The effect of histamine on the pulmonary and systemic circulations post-exercise

Introduction: Following exercise, systemic vasodilation persists, maintaining elevated blood flow resulting in post-exercise hypotension. Notably, blocking histamine attenuates this response suggesting an important role for histamine. To date, studies have focused exclusively on the systemic circulation, leaving the effects of histamine blockade on the pulmonary circulation and central hemodynamics unknown. Thus, the aim of this study was to investigate the role of histamine on post-exercise pulmonary and systemic hemodynamics. Methods: Healthy participants (age: 25±5yr) completed pulmonary function testing and a maximal cycling cardiopulmonary exercise test. Then on two separate days, participants ingested either placebo or 50mg of diphenhydramine hydrochloride (H1 receptor blockade) in a randomized order. Baseline measures included pulmonary artery systolic pressure (PASP), right and left ventricular function, femoral blood flow, mean arterial pressure, and spirometry. Participants completed a cycling-workout of 4x5-min @ 75% and 3x5-min at 110% of power output at the second ventilatory threshold. All measurements were repeated immediately post-exercise and throughout one hour of recovery. Results: Twenty participants were recruited and completed all testing. PASP was unaffected by blockade (p=0.20). However right-ventricular cardiac output was reduced (p=0.02) leading to a significant increase in pulmonary vascular resistance (p<0.01). Right-ventricular global longitudinal strain was increased with the blockade (p=0.03), maintaining right ventricular stroke volume (p=0.59). Left ventricular end-diastolic (p<0.01), end-systolic (p=0.04) and stroke volume (p=0.02) were increased with blockade compared to control but heart rate (p<0.01) and left-ventricular cardiac output (p<0.02) were reduced. The elevated femoral blood flow during recovery was attenuated with the blockade (p<0.01) but mean arterial pressure was unaffected (p=0.14). Forced vital capacity was significantly decreased with the blockade (p=0.02). Significance: Histamine receptor blockade did not alter pulmonary artery systolic pressure but reduced cardiac output and increased PVR, supporting that histamine contributes to pulmonary vasodilation. Although LV volumes were increased, the reduction in heart rate was of a greater magnitude and cardiac output was overall reduced. Consistent with previous work, femoral blood flow was attenuated following blockade, but MAP was unchanged likely due to the reduced cardiac output. Collectively, these findings support that histamine contributes to pulmonary vasodilation following exercise similar to the systemic circulation.