Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.

SummaryThe study was set up to investigate the awareness of elderly patients and medical doctors of medical restrictions to driving. Separate questionnaires were completed by patients and doctors. All were interviewed face-to-face, without prior warning and their immediate answers were recorded. In total, 150 elderly patients from the acute elderly care wards, rehabilitation wards and day hospital, and 50 doctors (including all grades from consultant to junior house oYcer) were interviewed. The main outcome measures were numbers of patients currently driving and previously driving; patients' awareness of how their medical condition aVected their ability to drive; doctors' spontaneous knowledge of medical conditions which restrict driving, current licensing policy, and restrictions for five specific medical conditions (epilepsy, myocardial infarction, stroke, 5-cm abdominal aortic aneurysm, and diabetes). Only 21 patients were current drivers, and six of these should not have been driving. While 103 perceived themselves eligible to drive, 46 had medical restrictions to driving. Seventeen of the 47 patients who perceived themselves not eligible to drive possibly did not have restrictions to driving. Doctors' knowledge of the current licensing policy and action to be taken if a patient was not eligible to drive was very poor. Knowledge of medical restrictions to driving was scanty, with few doctors giving the correct driving restrictions for the five specific conditions. We recommend that education of doctors regarding medical restrictions to driving should begin at an undergraduate level and be continued throughout their postgraduate career.

Background-Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse eVect on quality of life. Few studies have considered the eVects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. Methods-Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3-6 months after surgery (n = 53). Results-Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV 1 ; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p<0.05). Wedge resection (n = 13) produced a nonsignificant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (PṼ O 2 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; diVerence (95% CI) 6.72 (3.15 to 10.28); p<0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. Conclusions-Neither thoracotomy alone nor limited lung resection has a significant eVect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.

During normal progressive exercise, the gas exchange anaerobic threshold occurs when CO2 production (VCO2) and ventilation (VE) increase so as to depart from a linear relationship to O2 consumption (VO2). This is thought to represent a gas exchange response to metabolic acidosis due to lactate accumulation. Patients with McArdle's disease have previously been reported to exhibit a steepened ventilatory response relative to VCO2, despite an inability to produce lactate. However, the VCO2 response has not been studied. We therefore investigated the VCO2-VO2 and VE-VO2 relationships in seven McArdle's disease patients and seven control subjects during symptom-limited maximal treadmill exercise. Analysis of gas exchange showed that whereas all control subjects had an easily identifiable anaerobic threshold, four of the patients had none and the other three displayed an attenuated threshold. The occurrence of the threshold in one patient was associated with a small rise in lactate and in another patient with an abrupt rise in leg discomfort, suggesting a pain response. Ammonia and the purine metabolite hypoxanthine were elevated during exercise in all patients, suggesting that ammonia may be a product of adenosine monophosphate degradation. Free fatty acid levels were also elevated, and a shift toward utilization of lipid may contribute to abnormal gas exchange responses. It is concluded that lactic acidosis contributes to the gas exchange anaerobic threshold but that other factors, such as discomfort, may be involved in the excess Ve seen during heavy exercise.

Peripheral circulating levels of atrial natriuretic peptide may exhibit short-term variation compatible with a pulsatile pattern of secretion. We obtained samples every 2 min for 90 min from the antecubital vein of 16 patients with chronic cardiac failure and 13 controls. Overall levels were higher in the patients (median and quartiles 230 (125,325) vs. 26 (16,48) ng l-1; P < 0.001). In both groups there was considerable variability, with 10 (2-12) peaks, 9 (7-15) troughs (both defined as > 2 SD from the mean) and 16 (13-18) pulses (defined by computer) during the sampling period in controls, and a similar number in patients. We then carried out simultaneous sampling in the pulmonary artery, femoral artery and peripheral vein in eight subjects with normal cardiac function and six patients with impaired function due to valvular heart disease. The pattern of variability was preserved in all three sites in both groups, suggesting intermittent secretion rather than variable breakdown of the peptide in the lung. No changes in right atrial pressure or heart rate were observed to coincide with the variations, but levels of the peptide in the pulmonary artery correlated with right atrial pressure in patients (r = 0.87; P < 0.05). The mechanism of such periodicity and its pathophysiological importance remain unknown.

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.

There is no evidence of impairment of the exercise response in subjects with long-standing diabetes, and the apparent fall in left ventricular EF at peak exercise could be related to hemodynamic adaptation.

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