Haemodynamic effects of macrocyclic and linear gadolinium chelates in rats: role of calcium and transmetallation.
Several studies were undertaken to compare four magnetic resonance imaging (MRI) contrast media (CM) as regards acute haemodynamic effects in rats and to investigate the mechanisms involved. (1) Normotensive rats received a rapid bolus intravenous injection of 0.5 mmol kg-1 of each CM. The effects of Gd-DOTA, Gd-HP-DO3A, Gd-DTPA and Gd-DTPA-BMA on blood pressure (BP) were compared. (2) The haemodynamic effects of Gd-DTPA (0.5 mmol kg-1) were compared to those of isovolumic and isoosmolar Zn-DTPA and glucose solutions. (3) The haemodynamic profiles of Gd-DTPA and Gd-DTPA-BMA were recorded with and without addition of ionized calcium. (4) The mechanism of Gd-HP-DO3A-induced transient rise in BP was investigated by evaluating the effects of phentolamine or diltiazem pretreatment. For (1) the greatest drop in BP occurred following Gd-DTPA (a linear chelate) injection (-18 +/- 2% vs baseline, P < 0.01). Gd-DTPA-BMA, another lineate chelate, also induced a slight but significant reduction in BP (-8 +/- 2% at 45 s, P < 0.05). Gd-DOTA, a macrocyclic CM, had virtually no haemodynamic effects. For (2) the Gd-DTPA-induced drop in BP was greater than that of the osmolality-matched glucose control and lower than that of osmolality-matched Zn-DTPA. For (3) a transmetallation phenomenon versus free ionized calcium is possible in the case of both linear CM (Gd-DTPA and Gd-DTPA-BMA) since Ca2+ significantly reduced the CM-induced decrease in BP. For (4) a transient rise in BP was observed following Gd-HP-DO3A, another macrocyclic chelate, associated with a concomitant increase in stroke volume. This effect was antagonized neither by phentolamine nor by diltiazem. The decrease in BP following injection of Gd-DTPA or Gd-DTPA-BMA may not only be osmolality-related since (a) Gd-DOTA solution, whose osmolality is greater than that of Gd-DTPA-BMA, had a lesser effect, and (b) this hypotensive effect was corrected by a addition of ionized calcium. The transient Gd-HP-DO3A-induced rise in BP is probably the consequence of a positive inotropic effect.
Idée
J M
JM
Pharmacology Department, Laboratoire Guerbet, Aulnay-sous-Bois, France.
Berthommier
C
C
Goulas
V
V
Corot
C
C
Santus
R
R
Hermine
C
C
Schaefer
M
M
Bonnemain
B
B
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003287:Contrast Media / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology*; D019786:Gadolinium DTPA / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002614:Chelating Agents; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; C064925:gadodiamide; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium; D004110:Diltiazem; D019786:Gadolinium DTPA; D002118:Calcium; D010646:Phentolamine