Canine anti-endotoxin immunotherapy in cranial mesenteric arterial occlusion shock and canine parvovirus disease endotoxaemia.
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Date
1986
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Abstract
Endotoxin (LPS, lipopolysaccharide) forms an integral part of the outer cellular membrane of
gram negative bacteria (GNB). The canines' intestine always contains large amounts of GNB, and
hence LPS. If these GNB with their LPS, remain within the intestinal lumen, they are not
harmful to the host. When GNB do gain entry into a hosts' circulation a bacteraemia will occur
with a concurrent endotoxaemia. In the past, it had been accepted that GNB were, themselves,
primarily responsible for the mortality and morbidity of bacteraemic and septicaemic patients.
Evidence has emerged to indicate that this is not altogether true as isolated LPS, without the
presence of GNB, can also lead to fatalities. Circulating LPS is exceptionally chemically
stable and highly toxic to host cells. Antimicrobial chemotherapy can destroy GNB, but this
therapy does not reduce the toxicity of LPS, nor does it clear LPS from the circulation.
Destruction of the GNB by certain antibiotics can, in fact, increase the concentration of
circulating plasma LPS in a host. The functional integrity of the intestinal wall is highly
dependent upon an adequate blood supply, and the mucosal cells acts as the primary defence
against the potentially pathogenic, endogenous and exogenous GNB and LPS. Once these pathogens
become intravascular then the liver is the next most important organ of defence. Shock,
irrespective of its aetiology, without adequate therapy, leads to reduced micro-vascular
circulation, and thus a state of either localised or generalised hypoxia occurs. Partial or
complete intestinal vascular ischaemia will produce a state of regional hypoxia, and lead to
damage of the intestinal wall allowing GNB, with their LPS, or LPS by itself, to enter into the
hosts' blood circulation. Therefore, an aetiology that gives rise to any type of "classified
shock," may eventually give rise to concurrent endotoxaemia. In clinical practice there are
numerous different diseases, physical onslaughts, and either acquired or congenital anatomical
defects, that can give rise to intestinal vascular ischaemia, and hence, endotoxaemia. Many
treatment regimens to combat the effects of an endotoxaemia have been advocated over the years,
but this problem still has an unacceptably high mortality and morbidity index, probably because
almost all such therapeutic regimens fail to destroy the LPS molecule. Recent clinical studies
have shown that immunotherapy is effective in combating gram negative bacteraemia and
septicaemia in humans and animals. Research workers have been able to produce a "broad-
spectrum" or "polyvalent" equine, hyperimmune, anti-endotoxir, antibody-enriched plasma (ANTI-
LPS), with favourab"^ responses recorded when this plasma was used to treat a variety of
experimentally-induced endotoxin-shocked subjects. ANTI-LPS significantly reduced the mortality
in experimentally produced superior mesenteric arterial occlusion endotoxaemia in rabbits,
presumably by neutralizing and opsonizing the circulating plasma LPS. Equine practitioners have
reported successful results when ANTI-LPS was incorporated into the treatment of certain
medical and surgical equine endotoxic related problems. A ^/ery recent, independent, Canadian
study showed the effectivness of ANTI-LPS, where this preparation was tested against other
anti-LPS products, to treat experimentally-induced sepsis in rats. The polyvalent equine ANTI-
LPS was the most effective, in that its use resulted in the longest survival. In order to
establish the generality of the use of equine ANTI-LPS plasma, I have extended these studies to
the canine, since an abdominal vascular ischaemia carries a serious, high-risk, surgical
emergency with unsatisfactorily high mortality rates, despite successful surgical intervention
with concurrent supportive medical therapy. Twenty healthy dogs were divided into four groups;
a control group (n=5) and three experimentally treated groups (n=5 in each group). All twenty
dogs were subjected to the well-documented cranial (superior) mesenteric arterial occlusion
(CMAO) shock model. The three experimental groups received the polyvalent equine, ANTI-LPS at
different times and by two different routes, with no side effects being observed in any of
these dogs. One group (n=5)received ANTI-LPS s.c. before CMAO was performed, a second group (n=
5) received their dosage of ANTI-LPS i.v. during the three-hour occlusion period, and a third
group (n=5) received their dose s.c, within three minutes after the CMAO was released. Survival
was recorded when any dog lived for a minimum of 14 days after the occluded vessel was
released. All 5/5 (100%) controls died within 17 hours after the release of the occluded
vessel, whereas only one of the 15 (6,5%) experimentally ANTI-LPS treated dogs died (P
Description
Thesis (M. Med.Sc.)-University of Natal, Durban, 1986.
Keywords
Immunotherapy., Veterinary medicine., Theses--Medical biochemistry.