Progressive exercise training improves maximal aerobic capacity in individuals with well-healed burn injuries

Abstract

Long-term rehabilitative strategies are important for individuals with well-healed burn injuries. Such information is particularly critical because patients are routinely surviving severe burn injuries given medical advances in the acute care setting. The purpose of this study was to test the hypothesis that a 6-mo community-based exercise training program will increase maximal aerobic capacity (V̇o_2max) in subjects with prior burn injuries, with the extent of that increase influenced by the severity of the burn injury (i.e., percent body surface area burned). Maximal aerobic capacity (indirect calorimetry) and skeletal muscle oxidative enzyme activity (biopsy of the vastus lateralis muscle) were measured pre- and postexercise training in noninjured control subjects (n = 11) and in individuals with well-healed burn injuries (n = 13, moderate body surface area burned; n = 20, high body surface area burned). Exercise training increased V̇o_2max in all groups (control: 15 ± 5%; moderate body surface area: 11 ± 3%; high body surface area: 11 ± 2%; P < 0.05), though the magnitude of this improvement did not differ between groups (P = 0.7). Exercise training also increased the activity of the skeletal muscle oxidative enzymes citrate synthase (P < 0.05) and cytochrome c oxidase (P < 0.05), an effect that did not differ between groups (P = 0.2). These data suggest that 6 mo of progressive exercise training improves V̇o_2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response.

INTRODUCTION

Each year ~13,000 individuals sustain severe burn injuries that cover over 20% of their body surface area (2). Military conflicts are also a significant source of burn-related injuries, given that 5–20% of all battlefield injuries are burn related (10, 12, 44). Before the turn of the century, burns covering half a person’s body surface area were often fatal. However, today, individuals with severe burn injuries covering an ever greater percentage of body surface area routinely survive due to medical advances in the acute burn care setting (38). Consequently, more individuals are living with larger percentages of body surface area burned than ever before, but the long-term consequences of these injuries remain unclear.

The acute physiological responses associated with burn injuries have been the primary focus of prior research. However, we and others have described a number of the long-term consequences of severe burn injuries including impaired body temperature regulation, psychosocial barriers, decreased cutaneous sensation, functional impairment, increased likelihood of rehospitalization, impaired vascular function, altered cardiac function, and increased long-term mortality (4, 7, 24, 25, 30, 39–42). Related to these physical and physiological impairments, our laboratory recently reported that individuals with well-healed burn injuries have profoundly reduced aerobic capacity many years following the initial injury (17), a finding consistent with others (43).

The observation of low aerobic capacity in burned individuals not only reveals distinct maladaptations of the factors governing oxygen delivery and extraction of the oxygen at the active muscle but also highlights the increased cardiovascular disease and mortality risk within this population (3, 8, 14). Thus appropriate therapeutic strategies are needed for individuals with burn injuries, particularly for those well beyond the standard rehabilitative period after the injury (36). Only one study has investigated the effects of exercise training on individuals with well-healed burn injuries (19). Grisbrook et al. (19) reported that combined aerobic and resistance exercise training resulted in small but similar increases in aerobic capacity between burned and noninjured control groups. However, perhaps given the small number of individuals enrolled with burn injuries (n = 9), that study did not evaluate the potential influence of the magnitude of body surface area burned on changes in aerobic capacity to that exercise training program. Furthermore, it is unclear if the gains in aerobic capacity would differ if the exercise training program was longer in duration and not supervised, a scenario that would better reflect the type of exercise training program that individuals with burn injuries would participate in. Thus it remains unknown whether the extent of body surface area burned influences the capacity of individuals with well-healed burn injuries to increase aerobic capacity in response to a long-term unsupervised exercising training program.

Therefore, the purpose of this study was to determine if individuals with well-healed burn injuries are capable of improving aerobic capacity through a 6-mo community-based exercise training program after stratifying for body surface area burned. We tested the hypothesis that subjects with prior burn injuries covering <40% body surface area will have similar increases in aerobic capacity relative to noninjured control subjects, while subjects with >40% body surface area burned will exhibit less of an increase in aerobic capacity.

METHODS

Subjects

Written informed consent was obtained from all subjects subsequent to a verbal and written briefing of all experimental procedures. This study and informed consent were approved by the Institutional Review Boards at the University of Texas Southwestern Medical Center and Texas Health Presbyterian Hospital Dallas, and the study was performed in accordance with the principles outlined in the Declaration of Helsinki. Eleven nonburned control subjects and 33 individuals with well-healed burn injuries were studied from 2014 to 2019. Individuals were grouped based on whether the magnitude of the initial burn injury was greater than or less than 40% of their body surface area, as previously performed by our group (18, 35, 39, 41). This criterion value is determined in part by the United States Army guideline (AR 40-501) indicating that individuals with burn injuries covering 40% or more of their body surface area are no longer allowed to serve in the US Army. All burned subjects were studied at least 2 yr postinjury. Thirteen subjects with burn injuries covering 15–40% of body surface area were assigned to the moderate burn injury group, and 20 subjects with burn injuries covering >40% of body surface area were assigned to the high burn injury group. All subjects (including nonburned controls) were sedentary and had not participated in a consistent/structured exercise training regimen at any time over the prior 12 mo. Estimates of total physical activity were obtained from a commercially available monitor (Actical; Philips Respironics, Andover, MA). The activity monitor was worn on a belt placed near the umbilicus for 7 days during waking hours within ~2 wk of testing. The monitor measures motion “omnidirectionally” and estimates of total physical activity are measured in total kilocalories. Subject physical characteristics are shown in Table 1.

Table 1.

Subject characteristics

	Control	Moderate Burn Injury	High Burn Injury
Men/women	6/5	7/6	12/8
Age, yr	33 ± 8	35 ± 14	42 ± 11
Height, cm	170 ± 9	168 ± 10	170 ± 9
Body mass, kg	87 ± 24	77 ± 17	85 ± 19
7-Day awake physical activity, kcal	18,294 ± 1,178	17,771 ± 873	16,279 ± 1,088
Body surface area burned, %	–	26 ± 6	58 ± 15
Years from burn injury	–	16 ± 10	17 ± 12
Medication groups, n
Hypertension	3	2	1
Hypercholesterolemia	1	1	1
Hypothyroidism	2	1	2
Stimulants	2	0	0
Pain	0	4	2
Anti-inflammatory	0	1	1
Medical marijuana	0	3	2
Sedatives	0	2	3
Multivitamin	7	5	3
Antidepressant	0	3	4
Contraceptive	0	2	3
Allergy	0	3	1

Nonmedication values are means ± SD.

Exercise Training

All subjects participated in a community-based 6-mo progressive exercise training program based upon the Training Impulse approach outlined by Banister et al. (6) in which frequency, intensity, and duration gradually increase across the training period. Each bout of exercise was preceded with a warm-up period and concluded with a cool down period. Subjects chose to exercise via cycling, walking/jogging, and/or elliptical training, as long as they were able to achieve the prescribed heart rate with the employed exercise mode(s). Subjects were also encouraged to incorporate at least two of the aforementioned modes of exercise to facilitate a “cross-training” approach. Subjects performed “Base Pace” bouts of exercise for 30–40 min (months 1–3) and for 60 min (months 4–6) three to four times per week. Additionally, “Interval Training” was also included beginning at month 4. Months 4–6 also included “Recovery Training” bouts in which subjects exercised at a comfortable pace for 30 min per bout. Progressive resistance-based strength training, focusing on large muscle groups, began in month 2 of the program using fitness center-based devices (both machines and free weights, as preferred by the subject). The frequency and duration of the progressive exercise training protocol is outlined in Table 2.

Table 2.

Prescribed exercise frequency and duration on a monthly basis for the 6-mo exercise training program

	Base Pace	Intervals	Recovery Training	Strength Training
Month 1	12 at 30 min	None	None	None
Month 2	15 at 35 min	None	None	6 at 30 min
Month 3	15 at 40 min	None	None	6 at 30 min
Months 4–6	4 at 30 min and 4 at 60 min	8 sessions of 4 ×3 (4 min “on,” 3 min rest)	4 at 30 min	8 at 30 min

Each row depicts the frequency and duration prescribed for the indicated month, with individual exercise sessions prescribed on a weekly basis.

Training intensity was individualized based each subject’s heart rate responses at ventilatory threshold and maximal heart rate, both identified during a graded exercise test (see below). Furthermore, exercise intensity was increased as needed throughout the exercise training program to ensure that heart rate remained within the specified zone. Heart rate was monitored remotely for each subject using a heart rate monitor (Polar Vantage XL model 145900; Polar Electro, Woodbury, NY) that provided date and time stamps for onset and completion of each exercise bout. Data from the heart rate monitors were downloaded by the investigative team. The Base Pace bouts were performed at an intensity that resulted in a heart rate that was 10–20 beat/min less than heart rate at ventilatory threshold. For the Interval Training bouts, the intensity for the “on” period was ~10 beats/min less than maximal heart rate and was 4 min in duration. Each “on” period was followed by a 3 min of an active “off” period. The Recovery Training bouts were performed at a heart rate where the subject feels “comfortable” for the prescribed duration, which was expected to be ~30 beats/min less than heart rate at ventilatory threshold. The heart rate range for each training zone was identified and clearly explained to each individual before commencement of the exercise training program. Subjects were required to complete at least 80% of the prescribed exercise training sessions.

During the 6-mo training program, subjects received a weekly consultation with study personnel, inclusive of a debrief of the prior week’s training outcomes and compliance and a training plan that indicated the heart rate zone for each exercise bout to be performed for the upcoming week. Subjects were provided with local certified personal trainer support for the first 6 wk of training. Thereafter, subjects had access to personal trainer support as needed and per their request. All subjects exercised in temperature-controlled facilities, thereby controlling for potentially confounding influences of differing climates, as well as providing an increased measure of safety for thermally intolerant subjects.

Pre- and Postexercise Training Measurements

Before and after the 6-mo exercise training program, subjects were tested across 4 days using the following generalized schedule: day 1, steady-state exercise responses and maximal aerobic capacity (V̇o_2max); day 2, recovery day/body composition; day 3: V̇o_2max retest; and day 4, skeletal muscle biopsy. Subjects reported to the laboratory at ~8:00 AM each day. All testing was performed in a temperature-controlled laboratory (~22°C), and subjects were required to abstain from caffeine, nutritional supplements, alcohol, and physical activity for 24 h before the study. Subjects were also required to abstain from over-the-counter medications but were allowed to take prescription medications as needed at the time of the study.

Steady-state exercise responses.

Subjects performed 5 min of steady-state cycling exercise at fixed workloads of 50 and 75 W on an electronically braked ergometer (Lode Excalibur Sport, Groningen, The Netherlands). Seat and handlebar settings for the cycle ergometer were identical pre- and posttesting. Oxygen uptake and respiratory measures were continuously recorded via open-circuit indirect calorimetry (PARVO Medics True-One Metabolic Measurement System; Parvo Medics, Salt Lake City, UT). Heart rate was measured continuously (Polar Vantage XL model 145900; Polar Electro). Rating of perceived exertion was measured in minute 3 of each 5-min stage using the Borg 15-point category scale (9). Cardiac output was measured in the final min of each stage via inert gas rebreathing (0.5% nitrous oxide; Innocor; Innovision, Glamsbjerg, Denmark). Finally, ~1 µl of venous blood was obtained (capillary finger-stick) after completion of the cardiac output measurement for assessment of circulating lactate.

Maximal aerobic capacity.

Subjects performed two graded maximal cycle exercise tests to ensure the likelihood that a true V̇o_2max was obtained. Each maximal exercise test was separated by at least 48 h. The higher of the two V̇o_2max values obtained pre- and posttesting was used for analysis. Subjects began the test by cycling at 40 W. Thereafter, the workload was increased by 40 W every 2 min until subjects reached volitional fatigue. Oxygen uptake was determined via open-circuit indirect calorimetry. Heart rate was continuously measured, while ratings of perceived exertion were measured at rest, every 2 min during, and at the end of the test. Blood lactate concentration was measured 3 min after completion of the test. Confirmation of V̇o_2max was objectively identified based on a heart rate within 10 beats/min of age-predicted maximum (220 − age), a plateau in oxygen uptake despite an increase in workload, a rating of perceived exertion of 19 to 20, and/or a respiratory exchange ratio of >1.0 (28). All testing was similar to that performed previously by our laboratory in individuals with burn injuries (17).

Body composition.

Dual-energy X-ray absorptiometry was used to assess lean body mass and percent body fat before and after exercise training. Dual-energy X-ray absorptiometry scans were performed by Radiology Cores at Texas Health Presbyterian Hospital Dallas or University of Texas Southwestern Medical Center. The same scanner was used pre- and posttesting for a given subject.

Skeletal muscle oxidative enzyme activity.

Markers of oxidative capacity, cytochrome c oxidase and citrate synthase activities, were measured in skeletal muscle obtained via biopsy of the vastus lateralis. The skin and underlying fascia were anesthetized using 1% lidocaine HCl (Hospira Worldwide, Lake Forest, IL). Skeletal muscle was obtained at a depth of ~2–3 cm using a 6-G (5-mm outer diameter) Bergström biopsy needle inserted through a small incision made in the skin and muscle fascia. Harvested skeletal muscle tissue was blotted, removed of any adipose tissue, and flash frozen in liquid nitrogen, and stored at −80°C until analysis.

Citrate synthase activity was determined in muscle homogenates by evaluating the release of coenzyme A from the enzymatic reaction of acetyl CoA and oxaloacetate, as measured spectrophometrically by increasing absorbance at 412 nm. An extinction coefficient of 13.6 mM⁻¹·cm⁻¹ was used to calculate this enzyme activity. Cytochrome c oxidase activity was determined spectrophometrically in muscle homogenates by measuring the decrease in the absorbance at 550 nm of ferrocytochrome c that is oxidized to ferricytochrome c by cytochrome c oxidase. An extinction coefficient of 20 mM⁻¹·cm⁻¹ was used to calculate the rate of cytochrome c oxidation.

Statistical Analyses

Our primary outcome variables were analyzed using a two-way (group × time) mixed model ANOVA with repeated measures (JMP Pro 13; SAS Institute, Cary, NC). Planned comparisons were used to examine specific group-time interactions. General interactions were examined using Tukey’s post hoc procedure. Data are reported as means ± SE, unless otherwise indicated.

RESULTS

Exercise Training Impulse and Compliance

Exercise training stimulus was quantified by calculating the “training impulse” (TRIMP) for individual months and total TRIMP scores across the entire training period (6). As planned, TRIMP scores increased over the course of the 6-mo exercise training program (P < 0.05, main effect of time). Total TRIMP scores were greater for the control group [4,901 ± 451 arbitrary unit (AU)] when compared with the moderate (3,442 ± 439 AU; P < 0.05) and high (3,686 ± 306 AU; P = 0.08) burn injury groups. Compliance to the prescribed exercise training program did not differ between groups (control, 91 ± 2%; moderate, 90 ± 2%; high, 91 ± 2%; P = 0.7).

Steady-State Exercise Responses

Pre- and postexercise training responses to steady-state cycling exercise are shown in Fig. 1 and Table 3. Compared with pretraining, heart rate was decreased (P < 0.05, main effect of time) and stroke volume was increased (P < 0.05, main effect of time) after exercise training at both workloads of cycle exercise. The magnitude of reduction in heart rate during steady-state exercise did not differ across the three groups (50 W, P = 0.9; 75 W, P = 0.7; group × time interaction). Despite the robust improvement in stroke volume in the control group and modest improvement in the moderate and high burn injury groups, the overall response did not differ by group at both workloads (50 W, P = 0.1; 75 W, P = 0.1; group × time interaction). Lactate concentrations were reduced at both workloads postexercise training in all groups (P < 0.05, main effect of time), an effect that did not differ by group (50 W, P = 0.9; 75 W, P = 0.6; group × time interaction). Similarly, rating of perceived exertion was reduced following exercise training (P < 0.05, main effect of time) and did not differ by group (50 W, P = 0.3; 75 W, P = 0.5; group × time interaction). Compared with pretraining, oxygen uptake was reduced after exercise training at both workloads in the high burn injury group (both workloads, P < 0.05) but did not differ for control (50 W, P = 0.9; 75 W, P = 0.5) or moderate burn injury (50 W, P = 1.0; 75 W, P = 1.0) groups. Neither mean arterial blood pressure (50 W, P = 0.6; 75 W, P = 0.2; group × time interaction) nor cardiac output (50 W, P = 0.1; 75 W, P = 0.1; group × time interaction) differed from pre- to postexercise training.

Fig. 1.

Heart rate (top) and stroke volume (bottom) responses to steady-state cycling exercise are shown for control, moderate burn injury, and high burn injury groups at pre- and postexercise training. Open circles, pretraining; black circles, posttraining. *P < 0.05 vs. pretraining.

Table 3.

Pre- and postexercise training cardiometabolic responses to steady-state cycling exercise

	Control				Moderate Burn Injury				High Burn Injury
	50 W		75 W		50 W		75 W		50 W		75 W
	Pretraining	Posttraining	Pretraining	Posttraining	Pretraining	Posttraining	Pretraining	Posttraining	Pretraining	Posttraining	Pretraining	Posttraining
Mean arterial pressure, mmHg	101 ± 7	99 ± 3	100 ± 5	102 ± 7	109 ± 5	101 ± 3	109 ± 6	109 ± 6	105 ± 3	103 ± 3	109 ± 5	102 ± 4
Cardiac output, L/min	10.0 ± 0.3	10.6 ± 0.3	10.9 ± 0.4	11.8 ± 0.3	9.4 ± 0.6	9.7 ± 0.5	11.5 ± 0.5	10.8 ± 0.5	10.4 ± 0.3	9.9 ± 0.3	11.3 ± 0.5	11.1 ± 0.3
V̇o2, L/min	0.94 ± 0.03	0.93 ± 0.03	1.16 ± 0.03	1.11 ± 0.03	0.88 ± 0.03	0.88 ± 0.03	1.07 ± 0.03	1.07 ± 0.03	0.93 ± 0.03	0.87 ± 0.02*	1.14 ± 0.03	1.04 ± 0.02*
RPE, U	9 ± 1	8 ± 1*	11 ± 1	10 ± 1*	10 ± 1	8 ± 1*	12 ± 1	10 ± 1*	10 ± 1	9 ± 1*	12 ± 1	10 ± 1*
Lactate, mmol/L	2.5 ± 0.4	2.0 ± 0.4*	2.4 ± 0.4	1.6 ± 0.4*	2.5 ± 0.4	1.9 ± 0.2*	3.5 ± 0.7	2.1 ± 0.3*	2.1 ± 0.1	1.5 ± 0.1*	2.8 ± 0.3	1.8 ± 0.2*

Values are means ± SE. RPE, rate of perceived exertion.

^*P < 0.05 vs. pretraining within workload.

Maximal Aerobic Capacity

Responses to the maximal exercise test are shown in Fig. 2 and Table 4. Compared with the control group, and regardless of pre- and posttraining status, absolute and relative V̇o_2max, maximal workload, test duration, maximal heart rate, lactate, and heart rate were lower in burn injury groups (all P < 0.05, main effect of group). Rating of perceived exertion did differ between groups (P = 0.3).

Fig. 2.

Maximal workload (top) and V̇o_2max (bottom) are shown for control, moderate burn injury, and high burn injury groups at pre- and postexercise training. Open bars, pretraining; black bars, posttraining. *P < 0.05 vs. pretraining. †P < 0.05 vs. burn injury groups.

Table 4.

Reponses to maximal cycle ergometry pre- and postexercise training

	Control		Moderate Burn Injury		High Burn Injury
	Pretraining	Posttraining	Pretraining	Posttraining	Pretraining	Posttraining
Relative V̇o2max, ml·kg−1·min−1	33.3 ± 3.2	38.3 ± 3.5*	29.5 ± 3.2	31.4 ± 2.2*	26.6 ± 1.1	29.5 ± 1.4*
Test duration, min	10 ± 1	12 ± 1*	8 ± 1	10 ± 1*	8 ± 1	10 ± 1*
Heart rate, beats/min	189 ± 2	184 ± 3*	182 ± 3	179 ± 4*	172 ± 2	170 ± 2*
RPE, U	19 ± 1	19 ± 1	18 ± 1	18 ± 1	19 ± 2	19 ± 2
Lactate, mmol/L	12.6 ± 0.7	11.6 ± 1.0	9.8 ± 0.6	9.8 ± 0.4	9.9 ± 0.5	9.7 ± 0.7

Values are means ± SE. RPE, rate of perceived exertion.

^*P < 0.05 vs. pretraining within workload.

Exercise training increased absolute V̇o_2max by 15 ± 5% for the control group and by 11 ± 3 and 11 ± 2% for the moderate and high burn injury groups (all P < 0.05 vs. 0 change), the magnitude of which did not vary by group (P = 0.7). Similarly, maximal workload and test duration increased after exercise training for all groups (both P < 0.05, main effect of time) but did not vary by group (P = 0.5; group × time interaction). Maximal heart rate was reduced following exercise in all groups (P < 0.05, main effect of time). Lactate concentration (P = 0.6, main effect of time) and rating of perceived exertion (P = 0.4, main effect of time) did not differ pre- to postexercise training for all groups.

Body Composition

Total body mass did not differ between groups before exercise training Table 1 (P = 0.5) and was unchanged by exercise training (P = 0.7). Percent body fat (P = 0.4), total lean mass (P = 0.6), and total fat mass (P = 0.6) did not differ between groups. Exercise training reduced percent body fat for control (pretraining 34 ± 3% vs. posttraining 31 ± 3%), moderate burn injury (pretraining 32 ± 2% vs. posttraining 29 ± 2%), and high burn injury (pretraining 33 ± 2% vs. posttraining 31 ± 2%) groups (all P < 0.05, main effect of time). Total fat mass was reduced after exercise training in all groups (control, pretraining 30 ± 4 kg vs. posttraining 29 ± 4 kg; moderate burn injury, pretraining 25 ± 2 kg vs. posttraining 22 ± 2 kg; high burn injury groups, pretraining 28 ± 2 kg vs. posttraining 27 ± 3 kg; all P < 0.05, main effect of time). Additionally, exercise training increased total lean mass for control (pretraining 54 ± 2 kg vs. posttraining 55 ± 2 kg), moderate burn injury (pretraining 49 ± 3 kg vs. posttraining 51 ± 3 kg), and high burn injury groups (pretraining 53 ± 2 kg vs. posttraining 54 ± 2 kg) (all P < 0.05, main effect of time).

Skeletal Muscle Oxidative Enzyme Activity

Some subjects declined the muscle biopsy. As such, data reported herein are for a subset of participants (control, n = 10; moderate burn, n = 9; high burn, n = 13). Pre- and postexercise training citrate synthase and cytochrome c oxidase activities are shown in Fig. 3. Neither citrate synthase (P = 0.8) nor cytochrome c oxidase (P = 0.4) activity differed between groups before exercise training. Citrate synthase activity was increased for all groups after exercise training (P < 0.05, main effect of time). Likewise, exercise training augmented cytochrome c oxidase activity (P < 0.05, main effect of time).

Fig. 3.

Skeletal muscle citrate synthase (left) and cytochrome c oxidase (right) activities are shown for control, moderate burn injury, and high burn injury groups at pre- and postexercise training. Open bars, pretraining; black bars, posttraining. *P < 0.05 vs. pretraining.

DISCUSSION

The purpose of this study was to determine if individuals with well-healed burn injuries are capable of improving aerobic capacity through a 6-mo community-based exercise training program when stratifying for body surface area burned. We tested the hypothesis that subjects with prior burn injuries covering <40% body surface area will have similar increases in aerobic capacity relative to noninjured control subjects, while subjects with >40% body surface area burned will have less of an increase in aerobic capacity. In contrast to our hypothesis, aerobic capacity increased to the same extent in all three groups. In addition, indexes of cardiometabolic function were similarly improved for all three groups.

Exercise Training as a Rehabilitation Tool

We and others have shown previously that maximal aerobic capacity is disproportionally low in individuals with well-healed burn injuries (17, 43). In our previous study (17), we found that the differences in aerobic capacity were staggering in that V̇o_2max for ~76% of individuals with burn injuries were in the lowest 20th percentile rankings, relative to sex- and age-matched nonburned individuals. Similar conclusions are made when the data are compared with normative V̇o_2max values from the American Heart Association (16), in that 80% of the burned cohort have a V̇o_2max in the lowest quartile. The etiology underlying these observations is unclear but is thought to be related to increased metabolism and the associated catabolic response that occurs following a burn injury (15, 21–23), persistent cardiovascular deconditioning associated with prolonged bed rest during hospitalization and a subsequent sedentary lifestyle, and/or psychosocial reasons, in which burned individuals choose to not exercise perhaps due to the emotional discomfort some experience when burn scars are exposed in a public exercise setting (1, 31, 32, 41). Additionally, individuals with burn injuries may choose to not exercise due to a general lack of fitness and motivation (5), which may occur secondary to inhalation injury, pain sensation, medication, and positioning required to exercise relative to the location of burn injury (13).

In this study, we provide clear evidence, in a large group of individuals with well-healed burn injuries, that 6 mo of progressive exercise training increases maximal aerobic capacity equally regardless of the extent of injury. Our findings are in line with those of Grisbrook et al. (19) who demonstrated that 12 wk of supervised combined interval and resistance exercise training increased V̇o_2max to a similar extent in a small group of control subjects and individuals who averaged 6 yr postburn injury. However, Grisbrook et al. did not investigate the potential influence of the fraction of body surface area burned, resulting in data being pooled from subjects with as little as 22% body surface area burned with data from subjects with as much as 75% body surface area burned (n = 9 for entire burned group). That said, after stratifying subjects to two distinct groups based on body surface area burned, we found that the magnitude of improvement in V̇o_2max is similar between groups and comparable to that of the nonburned control group. Therefore, it appears that the extent to which an individual’s body surface area is burned does not lessen the capacity to increase maximal aerobic capacity in response to exercise training.

Steady-State Exercise Responses: Hallmarks of Cardiometabolic Adaptations to Exercise Training

In addition to maximal aerobic capacity, the typical cardiometabolic responses to submaximal steady-state exercise can be used to assess exercise training adaptation. For a given absolute metabolic demand, trained individuals have a larger stroke volume, lower heart rates and venous lactates, and lower ratings of perceived exertion. We utilized two stages of fixed workload cycle ergometry (50 and 75 W) to examine responses to varying levels of exercise intensity and to ensure that all subjects could complete each exercise stage. After exercise training, heart rate was consistently lower for each group during steady-state exercise, an effect that appeared to be mediated by improved stroke volume. Interestingly, the magnitude by which exercise training increased stroke volume was greatest in the control group, with only modest improvements in the moderate and high burn injury groups. Moreover, independent of group, venous lactate was reduced at submaximal workloads after exercise training, suggesting better lactate handling in skeletal muscle (29). Given these cardiometabolic adaptations following exercise training, it is no surprise that ratings of perceived exertion were also reduced across all groups.

Steady-state oxygen uptake was reduced in the high burn injury group after exercise training, despite utilizing fixed workloads and a cycle ergometer that automatically adjusts flywheel resistance in response to changing pedal cadence. The only plausible explanation for this difference is that metabolic efficiency increased in the high burn injury group, such that oxygen uptake is reduced at the same workload relative to pretraining. It is unclear at present why metabolic efficiency differs in the high burn injury group after exercise training but may be related to range of motion and joint mobility. Skin contractures (i.e., tightening of skin at or near areas of 2nd or 3rd degree burns) greatly reduce the range of motion and joint mobility in individuals with mature burn scars, an effect that we expect would be magnified in the high burn injury group given the absolute body surface injured. We speculate that exercise training improved range of motion and joint mobility in the high burn injury group thereby improving metabolic efficiency during cycle exercise, an effect that occurs secondary to the repetitive movements and the increase in skin temperature and blood flow during acute exercise (11). Indeed, exercise reduces the need for surgical contracture release in individuals with burn injury (34) and enhances range of motion at the knee more so than physical therapy alone (33).

Skeletal Muscle Enzyme Activity

To better elucidate the metabolic adaptations to exercise training in individuals with burn injuries, we analyzed the activity of the oxidative enzymes cytochrome c oxidase and citrate synthase in skeletal muscle biopsied from the vastus lateralis. Despite the profound catabolism and mitochondrial dysfunction that occur acutely following a burn injury (37), we found that cytochrome c oxidase and citrate synthase activities did not differ between control and burn injury groups. This finding suggests that the enzymatic changes in skeletal muscle do not persist well beyond (at least 2 yr) the acute burn period. In fact, cytochrome c oxidase and citrate synthase activities were nearly identical between control subjects and those with prior burn injuries.

It is well understood that exercise training can improve oxidative enzyme activity in skeletal muscle (26, 27). To our knowledge, we are the first to examine skeletal muscle enzyme activity in response to exercise training in individuals with burn injuries. We found that that the adaptive response of skeletal muscle to exercise training is not inhibited in individuals with prior burn injuries. Moreover, the observed improvements in oxidative enzyme activity likely contribute to some of the improved cardiometabolic responses observed during maximal and steady-state exercise (e.g., reduced lactate concentrations).

Experimental Considerations

Several experimental limitations warrant discussion. First, TRIMP scores (i.e., training intensity) were higher for the control group relative to both burn injury groups, despite a similar exercise training compliance. Because training intensity was individualized based each subject’s heart rate response at ventilatory threshold, it is no surprise that TRIMP scores were lower in the burn injury groups relative to the control group. Importantly, the magnitude of improvement in V̇o_2max did not differ between groups despite the difference in TRIMP scores. Furthermore, the prescribed training intensity for the burn injury groups likely reflects the training intensity individuals might choose should they begin their own exercise training program. Thus, while the overall training intensity may differ, the therapeutic efficacy of the exercise training program was clearly present among our many outcome variables. Second, there was a slight age difference between the high burn injury and low burn injury and control groups. Because age tended to differ between groups (P = 0.09) and given the known effect of age on maximal aerobic capacity, it is possible that potential benefits in the high burn injury group could be somewhat masked. However, pretraining maximal aerobic capacity did not differ between burn injury groups and we observed consistent increases in maximal aerobic capacity across the three groups, suggesting that the effect of age was likely minimal. Third, given that we assessed skeletal muscle oxidative enzyme activity in whole muscle homogenates we cannot say with certainty that the measures changes are specific to the mitochondria. Finally, our experimental design did not employ nonexercise groups. Because burned individuals are generally metabolically stable in the first year or two postinjury (20–22), it is unlikely that V̇o_2max and other outcome variables (e.g., muscle enzyme activities) would have changed during the 6-mo period in absence of the exercise program. Therefore, we are confident that the observed gains in cardiometabolic function were due to exercise training and not due to factors associated with the healing process.

Perspectives and Significance

Individuals with well-healed burn injuries have profoundly reduced aerobic capacity many years following the initial injury. While the beneficial effects of exercise training in individuals with burn injuries has been investigated previously, the majority of studies have evaluated the effects during the acute phase of recovery (i.e., while patients were still in the hospital or shortly following discharge). Our findings that a 6-mo exercise training program improves maximal aerobic capacity in individuals with burn injuries extends the previous observations by Grisbrook et al. (19). Importantly, our data indicate that the magnitude of body surface area burned does not inhibit the adaptive responses to exercise training. Thus individuals with prior burn injuries, irrespective of the magnitude of the initial injury, can realize the physiological benefits of exercise training and ultimately cardiovascular-specific, as well as all cause, morbidity and mortality (3, 8, 14).

GRANTS

This research was funded by the National Institute of General Medical Sciences Grants GM-068865 and GM-117693.

DISCLOSURES

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

AUTHOR CONTRIBUTIONS

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