The cardiovascular system is comprised of the heart, arteries, veins, capillaries and blood. This dynamic system includes complex interactions of mechanical, neural and humoral factors in both the central and peripheral arteries in response to short- and long-term changes via external stimuli. Alterations to the cardiovascular system, via structural and functional adaptations, play essential roles especially when the system is faced with physiological stresses such as physical activity and exercise training.
Many Canadian researchers have made significant contributions to the advancement of knowledge surrounding cardiovascular function, thereby leading to novel strategies to assess, understand, and influence the cardiovascular system as it relates to various stimuli including exercise, disease, and aging. This short synopsis will highlight the advancements in knowledge related to cardiovascular function made by Canadian
researchers with specific considerations for the understanding of the impact of varying exercise intensities and training modalities on cardiovascular function.
Cardiovascular function and blood flow
Prominent early research contributions to the understanding of cardiovascular function made by Canadians included determinations of the role of blood flow in limiting maximal metabolic rate. Jack Barclay performed this seminal investigation and discovered that maximal skeletal muscle metabolic rate and contractile performance were limited by blood flow in the canine gastrocnemius muscle (Barclay, 1975). Barclay would later confirm this finding in the mid 1980s via an oxygen delivery-independent blood flow effect on skeletal muscle fatigue (Barclay, 1986). It was discovered that increased blood flow, or hyperperfusion, of the stimulated muscles decreased fatigue by a mechanism independent of increased oxygen delivery. This led Barclay to question the mechanism responsible. At a similar time, Norman Gledhill wrote an interesting piece on the influence of changing blood volume on aerobic performance (Gledhill, 1985). The idea was that changes in blood volume could affect maximal aerobic performance through changes in cardiac output, and alterations in hemoglobin concentration could affect arterial oxygen content. In 1991, Barclay postulated that free radicals contributed to fatigue in oxidative skeletal muscle, suggesting perhaps that increases in blood flow could sequester free radicals (Barclay, 1991), while increases in blood volume and hemoglobin concentration would increase the amount of oxygen available for the exercising muscle (Gledhill, 1985).
These early studies examining the links between skeletal muscle blood flow and metabolic rate have provided the foundation for many interesting and impactful lines of research. In 1996, Richard Hughson led a series of studies examining the impact of muscle blood flow increases on muscle oxygen uptake at the onset of exercise (Hughson,1996). In the same year, trainees of Hughson, Michael Tschakovsky and Kevin Shoemaker, published research on the effect of vasodilation as it contributed to immediate exercise in humans and day-to-day repeatability of measuring forearm blood flow via ultrasonography during exercise, respectively (Tschakovsky, 1996; Shoemaker, 1996). Not only were Canadians interested in blood flow patterns of exercising skeletal muscle, but Marc Poulin examined the importance of cross-sectional area and blood flow patterns of the middle cerebral artery under reduced oxygen and increased carbon dioxide exposures (Poulin, 1996).
A year later, in 1997, Shoemaker added to Barclay’s findings about mechanisms related to blood flow to the exercising musculature (Shoemaker,1997). From this study it was discovered that neither acetylcholine nor nitric oxide were essential to the magnitude of the exercise response, as blood flow to the exercising forearm was unaffected when both substrates were blocked; however brachial artery diameter remained the same. Only resting blood flow was affected by the blocking of acetylcholine and nitric oxide. This led Shoemaker to conclude that a different cholinergic mechanism may be responsible for maintaining the hyperemic response during exercise. At the microvascular level, Coral Murrant was investigating the effects of both oxygen and nitric oxide on the intracellular oxidant status of skeletal muscle (Murrant, 1999). Murrant also employed advanced in situ animal models to examine muscle metabolism and muscle blood flow at the microvascular level during muscle contraction (Murrant, 2000).
Important findings from Murrant’s publications indicate that capillaries are capable of responding to stimuli in their immediate environment and are able to communicate with arterioles in close proximity. In the early 21st century, Kyra Pyke and supervisor Michael Tschakovsky examined the impact of controlling blood flow rates on the dilatory response of the brachial artery (Pyke, 2004). From this study they discovered the importance of controlling the shear rate stimulus when examining endothelial-dependent flow-mediated vasodilation between groups who differ in baseline brachial artery diameter. Again in 2004, Tschakovsky tested the hypothesis that rapid arterial vasodilation was proportional to contraction intensity at the onset of forearm exercise (Tschakovsky, 2004).
The results of these studies showed that immediate increases in forearm blood flow were proportional to contraction intensity from 5 to 70% of maximal voluntary contraction during the forearm exercise. The results of these detailed stimulus response studies supported the existence of a fast-acting vasodilatory mechanism once forearm exercise was initiated. It is evident that the early work of Barclay initiated a line of research where Canadian researchers continue to advance the knowledge about relationships between blood flow patterns and oxygen utilization in skeletal muscle as well as blood flow patterns and cerebrovascular function.
Cardiovascular function in clinical populations
Around the same time Canadians began to examine the effects of blood flow patterns on skeletal muscle, other researchers were interested in investigating cardiovascular function in various populations (i.e. clinical, aging). David Cunningham led a study in which he had unfit women (mean age 31 years) participate in a 9-week exercise training program and a subsequent 52-week program. Stroke volume increased by 28% while
exercising at 80% of maximal oxygen consumption after the 9-week program with peripheral adaptations occurring during the longer (i.e. 52-week) program (Cunningham, 1975). Shortly after, Donald Paterson, with David Cunningham and Norman Jones, examined the effects of exercise training on cardiovascular function in individuals who previously had experienced a myocardial infarction (Paterson, 1979). The patients performing high intensity exercise training experienced training-related increases in maximal oxygen uptake and stroke volume and reductions in heart rate at each work level in comparison to those in the low intensity training group. Paterson also published a seminal review of the effects of aging on the cardiorespiratory system (Paterson, 1992) in which he concluded that, despite the losses in absolute exercise capacity
inherent with aging, the ability to sustain a high intensity of aerobic exercise relative to age is preserved and that cardiorespiratory training in older men and women is effective in increasing maximal oxygen consumption. Scott Thomas, in 1993, examined cardiac output and left ventricular function in
response to exercise in older men (Thomas, 1993). In contrast to previous research in older participants, Thomas and colleagues found only small losses in cardiovascular response and left ventricular performance during light through strenuous exercise. Jack Goodman investigated the central and peripheral adaptations in post-coronary artery bypass surgery patients following twelve weeks of exercise training (Goodman, 1999). These findings suggested a significant improvement in maximal oxygen consumption after training accompanied by an increase in ejection fraction. Fast-forwarding to the 21st century, Canadian researchers including Victoria Claydon, Philip Millar, Mark Haykowsky, Darren Warburton, Don McKenzie and Cheri McGowan continued to investigate the role of cardiovascular function in various clinical populations; these included heart failure patients (Haykowsky, 2007), hypertensives (McGowan, 2006; Millar 2007), patients receiving transplants (Warburton, 2004), patients with chronic obstructive pulmonary disease (McKenzie, 2003) and patients with syncope (Claydon, 2004).
Cardiovascular function and exercise
The combination of cardiovascular function and exercise training has been a topic of interest for many Canadian researchers for many years. Within this topic is the ongoing debate of whether stroke volume plateaus during exercise of increasing intensity. This idea was attributed mostly to a decrease in the diastolic filling time as a result of increasing heart rate that occurs during increasing exercise intensity. Gledhill and colleagues were the first to acknowledge a difference in the stroke volume response to exercise between trained and untrained individuals (Gledhill, 1994). They proposed that enhanced diastolic filling with enhanced myocardial contractility were responsible for the increased stroke volume in trained persons. Gledhill also found that ventricular ejection times were longer, diastolic filling times were shorter, and blood volumes were higher in trained individuals compared to untrained (Gledhill, 1994). Warburton also added to this debate, discovering that stroke volume was elevated after plasma volume expansion, proposing that blood volume has an impact on the stroke volume response to exercise (Warburton, 1999).
In 1985, Norman Jones led studies that compared single-breath and carbon dioxide rebreathing techniques when examining cardiac output during exercise (Inman, 1985). Jones and colleagues discovered that the single-breath method significantly underestimated cardiac output values when compared to carbon dioxide rebreathing (Inman, 1985). Robert McKelvie, with Jones, followed this research by measuring cardiac output in non steady-state exercise with the carbon dioxide rebreathing technique (McKelvie, 1987). The work conducted in 1987 validated the carbon dioxide rebreathing method as an accurate and reproducible technique to measure cardiac output during progressive exercise tests with similar values at comparable oxygen consumption to those obtained in the steady-state. Much more research was performed in this area towards the beginning of the 21st century; for example Marc Poulin used ultrasound to assess blood flow of the cerebral artery during exercise in humans (Poulin, 1999).
Other Canadian researchers who have contributed to significant advances in the area of exercise and cardiovascular function include Robert Boushel, Darren Warburton, Mark Rakobowchuk, Darren Delorey and Michael Strickland. Specifically, Robert Boushel and colleagues were the first to use near-infrared spectroscopy (NIRS) in combination with tracer indocyanine green (ICG) to measure regional tissue blood flow (i.e. in calf muscle) during exercise in humans (Boushel, 2000). It was concluded that this technique (NIRS + ICG) might be useful for determining regional blood flow due to its highly spatial and temporal resolution.
Warburton and colleagues, in 2004, examined the effects of 12 weeks of either interval versus continuous exercise training on cardiorespiratory function and training-induced blood volume (i.e. hypervolemia) on aerobic power and left ventricular function. They concluded that 12 weeks of either modality of exercise resulted in similar improvements in aerobic power and left ventricular function, with training-induced hypervolemia accounting for nearly 50% of the changes in aerobic power after training (Warburton, 2004).
Again, comparing two different training modalities, Mark Rakobowchuk, under the supervision of Maureen MacDonald, looked at the effects of 6 weeks of sprint interval versus traditional endurance training on improving peripheral arterial stiffness and popliteal artery flow-mediated dilation in healthy humans. This study found that both low-volume sprint interval training (4-6 30 second “all-out” Wingate tests, 3 days/week) and high-volume endurance training (40-60 minutes of cycling at 65% of peak oxygen uptake, 5 days/week) resulted in similar improvements in peripheral arterial structure and function (Rakobowchuk, 2008). Michael Strickland, under the supervision of Mark Haykowsky, investigated whether fitness level affected the cardiovascular response to exercise. Healthy male participants were categorized into either low or high aerobic power groups. It was discovered that, compared to the less fit group, subjects with higher aerobic power had lower left ventricular filling pressures during exercise, suggesting superior diastolic function and compliance (Strickland, 2006). Darren Delorey, with Kevin Shoemaker and John Kowalchuk and under the supervision of Don Paterson, examined the effect of hypoxia on pulmonary oxygen uptake, leg blood flow and muscle deoxygenation during knee extension exercise. It was discovered that leg blood flow was 35% higher during a hypoxic state, resulting in a similar leg oxygen delivery between hypoxic and normoxic states.
Therefore it was concluded that oxygen delivery was not responsible for decreased oxygen uptake during the onset of exercise during hypoxia (Delorey, 2004). Thus, Canadian researchers have made significant advancements in the field of cardiovascular function and its relationship to exercise and different training modalities.
Contributions by these Canadian scientists to the advancement of research in the area of cardiovascular function during exercise and with exercise training are well documented. Equally important are the continuing contributions of their trainees to this dynamic field of research.
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