The majority of patients with intrapulmonary right-to-left shunting due to pulmonary arteriovenous malformations-exhibit good maximum exercise capacity (> 70% predicted) despite profound arterial oxygen desaturation. We studied seven such patients to assess tissue oxygen delivery during steady-state exercise. From rest to exercise [50 +/- 7 (SE) W] arterial saturation fell from 80 +/- 3 to 74 +/- 3%, and mean right-to-left shunt increased slightly from 31 +/- 4 to 34 +/- 5% (P = NS). Minute ventilation was high for oxygen uptake, and the ventilatory equivalent was raised (174 +/- 19% predicted) and was correlated with shunt size (r = 0.93). The majority of the patients maintained pulmonary alveolar blood flow within the predicted range for their power output, but total cardiac output was increased to 142 +/- 11% predicted due to flow through the shunt. Consequently, on exercise, oxygen delivery per unit oxygen consumption [2.3-3.3 (normal range 1.6-2.4)] and calculated mixed venous oxygen tension (27.0 +/- 0.8 Torr) were preserved. Arterial PCO2 rose on exercise by 2.8 +/- 1.2 Torr, in proportion to the ratio of flow through the shunt to total cardiac output (r = 0.73), but remained low (33.1 +/- 1.4 Torr) in absolute terms. The high cardiac output on exercise may be facilitated by a low pulmonary vascular resistance (0.33 +/- 0.08 mmHg.1-1.min, measured at rest), which may explain why exercise performance is better in these patients than in patients with equivalent hypoxemia from other causes.

Because chemicals introduced into the environment by humans can affect both long-term survivorship and reproduction of amphibians, discovering the specific mechanisms through which these chemicals act may facilitate the development of plans for amphibian conservation. We investigated the amphibian pheromonal system as a potential target of common environmental chemicals. By treating female red-spotted newts, Notophthalmus viridescens, to a commonly used insecticide, endosulfan, we found that the pheromonal system is highly susceptible to low-concentration exposure. The impairment of the pheromonal system directly led to disrupted mate choice and lowered mating success. There were no other notable physiologic or behavioral changes demonstrated by the animals at the insecticide concentrations administered. Our findings suggest that the amphibian pheromonal system is one of the systems subject to subtle negative effects of environmental chemicals.

To investigate the effects of exercise training and immobilization on peak O2 uptake (VO2) and effective O2 diffusive conductance (DO2) in skeletal muscle, three groups of purpose-bred hounds [control (C), exercise trained (E), and immobilized (I)] were studied. Group E exercised on a treadmill 1 h/day, 5 days/wk for 8 wk, while groups C and I were cage confined for 8 wk, with group I undergoing left hindlimb immobilization for the last 3 wk. Thereafter, each dog's left gastrocnemius was surgically isolated, pump perfused, and electrically stimulated to elicit peak VO2 in situ at three levels of arterial oxygenation. O2 delivery [(arterial O2 concentration x muscle blood flow)/100 g muscle] was kept constant among the three groups at each level of arterial oxygenation. Compared with group C, peak VO2/100 g muscle was 38, 33, and 19% greater and DO2/100 g muscle was 71, 75, and 68% greater during normoxia, moderate hypoxia, and severe hypoxia, respectively, in group E (P < 0.02), whereas no differences from control were found in group I. We conclude that O2 delivery is not the unique determinant of peak VO2 and that exercise training improves the functional blood-tissue gas exchange properties of the muscle itself. Immobilization sufficient to reduce muscle weight by 31% and citrate synthase activity by 68% has no effect on peak VO2/100 g muscle or DO2/100 g muscle.

No abstract

Intrapulmonary chemoreceptors (IPC) are CO(2)-sensitive sensory neurons that innervate the lungs of birds, help control the rate and depth of breathing, and require carbonic anhydrase (CA) for normal function. We tested whether the CA enzyme is located intracellularly or extracellularly in IPC by comparing the effect of a CA inhibitor that is membrane permeable (iv acetazolamide) with one that is relatively membrane impermeable (iv benzolamide). Single cell extracellular recordings were made from vagal filaments in 16 anesthetized, unidirectionally ventilated mallards (Anas platyrhynchos). Without CA inhibition, action potential discharge rate was inversely proportional to inspired PCO(2) (-9.0 +/- 0.8 s(-1). lnTorr(-1); means +/- SE, n = 16) and exhibited phasic responses to rapid PCO(2) changes. Benzolamide (25 mg/kg iv) raised the discharge rate but did not alter tonic IPC PCO(2) response (-9.8 +/- 1.6 s(-1). lnTorr(-1), n = 8), and it modestly attenuated phasic responses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduced tonic IPC PCO(2) response to -3.5 +/- 3.6 s(-1). lnTorr(-1) (n = 6), and severely attenuated phasic responses. Results were consistent with an intracellular site for CA that is less accessible to benzolamide. A model of IPC CO(2) transduction is proposed.