Global reperfusion

Our thesis is based on the implicit assumption that faster, more complete reperfusion will translate into better long-term patient outcomes. Three types of reperfusion strategies have been described (1) recanalization or antegrade reperfusion, (2) global reperfusion (flow augmentation or transarterial retrograde reperfusion), and (3) transvenous retrograde reperfusion (flow reversal) (Table 13.1 and Fig. 13.1). 

Global reperfusion (flow augmentation or transarterial retrograde reperfusion)... 

S-Adenosyl-L-methionine (50 mg/kg given i.p.ever day for 3 days 1 h before ischaemia/reper-fusion) in a combined model of permanent focal ischaemia and global reperfusion in the rat brain reduced the production of thiobarbituric acid-reactive substances after induction with ferrous salt as an indicator of brain lipid peroxidation (Villalobos et al. 2000). Total glutathione production was increased. These changes were accompanied by an increase in mitochondrial capacity to reduce tet-raphenyl tetrazolium. 

Figure 4.1 Time-course of free-radical production during aerobic (a) or anoxic (b) reperfusion of the isolated rat heart. Radical production was assessed using e.s.r. and quantified as the formation of a Af-tert-butyl-a-phenylnitrone (PBN) spin adduct. After a 35 min stabilization period of aerobic perfusion, hearts were made globally ischaemic for 15 min. Hearts were then reperfused, either with oxygenated buffer (a) (n = 6), or with anoxic buffer, switching to an oxygenated buffer after 10 min (b) (n = 5). The bars represent the standard errors of the means. Redrawn with permission from Garlick et af. (1987).

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)...

Shutenko Z, Henry Y, Pinard E, Seylaz J, Potier P, Berthet F. 1999. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol 57 199-208. 

Shen W. H., Zhang C. Y., and Zhang G. Y. (2003). Antioxidants attenuate reperfusion injury after global brain ischemia through inhibiting nuclear factor-kappa B activity in rats. Acta Pharmacol. Sinica 24 1125-1130. 

Clemens, J. A., Stephenson, D. T., Smalstig, E. B., Dixon, E. R, and Little, S. P. (1997). Global ischemia activates nuclear factor-kappa B in forebrain neurons of rats. Stroke 28, 1073-1080. Crack, P. J., Taylor, J. M., Ali, U., Mansell, A., and Hertzog, P. J. (2006). Potential contribution of NF-kappaB in neuronal cell death in the glutathione peroxidase-1 knockout mouse in response to ischemia-reperfusion injury. Stroke 37, 1533-1538. 

Fig. 4.2 (a) Aortic output during reperfusion after 25 min global ischemia of hearts preconditioned with different concentrations of isoproterenol, (b) Aortic output during reperfusion after 25 min global ischemia of hearts preconditioned with different concentrations of forskolin (l(r6-l(r 8 M). 

Fig. 4.3 Mechanical performance of retrogradely perfused hearts during reperfusion after 30 min global ischemia. (A) Hearts were pretreated with H89 (2 x ft) 6 M) for 10 min before onset of ischemia. (B, C) Hearts were preconditioned with 1 x 10 or 3 x 5 min ischemia or forskolin (1x5 min 0.3 x ft) 6 M). H89 (2 x 10-6 M) was administered for 5 min before and during the preconditioning protocols. p < 0.05 versus controls p < 0.05 versus PC 1 x 10 min or forskolin.

Values are mean ( SEM) in each group. Control, I/R, and I/R + Se groups represent 60 min perfused hearts, 30 min global ischemia plus 30 min reperfused hearts, and 10 min selenium (Se) perfusion prior to I plus 30 min global I plus 30 min R (with Se) hearts, respectively. p < 0.05 versus control. (Adapted from Turan et al. 2005.)... 

Studies by Hossmann et al. have shown that prolonged global ischemia may result in secondary deterioration during the reperfusion phase followed by depletion of energy metabolites, acidosis and a dramatic increase in lactate content (Hossmann et al. 1994). However, in some animals recovery can be observed that is dependent on successful reperfusion. This pathologic condition that imitates cardiac arrest in man, results in a rapid (< 10 min) and marked (68% of control) decrease in the ADC when measured by repeated MR diffusion imaging (Hossmann et al. 1994) (Fig. 4.6). 

Hossmann KA (1997) Reperfusion of the brain after global ischemia hemodynamic disturbances. Shock 8 95-101 Hossmann K-A (1987) Pathophysiology of cerebral infarction. In Vinken PJ, Bruyn GW, Klawans HL (eds) Handbook of clinical neurology. Elsevier, Amsterdam, pp 107-153 Hossmann K-A (1991) Animal models of cerebral ischemia. 1. 

Yunoki et al., 2002 SD rats Bilateral CCAo and MCAo 1 h, with reperfusion 25.5, 28.5, and 31.5 for 20 min 24 h preischemia, OR 33 and 34.5 for 20, 60, 120, or 180 min 24 h preischemia, OR 28.5 and 31.5 head-only (hypothermic preconditioning) Infarct volume 24 h postischemia Tolerance to ischemia (reduced infarct volume) greater with cooler, longer hypothermia, and restricted hypothermia effective as global hypothermia... 

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... 

Nakamura, T, Minamisawa, H., Katayama, Y, Ueda, M., Terashi, A., Nakamura, K., and Kudo, Y. 1999. Increased intracellular Ca2+ concentration in the hippocampal CAl area during global ischemia and reperfusion in the rat a possible cause of delayed neuronal death. Neuroscience 88, 51-61. 

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