Lipofundin(R) MCT/LCT 20% increase left ventricular systolic pressure in an ex vivo rat heart model via increase of intracellular calcium level / 대한마취과학회지

BACKGROUND: Lipid emulsions have been used to treat various drug toxicities and for total parenteral nutrition therapy. Their usefulness has also been confirmed in patients with local anesthetic-induced cardiac toxicity. The purpose of this study was to measure the hemodynamic and composition effects of lipid emulsions and to elucidate the mechanism associated with changes in intracellular calcium levels in myocardiocytes. METHODS: We measured hemodynamic effects using a digital analysis system after Intralipid(R) and Lipofundin(R) MCT/LCT were infused into hearts hanging in a Langendorff perfusion system. We measured the effects of the lipid emulsions on intracellular calcium levels in H9c2 cells by confocal microscopy. RESULTS: Infusion of Lipofundin(R) MCT/LCT 20% (1 ml/kg) resulted in a significant increase in left ventricular systolic pressure compared to that after infusing modified Krebs-Henseleit solution (1 ml/kg) (P = 0.003, 95% confidence interval [CI], 2.4-12.5). Lipofundin(R) MCT/LCT 20% had a more positive inotropic effect than that of Intralipid(R) 20% (P = 0.009, 95% CI, 1.4-11.6). Both lipid emulsion treatments increased intracellular calcium levels. Lipofundin(R) MCT/LCT (0.01%) increased intracellular calcium level more than that of 0.01% Intralipid(R) (P < 0.05, 95% CI, 0.0-1.9). CONCLUSIONS: These two lipid emulsions had different inotropic effects depending on their triglyceride component. The inotropic effect of lipid emulsions could be related with intracellular calcium level.

Lipofundin 20% induces hepatic lipid peroxidation in New Zealand white rabbits / Lipofundin 20% induce peroxidación lipídica hepática en conejos Nueva Zelanda blancos

Objective. The aim of the present work was to evaluate the effects of Lipofundin 20% on lipid peroxidation markers in the liver of New Zealand white rabbits. Materials and methods. The animals were treated with an intravenous injection (2 ml/kg) of the lipid emulsion during 8 days through the marginal ear vein. At the end of the experiment some lipid peroxidation parameters and lipid profile were tested through spectrophotography. Results. Lipofundin was found to induce a significant (p<0.05) increase of malondialdehyde, total hydroperoxides, and peroxidation potential. Also, high levels of total cholesterol, triglycerides, LDL - cholesterol and HDL-cholesterol were observed in treated animals compared with the control group (p<0.05). Conclusions. Data proved that Lipofundin induces hepatic lipid peroxidation in rabbits, mainly through a mechanism which involves an induction of hyperlipidemia.

Objetivo. El objetivo del presente trabajo fue evaluar los efectos del lipofundin 20% sobre marcadores hepáticos de peroxidación lipídica en conejos blancos Nueva Zelanda. Materiales y métodos. Los animales fueron tratados con una inyección intravenosa (2 ml/kg) de la emulsión lipídica durante 8 días por la vena marginal de la oreja. Al final del experimento algunos marcadores de peroxidación lipídica y el perfil lipídico fueron espectrofotométricamente determinados. Resultados. Se observó que el lipofundin indujo un incremento significativo (p<0.05) de malonildialdehído, hidroperóxidos totales y el potencial de peroxidación. También, altos niveles de colesterol total, triglicéridos, colesterol de LDL y colesterol de HDL fueron observados en los animales tratados respecto a los del grupo control (p<0.05). Conclusiones. Los resultados demostraron que el Lipofundin 20% induce peroxidación lipídica hepática en conejos, principalmente a través de un mecanismo que involucra la inducción de hiperlipidemia.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

PURPOSE: Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon (AmB-D) and two new different AmB formulations. METHODS: three products were studied: Fungizon, and two Fungizon /Lipofundin admixtures, which were diluted through two methods: in the first one, Fungizon was previously diluted with water for injection and then, in Lipofundin (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). RESULTS: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. CONCLUSION: The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.

OBJETIVO: A anfotericina B é um agente antifúngico de largo espectro bastante empregado na terapia antifúngica. Entretanto, esta molécula apresenta um alto nível de toxicidade que, na maioria das vezes, impede o seu uso contínuo na terapêutica médica. O objetivo deste artigo foi comparar a eficácia e a toxicidade in vitro do Fungizon (AmB-D) e de dois sistemas carreadores de AmB. MÉTODOS: Três produtos foram avaliados: o Fungizon , e dois sistemas oriundos da mistura entre o Fungizon e o Lipofundin , uma emulsão de uso parenteral. Tais sistemas foram obtidos por duas técnicas: Na primeira diluiu-se previamanete o Fungizon com água para injetáveis e em seguida inseriu-se o Lipofundin (AmB-DAL); o segundo método consistiu na diluíção extemporânea do Fungizon com a referida emulsão (AmB-DL). Dois modelos celulares foram empregados no estudo: os eritrócitos (RBC) oriundos de doadores humanos e a Candida tropicalis (Ct). A avaliação in vitro (liberação de K+ e hemoglobina, e o índice de sobrevivência celular-CSR) foi realizado com quatro concentrações de AmB (entre 50 e 0.05mg.L-1). RESULTADOS: Os resultados demonstram que a ação da AmB não só foi dependente da concentração como também variou de acordo com o modelo celular e o veículo que diluiu o Fungizon . Nas concentrações de 50 mg.L-1, apesar da liberação de hemoglobina ser quase que total para AmB-D (99.51), para a AmB-DAL e AmB-DL este valor tendeu a zero. Um p = 0.000 demonstrou que AmB-D foi significativamente mais hemolítico. CONCLUSÃO: A mistura Fungizon -Lipofundin aparenta ser um bom sistema para carrear a AmB tendo em vista seu elevado índice terapêutico demonstrado.