Echocardiographic contrast agents and left ventricular contractility: evaluation using an isolated rabbit heart model.
The effects of Albunex (Molecular Biosystems, Inc., San Diego, Calif.) and a second generation contrast agent, FS069, on left ventricular (LV) contractility were evaluated using an isolated rabbit heart model under constant loading conditions and heart rate. Contrast injections (2 ml total volume) were performed in two separate protocols (N1 = 6, N2 = 6). In protocol 1, various doses of Albunex (0.1 to 2.0 ml in saline solution) were used, and paired control injections of a matched dose of 5% solution of human albumin in saline solution were administered. In protocol 2, LV contractility was assessed during injections of the following solutions: (1) 1:250 suspension of FS069 in saline solution, which caused optimal myocardial contrast enhancement; (2) a 1:25 suspension of FS069; (3) a 1:25 suspension of FS069 prefiltered using an 8 microns pore filter; and (4) 2 ml saline solution as a control. Instantaneous LV pressure was analyzed for variations in peak systolic pressure (peak P) and maximum pressure derivative (peak P'), both indices of LV contractility under conditions of fixed heart rate and chamber volume. Albumin alone caused a transient, dose-dependent depression of LV contractility, reflected by decreases in both peak P and peak P' values. These decreases presumably were caused by the decreasing availability of ionized calcium as a result of calcium binding. No further decrease in contractility was noted when Albunex microspheres were present in the solution. Saline injections caused a transient minor increase in LV contractility, reflected by increases of 4.5% +/- 1.1% and 10.6% +/- 3.8% in peak P and peak P' values, respectively. These levels returned to baseline levels within 2 minutes. A similar response was observed when a 1:250 suspension of FS069 was used. The 1:25 suspension of FS069 caused a bimodal response, with initial rises in peak P and peak P' levels (5.2% +/- 3.6% and 12.8% +/- 6.5%, respectively), followed by minor reductions in contractility (2.0% +/- 2.4% and 1.7% +/- 2.1%, respectively). The latter decrease in contractility caused by the 1:25 suspension of FS069 was eliminated by filtering. The isolated rabbit heart model is a highly sensitive tool that allows accurate and direct assessment of possible adverse effects of intravascular contrast agents on LV contractility. Using this model, we showed that neither Albunex microspheres nor FS069 microspheres impaired myocardial contractility.
Mor-Avi
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V
Department of Medicine, University of Chicago Medical Center, Chicago, IL 60637, USA.
Shroff
S G
SG
Robinson
K A
KA
Cholley
B P
BP
Ng
A F
AF
Lang
R M
RM
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003287:Contrast Media / Q000494:pharmacology*; D004452:Echocardiography; D005466:Fluorocarbons / Q000494:pharmacology*; D066298:In Vitro Techniques; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D013599:Systole / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D000418:Albumins; C060687:Albunex; D003287:Contrast Media; C099458:FS 069; D005466:Fluorocarbons; D002118:Calcium