Adenosine is an endogenous nucleoside which stimulates respiration in man and other mammals. In animals adenosine appears to initiate respiratory stimulation within the carotid body, but whether this is the site of action in man is not known. We administered adenosine by intra-aortic infusion to 12 subjects undergoing cardiac catheterisation. When adenosine was infused at three sites proximal to the carotid circulation, minute ventilation was significantly higher than baseline values or those during adenosine infusion at a more distal site. These results support the hypothesis that adenosine-induced respiratory stimulation in man is mediated in the carotid body.

1 The effects on respiration of intravenous infusions of the endogenous nucleoside adenosine and its deaminated metabolite, inosine, administered in random order, singleblind, were compared in six healthy volunteers.2 The infusion rate of each nucleoside was initially 3.1 mg min-' and was increased stepwise every 2 min, as tolerated, up to a possible maximum of 23.4 mg ml-'. The maximum dose rates received by all subjects were 8.5 mg min' for adenosine and 16.8 mg min-for inosine.3 Adenosine infusion at rates of 6.1 mg min-' and above caused a significant increase in minute ventilation, principally due to an increase in tidal volume, with an associated significant fall in end-tidal Pco2. Mean inspiratory flow rate increased and expiratory duration decreased during adenosine infusion, but there was no change in inspiratory duration. 4 Adenosine infusion also caused a significant increase in heart rate and a slight, but significant increase in systolic blood pressure.5 Infusion of inosine at dose rates up to 16.8 mg min-' produced no pharmacological effects. 6 This study shows that adenosine by infusion produces sustained respiratory stimulation in man and demonstrates that it does not depend on prior conversion of adenosine to inosine or related metabolites and that it is not secondary to systemic hypotension.

The relationship between ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) during work were studied in four trained males during exercise-induced carbohydrate depletion. Repeated bouts of heavy treadmill exercise (6 min at 95% VO2 max) were performed once per hour for 24 h in order to promote a shift in energy substrate from carbohydrate to fat. Measurements of VO2 and VCO2 recorded during each minute indicated that VO2 was unaffected by the number of runs, whereas VCO2 showed a progressive reduction which amounted to 24% during the final run. A corresponding decline of 19% was observed in the respiratory exchange ratio. No significant change in VE occurred between any of the runs. It is concluded that during heavy, repeated, muscular exercise, reductions in VO2, strongly suggestive of an increased fat oxidation, are not accompanied by a corresponding change in ventilation.

The acute haemodynamic effects of intravenous infusion of adenosine, a dilator of most vascular beds, were studied in 16 patients (seven with coronary artery disease, nine with normal coronary arteries) undergoing cardiac catheterization for investigation of chest pain. At the lowest dose used (4.3 mg min-1) adenosine increased minute ventilation by 44% (P less than 0.01, n = 11) and reduced pulmonary vascular resistance by 20% (P less than 0.05) without causing other significant haemodynamic changes. Symptoms, including chest discomfort in 14 patients and dyspnoea in 11, limited the maximum dose to 8.5 +/- 2.3 mg min-1 (mean +/- SD, 108 +/- 24 micrograms kg-1 min-1). At this dose, adenosine reduced pulmonary and systemic vascular resistance (by 38% and 34%, respectively) and increased heart rate (by 34%), stroke index (by 12%) and cardiac index (by 52%). Systemic blood pressure and right atrial pressure did not change. Unexpectedly, adenosine increased left ventricular end-diastolic pressure (LVEDP) (from 5 +/- 6 to 14 +/- 10 mmHg, n = 8), pulmonary capillary wedge pressure (from 3 +/- 2 to 10 +/- 5 mmHg, n = 16) and consequently mean pulmonary artery pressure (from 10 +/- 2 to 16 +/- 5 mmHg). Minute ventilation increased by 84% (n = 11), resulting in hypocapnia (PCO2: 31 +/- 3 mmHg, n = 8) and alkalosis (pH: 7.46 +/- 0.02, n = 8). Oxygen consumption was unchanged during the infusion, but increased by 21% 5 min post infusion. All effects were similar in patients with and without coronary artery disease. Adenosine therefore causes pulmonary and systemic vasodilation and respiratory stimulation. Symptoms and an increase in LVEDP of uncertain cause, which occur with high doses, may limit the use of adenosine as a systemic vasodilator in conscious subjects. However at lower doses adenosine causes selective pulmonary vasodilation which merits further study.

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