Search PubMedSearch

Biomedical subjects

M A Inchiosa

Publications and source records attributed to M A Inchiosa.

6 recordsLinked to original sources

Development of a real-time algorithm for predicting sufentanil plasma levels during cardiopulmonary-bypass surgery using a systems approach.

During cardiopulmonary-bypass (CB) procedures, anesthesiologists have traditionally based the administration of narcotics on general dosage recommendations and past experience. Initial doses are usually based on body weight and supplemental amounts are given in anticipation of, or in response to, the effects of surgical stimuli. There has been considerable recent interest in using the population pharmacokinetics of narcotics to optimize the attainment and maintenance of drug plasma concentrations at analgesic target levels which will blunt the hemodynamic responses to noxious stimuli. Moreover, the undershooting or overshooting of the target can be reduced by application of these principles making drug administration more effective and safer. The present study concerns the development of a model for the computer-guided administration of sufentanil throughout surgical procedures involving CB; there is a paucity of studies which have attempted to model the pharmacokinetics of drugs during CB because of the lack of information on the effects of bypass conditions on the pharmacokinetic parameters. We have attempted to approach the effects of hypothermia on sufentanil clearance by applying a continuous temperature correction to the ultimate elimination rate constant (the terminal eigenvalue). This correction is based primarily on the anticipated effects of temperature on the enzyme-catalyzed reactions which are essential for the elimination of drug from the body. An algorithm for the application of the model is also presented.

Algorithms

Enhancement of bupivacaine sensory blockade of rat sciatic nerve by combination with phenol.

We sought to determine whether the addition of phenol would enhance a bupivacaine nerve block. The effects on nerve conduction of bupivacaine (0.125%) and phenol (0.5%), singly and combined, were evaluated in vivo on the rat sciatic nerve. Three groups of 10 animals each were used. The left sciatic nerve was infiltrated with 0.125% bupivacaine, 0.5% phenol, or a solution that contained 0.125% bupivacaine and 0.5% phenol. The right limb served as control (saline injected). Motor deficits (visual assessment) and sensory blockade (hot-plate assay) were evaluated at 30-min intervals after injection. Phenol injected alone produced no motor blockade. The incidence of motor blockade at 30 min for 0.125% bupivacaine was 70% (P = 0.003), and for the combination treatment, 80% (P = 0.001). The analgesia score derived from the hot-plate test was more and persisted longer for the combination treatment than for either 0.125% bupivacaine or 0.5% phenol given singly; e.g., the average sensory block score after 150 min for the combination treatment was 1.0 compared with 0.1 for either bupivacaine or phenol given alone (P = 0.003). Analysis of the areas under the sensory score-time curves also demonstrated enhanced blockade from the combination treatment, which would be consistent with a synergism of the separate Na(+)-channel blocking effects of charged and uncharged local anesthetics. These findings may suggest other candidates for clinically useful combinations of amine and neutral local anesthetics.

Animals

Characterization of the decreased ATPase activity of rat cardiac actomyosin in isoproterenol-induced cardiac hypertrophy.

Daily administration of d,l isoproterenol-HCl (5 mg/kg) in rats for periods of 14-21 days results in marked cardiac hypertrophy and a decrease in cardiac actomyosin ATPase activity. Actomyosin suspensions (ionic strength 0.08) from right and left ventricles showed average decreases in ATPase activity of 37.1% (p less than 0.005) and 35.7% (p less than 0.05), respectively, for animals treated with isoproterenol for 14 days. Isolated myofibrils from combined ventricular muscle of another group of animals that received the same isoproterenol treatment showed an average decrease in ATPase of 36.4% (p less than 0.0025). The later experiments also demonstrated that the decrease in ATPase activity was not Ca++ sensitive suggesting the lack of involvement of a change in the calcium regulatory factors (tropomyosin-troponin complex). In contrast to these findings, purified myosin from treated animals and actomyosin assayed under conditions which essentially reflect myosin ATPase activity uninfluenced by actin interaction (actomyosin in solution, ionic strength 0.6), did not demonstrate a change in ATPase from controls. It was concluded that the decrease in cardiac actomyosin ATPase in isoproterenol treated rats involved primarily a defect in actin or the interaction of actin with other components of the contractile protein complex.

Actomyosin