Histamine H3 activation depresses cardiac function in experimental sepsis.
In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.
Li
X
X
Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E OZ3.
Eschun
G
G
Bose
D
D
Jacobs
H
H
Yang
J J
JJ
Light
R B
RB
Mink
S N
SN
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004927:Escherichia coli Infections / Q000503:physiopathology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000097:blood; D017442:Histamine Agonists / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D018100:Receptors, Histamine H3 / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D017442:Histamine Agonists; D018100:Receptors, Histamine H3; D006632:Histamine