Am. J. Respir. Crit. Care Med.,
Volume 160, Number 4, October 1999, 1142-1149
Histamine H3 Receptor Blockade Improves Cardiac
Function in Canine Anaphylaxis
CARLA
CHRUSCH,
SATYENDRA
SHARMA,
HELMUT
UNRUH,
EDGAR
BAUTISTA,
KRIKA
DUKE,
ALLAN
BECKER,
WAYNE
KEPRON,
and
STEVEN N.
MINK
Department of Medicine, Sections of Respiratory Disease and Critical Care Medicine; Department of Medicine,
Section of Respiratory Medicine; Department of Allergy and Immunology; Section of Thoracic Surgery;
and Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada
In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins,
and leukotrienes on causing cardiovascular collapse and the extent to which receptor blocking
agents and pathway inhibitors may prevent this collapse are not clear. In a ragweed model of anaphylaxis, we examined whether pretreatment with H1, H2, H3 receptor blockers, and cyclooxygenase and leukotriene pathway inhibitors was useful in preventing the depression in left ventricular
(LV) contractility known to occur in this model. The dose of allergen was varied to produce similar degrees of shock between treatments. The animals were studied under pentobarbital anesthesia in
which the treatment studies were approximately 3 wk apart. LV volumes were measured by sonomicrometric techniques. During challenge, mean arterial blood pressure (
), cardiac output (
), and
LV end-diastolic pressure (LVEDP) decreased approximately 50% compared with preshock values in
all treatments. Histamine H3 receptor blockade was associated with higher heart rates (HR) and
higher stroke work (SW) (p < 0.05) as compared with the other treatment studies. We conclude that
histamine H3 activation by inhibiting adrenergic neural norepinephrine release contributes to cardiovascular collapse in AS.
