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Abstract

The main aim of this study was to assess the kinetics of intracellular free calcium (Ca(2+)i) handling by isolated rat hearts rendered ischemic for 30 min followed by 30 min of reperfusion analyzing the upstroke and downslope of the Ca(2+)i transient. Changes in mechanical performance and degradation of membrane phospholipids--estimated by tissue arachidonic acid content--were correlated with Ca(2+)i levels of the heart. The fluorescence ratio technique was applied to estimate Ca(2+)i. The disappearance of mechanical activity of the heart preceded that of the Ca(2+)i transient in the first 2 min of ischemia. The slope of upstroke of the Ca(2+)i transient, reflecting Ca2+ release, decreased by 60%, while the duration of the downslope of the transient, reflecting Ca2+ sequestration, expressed a significant prolongation (105 +/- 17 vs. 149 +/- 39 msec) during the first 3 min of ischemia. At about 20 min of ischemia end-diastolic pressure expressed a 3.5-fold increase (contracture) when the fluorescence ratio showed a 2-fold elevation. Reperfusion was accompanied with a further precipitous increase in end-diastolic pressure, while resting Ca(2+)i remained at end-ischemic levels. Increases in the arachidonic acid (AA) content of the ischemic and postischemic hearts were proportional to Ca(2+)i levels. In summary, the present findings indicate that both calcium release and removal are hampered during the early phase of ischemia. Moreover, a critical level of Ca(2+)i and a critical duration of ischemia may exist to provoke contracture of the heart. Upon reperfusion the hearts show membrane phospholipid degradation and signs of stunning exemplified by elevated AA levels, partial recovery of Ca(2+)i handling and sustained depression of mechanical performance.

Brain-Specific Serine-47 Modification of Cytochrome c Regulates Cytochrome c Oxidase Activity Attenuating ROS Production and Cell Death: Implications for Ischemia/Reperfusion Injury and Akt Signaling

“…Our model proposes that cell signaling pathways target the ETC. However, under conditions of stress, such as ischemia/reperfusion, there is an influx of calcium into the mitochondria [48][49][50]. It has been demonstrated that calcium is a potent activator of the mitochondrial ETC [51].…”

The Role of Oxidative Stress and Antioxidants in Cardiovascular Comorbidities in COPD

“…Hypoxemia observed in more severe COPD and during exacerbations can increase the risk of cardiac ischemia, and due to altered repolarization, the risk of ventricular arrhythmias and sudden cardiac death [ 199 , 201 , 203 ]. In addition, cardiac ischemia exposes the heart to oxidative stress that causes derangements in cardiomyocyte homeostasis, such as disturbed calcium handling and lipid signaling [ 204 , 205 , 206 ]. Cardiac dysfunction further aggravates tissue hypoxia that perpetuates systemic oxidative stress.…”