Exercise directly enhances myocardial tolerance to ischaemia-reperfusion injury in the rat through a protein kinase C mediated mechanism

Abstract

Objective-To determine whether exercise is capable of protecting the myocardium from experimental infarction and to explore the involvement of protein kinase C, a key signalling protein, in the development of any protection observed. Methods-Rats were exercised on a treadmill for 30 minutes at 23-27 m/min. Sham treated animals were placed on the stationary treadmill but not exercised. Twenty four hours later, hearts were LangendorV perfused and subjected to 35 minute left main coronary artery occlusion followed by 120 minute reperfusion. Infarct size was determined by tetrazolium staining and expressed as a percentage of the risk zone (I/R%). To examine the potential signalling pathway, animals were treated with either the selective protein kinase C inhibitor chelerythrine, 5 mg/kg intraperitoneally, or with vehicle 10 minutes before the exercise or sham treadmill period. Results-In the non-exercised group, mean (SEM) I/R was 48.4 (3.0)%. In the exercised group, infarct size was reduced to 17.3 (3.0)% (p < 0.01). Infarct size limitation induced by exercise was abolished by chelerythrine (I/R 45.0 (6.0)%). Chelerythrine pretreatment alone did not have any eVect on infarct size (I/R 51.1 (3.9)%). DiVerences in infarct size were independent of risk zone size and myocardial contractile function during ischaemia-reperfusion. Conclusions-Experimental moderate exercise induces protection against myocardial infarction 24 hours later. Protein kinase C activation during exercise appears to be an important signal mediator of this protective response. (Heart 2001;85:331-336)

Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction

“…Exercise has been shown to enhance myocardial tolerance to ischemia in a rat ischemia-reperfusion injury model through a PKC-mediated mechanism (30). However, previously, swimming exercise has been shown to have no effect on remodeling of infarcted or noninfarcted myocardium (1).…”

Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart

“…Exercise training, however, has been consistently shown to confer sustainable protection against myocardial infarction in animal models (10,26,40,56,57) and has been associated with improved survival following an ischemic event in humans (27,43). Despite substantial efforts to characterize the cardioprotective phenotype evoked by exercise training over the past decade, the precise mechanisms by which exercise reduces infarct size have not been fully elucidated.The infarct-sparing effect of exercise has been reported following both long-term (Ͼ10 wk) (9, 10, 40) and short-term (1-5 days) training regimens (11,26,56). The majority of these studies have attributed the cardioprotection to an exercise-induced increase in manganese superoxide dismutase (MnSOD) protein in the heart and an associated resistance to myocardial oxidative stress during ischemia and reperfusion (10,26,57).…”

“…The infarct-sparing effect of exercise has been reported following both long-term (Ͼ10 wk) (9, 10, 40) and short-term (1-5 days) training regimens (11,26,56). The majority of these studies have attributed the cardioprotection to an exercise-induced increase in manganese superoxide dismutase (MnSOD) protein in the heart and an associated resistance to myocardial oxidative stress during ischemia and reperfusion (10,26,57).…”

“…A variety of preconditioning stimuli has proven to be effective at reducing myocardial infarct size when administered immediately before ischemia (e.g, ischemic preconditioning and adenosine receptor agonists), but the protective effect of these treatments is lost after repetitive administration (38,53). Exercise training, however, has been consistently shown to confer sustainable protection against myocardial infarction in animal models (10,26,40,56,57) and has been associated with improved survival following an ischemic event in humans (27,43). Despite substantial efforts to characterize the cardioprotective phenotype evoked by exercise training over the past decade, the precise mechanisms by which exercise reduces infarct size have not been fully elucidated.…”

Exercise improves postischemic function in aging hearts

“…ENHANCED CARDIOPROTECTION against ischemia-reperfusion (I/R) injury has been observed after one to three exercise bouts (4,11,13,15,23,27,34,36,38). Exercise, along with brief heat shock or ischemia, is among a group of the manipulations that have been reported to induce the late phase of preconditioning against I/R (for reviews, see Refs.…”