Passive Heat Stress Prevents Endothelial Ischemia‐Reperfusion Injury in Young Healthy Humans
Authors: Brunt Vienna E , Jeckell Andrew T , Ely Brett R , Howard Matthew J , Francisco Michael A , Minson Christopher T 
Published: November 2023

Endothelial ischemia‐reperfusion (I/R) injury is a primary cause of poor outcomes following ischemic events such as heart attack and stroke. Acute interval exercise has recently been shown to protect against brachial artery I/R injury. Passive heat exposure results in many of the same cardiovascular adaptations as exercise (e.g. acute elevations in body core temperature and vascular shear stress as well as chronically improved vascular function). Therefore, we sought to determine whether an acute bout of hot water immersion can also protect against endothelial I/R injury.METHODSNine (5 male, 4 female) young (23±2 years), healthy subjects participated in two trials in random order 7–21 days apart, which involved: 1) 60‐min of seated rest (time control), or 2) 60‐min of hot water immersion in a 40.5°C tub (peak rectal temperature: 38.9±0.1°C). Brachial artery flow‐mediated dilation and forearm post‐occlusive reactive hyperemia were measured as a markers of macro‐ and micro‐vascular function at three time points: (1) before and (2) 60‐min following the intervention (enough time for rectal temperature to return to baseline following hot water immersion), and (3) immediately following I/R injury, achieved by inflating a cuff around the upper arm to 250mmHg for 20‐min followed by 20‐min of reperfusion. Data are mean ± S.E.RESULTSThere were no differences in baseline or post‐time control data across the two trials. I/R injury reduced FMD from 7.4±0.7 to 5.5±0.6% (p=0.02) on the time control day and this reduction was prevented following hot water immersion (7.0±0.7 to 7.6±1.0%; p=0.59). However, when FMD was corrected for the shear stimulus (FMD/area under the curve shear rate up to peak dilation), there was no effect of I/R injury on corrected FMD on the time control day (3.4±0.3 to 3.3±0.3%/SRAUC; p=0.70); whereas corrected FMD improved following hot water immersion (3.5±0.4 to 4.8±0.5%/SRAUC; p=0.006) and remained elevated following I/R injury (5.7%±0.8%/SRAUC; p<0.001 vs. pre‐intervention). In the microvasculature, I/R injury tended to impair reactive hyperemia, measured as peak vascular conductance (2.4±0.4 to 2.0±0.4 ml/min/mmHg, p=0.07), and this impairment with I/R injury was mitigated by hot water immersion (2.3±0.4ml/min/mmHg; p=0.24 vs. pre‐intervention).CONCLUSIONSContrary to previous reports, I/R injury does not appear to impair the brachial artery's ability to dilate to a given stimulus. Instead, damage likely occurs downstream in the microvasculature, impairing reactive hyperemia and the shear stimulus. A single bout of hot water immersion improves brachial artery dilation for a given stimulus, even after core temperature has returned to baseline, resulting in protection against I/R injury. Similar to exercise, repeated bouts of passive heat stress may be protective for reducing the severity of vascular I/R injury associated with ischemic events.Support or Funding InformationSupported by AHA Grant #14PRE20380300 and the Eugene and Clarissa Evonuk Memorial Foundation