Decoding Physiology With Muscle Oxygenation (SmO2)
The human body is a repository of physical patterns: heartbeats, muscle movements, neural activity, cyclic temperature changes, and more. These patterns contain information rich messages that can be excavated, refined, and decoded. To do so we need sophisticated tools and interfaces to effectively access and evaluate such information.
The multidisciplinary team and NNOXX has developed a novel wearable device that enables exercisers to collect and convert physical patterns into beneficial forms in order to gain insights into the human body and ultimately enhance performance.
The NNOXX Wearable: the world’s first device to non-invasively measure active nitric oxide, and other biomarkers of tissue metabolism, in the blood.
For example, the NNOXX wearable can assess two of the primary determinants of exercise capacity: oxygen delivery and oxygen utilization. Since the NNOXX biosensor uses a non-invasive optical technique to record its measurements it’s appealing for a wide range of training and competition scenarios.
Muscle oxygenation is a measurement of the percentage of total hemoglobin that is carrying oxygen in the capillaries of a muscle tissue and the subsequent transfer of oxygen to myoglobin, the oxygen carrying molecule located in said muscle. Muscle oxygenation is a localized oxygen saturation measurement that is influenced by muscle blood flow, exercise intensity, and alterations in hemoglobin’s oxygen dissociation curve. Muscle oxygenation is measured with a non-invasive optical technique that allows an exerciser to determine the relative amount of hemoglobin and myoglobin that are oxygen bound. The resulting muscle oxygenation measurement, called SmO2, is expressed as a percentage of a zero to one hundred scale.
It is important to note that muscle oxygenation is measured in the microvascular capillary beds whereas pulse oximetry which measures oxygen saturation in the arteries. While SmO2 and peripheral oxygen saturation, termed SpO2, are both measures of a tissue’s oxygenation level they are recorded in different regions of the circulation and as a result cannot be used interchangeably. For example, muscle oxygenation reflects the dynamic balance between oxygen delivery to the working muscles and oxygen consumption in the capillary beds of said muscles. Peripheral oxygenation on the other hand reflects the function of the pulmonary system, and as a result there are very small variations in SpO2 in healthy individuals.
The benefit of muscle oxygenation measurements is that they allow quantitative measurements to be made in the skeletal muscles, which provides a means for assessing two of the major determinants of exercise capacity: oxygen delivery and oxygen utilization. The non-invasive nature of muscle oxygenation measurements makes them appealing for use in dynamic environments and for activities of daily living.
A comparison of muscle oxygenation (SmO2) measurements recorded with the NNOXX wearable and a competing device during a 30-second sprint.
One of the key differentiating factors between NNOXX’s muscle oxygenation measurements and their competitors is that the NNOXX biosensor is capable of recording measurements at a greater frequency as compared with other muscle oximeters. This allows exercisers to see the full variation in the muscle oxygenation measurements on a muscle contraction by muscle contraction basis whereas competing devices cannot capture this variation. As a result, NNOXX’s biosensor device is the only one capable of quantifying the oxygen cost per muscle contraction.
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The primary function of skeletal muscle is to contract and produce movement of the joints, which is an incredibly energy intensive activity. As a result, the skeletal muscles demand a considerable amount of blood flow in order to provide oxygen and remove metabolic waste products in an efficient manner. The delivery of oxygen and removal of metabolic waste products is the responsibility of the circulatory system, which is laid out in a highly organized fashion with the muscle. Arterioles give rise to capillaries that run parallel to muscle fibers with each muscle fiber being surrounded by three to four capillaries.
At rest the skeletal muscle’s need for oxygen is minimal and as a result only a fourth of capillaries are open and actively perfused with blood. In contrast, during high intensity exercise all of the capillaries may be perfused with blood, which increases the total number of open and active capillaries surrounding muscle fibers. The arrangement of capillaries around individual muscle fibers and the ability to open capillaries when needed minimizes the distance that oxygen must travel when it diffuses into the skeletal muscle cell. This allows for an efficient exchange of gasses between blood in the microvascular capillaries and the muscle cells, especially when oxygen demand in the muscle is high.
During maximal effort full-body exercise muscle blood flow can increase by more than twenty fold above resting levels. Therefore, skeletal muscle has a very large flow reserve, which is made possible by alterations in blood vessel tone between resting and exercise conditions. At rest blood vessel tone is high, which limits skeletal muscle blood flow, and vice versa during exercise. Blood vessel tone at any moment is determined by the interplay between sympathetic vasoconstrictor activity, which decreases muscle blood flow, and metabolic vasodilator activity, which increases muscle blood flow. At rest vasoconstrictor activity dominates, leading to an increase in blood vessel tone, whereas metabolic vasodilator activity dominates during exercise, exerting the opposite effect. There are additional factors impacting blood flow as well, such as skeletal muscle contraction.
The blood flow response to skeletal muscle contraction depends on both the type and strength of muscle contractions. During rhythmic muscle contractions below 30% of an individual’s maximum voluntary contraction strength, blood flow decreases during the contractile period and increases during the relaxation periods between muscle contractions. When the force of a muscle’s contraction rises above 30% of maximum voluntary contraction strength, as is often the case during resistance training, it can lead to venous occlusion. During venous occlusion muscle blood volume will increase significantly since blood is capable of entering the muscle through the arterioles, but cannot leave the muscle through the venules and veins. As a result, blood pools in the capillary beds. If maximum voluntary contraction strength exceeds 70% an arterial occlusion can occur, which means both arterial inflow and venous outflow are restricted. In this case oxygenated blood cannot enter the muscle, nor can metabolic waste products leave the muscle.
In addition to mechanical factors impacting muscle blood flow, there are also local metabolic mechanisms that are responsible for dilating skeletal muscle blood vessels during exercise. For example, when blood flow is compromised during sustained high force muscle contractions, muscle oxygen saturation will plummet and the tissue will become hypoxic. Tissue hypoxia then provides a signal for the blood vessels to dilate. The precise mechanism for how tissue hypoxia induces vasodilation is complex and involves an acute increase in interstitial adenosine and potassium ions upon the start of muscle contraction, followed by endothelial nitric oxide release and red blood cell mediated active nitric oxide release, among other factors such as dissolved carbon dioxide. Collectively, these factors that increase muscle blood flow during exercise make up the active hyperemic response.
Until recently it was not possible to differentiate between the neural, mechanical, metabolic regulators of muscle blood flow with a wearable device. The previous generation of muscle oximeters do not measure blood flow directly. Instead, they measure a surrogate measure called total hemoglobin, or THb short.
Total hemoglobin is a measure of muscle blood volume, not blood flow, which poses a number of challenges. For example, during exercise you the aforementioned muscle oximeters will display a simultaneous decrease in muscle oxygenation and an increase in total hemoglobin. Because these devices measure blood volume, and not blood flow, it’s not possible to discern if that increase in blood volume is due to venous occlusion, hypoxic vasodilation, or some combination of the two. Similarly, if total hemoglobin goes down during exercise they cannot discern whether that is due to a compression of blood vessels during muscle contraction, sympathetic vasoconstriction, or a left shift in hemoglobin dissociation curve from over-expelling carbon dioxide.
In order to differentiate between the various factors that regulate muscle blood flow NNOXX has developed a novel measure of active nitric oxide release called personal nitric oxide, or PNO for short.
An athlete’s PNO level during a ~45 second all-out bike sprint.
PNO is a dynamic measurement of active nitric oxide release from the red blood cells during exercise. To fully appreciate the range of applications for measuring an individual’s PNO level it’s important to understand the varying roles that active nitric oxide and S-nitrosothiols play in human biology, which will be the topic of a future article.
