Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting.

BACKGROUND: Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video-conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. METHODS: Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video-conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. RESULTS: A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien-Dindo grade I-II complications occurred in 16 patients; there was no grade III-IV morbidity or 30-day in-hospital mortality. The median follow-up for the whole cohort was 18·7 months, and the 2-year survival rate from time of first review at the national PM MDT was 68·3 per cent. CONCLUSION: The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.

ANTECEDENTES: El mesotelioma peritoneal (peritoneal mesothelioma, PM) es una neoplasia primaria del peritoneo muy poco frecuente, con una incidencia creciente en todo el mundo. La cirugía citorreductora (cytoreductive surgery, CRS) con quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) se ha mostrado prometedora como estrategia de tratamiento. En marzo de 2016, se organizó una reunión por videoconferencia del equipo multidisciplinar nacional de PM (national PM multi-Disciplinary Team, MDT) en el Reino Unido e Irlanda, con el objetivo de planificar un tratamiento óptimo, registrar los resultados y proporcionar evidencia de los beneficios de la centralización. Este manuscrito presenta las actividades y los resultados de los primeros 2,5 años. MÉTODOS: Entre marzo de 2016 y diciembre de 2018, 155 pacientes con PM, remitidos a centros de cirugía oncológica peritoneal en Basingstoke, Good Hope Hospital en Birmingham, Christie Hospital en Manchester y Mater Misericordiae en Dublín, fueron discutidos en el National PM MDT a través de una videoconferencia. El MDT estaba compuesto por cirujanos, radiólogos, enfermeras especializadas y patólogos. Los pacientes fueron considerados para CRS e HIPEC si se determinaba que eran aptos para la cirugía y si las imágenes radiológicas sugerían que se podía lograr una citorreducción quirúrgica completa. Se analizó la morbilidad y mortalidad después de la cirugía. Se realizó un análisis de supervivencia tras la discusión en el MDT. RESULTADOS: En total, se discutieron 155 pacientes (tasa varón/mujer 0,96) con una edad media de 57 ± 17 años. Hasta el momento, 22 (14,2%) habían sido sometidos a CRS y HIPEC y la mediana de PCI en el grupo quirúrgico fue de 17,0. La citorreducción completa se logró en 19 (86,4%), las complicaciones de Clavien-Dindo grado I/II ocurrieron en 16/22, sin morbilidad de grado III/IV, ni mortalidad a los 30 días. La mediana de seguimiento fue de 15,0 meses y la supervivencia a los 2 años desde el momento de la revisión en el National PM MDT fue del 66,7%. CONCLUSIÓN: El National PM MDT centralizado fue eficaz en la selección de pacientes adecuados para CRS e HIPEC, presentando un buen resultado a partir de dicha selección.

Determinants of novel object and location recognition during development.

In the novel object recognition (OR) paradigm, rats are placed in an arena where they encounter two sample objects during a familiarization phase. A few minutes later, they are returned to the same arena and are presented with a familiar object and a novel object. The object location recognition (OL) variant involves the same familiarization procedure but during testing one of the familiar objects is placed in a novel location. Normal adult rats are able to perform both the OR and OL tasks, as indicated by enhanced exploration of the novel vs. the familiar test item. Rats with hippocampal lesions perform the OR but not OL task indicating a role of spatial memory in OL. Recently, these tasks have been used to study the ontogeny of spatial memory but the literature has yielded conflicting results. The current experiments add to this literature by: (1) behaviorally characterizing these paradigms in postnatal day (PD) 21, 26 and 31-day-old rats; (2) examining the role of NMDA systems in OR vs. OL; and (3) investigating the effects of neonatal alcohol exposure on both tasks. Results indicate that normal-developing rats are able to perform OR and OL by PD21, with greater novelty exploration in the OR task at each age. Second, memory acquisition in the OL but not OR task requires NMDA receptor function in juvenile rats [corrected]. Lastly, neonatal alcohol exposure does not disrupt performance in either task. Implications for the ontogeny of incidental spatial learning and its disruption by developmental alcohol exposure are discussed.

Infants attend to second-order relational properties of faces.

Two experiments investigated whether 7-month-old infants attend to the spatial distance measurements relating internal features of the human face. A visual preference paradigm was used, in which two versions of the same female face (one either lengthened or shortened, and one nonmodified) were presented simultaneously. In Experiment 1, infants looked longer at the nonmodified faces, which were determined to match the average distance relationships found in a sample of faces drawn from the same population. Longer looking times for modified faces were found in Experiment 2, in which the nonmodified faces were unusually long and the modified faces conformed to average distance measurements. It is proposed that infants' attention to the spatial relations of internal face features is an optimal tool for lifelong face recognition.

Hemodynamic responses during leg press exercise in patients with chronic congestive heart failure.

To increase muscle mass and strength in patients with chronic congestive heart failure (CHF), there is a need for implementing resistance exercises in exercise training programs. This study sought to assess the safety of rhythmic strength exercise with respect to left ventricular function in 9 patients with stable CHF, compared with 6 stable coronary patients with mild left ventricular dysfunction (control group). With use of right-sided catheterization, changes in left ventricular function were assessed during double leg press exercise at loads of 60% and 80% of maximum voluntary contraction. The exercise sessions lasted 14 minutes each, divided into work and recovery phases of 60/120 seconds. In CHF, during exercise at a 60% load, there was a significant increase in heart rate (mean +/- SEM 90 +/- 4 beats/min; p <0.05), mean arterial blood pressure (95 +/- 3 mm Hg; p <0.01), diastolic pulmonary artery pressure (20.2 +/- 2.7 mm Hg; p <0.01), and cardiac index (3 +/- 0.3 L/m2/min; p <0.05). Additionally, during leg press exercise at an 80% load, there was a significant decrease in systemic vascular resistance (1,086 +/- 80 dynes x s x cm(-5); p <0.001), an increased cardiac index (3.4 +/- 0.1; p <0.001), and left ventricular stroke work index (75 +/- 5 g x m/m2; p <0.01), suggesting enhanced left ventricular function. Compared with controls, in CHF the magnitude of changes in hemodynamic parameters during exercise, demonstrated at a 60% load, was significantly smaller (systemic vascular resistance: [mean] 1,613 --> 1000 vs 1472 --> 1,247 dynes x s x cm(-5); cardiac index: 2.4 --> 3 vs 2.8 --> 4.4 L/m2/min, and stroke work index: 60 --> 69 vs 114 --> 155 g x m/m2; p <0.05 each). Nevertheless, changes indicated an enhanced contractile function of the left ventricle in CHF. This study demonstrates stability of left ventricular function during resistance exercise in well-compensated CHF patients with optimal drug therapy, as well as the appropriateness of the chosen mode and intensity applied as these factors relate to cardiovascular stress. This conclusion cannot be extrapolated to patients with less well-compensated heart failure, or to more protracted resistance training.

Comparison of left ventricular function during interval versus steady-state exercise training in patients with chronic congestive heart failure.

This study sought to assess the safety of interval exercise training in patients with chronic congestive heart failure (CHF) with respect to left ventricular (LV) function. For effective rehabilitation in CHF, both aerobic capacity and muscle strength need to be improved. We have previously demonstrated in both coronary artery bypass surgery and patients with CHF that interval exercise training (IET) offers advantages over steady-state exercise training (SSET). However, because LV function during IET has not yet been studied, the safety of this method in CHF remains unclear. To assess LV function during IET and SSET, at the same average power output, 11 patients with stable CHF were compared with 9 stable coronary patients with minimal LV dysfunction (control group). Using first-pass radionuclide ventriculography, changes in LV function were assessed during work versus recovery phases, at temporally matched times between the fifth and sixteenth minute of IET and SSET. In CHF during IET, there were no significant variations in the parameters measured during work and/or recovery phases. During the course of both IET and SSET, there was a significant increase in LV ejection fraction (5 vs 4 U; p <0.05 each), accompanied by increased heart rate (6 vs 8 beats/min; p <0.05 each) and cardiac output (2.4 vs 1.8 L/min; p <0.01 and p <0.05). In CHF, the magnitude of change in LV ejection fraction during IET was similar to that seen in controls. Both LV ejection fraction and the clinical status in patients with CHF remained stable during IET. Because IET appears to be as safe as SSET with respect to LV function, IET can be recommended for exercise training in CHF to apply higher peripheral exercise stimuli and with no greater LV stress than during SSET.

Active immunization against somatostatin alters regulation of gastrin in response to gastric acid secretagogues.

We have examined the coupling between somatostatin, gastrin, and gastric acidity, using sheep chronically immunized against somatostatin. All immunized sheep had high-titer (3.2 x 10(5) +/- 1.1 x 10(4) M), high-affinity (1.5 x 10(11) +/- 1.2 x 10(10) l/mol) antibodies. However, basal gastrin and gastric acidity were similar to those in control animals, indicating that an inhibitory somatostatin tone was not required for the maintenance of normal basal gastrin and gastric acidity. Omeprazole (a proton pump inhibitor) increased gastric pH to a similar extent in both the control and immunized groups but resulted in a smaller increase in plasma gastrin in the immunized sheep, thus calling into question the assumption that hypergastrinemia associated with hypochlorhydria is the result of somatostatin withdrawal. Pentagastrin- or histamine-stimulated somatostatin secretion reversed or attenuated the omeprazole-induced hypergastrinemia in control but not immunized sheep, demonstrating a functional role for somatostatin and the biological efficacy of the somatostatin immunization. In a separate series of omeprazole-treated sheep, restoration of an acidic gastric pH with intragastric HCl reversed the hypergastrinemia in both control and immunized animals. We conclude that somatostatin is not essential for the acid-mediated regulation of gastrin. The use of a chronically immunized model as opposed to the acute administration of somatostatin antibodies has important advantages in determining the steady-state regulatory role of somatostatin.

Delayed VO2 kinetics during ramp exercise: a criterion for cardiopulmonary exercise capacity in chronic heart failure.

PURPOSE: Kinetics of VO2 at onset of constant work rate exercise was previously shown to be slowed in patients with chronic heart failure (CHF) compared with that in healthy normals. Because bicycle ergometry with ramp protocol is usually used for exercise testing with CHF patients, it would be of practical importance if it can be shown that a delay in the time interval of linear increase of VO2 (TILIV) to work rate occurs after beginning ramp exercise. Data of central hemodynamics (CHF) and noninvasive cardiopulmonary parameters (CHF, normals) should also correlate with VO2 delay time if this parameter is related to cardiopulmonary exercise capacity. METHODS: Fifteen males with CHF (mean +/- SEM: age 52 +/- 2 yr; ejection fraction 32 +/- 4%; peak cardiac index 3.9 +/- 0.3 L x m(-2) x min(-1)) and 28 healthy males (50 +/- 1 yr) were assessed. During ramp bicycle ergometry (3 min unloaded, work rate increments of 12.5 W x min(-1)), VO2 was measured breath by breath. RESULTS: After the onset of ramp exercise, there was a difference in the TILIV between patients and normals (83.7 +/- 3.6 vs 66.8 +/- 2.9 s; P < 0.001). Significant differences between both groups were also found for VO2 at ventilatory threshold (VT) (10.1 +/- 0.1 vs 15.2 +/- 0.7 mL x kg(-1) x min(-1); P < 0.0001), VO2 at VT relative to predicted VT (58 +/- 4 vs 97 +/- 4%; P < 0.0001), peak VO2 (13.2 +/- 1.0 vs 34 +/- 1.4 mL x kg(-1) x min(-1), P < 0.001), and increase of systolic blood pressure (36 +/- 7 vs 71 +/- 5 mm Hg; P < 0.0001). In CHF, the TILIV correlated significantly with peak cardiac index and VO2 at VT (r = -0.71; P < 0.005 each), relative value of VO2/kg at VT (r = -0.61; P < 0.03), peak VO2/kg (r = -0.63; P < 0.01), and increase of systolic blood pressure (r = -0.52; P < 0.02). In the normals only VO2/kg at VT correlated significantly with TILIV (r = -0.41; P < 0.03). In patients, stepwise regression analysis identified three predictors which could explain 79% of the variance of TILIV: VO2/kg at VT (r2 = 0.51), peak cardiac index (r2 = 0.20), and peak VO2/kg (r2 = 0.08). CONCLUSION: TILIV, determined at the onset of ramp exercise, is prolonged in CHF patients compared with that in normals and reflects severity of functional impairment because of reduced cardiac index and aerobic capacity. TILIV can provide information about changes in cardiopulmonary exercise capacity and thus can be used for follow-up and treatment studies in CHF.

Predictors of response to exercise training in severe chronic congestive heart failure.

We prospectively assessed whether baseline central hemodynamics and exercise capacity can predict improvement of VO2 at ventilatory threshold (VT) after exercise training in patients with severe chronic congestive heart failure. Eighteen patients (mean +/- SEM; age 52 +/- 2 years), half of them listed for transplant, underwent 3 weeks of exercise training (interval cycle and treadmill walking; 5 x/week) and 3 weeks of activity restriction in a random-order crossover trial. Baseline data were not significantly different for groups with exercise training first and activity restriction first: cardiac index at rest (2.1 +/- 0.1 L/m2/min), maximum cardiac index (3.1 +/- 0.2 L/m2/min) (Fick), and echocardiographic ejection fraction (21 +/- 1%). The same was true for cardiopulmonary exercise data (cycle ergometry; up 12.5 W/min): VO2 at VT (9.3 +/- 0.4 ml/kg/min), maximum VO2 (12.2 +/- 0.7 ml/kg/min), VT in percentage of predicted maximum VO2 (31 +/- 2%), heart rate at VT (95 +/- 4 beats/min), and decrease of dead space-to-tidal volume ratio from rest to VT (33 +/- 1 --> 29 +/- 1). Improvement of VO2 at VT after training (2.2 +/- 0.4 ml/kg/min; p <0.001) was not related to baseline central hemodynamics (r = <0.10 for each), but was greater in patients with a lower baseline VO2 at VT (r = -0.65; p <0.01), peak VO2 (r = -0.66; p <0.01), VT in percentage of predicted maximum VO2 (r = -0.74; p <0.001), heart rate at VT (r = -0.63; p <0.01), and smaller decrease of dead space-to-tidal volume ratio from rest to VT (r = 0.65; p <0.01). Ejection fraction after exercise training (24 +/- 2%) and activity restriction (23 +/- 2%) did not differ significantly compared with baseline, and patient status (heart failure and cardiac rhythm) remained stable. Three parameters accounted for 84% of the variance of improvement in VO2 at VT: VO2 at VT in percent predicted maximum VO2, decrease of dead space-to-tidal volume ratio, and heart rate at VT. The findings suggest that there was a greater increase in VO2 at VT after exercise training in patients with greater peripheral deconditioning at baseline. The improvement was unrelated to central hemodynamics. Clinically stable patients with severe chronic congestive heart failure, potential heart transplant candidates, and those awaiting transplantation may benefit from involvement in a short-term exercise training program.

Short-term reproducibility of cardiopulmonary measurements during exercise testing in patients with severe chronic heart failure.

Eleven men with severe chronic heart failure (peak cardiac index 4.0 +/- 0.2 L/m2/min), six on a heart transplantation waiting list, were prospectively assessed. To determine reproducibility of cardiopulmonary and hemodynamic variables for clinical purposes during ramp bicycle ergometry, the patients underwent two ramp bicycle ergometer tests (3 minutes unloaded, work rate increments of 12.5 W/min) with a 1-week interval between tests. Oxygen uptake (VO2) carbon dioxide production (VCO2), and ventilation were measured breath by breath, and calculations were performed to determine gas exchange ratio, oxygen pulse, ventilatory equivalents of oxygen and carbon dioxide, and end-tidal partial pressure for oxygen and carbon dioxide. Additionally, heart rate, blood pressure, and lactate levels were assessed. Measurements were performed at submaximum work rate levels of 25 W, 50 W, and 75 W at ventilatory threshold and at peak work rate. At all measurement points, the coefficient of variation for cardiopulmonary variables was between 1.4% and 7.1% for submaximum work rate levels, between 1.2% and 4.4% at ventilatory threshold, and between 2.4% and 7.1% at peak work rate. For heart rate, blood pressure, and lactate levels, coefficient of variation was between 2.7% and 5.7% for submaximum work rate levels, between 1.4% and 6.1% at ventilatory threshold, and between 1.2% and 5.5% at peak work rate. The data suggest high reproducibility for duplicate measurements of cardiopulmonary and hemodynamic variables during ramp bicycle ergometry in patients with severe chronic heart failure. The results may be used to determine whether any variable in a single patient is significantly different from that obtained in a previous exercise test or if the change is within experimental error.

Effects of exercise training and activity restriction on 6-minute walking test performance in patients with chronic heart failure.

Eighteen hospitalized patients with severe chronic heart failure (ejection fraction [mean +/- SEM] 21% +/- 1%) underwent 3 weeks of exercise training (interval bicycle ergometer and treadmill walking training exercises) and 3 weeks of activity restriction in a random-order crossover trial. Before and after exercise training and after activity restriction, a 6-minute walking test was performed to determine the maximum distance walked, hemodynamic and cardiopulmonary responses, norepinephrine levels, and ratings of leg fatigue and dyspnea while walking. A ramp test on bicycle ergometer (increments of 12.5 W/min) was performed before and after exercise training and activity restriction to determine peak oxygen uptake. After training, the maximum distance walked was increased by 65% (from 232 +/- 21 m at baseline to 382 +/- 20 m; p < 0.001), whereas after activity restriction (253 +/- 19 m) there was no significant difference compared with baseline. No significant differences in hemodynamic and cardiopulmonary parameters (with the exception of the ventilatory equivalent for carbon dioxide and perceived exertion) or norepinephrine levels were observed during walking tests. Improvement in maximum distance walked correlated significantly with training-induced increase in peak oxygen uptake measured during bicycle ergometry (r = 0.47, p < 0.05). The lower the maximum distance walked at baseline, the more pronounced the training-induced prolongation of maximum distance (r= -0.73; p < 0.001). These data support the value of exercise training in patients with severe chronic heart failure for improving maximum distance walked, as documented by the 6-minute walking test. The impairment of walking test performance during activity restriction suggests a need for long-term exercise training programs.

Interval training in patients with severe chronic heart failure: analysis and recommendations for exercise procedures.

This study analyzes a new exercise training procedure, which includes interval exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery phases) and on treadmill (60-s work and recovery phases each). Training was applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/- SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from 12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A specific steep ramp test (work rate increments 25 W.10 s-1) was developed to derive exercise intensity for work phases in IntCT, which was 50% of the maximum work rate achieved. Steep ramp test was performed at the start of the study to determine the initial training work rate, then weekly to readjust it. Since the maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172 +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/- 4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were measured. There was no significant change in heart rate, blood pressure, and ratings of perceived exertion (RPE) using a Borg Scale between the first and the third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80 +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training intensity. When compared with the commonly used intensity level of 75% peak VO2 from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed training work rate was more than doubled (240%; P < 0.0001) while cardiac stress was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of RPE corresponded to those measured at 75% peak VO2. Interval exercise training is thus recommended for selected patients with CHF as it allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp test, training work rate can be determined and readjusted weekly during initial training period.

Cardiopulmonary determinants of functional capacity in patients with chronic heart failure compared with normals.

BACKGROUND: Patients with chronic heart failure (CHF) are characterized by abnormal gas exchange and ventilatory responses to exercise. HYPOTHESIS: This study compares variables obtained from cardiopulmonary exercise testing in 35 patients with CHF with 35 age- and weight-matched healthy subjects. A second goal was to obtain cardiopulmonary variables measured at ventilatory threshold to distinguish patient changes from those of healthy subjects. METHODS: Exercise testing was carried out using bicycle ergometry with ramplike protocol (work rate increments 12.5 W/min). Gas exchange and ventilation were measured breath by breath. RESULTS: Compared with healthy subjects, the VO2 in patients was lower at identical work rates (p < 0.004) and at ventilatory threshold (p < 0.0001), and the slope of the VO2 curve during incremental exercise was flatter (p < 0.05). With the exception of heart rate, the variables for VO2, VCO2, ventilation, O2 pulse, ventilatory equivalents for O2 and CO2, and VD/VT (physiologic deadspace to tidal volume ratio), as well as lactate differed significantly at identical work rates. With the exception of VD/VT, all cardiopulmonary variables showed significant differences in their slopes during exercise. By means of a discriminant analysis, VCO2 and ventilation proved to be the most distinguishing variables at ventilatory threshold between patients with CHF and healthy subjects. CONCLUSIONS: These results indicate the clinical usefulness of cardiopulmonary exercise testing when assessing functional impairment due to CHF. For treatment evaluation, not only VO2 but also VCO2 and ventilation responses to exercise should be considered.

Effects of short-term exercise training and activity restriction on functional capacity in patients with severe chronic congestive heart failure.

Previous exercise training studies in patients with chronic congestive heart failure (CHF) were performed for periods lasting > 2 months, and effects of activity restriction on exercise induced-benefits were not systematically assessed. With one exception study, patients were not reported to be transplant candidates. In this random-order crossover study, effects of 3 weeks of exercise training and 3 weeks of activity restriction on functional capacity in 18 hospitalized patients with severe CHF [(mean +/- SEM) age 52 +/- 2 years; ejection fraction 21 +/- 1%; half of them on a transplant waiting list] were assessed. The training program consisted of interval exercise with bicycle ergometer (15 minutes) 5 times weekly, interval treadmill walking (10 minutes), and exercises (20 minutes), each 3 times weekly. With training, the onset of ventilatory threshold was delayed (p < 0.001), with increased work rate by 57% (p < 0.001) and oxygen uptake by 23.7% (p < 0.001). On average, there was a 14.6% decrease in slope of ventilation/carbon dioxide production before the onset of ventilatory threshold (p < 0.05), and ventilatory equivalent of carbon dioxide production by 10.3% (p < 0.01). At the highest comparable work rate (56 +/- 5 W) the following variables were decreased: heart rate (7.3%; p < 0.05), lactate (26.6%; p < 0.001), and ratings of perceived leg fatigue and dyspnea (14.5% and 16.5%; p < 0.001 each). At peak exercise, oxygen uptake was increased by 19.7% (p < 0.01) and oxygen pulse by 14.2% (p < 0.01). There was a correlation of baseline peak oxygen uptake and increase of peak oxygen uptake due to training (r = -0.75; p < 0.004). Independently of the random order, data after activity restriction did not differ significantly from data measured at baseline. Patients with stable, severe CHF can achieve significant improvements in aerobic and ventilatory capacity and symptomology by short-term exercise training using interval exercise methods. Impairments due to activity restriction suggest the need for long-term exercise training.

Aerobic capacity and functional classification of patients with severe left-ventricular dysfunction.

Classes I/II and III of the classification systems of the New York Heart Association (NYHA), Canadian Cardiovascular Society (CCS) and American Medical Association (AMA) were compared with each other and with the Weber classification (O2 uptake, VO2/kg during treadmill walking) in 35 male patients with severe left ventricular dysfunction. Measured end points were ventilatory threshold (VT) and peak exercise. Also investigated was whether the CCS and AMA scales, due to their more stringent differentiation, are more precise than the NYHA system in determining a limited physical capacity and whether there are other differentiating factors useful in classification which may be derived from cardiopulmonary exercise testing. At the VT, the mean VO2/kg did not differ significantly in any classification system between classes I/II and III (12.8 +/- 2.5 vs. 11.1 +/- 2.3 ml/kg/min) and corresponded to Weber class B. At peak exercise, the mean VO2/kg only differed significantly within the NYHA classification; classes I/II (16.3 +/- 3.1 ml/kg/min) corresponded to Weber class B, and class III (13 +/- 3 ml/kg/min) to Weber class C. The individual values displayed a large scatter. Factors differing in classes I/II and III of all three systems at peak exercise were the ventilatory equivalent of O2 and CO2 as well as end-tidal partial pressure for O2 and CO2. At VT these factors showed a separating character only in the AMA classification. It is not possible to determine objective functional impairment by use of the NYHA, CCS and AMA systems because they are not analogous to the Weber system. Nevertheless, these classification systems can be used for clinical assessment and follow-up.

Influence of different exercise protocols on functional capacity and symptoms in patients with chronic heart failure.

This study compares hemodynamic, metabolic, and gas exchange responses, catecholamine levels, and symptoms in 35 male patients with chronic heart failure (CHF) ([mean +/- SD] age 53 +/- 11 yr; ejection fraction 24 +/- 11%) during three differently graded exercise test protocols. On three consecutive days patients performed cycle ergometry supine, with prolonged steps (prol BE) and right heart catheterization, ramplike cycle ergometry sitting (ramp BE), and ramplike treadmill walking (TMW). As in routine clinical practice, the prol BE was terminated when pathologic central hemodynamics and/or increased symptomology occurred, and ramp BE and TMW due to increased symptomology and/or physician's decision. During prol BE at ventilatory threshold (VT) the VO2 (8.6 +/- 1.8 ml.kg-1.min-1) was lower than during ramp BE (9.3 +/- 2.1 ml.kg-1.min-1) (P < 0.017) and TMW (11.8 +/- 2.3 ml.kg-1.min-1) (P < 0.0001). Prol BE, ramp BE, and TMW also differed significantly with respect to ventilation (22 +/- 7 l.min-1; 26 +/- 6 l/min-1; 29 +/- 7 l.min-1; P < 0.01) and heart rate (100 +/- 15 beats.min-1; 103 +/- 18 beats.min-1; 110 +/- 16 beats.min-1; P < 0.017). No differences were found in lactate levels, catecholamine levels, and ratings of leg fatigue and dyspnea. At test termination, the peak VO2 during prol BE (100.8 +/- 3.3 ml.kg-1.min-1) was lower than during ramp BE (13.3 +/- 4.1 ml.kg-1.min-1) (P < 0.0001) and TMW (14.7 +/- 3.4 ml.kg-1.min-1) (P < 0.0001). Peak norepinephrine value during ramp BE (4.531 +/- 2.788 nmol.l-1) was higher than during prol BE (3.707 +/- 2.262 nmol.l-1) (P < 0.001). Among the three tests, no significant differences were found for peak values of heart rate, lactate, and ratings of dyspnea. Although the VO2.kg-1 at VT was significantly higher during ramp BE and TMW compared to prol BE (P < 0.001), the values expressed as a percent of peak VO2.kg-1 were significantly lower (70 +/- 4%; 72 +/- 6%; 79 +/- 3%; P < 0.017). A systematic effect on aerobic capacity with reduced peak values during ramp BE and TMW was demonstrated when test termination was based primarily on pathological findings of central hemodynamics from prol BE.

Physical responses to different modes of interval exercise in patients with chronic heart failure--application to exercise training.

METHOD: In exercise training with chronic heart failure patients, working muscles should be stressed with high intensity stimuli without causing cardiac overstraining. This is possible using interval method exercise. In this study, three interval exercise modes with different ratios of work/ recovery phases (30/60 s, 15/60 s and 10/60 s) and different work rates were compared during cycle ergometer exercise in heart failure patients. Work rate for the three interval modes was 50% (30/60 s), 70% (15/60 s) and 80% (10/60 s) of the maximum achieved during a steep ramp test (increments of 25 w/10 s) corresponding to 71, 98 and 111 watts on average. Metabolic and cardiac responses to the three interval exercises were then examined including catecholamine levels and perceived exertion. Parameters measured during interval exercise were compared with an intensity level of 75% peak VO2, determined during an ordinary ramp exercise test (increments of 12.5 W.min-1). RESULTS: (mean +/- SEM) (1) In all three interval modes, VO2, ventilation and lactate did not increase significantly during the course of exercise. Mean values during the last work phase were between 754 +/- 30 and 803 +/- 46 ml.min-1 for VO2, between 26 +/- 3 and 28 +/- 1 l.min-1 for ventilation and between 1.24 +/- 0.14 and 1.29 +/- 0.10 mmol.l-1 for lactate. (2) In mode 10/60 s, heart rate and systolic blood pressure increased significantly (82 +/- 4 --> 85 +/- 4 beats.min-1; 124 +/- 5 --> 134 +/- 5 mmHg; P < 0.05 each), while in mode 15/60 s catecholamines increased significantly (norepinephrine 0.804 +/- 0.089 --> 1.135 +/- 0.094 nmol.l-1; P < 0.008; epinephrine 0.136 +/- 0.012 --> 0.193 +/- 0.019 nmol.l-1; P < 0.005). (3) In all three modes, rating of leg fatigue and dyspnoea increased significantly during exercise but remained within the range of values considered 'very light to fairly light' on the Borg scale. (4) Compared to an intensity level of 75% peak VO2, work rate during interval work phases was between 143 and 221%, while cardiac stress (rate-pressure product) was significantly lower (83-88%). CONCLUSION: All three interval modes resulted in physical response in an acceptable range of values, and thus can be recommended.

Ventilatory and lactate threshold determinations in healthy normals and cardiac patients: methodological problems.

In healthy normal individuals (n = 69), coronary patients with myocardial ischaemia (n = 27) and patients with chronic heart failure (CHF, n = 33), four widely applied methods to determine ventilatory threshold (VT) were analysed: V-slope, ventilatory equivalent for O2 (EqO2), gas exchange ratio (R) and end-tidal partial pressure of oxygen. Lactate threshold [LAT, log lactate vs log oxygen uptake (VO2)] was also determined. Analysis focused on rate of success of threshold determination, comparability of threshold methods, reproducibility and interobserver variability. Cycle ergometry protocols with ramp-like mode and graded steady-state mode used in exercise testing were considered separately. In healthy normal individuals and coronary patients with myocardial ischaemia, at least three VT could be determined during ramp-like mode and two VT during graded steady-state mode, 82% of the time. For CHF patients, the rate of successful determination of VT was lower. Compared to LAT, VO2 at VT was significantly higher using R and EqO2 methods of VT determination in healthy normal subjects (P < 0.01), and significantly higher when using all four methods in coronary patients (P < 0.01 or P < 0.05, respectively). No difference was observed between VO2 at VT and LAT in CHF patients. In healthy normal individuals, day-to-day reproducibility of VT and LAT was high (error of a single determination from duplicate determinations was between 3.9% and 6.2% corresponding to a VO2 of 52.2 and 89.2 ml.min-1). Interobserver variability was low (error between 0.3% and 5% corresponding to a VO2 of 9.8 and 68 ml.min-1). In CHF patients, interobserver variability was moderately greater (error between 4.6% and 8.2%, corresponding to a VO2 of 35.1 and 62.4 ml.min-1). To optimize threshold determination, standardized procedures are suggested.

The influence of aging on muscle strength and muscle fiber characteristics with special reference to eccentric strength.

It is well established that aging seriously reduces isometric and concentric muscle strength due to atrophy, deterioration of mechanical properties, and motor unit loss. However, there is limited information on the impact of aging on eccentric strength despite the fact that such forces play an equally important role during daily activities. The purpose of this study was to examine the influence of aging on three expressions of muscle strength (isometric, concentric, and eccentric) in relation to muscle fiber characteristics, with special emphasis on eccentric force. Sedentary but healthy men (age range 18-80 years, n = 60) and women (20-74 years, n = 30) were tested for maximal effort isometric, concentric, and eccentric (1.05, 2.09, 3.14 rads.s-1) quadriceps strength, body composition, and muscle fiber characteristics of the vastus lateralis (men only). There was a significant (p < .05) approximately 30 N per decade decline in isometric and concentric forces, but only 9 N per decade reduction in eccentric strength. There was a significant reduction in Type II muscle fiber area with aging (p < .05). Isometric, eccentric, and concentric force correlated r = .33, r = .32 (p < .05), and r = .12 (p > .05) with Type II muscle fiber area, respectively. The correlation between age and fat-free mass/force ratio ranged from r = .39 to .43 in men and r = .27 to .50 in women. The data suggest a relative preservation of eccentric strength with aging in men and women that seems to be independent of muscle mass or muscle fiber type or size.