Kinetics, dose response, tachyphylaxis and cross-tachyphylaxis of vascular leakage induced by endotoxin, zymosan-activated plasma and platelet-activating factor in the horse.

This research investigates the reactions of horses to different substances (endotoxin, zymosan-activated plasma, and platelet-activating factor) which cause blood vessels to leak, potentially explaining poor outcomes in cases of horse endotoxemia.

Overview of the Study

• This study examined blood vessels leakage caused by the administration of various substances like endotoxin, zymosan-activated plasma (ZAP), and platelet-activating factor (PAF) in horses. The amount of leaking was measured using 125-iodine human serum albumin (125I-HSA), a common medical tracer, as an indicator.
• The research involved nine Thoroughbred horses, a breed that is popular in equestrian sports. Possible reactions to the substances, as well as the rate of response, were carefully measured and recorded.

Findings on Substance Responses

• The research identified that ZAP and PAF led to an increase in vascular permeability (or leakage) directly linked to the dosage. The highest occurrence of leaks happened just 15 minutes post-injection.
• The leakage caused by endotoxin was also dose-dependent, but the maximum leakage was observed 2 hours after the administration of the substance. This suggests a delayed response compared to the reactions to ZAP and PAF.

Tachyphylaxis Observation

• In medical terms, tachyphylaxis refers to a decrease in response to a drug after being repeatedly administered. The research found that skin areas that had been injected with endotoxin before did not react to a second injection for up to five days. This phenomenon is a prime example of tachyphylaxis.
• However, this didn’t hold true when endotoxin was followed by an injection of either ZAP or PAF. In these cases, even the previously endotoxin-injected areas showed increased vascular leakage. This comparative increase in response was also found when compared to the control sites, which had been injected with saline instead of endotoxin.

Implications of the Study

• The findings of this research can be significant for understanding and treating cases of endotoxemia in horses. The observed decreased response to endotoxin after an initial exposure, and the contrastingly high response to other substances like ZAP and PAF, might contribute to the often poor prognosis of endotoxemia in horses.