Histamine H3 activation depresses cardiac function in experimental sepsis

In the heart,histamine (H₃) receptors mayfunction as inhibitory presynaptic receptors that decrease adrenergicnorepinephrine release in conditions of enhanced sympathetic neuralactivity. We hypothesized thatH₃-receptor blockade might improvecardiovascular function in sepsis. In a canine model ofEscherichia coli sepsis, we found thatH₃-receptor blockade increasedcardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg,P < 0.05), and left ventricularcontractility compared with pretreatment values. Plasma histamineconcentrations increased modestly in theH₃-blocker-sepsis groupcompared with values obtained in a nonsepsis-time-control group.In an in vitro preparation, histamineH₃ activation could be identifiedunder conditions of septic plasma. We conclude that activation ofH₃ receptors may contribute tocardiovascular collapse in sepsis.

     

The effect of repeated intermittent hypoxia on pulmonary vasoconstriction in the newborn

The effect of repeated intermittent hypoxia upon the basal pulmonary vascular tone in the newborn period is unknown. We therefore studied the central hemodynamic response to seven repeated intermittent hypoxic challenges in acutely prepared piglets under 2 weeks of age. Catheters were placed in the aorta, pulmonary artery, and atria, and an electromagnetic flow probe was positioned around the main pulmonary artery. Each hypoxic challenge (Fio2 = 0.14) lasted 5 min, and was separated by an equal duration of ventilation with air. Nine control animals were ventilated with air for 90 min, a period of time equivalent to the seven challenges in the experimental group, and subjected to one hypoxic challenge at the end. Hypoxia uniformly induced pulmonary vasoconstriction. Repeated intermittent hypoxic challenges produced a progressive increase in pulmonary artery pressure and vascular resistance, both during air ventilation and hypoxia. For each challenge, the vascular resistance value achieved during hypoxia was directly related to the immediately preceding air ventilation one, and the magnitude of hypoxic pulmonary vasoconstriction, defined as the incremental change in resistance from air to hypoxia, was not different from the first to the last challenge in the experimental group. In the control group the pulmonary vascular tone did not change during the 90 min of air ventilation, and the single hypoxic challenge induced an increase in pulmonary vascular pressure and resistance similar in magnitude to the first challenge in the experimental group. Indomethacin administration to five experimental animals, after the last challenge, reversed the increase in air ventilation pulmonary artery pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)