Hemodynamic responses to Pasteurella haemolytica inoculation in calves given type 2 serotonergic antagonist

The effects of saline (control, group C) and metrenperone (treated, group M) on systemic and pulmonary hemodynamics were determined in conscious 7- to 15-day-old calves after they were intratracheally inoculated with Pasteurella haemolytica. Metrenperone, a specific serotonin (5-hydroxytryptamine) receptor antagonist, was injected intramuscularly (100 micrograms.kg-1) 2 h after the calves were inoculated. Central venous, pulmonary arterial and capillary wedge, and systemic arterial pressures were measured, using fluid-filled catheters. Cardiac output was measured by the thermodilution technique. Heart rate, stroke volume, and pulmonary and systemic vascular resistances were calculated. The parameters were measured hourly from the 1st to the 10th h after inoculation. In group C, cardiovascular response to P. haemolytica inoculation was marked and typically consisted of two systemic hypotensive phases and two pulmonary hypertensive phases. The first phase occurred by the 2nd h post inoculation and was induced by a transient bradycardia and a systemic vasodilation, leading to profound hypotension and reduced venous return. Cardiac performance then transiently recovered, but systemic hypotension persisted. The second hypotensive hypodynamic phase occurred by the 7th h after inoculation, and was associated with a decline in stroke volume, an increase in heart rate, and pulmonary hypertension and vasoconstriction. In group M, the early response to P. haemolytica exposure was similar to that in controls, indicating that, as in sheep, 5-hydroxytryptamine does not contribute to the early hypodynamic response to endotoxemia. In contrast, metrenperone completely abolished late increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that 5-hydroxytryptamine contributes to the late pulmonary vasoconstriction. Metrenperone treatment also allowed better restoration of heart rate, and hence, cardiac output was maintained. In conclusion, 5-hydroxytryptamine might have a role in mediating pasteurellic endotoxin induced changes in pulmonary hemodynamics through its type-2 receptors.