Postgrad Med J: first published as 10.1136/pgmj.61.721.957 on 1 November 1985. Downloaded from Postgraduate Medical Journal (1985) 61, 957-961 Mechanism of disease: Update Chest pain and the hyperventilation syndrome - some aetiological considerations Leisa J. Freeman and P.G.F. Nixon Cardiac Department, Charing Cross Hospital (Fulham), Fulham Palace Road, Hammersmith, London W6 8RF, UK. Chest pain is reported in 50-100% ofpatients with the coronary arteriograms. Hyperventilation and hyperventilation syndrome (Lewis, 1953; Yu et al., ischaemic heart disease clearly were not mutually 1959). The association was first recognized by Da exclusive. This is a vital point. It is time for clinicians to Costa (1871) '. .. the affected soldier, got out of accept that dynamic factors associated with hyperven- breath, could not keep up with his comrades, was tilation are commonplace in the clinical syndromes of annoyed by dizzyness and palpitation and with pain in angina pectoris and coronary insufficiency. The his chest ... chest pain was an almost constant production of chest pain in these cases may be better symptom . .. and often it was the first sign of the understood if the direct consequences ofhyperventila- disorder noticed by the patient'. The association of tion on circulatory and myocardial dynamics are hyperventilation and chest pain with extreme effort considered. and disorders of the heart and circulation was ackn- The mechanical work of hyperventilation increases owledged in the names subsequently ascribed to it, the cardiac output by a small amount (up to 1.3 1/min) such as vasomotor ataxia (Colbeck, 1903); soldier's irrespective of the effect of the blood carbon dioxide heart (Mackenzie, 1916 and effort syndrome (Lewis, level and can be accounted for by the increased oxygen copyright. 1918). consumption that is caused by the overbreathing. In 1941, Paul Wood declared that hyperventilation When hyperventilation is performed with a gas mix- played a minor and subsidiary role in the production ture that ensures hypercapnia other circulatory res- of chest pain in this syndrome and he considered the ponses are due to the elevated Paco2 such as peri- basic disorder to be psychiatric. This view has contin- pheral venous dilatation, increased venous pressure, ued, with a few notable exceptions, in English car- and a higher rate ofventilation. Hyperventilation with diological circles (Evans & Lum, 1977; Nixon, 1982). a gas mixture that induces the usual hypocapnia Friedman (1945) was the first to describe two distinct produces a fall of central venous pressure, a small fall types ofchest pain. A dull, aching and predominantly ofpulmonary artery pressure and a reduction ofup to left sided pain in 42% ofpatients was considered to be 40% in coronary blood flow. There is also a rise in http://pmj.bmj.com/ due to fatigue of the intercostal muscles. In the arterial blood lactate. The left ventricular end diastolic remainder, the pain was sharp, piercing and less pressure is unchanged (Richards, 1965), or increased sustained, and was associated with forceful heart (Al-Abassi et al., 1984). beatings, considered to reflect undamped autonomic Neil & Hattenhauer (1975) have shown that hy- nervous discharge. A third type of pain was added by perventilation interferes with myocardial oxygen sup- Wheatley (1975) and Margarian (1982). They des- ply in man by a combination ofcoronary vasoconstric- cribed a heavy substernal pain radiating to the neck tion which decreases coronary blood flow, and an on October 1, 2021 by guest. Protected and arms whose characteristics were sufficiently increase in the oxygen affinity of the blood in the similar to Heberden's angina so as to cause diagnostic coronary capillaries (Bohr shift to the left). Confusion confusion in some cases. about the effect ofhyperventilation on coronary blood The extent ofthis difficulty is highlighted by a recent flow has resulted from experiments on dogs which, study of patients whose history of chest pain had unlike man, hyperventilate naturally in order to lose convinced cardiologists that investigation with coron- heat. ary arteriography was essential (Bass et al., 1983). The In recent years the contribution of coronary spasm hyperventilation syndrome was found in 62% of to the pathogenesis of cardiac pain has been increas- patients with normal/near normal coronary ingly recognized and the provocation of spasm has arteriograms and 7% of patients with abnormal become a routine test in some laboratories. Ergon- ovine, tris buffer and hyperventilation, and more Correspondence: L.J. Freeman, M.B., M.R.C.P. recently hyperventilation alone have been employed Accepted: 3 May 1985 effectively. Girotti et al. (1982) have found that ) The Fellowship of Postgraduate Medicine, 1985 Postgrad Med J: first published as 10.1136/pgmj.61.721.957 on 1 November 1985. Downloaded from 958 L.J. FREEMAN and P.G.F. NIXON EXTRACELLULAR ALKALOS IS ohr effect f XH ncreased tissue 02 consumption DECREASED EXTRACELLULAR Ca. ECREASED EXTRACELLULAR K. [Ca2]04 [K+]04 Increased permeability to Na abnormal resting cell Heightened neuromuscular excitability iembrane potential Skeletal muscle spasm lyperpolarised state) REDUCED CO2 _ INTRACELLULAR TENSION ALKALOSIS [PH] If INCREASED I NTRACELLULAR CALC I UM [Ca2+] SYMPATHETIC NEURONAL CATECHOL. RELEASE e.g. platelet agglutination. MYOCARDIUM VASCULAR BED tonet Coronary artery copyright. MECHANICAL ELECTR I CAL Coronary arteriolar tonet Systolic contraction f Depolarisation impaired Peripheral resistance Diastolic relaxation X Increased slow Ca currents Capacitance vessel tonet Compliance i Predisposition to arrhythmia LVDPt Figure 1 The mechanisms by which hyperventilation, causing a fluctuating reduction of the blood CO2 tension, induces vasomotor instability and disturbances of function (courtesy of Abbasi personal communication). http://pmj.bmj.com/ I O= extracellular concentration, e.g. [K' J+] decreased concentration of extracellular ionized potassium. [ ] =intracellular concentration, e.g. [Ca2+]It increased intracellular concentration of ionized calcium. LVDP = Left ventricular end-diastolic pressure. hyperventilation alone had a 70% sensitivity and occurs mainly due to the influx of freely exchangeable 100% specificity for the production of spasm in such extracellular calcium ions into the cell through the patients. 'slow calcium' channels, thus depleting the concentra- The falling carbon dioxide tension of the blood tion ofextracellular calcium ions. (It is only this phase on October 1, 2021 by guest. Protected (Paco2) associated with hyperventilation causes a that can be blocked by the calcium blocking agents rapid migration of carbon dioxide from the cells and such as verapamil and nifedipine) (Ginsberg et al., so the intracellular pH rises (Yasue et al., 1981) 1980). This effect is probably not limited to the (Figure 1). As a result the intracellular ionized calcium coronary arteries since spasm in forearm vessels and also rises, principally by two mechanisms which are other arteries has occurred during provocation by both pH dependent (a more alkaline medium increases hyperventilation, which suggests that these patients the amplitude of the response). There is an initial may have a generally higher degree ofvasoconstrictor phase where tightly bound intracellular calcium ions reactivity (Rasmussen et al., 1984). The potent effect are released from sites such as the sarcoplasmic of hyperventilation on cerebral blood flow is also well reticulum and mitochondria which accounts for up to documented. The earlier title of vasomotor ataxia 70% ofthe maximum tension generated by the smooth applied to the hyperventilation syndrome is still apt. muscle contraction. The slower and more tonic phase Hyperventilation has also been known for some Postgrad Med J: first published as 10.1136/pgmj.61.721.957 on 1 November 1985. Downloaded from CHEST PAIN AND THE HYPERVENTILATION SYNDROME 959 time to produce 'pseudoischaemic' changes in the circumstances the ST segment depression may indeed electrocardiogram. T wave flattening and QT prolon- be hypoxic. gation occur as a result of a respiratory alkalosis but The second feature of the electrocardiogram which the cause for the more marked ST segment depression we have noticed in patients who hyperventilate is the is still not clear. The autonomic nervous system is markedly increased incidence of ectopics. These are considered to play the major contributing role (Lary & commonly of a right ventricular type, described by Goldschlarger, 1974). An initial fall in the Paco2 Rosenbaum (1969) as benign (Figure 2). At Charing produces a greater selective suppression of parasym- Cross Hospital the random observation of such an pathetic activity, leading to sympathetic dominance. ectopic has frequently yielded a diagnostic history and In addition, analysis of urinary catecholamine excre- positive provocation testing. We are not yet in a tion in patients who hyperventilate has shown that position to comment on the pathogenesis of the right adrenaline output can be increased by up to three ventricular ectopy. What is certain is that the subjec- times that of normals (Folgering & Cox, 1981). A tive sensation of a single ectopic is uncomfortable in combination ofautonomic imbalance and high adren- hyperventilators and recurrent ectopy is commonly aline drive may contribute to asynchronous myocar- reported as painful. dial repolarization with electrocardiographic abnor- In order to accommodate the foregoing we would malities (Gardin