Onset of cardiovascular drift during progressive heat stress in young adults (PSU HEAT project)

Abstract

With climate change, humans are at a greater risk for heat-related morbidity and mortality, often secondary to increased cardiovascular strain associated with an elevated core temperature (T_c). Critical environmental limits (i.e., the upper limits of compensable heat stress) have been established based on T_c responses for healthy, young individuals. However, specific environmental limits for the maintenance of cardiovascular homeostasis have not been investigated in the context of thermal strain during light activity. Therefore, the purposes of this study were to 1) identify the specific environmental conditions (combinations of ambient temperature and water vapor pressure) at which cardiovascular drift [i.e., a continuous rise in heart rate (HR)] began to occur and 2) compare those environments to the environmental limits for the maintenance of heat balance. Fifty-one subjects (27 F; 23 ± 4 yr) were exposed to progressive heat stress across a wide range of environmental conditions in an environmental chamber at two low metabolic rates reflecting minimal activity (MinAct; 159 ± 34 W) or light ambulation (LightAmb; 260 ± 55 W). Whether systematically increasing ambient temperature or humidity, the onset of cardiovascular drift occurred at lower environmental conditions compared with T_c inflection points at both intensities (P < 0.05). Furthermore, the time at which cardiovascular drift began preceded the time of T_c inflection (MinAct P = 0.01; LightAmb P = 0.0002), and the difference in time between HR and T_c inflection points did not differ (MinAct P = 0.08; LightAmb P = 0.06) across environmental conditions for either exercise intensity. These data suggest that even in young adults, increases in cardiovascular strain precede the point at which heat stress becomes uncompensable during light activity.

NEW & NOTEWORTHY To our knowledge, this study is the first to 1) identify the specific combinations of temperature and humidity at which an increase in cardiovascular strain (cardiovascular drift) occurs and 2) compare those environments to the critical environmental limits for the maintenance of heat balance. We additionally examined the difference in time between the onset of increased cardiovascular strain and uncompensable heat stress. We show that an increase in cardiovascular strain systematically precedes sustained heat storage in young adults.

INTRODUCTION

Over the past several decades, average global temperatures have increased and are expected to continue increasing throughout the 21st century (1). The increase in average global temperatures has resulted in an increase in the frequency, duration, and severity of heat waves (2). As a result of this warming climate, the number of excess deaths during extreme heat events has increased significantly, from ∼752 deaths in 2008 to ∼2,337 in 2011 in the United States alone (3). Furthermore, future climate projections predict up to 45,930 and 117,333 excess heat-related deaths in Europe by the years 2064 and 2099, respectively (4). Most of the excess mortality during extreme heat events is not primarily heat-related (i.e., due solely to hyperthermia or heat stroke) (5, 6); according to epidemiological reports, cardiovascular events (5, 7, 8) are a contributing cause in most heat-related deaths.

Thermoeffector responses to heat stress include increases in sweating and skin blood flow, requiring redistribution of blood to the periphery. Such redistribution of blood requires an increase in cardiac output, which is primarily driven by increases in heart rate (HR) (9, 10). Cardiovascular drift is a phenomenon, whereby HR and potentially other cardiovascular responses begin a continuous time-dependent change or “drift” (11). This progressive rise in HR indicates an increase in cardiovascular strain and has mostly been examined during prolonged moderate-intensity exercise (11). The cardiovascular strain induced by prolonged exposures to heat stress contributes to negative health outcomes during activities of daily living or even in the absence of exercise, i.e., during environmental heat waves (12). For example, during the 2003 heat wave in France, as the severity of cardiovascular strain increased, the survivability rate decreased in elderly adults (13, 14).

The ongoing PSU HEAT (Pennsylvania State University-Human Environmental Age Thresholds) Project aims to determine the combinations of temperature and humidity above which risk of heat-related morbidity and mortality begins to increase. Our laboratory has recently established critical environmental limits [i.e., the specific combinations of temperature and humidity above which a stable core temperature (T_c) cannot be maintained] in a large heterogeneous sample of young adults during progressive heat stress across a wide range of environmental conditions at metabolic rates approximating those of activities of daily living (MinAct; ∼0.45 L/min V̇o₂) and light ambulation (LightAmb; ∼0.85 L/min V̇o₂) (15, 16). However, we have not characterized the attendant cardiovascular responses during these progressive heat stress protocols.

Kamon et al. (17–19) demonstrated that, similar to T_c, HR is maintained at equilibrium during progressive heat stress until a specific combination of temperature and humidity (i.e., a critical limit) is reached, causing HR to begin to continuously rise. They further noted that, at least in some cases, the HR inflection preceded the T_c inflection (18, 19). However, those studies were only conducted at one to two fixed dry-bulb temperatures (T_db) with increasing ambient water vapor pressure (P_a) and only during exercise at 30% V̇o_2max (because of industrial ramifications). Importantly, those findings were anecdotal and no analyses were conducted to specifically examine whether and how the HR inflection differed from the T_c inflection. Thus, the specific combinations of temperature and humidity above which cardiovascular drift begins, and whether this systematically precedes critical environmental limits for the maintenance of heat balance across a wide range of stressful environments, remain unknown. Identifying such environments allows for the development of safety guidelines and alert communications for impending heat events in which risk of heat-related morbidity and mortality is greatest. Therefore, the purpose of this investigation was to identify the specific environmental conditions (ambient temperature and water vapor pressure) at which cardiovascular drift begins relative to those at which a continuous rise in T_c (onset of uncompensable heat stress) is observed. Finally, we examined the temporal relation between the upward inflections in HR and T_c across a wide range of environmental conditions. Identifying the specific environmental conditions in which an increase in cardiovascular strain occurs, as well as the time difference between the upward inflection of HR and T_c, may provide useful safety information during impending severe heat events. By first identifying these environments in young adults, these data can be used for comparative purposes with future data in more vulnerable populations.

METHODS

Subjects

All experimental procedures were approved in advance by the Institutional Review Board at the Pennsylvania State University. Oral and written consents were obtained voluntarily from all subjects before participation and in accordance with the guidelines set forth by the Declaration of Helsinki. All testing was conducted in environmental chambers housed in Noll Laboratory at the Pennsylvania State University.

Subject characteristics are presented in Table 1. Fifty-one (27 F; 23 ± 4 yr) subjects participated in the study. All subjects were healthy, normotensive, nonsmokers, and were not taking any prescription medications that might affect the physiological variables of interest in this study. Subjects were representative of the population in this age group with respect to body size and aerobic fitness (20, 21). No attempt was made to control for menstrual status or contraceptive use (22). Maximal aerobic capacity (V̇o_2max) was determined using open-circuit spirometry during a graded exercise test performed on a motor-driven treadmill. During the experiments, subjects wore thin, short-sleeved cotton tee-shirts, shorts, socks, and walking/running shoes plus sports bras for the women.

Table 1.

Subject characteristics

Characteristics	Mean ± SD	Range
Age, yr	23 ± 4	18–34
Height, m	1.73 ± 0.10	1.57–1.98
Weight, kg	75 ± 16	48–117
AD, m2	1.88 ± 0.22	1.48–2.40
AD·wt−1, m2·kg−1	0.026 ± 0.002	0.020–0.031
V̇o2max, mL·kg−1·min−1	46.6 ± 12.0	27.5–79.1
V̇o2max, L/min	3.36 ± 0.99	1.39–4.83

n = 51 subjects; 27 F/24 M. A_D, DuBois body surface area; A_D·wt⁻¹, body surface area-to-mass ratio; V̇o_2max, maximal oxygen consumption.

Testing Procedures

Experimental trials were conducted on separate days with at least 72 h between visits. Before each experimental session, subjects were instructed to abstain from alcoholic beverages and vigorous exercise for 24 h and from caffeine for 12 h. Upon arrival, participants provided a urine sample to ensure euhydration, defined as urine specific gravity ≤ 1.020 (USG; PAL-S, Atago, Bellevue, WA) (18). Subjects performed light physical activity in an environmental chamber at two low metabolic intensities reflecting the metabolic demand of activities of daily living (MinAct; 83.7 ± 11.7 W·m⁻²) or slow walking (LightAmb; 136.1 ± 15.0 W·m⁻²) (23, 24). Subjects cycled on a cycle ergometer (Lode Excalibur, Groningen, The Netherlands) against zero resistance at a cadence of 40–50 rpm for MinAct trials and walked on a motor-driven treadmill at a speed of 2.2 min/h and grade of 3% for LightAmb trials.

Progressive heat stress was performed as previously described (15, 25) using a controllable environmental chamber at four constant T_db of 34°C, 36°C, 38°C, and 40°C and three constant P_a of 12, 16, and 20 mmHg. Following a 30-min equilibration period, either the P_a (during constant T_db trials, P_crit) or T_db (during constant P_a trials, T_crit) in the environmental chamber was increased in a stepwise fashion (1 mmHg or 1°C) every 5 min. We have previously reported excellent reliability and validity of this protocol to identify critical environmental limits (26). During each experiment, chamber data [i.e., T_db, P_a, and relative humidity (rh)], T_c, and HR were continuously monitored, and subjects free-pedaled or walked continuously until a clear rise in T_c was observed. Each subject completed experimental trials in multiple environmental conditions at both metabolic rates. Experimental trials lasted ∼90–120 min.

Determination of Critical Environments for Core Temperature and Cardiovascular Strain

As previously described (15, 16, 26), the critical environmental limit was determined from the raw data by identifying the inflection point at which a continuous rise in T_c began to occur following an elevated steady state that was proportionate to the metabolic demand of the activity. Similarly, increases in cardiovascular strain were determined from the raw data by identifying the point at which a continuous rise in HR occurred following an elevated steady state. To determine the inflection point for HR and T_c, a line was drawn between the data points starting at the point of equilibration, and a second line was drawn from the inflection point to the completion of the study (see Fig. 1). The average T_db, P_a, and rh for the 2 min immediately preceding the inflection point of HR and T_c were defined as the critical environmental limit for cardiovascular strain and the maintenance of heat balance, respectively. Following the T_c inflection point, subjects continued exercising in the environmental chamber for ∼15–30 min to ensure a clear and continuous rise in T_c occurred. Inflection points were determined by visual inspection, as previously reported (22, 27–29). We have previously demonstrated excellent interrater reliability for the determination of the T_c inflection point (ICC = 0.913) (27, 28).

Figure 1.

Representative tracing of the time course of core (gastrointestinal) temperature (T_c; open circles) and HR (red circles) for one subject during a progressive heat stress protocol. Lines are drawn through the data points to represent the equilibration and postinflection phases. The point at which the lines intersect for T_c represents the critical environmental limit (i.e., the point at which heat stress becomes uncompensable). The point at which the lines intersect for HR represents the initiation of cardiovascular drift (i.e., an increase in cardiovascular strain). The difference in time between HR and T_c inflections is denoted by Δt. HR, heart rate; T_c, core temperature.

Measurements

Gastrointestinal temperature telemetry capsules (VitalSense, Philips Respironics, Bend, OR) were provided for subjects to ingest 1–2 h before reporting to the laboratory in accordance with previously published data demonstrating that ingestion times from 1 to 12 h before use do not influence the precision of T_c data (30). T_c and HR data were continuously transmitted to a PowerLab data acquisition system and LabChart signal processing software (ADInstruments, Colorado Springs, CO) using an Equivital wireless physiological monitoring system (Equivital Inc., New York, NY).

Oxygen consumption (V̇o₂; L/min) and respiratory exchange ratio were determined at two time points (5 and 60 min after the onset of exercise) using indirect calorimetry (Parvo Medics TrueOne 2400, Parvo, UT). Sweat rate was determined during each experiment from the loss of nude body mass on a scale accurate to ±10 g. Fluid intake was prohibited between the initial and final measurements of nude body mass.

Statistical Analysis

No a priori sample size determination was conducted for the aims of the current manuscript; however, a post hoc analysis using a Cohen’s d effect size of 1.07 calculated from the average difference of either T_db (T_crit trials) or P_a (P_crit trials) between HR and T_c inflection suggested that seven subjects would yield sufficient statistical power (power 1−β = 0.80, α = 0.05) to detect meaningful differences if they existed. All ANOVAs were performed using GraphPad Prism, v. 9.2, GraphPad Software, San Diego, CA. All t tests were performed using IBM SPSS Statistics, v. 28, IBM Corp., Armonk, NY. Paired-samples t tests were performed to compare T_db, P_a, and rh between HR and T_c inflection points for each environmental condition and exercise intensity. Independent-samples t tests were performed to examine potential sex differences in the time between HR and T_c inflection points (Δt) across all environments for each exercise intensity. A two-way repeated-measures ANOVA was performed to compare the time to HR and T_c inflection across environmental conditions for both exercise intensities. A one-way ANOVA was used to examine the difference in % body mass loss and Δt across environmental conditions for each exercise intensity. An additional one-way ANOVA was used to examine differences in subject characteristics across environmental conditions for each exercise intensity. Group data are presented as means ± SD.

RESULTS

Subject characteristics are presented in Table 1. There were no differences in age, height, weight, body surface area (A_D), body surface area-to-mass ratio (A_D/kg), or V̇o_2max among experimental conditions for the two exercise intensities (all P ≥ 0.05).

Percent body mass loss was <2% in every environmental condition for both exercise intensities. The grand means for body mass loss were 0.7 ± 0.5% and 0.9 ± 0.4% for MinAct and LightAmb, respectively. There were no differences in % body mass loss between environmental conditions during MinAct [from 0.47% (20 mmHg) to 0.94% (12 mmHg); all P > 0.05]. During LightAmb, % body mass loss ranged from 0.75% (20 mmHg) to 1.48% [38°C; significantly greater than 34°C, 12 mmHg, 16 mmHg, and 20 mmHg (all P ≤ 0.02)].

Time of HR and T_c Inflection Points

The times at which HR and T_c inflections occurred are presented in Table 2. There was a main effect of physiological response (i.e., HR vs. T_c) (MinAct: P = 0.01; LightAmb; P = 0.0002), such that the HR inflection preceded the T_c inflection for both exercise intensities. However, there was no effect of environmental condition (MinAct: P = 0.14; LightAmb: P = 0.07) or interaction (physiological response × environment: MinAct: P = 0.61; LightAmb: P = 0.50). Furthermore, there was no effect of environmental condition on Δt for MinAct (P = 0.08) nor LightAmb (P = 0.06) trials. There were no sex differences for Δt across all environmental conditions for MinAct (P = 0.17) or LightAmb (P = 0.28) trials.

Table 2.

Time points of heart rate and core temperature inflection for each experimental condition

Environment	n	HR Inflection, min	Tc Inflection, min	Δt, min
MinAct
34°C	8	64 ± 17	99 ± 13	35 ± 13
36°C	11	55 ± 20	77 ± 21	22 ± 22
38°C	8	81 ± 22	92 ± 21	12 ± 13
40°C	9	78 ± 34	103 ± 35	25 ± 19
20 mmHg	7	74 ± 27	88 ± 22	14 ± 13
16 mmHg	13	60 ± 25	83 ± 19	23 ± 19
12 mmHg	13	59 ± 24	81 ± 34	22 ± 22
LightAmb
34°C	14	54 ± 23	77 ± 25	24 ± 14
36°C	9	59 ± 16	76 ± 13	17 ± 11
38°C	7	79 ± 20	90 ± 9	11 ± 16
40°C	8	66 ± 32	84 ± 22	18 ± 15
20 mmHg	10	63 ± 17	71 ± 8	8 ± 14
16 mmHg	17	58 ± 18	79 ± 13	21 ± 14
12 mmHg	19	49 ± 19	75 ± 16	26 ± 16

Values are represented as means ± SD; n represents number of subjects. The time to HR and Tc inflection was analyzed using a two-way repeated-measures ANOVA. The difference in time (Δt) between HR and T_c inflection was analyzed using a one-way ANOVA. Physiological response (i.e., HR vs. T_c): P = 0.01 (MinAct), P = 0.0002 (LightAmb); environmental condition: P = 0.14 (MinAct), P = 0.07 (LightAmb); interaction (physiological response × environmental condition): P = 0.61 (MinAct), P = 0.50 (LightAmb). HR, heart rate; LightAmb, light ambulation; MinAct, minimal activity; T_c, core temperature; Δt, difference in time between HR and core temperature inflection points.

Critical Environmental Limits

Figure 2 depicts individual data points for HR and T_c inflection points in each environmental condition during MinAct (Fig. 2) and LightAmb (Fig. 2). In every environmental condition, the HR inflection preceded the T_c inflection during MinAct trials (all P < 0.05). During LightAmb trials, the critical environmental loci were lower for HR compared with T_c in every environmental condition (P < 0.05) except 38°C (P = 0.12).

Figure 2.

Critical environmental loci for HR (red circles) and T_c (open circles) inflection points for P_crit (left) and T_crit (right) trials during minimal activity (MinAct; A) and light ambulation (LightAmb; B). Each individual’s response is illustrated by connecting lines. Data were analyzed using a paired-samples t test. *P < 0.05 between HR and T_c critical environmental loci. HR, heart rate; LightAmb, light ambulation; MinAct, minimal activity; P_crit, critical water vapor pressure; Pa, ambient water vapor pressure; T_c, core temperature; T_crit, critical dry-bulb temperature; Tdb, dry-bulb temperature.

The critical environmental loci for HR and T_c are plotted on a standard psychrometric chart (Fig. 3). Heat stress is compensable for T_c in environments that are below and to the left of the critical environmental loci on standard psychrometric charts. However, environments that are above and to the right of the T_c critical environmental loci are uncompensable and therefore heat balance cannot be maintained. Summary data for T_db, P_a, and % relative humidity (%rh) at the critical environments are presented in Table 3. The greater %rh at the HR compared with T_c inflection point during T_crit trials was a function of a lower T_db at a given P_a.

Figure 3.

Standard psychrometric charts showing empirically derived mean critical environmental limits (sold lines) for HR (red) and T_c (black) during minimal activity (MinAct; 69 trials) (A) and light ambulatory activity (LightAmb; 84 trials) (B). Across environments, HR began to increase disproportionately in lower environmental conditions (i.e., shifted downward and to the left) compared with T_c inflection for MinAct (P < 0.05) and LightAmb (P < 0.05). HR, heart rate; T_c, core temperature.

Table 3.

Environmental conditions at the heart rate and core temperature inflection point for each experimental condition

	34°C	36°C	38°C	40°C	20 mmHg	16 mmHg	12 mmHg
MinAct
	n = 8	n = 11	n = 8	n = 9	n = 7	n = 13	n = 13
Tdb, °C
HR	–	–	–	–	42.2 ± 2.2*	43.6 ± 2.8*	46.8 ± 2.7*
Tgi	–	–	–	–	43.9 ± 2.1	46.3 ± 2.0	49.4 ± 2.6
Pa, mmHg
HR	29.0 ± 1.6†	27.4 ± 2.4†	28.0 ± 2.3†	25.3 ± 2.7†	–	–	–
Tgi	32.3 ± 1.6	29.9 ± 2.1	29.8 ± 2.3	27.7 ± 2.4	–	–	–
rh, %
HR	72.9 ± 5.1ϕ	61.7 ± 5.3ϕ	56.8 ± 5.2ϕ	45.2 ± 5.0ϕ	31.7 ± 3.3	24.0 ± 3.0	15.4 ± 2.1
Tgi	80.9 ± 4.1	67.3 ± 4.8	60.5 ± 5.1	50.2 ± 4.3	29.1 ± 2.7	21.1 ± 1.6#	13.7 ± 2.0#
LightAmb
	n = 14	n = 9	n = 7	n = 8	n = 10	n = 17	n = 19
Tdb, °C
HR	–	–	–	–	37.6 ± 1.7*	39.7 ± 2.1*	40.6 ± 2.1*
Tgi	–	–	–	–	39.1 ± 1.0	42.2 ± 1.7	43.7 ± 2.0
Pa, mmHg
HR	21.6 ± 3.3†	21.6 ± 1.8†	22.0 ± 2.2	18.7 ± 3.8†	–	–	–
Tgi	24.1 ± 3.1	24.3 ± 1.5	23.3 ± 0.7	21.0 ± 1.7	–	–	–
rh, %
HR	53.7 ± 7.7ϕ	48.9 ± 4.1ϕ	44.0 ± 4.5	33.7 ± 6.9ϕ	40.8 ± 3.8	29.6 ± 3.3	21.2 ± 2.6
Tgi	60.7 ± 8.0	54.8 ± 3.3	46.6 ± 2.1	37.9 ± 3.0	37.9 ± 1.6#	25.9 ± 2.5#	18.7 ± 2.4#

Values are represented as means ± SD. Data were analyzed using a paired-samples t test; n represents number of subjects *P < 0.05 compared with T_db at T_gi inflection; †P < 0.05 compared with p_a at T_gi inflection; ϕP < 0.05 compared with rh at T_gi inflection; #P < 0.05 compared with rh at HR inflection. LightAmb, light ambulation; MinAct, minimal activity; P_a, ambient water vapor pressure; rh, relative humidity; T_db, dry-bulb temperature; T_gi, gastrointestinal temperature.

DISCUSSION

The PSU HEAT Project is an ongoing project designed to determine critical environmental limits beyond which thermal balance cannot be maintained for various populations. Those psychrometric limits established by T_c responses in young adults have been previously published (15) and updated (16). To our knowledge, this is the first study to examine the specific environments at which continuous increases in cardiovascular strain (cardiovascular drift) begin to occur relative to the critical environmental limits for heat balance. Our findings demonstrate that cardiovascular drift begins at lower combinations of temperature and humidity than those environments in which heat balance cannot be maintained during activities that approximate the metabolic rates associated with activities of daily living or leisurely walking in young adults. Furthermore, our findings suggest that regardless of the environmental condition or exercise intensity, cardiovascular drift precedes impending heat imbalance in young adults.

During severe passive heat stress, cardiac output can increase by two- to threefold (10, 31, 32). Since stroke volume is maintained or slightly increased in young subjects, a progressive rise in HR, commonly referred to as cardiovascular drift, is the primary driving factor for the increase in cardiac output (9, 10). The onset of cardiovascular drift results in an increase in cardiovascular strain due to increases in ventricular work of the heart (9, 33).

To our knowledge, no study has specifically examined whether or not cardiovascular drift systematically occurs before a continuous rise in T_c during progressive heat stress. Kamon et al. (18, 19) observed that cardiovascular drift preceded a continuous rise in T_c during progressive heat stress in some, but not all, subjects. However, those studies were conducted during progressive heat stress in a relatively narrow range of environments where T_db was fixed and P_a was increased during exercise at 30% V̇o_2max, and no analyses were performed to determine whether, on average, the HR inflection differed from the T_c inflection. Therefore, the present study examined differences in HR and T_c responses during two types of progressive heat stress across a wide range of environments. Furthermore, the current study included two low exercise intensities that closely resembled the metabolic costs of leisurely walking (LightAmb; ∼0.85 L/min V̇o₂) and activities of daily living (MinAct; ∼0.45 L/min V̇o₂) (23, 24). As such, the findings from the current study are more applicable to everyday life for the majority of the population, and therefore more relevant to heat wave morbidity and mortality.

To visualize a broad range of environments associated with compensable and uncompensable heat stress, critical environmental limits can be plotted on a psychrometric chart. Environments that are below and to the left of the critical environmental limit lines are compensable and, therefore, heat balance can be maintained for most individuals in a given population. However, environments that are above and to the right of the critical environmental limit lines are uncompensable, and heat balance cannot be maintained, causing a continuous rise in T_c. As demonstrated by Fig. 3, the onset of cardiovascular drift occurred at lower combinations of ambient temperature and humidity compared with the critical environmental limits for heat balance. As such, those environments that first elicited a continuous rise in HR are psychrometrically compensable for most individuals.

Although speculative, it is possible that HR begins to increase as a cardiovascular adjustment for the continued maintenance of heat balance in environments that are approaching the limits of compensability. This is supported by our findings that Δt did not differ across environmental conditions for either metabolic rate. These findings suggest that regardless of the environment and exercise intensity, an increase in cardiovascular strain occurs ∼20 min before uncompensable heat stress in our protocols. Although fluid intake was prohibited during the trials, body mass loss was <2% (MinAct: 0.7 ± 0.5%; LightAmb; 0.93 ± 0.4%) across all environments for both exercise intensities; thus, dehydration was minimal, and a reduction in plasma volume was most likely not responsible for the onset of cardiovascular drift.

Although the exact mechanism causing this cardiovascular adjustment is unknown, there are two possibilities worth mentioning. One possibility is that HR increases to maintain a stable blood pressure. At rest, heart rate is elevated in hot environments compared with thermoneutral environments, as a cardiovascular adjustment to maintain mean arterial pressure (9, 32, 33). During progressive heat stress, the onset of cardiovascular drift may precede uncompensable heat stress to maintain mean arterial pressure to compensate for venous pooling and increases in skin blood flow via cutaneous vasodilation. A second possibility for the increase in heart rate is the effect of blood temperature on the sinoatrial node. As local blood temperature increases, the firing rate of the sinoatrial node increases (34–36). However, blood temperature was not measured in this study. It is possible that a rise in blood temperature preceded a rise in gastrointestinal temperature, resulting in an increase in heart rate before uncompensable heat stress (37).

These results provide important insight regarding increased cardiovascular strain during progressive heat stress. To date, the PSU HEAT Project has focused on the boundaries of compensable and uncompensable heat stress for T_c. The findings presented herein suggest that HR responses, notably cardiovascular drift, may be used for predicting impending heat storage in young adults across a wide range of environments at low exercise intensities. Furthermore, given that a primary cause of excess deaths during extreme heat events are cardiovascular in origin (8, 38, 39), the findings from this study may provide useful information for the development of safety guidelines, policy decisions, and evidence-based alert communication to mitigate cardiovascular-related, as well as excessive heat-related, morbidity and mortality during future extreme heat events.

DATA AVAILABILITY

Data will be made available upon reasonable request.

GRANTS

This research was supported by the National Institute on Aging Grant T32 AG049676 to the Pennsylvania State University (to R.M.C.) and the National Institutes of Health Grant R01 AG067471 (to W.L.K.).

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

W. Larry Kenney is an editor of Journal of Applied Physiology and was not involved and did not have access to information regarding the peer-review process or final disposition of this article. An alternate editor oversaw the peer-review and decision-making process for this article.

AUTHOR CONTRIBUTIONS

R.M.C. and W.L.K. conceived and designed research; R.M.C., K.G.F., and S.T.W. performed experiments; R.M.C. and K.G.F. analyzed data; R.M.C., S.T.W., and W.L.K. interpreted results of experiments; R.M.C. and K.G.F. prepared figures; R.M.C. drafted manuscript; R.M.C., K.G.F., S.T.W., and W.L.K. edited and revised manuscript; R.M.C., K.G.F., S.T.W., and W.L.K. approved final version of manuscript.