Author(s)
Emmanuel Ako, Nathaniel Barber, Grzegorz T. Kowalik, Jennifer Steeden, John Porter, John Walker, Vivek Muthurangu
Date
2016-04-05
Source
https://jcmr-online.biomedcentral.com/articles/10.1186/1532-429X-18-S1-O69

Background:
Exercise intolerance is a common feature of many diseases. The causes are difficult to determine and often multifactorial,
including secondary cardiac-respiratory dysfunction, as well as skeletal muscle abnormalities. We have developed MR augmented
cardiopulmonary exercise testing (CPET) that allows simultaneous evaluation of cardiac output, estimate mean pulmonary artery pressures
and tissue oxygen extraction in addition to conventional CPET measures. To demonstrate the utility of this technique we performed MRCPET on patients with sickle cell disease (SCD). The aim of this study was to demonstrate that MR-CPET could be used to define the
physiological factors associated with their poorly understood exercise intolerance.

Methods:
14 patients with homozygous sickle cell disease (age: 35.3, 30-41 yrs) and 14 healthy ethnic matched volunteers (age: 30.8,
25-37 yrs) underwent MR-CPET. Exercise was performed on MR-compatible ergometer (Lode, The Netherlands) and VE, VO2, and VCO2
were assessed using a respiratory gas analyser (Ultima, MedGraphics, USA). Aortic flow and septal curvature ratio (an index of mean
pulmonary artery pressure) were measured during exercise. MR data was used to derive CO, HR, SV and Septal Curvature Ratio (SCR)
during exercise. Tissue oxygen extraction was calculated using the Fick principle.

Results:
Peak VO2 (0.7±0.2 vs 1.1±0.3 L/min, p<0.001), CO (12±1.4 vs 13±1.3 L/min, p<0.05), SCR (0.6±0.1 vs 0.8±0.1, p<0.001)
and tissue oxygen extraction (0.51±0.13 vs 0.90±0.19 mlO2/mlBlood, p<0.001) were all significantly lower in SCD patients compared to
controls.

Conclusions:
Using MR-CPET we have been able to show for the first time that exercise intolerance in SCD is due to reduced skeletal
muscle oxygen extraction and increased pulmonary pressures during exercise. This may be due to vascular network rarefaction,
muscle and lung fibrosis, or reduced mitochondrial function; all of which have been demonstrated in histology specimens in SCD. This
demonstrates the power of MR-CPET and we believe this technique could aid in better understanding of exercise intolerance and possibly
better therapeutic interventions.

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