title: Time related changes in calcium handling in the isolated ischemic and reperfused rat heart.
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.
authors.affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Miklós
authors.forename: Tamás
authors.initials: T
authors.lastname: Ivanics
authors.forename: Theo H M
authors.initials: TH
authors.lastname: Roemen
authors.forename: Ger J
authors.initials: GJ
authors.lastname: van der Vusse
authors.forename: László
authors.initials: L
authors.lastname: Dézsi
authors.forename: Mária
authors.initials: M
authors.lastname: Szekeres
authors.forename: Péter
authors.initials: P
authors.lastname: Kemecsei
authors.forename: András
authors.initials: A
authors.lastname: Tóth
authors.forename: Márk
authors.initials: M
authors.lastname: Kollai
authors.forename: László
authors.initials: L
authors.lastname: Ligeti
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003971:Diastole; D006352:Heart Ventricles / Q000378:metabolism; D007477:Ions; D007511:Ischemia; D008297:Male; D015428:Myocardial Reperfusion Injury; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D017725:Ventricular Pressure
chemical_list: D007477:Ions; D016718:Arachidonic Acid; D002118:Calcium