The effect of local passive heating on skeletal muscle histamine concentration: Implications for exercise-induced histamine release

Aerobic exercise induces mast cell degranulation and increases histamine formation by histidine decarboxylase, resulting in an ~150% increase in intramuscular histamine. The purpose of this study was to determine if the increase in skeletal muscle temperature associated with exercise is sufficient to explain this histamine response. Specifically, we hypothesized that local passive heating that mimics the magnitude and time-course of changes in skeletal muscle temperature observed during exercise would result in increased intramuscular histamine concentrations comparable to exercising values. Seven subjects participated in the main study in which pulsed short-wave diathermy was used to passively raise the temperature of the vastus lateralis over 60 min. Heating increased intramuscular temperature from 32.6 (95% CI 32.0 to 33.2) to 38.9 (38.7 to 39.2) oC (P < 0.05) and increased intramuscular histamine concentration from 2.14 (1.92 to 2.36) to 2.97 (2.57 to 3.36) ng/ml (P < 0.05), an increase of 41%. In a follow-up in vitro experiment utilizing human-derived cultured mast cells, heating to comparable temperatures did not activate mast cell degranulation. Therefore, it appears that exercise-associated changes in skeletal muscle temperature are sufficient to generate elevations in intramuscular histamine concentration. However, this thermal effect is most likely due to changes in de novo histamine formation via histidine decarboxylase and not due to degranulation of mast cells. In conclusion, physiologically relevant increases in skeletal muscle temperature explain part, but not all, of the histamine response to aerobic exercise. This thermal effect may be important in generating the positive adaptations to exercise training.

Severe scombroid poisoning and life-threatening hypotension

Scombroid fish poisoning (SFP), the most common fish-related illness worldwide, is a histamine response caused by the heat stable toxin histamine. A healthy 48-year-old woman and co-author of this paper developed palpitations, tachycardia and hypotension 10 min after a tuna steak dinner. She subsequently developed numbness of her face, flushing, conjunctival erythema, abdominal pain, nausea, vomiting, diarrhoea, headache and chest pain. Her ECG revealed tachycardia with ST depression. Her hypotension did not respond to fluid resuscitation, and she required phenylephrine. Based on exposure history, clinical syndrome, exclusion of other diseases and consultation with poison control, a diagnosis of scombroid poisoning was established. The state health department was notified. The patient was weaned off vasopressors, dosed famotidine and discharged 43 hours after fish ingestion with no symptoms and normal ECG. SFP is an often misdiagnosed and underreported illness with the potential to cause life-threatening hypotension.

Cosensitivity of vagal mucosal afferents to histamine and 5-HT in the rat jejunum

A complex sensitivity of afferent nerves in the mesentery of the rat jejunum to systemic administration of histamine has recently been demonstrated. In the present study, we aimed to characterize subpopulations of mesenteric afferents that mediate this afferent nerve response. Multiunit afferent discharge was recorded from mesenteric nerves supplying the proximal jejunum in anesthetized rats. The majority of mesenteric bundles (84%) exhibited biphasic responses to histamine (8 μmol/kg), and these bundles also responded to 2-methyl-5-HT (2m5HT). In contrast, monophasic responses lacked a short-latency component, and these bundles failed to respond to 2m5HT. Single-unit analysis revealed a population of afferents that possessed cosensitivity for 2m5HT and histamine. This population of afferents was absent in chronically vagotomized animals, whereas mucosal anesthesia with luminal lidocaine reversibly converted the biphasic profile to a monophasic one. Ondansetron (500 μg/kg) blocked the response to 2m5HT with no effect on the profile of the histamine response, whereas pyrilamine (5 mg/kg) blocked the histamine response without affecting the response to 2m5HT. We conclude that histamine-sensitive afferents exist in the rat proximal jejunum that also respond to 5-HT via the 5-HT3receptor. These fibers appear to be vagal afferents originating in the intestinal mucosa and may be involved in the organization of mast cell-mediated responses.