Different effects of histamine H₁ and H₂ stimulation on left ventricular contractility in pigs

Histamine decreases ventricular contractility in some settings but increases it in others. To better understand these apparently discrepant results, we measured hemodynamics and left ventricular pressure (Miller catheter) and volume (ultrasonic crystals) in atrially paced, α- and β- antagonist-treated pigs. Histamine was infused (0.5-10 μg · kg^-1 · min^{- 1}) before and after H₂-antagonist (ranitidine) pretreatment. Changes in left ventricular contractile function were measured as shift of the end- systolic pressure-volume relationship (δESPVR) at a pressure of 100 mmHg. We found that at low doses (0.5 and 1 μg · kg^-1 · min^-1), histamine significantly decreased δESPVR (-1.1 ± 1.4 ml, P < 0.05) after H₂- antagonist pretreatment. At doses above 1 μg · kg^-1 · min^-1, histamine increased contractility in a dose-response fashion [maximum effect: 5.1 ± 3.3 ml, dose resulting in 50% effect (ED₅₀): 0.75 ± 1.79 μg · kg^-1 · min^-1] that was best described using a Hill coefficient of 2. Ranitidine increased the ED₅₀ by approximately one order of magnitude (0.75 ± 1.79 to 9.50 ± 2.60 μg · kg^-1 · min^-1, P < 0.05). We conclude that in vivo, at higher doses, histamine increases left ventricular contractility via H₂- receptor stimulation, whereas at low doses histamine decreases left ventricular contractility, probably via Hi-receptor stimulation.