How does hyperventilation cause coronary vasospasm?

Hyperventilation may be an important cause of coronary vasospasm and chest pain. 1 The mechanism likely revolves around the competition between the effects of hydrogen and calcium ions on the smooth muscle of coronary arteries. 2

Respiratory alkalosis induced by hyperventilation causes a reduction of hydrogen ions which, under physiologic conditions, compete with calcium ion, an important trigger for arterial smooth muscle contraction. Lower hydrogen ion concentrations tips the balance in favor of calcium’s effects on transmembrane channels and myofibrillar ATP-ase of the smooth muscle and causes vasoconstriction.2

In fact, hyperventilation has been used to reproduce coronary spasm during angiography in patients with non-obstructive coronary artery disease and angina symptoms.The efficacy of hyperventilation in inducing an alkalotic state during this test is verified by obtaining an arterial blood gas after 6-minutes of hyperventilation.  A basic Tris-buffer to enhance alkalotic provocation was also used in earlier studies. 2

In addition to producing spasm and angina, hyperventilation-induced alkalosis has been associated with frank transmural myocardial infarction and ischemia-related arrhythmias such as ventricular tachycardia. 2,4,5

So in the appropriate context, hyperventilation may not be so benign!


  1. Freeman LJ, Nixon PGF. Chest pain and the hyperventilation syndrome-some aetiologic considerations. Postgrad Med J 1985;61:957-61.
  2. Yasue HM, Nagao S, Omote A, et al. Coronary arterial spasm and Prinzmetal’s variant form of angina induced by hyperventilation and Tris-buffer infusion. Circulation 1978;58:56-62.
  3. Zaya M, Mehta PK, Merz NB, etal. Provocative testing for coronary reactivity and spasm. J Am Coll Cardiol 2014; 63:103-9.
  4. Magarian GJ, Jones S, Calverley T. Hyperventilation testing for coronary vasospasm: induction of spontaneous ventricular tachycardia in association with transmural ischemia without obstructive coronary disease. 1990; 120:1447-49.
  5. Chelmowski MK, Keelan MH. Hyperventilation and myocardial infarction. Chest 1988;93:1095-96.

Contributed by Ramya Chitra Mosarla, Medical Student, Harvard Medical School

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How does hyperventilation cause coronary vasospasm?

My patient with a recent fall has a low serum 25 (OH) D level. Can vitamin D (VD) deficiency be associated with falls?

Short answer: Yes! Although the essential role of VD in calcium homeostasis and bone health is widely recognized, the extra-skeletal impact of its deficiency is often overlooked, including its effect on muscle function.  In fact, in 30% of patients, VD deficiency may present as proximal muscle weakness before any biochemical signs develop (eg, hypocalcemia, high alkaline phosphatase), likely mediated through VD receptors in muscle tissue 1,2. 

A recent meta-analysis of fall prevention with supplemental vitamin D concluded that at a dose of 700-1000 IU, supplemental vitamin D reduced falls by 19% within 2-3 months of treatment initiation among patients 65 y or older2; this benefit was not affected by type of supplemental VD, gender, age, or level of independence, and may be independent of additional calcium supplementation.  No fall reduction was observed with a daily dose < 700 IU or achieved serum 25 (OH)D levels below 60 nmol. 


  1. Rasheed K, Sethi P, Bixby E. Severe vitamin D deficiency induced myopathy associated with rhabdomyolysis. N Am J Med Sci 2013;5:334-336.
  2. Bischoff-Ferrari HA, Dawson-Hughes B, Orav JE, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomized controlled trials. BMJ 2009;339:b3692.

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My patient with a recent fall has a low serum 25 (OH) D level. Can vitamin D (VD) deficiency be associated with falls?