TxA2-mediated myocardial ischemia as a consequence of an acute lung inflammatory reaction in the rabbit

Abstract

Summary. Epidemiological studies link acute infection of the respiratory tract to a transient increased risk of acute myocardial infarction. The underlying mechanisms remain unknown. We hypothesized that vasoactive mediators produced by inflammatory cells in the lungs and drained in the coronary circulation may trigger acute myocardial ischemia. To test this hypothesis we used an experimental model in the rabbit. Injection of the bacterial‐derived peptide N‐formyl‐Met‐Leu‐Phe (or N‐formyl‐Methionyl‐Leucyl‐Phenylalanine)(fMLP) in the jugular vein induced massive recruitment of both polymorphonuclear leukocytes (PMN) and platelets in the microcirculation of the lungs, accompanied by rapid and marked increase of leukotriene B4, cysteinyl leukotrienes and thromboxane (Tx) A2 in the aortic blood. In all animals, fMLP evoked ischemic electrocardiographic changes: within the first minute of infusion a profound depression of the ST segment and inversion of the T wave were observed. Mean aortic pressure and heart rate fell to 64.0 ± 6.9 and 83.5 ± 3.1% of the basal levels at 3 and 10 min, respectively. All these alterations were transient. Aspirin, prevented electrocardiographic ischemic changes, reverted bradycardia and hypotension but did not significantly modify either PMN or platelet recruitment nor leukotriene synthesis. Ridogrel, a Tx‐synthase and receptor inhibitor, prevented ECG alterations and bradycardia, but did not prevent and even worsened hypotension; it blocked platelet, but not PMN, sequestration. Pretreatment of animals with intravenous high dose of aspirin prevented ridogrel‐dependent hypotension and platelet inhibition, suggesting that PGI2 contributes to the effects of Tx‐synthase and receptor inhibitor. In hypercholesterolemic rabbits, ECG alterations persisted longer than in normal controls. In summary, our results indicate that acute activation of PMN and platelets in the lungs provokes transient myocardial ischemia, in normal animals that is exacerbated in hypercholesterolemic rabbits. TxA2 appears to be the major mediator of this phenomenon. Moreover the data suggest that a balance between TxA2 and PGI2 plays a pivotal role in platelet activation and recruitment in our model.

Myocardial infarction associated with pseudoephedrine use and acute streptococcal infection in a boy with normal coronary arteries

“…These data suggest that endothelial dysfunction after acute infection or inflammation may be a transient risk factor for cardiovascular events, may trigger abnormal vascular behaviour, and may facilitate Constriction of the coronary arteries is considered an important component in the pathogenesis of acute myocardial ischemia. Cysteinyl leukotrienes and thromboxane A2, produced in acute infections and inflammations, are potent vasoactive mediators able to modify cardiac and coronary function; in fact, they induce coronary artery constriction, which may be rapidly transient in normal people (9). The duration of this effect may be longer with the use of a potent vasoconstrictor drug like pseudoephedrine.…”