Local Repolarization Abnormalities Induced by Transcatheter Radiofrequency Ablation in Pigs

Radiofrequency (RF) ablation alters action potential repolarization of myocardial cells and, theoretically, tbis should induce ST-T segment changes in the ECG. Since these ECG abnormalities have been rarely reported in patients submitted to RF ablation we assess the ability of the procedure to caase ST-T segment changes in local electrograms. Epicardial ECG mapping was performed in 17 anesthetized open chest pigs submitted to endocardial (n = 9) or to epicardial (n = 8) unipolar radiofrequency ablation (500 kHz, 20 W for 5-10 s). To characterize the cellular electrophysiological alterations induced by RE ablation transmembrane action potentials were recorded at various distances from the ablation lesion; these were compared with seven control pigs. Endocardial RE ablation induced a transient (< 5 min) change of 6.1 ± 2.4 m V in T wave amplitude (baseline: 12.8 ± 5.6 mV, P < O.OOl) in 141 out of 269 epicardial electrodes. T wave changes were associated with shortening in local activation time (20.1 ± 2.3 ms at baseline vs 18.5 ± 2.5 ms at 60 s after ablation, P = 0.03). RE current caused persistent ST segment elevation at the center of the ablation lesion with no transmural expansion. Intracellular potentials along a 2-6-mm wide myocardial band bordering the RE lesion showed lower amplitude (101 ± 7.0 mV vs 71 ± 23 mV, P < 0.01) and shorter duration (254 ± 44 ms vs 156 ± 29 ms, P < 0.01) than control hearts. The center of the ablation lesion was electrically anexcitable. We concluded that RF ablation alters cellular electrophysiology in small areas surrounding the ablation lesion and this causes short-lasting transmural changes in T wave amplitude and nontransmural ST segment elevation.     

Gastrointestinal permeability in food-allergic eczematous children

Gastrointestinal permeability has been studied in a group of clinically proven food-allergic eczematous children and compared with a control group using lactulose and L-rhamnose as probe markers. No significant difference was demonstrated in baseline permeability measurements between eczematous and control children using isotonic or hypertonic oral loading. Similarly after antigen-challenge permeability results showed no significant difference from the controls although two of the ten eczematous children challenged showed increased permeability to lactulose. These findings support the hypothesis that once sensitized the physiological absorption of dietary antigen may be sufficient to maintain an allergic response in the skin.     

Drug Metabolic Enzymes in Developmental Toxicology

Although much is known about the metabolism of environmentaltoxicants in adult organisms, little information exists on therole of cytochrome P450 (CYP) enzymes during development. Thedeveloping organism is remarkably dynamic, presenting a constantlychanging metabolic profile as various enzyme systems are activatedor repressed. This may explain the markedly different sensitivitiesto various toxicants that are exhibited throughout the developmentalperiod. The application of molecular biological methods hasprovided important information on the roles of these enzymesin modulating the response of the developing organism to toxicologicalexposures. The first talk will focus on the identification androle of CYPs during early organogenesis, particularly on howthese enzymes influence the response of the conceptus and earlyembryo to toxic chemicals. The second presentation will discussthe identification of CYPs expressed during human development,as many of the enzymes present in adults are not expressed inthe fetus. The third speaker will discuss the developmentalconsequences of loss of expression of particular metabolic enzymes,focusing on recent studies employing knockout mice to examinethe role of drug metabolic enzymes during development. The lasttwo talks will discuss some of the short- and long-term consequencesof in utero exposures to toxic chemicals and the role of CYPin modulating the toxic response of the developing organism.The first of these will focus on the role of CYP2E1 in humanfetuses during late gestation and the response of this enzymeto inducing agents such as alcohol. The last talk will discussthe role of CYP1A1 in the activation of the Ki-ras oncogenefollowing in utero exposure to carcinogens as a mechanism forlung tumor formation in a pharmacogenetic mouse model.     

PATTERNS AND INTENSITY OE AUTOFLUORESCENCE AND ITS RELATION TO MELANIN IN HUMAN EPIDERMIS AND HAIR

The skin of 41 patients including 16 blacks, 15 Caucasians, and 10 Hispanics, was observed using a fluorescent microscope. Three patterns of autofluorescence were observed: intercellular, cytoplasmic, and a combination of intercellular and cytoplasmic. The hair of 75 subjects, including 18 Negroes and 55 Caucasians, was observed. Two patterns were found: medullar and at the cortex. Skin form black patients was associated with the cytoplasmic pattern of autofluorescence. Compared to lighter skin, black skin was also significantly associated with increased intensity of autofluorescence, indicating that autofluorescence of the epidermis parallels the clinical degree of pigmentation. In the hair of 75 subjects, similar results were obtained: Negro hair exhibited more fluorescence than Caucasian hair, and darker hair (brown to black) exhibited more fluorescence than lighter hair (blond). This may be related to melanin and it breakdown products.