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Specialist Registrar Department of Cardiac Surgery Royal Hospital for Sick Children Yorkhill NHS Trust Dalnair Street Glasgow G3 8SJ, Scotland fax 44 141 201 9204 drrajashahzad{at}hotmail.com
Published Online, October 4, 2005. www.theannals.com, DOI 10.1345/aph.1E665a
Despite theoretical concerns of reduced myocardial tolerance to ischemia or promotion of cardiac arrhythmias, randomized trials and retrospective analyses do not support an increased cardiac risk with sildenafil.2 More importantly, sildenafil does not appear to compromise coronary blood flow in either coronary artery disease or normal coronary arteries. In fact, data from preclinical (canine) and human studies clearly show that sildenafil increases coronary blood flow during exercise in coronary arteries with critical stenosis, resulting in an improvement in the subendocardial/epicardial flow ratio and thereby ameliorating the effects of myocardial ischemia.3 Furthermore, coronary flow reserve significantly increases in both stenosed and reference arteries 45 minutes after treatment with oral sildenafil 100 mg compared with baseline, suggesting that sildenafil is unlikely to cause coronary steal.3 These data clearly negate the hypothetical causal relationship between sildenafil administration and occurrence of AMI proposed by Kekilli et al.1
On the other hand, Kekilli's case is a classic example of AMI with angiographically normal coronary arteries and no previous cardiac history. This type of AMI is a first coronary event in young patients (mean age 47.7 y) having few coronary risk factors (54.3%, only 1 risk factor); smoking is the most typical risk (73.9%). The anterior location is prevalent. The patient reported by Kekilli et al.1 fits this picture.
Several different mechanisms have been postulated for an AMI in patients with normal coronary arteries. These mechanisms include in situ thrombosis or embolization with subsequent clot lysis and recanalization, coronary artery spasm, cocaine abuse, and myocarditis. Recently, vascular endothelial dysfunction has been suggested to explain the mechanism of this syndrome, particularly in relation to tobacco or cocaine.4 A logical conclusion derived from evidence provided by Kekilli et al.1 would suggest that their patient was a victim of sudden plaque rupture secondary to smoking-induced endothelial function.
Cigarette smoking induces endothelial damage, which may be the initial mechanism for development of an atherosclerotic plaque. Tobacco has a direct toxic effect on the human endothelium that is associated with an increase in the number of endothelial cells with nuclear damage in the circulating blood.4 In asymptomatic young smokers, tobacco induces a dose-dependent impairment of endothelial dysfunction.5 Young heavy smokers with angiographically normal coronary arteries have an abnormal coronary vasoconstriction induced by acetylcholine, which means that nitric oxide (NO) is probably decreased locally.4 Since NO inhibits aggregation and adhesion of platelets and also has a synergistic anti-aggregatory effect with prostacycline,4 a decrease in NO release may be involved in the initiation of augmented platelet aggregation, resulting in coronary thrombosis in non-stenosed coronary arteries similar to what Kekilli et al.1 witnessed. I therefore conclude that, in this case, it would not be fair to pronounce sildenafil guilty on the basis of hearsay information when all corroborative evidence clearly suggests that smoking is the culprit.
References
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