Hemodynamic Effects of Intraatrial Administration of Deferoxamine or Deferoxamine-Pentafraction Conjugate to Conscious Dogs

Abstract

Deferoxamine (DFX) is a specific Fe3+ chelator that is used to manage iron overload, and is being evaluated as an agent to reduce ischemic organ damage that involved iron-mediated .cntdot. OH formation. However, high intravascular doses cause significant hemodynamic changes that may limit or counteract beneficial effects. We used conscious, closed-chest dogs to test the hypothesis that conjugating DFX to pentafraction, a high molecular weight fraction of pentastarch, could reduce such hemodynamic changes. We infused 50 mg/kg of body weight of native DFX, or an equivalent dose as DFX-pentafraction, intraatrially over 15 min. Within 10 min of starting the infusion, DFX increased heart rate from predrug values of 105 .+-. 11 (mean .+-. SEM; N = 9) to 158 .+-. 13 beats/min, and reduced left ventricular (LV) systolic pressure from 131 .+-. 3 to 99 .+-. 16 mm Hg, LV endiastolic pressure from 12 .+-. 3 to 3 .+-. 3 mm Hg, and mean arterial pressure (MABP) from 101 .+-. 5 to 74 .+-. 13 mm Hg. In two dogs, MABP decreased to .ltoreq. 35 mm Hg. These parameters returned to predrug values by 60 min after infusion. All of these changes were statistically significant (p < 0.05). In contrast, infusing DFX-pentafraction (N = 9) caused no significant cardiac or hemodynamic changes other than a transient and slight (approximately 7%) increase in systolic arterial pressures. This conjugate, which prolongs the plasma half-life and does not alter the iron-chelating activity of native DFX, eliminates many undesirable hemodynamic actions. It may be a useful therapeutic alternative to native DFX in some settings.