ACTUACIÓN ANTE SOSPECHA O CONFIRMACIÓN DE CASOS EN EL CENTRO

As the metaboreflex has evolved to sense the need to increase oxygen delivery to skeletal muscle, it follows that it must be a product of muscle metabolism that stimulates the metaboreceptors. What that metabolic stimulus is has been a source of much debate. Rotto & Kaufman attempted to address this question in a cat model through the intra-arterial injection of exogenous substances believed to be the metabolic products of muscular contraction. Substances used were chosen on the basis of studies looking at contraction of skeletal muscle and which metabolites are elevated in the venous outflow of working muscle. Only lactic acid and arachidonic acid had excitatory actions on the discharge of group III and IV afferents innervating the triceps surae muscle. Lithium, sodium lactate and adenosine did not have a substantial effect. Further work by the same group suggested that arachidonic acid potentiates the responses of group III muscle afferents to static contractions, probably through increased sensitivity of the mechanoreflex. Indomethacin and aspirin, both inhibitors of cyclo-oxygenase, appear to attenuate the response of group IV afferents to static contraction , and the prostaglandins PGE2 and PGF1α in effluent blood from exercised muscle haven been shown to correlate with metaboreflex activity in patients with heart failure . Adenosine has also been implicated in the generation of the metaboreflex in patients with heart failure: caffeine, an adenosine receptor antagonist, attenuates the rise in muscle sympathetic nerve activity (MSNA) with isometric handgrip exercise . The role of interstitial potassium, as suggested by Wildenthal et al and Rybicki et al has been called into question following experiments on humans documenting the lack of correlation between venous potassium from the exercising forearm and MSNA

response during static and dynamic handgrip exercise . A recent review promoted the idea that ATP could be important in evoking the metaboreflex .

Hydrogen ion and the development of acidosis within skeletal muscle are thought to stimulate the metaboreflex. Hydrochloric acid injected into the arterial supply of triceps surae of the cat increases heart rate, blood pressure and ventilation . Equimolar lactic acid had an even more potent effect on cardiorespiratory reflexes, though injection of sodium lactate at neutral pH did not have any effect. Lactic acid is a metabolite of anaerobic glycolysis, so it would make sense that it has a part to play in the generation of a signal that more oxygen is required. With the advent of 31_{P Nuclear} Magnetic Resonance Spectroscopy (31_{P NMR), it has become possible to test this} hypothesis on humans. Victor et al asked 11 healthy human volunteers to perform static and rhythmic handgrip exercise whilst recordings of 31_{P NMR spectra and MSNA} were made. During the first 2 minutes of exercise, ADP increased and PCr/Pi (ratio of phosphocreatine to inorganic phosphate) declined with no change in pH or MSNA. During the 3rd _{and 4}th _{minutes of exercise, there was little further change in PCr/P}

i, but pH decreased. MSNA increased progressively as pH decreased, suggesting that the development of acidosis is a potent stimulant of MSNA. Prolonged bouts of rhythmic handgrip exercise at a low workload, however, can lead to a progressive rise in MSNA without the development of significant muscle acidosis , suggesting that the mechanoreflex is perhaps more important in this setting.

Interesting insight into the role of lactic acid and acidosis has been gained from a group of patients with McArdle’s disease, who do not produce lactic acid due to a hereditary deficiency of myophosphorylase. Even this has proven to be controversial. Pryor et al

found that there was an abnormal MSNA response to static handgrip exercise in patients with McArdle’s disease, and Fadel et al produced similar results, whilst demonstrating that the MSNA response to other reflex stimuli (for example the cold pressor test) is intact. These data suggest that the glycogenolytic pathways are necessary for metaboreflex-mediated sympathoexcitation to occur during static exercise in humans. This is contradicted by the work of Vissing et al , who found that patients with McArdle’s disease had a normal MSNA response to static handgrip exercise to fatigue, despite muscle pH not falling with exercise as happened in the healthy control subjects. They also studied one patient with mitochondrial myopathy, who developed a profound muscle acidosis with exercise, but did not have an enhanced MSNA response to exercise. It could be argued that MSNA in patients with McArdle’s disease is stimulated by an increase in central command or mechanoreflex activation, though if this were the case, an immediate increase in MSNA would be expected: the time course of the MSNA response to exercise more closely resembles that of a metaboreflex mediated increase in MSNA. Further work by the same group looking at post-exercise muscle ischaemia, which causes prolonged metaboreceptor activation, found that metaboreflex activity was normal in this group despite a failure to produce lactate . Finally, it was noted in one study on healthy human volunteers that muscle pH continued to fall after cessation of exercise, whereas MSNA, heart rate and blood pressure all rapidly returned to baseline : this was taken as evidence that intramuscular acidosis is not the sole factor driving cardiovascular responses to exercise.

1.2.4 The function of the muscle metaboreflex: whole body versus small muscle