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Biomedical subjects

M A Inchiosa

Publications and source records attributed to M A Inchiosa.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

Effects of ibuprofen on doxorubicin toxicity.

The cardiotoxicity of doxorubicin (Adriamycin) restricts the usefulness of this potent antineoplastic agent. Since the cardiotoxic mechanism (generation of oxygen radicals) is distinct from the primary chemotherapeutic mechanism (intercalation of DNA) efforts to decrease the cardiotoxic potential are warranted. Three nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen and sulindac were tested for effects upon survival in the chronic mouse model of doxorubicin cardiotoxicity. The original premise in these studies was that nonsteroidal anti-inflammatory drugs, through inhibition of cyclooxygenase activity, would suppress the attending generation of superoxide anions and reduce a synergism with oxygen radicals produced by redox cycling of doxorubicin. Acetaminophen was included in the studies as an example of an analgesic agent which lacks anti-inflammatory efficacy. Doxorubicin (4 mg/kg) was injected intraperitoneally at 3-week intervals in Swiss-Webster mice. The interventions were administered in equianalgesic doses in the drinking water for 2 days before and 3 days after the doxorubicin injections. Ibuprofen (1 mg/ml) increased survival from 16.0%, for doxorubicin alone, to 63.6% (p less than 10(-6); none of the other interventions demonstrated protection. Ibuprofen-treated mice also lost less weight during the treatment period than all other doxorubicin injected animals (p less than 10(-6]. Since the three antiinflammatory drugs tested are all cyclooxygenase inhibitors, but only ibuprofen inhibits neutrophil infiltration, the latter mechanism is proposed as the primary basis for the observed protection.

Acetaminophen↗
PubMed1986

Correlation between thiopental induction dose and the volume of distribution of caffeine in human subjects.

The correlation between the apparent volume of distribution (aVd) of caffeine and the induction dose of thiopental was studied in 23 patients. Caffeine, which has an effective partition coefficient that approaches that of thiopental, was used as an indicator substance to estimate the immediate volume of distribution of thiopental. The immediate volume of distribution is critical in determining thiopental induction dose. The aVd of caffeine was determined noninvasively from serial saliva samples after consumption of caffeine, which was given to the patients as coffee. A strong correlation (r = .69; P less than .01) was found between the aVd of caffeine and the anesthetic induction dose of thiopental when the loss of eyelid reflex was used as the end point. The correlation between thiopental induction dose and body weight for the same individuals (r = .188) was not statistically significant.

Adult↗
PubMed1986

Single-dose pharmacokinetics of oral ciprofloxacin in patients with cystic fibrosis.

The single-dose pharmacokinetics of oral ciprofloxacin were studied in ten patients with cystic fibrosis aged 18 to 34 years. Each patient received three different drug doses (500 mg, 750 mg, and 1,000 mg) at successive one-week intervals. Dosing and drug assays were double blinded. Blood and urine were assayed over the 48 hours following each dose. Ciprofloxacin was absorbed from the gastrointestinal tract. Peak serum concentrations averaged 2.8, 4.5, and 4.6 micrograms/mL respectively at the three doses, well above the mean inhibitory concentrations of most isolates of Pseudomonas aeruginosa. Time to peak concentration was approximately two hours. The range of sputum levels in three patients was 1.1-2.1 micrograms/mL at four hours after the three doses. The serum elimination half-life was 3.7 hours and was independent of dose. Urinary recovery was 26%; greater than 90% of urinary excretion occurred within the first 12 hours. The results of this study indicate that ciprofloxacin has potential for use in the treatment of P aeruginosa infections in patients with cystic fibrosis.

Administration, Oral↗
PubMed1985

Cardiac actomyosin ATPase activity after chronic doxorubicin treatment.

Doxorubicin (Adriamycin), a potent antineoplastic drug, produces progressive cardiotoxicity which may lead to ultimate cardiac failure. The effects of chronic doxorubicin treatment on cardiac actomyosin ATPase were the principal focus of the present studies. This approach was based on the established correlation between cardiac contractility and contractile protein ATPase activity. Rabbits were injected intravenously with doxorubicin (4 mg/kg) at weekly intervals for 1-7 weeks. Body weight increase was attenuated in the treated animals; heart weight/body weight ratio was unchanged. Actomyosin and water contents of ventricular muscle were not different in doxorubicin-treated as compared with vehicle control animals. Cellular damage was detected histologically after one dose of doxorubicin (equivalent to a single clinical dose), and was extensive after 4-5 weeks of treatment. Animals which received 1-2 injections of doxorubicin demonstrated a 29% average increase in actomyosin ATPase activity as compared to vehicle controls; this difference was highly significant (p less than 0.001). Further treatment with doxorubicin tended to progressively decrease ATPase activity. It is suggested that the increased actomyosin ATPase activity seen with low total doses of doxorubicin may represent a compensatory mechanism for maintenance of contractility; this interpretation is supported by the clinical observation that the morphologic evidence of progressive doxorubicin toxicity is not associated with a parallel decrease in contractility, until severe cumulative toxicity has been induced.

Adenosine Triphosphatases↗
PubMed1981

Inhibition of actomyosin superprecipitation by an indole derivative of epinephrine.

A zwitterion indole metabolite of epinephrine, an inhibitor of actomyosin ATPase, has been shown to delay or prevent superprecipitation of cardiac and skeletal muscle actomyosin in a concentration-dependent manner. Inhibition of superprecipitation was not solely dependent on inhibition of actomyosin ATPase activity, suggesting that the ATPase inhibitor directly interfered with interaction of actin and myosin. Such an effect may occur by attachment of the indole derivative to free sulfhydryl groups involved in actin-myosin association as previously postulated for inhibition of ATPase activity.

Actomyosin↗
PubMed1979

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↗