Prevention of the hemodynamic effects of iopromide-carrying liposomes in rats and pigs.
OBJECTIVE
Intravenous injection of liposomes is able to trigger allergy-like reactions that affect the cardiopulmonary system. The mechanism of these effects is still not totally clear. Because prediction of adverse reactions and the consequent exclusion of reactive patients do not seem feasible, prevention might have a considerable impact.


METHODS
Two small, multilamellar liposome batches with the encapsulated contrast agent iopromide, which differed by size and buffer composition, were injected into anesthetized rats (n = 5 per group) and pigs (n = 6 per group). Blood pressure (BP), cardiac output (CO), contractility (dP/dt; in rats), total peripheral resistance (TPR; in rats), pulmonary vascular resistance (in pigs), and pulmonary arterial pressure (PAP; in pigs) were monitored. Saline, mannitol solution, the two buffers, and the contrast medium were used as controls.


RESULTS
Significant changes in hemodynamic parameters were observed not only between liposomes and controls but also between the two liposome preparations. In rats, a significant decrease in BP followed by its normalization and subsequent increase, a decrease in CO followed by an increase, a decrease in TPR, and a decrease in dP/dt followed by an increase were observed. In pigs, the effects were different both in quality and in quantity (more intense) compared with those in rats. In this species, an increase in BP, a decrease in CO, an increase in TPR, and an increase in PAP were found. Pretreatment with acetylsalicylic acid was able to prevent the hemodynamic changes induced by the liposomes.


CONCLUSIONS
Allergy-like side effects induced by liposome injection strongly depend on the size, electric charge, and composition of the particles. The mechanism triggered by liposome injection probably is complex and can be effectively blocked by pretreatment with acetylsalicylic acid.
Krause
W
W
Research Laboratories of Schering AG, Berlin, Germany. Werner.Krause@Schering.de
Gerlach
S
S
Muschick
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003287:Contrast Media / Q000008:administration & dosage* / Q000009:adverse effects; D003627:Data Interpretation, Statistical; D006439:Hemodynamics / Q000187:drug effects*; D006967:Hypersensitivity / Q000517:prevention & control*; D007472:Iohexol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008081:Liposomes / Q000009:adverse effects*; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003287:Contrast Media; D008081:Liposomes; D007472:Iohexol; C038192:iopromide; D001241:Aspirin