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.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||3 38-3|
|Publication status||Published - 1 Jan 1995|
- end-systolic pressure-volume relationship
- H antagonist