Abstract
BackgroundThe importance of apoptosis in the injury sustained by the human myocardium during ischaemia and reoxygenation and the underlying mechanisms remain unclear. To quantify apoptosis and necrosis induced by simulated ischaemia/reoxygenation in the human atrial myocardium, free-hand sections of right atrial appendage (n = 8/group) were subjected to 90 minutes simulated ischaemia followed by 2, 8 and 24 hours reoxygenation.ResultsApoptosis, as assessed by TUNEL, was greater than necrosis after 90 minutes simulated ischaemia and 2 hours reoxygenation (35.32 ± 3.22% vs 13.55 ± 1.3%; p < 0.05) but necrosis was greater than apoptosis by 24 hours reoxygenation (45.20 ± 2.75% vs 4.82 ± 0.79%; p < 0.05). Total caspase activation was similar after 90 minutes simulated ischaemia followed by 2 hours and 24 hours reoxygenation (515270 ± 99570 U vs 542940 ± 95216 U; p = NS). However, caspase-3 like activation was higher at 2 hours than at 24 hours reoxygenation (135900 ± 42200 U vs 54970 ± 19100 U; p < 0.05). Inhibition of caspase-3 by z.DEVD.fmk (70 nM) almost completely abolished apoptosis from 23.26 ± 2.854% to 0.73 ± 0.28 % (p < 0.05), without affecting necrosis.ConclusionCell death by apoptosis and necrosis in the human myocardium subjected to simulated ischaemia/reoxygenation depends on the degree of the ischaemic insult and have a different time-course with apoptosis happening early during reoxygenation and necrosis becoming more important later. Importantly, the apoptosis induced by simulated ischaemia/reoxygenation is mainly mediated by activation of caspase-3 but it does not affect necrosis.
Highlights
The importance of apoptosis in the injury sustained by the human myocardium during ischaemia and reoxygenation and the underlying mechanisms remain unclear
The present studies have shown the apoptosis induced by simulated ischaemia/reoxygenation is mainly mediated by activation of caspace-3 but that it does not affect necrosis
The degree of necrosis increased with extension of ischaemia, apoptosis was greater than necrosis (32.0 ± 3.2% vs 10.7 ± 1.9; p < 0.05) after 90 minutes of ischaemia and two hours of reoxygenation and the reverse was seen after 180 minutes of ischaemia (12.6 ± 1.9% vs 27.1% ± 2.8%; p < 0.05)
Summary
The importance of apoptosis in the injury sustained by the human myocardium during ischaemia and reoxygenation and the underlying mechanisms remain unclear. Studies in a dog model of coronary artery ligation have shown that necrosis, quantified histologically, develops rapidly after ischaemia and is directly proportional to the ischaemic time [5], there is evidence in the literature suggesting that necrosis may result secondary to reperfusion injury [4]. It has been suggested (page number not for citation purposes). BMC Physiology 2005, 5:14 http://www.biomedcentral.com/1472-6793/5/14 % nuclei
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