Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1.

Hypoxia-inducible factor (HIF)-1 is stabilized by hypoxia and iron chelation. We hypothesized that HIF-1 might be involved in pulmonary vascular regulation and that infusion of desferrioxamine over 8 h would consequently mimic hypoxia and elevate pulmonary vascular resistance. In study A, we characterized the pulmonary vascular response to 4 h of isocapnic hypoxia; in study B, we measured the pulmonary vascular response to 8 h of desferrioxamine infusion. For study A, 11 volunteers undertook two protocols: 1) 4 h of isocapnic hypoxia (end-tidal PO(2) = 50 Torr), followed by 2 h of recovery with isocapnic euoxia (end-tidal PO(2) = 100 Torr), and 2) 6 h of air breathing (control). For study B, nine volunteers undertook two protocols while breathing air: 1) continuous infusion of desferrioxamine (4 g/70 kg) over 8 h and 2) continuous infusion of saline over 8 h (control). In both studies, pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by Doppler echocardiography via the maximum pressure gradient during systole across the tricuspid valve. Results show a progressive rise in pressure gradient over the first 3-4 h with both isocapnic hypoxia (P < 0.001) and desferrioxamine infusion (P < 0.005) to increases of ~16 and 4 Torr, respectively. These results support a role for HIF-regulated gene activation in human hypoxic pulmonary vasoconstriction

Does sleep-dependent consolidation favour weak memories?

Sleep stabilizes newly acquired memories, a process referred to as memory consolidation. According to recent studies, sleep-dependent consolidation processes might be deployed to different extents for different types of memories. In particular, weaker memories might benefit greater from post-learning sleep than stronger memories. However, under standard testing conditions, sleep-dependent consolidation effects for stronger memories might be obscured by ceiling effects. To test this possibility, we devised a new memory paradigm (Memory Arena) in which participants learned temporospatial arrangements of objects. Prior to a delay period spent either awake or asleep, training thresholds were controlled to yield relatively weak or relatively strong memories. After the delay period, retrieval difficulty was controlled via the presence or absence of a retroactive interference task. Under standard testing conditions (no interference), a sleep-dependent consolidation effect was indeed observed for weaker memories only. Critically though, with increased retrieval demands, sleep-dependent consolidation effects were seen for both weaker and stronger memories. These results suggest that all memories are consolidated during sleep, but that memories of different strengths require different testing conditions to unveil their benefit from post-learning sleep

Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography.

Hypercapnia has been shown in animal experiments to induce pulmonary hypertension. This study measured the sensitivity and time course of the human pulmonary vascular response to sustained (4 h) hypercapnia and hypocapnia. Twelve volunteers undertook three protocols: 1) 4-h euoxic (end-tidal Po(2) = 100 Torr) hypercapnia (end-tidal Pco(2) was 10 Torr above normal), followed by 2 h of recovery with euoxic eucapnia; 2) 4-h euoxic hypocapnia (end-tidal Pco(2) was 10 Torr below normal) followed by 2 h of recovery; and 3) 6-h air breathing (control). Pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by using Doppler echocardiography via the maximum tricuspid pressure gradient during systole. Results show progressive changes in pressure gradient over 1-2 h after the onset or offset of the stimuli, and sensitivities of 0.6 to 1 Torr change in pressure gradient per Torr change in end-tidal Pco(2). The human pulmonary circulatory response to changes in Pco(2) has a slower time course and greater sensitivity than is commonly assumed. Vascular tone in the normal pulmonary circulation is substantial