Abstract
Spinal cord injury (SCI) is a debilitating disorder, causing cardiovascular dysfunction at rest and during orthostasis [as simulated by lower-body negative pressure (LBNP)], which differs with the level, completeness, and time since injury. However, the effect of SCI on cerebrovascular function remains unclear. In addition, the effects of passive heat stress (PHS) on integrative cerebrovascular and cardiorespiratory function at rest and during orthostasis following SCI are unknown. In able-bodied individuals, although PHS markedly increases the susceptibility to syncope, the mechanisms by which this occurs are poorly understood but are ultimately reflected in critical reductions in cerebral blood flow (CBF) during orthostatic stress. Therefore, the central aim of this thesis was to investigate the effects of chronic tetraplegic SCI on modulation of cardiovascular and cerebrovascular function at rest and during orthostasis with and without PHS. A secondary aim was to investigate the role of the potential mediator(s) of reduced CBF and orthostatic tolerance during PHS using multiple increments in body core temperature [Tc; +0.5°C, +1.0°C, and heat tolerance (+1.5°C or +2.0°C)]. This was undertaken in able-bodied individuals only, using mean middle cerebral artery blood flow velocity (MCAvmean) as an index of CBF.
The purpose of Chapter 3 (first data Chapter) was to assess whether chronic tetraplegic SCI alters cerebrovascular function, in particular the brain’s capability to buffer changes in arterial blood pressure (termed dynamic cerebral autoregulation [CA]) and its responsiveness to changes in carbon dioxide (CO2; termed cerebrovascular reactivity). Dynamic CA gain and phase [as an index of the relative amplitude and latency of the relationship between arterial blood pressure and MCAv] were unaltered in all frequency ranges; however, the very-low frequency coherence (similar to correlation coefficient) of dynamic CA was reduced by ~21% in tetraplegia. Full MCAvmean reactivity was unchanged in tetraplegia, however its modulation was affected by tetraplegia in the hypercapnic range. Changes that were evident in dynamic CA coherence and during hypercapnia following chronic tetraplegia, may be indicative of cerebrovascular adaptation.
The purpose of Chapter 4 was to examine the roles of potential mediators of reductions in MCAvmean and orthostatic tolerance with increasing severity of thermal strain (elevations in Tc). The reduction in partial pressure of end-tidal CO2 (PETCO2) was able to account for all of the progressive reduction in MCAvmean with increasing Tc, whereas during superimposed orthostatic stress (LBNP-induced) the reduction in PETCO2 accounted for only one third of the reduction in MCAvmean at terminal MCAvmean. Of note, Tc did not influence the reductions in MCAvmean during asymptomatic-LBNP (i.e., no signs of syncope), indicating that the baseline reductions in MCAvmean with elevations in Tc are the major risk factor for orthostatic intolerance.
The purpose of Chapter 5 was to investigate whether the control of cardiorespiratory and cerebrovascular function is altered during PHS in chronic tetraplegic SCI. At matched elevations in Tc, reductions in PETCO2 were similar between tetraplegic and able-bodied individuals. However the majority of the tetraplegics’ cerebrovascular and cardiovascular variables were unresponsive to PHS to +1.0°C. Independent of group, dynamic CA and hypercapnic MCAvmean and cerebrovascular conductance reactivities were reduced. These findings indicate that PHS-induced elevations in sympathetic nervous activity (occurs in able-bodied individuals only) was not responsible for the reductions in dynamic CA and hypercapnic cerebrovascular reactivity.
The purpose of Chapter 6 was to assess whether the control of cardiorespiratory and cerebrovascular function during orthostasis is altered in chronic tetraplegic SCI at normothermia or due to PHS. During asymptomatic-LBNP, reductions in mean arterial blood pressure (MAP) were larger in tetraplegia than in able-bodied individuals. Despite this, reductions in MCAvmean were similar, indicative of maintained or improved static CA in tetraplegic SCI. The preliminary findings of the cerebrovascular and cardiorespiratory responses leading to pre-syncope indicate that with similar reductions in MAP, MCAvmean was higher in tetraplegic than in able-bodied individuals. Although the mechanisms are unclear, such a response may be viewed as an adaptation in static CA following chronic tetraplegia.
In conclusion, despite marked cardiovascular dysfunction with tetraplegia, it appears that cerebrovascular function during normothermic baseline and asymptomatic-LBNP may be compensated. Further research is required to confirm these findings and identify the mechanisms by which such changes may occur. During PHS, tetraplegics’ cerebrovascular and cardiorespiratory variables were largely unresponsive, and orthostatic tolerance was unaltered. Passive heat stress caused reductions in dynamic CA and hypercapnic MCAvmean and cerebrovascular conductance reactivities independently of group, indicating that such changes are not largely influenced by heat-induced increases in sympathetic nervous activity. In able-bodied individuals, heat-induced hypocapnia seems able to account for all of the reduced CBF with rising Tc, whereas the early and marked reduction in MAP may have a more prominent role in orthostatically-induced reductions in CBF.