Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure

OBJECTIVES: This study sought to establish the chemosensitivity of patients with chronic heart failure. BACKGROUND: The ventilatory response to exercise is often increased in patients with chronic heart failure, as characterized by the steeper regression slope relating minute ventilation to carbon dioxide output. We hypothesized that the sensitivity of chemoreceptors may be reset and may in part mediate the exercise hyperpnea seen in this condition. METHODS: Hypoxic and peripheral hypercapnic chemosensitivity were studied in 38 patients with chronic heart failure (35 men, 3 women; mean [+/-SE] age 60.2 +/- 1.3 years; radionuclide left ventricular ejection fraction 25.7 +/- 2.3%) and 15 healthy control subjects (11 men, 4 women; mean age 54.9 +/- 3.0 years) using transient inhalations of pure nitrogen and single breaths of 13% carbon dioxide, respectively. The change in chemosensitivity during mild exercise (25 W) was assessed in the first 15 patients and all control subjects. Central hypercapnic chemosensitivity was also characterized in 25 patients and 10 control subjects by the rebreathing of 7% carbon dioxide in 93% oxygen. Cardiopulmonary exercise testing was performed in all subjects. RESULTS: Maximal oxygen consumption was 16.6 +/- 0.9 versus 29.7 +/- 2.2 mol/kg per min (p < 0.0001), and the ventilation-carbon dioxide output regression slope was 37.2 +/- 1.5 versus 26.5 +/- 1.4 (p < 0.0001) in patients and control subjects, respectively. Hypoxic and central hypercapnic chemosensitivity were enhanced in patients (0.707 +/- 0.076 vs. 0.293 +/- 0.056 liters/min per % arterial oxygen saturation [SaO2], p = 0.0001 and 3.15 +/- 0.41 vs. 2.02 +/- 0.25 liters/min per mm Hg, p = 0.025, respectively) and correlated significantly with the ventilatory response to exercise. Hypoxic chemosensitivity was augmented during exercise in patients and in control subjects but remained higher in the former (1.530 +/- 0.27 vs. 0.685 +/- 0.12 liters/min per %SaO2, p = 0.01). The peripheral hypercapnic chemosensitivity of patients at rest and during exercise was similar to that in control subjects, consistent with its lesser contribution to overall carbon dioxide chemosensitivity. CONCLUSIONS: Enhanced hypoxic and central hypercapnic chemosensitivity may play a role in mediating the increased ventilatory response to exercise in chronic heart failure.     

Can the ventilatory equivalent for carbon dioxide predict the severity of functional impairment in patients with cardiac insufficiency?

OBJECTIVE: To evaluate whether the changes in the ventilatory equivalent for carbon dioxide (VE/VCO2), during the early stages of cardiopulmonary exercise testing, can predict maximal oxygen consumption (VO2max) in patients with chronic heart failure. METHODS: We studied 38 patients (30 males, mean age 56 +/- 11 years) with chronic heart failure. All patients performed maximal symptom limited, treadmill exercise test with breath-by-breath respiratory gas analysis. They were divided in two groups according to their maximal oxygen consumption (group I-VO2max above 14 ml/kg/min and group II-VO2max below 14 ml/kg/min). In both groups, we analysed VE/VCO2 at rest, at the anaerobic threshold (AT) and at peak exercise, and the percentage of VE/VCO2 reduction from rest to AT. RESULTS: Eleven patients had a VO2max below 14 ml/kg/min (group II). At rest VE/VCO2 = 53 +/- 13 in group II versus 47 +/- 10 in group I (p = 0.048), at the AT VE/VCO2 = 46 +/- 12 in group II versus 36 +/- 7 in group I (p = 0.001) and at peak exercise VE/VCO2 = 46.2 +/- 13 in group II versus 36.2 +/- 6 in group I (p = 0.0002). There was a 24% reduction in the VE/VCO2, from rest to AT in group I, compared to a 16% reduction in group II (p = 0.004). A reduction in the VE/VCO2 from rest to AT less than 16% predicted a VO2max below 14 ml/kg/min with a sensitivity of 60% and a specificity of 93%. CONCLUSIONS: Patients with severe functional impairment have higher values of VE/VCO2 in all exercise stages. A reduction of VE/VCO2 from rest to anaerobic threshold of less than 16% is a high specific predictor of a VO2max below 14 ml/kg/min.     

Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.     

Loss of endothelium mediated vascular relaxation as a response to various clamping pressures. Part II. Direct measurements of clamping pressures and scanning electron microscope study

BACKGROUND: Accurate prognosis in chronic heart failure has become increasingly important in assessing the efficacy of treatment and in appropriately allocating scarce resources for transplantation. Previous studies of severe heart failure have been limited by short follow-up periods and few deaths. OBJECTIVE: To establish clinical, hemodynamic, and cardiopulmonary exercise test determinants of survival in patients with heart failure. DESIGN: Retrospective study. SETTING: Hospital-based outpatient heart failure clinic. PARTICIPANTS: 644 patients referred for evaluation of heart failure over 10 years. MEASUREMENTS: Age, cause of heart failure, body surface area, cardiac index, ejection fraction, pulmonary capillary wedge pressure, left ventricular dimensions, watts achieved during exercise, heart rate, maximum systolic blood pressure, and oxygen uptake (VO2) at the ventilatory threshold and at peak exercise were measured at baseline. Univariate and multivariate analyses were done for clinical, hemodynamic, and exercise test predictors of death. A Cox hazards model was developed for time of death. RESULTS: During a mean follow-up period of 4 years, 187 patients (29%) died and 101 underwent transplantation. Actuarial 1-year and 5-year survival rates were 90.5% and 73.4%, respectively. Resting systolic blood pressure, watts achieved, peak VO2, VO2 at the ventilatory threshold, and peak heart rate were greater among survivors than among nonsurvivors. Cause of heart failure (coronary artery disease or cardiomyopathy) was a strong determinant of death (relative risk for coronary artery disease, 1.73; P< 0.01). By multivariate analysis, only peak VO2 was a significant predictor of death. Stratification of peak VO2 above and below 12, 14, and 16 mL/kg per minute demonstrated significant differences in risk for death, but each cut-point predicted risk to a similar degree. CONCLUSIONS: Peak VO2 outperforms clinical variables, right-heart catheterization data, exercise time, and other exercise test variables in predicting outcome in severe chronic heart failure. Direct measurement of VO2 should be included when clinical or surgical decisions are being made in patients referred for evaluation of heart failure or those considered for transplantation.     

The prevalence of hypertension and the state of cardiovascular health in Venezuela and surrounding nations

BACKGROUND: Exertional dyspnea is a common symptom in patients with heart failure, and the mechanisms responsible for the symptom are unknown. The purpose of this study was to identify factors responsible for the symptom of exertional dyspnea in patients with heart failure. METHODS: Resting pulmonary-function tests and maximal cardiopulmonary exercise tests were performed in 71 patients with New York Heart Association functional class II-IV symptoms (mean ejection fraction 30.6%; mean age, 68 years). RESULTS: The severity of dyspnea at peak exercise, which patients rated as 3 to 10 on a 1 to 10 severity scale, did not correlate with rest or exercise hemodynamic, spirometric, or metabolic variables, including peak oxygen uptake (VO2), minute ventilation (Ve), and respiratory rate, or with derived variables including Ve/VO2, Ve/VCO2, and the dyspnea index (Ve/maximum voluntary ventilation). Additionally, these variables did not differ between patients who reported limitation of exercise by dyspnea and those who were limited by fatigue. CONCLUSIONS: The symptom of exertional dyspnea in patients with heart failure is not determined by abnormalities in ventilatory function or demand.     

Direct and indirect assessment of skeletal muscle blood flow in patients with congestive heart failure

Techniques which are currently used to measure skeletal muscle blood flow (SMBF) in patients with congestive heart failure (CHF) are neither convenient nor accurate. They have led to discrepant results in patients with congestive heart failure and are, in part, responsible for the ongoing debate regarding the factors which limit the rise in body oxygen consumption during exercise in these patients. However, direct measurement of SMBF may not be needed during exercise in patients with severe CHF. Their skeletal muscles maximally extract oxygen. Consequently, increase in oxygen consumption by the skeletal muscles is only mediated by a concomitant increase in SMBF. In patients with severe CHF, peak body oxygen consumption attained during maximal exercise closely depends on the rise in SMBF, and thus provides an indirect measurement of SMBF.     

Rupture of Valsalva''s sinus of subacute development

In this study, the effects of forearm static exercise were determined on local blood flow and oxygen consumption in 15 normal individuals (NL) and their responses were compared with ten patients in congestive heart failure (CHF). Forearm blood flow was determined by a plethysmographic technique before and during 15% of maximum voluntary contraction of the forearm. Regional arterial and venous oxygen contents were sampled and forearm oxygen consumption calculated by the Fick principle. At rest, forearm blood flow was less in patients with heart failure than in normal individuals; however, this was compensated for by an increased oxygen extraction, thus maintaining forearm oxygen consumption at a normal level. In contrast, during static exercise, forearm blood flow failed to rise normally with heart failure (NL 9.31; CHF 4.35 ml/min-100 ml, P less than 0.001) and the increased oxygen extraction was not sufficient to maintain a normal forearm oxygen consumption (NL .82; CHF .44 ml/min-100 ml, P less than 0.01). Therefore, patients with congestive heart failure demonstrate regional circulatory and metabolic abnormalities during static exercise that are comparable to those present during dynamic exercise. Because of a limited ability of their skeletal muscle resistance vessels to respond to dilator stimuli, they have an attenuation of their exercise hyperemia which leads to an earlier shift to anaerobic metabolism.     

Oxygen deficit during exercise testing in heart failure. Relation to submaximal exercise tolerance

Measurements of oxygen deficit during submaximal exercise were correlated with the anaerobic threshold (as measured by gas exchange analysis), peak work rate on a ramp protocol, and the ability to perform constant work rate exercise in 10 male patients with New York Heart Association class 2 congestive heart failure and 12 age- and gender-matched normal controls. All subjects performed a maximal ramp exercise test for measurement of the anaerobic threshold. In addition, several 15-min constant work rate exercise sessions were conducted to evaluate oxygen deficit, measured as the area between the "ideal" square curve of oxygen consumption at the onset of constant work rate exercise and the actual exponentially shaped curve. Since the oxygen deficit significantly correlated with the plateau oxygen consumption during the 25-W constant work rate exercise (r = 0.61, p = 0.002), the oxygen deficit was normalized by the rectangular area of 15-min oxygen consumption above baseline. This normalized value significantly correlated with the inverse of the anaerobic threshold (r = 0.81, p < 0.0001). The logarithm of the normalized oxygen deficit significantly correlated with the maximum ramp work rate (r = -0.86, p < 0.0001) and the highest constant work rate sustained for 15 min (r = -0.82, p < 0.0001). In addition, the time to reach plateau oxygen consumption for the 25-W exercise significantly correlated with the inverse of the anaerobic threshold (r = -0.78, p < 0.0001), the maximum ramp work rate (r = -0.76, p < 0.0001), and the highest constant work rate sustained for 15 min (r = -0.74, p < 0.0001). Thus, the oxygen deficit seen in patients with heart failure during constant work rate exercise results from abnormally slow oxygen uptake kinetics and correlates with exercise capacity as measured by anaerobic threshold (via gas exchange analysis) and maximal and submaximal exercise tolerance. Oxygen deficit warrants further evaluation as a submaximal index of functional capacity in patients with heart failure.     

Oxygen uptake kinetics during low level exercise in patients with heart failure: relation to neurohormones, peak oxygen consumption, and clinical findings

OBJECTIVE: To investigate whether oxygen uptake (VO2) kinetics during low intensity exercise are related to clinical signs, symptoms, and neurohumoral activation independently of peak oxygen consumption in chronic heart failure. DESIGN: Comparison of VO2 kinetics with peak VO2, neurohormones, and clinical signs of chronic heart failure. SETTING: Tertiary care centre. PATIENTS: 48 patients with mild to moderate chronic heart failure. INTERVENTIONS: Treadmill exercise testing with "breath by breath" gas exchange monitoring. Measurement of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and noradrenaline. Assessment of clinical findings by questionnaire. MAIN OUTCOME MEASURES: O2 kinetics were defined as O2 deficit (time [rest to steady state] x DeltaVO2 -sigmaVO2 [rest to steady state]; normalised to body weight) and mean response time of oxygen consumption (MRT; O2 deficit/DeltaVO2). RESULTS: VO2 kinetics were weakly to moderately correlated to the peak VO2 (O2 deficit, r = -0.37, p < 0.05; MRT, r = -0.49, p < 0.001). Natriuretic peptides were more closely correlated with MRT (ANF, r = 0.58; BNP, r = 0.53, p < 0.001) than with O2 deficit (ANF, r = 0.48, p = 0.001; BNP, r = 0.37, p < 0.01) or peak VO2 (ANF, r = -0.40; BNP, r = -0.31, p < 0.05). Noradrenaline was correlated with MRT (r = 0. 33, p < 0.05) and O2 deficit (r = 0.39, p < 0.01) but not with peak VO2 (r = -0.20, NS). Symptoms of chronic heart failure were correlated with all indices of oxygen consumption (MRT, r = 0.47, p < 0.01; O2 deficit, r = 0.39, p < 0.01; peak VO2, r = -0.48, p < 0. 01). Multivariate analysis showed that the correlation of VO2 kinetics with neurohormones and symptoms of chronic heart failure was independent of peak VO2 and other variables. CONCLUSIONS: Oxygen kinetics during low intensity exercise may provide additional information over peak VO2 in patients with chronic heart failure, given the better correlation with neurohormones which represent an index of homeostasis of the cardiovascular system.     

Replication bypass and mutagenic effect of alpha-deoxyadenosine site-specifically incorporated into single-stranded vectors

OBJECTIVES: The aims of the study were to 1) assess the effects of 12 weeks of exercise training at low work loads (i.e., corresponding to < or = 50% of peak oxygen consumption [Vo2]) on peak Vo2 and hyperemic calf blood flow in patients with severe congestive heart failure; and 2) evaluate left ventricular diastolic pressure and wall stress during exercise performed at work loads corresponding to < or = 50% and 70% to 80% of peak Vo2. BACKGROUND: Whether the benefits of exercise training can be achieved at work loads that result in lower left ventricular diastolic wall stress than those associated with conventional work loads is unknown in patients with severe congestive heart failure. METHODS: Sixteen patients with severe congestive heart failure trained at low work loads for 1 h/day, four times a week, for 12 weeks. Peak Vo2 and calf and forearm reactive hyperemia were measured before and during training. Nine of the 16 patients underwent right heart catheterization and echocardiography during bicycle exercise at low and conventional work loads (i.e., 50% and 70% to 80% of peak Vo2, respectively). RESULTS: The increase in left ventricular diastolic wall stress was substantially lower during exercise at low work loads than during exercise at conventional work loads, (i.e., [mean +/- SEM] 23.3 +/- 7.4 vs. 69.6 +/- 8.1 dynes/cm2 (p < 0.001). After 6 and 12 weeks of training, peak Vo2 increased from 11.5 +/- 0.4 to 14.0 +/- 0.5 and 15.0 +/- 0.5 ml/kg per min, respectively (p < 0.0001 vs. baseline for both). Peak reactive hyperemia significantly increased in the calf but not in the forearm. The increases in peak Vo2 and calf peak reactive hyperemia correlated closely (r = 0.61, p < 0.02). CONCLUSIONS: In patients with severe congestive heart failure, peak Vo2 is enhanced by exercise training at work loads that result in smaller increases in left ventricular diastolic wall stress than those observed at conventional work loads.     

Expression of cellular prion protein in activated hepatic stellate cells

OBJECTIVES: We tested the hypothesis that, in patients with stable heart failure, measuring big endothelin-1 (ET-1) plasma level at rest predicts short-term prognosis better than peak oxygen consumption (VO2max) at exercise. BACKGROUND: Cardiopulmonary exercise testing and evaluation of neurohumoral plasma factors are established tools to estimate survival in patients with heart failure. No data, however, exist comparing the prognostic value of both marker categories simultaneously. METHODS: Two hundred twenty-six heart failure patients were studied in regard to a combined end point of death and prioritization for urgent cardiac transplantation within 1 year follow-up. RESULTS: During the study period 149 patients were without cardiac events (group A), 69 patients died or were urgently transplanted (group B) and 8 patients were alive after a nonurgent heart transplant operation. Norepinephrine (p < 0.0001), atrial natriuretic peptide (p < 0.001), big endothelin plasma levels (p < 0.0001 as well as workload, VO2max and achieved percentage of predicted peak oxygen consumption (pVO2max) (all p < 0.0001) differed significantly between groups A and B. In multivariate stepwise regression analysis, however, only big ET-1 plasma concentration (chi2=74.4, p < 0.0001), New York Heart Association function class (chi2=33.9, p < 0.0001), maximal workload (chi2=7.2, p < 0.01, and plasma atrial natriuretic peptide (ANP) concentration (chi2=4.6, p < 0.05) were independently related to outcome. Peak oxygen consumption or pVO2max did not reach statistical significance in this model. Event-free survival rates were significantly lower in patients with a big ET-1 level of 4.3 fmol/ml or more than with lower big ET-1 levels (p < 0.0001). CONCLUSION: We conclude that in patients with chronic heart failure who are stable on oral therapy measuring big ET-1 and ANP plasma levels may be a valuable noninvasive adjunct to improve the prognostic accuracy of detecting high risk patients compared with exercise testing alone.     

Methodology and repeatability of a standardised treadmill exercise test for clinical evaluation of fitness in horses

This paper describes the methodology necessary to perform a clinical exercise test and the expected variability in an individual horse's exercise test measurements based on comparing the results of two repetitions of the test with six horses. The exercise test measurements were obtained with an open flow respiratory gas analysis system, fast time response lactate analyser and an on-board heart rate monitor during an incremental inclined treadmill exercise test. With the exception of peak venous lactate concentration (LACpeak), the results indicate that the mean variability in peak oxygen consumption (VO2peak) peak carbon dioxide production (VCO2peak), peak respiratory exchange ratio (Rpeak), peak heart rate (HRpeak), peak packed cell volume (PCVpeak), peak total plasma protein (TPPpeak) and the maximum number of steps completed during the exercise test (STEPmax) was less than 5 per cent. Variation in the regression analysis of VO2, VCO2 and HR versus velocity was also less than 5 per cent. Slightly higher variation was recorded for LAC and R. Mean variation in the regression analysis of PCV and TPP versus velocity was more than 16 per cent. Mean variation for all of the post exercise test measurements was less than 10 per cent at 1, 5 and 15 mins post exercise. Therefore, the results obtained during a single exercise test are a reliable assessment of a horse's metabolic capability.     

Comparison of three methods of ulnar fixation in horses

BACKGROUND: This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure. METHODS AND RESULTS: The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo2) was 17.4 mL/min/kg (range, 14.2-19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13-40%). Exercise duration in the captopril group showed a significant increase after 12 weeks (P < .05) of treatment compared with the spirapril group. Peak oxygen consumption tended only to increase in the captopril-treated patients compared with the spirapril-treated patients. Serum ACE activity was significantly different between the two treatment groups during treatment (P < .0001) and showed only a significant decrease in the spirapril group. There was no difference in improvement of quality of life between the two treatment groups. CONCLUSIONS: This study showed that the effects of the ACE inhibitors spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.     

Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.     

Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure. Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletal muscle energy production in male patients with congestive heart failure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercise was studied in 10 patients with chronic congestive heart failure (ejection fraction 0.22 +/- 0.05; peak oxygen consumption, VO2 15.1 +/- 4.9 ml.min-1.kg-1) and in nine healthy subjects (peak VO2 33.5 +/- 6.7 ml.min-1.kg-1). Activities of skeletal muscle enzymes were measured from the vastus lateralis muscle of 48 patients (ejection fraction 0.24 +/- 0.06, peak VO2 17.4 +/- 5.4 ml.min-1.kg-1) and 36 healthy subjects (peak VO2 38.3 +/- 8.4 ml.min-1.kg-1). RESULTS: Although blood lactate levels were lower in patients than in healthy subjects (2.2 +/- 0.3 vs 5.2 +/- 0.6 mmol.l-1; P < 0.001) at peak exercise (96 +/- 11 W for patients and 273 +/- 14 W for controls), skeletal muscle lactate was similarly elevated (25.6 +/- 3.2 vs 22.7 +/- 2.7 mmol.kg-1) and creatine phosphate was equally depressed (P < 0.02) to low levels (7.0 +/- 1.9 vs 6.7 +/- 0.9 mmol.kg-1). The muscle ATP decreased by 21% (P < 0.05) and 8% (P < 0.01) in the patients and controls, respectively. Activities of rate limiting enzymes of the citric acid cycle (alpha-ketoglutarate dehydrogenase) and oxidation of free fatty acids (carnitine palmitoyltransferase II) were 48% and 21% lower than in controls, but the mean phosphofructokinase activity was unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performance during heavy exercise is the same in congestive heart failure and healthy subjects, a high rate of skeletal muscle lactate accumulation and high-energy phosphate depletion. In congestive heart failure, the low activity of aerobic enzymes is likely to impair energy production and lead to lactate acidosis at low workloads.     

Imidazolylpropylguanidines as histamine H2 receptor agonists:3D-QSAR of a large series

Functional impairment has long been recognized as an important factor in the risk paradigm among patients with heart disease. In chronic heart failure, this issue has been even more important in recent years because of the steady growth in the number of patients awaiting heart transplantation relative to the available pool of donor hearts. The use of gas-exchange techniques to assess patients with heart failure has attracted interest because these techniques provide a more precise, reproducible, objective, and physiologic expression of exercise tolerance. Numerous studies published in the 1990s demonstrate that maximal oxygen uptake (peak VO2) is an independent predictor of mortality in patients with heart failure. Achievement of a peak VO2 that is less than 14 mL/kg/min has been recognized as one of the relative indications for transplantation, because patients who achieve a measurement that is higher than 14 mL/kg/min have a 1-year mortality rate similar to that of patients who undergo transplantation (i.e., > 90%). However, some debate exists regarding the optimal cutpoint that separates survivors from nonsurvivors, and studies have not consistently defined the timing of the test relative to optimization of medical therapy. It has also been debated which hemodynamic variables, at rest or during exercise, should be used in combination with peak VO2 to optimally stratify risk in these patients. This article reviews the applications of cardiopulmonary exercise testing in prognosis among patients with chronic heart failure.     

Assisted implantation: direct intraendometrial embryo transfer

LVAD use in the heart failure population is increasing and allows severely impaired patients an opportunity for exercise rehabilitation before cardiac transplantation. Although the LVAD provides nearly all of the cardiac output at rest, the native left ventricle contributes a modest amount during exercise, with the LVAD capable of providing a mechanical cardiac output of 10 L/min or greater. Given the parameters of the LVAD, exercise training responses should yield greater changes in submaximal exercise tolerance rather than changes in peak oxygen consumption. Heart rate and LVAD rate are driven by separate mechanisms but increase similarly during exercise. Blood pressure responses are somewhat variable early post LVAD implantation but normalize. Ratings of perceived exertion appear to be reliable and useful in this population. Evidence to date suggests that early mobilization and progressive exercise training in this population is safe and improves the transplantation experience. Although central contributions to oxygen consumption are limited by the inherent mechanical parameters of the LVAD, adequate cardiac output is provided for routine physical activities and moderate exercise training while the patient awaits transplantation.     

Physical factors influencing the oviposition of Lutzomyia migonei (Diptera: Psychodidae) in laboratory conditions

Anthropometric and demographic characteristics are important determinants of exercise performance in healthy subjects, but their influence has not yet been studied in severe chronic heart failure, although peak oxygen uptake is frequently assessed in such patients for prognostic purposes. The aim of the present analysis was to examine the association between peak oxygen uptake and age, gender, and measures of body size in patients with severe chronic heart failure. We selected 122 (99 male) adult heart transplant candidates who were able to perform a bicycle ergometer test with respiratory gas analysis until voluntary fatigue. Peak oxygen uptake was higher in male than in female patients, both before and after adjustment for weight. In single regression analysis on the total study population, peak oxygen uptake was positively related to weight and to height, but inversely to age (r = 0.59 (P < 0.001), 0.42 (P < 0.001), and -0.33 (P < 0.001), respectively). Multiple stepwise regression analysis identified weight (P < 0.001), age (P < 0.001), and gender (P < 0.01) as independent determinants of peak oxygen uptake (cumulative R2 = 0.45). Similar to the findings in healthy subjects, peak oxygen uptake of patients with severe chronic heart failure is influenced by anthropometric and demographic characteristics.     

Exercise training in heart failure improves quality of life and exercise capacity

AIMS: Benefit from exercise training in heart failure has mainly been shown in men with ischaemic disease. We aimed to examine the effects of exercise training in heart failure patients < or = 75 years old of both sexes and with various aetiology. METHODS AND RESULTS: Fifty-four patients with stable mild-to-moderate heart failure were randomized to exercise or control, and 49 completed the study (49% > or = 65 years; 29% women; 24% non-ischaemic aetiology; training, n = 22; controls, n = 27). The exercise programme consisted of bicycle training at 80% of maximal intensity over a period of 4 months. Improvements vs controls were found regarding maximal exercise capacity (6 +/- 12 vs -4 +/- 12% [mean +/- SD], P < 0.01) and global quality-of-life (2 [1] vs 0 [1] units [median ?inter-quartile range?], P < 0.01), but not regarding maximal oxygen consumption or the dyspnoea-fatigue index. All of these four variables significantly improved in men with ischaemic aetiology compared with controls (n = 11). However, none of these variables improved in women with ischaemic aetiology (n = 5), or in patients with non-ischaemic aetiology (n = 6). The training response was independent of age, left ventricular systolic function, and maximal oxygen consumption. No training-related adverse effects were reported. CONCLUSION: Supervised exercise training was safe and beneficial in heart failure patients < or = 75 years, especially in men with ischaemic aetiology. The effects of exercise training in women and patients with non-ischaemic aetiology should be further examined.     

Influences of morphine on the ventilatory response to isocapnic hypoxia

BACKGROUND: The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. METHODS: The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). RESULTS: At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). CONCLUSIONS: Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.