Effects of infused histamine: correlation of plasma histamine levels and symptoms.
Level 3 - non-randomized controlled study
Non-randomized interventional human challenge and pharmacologic blockade study.
PubMed 6120967 · doi:10.1016/s0091-6749(82)80005-5
What was done
Human subjects received sequential 30-minute infusions of histamine base at escalating doses (0.05, 0.1, 0.25, 0.5, and 1.0 mcg/kg/min). Plasma and urine histamine concentrations were measured during infusions under control conditions (no medications) and following pretreatment with an H1-receptor antagonist (hydroxyzine), an H2-receptor antagonist (cimetidine), or both, to evaluate plasma thresholds for tachycardia, diastolic hypotension, flushing, and headaches.
What was found
Resting baseline plasma histamine was 0.62 +/- 0.12 ng/ml and increased in direct proportion to infusion rates. The mean plasma histamine thresholds required to elicit physiological responses were: 1.61 +/- 0.30 ng/ml for a 30% increase in heart rate, 2.39 +/- 0.52 ng/ml for significant flushing and headache, and 2.45 +/- 0.13 ng/ml for a 30% increase in pulse pressure. Cimetidine pretreatment did not alter the threshold for symptoms, hydroxyzine significantly raised the threshold for a 30% heart rate increase, and combined hydroxyzine plus cimetidine significantly raised the threshold for all responses. Urinary histamine increased in direct proportion to infusion rates.
Why it matters
The study defines quantitative plasma histamine concentration thresholds for distinct clinical symptoms in humans and shows that dual H1 and H2 blockade is required to blunt the full spectrum of vascular and cardiac responses.
Limits
The abstract does not state the number of subjects (n), their baseline health or demographic characteristics, nor whether the administration order of pretreatment conditions was randomized or blinded.
Cited by
- partial In a human study where participants were injected with liquid histamine, increasing histamine within the upper-normal range caused increased heart rate and anxiety as the first symptoms.