Cardioprotective Benefit of Passive Heat Therapy in Higher-Level Spinal Cord Injury: Safety and Proof of Concept

The risk of cardiovascular diseases for people with a spinal cord injury (SCI) is approximately 3x greater than the general population, and Cardiovascular (CV) diseases account for \~40% of deaths in SCI. Traditional CV risk factors are unable to fully explain these outcomes. This group also has other secondary complications that are concerning, including susceptibility to infections and metabolic health issues. Some of the increased risk in SCI is due to a relatively sedentary lifestyle and insufficient exercise capability. This is particularly insidious in those living with tetraplegia with poor cardiovascular responses to exercise or even the inability to exercise due to upper limb paralysis.

Heat therapy in the form of hot baths and saunas has been utilized for centuries, with common reports of improved quality of life and overall improved well-being. A 20-year prospective study on 2,315 middle-aged men (at enrolment) in Finland reported that regular sauna bathing was associated with reduced risk of sudden cardiac death, coronary heart disease, CV disease, and all-cause mortality. Further, more frequent sauna bathing sessions were related to a considerably decreased risk of fatal cardiac and CV events, as well as all-cause mortality independently from conventional risk factors, activity levels, and diet. The mechanisms which underlie these improvements remain largely unknown. It has been proposed that CV benefits of exercise training are partly mediated by repeated increases in core temperature. Exercise and heat stress elicit many common physiological responses, including increases in core temperature, heart rate and contractility, redistribution of blood flow, and changes in conduit vessel endothelial shear stress, all of which are believed to improve CV health. Additionally, heat exposure and exercise induce the expression of heat shock proteins, which stabilize a variety of other proteins that reduce vascular inflammation and oxidative stress, improve NO bioavailability, promote angiogenesis, and improve glucose signaling.

SCI results in a host of physiological changes that greatly increase CV risk and vascular dysfunction following injury. Increased arterial stiffness and vascular resistance are common features in SCI, likely secondary to the loss of sympathetic innervation below the lesion, increased circulating vasoconstrictors, and subsequent oxidative stress and vascular inflammation. Heat exposure is a stress to the CV system, like exercise, which may result in numerous chronic adaptations that improve vascular and metabolic function, resulting in a profoundly reduced risk of CV disease.

Passive heat therapy may provide a novel and practical approach to help these individuals. There have been observed profound improvements in vascular and metabolic function as well as indications of benefits to the immune system and reductions in inflammation in healthy but sedentary able-bodied people after long-term passive heat exposure. Similar benefits were observed in obese women with polycystic ovary syndrome. Recent studies in SCI with lower limb and full-body (only in low level SCI) immersion have demonstrated the potential of hot water immersion to be safe, with the potential to stimulate a cardio-protective response. The proposed pilot study is the first step in developing a unique approach for combating CV dysfunction in the SCI population.

Specifically, the goal of this pilot study is to build on the current literature and demonstrate the safety, tolerance, and effectiveness (providing a mild/moderate exercise response) of a \~ 45-minute full-body hot water immersion in those with higher level SCI (T7-C4). Ultimately, the investigators will develop a protocol for translating these and future findings to the home environment and use of a typical bathtub, thereby demonstrating that passive heat therapy is a viable approach to improve health in the SCI population.

Water immersion is the preferred method of heating since it is capable of increasing core temperature and heart rate at a rate similar to moderate-intensity exercise. It is difficult to achieve increases in core temperature solely via air convection, including in paraplegic SCI, as participants rapidly acclimate to the heat with increased sweating, limiting the rise in core temperature and heart rate. In addition, hot tubs, whirlpools, and baths are available in the community, and most should provide wheelchair access. In addition, a water bath in the home is an acceptable alternative to a hot tub to sufficiently raise core body temperature. Furthermore, water is an excellent conductor of heat, and will provide uniform heating across the participants' body. This helps eliminate "hot spots" that could result in a burn, particularly in insensate areas of skin.

For this study, up to 16 individuals will be recruited from International Collaboration on Repair Discoveries (ICORD) Physical Activity Research Centre (PARC) Community as well as from the larger SCI community who live with a T7-C4 injury. In addition, the investigators will be recruiting up to 6 control participants who are otherwise healthy individuals who do not live with an SCI. During the single, approximately 45-minute exposure to this passive heating modality the investigators will be measuring heart rate, blood pressure (mean arterial pressure), cardiac output, respiration rate and core temperature. This descriptive study will have each participant attend the lab for a single session.

After a 20 min of baseline data collection period the participant will be transferred to the hot tub using a standard Hoyer lift and sling. While in the hot tub they will remain in a semi-reclined position. Initially the participant will be submersed up to the clavicular level with one arm out of water until the core temperature reaches 38.5 C (about 20 - 25 minutes), once this temperature has been reached, they will be positioned so that the water level lays between the waist and mid-sternum. The water level on the participant's body will be adjusted such that a core temperature of 38.5 C for 20 minutes (typical moderate exercise duration) is maintained. If the participants core temperature exceeds 39.5 C the session will be terminated and the participant removed from the hot tub. While in the hot tub the participant may drink water ad lib with the volume recorded.

While submersed in the hot tub:

• Core temperature, blood pressure, blood flow, and heart rate will be monitored continuously
• Oxygen consumption will be assessed every 5 minutes
• Cardiac output will be assessed every 10 minutes

Once the \~45 min of immersion has been completed the participant will be removed from the hot tub using the Hoyer lift and placed back on the plinth in a semi-reclined position for 20 minutes of recovery/rest. While in this recovery position core temperature, blood pressure, blood flow, and heart rate will be monitored continuously.

After this initial recovery period the investigators will assist the participant as necessary to help the participant get dressed, weighed, testing equipment removed and will continue resting comfortably in the participant's everyday wheelchair for 60-90 min.

The outcome variables to be examined include the following:

• Heart rate
• Blood pressure (systolic, diastolic, mean arterial pressure, beat to beat)
• Core temperature (via CorTemp© "smart pill and Bear Hugger)
• Cardiac output
• Oxygen consumption
• Brachial and cerebral artery blood flow
• End tidal gas - respiration rate
• Weight loss

Each of the outcome variables will be examined in both an individual and pooled manner (average and standard deviation). In addition, any potential group trends (e.g., injury level [thoracic versus cervical] and severity [ American Spinal Injury Association Impairment Scale (AIS) score]) in terms of the response to the passive heating stimulus will be examined.