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Signal Transduction and Cardiac Hypertrophy pp 69–83Cite as

Role of Mitochondrial KATP Channels in Improved Ischemic Tolerance of Chronically Hypoxic Adult and Immature Hearts

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

Summary

Adaptation to chronic hypoxia increases cardiac tolerance to acute ischemia/reperfusion injury, which manifests itself as a reduction of myocardial infarct size, improvement of post-ischemic contractile dysfunction and limitation of life-threatening ventricular arrhythmias. Hearts of chronically hypoxic adult animals can be further protected by classic ischemic preconditioning but the effects of these two phenomena are not additive. It appears that adaptation to hypoxia does not increase the total capacity of endogenous protective mechanisms. Moreover, the antiarrhythmic threshold of preconditioning is increased in chronically hypoxic animals.

Hearts of newborn animals which are “adapted” to hypoxic conditions in utero are more tolerant to ischemia/reperfusion injury than adults and can be further protected neither by preconditioning nor by prenatal exposure to chronic hypoxia. Decreasing cardiac ischemic tolerance after birth can be prevented by postnatal exposure to chronic hypoxia. In the rat, preconditioning develops only during the first postnatal week; unlike in adults, combination of chronic hypoxia and preconditioning provides better protection than each of the two conditions alone.

Although the detailed mechanism of cardioprotection induced by chronic hypoxia is unknown, several studies using selective pharmacological modulators of mitoKATP suggest that activation of these channels plays an important role. Considering their involvement also in various forms of preconditioning, mitoKATP may serve as the common component of both short-term and long-term cardioprotective mechanisms.

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Authors and Affiliations

  1. Department of Developmental Cardiology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Dr. František Kolář, Ivana Ošt’ádalová, Bohuslav Ošt’ádal, Jan Neckář & Ondrej Szárszoi

  2. Centre for Experimental Cardiovascular Research, Prague, Czech Republic

    Dr. František Kolář, Ivana Ošt’ádalová, Bohuslav Ošt’ádal, Jan Neckář & Ondrej Szárszoi

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  1. Dr. František Kolář
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Correspondence to František Kolář .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

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Kolář, F., Ošt’ádalová, I., Ošt’ádal, B., Neckář, J., Szárszoi, O. (2003). Role of Mitochondrial KATP Channels in Improved Ischemic Tolerance of Chronically Hypoxic Adult and Immature Hearts. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_6

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