Fiberoptic tracheal intubation using a nipple guide.
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Bronchoscopy↗
Biomedical subjects
L D Voulelis
Publications and source records attributed to L D Voulelis.
Daunorubicin-induced cardiac injury in the rabbit: a role for daunorubicinol?
This study evaluated potential contributions of daunorubicin and its principle metabolite, daunorubicinol, to the cardiotoxicity of daunorubicin therapy. Daunorubicin (15 mg/kg) or placebo (normal saline) was administered by iv bolus to New Zealand white rabbits and 3 to 4 days later, hearts were removed to measure contractility (dF/dt), concentrations of daunorubicin and daunorubicinol, and evidence of oxidative stress on glutathione and glutathione peroxidase. Contractile function of isolated atria and papillary muscles was depressed (p < 0.05). Daunorubicinol exceeded daunorubicin concentration in the heart (p < 0.005) with a ratio of metabolite to parent drug of 26 in atrial and 32 in ventricular tissue. There was a significant correlation between peak plasma (r = -0.63; p < 0.05) or cardiac concentration (r = -0.78; p < 0.02) of daunorubicinol, but not daunorubicin, and depression of dF/dt in papillary muscles. In separate in vitro studies, daunorubicinol at a concentration (5.5 micrograms/g tissue or 10 microM) approximating that observed ex vivo in heart inhibited Ca2+ uptake into cardiac sarcoplasmic reticulum vesicles by 39 +/- 3%, whereas 10 microM daunorubicin (14-fold higher than actual ex vivo cardiac concentrations) did not demonstrate any detectable inhibition. Daunorubicin treatment failed to significantly alter concentrations of GSH or GSSG or activities of glutathione peroxidase in the heart. Thus, cardiac dysfunction observed 3 to 4 days after a single dose of daunorubicin did not clearly relate to oxidative stress, but was associated with a cardiac concentration of daunorubicinol that appeared sufficiently high to impair Ca2+ metabolism.
Animals↗
Aging alters the force-frequency relationship and toxicity of oxidative stress in rabbit heart.
Adult (6 months) and senescent (greater than 5 years) rabbit atria were studied under conditions known to increase cytoplasmic calcium (increased frequency of contraction and oxidative stress). At a contraction frequency of 1/sec, cardiac relaxation (90% relaxation time) was similar in senescent and adult atria but at a frequency of 2 or 3/sec, relaxation was significantly slower in senescent preparations (P less than 0.05). Additional experiments indicated that H2O2 (500 microM), a powerful oxidant, increased resting force and decreased developed force (DF) much more rapidly in senescent than adult atria; the maximum decrease in DF, however, was less in senescent preparations (adult = 81 +/- 6% and senescent = 42 +/- 27% of pre-H2O2 values; P less than 0.05). Age-related differences in effects of H2O2 did not result simply from a decreased ability of senescent hearts to detoxify an oxidative stress by the glutathione pathway. Both basal glutathione (GSH) concentrations and the H2O2-mediated decreases in GSH were similar in adult and senescent ventricular preparations, as were activities of glutathione peroxidase and glutathione reductase. These observations suggest that interventions known to increase cytoplasmic calcium can amplify age-related impairments of cardiac relaxation through mechanisms that may be independent of the glutathione pathway.
Aging↗