TY - JOUR
T1 - Pretreatment with the iron chelator desferrioxamine fails to provide sustained protection against myocardial ischaemia-reperfusion injury
AU - Reddy, B. Ramesh
AU - Wynne, Joshua
AU - Kloner, Robert A.
AU - Przyklenk, Karin
N1 - Funding Information:
Supported in part by a research fellowship from the American Heart Association (Michigan Affiliate) awarded to BRR.
PY - 1991/9
Y1 - 1991/9
N2 - Study objective - The aim was to determine whether the potent iron chelator desferrioxamine, previously shown by our laboratory and others to cause acute limitation of infarct size, would provide sustained protection against myocardial ischaemia-reperfusion injury.Design - Anaesthetised dogs underwent a 2 h transient coronary artery occlusion. After surgical preparation, each dog was randomised into one of two groups receiving either desferrioxamine or equivalent infusion of saline. Infusion of desferrioxamine was initiated 30 min before occlusion at an initial dose of 10 mg·kg-1 for the first hour of the protocol, followed by a maintenance dose of 1.5 mg·kg-1·h-1 throughout the remainder of the ischaemic period and the initial 4 h of reperfusion. The animals were reanaesthetised the following day and killed 20-24 h following reperfusion. Variables measured included heart rate and arterial pressures; regional myocardial blood flow; urinary iron content; and infarct size. In addition, % wall thickening in the ischaemic-reperfused myocardium was assessed by echocardiography in a limited number of animals.Experimenal material - 12 mongrel dogs weighing 22(SEM 4) kg were used, n = 6 in each group.Measurements and main results - Both groups were equally and severely ischaemic during coronary artery occlusion. Desferrioxamine caused a modest and transient reduction in mean arterial pressure during the ischaemic episode, but had no effect on heart rate or myocardial blood flow. As expected, urinary iron content was significantly higher in treated animals v controls, at 465(SEM 107) v 55(23) μg, p<0.01, indicating that desferrioxamine effectively chelated free iron. However, it failed to exert a significant cardioprotective effect: infarct size did not differ between control and treated groups [54(4)% v 58(5)% of the myocardium at risk], and wall thickening was similar throughout occlusion and reperfusion in control and desferrioxamine treated animals.Conclusions - Despite substantial reduction in infarct size previously observed at 4 h following reflow with the same dose and regimen of desferrioxamine treatment, results of the present study indicate that desferrioxamine did not provide sustained protection against myocardial ischaemia-reperfusion injury. We therefore conclude that desferrioxamine delays - but does not prevent - myocyte necrosis in this canine model.
AB - Study objective - The aim was to determine whether the potent iron chelator desferrioxamine, previously shown by our laboratory and others to cause acute limitation of infarct size, would provide sustained protection against myocardial ischaemia-reperfusion injury.Design - Anaesthetised dogs underwent a 2 h transient coronary artery occlusion. After surgical preparation, each dog was randomised into one of two groups receiving either desferrioxamine or equivalent infusion of saline. Infusion of desferrioxamine was initiated 30 min before occlusion at an initial dose of 10 mg·kg-1 for the first hour of the protocol, followed by a maintenance dose of 1.5 mg·kg-1·h-1 throughout the remainder of the ischaemic period and the initial 4 h of reperfusion. The animals were reanaesthetised the following day and killed 20-24 h following reperfusion. Variables measured included heart rate and arterial pressures; regional myocardial blood flow; urinary iron content; and infarct size. In addition, % wall thickening in the ischaemic-reperfused myocardium was assessed by echocardiography in a limited number of animals.Experimenal material - 12 mongrel dogs weighing 22(SEM 4) kg were used, n = 6 in each group.Measurements and main results - Both groups were equally and severely ischaemic during coronary artery occlusion. Desferrioxamine caused a modest and transient reduction in mean arterial pressure during the ischaemic episode, but had no effect on heart rate or myocardial blood flow. As expected, urinary iron content was significantly higher in treated animals v controls, at 465(SEM 107) v 55(23) μg, p<0.01, indicating that desferrioxamine effectively chelated free iron. However, it failed to exert a significant cardioprotective effect: infarct size did not differ between control and treated groups [54(4)% v 58(5)% of the myocardium at risk], and wall thickening was similar throughout occlusion and reperfusion in control and desferrioxamine treated animals.Conclusions - Despite substantial reduction in infarct size previously observed at 4 h following reflow with the same dose and regimen of desferrioxamine treatment, results of the present study indicate that desferrioxamine did not provide sustained protection against myocardial ischaemia-reperfusion injury. We therefore conclude that desferrioxamine delays - but does not prevent - myocyte necrosis in this canine model.
KW - Contractile function
KW - Coronary occlusion
KW - Myocardial infarct size
KW - Oxygen free radicals
KW - Reperfusion
UR - http://www.scopus.com/inward/record.url?scp=85047677185&partnerID=8YFLogxK
U2 - 10.1093/cvr/25.9.711
DO - 10.1093/cvr/25.9.711
M3 - Review article
C2 - 1799904
AN - SCOPUS:85047677185
VL - 25
SP - 711
EP - 718
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 9
ER -