Abstract
We determined the response characteristics and functional correlates of the dynamic relationship between the rate (Δ) of oxygen consumption ( <img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1188">O2) and the applied power output (work rate = WR) during ramp-incremental exercise in patients with mitochondrial myopathy (MM). Fourteen patients (7 males, age 35.4 ± 10.8 years) with biopsy-proven MM and 10 sedentary controls (6 males, age 29.0 ± 7.8 years) took a ramp-incremental cycle ergometer test for the determination of the <img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1189">O2 on-exercise mean response time (MRT) and the gas exchange threshold (GET). The Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1190">O2/ΔWR slope was calculated up to GET (S1), above GET (S2) and over the entire linear portion of the response (S T). Knee muscle endurance was measured by isokinetic dynamometry. As expected, peak <img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1191">O2 and muscle performance were lower in patients than controls (P < 0.05). Patients had significantly lower Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1192">O2/ΔWR than controls, especially the S2 component (6.8 ± 1.5 vs 10.3 ± 0.6 mL·min-1·W-1, respectively; P < 0.001). There were significant relationships between Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1193">O2/ΔWR (S T) and muscle endurance, MRT-<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1194">O2, GET and peak <img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1195">O2 in MM patients (P < 0.05). In fact, all patients with Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1196">O2/ΔWR below 8 mL·min-1·W-1 had severely reduced peak <img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1197">O2 values (<60% predicted). Moreover, patients with higher cardiopulmonary stresses during exercise (e.g., higher Δ ventilation/carbon dioxide output and Δ heart rate/Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1198">O2) had lower Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1199">O2/ΔWR (P < 0.05). In conclusion, a readily available, effort-independent index of aerobic dysfunction during dynamic exercise (Δ<img border=0 width=11 height=13 src="548_files/image001.gif" v:shapes="_x0000_i1200">O2/ΔWR) is typically reduced in patients with MM, being related to increased functional impairment and higher cardiopulmonary stress.
Highlights
The rate (Δ) of change in oxygen consumption ( O2) relative to power output during rampincremental exercise depends on the ability of the cardiocirculatory system to deliver, and the muscle capacity to extract, O2 from arterial blood [1,2]
This study has provided novel evidence that a readily available index of “aerobic efficiency” during ramp-incremental cycle ergometer exercise (Δ O2/ΔWR) is typically reduced in patients with Mitochondrial myopathy (MM), in the supra-gas exchange threshold (GET)
The Δ O2/ΔWR was associated with worsening maximal and submaximal ( O2GET) markers of aerobic impairment and reduced peripheral muscle performance
Summary
The rate (Δ) of change in oxygen consumption ( O2) relative to power output (work rate, WR) during rampincremental exercise depends on the ability of the cardiocirculatory system to deliver, and the muscle capacity to extract, O2 from arterial (capillary) blood [1,2]. For instance, have shown that a flatter-than-normal Δ O2/ΔWR is a sensitive marker of abnormal O2 delivery and utilization in a number of systemic pathological conditions ranging from congestive heart failure to systemic lupus erythematosus [6-11]. Mitochondrial myopathy (MM) is the collective term for disease conditions in which the diminished rate of cellular O2 utilization may place a burden on several systems in order to enhance O2 uptake and delivery [13-15]. Patients with MM commonly present hyperventilatory and hypercirculatory patterns of response to dynamic exercise [16-20]. These abnormalities are likely to be related to the fundamental pathophysiological abnormality in MM, i.e., impaired O2 extraction.
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