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

Journal article

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.

Authors: Balanos, G; Dorrington, K; Robbins, P

• Publication status: Published
• Journal: Journal of applied physiology (Bethesda, Md. : 1985)
• Volume: 92
• Issue: 6
• Pages: 2501-2507
• Publication date: 2002-06-01
• DOI: 10.1152/japplphysiol.00965.2001
• EISSN: 1522-1601
• ISSN: 8750-7587
• Language: English
• Keywords: Deferoxamine; Hypoxia-Inducible Factor 1, alpha Subunit; Nuclear Proteins; Anoxia; Pulmonary Circulation; Male; Stroke Volume; Humans; Transcription Factors; DNA-Binding Proteins; Heart Rate; Cardiac Output; Hypoxia-Inducible Factor 1; Vascular Resistance; Iron Chelating Agents; Echocardiography; Female