Ischaemic exercise test
This test is useful in the differential diagnosis of metabolic causes of muscle weakness, fatigue and cramps eg disorders of glycolysis and myoadenylate deaminase. These disorders should be considered in all children who complain of muscle cramps and exercise intolerance.
There are anecdotal reports of the development of rhabdomyolysis if patients with underlying acquired (eg alcoholic or hypothyroid) or inherited myopathies are strenuously exercised.
Principle of the test:
Normal subjects will exhibit a rise in both lactate and ammonia during ischaemic exercise. Glycolysis only proceeds to lactate during ischaemic exercise since oxygen is required for further metabolism in the TCA cycle. Ammonia rises as a result of amino-acid deamination by myoadenylate deaminase to provide substrates for the TCA cycle. Intact pathways are required for such rises in lactate and ammonia.
This test will be painful to perform and the subject will need encouragement to ensure that sufficient exercise is performed for a valid test.
The subject should rest for 30 min prior to the test.
- 6 lithium heparin tubes for Ammonia
- 6 special tubes for lactate (discuss with lab)
- Ice for sample transport
At each time point samples should be taken for lactate (1 mL) and ammonia (1 mL). The tubes for ammonia should be kept on ice and transported to the laboratory a.s.a.p.
- A sphygmomanometer cuff is placed on the upper arm and an intravenous cannula inserted in the antecubital vein which should be kept patent with heparinised saline.
- A baseline blood sample is drawn from the occluded arm.
- The cuff is inflated above systolic pressure and the subject should squeeze the sphygmomanometer bulb once every few seconds for 2 minutes. It is essential that the exercise should continue to produce muscle pain and that the fingers are extended fully between contractions. Patients may find it helpful and encouraging to be advised of the time they have exercised.
- The cuff is deflated.
- Further bloods are taken from the occluded arm 1, 2, 3, 5 and 7 min after deflating the cuff.
Normal subjects obtain relatively instantaneous relief of pain and can move their fingers immediately on release of the cuff. Patients with metabolic defects often cannot exercise for 2 minutes, develop an marked forearm contracture, and are unable to extend their fingers.
A normal response is shown by maximum rises (between baseline and peak values) in both plasma lactate > 2.2 mmol/L and in plasma ammonia > 70 µmol/L. An adequate increment in one analyte alone does not exclude disease. A failure of both lactate and ammonia to rise suggests that the subject did not exercise adequately and the test should be repeated. The absence of a venous lactate response to ischaemic exercise is characteristic of all diseases in which there is an impairment in the conversion of glycogen to glucose or lactate in muscle. The absence of a rise in ammonia with a normal lactate rise is characteristic of myoadenylate deaminase deficiency.
Sensitivity and specificity:
Failure of lactate to rise after this test confirms a diagnosis of a disorder of glycolysis but this test cannot be used to exclude partial expression of these diseases.
- Coleman RA, Stajich JM, Pact VW, Pericak-Vance MA. The ischemic exercise test in normal adults and in patients with weakness and cramps. Muscle & Nerve 1986;9:216-221.
- Kanbe K, Nagase M, Udagawa E. Acute alcoholic rhabdomyolysis associated with abnormal ischemic exercise test. Muscle & Nerve 1993;16:1269-1270.
- Riggs JE. Acute exertional rhabdomyolysis in hypothyroidism: the result of a reversible defect in glycogenolysis. Militar Med 1990;155:171-172.
- Taylor RG, Lieberman JS, Portwood MM. Ischemic exercise test: failure to detect partial expression of McArdle's disease. Muscle & Nerve 1987;10:546-551.
JHB 4 July 2010