Effect of infusing histamine into pulmonary or bronchial artery on sheep pulmonary fluid balance

We determined the dose-response curve for the effect of histamine on pulmonary fluid and protein exchange when histamine was infused directly into the bronchial artery or pulmonary circulation in anesthetized sheep with a right thoracotomy and an acutely prepared lung lymph fistula. We measured pulmonary hemodynamics, lung lymph flow, and lymph-to-plasma protein concentration ratios in 14 sheep. We infused histamine at constant rates of 0.1, 1, 3, and 10 micrograms/kg . min until a steady state was achieved at each level for 1 h. In the bronchial circulation the lowest effective dose of histamine was 1 microgram/kg . min, which increased lymph flow at constant ratio of lymph to plasma protein concentration. Lymph flow increased further as the dose of infused histamine increased. Infusions into the pulmonary circulation had similar effects, but in addition, pulmonary vascular resistance decreased. The dose-response curves for the effects of histamine on lung lymph and protein flow were identical for the 2 routes of infusion. The effect of histamine was to increase lung microvascular permeability modestly. We conclude that the site of continued action of histamine is probably in the pulmonary microcirculation, because for any given infusion rate, the local concentration of histamine in the bronchial microcirculation must be much greater than that in the pulmonary microcirculation because the ratio of blood flows is so different.