Physiological response to the six-minute walk test in pulmonary arterial hypertension.

The 6-min walk test (6MWT) is commonly used to evaluate exercise capacity in patients with pulmonary arterial hypertension (PAH). However, little is known about the corresponding metabolic stress as measured by cardiopulmonary exercise testing. The present study, therefore, measured ventilatory variables and heart rate during the 6MWT and symptom-limited incremental maximal exercise testing in 20 patients with PAH. The distance walked in 6 min was 450+/-22 m (mean+/-se). During the 6MWT, ventilation, O2 consumption, CO2 production and heart rate increased during the first 3-4 min, and then remained stable. As compared with the maximum values measured during the cardiopulmonary exercise test, O2 consumption tended to be higher (14.2+/-0.6 versus 12.9+/-0.7 mL.kg-1.min-1), while maximum ventilation (46+/-3 versus 57+/-4 L.min-1), respiratory quotient (0.90+/-0.02 versus 1.15+/-0.02) and heart rate (119+/-4 versus 135+/-4 beats.min-1) remained lower. In conclusion, patients with pulmonary arterial hypertension exercise at higher aerobic capacity and lower metabolic stress during the 6MWT than during a cardiopulmonary exercise test.

Exercise testing in pulmonary arterial hypertension and in chronic heart failure.

Exercise capacity is reduced in pulmonary arterial hypertension and in chronic left heart failure, but it is not known whether the cardiopulmonary exercise testing profile is different in the two conditions at the same severity of functional limitation. Nineteen patients with pulmonary arterial hypertension and 19 with chronic heart failure underwent a 6-min walk test and symptom-limited maximal incremental cycle ergometry. The patients with pulmonary arterial hypertension and chronic heart failure did not differ in New York Heart Association Functional Class (mean +/- SEM 2.8 +/- 0.1 versus 2.8 +/- 0.2), 6-min walking distance (395 +/- 30 versus 419 +/- 20 m), peak work-rate, oxygen consumption, ventilation and cardiac frequency. However, patients with pulmonary arterial hypertension exhibited higher dyspnoea scores (5.8 +/- 0.6 versus 3.8 +/- 0.5) higher ventilatory equivalents for carbon dioxide (58 +/- 3 versus 44 +/- 3 at the anaerobic threshold) and lower peak oxygen pulse (5.9 +/- 0.4 versus 8.7 +/- 0.5 mL x beat(-1), or 53 +/- 4 versus 64 +/- 4% of the predicted value). It is concluded that the cardiopulmonary exercise testing profile in pulmonary arterial hypertension differs from that in chronic heart failure by showing more dyspnoea at comparable work-rates, related to greater reductions in ventilatory efficiency and stroke volume.

[The heart surgery department]. / Le Service de Chirurgie Cardiaque.

The initial development of cardiac surgery at Erasme Hospital was closely related to the achievements in thoracic organ transplantation, with numerous synergies between other clinical and research units of the Faculty of Medicine. New advances in biology and biotechnology have met the challenges of modern cardiology, in the fields of advanced heart failure, refractory angina, rhythm disturbances or minimally invasive surgery. Fundamental aspects of clinical practice have been the subject of laboratory investigations, resulting in fruitful interactions and promising scientific outlooks.

Haemodynamic response to dynamic exercise after heart-lung transplantation.

The purpose of this study was to investigate the haemodynamic response to dynamic exercise after heart-lung transplantation (HLT). Nine stable HLT recipients (6 males) were studied 12-55 months after transplantation. While sitting on a cycle ergometer, they first underwent a maximal symptom-limited exercise test (power increment was 10 W x min(-1)) to determine the maximal tolerable workload. On the next day, they performed a second exercise test at 0, 40, 60 and 80% of their predetermined maximal workload (mean+/-sD: 108+/-20 W). Stage duration was 6 min. Respiratory, gas exchange, and haemodynamic measurements were performed at rest, during the last minute of each stage, and after recovery. Haemodynamic variables at rest were within normal limits except heart rate (HR) which was greater and stroke volume index (SVI) which was lower than normal. Peak oxygen consumption was 61+/-8% of predicted. HR showed an initial slow increase followed by a steeper rise, and a delayed return to baseline during the recovery period. SVI and cardiac index (CI) increased at the onset of exercise but did not change significantly at 40-80% of the maximal workload. Pulmonary capillary wedge pressure increased from 4+/-2 mmHg at rest to 14+/-3 mmHg at maximal exercise. It is concluded that during dynamic exercise, heart-lung transplantation recipients demonstrate a chronotropic incompetence, a reduced increase in cardiac index and stroke volume index, and an excessive rise in left ventricular filling pressures. These alterations may contribute to the persistent exercise limitation.

Renal responses to exercise in heart and kidney transplant patients.

There is a lack of information about renal responses in heart and kidney transplant patients after intense physical exercise. Eleven heart and ten kidney transplant recipients, as well as two control groups of healthy subjects, were given a maximum exercise test on a bicycle ergometer. One control group was also given a moderate load corresponding to the peak load of the kidney transplant group. Blood and urine samples were collected before and after exercise and assayed for lactate, creatinine, total protein, and albumin. The glomerular filtration rate remained stable at the end of exercise in the transplant patients, while there was a slight (17%) decrease in the control group. Albumin excretion rates after maximum exercise attained a mean of 237 micrograms.min-1 in the control group and a mean of 45 and 16 micrograms.min-1, respectively, in the heart and kidney groups. Postexercise proteinuria seemed to be related to the absolute intensity of the event, but kidney transplant patients showed a reduced effect as compared to heart transplant patients. We conclude that short-term, maximum exercise in heart and kidney transplant recipients is not detrimental to kidney function.

Long-term follow-up of heart transplant patients.

The present study was designated to assess long term functional capacity, blood pressure and renal function at 12 and 60 months after heart transplantation. The data of sixty heart transplant recipients were retrospectively reviewed. At rest, radionuclide ejection fraction and cardiac index measured by thermodilution were within normal range, demonstrating normal left systolic function. In all patients, exercise tests were performed sitting on a bicycle. Peak oxygen uptake decreased from 23 +/- 6 to 19 +/- 6 ml/kg/min (mean +/- S.D.) respectively at 12 and 60 months after surgery (p < 0.01), which represent a 17% diminution in functional capacity. This decrease is nevertheless only related with a 10 kg increase in total body weight (69 +/- 9; 79 +/- 12 kg; p < 0.001) and thus absolute peak oxygen uptake remained unchanged. Blood pressure rised significantly since the first month after transplantation. Sixty-seven percent of recipients had systemic hypertension at 60 months, despite medical therapy. A decline in renal function was observed in all patients, beginning after the first year of transplantation.

Does cardiac denervation affect the short-term blood pressure variability in humans?

OBJECTIVE: To explore the repercussion of cardiac denervation on the short-term blood pressure variability in humans, in order to assess the extent to which the variability of blood pressure is linked to the variability of heart rate. METHODS: Beat-to-beat blood pressure and RR interval time were recorded in 16 heart-transplanted patients and were compared with those of 10 healthy control subjects in the resting supine, sitting and standing positions. Blood pressure and RR interval variabilities were assessed by spectral analysis. RESULTS: The total blood pressure power and the sitting very low-frequency, low-frequency, low-frequency and high-frequency blood pressure variability were similar in the heart-transplanted patients and in the controls, despite a marked reduction in the RR interval variability in the heart-transplanted patients. However, the heart-transplanted patients had lower standing low-frequency blood pressure variability than the control subjects. Moreover, very low-frequency and low-frequency RR interval variabilities reappeared in the long-term heart-transplanted patients but not in the short-term heart-transplanted patients (range of time after transplantation 53-124 and 3-25 months, respectively). CONCLUSIONS: Short-term RR interval fluctuations are not mandatory for the maintenance of normal blood pressure variability in the supine and sitting positions, but may contribute to the increase in the low-frequency blood pressure variability which occurs normally in the standing position. Moreover, the long-term heart-transplanted patients had increased RR interval variability, which may have been caused by the reappearance of limited autonomic cardiac modulation. However, this increased RR interval variability did not affect the corresponding blood pressure variability.

Respiratory dysfunction in congestive heart failure: correction after heart transplantation.

Severe chronic congestive heart failure (CCHF) is known to induce a restrictive ventilatory defect, with a small decrease in lung transfer factor for carbon monoxide (TLCO). The aim of the present work was to assess the reversibility of this dysfunction. We studied a group of 47 patients with CCHF, before and one year after heart transplantation. The measurements included static and dynamic lung volumes, TLCO and cardiac function. On initial evaluation, vital capacity (VC), total lung capacity (TLC) and TLCO were reduced to 76, 79 and 64% of the predicted value (% pred), respectively. Forced expiratory volume in one second (FEV1) was decreased to 69% pred, with a FEV1/VC ratio below 0.70 in 13 out of 47 patients. One year after transplantation, cardiac function had markedly improved, as shown by a normalized left ventricular ejection fraction (from 18% preoperatively to 59% postoperatively), and mean pulmonary wedge pressure (from 26 to 12 mmHg). At this time, VC (94% pred) and TLC (98% pred) were within the normal range, whereas TLCO remained low (67% pred). The FEV1/VC ratio did not change, even in the subgroup with an initial low value. Smoking habits did contribute to the low TLCO and FEV1/VC ratio. In conclusion, respiratory dysfunction induced by CCHF is reversible, with the exception of the reduction in TLCO, which probably reflects permanent changes in the lung vasculature. CCHF does not induce an obstructive ventilatory pattern.

Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise.

Almitrine, a peripheral chemoreceptor agonist, has been reported to increase arterial O2 saturation (SaO2) without changing minute ventilation (VE) during hypoxic exercise (Giesbrecht et al. J. Appl. Physiol. 70: 1770-1774, 1991). To explain this finding, we studied pulmonary hemodynamics (right heart catheterization) and gas exchange (multiple inert gas elimination technique) in six healthy volunteers at rest and during heavy exercise in normobaric normoxia (fractional concentration of O2 in inspired air 0.21) or hypoxia (fractional concentration of O2 in inspired air 0.125), before and after 75 mg of almitrine taken orally. During normoxic exercise, at a mean O2 uptake (VO2) of 4.0 l/min, almitrine increased arterial PO2 (PaO2) (P < 0.05), SaO2 (P < 0.01), and VE (P < 0.05) and decreased arterial PCO2 (P < 0.01), without affecting pulmonary hemodynamics or ventilation-perfusion distributions. During hypoxic exercise, at a mean VO2 of 3.0 l/min, almitrine increased SaO2 (P < 0.01) and VE (P < 0.01) and decreased arterial PCO2 (P < 0.05), with no effect on PaO2 or on ventilation-perfusion distributions and with a slight pulmonary vasoconstriction (P < 0.01). Almitrine during hypoxia did not affect cardiac output or calculated O2 diffusing capacity, but it did increase the slope of the VE/VO2 relationship (P < 0.01). We conclude that during hypoxic exercise, a pharmacological stimulation of the peripheral chemoreceptors improves SaO2 but not PaO2 by means of increased ventilation and an associated leftward shift of the oxyhemoglobin dissociation curve.

Relationship of middle cerebral artery blood flow velocity to intensity during dynamic exercise in normal subjects.

Cerebral blood flow has been reported to increase during dynamic exercise, but whether this occurs in proportion to the intensity remains unsettled. We measured middle cerebral artery blood flow velocity (vm) by transcranial Doppler ultrasound in 14 healthy young adults, at rest and during dynamic exercise performed on a cycle ergometer at a intensity progressively increasing, by 50 W every 4 min until exhaustion. Arterial blood pressure, heart rate, end-tidal, partial pressure of carbon dioxide (PETCO2), oxygen uptake (VO2) and carbon dioxide output were determined at exercise intensity. Mean vM increased from 53 (SEM 2) cm.s-1 at rest to a maximum of 75 (SEM 4) cm.s-1 at 57% of the maximal attained VO2 (VO2max), and thereafter progressively decreased to 59 (SEM 4) cm.s-1 at VO2max. The respiratory exchange ratio (R) was 0.97 (SEM 0.01) at 57% of VO2max and 1.10 (SEM 0.01) at VO2max. The PETCO2 increased from 5.9 (SEM 0.2) kPa at rest to 7.4 (SEM 0.2) kPa at 57% of VO2max, and thereafter decreased to 5.9 (SEM 0.2) kPa at VO2max. Mean arterial pressure increased from 98 (SEM 1) mmHg (13.1 kPa) at rest to 116 (SEM 1) mmHg (15.5 kPa) at 90% of VO2max, and decreased slightly to 108 (SEM 1) mmHg (14.4 kPa) at VO2max. In all the subjects, the maximal value of vm was recorded at the highest attained exercise intensity below the anaerobic threshold (defined by R greater than 1). We concluded that cerebral blood flow as evaluated by middle cerebral artery flow velocity increased during dynamic exercise as a function of exercise intensity below the anaerobic threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise and heart transplantation. A review.

Results of heart transplantation as therapy for end-stage cardiac diseases are encouraging not only because of actuarial survival curves but also because of the recovered quality of life for the heart transplant recipient. Although heart transplantation drastically improves the physical capacity of the patients, heart recipients still have a reduced maximal aerobic capacity compared to healthy people. Altered resting and exercise haemodynamics, due to cardiac denervation, are a common finding after orthotopic heart transplantation: increases in heart rate and stroke volume at exercise are first linked with the augmented venous return and later with the increased plasmatic nor-adrenaline level. Maximal heart rate and stroke volume are both reduced when compared to innervated heart. Reduced cardiac output response to exercise therefore results in early anaerobic metabolism, acidosis, hyperventilation and diminished physical capacity. In spite of an altered ventilatory adaptation to exercise, characterised by hyperpnoea in most transplant patients, ventilation is not the limiting factor for exercise in heart recipients without associated obstructive pulmonary disease. Endurance training restores lean tissue, decreases submaximal minute ventilation, increases peak work output, maximal ventilation and peak heart rate. Guidelines for prescribing exercise are not yet standardised due to the limited number of studies on a sufficient cohort of heart recipients. Nevertheless, recommendations similar to those used for persons with coronary heart disease, with modifications due to the denervated heart, seem to be used. The cardiocirculatory and pulmonary capacity of heart transplant recipients allow them to undertake endurance sports activities such as walking, jogging, cycling and swimming, and these should be encouraged.

Increased platelet aggregability and prostacyclin biosynthesis induced by intense physical exercise.

Changes in platelet aggregability during maximal bicycle ergometry were studied in healthy untrained subjects. Ex vivo platelet aggregation in response to ADP and collagen was measured in whole blood by impedance aggregometry or by direct electronic counting in an Ultra-Flo 100 platelet counter. This last method revealed that the platelet aggregation induced by low concentration of ADP (0.5 - 1.0 microM) was significantly enhanced during exercise. The plasma level of beta-thromboglobulin and the urinary excretion of 2,3--dinor-6-keto prostaglandin F1 alpha were also increased. These data indicate that an intense physical exercise enhances the aggregability of human platelets and induces a compensatory increase in prostacyclin biosynthesis.

[Functional non-invasive cardio-respiratory evaluation a month and a year after orthotopic heart transplantation]. / Evaluation fonctionnelle cardio-respiratoire non invasive un mois et un an après transplantation cardiaque orthotopique.

Cardio-respiratory stress tests of 14 patients, performed one month and one year after orthotopic heart transplant, are compared in order to demonstrate the functional and metabolic improvements of their adaptation to stress. At maximal stress, we note a 33 p. cent increase of the oxygen consumption (p 0.001), an 11 p. cent increase of the heart rate (p 0.025) and an 18 p. cent increase of the systolic arterial pressure (p 0.005). Respiratory quotients and respiratory equivalent for oxygen are significantly lower (p 0.008) while there was no significant variation of ventilation/minute, respiratory rate, and the normal capacity. At the sub-maximal level, the only significant differences observed are the decrease of the respiratory quotient (p 0.01), the ventilation/minute (p 0.025), the respiratory equivalent for oxygen (p 0.005) and the respiratory rate (p 0.03). The improvement of the physical condition observed in heart transplants seems related to a better peripheral adaptation to stress (lower respiratory quotients, reflection of the decreased demand on anaerobic metabolism) permitting a lesser demand on the ventilatory response to stress.

Psychosocial and physical rehabilitation after heart transplantation: 1-year follow-up.

Experience on the rehabilitation of 62 heart-transplanted patients with a mean follow-up period of 15 months and a total survival rate of 79% is reported. From the present study we may conclude that: (a) One month after surgery, oxygen consumption of transplanted patients compared to coronary artery bypass-grafted patients was statistically lower (p less than 0.025). An excess ventilation was observed in transplanted patients in relation mainly to an excessive increase in blood lactates. (b) Improvement of maximal working capacity observed immediately after grafting was still enhanced after 1 year of a comprehensive rehabilitation program (p less than 0.001). This improvement was more related with an improvement of the respiratory function and of the peripheral factors than with a circulatory effect. (c) Four months after transplantation 71% of the patients still at work 6 months before operation returned to work. (d) The quality of life, well-being and heart acceptation demonstrated an immediate increase in physical items after transplantation while psychosocial items decreased postoperatively and normalized after weeks or months.

[Effects of physical training on the denervated human heart after orthotopic cardiac transplantation]. / Effets de l'entraînement physique sur le coeur humain dénervé après transplantation cardiaque orthotopique.

Three patients who had undergone an orthotopic cardiac transplantation followed a course of supervised intermittent physical training (60 to 80 per cent of the maximum load) involving three weekly sessions of thirty minutes, for a period of 150 +/- 80 days. During maximal effort, we observed increases of 50 per cent in the load in watts (0.05 less than p less than 0.1), 40 per cent in oxygen consumption (0.1 less than p less than 0.2), 10 per cent in heart rate (p = 0.5) and 21 per cent in systolic blood pressure (0.7 less than p less than 0.8). The respiratory equivalent for oxygen decreased by 21 per cent (0.025 less than p less than 0.05) and the respiratory quotient by 5 per cent (0.4 less than p less than 0.05). For a given submaximal effort (30 watts) the following decreases were observed: 9 per cent in oxygen consumption (V'O2) (0.1 less than p less than 0.2), 32 per cent in the minute ventilation (V'E) (0.05 less than p less than 0.1), 22 per cent in the respiratory equivalent for oxygen (REO2) (0.025 less than p less than 0.05), 8 per cent in the respiratory quotient (RQ) (0.2 less than p less than 0.3) and 11 per cent in the heart rate (HR) (0.1 less than p less than 0.2). The systolic blood pressure (SBP) increased by 6 per cent (0.2 less than p less than 0.3). No changes were observed in these parameters in the postoperative follow-ups (10 to 24 months) of two patients who did not undergo physical training. Physical training is, therefore, necessary in the process of physical readaptation of patients after orthotopic cardiac grafts.

[Early exercise test after revascularization and rehabilitation]. / Epreuve d'effort précoce après revascularisation coronaire et revalidation.

Ergospirometry was performed on 51 patients before their discharge from hospital, that is between the seventh and tenth days after myocardial revascularization by cardiac bypass surgery. The aim of our study is to show that this type of measurement can be performed with reasonable safety and that it gives an accurate assessment of the patient's ability to withstand exercise. It employs a metabolic approach: study of oxygen consumption (V'O2), carbon dioxide release (V'CO2), the respiratory quotient (RQ), the minute ventilation (V'E) and the respiratory equivalent for oxygen (REO2). The patients withstood a mean load of 82 +/- 17.7 watts for a mean V'O2 of 1.186 +/- 0.258 l/min STPD and a mean V'E of 46.5 +/- 10 l/min BTPS. Changes in respiratory and metabolic parameters as a function of load are discussed, as is the advice that can be given to the patient regarding physical rehabilitation.

Metabolic implications during a 20-km run after heart transplantation.

The aim of the present study was to evaluate a heart transplanted patient who ran a 20-km race 9 months after surgery. Thirty-six healthy male subjects were studied during the same run and served as control group. Biochemical variables were determined in blood and urine samples collected before and after the race. Post-exercise blood urea increased by 23% (P less than 0.05) in the control group but remained unchanged in the patient. Blood lactate increased far more in the transplanted patient (7.07 mmol/L) than in the control subjects (2.53 mmol/L). The exercise induced a 5.46- and 0.67-fold increase in creatine phosphokinase activity in the transplanted patient and control group, respectively. The creatinine and urea urinary excretion and clearance decreased by 40%-60% after exercise for all subjects. It may be concluded that the heart transplanted patient responded for most registered variables in the same way as normal subjects, but some differences occurred on the renal side due to the use of an immunosuppressive drug.

Study of the influence of nifedipine on the pharmacokinetics and pharmacodynamics of propranolol, metoprolol and atenolol.

The influence of chronic therapy with nifedipine on the pharmacokinetics of propranolol 80 mg twice daily, metoprolol 100 mg twice daily and atenolol 100 mg once daily was investigated in eight healthy volunteers. Nifedipine 10 mg three times daily did not affect the pharmacokinetics of metoprolol and atenolol whereas nifedipine shortened the time to peak plasma concentration for propranolol by about 1 h. Propranolol, metoprolol and atenolol provoked comparable decreases in heart rate measured at rest and during exercise. The beta-adrenoceptor blocking properties of propranolol, metoprolol and atenolol were not affected by concomitant therapy with nifedipine. The present study did not show significant pharmacokinetic and pharmacodynamic interactions between nifedipine and lipophilic beta-adrenoceptor blockers.