Abstract
Methicillin concentrations were measured in serum, normal heart valves, damaged heart valves, myocardium, and extravascular fluid from 12 New Zealand white rabbits to assess the influence of valvular damage on methicillin penetrations. Fibrin scarring of the aortic valve was induced by the placement of a polyethylene catheter through the aortic leaflet for 4 days. Each rabbit was then given a 40-mg/kg intravenous bolus dose of methicillin. Serum concentrations were collected, and animals were sacrificed 5, 15, 30, and 60 min after the dose. Normal and damaged heart valves from six different rabbits were desiccated to evaluate the fluid content of each. The time course of methicillin in damaged aortic valves was similar to that in serum and followed a bioexponential decline. The pharmacokinetic profile of methicillin in normal heart muscle and normal heart valves was clearly different from that of serum and damaged heart valves. Damaged valves showed a rapid and complete equilibrium with serum, whereas normal heart valve and muscle methicillin concentrations were consistently lower than serum concentrations at all times after the rapid bolus dose. The greater extravascular fluid content in damaged heart valves (P less than 0.001) compared with that in normal heart valves may be associated with the greater extent of penetration into damaged heart valves. Equilibrium between serum and damaged valves may be achieved more rapidly because the damaged area is composed of platelet and fibrin matrix and lacks the membrane integrity of normal heart valve tissue.
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