A reduced oxygen supply to the heart causes coronary vasodilatation in the first instance. But if the hypoxia is severe or prolonged, the dilatation passes off and coronary vasospasm develops leading to a vicious circle with a further reduction of myocardial oxygenation. The spasm is associated with increased outflow of prostaglandin (PG)-like material and can be prevented or reversed by inhibitors of PG synthesis such as indomethacin or antagonists of PG action such as chloroquine. The spasm does not appear to be caused by thromboxane (TX) A2 since selective inhibitors of TXA2 synthesis enhance the hypoxic spasm and by themselves can cause spasm even in oxygenated hearts. The mechanism may be related to loss of negative feedback control of the PG pathway by TXA2. Oxygen may enhance TXA2 production and reduce formation of vasoconstrictor PGs, while smoking, because of the formation of carboxyhaemoglobin, may have the opposite effect. Oestradiol and testosterone do not influence the hypoxic spasm but progesterone at physiological concentrations blocks it completely. Progesterone may be the protective female hormone and the increased susceptibility to myocardial infarction in women on oral contraceptives may be related to reduced formation of endogenous progesterone.
PIP: The role of coronary vasospasm in many heart attacks has been reported. The paper presents a quite different mechanism, overproduction of prostaglandins (PGs), as the major factor in producing both the spasm and disorders of the rhythm which often accompany it. Coronary vasodilatation is caused by a reduced oxygen supply to the heart. If the hypoxia is severe or prolonged, coronary vasospasm results, leading to a further reduction of myocardial oxygenation. Increased outflow of PG-like material is related with the spasm, which can be prevented or reversed by infusion of inhibitors of PG synthesis (e.g., indomethacin) or of antagonists of PG action (chloroquine). The mechanism of the spasm may be associated with loss of negative feedback control of PG pathway by TXA2 (thromboxane). Oxygen may stimulate TXA2 production and reduce formation of vasoconstrictor PGs; the opposite effect is achieved with smoking due to formation of carboxyhaemoglobin. Estradiol and testosterone have no effect on hypoxic spasms; progesterone at physiological concentration blocks it entirely. Increased susceptibility to myocardial infarction of women on oral contraceptives is associated with reduced formation of endogenous progesterone, possibly the protective female hormone.