Ischaemia‐reperfusion induced alterations of mitochondrial function in hypertrophied rat heart

Abstract

The impact of in vivo ischaemia and ischaemia-reperfusion (I-R) on mitochondrial respiratory function was investigated in hypertrophied (HP) hearts with aortic constriction compared with control hearts using an open-chest rat surgical model. Moreover, mitochondrial susceptibility to superoxide radicals (O2-.) in vitro was examined in HP and control hearts with or without I-R. With the site I substrates pyruvate-malate, mitochondrial state 4 (basal) respiration and the respiratory control index (RCI) were not affected by either ischaemia alone or I-R in both HP and control hearts. State 3 (ADP-stimulated) respiration was increased with I-R in control hearts, but showed a reduction after I-R in the HP hearts. Exposure of mitochondria to O2-. (20 nM hypoxanthine in the presence of 0.13 unit mL-1 xanthine oxidase) significantly increased state 4 respiration, whereas state 3 respiration and RCI were decreased in all treatment groups. I-R hearts in both HP and control showed greater increases in state 4 respiration with O2-. than either sham or ischaemic hearts. HP hearts exhibited a significantly lesser extent of inhibition in state 3 respiration and RCI by O2-. compared with control hearts. These changes in mitochondrial respiratory properties were not observed with the site II substrate succinate. Myocardial reduced vs. oxidized glutathione ratio was significantly decreased after I-R in both control and HP hearts. Malondialdehyde content showed an increase with I-R, but the increase was significant only in control hearts. These data indicate that short-term in vivo I-R does not impair heart mitochondrial respiratory function, but renders the organelles more vulnerable to imposed oxidative stress. Mitochondria from the HP hearts are more resistant to free radical damage under normal and ischaemic conditions; however, this advantage is severely compromised after reperfusion.

Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats

“…This situation occurs frequently, as seen by the large number of patients treated by coronary angioplasty and heart transplantation. In such conditions, ROS may participate in the apoptotic and necrotic cell death, leading to the irreversible loss of cardiac tissue and, in many cases, to heart failure (25).…”

Glutathione deficiency intensifies ischaemia‐reperfusion induced cardiac dysfunction and oxidative stress

“…Rat myocardial I‐R was produced by the occlusion and release of the main descending branch of the left coronary artery (LCA), as previously described (Ji et al . 1993, 1994, Leichtweis et al . 1996).…”

“…Heart mitochondria were isolated from a portion of left ventricle/apex tissue (∼100 mg) placed in an ice‐cold buffer medium containing 0.25 M sucrose, 1.0 m M EDTA, 20 m M KCl, and 5.0 m M HEPES (pH=7.4) according to a previously described method with some modifications (Leichtweis et al . 1996).…”

“…Rats under these treatments were compared with normal rats subjected to an in vivo regional I‐R regimen used in our previous studies (Ji et al . 1993, Leichtweis et al . 1996).…”

Elevated MnSOD is not required for exercise-induced cardioprotection against myocardial stunning

“…We selected the male Sprague-Dawley rat for these I/R experiments because it is a well-accepted model for studying exerciseinduced myocardial adaptations and myocardial responses to I/R and it is the best-characterized model for isolated, perfused hearts in small mammals (12,13,30,34,35). Rats (4 mo old) were randomly assigned to one of four experimental groups (n ϭ 20/group): 1) sedentary control (S-C); 2) exercise trained, no treatment (E-C); 3) exercise trained, antisense oligonucleotide (E-AS); and 4) exercised trained, mismatch oligonucleotide (E-MM).…”