Chapters authored
Fat Embolism: What We Have Learned from Animal Models
Pulmonary fat embolism may not be diagnosed before unrelated autopsy and have little clinical impact or lead to acute lung injury with fulminant fat embolism syndrome (FES). The fat may come from various anatomic locations, bone marrow being the most common. There is no specific treatment. This review discusses animal models that can lead to a better understanding of pathophysiological mechanisms underlying this condition and indicates the importance of specific cellular constituents. A hypothesis is postulated that there is a vicious cycle involving oleic acid and angiotensin II (both of which are pulmonary toxicants): oleic acid is derived from lipid embolism by pulmonary lipases that are stimulated by angiotensin; oleic acid also promotes local generation of angiotensin. The potential role of fatty acid receptors and the resolution of this cycle are discussed. Studies show there is potential for long-term effects that might not be revealed in the immediate post-recovery period. Evidence is reviewed that animals are vulnerable to “second hit” effects at a time remote from the initial event. Some beneficial pharmacological treatments are described. These include different drugs acting on the renin-angiotensin system (RAS) that could eventually serve alone or in combination for treatment or prevention. Future therapeutic developments are discussed.
Part of the book: Embolic Disease
From Angiotensin to Renin to Prorenin and from the Adrenal to the Kidney to the Placenta and the Lungs: An Historical Journey
In 1966 I carried out a study on the role of calcium on angiotensin’s stimulant effects on the adrenal medulla. Since then I have been studying the renin-angiotensin system (RAS) for over a half-century in a wide variety of biological preparations, while awareness of its complexity has exploded. My journey has involved studies on genes, proteins, organelles, cells, tissues, glands, organs and whole animals. This chapter reviews what my colleagues and I have learned from these different levels of organization and is not meant to be an update on all features of the RAS. My studies have included experiments on: perfused cat adrenal glands; genetic and second messenger control of catecholamine synthesis and secretion from cultured bovine chromaffin cells and from rats in vivo; renin storage and release in the rat kidney and secretory granules; properties of isolated renin, prorenin and renin-like proteins; hormonal and second messenger control of prorenin secretion from human utero-placental tissues; renin/prorenin in a variety of tumors; and the effect of RAS drugs in a rodent model of pulmonary fat embolism. This most recent study has direct clinical application. I conclude with what I have learned about biomedical research and lessons for the future.
Part of the book: Selected Chapters from the Renin-Angiotensin System