adult life, 22 had previously undergone Blalock-Taussig shunt operation. Possible modifying effects of the shunt on pulmonary ventilation and perfusion and on exercise tolerance were investigated with spirometry, radiospirometry and bicycle ergometry. The observed ventilatory volumes and capacities and diffusing capacity were significantly lower than the predicted values. Vital capacity was significantly reduced in patients with adverse NYHA or haemodynamic classification. Between the various NYHA or haemodynamic groups no statistically significant difference was demonstrable in pulmonary function or diffusing capacity or in airway resistance. Ventilatory obstruction was found also in patients without previous shunt. Other lung function tests showed no significant difference between the shunt and the non-shunt group. Nor was distribution of lung perfusion significantly affected by shunt. No correlation was seen between lung function and bicycle ergometric findings. However, in non-shunt patients who had ventilatory obstruction or impaired diffusing capacity, exercise tolerance was significantly higher than in patients who had had palliative shunt.

Adult↗

Superiority of nonpharmacologic therapy compared to propranolol and placebo in men with mild hypertension: a randomized, prospective trial.

We compared the effects of nonpharmacologic therapy, propranolol monotherapy, and placebo on blood pressure, metabolic, exercise, and quality of life variables in a 12-week, randomized, placebo-controlled trial of 79 male patients with hypertension. A significant reduction in diastolic blood pressure was observed with both nondrug therapy (-8.0 +/- 1.08 mm Hg) and propranolol (-9.5 +/- 1.46 mm Hg) compared to placebo (-0.1 +/- 2.01 mm Hg). However, only patients receiving nonpharmacologic therapy showed a reduced body mass index, lower total and low-density lipoprotein serum cholesterol levels, and increased exercise tolerance compared to both propranolol and placebo. Patients receiving propranolol felt less anxious and unsure but showed a significant decrement in nocturnal penile tumescence compared to both placebo and nondrug therapy. Patients receiving nondrug therapy felt more energetic and reported improved sexual arousal and greater sexual satisfaction after treatment. Reductions in blood pressure in the nondrug treatment group were related to both weight reduction and improved fitness. We conclude that nondrug therapy is effective in controlling blood pressure in men with mild hypertension and is associated with improvements in weight, lipoprotein levels, and exercise tolerance compared to both propranolol and placebo. Quality of life assessments further support the use of nondrug therapy in this context.

Diet, Reducing↗

Alexithymia may influence the diagnosis of coronary heart disease.

A number of psychosomatic studies have suggested that alexithymia, impairment in identifying and expressing inner feelings, might somehow affect the course of various illnesses. However, none of these studies have distinguished between an impact of alexithymia on actual pathophysiological change versus an impact only on illness behavior. In the present study, a population-based random sample of 2297 middle-aged men from Eastern Finland was evaluated for alexithymia using the Finnish version of the self-report Toronto Alexithymia Scale (TAS). Although high TAS scores were associated with prior diagnosis of coronary heart disease (CHD), they were not associated with greater prevalence of ischemia on an exercise tolerance test. The results of B-mode ultrasonography of the carotid artery for those who had a CHD diagnosis showed that carotid atherosclerosis actually decreased significantly as alexithymia increased. An interaction analysis indicated that alexithymia was related to increased probability of being diagnosed with CHD only among those who had mildly or moderately progressed carotid atherosclerosis, and not among those with the most severe progression. Alexithymia was associated with higher perceived exertion, and to some extent, with more self-reported symptoms during the exercise tolerance test. The findings support the hypothesis that alexithymia relates to increased symptom reporting rather than pathophysiological changes in CHD. The results also suggest that alexithymic men may get diagnosed earlier, perhaps because of their different illness behavior.

Adult↗

A placebo-controlled trial of captopril in refractory chronic congestive heart failure. Captopril Multicenter Research Group.

Ninety-two patients with heart failure refractory to digitalis and diuretic therapy had captopril (n = 50) or placebo (n = 42) added to their therapeutic regimen in a randomized, double-blind trial. During a 2 week dosage titration period, one captopril-treated patient died of an intracerebral hemorrhage. Over the remaining 10 week evaluation period, 1 captopril-treated patient (2%) was excluded from the study because of treatment failure as compared with 12 discontinuations (4 deaths and 8 failures [29%]) among the placebo group (p less than 0.001). Eighty percent of patients in the captopril group exhibited some degree of clinical improvement, whereas only 27% in the placebo group did so (p less than 0.001). The therapeutic advantage of captopril over placebo was evidenced by a mean improvement of 0.52 (2.8 +/- 0.1 to 2.3 +/- 0.1) in the New York Heart Association functional class value as compared with 0.03 (2.9 +/- 0.1 to 2.8 +/- 0.1) with placebo (p less than 0.0001). There was a 24% mean increase in exercise tolerance with captopril (495 +/- 22 to 614 +/- 27 seconds) as compared with 0.4% with placebo (480 +/- 28 to 483 +/- 43 seconds) (p less than 0.01); the captopril group had an increase in the ejection fraction from a mean baseline value of 0.19 +/- 0.02 to 0.22 +2- 0.02 as compared with 0.19 +/- 0.02 to 0.18 +/- 0.002 (p less than 0.05) in the placebo group. A cohort analysis revealed that improvement in exercise tolerance with captopril was gradual and progressive throughout the 12 weeks. Improvement in specific symptoms of heart failure, that is, dyspnea, fatigue and orthopnea, and the reduction of edema also were greater in the captopril-treated patients (p less than 0.05 to p less than 0.001). Captopril therapy was well tolerated, although symptomatic hypotension after the first dose caused withdrawal of three patients (3%) from the study. It was concluded that captopril is an effective adjunctive treatment to digitalis and diuretic drugs for patients with refractory heart failure.

Adult↗

Mechanism of action of beta-adrenergic receptor blocking agents in angina pectoris: comparison of action of propranolol with dexpropranolol and practolol.

The effect on exercise tolerance of racemic propranolol has been assessed in eight angina pectoris patients and compared with that of dexpropranolol (the dextro isomer of propranolol), practolol (I.C.I. 50172), and saline. Dexpropranolol has the same local anaesthetic action as propranolol with negligible beta-adrenergic receptor blocking activity, while practolol is a cardio-selective beta-adrenergic blocking agent which does not have local anaesthetic activity.Saline and dexpropranolol had no significant effect on exercise time; racemic propranolol and practolol improved exercise tolerance in six subjects, the response to the two drugs being very similar in individual patients. It was concluded that the beneficial effect of propranolol in angina pectoris results from its action as a beta-adrenergic receptor blocking agent and is not due to its local anaesthetic, or quinidine-like, activity.

Acetanilides↗

Two minute walking distance in cystic fibrosis.

We have evaluated the 'two minute walking distance' in children with cystic fibrosis as an objective measurement of exercise tolerance. There was a strong correlation between walking distance and height in 89 normal children (r = 0.72). Fifty children with cystic fibrosis showed a similar correlation (r = 0.56) with a mean result of 94% of that expected for height compared with the normal children. There was a training effect in the normal children with the second walk being significantly better than the first, but this was not evident in children with cystic fibrosis. The test was reproducible with no significant change in 12 children retested after one to three months. Sixteen children with cystic fibrosis admitted for treatment of chest disease showed a significant improvement in walking distance with treatment. Children as young as 5 years old can perform a walking distance test. It seems to be an objective way of assessing exercise tolerance and can help in evaluating response to treatment.

Adolescent↗

Reduced side effects by low dose of acetylsalicylic acid (ASA) in patients with myocardial infarction; estimations of serum thromboxane B2 and PGF2 alpha.

In a secondary prevention study 867 male and female patients with myocardial infarction (MI) were divided 3 weeks after onset of MI into 4 treatment groups: I - 273 patients received additionally to their common medication 1000 mg ASA/d; II - 313 patients got 60 mg ASA/d; III - 208 patients 30 mg ASA/d resp.; IV - 73 patients received no ASA administration due to ASA contraindications. One year after onset of MI the following parameters were checked: mortality, malignant arrhythmia, exercise tolerance, gastrointestinal symptoms and hemorrhage as typical side effects of ASA, formation of thromboxane B2 and PGF2 alpha in clotting whole blood. The low dose of 30 mg ASA/d reśultes in a clear reduction of ASA side effects (6,4% of patients with symptoms) in comparison to group I (15,9% of patients with symptoms), in a tendency to decreased mortality, and in unchanged frequency of malignant arrhythmias resp. Concerning the maximum exercise tolerance no significant difference could be observed in all 4 groups investigated. Estimations of serum thromboxane B2 by radioimmunoassay and gas chromatography revealed strong inhibitions of the thromboxane formation in all patients with ASA administrations; even the low dose of 30 mg ASA/d decreased thromboxane B2 by more than 95%.

Adult↗

The prevalence and significance of a patent foramen ovale in pulmonary hypertension.

In order to determine the prevalence and significance of a patent foramen ovale (PFO) in pulmonary hypertension, 58 patients were studied with transesophageal echocardiography, right-sided heart catheterization, and exercise testing. In order to examine if a PFO might be associated with a better outcome, survival was estimated, based on a formula derived from the National Institutes of Health Primary Pulmonary Hypertension Registry, for the patients with primary pulmonary hypertension (PPH). A PFO was found in 26 percent (15 of 58) of all patients studied, 25 percent (10 of 40) of those with PPH, and 28 percent (5 of 18) of those with secondary pulmonary hypertension. We found no significant difference in any hemodynamic variable or exercise tolerance between the patients with and without a PFO, or for subsets of patients with primary and secondary pulmonary hypertension. We also found no significant difference in the 1-, 2-, 3-, 4-, or 5-year estimated survival, for the patients with PPH between those with and without a PFO. The prevalence of a PFO in pulmonary hypertension appears similar to the normal population. A PFO provides no detectable influence on resting hemodynamics or exercise tolerance in patients with pulmonary hypertension and is not clearly associated with patients expected to survive longer.

Adolescent↗

[Effect of intravenous ambroxol hydrochloride on lung function and exercise capacity in patients with severe chronic obstructive pulmonary disease].

The effect of Ambroxol hydrochloride on spirometry, pulmonary gas exchange and exercise capacity in patients with COPD were evaluated. Twenty patients mean age 59 +/- 9 yr presenting with severe airways obstruction were divided by random number to two groups: treated (L) and control (K). L patients received iv infusion of one gram of Ambroxol in 500 ml of 0.9% saline daily, for 5 days. K patients received infusions of 500 ml 0.9% saline at the same intervals. Blood gases, capnography and incremental exercise test on cycloergometer were performed before treatment and after the fifth dose of the drug or placebo. Before treatment spirometry, blood gases, capnometric++ indices and exercise tolerance were similar in both groups. After treatment in patients from L group an increase in VC from 1.78 +/- 0.61 L to 2.04 +/- 0.58 L (p < 0.01), FEV1 from 0.96 +/- 0.43 L to 1.11 +/- 0.49 L (p < 0.01), MEF25 from 1.36 +/- 0.93 L/sec to 1.61 +/- 0.96 L/sec (p < 0.01) was found. End-tidal carbon dioxide in 60 sec hyperventilation test decreased from 3.7% to 2.9% (p < 0.001). There were no differences in exercise tolerance and blood gases after treatment. In the control group all studied variables remained unchanged. We conclude that Ambroxol improves airways patency in patients with severe COPD.

Aged↗

The role of inspiratory muscle function and training in the genesis of dyspnoea in asthma and COPD.

The cardinal symptom of both asthma and COPD is dyspnoea, and from a patient perspective, the most troublesome. There are a multitude of inputs to the sensation of dyspnoea, few of which are readily modifiable. The level of inspiratory muscle work contributes to the sense of respiratory muscle effort and thence dyspnoea. Inspiratory muscle work is elevated in patients with COPD and asthma due to hyperinflation and an increased ventilatory requirement for exercise. Treatment tends to concentrate on reducing the load upon the inspiratory muscles induced by hyperinflation. Bronchodilators are the mainstay of treatment for COPD and asthma; they reduce hyperinflation, inspiratory muscle loading and dyspnoea. In addition, programmes of pulmonary rehabilitation have an excellent evidence base for improving dyspnoea, exercise tolerance and quality of life. However, provision within the NHS is limited and not all patients are suitable. One component of pulmonary rehabilitation that can be implemented safely in a home-based setting is specific inspiratory muscle training (IMT). There is a strong theoretical rationale for IMT in patients with airway obstruction, which is also supported by empirical evidence. IMT offers a relatively accessible non-pharmacological treatment for dyspnoea that also improves exercise tolerance and quality of life.

Journal Article↗

A pilot experience with permanent biventricular pacing to treat advanced heart failure.

BACKGROUND: The prognosis and quality of life of patients with advanced heart failure remain poor. The purpose of this study was to evaluate new nonpharmacologic approaches. Biventricular pacing was proposed in this indication, based on the encouraging results of acute hemodynamics studies. METHODS: Fifty patients with drug-resistant heart failure (New York Heart Association [NYHA] class III/IV, 16 of 34) were consecutively implanted with biventricular pacemakers. All patients had severe dilated cardiomyopathy and intraventricular conduction delay. Survival, NYHA class, electrocardiogram, echocardiographic data, and exercise tolerance were assessed over a mean follow-up period of 15.4 +/- 10. 2 months. RESULTS: At the end of follow-up, 55% of patients were alive without heart transplantation or left ventricular assistance device. The mortality rate was significantly lower in class III (12. 5%) than in class IV patients (52.5%). In survivors, biventricular pacing significantly improved symptoms (NYHA class 2.2 +/- 0.5 at follow-up vs 3.7 +/- 0.5 at baseline) and exercise tolerance ((. )VO(2) peak 15.5 +/- 3.4 mL/min per kilogram at follow-up vs 11.1 +/- 3 mL/min per kilogram at baseline). CONCLUSIONS: Biventricular pacing appears to improve the functional status of patients with dilated cardiomyopathy with advanced heart failure. The technique appears to be attractive as an additive treatment, especially in class III patients. Controlled randomized studies are needed to validate this novel concept.

Aged↗

[Pharmacological management of stable COPD].

Pharmacotherapy for stable COPD depends on the severity of the disease. Thus, decisions on therapeutic interventions should be based not solely on the degree of airflow obstruction but also on symptoms, exercise tolerance, frequency and severity of exacerbations, and health-related quality of life. The progressive nature of COPD necessitates a stepwise increase of medication (step-up approach) depending on the severity of the disease. Although none of the currently available medications has been shown to modify the abnormal reaction to inhaled noxious particles and gases that lead to COPD, pharmacotherapy has beneficial effects on the clinical course of the disease by controlling symptoms, increasing exercise tolerance and improving general health status.

Administration, Inhalation↗

[Results of heart valve replacement. Prognosis--occupational and general disability--occupational rehabilitation].

The success of valve surgery has led to a marked improvement in prognosis, quality of life and exercise tolerance in patients with symptomatic valvular heart disease. The degree of subjective and objective improvement depends on multiple preoperative factors like NYHA status, left ventricular function, valve lesion and type of valve replaced as well as peri- and postoperative factors like the occurrence of a perioperative myocardial infarction, the degree of intraoperative myocardial damage, the type of valve replaced and the speed and degree of postoperative regression of left ventricular hypertrophy and dilatation. The postoperative exercise tolerance is a major determinant for postoperative vocational rehabilitation. Therefore the individual functional assessment of patients postoperatively is of major importance.

Aortic Valve↗

[Functional changes of the cardiovascular system and their pharmacological correction during suited immersion].

In the course of 126 man/exposures of 3 hours to 3 days in duration, in which 39 test subjects took part, circulation responses to the upright and supine body position during suited immersion as well as orthostatic and exercise tolerance after immersion were investigated. During 24 man/exposures for 2 days the subjects were administered per os placebo or one of the four neurotrophic drugs: sydnocarb, sydnogluton, sydstrigluton, estrigluton. Clinical observations, instrumented data and methodical features of the immersion model used give evidence that the suited immersion has advantages over currently used procedures simulating the effects of hypogravity. The drugs allowed cardiovascular correction that increased aerobic capacity of the body and enhanced cardiovascular orthostatic and exercise tolerance.

Cardiovascular Diseases↗

Overview of treprostinil sodium for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a life-threatening disorder that refers to a group of diseases characterized by an abnormal elevation of the blood pressure within the pulmonary circulation due to a vasculopathy of the pulmonary microcirculation (1). If left untreated, the overall prognosis of pulmonary arterial hypertension is poor, with a 5-year survival rate of 34%. The most common cause of death is progressive right-sided heart failure (2). There is no pharmacologic cure for pulmonary arterial hypertension, and a team approach is required for the proper care of these patients (3). Treatment is directed at improving clinical symptoms, increasing exercise tolerance and extending survival. Until just a few years ago, standard treatment options for the treatment of pulmonary arterial hypertension were limited and included coumarin derivatives, calcium channel blockers, diuretics, digoxin and oxygen supplementation (4). In the last decade, the therapeutic options for pulmonary arterial hypertension have made considerable advances. In at least three major randomized controlled trials, the continuous intravenous infusion of epoprostenol, a synthetic salt of prostacyclin with potent vasodilatory ability, has been shown to improve exercise tolerance, hemodynamics, survival and quality of life in patients with New York Heart Association (NYHA) functional classes III and IV with either primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma (5-9). Epoprostenol has now become a mainstay therapy in the long-term treatment of primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma. Nevertheless, epoprostenol is far from an ideal form of therapy. Issues such as the short half-life of the drug, need for continuous central intravenous access and significant side effects have led to the development of more stable prostacyclin analogues as alternative therapies for primary pulmonary hypertension. These alternative therapies include iloprost (inhaled delivery) and treprostinil (subcutaneous delivery). As a result, the Food and Drug Administration (FDA) recently approved treprostinil for the treatment of pulmonary arterial hypertension in patients with NYHA classes II-IV. This review will offer a discussion of the basic pharmacology of treprostinil, its similarities to and differences from epoprostenol, the animal studies as well as the initial investigational studies leading to its FDA approval, and clinical uses of the drug alone or in combination with newer therapies directed at pulmonary arterial hypertension developed over the last decade.

Antihypertensive Agents↗

[Clinical significance and pathogenic mechanisms of insulin resistance in chronic renal insufficiency (part II): pathogenic factors of insulin resistance in chronic renal insufficiency].

INTRODUCTION: Factors implicated in the pathogenesis of insulin resistance in chronic renal failure are: uremic toxins, exercise tolerance, metabolic acidosis, secondary hyperparathyroidism, vitamin D deficiency. Many of them may contribute, but are not the main cause of insulin resistance in uremia. The aim of this review is to debate about each, separately. UREMIC TOXINS: Hippurate and pseudouridine are specific for uremia and inhibit glucose utilization at concentrations found in sera of uremic subjects. Partially purified toxins from uremic sera, after hemodialysis therapy, ameliorate beta-cell response to hyperglycemia and increase tissue sensitivity to insulin. EXERCISE INTOLERANCE: Exercise intolerance is common among hemodialysis patients, and also it can be the cause of insulin resistance. Moderate endurance training program improved both the exercise tolerance and insulin sensitivity in patients on hemodialysis. METABOLIC ACIDOSIS: Metabolic acidosis is frequent in uremia, but not in hemodialysis patients. Treatment of metabolic acidosis increases insulin sensitivity and insulin secretion, but significant degree of insulin resistance still exists in uremic patients. SECONDARY HYPERPARATHYROIDISM: After surgical correction of hyperparathyroidism, in hemodialysis patients, glucose tolerance and insulin secretion increase without significant changes in insulin sensitivity. Defect in insulin release attributable to reduced ATP content in the pancreatic islets induced partially by high intracellular calcium, secondary to augmented PTH-induced calcium entry into cells. VITAMIN D DEFICIENCY: Acute and chronic intravenous 1,25-Dihydroxycholecalciferol therapy corrects insulin resistance in dialysis patients, in absence of PTH suppression. These results are consistent with the hypothesis that 1,25(OH)2 D3 deficiency is a primary factor of insulin resistance. ERYTHROPOIETIN THERAPY: Corrects insulin resistance beside anaemia. CONCLUSION: Now we know more about pathogenesis of insulin resistance in uremic patients, and we must begin with early treatment of every pathogenic factor. Insulin sensitivity improved after hemodialysis, although it was still lower than control values.

Humans↗

Cardiorespiratory function in surgically treated thoracic scoliosis with respect to degree and apex of scoliotic curve.

We studied the relationship of deterioration of cardiorespiratory function with respect to degree and localisation of apex of spinal curvature. The study comprised 33 patients (27 females and 6 males) aged 15 (11-21) years, surgically treated for an average scoliotic angle of 72 degrees (55-129 degrees, after Cobb) which was postoperatively reduced to 32.6 degrees (13-74 degrees). The static and dynamic cardiorespiratory function parameters were tested (pre-operatively and 24 months after surgery) by spirometry and plethysmography, arterial blood gas analysis, and the exercise tolerance test. In terms of the site and apex of the thoracic curve as determined by spine X-ray, patients were divided into two groups: upper thoracic scoliosis with the apex between T5 and T8 and lower thoracic scoliosis with the apex between T9 and T11. Only upper thoracic scoliosis with Cobb angle of more than 70 degrees correlated (r = -1) with restrictive ventilation disorder (vital capacity 68%) and latent hypoxaemia (uptake O2 ml/kg/min 63%) demonstrated during the exercise tolerance test (p > 0.05). The results of the test have demonstrated that surgically obtained 54% correction of the scoliotic curve improves pulmonary function (p < 0.05). However, the improvement does not match the degree of achieved scoliotic curve correction, what means that even in surgically treated high-angled thoracic scoliosis exists an increased risk of morbidity and mortality.

Adolescent↗

Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost.

OBJECTIVE: To compare prostacyclin with an analogue, iloprost, in treatment of severe pulmonary hypertension. PATIENTS: Eight patients with severe pulmonary hypertension: primary in five, thromboembolic pulmonary hypertension in three. METHODS: All patients underwent right heart catheterisation. Mean (SEM) right atrial pressure was 9.9 (2.2) mm Hg, mean pulmonary artery pressure 67.4 (3.0) mm Hg, cardiac index 1.75 (0.13) l/min/m2 and mixed venous oxygen saturation 59.1(3.1)%. Continuous intravenous epoprostenol (prostacyclin, PGI2) or iloprost was given for phase I (three to six weeks); the patients were then crossed over to receive the alternate drug in an equivalent phase II. MAIN OUTCOME MEASURES: Exercise tolerance was measured at baseline and at the end of phase I and II with a 12 minute walk; distance covered, rest period, percentage drop in arterial oxygen saturation (delta Sao2%) and percentage rise in heart rate (delta HR%). RESULTS: Walking distance covered rose from (mean (SEM)) 407.5 (73) to 591 (46) m with PGI2 (p = 0.004) and to 602.5 (60) m while on iloprost (p = 0.008). Rest period decreased from 192 (73) seconds at baseline to 16 (16) seconds with PGI2 (p = 0.01) and to 58 (34) seconds with iloprost (p = 0.008). Delta HR% was 37.5(6)% at baseline, 35(3)% on PGI2, and 24(6)% on iloprost (p = 0.04). CONCLUSIONS: Both intravenous PGI2 and iloprost caused significant improvement in exercise tolerance. Iloprost offers an alternative to PGI2 treatment of severe pulmonary hypertension.

Adult↗