Drugs with class III antiarrhythmic activity are potential human teratogens because of their ability to cause bradycardia in the embryo during the organogenic period. Three drugs with class III antiarrhythmic activity, almokalant, dofetilide and d‐sotalol, were compared in vitro using rat embryo culture. Each of these drugs caused a concentration‐dependent bradycardia in 11‐ or 13‐day rat embryos. For each drug the effective concentration was considerably greater than the human therapeutic plasma concentration. The reproductive outcome was also compared in vivo in Sprague‐Dawley rats by oral administration of almokalant or dofetilide on single days during the organogenic period. Both drugs caused increased resorptions and the same stage‐dependent malformations. Dosing on gestational day (GD) 11 was associated with right‐sided oblique cleft lip and short tail, while dosing on day 13 caused digital hypoplasia and/or amputation. Susceptibility to these drugs started on GD 9 when the embryonic heart starts beating and ended on GD 15. The malformations were preceded by hemorrhage; which is consistent with the proposed pathogenesis that the drug‐induced bradycardia caused embryonic hypoxia/ischemia. This study indicates that the induction of malformations/embryonic death by class III antiarrhythmic drugs which inhibit lkr is a class effect secondary to a common pharmacological action on the embryonic heart. © 1996 Wiley‐Liss, Inc.

Morphological differences between old-growth trees and saplings of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) may extend to differences in needle anatomy. We used microscopy with image analysis to compare and quantify anatomical parameters in cross sections of previous-year needles of old-growth Douglas-fir trees and saplings at the Wind River Canopy Crane site in Washington and at three sites in the Cascade Mountains of Oregon. We also compared needle anatomy across a chronosequence of 10-, 20-, 40- and 450-year-old Douglas-fir trees from the Wind River site. Anatomy differed significantly between needles of old-growth trees and saplings at all sites, suggesting a developmental change in needle anatomy with increasing tree age. Compared with needles of old-growth trees, needles of saplings were longer and had proportionately smaller vascular cylinders, larger resin canals and few hypodermal cells. Astrosclereids, which sequester lignin in their secondary cell walls and occupy space otherwise filled by photosynthetic cells, were scarce in needles of saplings but abundant in needles of old-growth trees. Needles of old-growth trees had an average of 11% less photosynthetic mesophyll area than needles of saplings. The percentage of non-photosynthetic area in needles increased significantly with increasing tree age from the chronosequence of 10-, 20-, 40- and 450-year-old trees at the Wind River site. This reduction in photosynthetic area may contribute to decreased growth rates in old trees.

A system which imposes a range of water stress levels was developed and evaluated. Water stress was controlled by employing a screen to suspend roots above a water column of known height. Levels

Monoterpene levels in current year needles of Douglas fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings were measured at the end of 4 years of exposure to ambient or elevated CO2 (+179 micro mol mol-1), and ambient or elevated temperature (+0.3.5;C). Eleven monoterpenes were identified and quantified using gas chromatography/flame ionization detector/mass spectroscopy, with eight of these compounds regularly occurring in all trees examined. Elevated CO2 exposure significantly reduced the levels for four of the eight main compounds in needles. Total monoterpene production was reduced by 52% (P < 0.05). Elevated temperature also reduced monoterpene levels (P < 0.07). The combination of elevated temperature and elevated CO2 resulted in a 64% reduction in total monoterpenes compared with needles on ambient temperature trees. Two-way anova showed no significant temperature-CO2 interaction. It is hypothesized that seasonal reductions in needle monoterpene pools under elevated CO2 and temperature conditions may be due to a combination of competing carbon sinks, including increased carbon flux through the roots.

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