Methicillin distribution in serum and extravascular fluid and its relevance to normal and damaged heart valves

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Abstract
We evaluated the distribution of methicillin into normal and damaged heart valves and the accuracy with which subcutaneous plastic chambers reflected tissue uptake of this antibiotic. A total of 24 male New Zealand rabbits were given constant infusion doses of methicillin through central venous catheters. Five of these animals had their aortic and mitral valves damaged by catheterization of the left ventricle. A total of 19 rabbits had perforated plastic chambers inserted subcutaneously 7 to 10 days before methicillin infusion. In all animals more than 80% of the total infused dose of methicillin was accounted for in the serum, urine, and tissues. In the 12 animals infused to steady state (less than 7 h), the steady-state serum concentrations (11 to 120 micrograms/ml) were equal to the concentrations attained in either peritoneal or tissue chamber fluids. In the 12 animals sacrificed before 7 h, tissue chamber concentrations lagged behind serum and heart tissue concentrations in attaining steady state. Steady-state concentrations in normal heart valves and heart muscles failed to increase proportionally to increased constant infusion doses (8.7 to 87.2 mg/kg per h). The steady-state methicillin concentrations in fibrin-scarred heart valves were invariably higher than the steady-state concentrations in the normal right heart of the same animals (P less than 0.05). Tissue uptake of methicillin was altered in scarred heart valves as compared to normal heart valves, and large-volume subcutaneous tissue chambers misrepresented the uptake rate of methicillin into heart tissues and valves.