Hot and heavy volume loading in the heat-stressed, haemorrhagic male: modulating the Frank–Starling curve

The Frank–Starling mechanism is a fundamental concept in understanding cardiovascular physiology. The ability of the heart to alter its contractile response to different volume loading stimuli enables the body to respond to numerous perturbations including exercise, hypohydration, and orthostatic challenges which can initiate both gradual and rapid shifts in central blood volume.

Lower-body negative pressure (LBNP) is an innovative technique commonly employed in research studies to non-invasively alter central blood volume. Although its development facilitated the examination of post-spaceflight physiological challenges, recent research has found great benefit in this technology for modulating cardiovascular haemodynamics for military trauma care and environmentally induced changes in cardiac stress. Graded LBNP promotes venous pooling in the lower extremities. This leads to reductions in central blood volume and thus stroke volume, with a compensatory increase in heart rate (Cooke et al. 2004). Lower central blood volume is further exacerbated in situations of heat stress; however, the effects of volume loading on the classic Frank–Starling relationship between stroke volume and left ventricular filling pressure have not been thoroughly examined. To date, LBNP cold stress studies have demonstrated stroke volume can be maintained, potentially modulating the Frank–Starling mechanism as a result of increased afterload (Cui et al. 2005). Together, these findings clearly illustrate that an individual's thermal status directly influences the heart's operating point on the Frank–Starling curve, as cold stress shifts the operating point towards the flatter section and heat stress causes a shift to the steeper section.

In a recent issue of The Journal of Physiology, Bundgaard-Nielsen et al. (2010) investigated the effect of volume loading on the Frank–Starling mechanism in heat-stressed males with reduced central blood volume (via LBNP). The authors hypothesized that artificially increased circulating volume in heat-stressed individuals would change the operating point to a flatter segment of the Frank–Starling curve, thus attempting to normalize the cardiovascular physiological response. In effect, the heat-stressed and normothermic individuals would respond similarly as volume loading would attenuate the decline in stroke volume for any given reduction in left ventricular filling pressure. To test this hypothesis, eight healthy male volunteers participated in all of the following study conditions: (1) normothermia, (2) whole-body heating, and (3) whole-body heating with volume loading. Participants were fitted with a water-perfused suit and placed in the supine position in the lower body negative pressure (LBNP) chamber. A minimal LBNP stimulus of 15 mmHg, immediately followed by 30 mmHg, was implemented. During each condition, right heart catheterization enabled the direct assessment of pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and stroke volume (via thermodilution). In the final condition, intravascular volume loading was completed with the administration of saline and a synthetic colloid. A strength of this study design was that it enabled all participants to act as their own controls while the Frank–Starling mechanism was modulated by thermal stress and volume loading.

Interestingly, the LBNP stimulus elicited a larger decrease in the stroke volume to PCWP ratio during heat stress relative to normothermia. However, volume loading during heat stress normalized the stroke volume to PCWP ratio during LBNP, thus producing results similar to the normothermia condition. These study findings support previous research suggesting that impaired blood pressure regulation during simulated haemorrhage in heat-stressed males is modulated by the Frank–Starling mechanism. More importantly, this novel study expanded upon previous research by revealing that volume loading can actually correct impaired blood pressure regulation associated with the Frank–Starling mechanism. Central blood volume expansion shifted the operating point to a flatter segment of the curve, thereby preserving stroke volume and cardiac output.

An alternative hypothesis may also be responsible for the findings observed in the current study. The application of LBNP similarly reduced mean arterial pressure in all three conditions, including the normothermia, whole-body heating, and whole-body heating with volume loading condition. Volume loading did not protect against the reduction in mean arterial pressure, which is surprising as we anticipated an absolute increase in pressure following this final condition. Nevertheless, Bundgaard-Nielsen et al. (2010) suggested that while the decrease in mean arterial pressure and increase in systemic vascular resistance may provide an alternative explanation for their observed shift in the Frank–Starling curve due to heat stress, a combination of increased contractility with reduced afterload is likely to be responsible.

The authors elegantly examined possible changes in one of the most rudimentary cardiovascular physiology concepts, the Frank–Starling mechanism, and have left the intriguing possibility of follow-up studies, including: (1) the acute versus chronic Frank–Starling response to heat stress and volume loading, (2) the influence of cardiovascular fitness and sex differences, (3) the relative contribution of contractility and blood pressure in modulating the Frank–Starling curve, and (4) the influence of cold stress with or without volume loading on the Frank–Starling mechanism.

This study examined the modulation of the Frank–Starling curve during an acute bout of whole-body heating with volume loading. We were specifically interested in this novel finding and wondered whether chronic bouts of heat stress, which firefighters and military personnel typically encounter, elicit an adapted physiological response akin to heat training in the exercising human. While this question warrants future investigation, a recent Journal of Physiology article by Green et al. (2010) revealed that repeated thermal heat stress was a key physiological stimulus for enhancing microvascular vasodilator function; therefore, we hypothesize that the current study findings may be further exacerbated in those humans who experience chronic bouts of heat stress.

Whether current study findings can be generalized to other populations, including highly trained males and females, remains unclear. Undoubtedly, the current study findings have practical implications for highly trained individuals who are often exposed to thermal stress, including military personnel and firefighters. In fact, previous research has indicated that orthostatic intolerance and heat stress may be altered by cardiovascular fitness with highly trained individuals experiencing greater intolerance. This relationship is likely to be due to a greater decline in stroke volume, attenuated carotid baroreflex responsiveness during conditions of reduced central blood volume, and diminished reactivity of blood vessels to sympathetic stimulation. Therefore, the inclusion of both untrained and highly trained individuals would have further expanded our understanding of orthostatic intolerance and volume loading during heat stress. Surprisingly, females were also excluded from the current study despite previous work identifying that females exhibit greater orthostatic intolerance due to adrenergic responses and/or decreased cardiac filling. Whether sex differences modulate the relationship between heat stress, stroke volume, and left ventricular filling pressure warrants follow-up studies.

The current study suggested that a combination of both increased contractility and decreased afterload are responsible for the leftward shift in the Frank–Starling curve. Clinically, it would be interesting to examine the relative contribution of increased contractility and reduced afterload in modulating the Frank–Starling curve among different heat stressed populations, including the response of those individuals with impaired blood pressure regulation. In this case, it is unclear whether heat stressed individuals with high blood pressure would have a compromised Frank–Starling curve response.

The modulation of the Frank–Starling mechanism under different environmental conditions also remains unclear. In particular, normothermia with volume loading would enable the authors to clearly differentiate the effects of thermal stress from volume loading. This increase in circulating volume may have been able to attenuate reductions in cardiac output typically observed from LBNP and further thermal stress induced reductions in central volume. Previous studies examining the cardiovascular response to LBNP have also included cold stress to modulate the Frank–Starling mechanism. In fact, the authors of the current study have previously investigated the effects of skin-surface cooling on cardiovascular dynamics. They have demonstrated significantly reduced cardiac output compared to the normothermia condition; however, the reduction in CVP was attenuated compared to normothermia (Cui et al. 2005). These findings indicate that the maintenance of CVP is a key mechanism to maintain cardiac function during reductions in central blood volume.

Finally, we commend the authors of this current study on their ability to show a physiologically relevant change in the Frank–Starling curve with a low LBNP stimulus and volume loading. Specifically, current study findings evolved from lower LBNP stimuli levels than previous work as the authors cited significant orthostatic intolerance with greater stimuli. Greater LBNP stimuli may have elicited even greater reductions in the stroke volume to PCWP ratio, and as a result, perturbed the Frank–Starling curve to a steeper operating point.

In conclusion, findings from Bundgaard-Nielsen et al. (2010) provide novel evidence that the Frank–Starling mechanism is tightly modulated by central blood volume expansion, especially in heat stressed males. These novel findings should be further substantiated in follow-up studies with other populations and additional environmental factors.