The diminished efficiency and altered dynamics of respiration in experimental pulmonary congestion

Quantitative measurements of the relative efficiency of respiration in the normal lung, as contrasted with the congested lung, have not been made in the intact experimental animal. In 1934 Christie and Meakins,¹ utilizing simultaneous determinations of dynamic intrapleural pressure and of tidal exchange in patients with congestive heart failure, demonstrated a marked decrease in pulmonary distensibility. With appropriate treatment, distensibility was found to increase as the patient improved. In the present study, an approach similar to that of these authors has been used, and studies of the efficiency of respiration have been made on normal dogs at rest and during hyperpnea (produced by the inhalation of carbon dioxide) and contrasted with the relative efficiency of respiration after pulmonary congestion induced by rapid venous infusion. With this approach, a quantitative comparison of the work necessary to achieve a given amount of tidal exchange has been possible in an animal with normal lungs and in the same animal after severe pulmonary congestion. From measurements of tidal exchange, ventilation, and intrapleural pressure fluctuations, a representation of the dynamic changes in these factors during progressive pulmonary congestion has been obtained.     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.