Heart Subjects

Figure 4.8 Reduction of Na/K ATPase activity in isoiated guinea-pig hearts subjected to ischaemia/reperfusion and its prevention by various agents control non-ischaemic hearts (Nl) guinea-pig hearts subjected to global ischaemia for 2 h and subsequently reperfused for 1 h (IR). In other preparations, superoxide dismutase (SOD) 100 U/ml, catalase (CAT) 150 U/ml, dimethylsulphoxide (DMS) 50 mu, histidine (HIS) 10 mu, vitamin E (TOC)...

Darley-Usmar, V., O Leary, V. and Stone, D. (1989). The glutathione status of perfused rat hearts subjected to hypoxia and teoxygenation the oxygen paradox. (Corrected and republished article originally printed in Free Rad. Res. Commun. 5, 283-289. 

Sodium selenite, at nanomolar concentrations, improved the depressed cardiac performance of the isolated heart subjected to ischemia/reperfusion injury. As ischemia/reperfusion-mediated cardiac function has been reported to occur mainly due to the development of oxidative stress and intracellular Ca2+ overload (Bolli and Marban 1999), it is likely that selenium could protect the heart... 

Since oxidative stress has been reported to produce subcellular redistribution and activation of NF-kB, we measured total NF-kB content in cytosolic and particulate fractions of the hearts subjected to ischemia/reperfusion. In another set of experiments, the activation of NF-kB protein was studied by measuring the total NF-kB and phospho-NF-KB in the heart homogenate. Elevated ratios of NF-kB in particulate versus cytosolic fraction and of phospho-NF-KB and total NF-kB in the hearts subjected to ischemia/reperfusion were reduced by selenium. As oxidative stress has been reported to produce subcellular redistribution and activation of NF-kB and antioxidants have been shown to prevent this alteration (Cargnoni et al. 2002), it is possible that our observation on selenium-induced NF-kB translocation might be due to its antioxidant action. It should be noted that since selenium treatment could reduce the tumor necrosis factor-cc (TNF-ct)-mediated activation of NF-kB (Kim and Stadtman 1997), it suggests a possible involvement of a reduction in the formation of TNF-tx in the hearts subjected to ischemia/reperfusion by selenium. 

Figure 1 Infarct size (IS) expressed as a percent of the area at risk (AAR) in intact rat hearts subjected to vehicle (control), ischemic preconditioning (PC), or naloxone (NL) in the absence of PC, NL treatment prior to PC (NL + PC), and NL treatment after PC (PC + NL) but before the index ischemic period. The filled squares are the mean + SE of each group. P <. 05 vs. the control group. (From Ref. 28.)...

Fig. 6. (a) The ESR spectrum of DMPO-OH (solid dots) adduct in coronary effluent collected during 2 min of aerobic reperfusion in the rat heart subjected to a 20 min period of normothermic global ischemia. An unidentified nitroxide metabolite (open circles) was also detected in the effluent, (b) Effluent from the same heart, prior to ischemia, during aerobic perfusion with 40 mM DMPO. (Inset) Time course of DMPO-OH formation as a function of reperfusion time. Note that when catalase was present in the collection tubes, the overall signal intensity of the radical adduct was... 

Spin trapping can also be used to investigate the different dose-response effects of SOD in rat and rabbit hearts, subjected to ischemia and reperfusion. Does the spin-adduct formation also follow a bell-shaped dose-response relationship observed with SOD Additional studies are clearly needed to explain the protective and deleterious aspects of SOD in ischemia and reperfusion injury. 

The practically most important class of drugs directly acting on any adrenergic receptor are the p-blockers (Figure 10.12). They are mainly used to reduce the workload on a heart subject to impaired perfusion due to atherosclerotic blood vessel obliteration. The most severe consequence of this impaired perfusion is myocardial infarction, which consists in the irreversible damage to the regions of heart muscle tissue downstream of an obliterated artery. Patients... 

In the present paper we have analyzed the changes in iron and ferritin levels in ischemia and reperfrision of the isolated rat heart subjected to prolonged ischemia, with and... 

Hemodynamic parameters of hearts subjected to ischemia with and without PC... 

In the coronary artery-occluded Langendorff rat heart model, irreversible injury occurred within 20 min of ischemia (28). Disruption of the sarcolemma was observed in canine hearts subjected to 15(29, 30) to 20 min of coronary occlusion and reperfusion (31). 

Increased JNKs activation in response to ischemia and reperfusion is observed in an adult rabbit cardiomyocytes model of simulated ischemia and reoxygenation. Attenuation of JNKs activity by transfection with a dominant negative mutant of the upstream activator of JNKs, JNK kinase-2 or JNK interacting protein-1, JIP-1, reduced cell death.151 Furthermore, ischemia and reperfusion induced JNKs activation was decreased in perfused hearts subjected to ischemic preconditioning or heat stress treatment.152... 

Figure 26. Western blots. Heat induces Hsp7i) protein expression in rat myocardium (A). Heat reduces the phosphorylation of p54 and p46 JNK in rat heart subjected to zero-flow global ischemia and reperfusion (B). This is probably the effect of a negative interaction between Hsp70 and JNKs (modified by Pantos132), Normal stands for normal hearts and Heat stands for hearts subjected to heal stress.

A detrimental effect caused by androgens is also reported. Blockade of the endogenous testosterone by flutamide or depletion of testosterone (castration) improved myocardial function of the perfused rat hearts subjected to ischemia and reperfusion. This response was associated with decreased caspase l, caspase-3, caspase-11, decreased TNF-alpha, IL-1 beta, IL-6, decreased ischemia and reperfusion induced p38 MAPK activation and increased Bcl-2 expression in castrated and flutamide treated males.15 Accordingly, supraphysiological doses of nandrolone taken during exercise or under sedentary conditions increased myocardial susceptibility to ischemia and reperfusion injury in perfused rat hearts. Pre-ischemic c-AMP concentrations and pre-ischemic and reperfusion TNF-alpha concentrations were found to be increased in those hearts.16... 

The cardioprotective effect of melatonin is demonstrated in several studies in in vivo and ex vivo experimental rat models or cardiomyocytes, as reviewed by Reiter.30 Melatonin administration in perfused rat hearts subjected to ischemia and reperfusion increased postischemic recovery of function, reduced the duration of ventricular tachycardia and ventricular fibrillation and this was associated with decreased lipid peroxidation products and OH radical formation, indicating an antioxidant effect of melatonin.31 Furthermore, in pinealectomized rats, occlusion of the left coronary artery followed by reperfusion resulted in significant increase in infarct size than in intact animals.32 Melatonin acts as scavenger of oxygen or nitrogen based reactants, stimulates antioxidant enzymes, stabilizes cellular membrane, increases the efficiency of oxidative phosphorylation, reduces leukocyte recruitment and adhesion molecule expression and reduces homocysteine induced damage (reviewed by Duncker33). 

The role of thyroid hormone in the response of the heart to ischemia and reperfusion has not been extensively investigated due to the fact that thyroid hormone accelerates heart rhythm and increases oxygen consumption, effects which could be detrimental in the setting of ischemia and reperfusion. However, accumulating experimental evidence shows that either acute or chronic pretreatment with thyroid hormone can lead to cardioprotection. In an isolated working rat heart model, cardiac work and cardiac efficiency were increased after no-flow global ischemia and reperfusion in hearts acutely pretreated with Tr74 Furthermore, thyroxine pretreatment for two weeks resulted in increased recovery of function in isolated rat hearts subjected to zero-flow... 

Thyroid hormone pretreatment has not been consistently resulted in cardioprotec-tion. Postischemic recovery of function has been reported to be reduced in hyperthyroid hearts subjected to no-flow global ischemia.79-81 However, this discrepancy is due to differences in the experimental design (reviewed by Pantos73). 

Figure 3. Lcll ventricular pressure recordings obtained from isolated rat hearts subjected to zero-flow global ischemia and reperfusion. Ischemic contracture is exacerbated in thyroxine treated hearts (13) and is suppressed in the hypothyroid hearts (C) as compared to normal hearts (A). Recovery of left ventricular developed pressure is increased in both hypothyroid and hyperthyroid as compared to normal hearts. LVDP is defined as the difference between systolic and diastolic left ventricular pressure (data from our laboratory).

Matsumoto-Ida M, Akao M, Takeda T, Kalo M, Kita T (2006) Real-time 2-photon imaging of mitochondrial function in perfused rat hearts subjected to ischemia/reperfusion. Circulation 114 1497-1503... 

Petrosillo, G., Ruggiero, F.M., Di Venosa, N. and Paradies, G., Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion role of reactive oxygen species and cardiolipin, Faseb J 17 (2003) 714-716. 

---