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Human Cardiac Mast Cells and Their Role in Severe Allergic Reactions

Last updated on November 17th, 2021

Although great strides have been made in the treatment of bronchial asthma, asthma-associated mortality is increasing in many countries. The first record of asthma dates back 30 centuries, but it is only during recent decades that systematic attempts have been made to understand the pathophysiology of this condition and to treat the disorder. At the beginning of this century, William Osier reported that acute attacks of bronchial asthma never result in death. As a consequence, generations of physicians were taught that death from asthma essentially never occurs. Death as a complication of asthma was demonstrated in 1922 when Huber and Koessler described 21 fatal cases. An additional 176 deaths from asthma were reported in 1952. Subsequently, such observations became more commonplace.

Very few of the 200 deaths reported from asthma before 1953 occurred in children. This situation changed dramatically in the next decades. In the United Kingdom, mortality from asthma among young patients rose and around the 1960s asthma became a common cause of death in this age group. A similar pattern was recently reported in Swedish children.

Increased risk of death from asthma has also been documented in several long-term studies. Lang and Polansky reported elevated rates of asthma deaths in Philadelphia between 1969 and 1991. In agreement with others, they found that the number of deaths had increased despite a decline in the concentrations of major air pollutants. Fatal asthma was significantly more common in poor people and in minority residents, particularly blacks. A long-term study conducted in Rochester (MN, USA) showed that survival was worse than expected in patients affected by asthma associated with obstructive pulmonary diseases.

Similarly, in prospective studies performed in Copenhagen, self-reported asthma was associated with an excess of mortality, mainly from respiratory diseases. It remains to be established whether this is a true picture or the result of misclassification between asthma and chronic obstructive pulmonary disease.

Despite these frightening findings, there is a surprisingly modest interest and lack of information about prevention of deaths from bronchial asthma and from allergic diseases. In this review we shall first delineate the possible cardiovascular alterations in bronchial asthma and in allergic diseases; secondly, we shall emphasize the role of cardiac mast cell activation during allergic reactions; and, thirdly, we shall briefly review the extensive evidence of the cardiovascular effects of mast cell-derived mediators in humans.


Cardiovascular Alterations in Bronchial Asthma, Anaphylaxis and Allergic Drug Reactions

Asthma-related deaths can occur after a prolonged attack of asthma or they can occur suddenly. It has been well documented that sudden death from asthma may occur outside or inside the hospital, without obvious earlier long-term deteriorations, or after a prolonged, insufficiently treated attack. The view that asthma-related deaths were largely a result of limited airflow was supported by pathological observations and probably applies to patients who died after a prolonged attack of asthma. It is unlikely that intraluminal mucoid secretions and smooth muscle contractions can explain all cases of sudden unexpected deaths. A cause of these sudden deaths could be arrhythmia or coronary spasm.

During a severe attack of asthma, cardiopulmonary functions are impaired; this is manifested by reduced airflow rates, a ventilation-perfusion imbalance leading to hypoxaemia and hypercapnia, increased pulmonary vascular resistance and right ventricular systolic overload. Cardiovascular changes have been reported in patients during exacerbations of bronchial asthma. P pulmonale has been found in approximately 15% of patients in status asthmaticus. In addition, pulsus paradoxus (fluctuation of 10 mmHg or greater) can be detected even in mild obstruction and is frequently absent in severe obstruction.

Cardiovascular alterations are evident in patients with systemic anaphylaxis. Anaphylactic shock is frequently characterized by ECG alterations consisting of ischaemic ST waves, arrhythmias and atrial fibrillations. These findings suggest that the human heart is involved in tissue sensitization and in some instances of sudden death. Anaphylactic reactions following insect sting or acute urticaria can be associated with coronary spasm or acute myocardial infarction. Moreover, profound myocardial depression can be found in patients with systemic anaphylaxis presumably owing to the negative inotropic effects of mast cell-derived mediators.

Myocardial infarction can also occur consequent on idiopathic anaphylaxis. Pathological observations have demonstrated that lesions to the cardiovascular system may be the cause of death in patients who died from anaphylactic shock. In particular, the myocardial lesions found in some patients with systemic anaphylaxis could represent the anatomical basis for the development of irreversible cardiac failure.

Cardiac Pathology in Patients with Fatal Asthma

Evidence from pathological studies of patients who have died from asthma points to asphyxia secondary to severe airway obstruction as the cause of death. Cardiac involvement in such cases has attracted little attention, but reports of cardiac abnormalities are on the increase. Initially, cardiac lesions in patients with fatal asthma were labelled ‘focal necrosis’ or ’subendocardial myolysis and necrosis’ and they were generally attributed to catecholamine treatment of the disease. However, Drislane et al. demonstrated myocardial contraction band necrosis (MCBN) in asthmatic patients with fatal asthma who did not receive exogenous catecholamines.

Although the mediators responsible for MCBN have not been identified, it is possible that drugs used to treat asthma may predispose to its development. Alternatively, central nervous system stimulation, or the local release of vasoactive mediators from immunologically activated cardiac mast cells, might be responsible for MCBN, at least in part.

Our microscopic examination of sections of hearts obtained from patients undergoing heart transplantation and from subjects who died from non-cardiovascular causes showed that mast cells were present in all preparations. Mast cells were localized around blood vessels and between myocardial fibres. In situ electron microscopic examination of cardiac mast cells revealed a small percentage (c. 5%) of activated, i.e. partially degranulated, mast cells. This observation is clinically relevant because it implies that immunological and non-imunological stimuli can activate human heart mast cells to release vasoactive and pro-inflammatory mediators.

The finding of cardiac morphological abnormalities in patients who died from asthma suggests a link between death and cardiac lesions in some of these patients. The relationship between cardiac damage and fatal asthma highlights the need for studies on post-mortem cardiac and pulmonary samples from patients who died from asthma or consequent to anaphylactic reactions.

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