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M C DeTraglia

Publications and source records attributed to M C DeTraglia.

10 recordsLinked to original sources

Isoflurane and halothane inhibit tetanic contractions in rabbit myocardium in vitro.

Rabbit right ventricular papillary muscles were tetanized by rapid stimulation in the presence of 1 microM ryanodine, an inhibitor of sarcoplasmic reticular function. Tetanic contractions elicited in this manner increased in strength as extracellular calcium concentration [Ca+2]ext was raised from 0.5 to 5 mM, exhibited saturation behavior above [Ca+2]ext = 5 mM, and were blocked by nifedipine. Accompanying membrane potentials depolarized to +10 mV and repolarized to -60 mV between stimuli. These data suggest that rabbit myocardial tetany is supported in large part by extracellular calcium influx via slow (L-type) calcium channels, consistent with similar recent findings in the ferret. At [Ca+2]ext = 2.5 mM, isoflurane (0.6-2.3%, gas phase) and halothane (0.4-1.5%) inhibited the strength of tetanic contractions in dose-dependent fashion. At [Ca+2]ext = 20 mM neither isoflurane (1.2%) nor halothane (0.8%) inhibited tetanic contraction strength. These data demonstrate that isoflurane and halothane inhibit contractile activity that is dependent on transsarcolemmal calcium influx via pathways independent of the ryanodine-sensitive sarcoplasmic reticulum. The exact sites of inhibition (e.g., slow channel vs. intracellular transit vs. myofibrillar binding) are not identified, but inhibition by either anesthetic may be competitively reversed by high extracellular calcium concentrations.

Animals↗

Differential effects of inhalation anesthetics on myocardial potentiated-state contractions in vitro.

The effects of enflurane, halothane, and isoflurane on myocardial potentiated-state contractions were examined in a study in which each of the anesthetics was presented, in random order, to each of eight isolated rabbit papillary muscles. Post-rest potentiated-state contractions were elicited by imposing a stimulus at precisely timed intervals following a 2-Hz steady-state stimulus train. The strength of these contractions is known to be highly dependent on sarcoplasmic reticulum (SR) Ca2+ release. The increment in tension developed in potentiated state, as compared to the steady state, is directly attributed to the potentiation process, and is defined here as potentiated-state strength (PSS). Effects of enflurane, halothane, and isoflurane on the time course of development of the potentiated state were characterized, as were the effects of incremental doses of these anesthetics on PSS. Anesthetic gas phase concentrations that produced 50% depression of contractile tension at 0.05 Hz steady-state stimulation were 0.6% halothane, 1.4% isoflurane, and 1.6% enflurane. Muscles exhibited maximal PSS of 0.91 +/- 0.01 g/mm2 in the absence of anesthetics. Halothane (0.6%) and enflurane (1.6%) caused significant depression of PSS to 0.45 +/- 0.06 and 0.61 +/- 0.06 g/mm2, respectively, while isoflurane (1.4%) preserved PSS at 0.95 +/- 0.09 g/mm2. Concentration profiles showed that the depression of PSS by halothane and enflurane was dose dependent. Isoflurane, up to 2.3%, failed to depress PSS. The time interval for development of optimum PSS, 1.5 to 2.0 s, was unaffected by any of the anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo comparison of two mixed venous saturation catheters.

The accuracy and stability of mixed venous saturation pulmonary arterial catheters under adverse physiologic conditions has not been assessed. Either a Shaw Opticath catheter (three-wavelength) or a Swan-Ganz oximetry TD catheter (two-wavelength) was calibrated in vitro and positioned in the pulmonary artery in each of ten mongrel dogs. The in vivo saturations were compared to measured saturations from anaerobically collected mixed venous blood analyzed with a reference cooximeter at each step in the protocol. Oxygen delivery was varied to obtain a broad range of mixed venous saturations (Sv-O2) by altering inspired oxygen concentration, isovolemic hemodilution, reducing cardiac output, and increasing afterload. Calculated oxygen consumption varied from 128 to 311 ml/min. Pre-insertion calibration for both catheter types compared favorably with the cooximeter prior to physiologic manipulations, although the three-wavelength catheter more closely approximated the cooximeter. The three-wavelength catheter tracked measured Sv-O2 accurately under adverse conditions for up to 10 h (R = .994; SEE = 2.2%). The two-wavelength catheter tended to drift under the same conditions (R = .808; SEE = 10.6%). At the conclusion of the experiment, the two-wavelength system was uniformly higher then the cooximeter by 5-31% with a mean of 21% (P less than or equal to .003 as compared with the initial difference by paired Student's t test). Pending further analysis of the tendency of the two-wavelength system to drift it would seem prudent to limit its clinical application.

Anesthesia, General↗

Promutagen activation with mammalian and avian S9 liver microsomes.

Metabolic activation activity of Aroclor 1254 induced rat liver microsomes (S9) were compared with uninduced microsomes obtained from beef, pig, sheep and chicken liver. Using the Ames Salmonella typhimurium mutagenesis assay (strains TA98 and TA100), in conjunction with benzo(a)pyrene and 2-aminoanthracene, the highest promutagen activation levels were obtained with chicken liver S9. The S9 from the other domestic animals gave results which were close to those of the induced rat S9 values. Enhanced promutagen activation activity was observed with chicken S9 following freeze drying and reconstitution of the S9 preparation.

Animals↗

Application of light sensitive chemicals to probe protein structure and function.

These results suggest that important information regarding the conformation of complementary binding sites and the behavior of various charged states of inhibitors can be obtained from studies of the pH dependence of photoaffinity labeling experiments. This information may assist in identifying the pKas of key residues controlling the binding interaction. This technique should prove very useful in probing binding site structure on nonfunctioning targets, such as enzyme zymogens, as well as complicated receptor interactions.

Affinity Labels↗

Characterization of azidobenzamidines as photoaffinity labels for trypsin.

Meta- and para-azidobenzamidine have been prepared and evaluated as photoaffinity labels. The compounds inhibit trypsin reversible in the dark and are competitive with substrate binding. Upon photolysis, irreversible noncompetitive inhibition is observed and is dependent upon concentration, photolysis time, and pH. Specificity of the probes is indicated by experiments in which p-tosyl-l-arginine methyl ester, a trypsin substrate, is used to protect against photoinactivation. Maximum inactivation of trypsin is achieved at pH 6.2 using either azidobenzamidine derivative. Evaluation of the pH dependence of photoaffinity labeling may provide a sensitive tool for probing conformational changes in inhibitor binding sites. These studies provide a basis for the use of azidobenzamidines as photoaffinity analogs of lysine and arginine side chains.

Affinity Labels↗