Effect of ischemia-reperfusion on the post-rest inotropy of isolated perfused rat heart.
This paper aims to study the effect of ischemia-reperfusion on the post-rest inotropy and to characterize post-rest B1:B2 ratio as an index of intracellular Ca(2+) overload. When the rest interval between the cardiac beats is increased, the magnitude of the post-rest beats is increased. First beat (B1) is maximally potentiated with exponential decline of the second (B2) and subsequent beats, thereby establishing a normal B1:B2 ratio of post- rest inotropy of the cardiac muscle. The rest potentiation of B1 and subsequent decay in the magnitude B2 is thought to develop from the time-dependent changes in the Ca(2+)-uptake and release from the sarcoplasmic reticulum (SR). Ca(2+)-kinetics of SR can be modulated by a variety of interventions which produce Ca(2+) loading of the SR.


METHODS
Isolated perfused (K-H buffer, 34 degrees C) rat hearts were paced at 1 Hz (steady state frequency). Interbeat intervals between 1s and 10s were introduced and the recovery in the left ventricular contractile force (Pmax) of post-rest B1 and B2 for each interval was recorded. Their relative relationship was computed and compared under control and experimental conditions.


RESULTS
High extracellular Ca(2+) (2.50 to 7.0 mM) or low extracellular Na(+) (50% of control), and ischemia (60 min, 34 degrees C) - reperfusion (30 min, 34 degrees C) caused the reversal of the control relationship of the B1 to B2, with B2 being more potentiated than B1, accompanied by the appearance of after-contractions during the rest intervals of 4s or more. The mean (+/- SE) control B1:B2 ratio (at 4s interval) of 1.12 +/- 0.05 was significantly (P<0.001) reduced to 0.93 +/- 0.07; 0.89 +/- 0.01; and 0.96 +/- 0.02 after high Ca(2+) (6 mM) perfusion, low Na(+)(50%) perfusion and ischemia-reperfusion respectively. Simultaneous perfusion with ryanodine (1 microM) abolished the after-contractions and significantly increased the reduced ratios. The time course of changes in B1:B2 ratio after graded ischemia-reperfusion showed a significant fall in the ratio between 30 and 60 min of ischemia. A parallel change in Pmax and a significant rise in the left ventricular end-diastolic pressure, indicating an irreversible phase of the injury was recorded. No significant changes in B1:B2 ratio were detected during the reversible phase (<30 min) of the ischemia-reperfusion injury.


CONCLUSIONS
Ischemia-reperfusion induces significant alterations in the relative ratio of the post-rest contractions of the left ventricle in isolated perfused rat heart. The altered ratios were characterized to predict the irreversibility of the reperfusion injury and to index the extent of Ca(2+)-loading of the sarcoplasmic reticulum.
Juggi
J S
JS
Department of Physiology, Faculty of Medicine, Kuwait University, Kuwait. oomen@hsc.kuniv.edu.kw
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D012146:Rest / Q000502:physiology*; D013997:Time Factors
D002118:Calcium