Platelet-activating factor and shock.

The aim of this chapter was to highlight the major components of PAF actions which lead to a state of shock, i.e. inadequate perfusion of essential organs which if sustained over a critical period of time, leads to irreversible damage in essential organs and eventually death. The heart, the pulmonary vessels and the microcirculation seem to be the primary target organs to PAF-induced hypotension. The effects of PAF on the pulmonary airways in some species (bronchoconstriction) might lead to hypoxemia and further exacerbate organ function. Thrombocytopenia, leukopenia and activation of the complement system are also important in PAF-induced shock by promoting thrombi formation and generation of multiple secondary mediators (e.g. histamine kinins, TXA2, leukotrienes, oxygen radicals). Identification of PAF production during specific or generalized pathophysiological processes is a critical step to implicate this vasoactive lipid in disease processes. So far, only limited information has been derived from studies involving immune responses (anaphylaxis) or bacterial endotoxins. Yet, the growing number of selective and potent PAF antagonists provide important information on the potential role of PAF in shock states. Such evidence, summarized in table I, is of great importance in designing new therapeutic strategies to a highly complex and lethal disease such as septicemia. However, the data summarized in table I clearly show that little is known on the mechanism of action of the various PAF antagonists. It is also important to note that PAF-induced shock and death can be prevented by drugs which are not necessarily PAF antagonists. For example, dexamethasone is extremely efficient in preventing PAF-induced shock and death in the mouse [24, 39] and thyrotropin releasing hormone in the guinea pig [15]. Therefore, it is conceivable that pathological conditions in which PAF might play a fundamental role might be reversed by pharmacological interventions which activate physiological mechanisms which can overcome and reverse the pathological processes activated by PAF. In conclusion, PAF is a powerful vasoactive lipid which can produce severe derangements in essential biological functions which can lead to death. The role of PAF in pathological processes in vivo is well supported in conditions such as anaphylaxis and endotoxemia. Yet, direct proof for PAF production in other shock states, such as multiple trauma, ischemia, inflammation and hemorrhage, is still missing. Furthermore, it is important to keep in mind that in shock, trauma or inflammation, multiple mediators in addition to PAF are formed.(ABSTRACT TRUNCATED AT 400 WORDS)