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Tolerance to ischaemia and ischaemic preconditioning in neonatal rat heart
I Ostadalova1, B Ostadal, F Kolár
1Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Insights
Neonatal hearts show decreasing tolerance to ischemia, but preconditioning offers protection by day 7. This suggests an endogenous protective mechanism develops in early postnatal life.
Area of Science:
- Cardiology
- Neonatal Physiology
- Ischemic Tolerance
Background:
- Ischemic preconditioning is well-studied in adult hearts but not in neonatal hearts.
- Understanding early cardiac tolerance to ischemia is crucial for neonatal care.
Purpose of the Study:
- To investigate the development of cardiac tolerance to ischemia in neonatal rat hearts.
- To examine the protective effects of preconditioning in early postnatal life.
- To explore the role of protein kinase C (PKC) isoforms in neonatal cardiac protection.
Main Methods:
- Neonatal rat hearts (days 1, 4, 7) were subjected to global ischemia and reperfusion using the Langendorff system.
- Contractile function was measured, and preconditioning was induced via brief ischemic episodes.
- Protein kinase C (PKC) isoform expression and translocation were analyzed using Western blot.
Main Results:
- Cardiac tolerance to ischemia decreased from postnatal day 1 to day 7.
- Preconditioning showed no protective effect on days 1 or 4 but was effective on day 7.
- PKC isoforms alpha, delta, epsilon, and zeta were expressed, but no translocation was observed after preconditioning on day 7.
Conclusions:
- Neonatal hearts exhibit decreasing tolerance to ischemia during the first week of life.
- Ischemic preconditioning demonstrates a protective effect specifically on day 7 of postnatal life.
- The findings suggest an endogenous protective mechanism develops in the neonatal heart against ischemia.
Abstract:
Although there is much information on ischaemic preconditioning in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine the early development of cardiac tolerance to ischaemia and the possible protective effects of preconditioning, rat hearts isolated on days 1, 4 and 7 of postnatal life were perfused (Langendorff) with Krebs-Henseleit solution at constant pressure, temperature (37 degrees C) and rate (200 beats/min). Developed force (DF) of contraction was measured by an isometric force transducer, and analysed using an on-line computer. Hearts were exposed to 40 or 60 min of global ischaemia followed by 30 min of reperfusion. Preconditioning was induced by three 3-min periods of global ischaemia, each separated by 5-min periods of reperfusion. Developmental changes in expression of protein kinase C (PKC) isoforms, and their activation following preconditioning, were estimated using Western blot analysis. Recovery of contractile function during reperfusion decreased from day 1 (48 +/- 2%) to day 4 (42 +/- 1%) and day 7 (33 +/- 2%). Preconditioning failed to improve ischaemic tolerance on day 1 (46 +/- 2%) and on day 4 (43 +/- 3%), but pronounced effect was observed on day 7 (40 +/- 2%). Prolonging the period of sustained ischaemia from 40 to 60 min on day 1 did not lead to a better recovery of contractile function in preconditioned hearts. PKC isoforms alpha, delta, epsilon and zeta were expressed in the ventricular myocardium during the first week of life, but there was no evidence of translocation following preconditioning on day 7. It may be assumed that the decreasing tolerance of the heart to ischaemia during early postnatal life is counteracted by the development of an endogenous protection.