The Heat Intolerant Phenotype. Physiological Responses And Lymphocyte Transcriptome

Abstract

INTRODUCTION: During physical training in the heat, extreme metabolic heat storage manifests (pending on the individual features) as a rise in body core temperature (Tc). Individuals, previously exposed to heat exhaustion/stroke and demonstrating an earlier/faster Tc and heart rate rise within a cohort study, are defined as "heat intolerant" (HI). Whether HI is a transient phenotypic or genotypic response is yet unknown. PURPOSE: To investigate whether HI and heat tolerant (HT) subjects differ in their lymphocyte gene profile. METHODS: 68 healthy young male volunteers, 1-3 months post-exertion heatstroke, underwent a heat tolerance test (HTT), consisting of walking on a treadmill for 2h at a speed of 5 km·h-1 and 2% grade in a climatic chamber (40°C, 40% relative humidity). Tc, Tskin (3 sites), and heart rate were continuously monitored and recorded. Blood samples were drawn before, at the end of the HTT and after 1h of recovery in an air-conditioned room (23°C). Global gene profile of 6 HT and 6 HI lymphocytes RNA samples (2 pools per group) was detected and analyzed using two-color gene chips and bioinformatic tools. RESULTS: According to the HTT, 10 subjects were diagnosed as HI and 58 subjects as HT. Tc at the end of HTT was elevated by 1.4 and 0.77°C in the HI and the HT subjects, respectively. Tskin vs. Tc, indicative of skin blood flow, implied a HI sluggish response (vs. HT) (P<0.01). Two different gene chip experimental paradigms indicated differences in gene profiles of the HI vs. the HT group, prior to and following recovery from HTT. Basal differences in biological functional categories among the groups included genes associated with immune responses, stress (e.g., apoptotic pathways), transport, molecular processes (DNA and RNA regulation and organization) and metabolism. CONCLUSIONS:: This study (as well as our previous reports) characterizes a distinct HI physiological phenotype. This characterization of the HI phenotype demonstrates a differential genomic profile found even prior to heat stress tests, adding a novel category to the defined reasons for potential congenital HI.