Parallel temperature dependence of contracture-associated enzyme release due to anoxia, 2,4-dinitrophenol (DNP), or caffeine and the calcium paradox.
PDF (4.1M)
Journal: 1984/July - American Journal of Pathology
ISSN: 0002-9440
PUBMED: 6742111
Abstract:
Hypothermia during calcium-free perfusion of hearts protects them from injury caused by subsequent calcium repletion at 37 C (calcium paradox). Injury to calcium-free hearts is also associated with contracture caused by anoxia, 2,4-dinitrophenol (DNP), or caffeine. This study was done for the purpose of determining whether hypothermia during calcium-free perfusions protects hearts from contracture-associated injury. Langendorff-perfused rat hearts were studied in four experimental groups: I) Anoxia: Thirty minutes of anoxic perfusion at 37 C was followed by thirty minutes of anoxic calcium-free perfusion at 37-18 C. II) Calcium paradox: Five minutes of calcium-free perfusion at 37-18 C was followed by calcium repletion at 37 C. III, IVa) Caffeine or DNP: Five minutes of calcium-free perfusion at 37-18 C was followed by addition of 10 mM caffeine or 1 mM DNP in calcium-free medium at 37 C or, IVb) 1 mM DNP in calcium-free medium at 22 C. Injury was assessed by measurement of serial releases of creatine kinase (CK) in effluents and by cellular morphology. The results show that progressive hypothermia to 22 C during calcium-free perfusion periods produced a progressive reduction of CK release and morphologic evidence of injury due to anoxia, caffeine, or DNP, which closely paralleled protection of hearts from the calcium paradox. Protection from injury in all experimental groups was associated with preservation of sarcolemmal membrane integrity and prevention of cell separations at intercalated disk junctions. It is proposed that weakening of intercalated disks occurs during calcium-free perfusions and may be a cause of mechanical fragility of the sarcolemma. Hypothermia may protect hearts from contracture-associated injury by preserving the integrity of intercalated disk junctions during periods of extracellular calcium depletion.
Open in
PUBMED | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(5)
References
(23)
Diseases
(1)
Drugs
(3)
Chemicals
(4)
Organisms
(2)
Anatomy
(2)
Similar articles
Articles by the same authors
Discussion board
Am J Pathol 116(1): 94-106
PMID: 6742111

Parallel temperature dependence of contracture-associated enzyme release due to anoxia, 2,4-dinitrophenol (DNP), or caffeine and the calcium paradox.

Abstract

Hypothermia during calcium-free perfusion of hearts protects them from injury caused by subsequent calcium repletion at 37 C (calcium paradox). Injury to calcium-free hearts is also associated with contracture caused by anoxia, 2,4-dinitrophenol (DNP), or caffeine. This study was done for the purpose of determining whether hypothermia during calcium-free perfusions protects hearts from contracture-associated injury. Langendorff-perfused rat hearts were studied in four experimental groups: I) Anoxia: Thirty minutes of anoxic perfusion at 37 C was followed by thirty minutes of anoxic calcium-free perfusion at 37-18 C. II) Calcium paradox: Five minutes of calcium-free perfusion at 37-18 C was followed by calcium repletion at 37 C. III, IVa) Caffeine or DNP: Five minutes of calcium-free perfusion at 37-18 C was followed by addition of 10 mM caffeine or 1 mM DNP in calcium-free medium at 37 C or, IVb) 1 mM DNP in calcium-free medium at 22 C. Injury was assessed by measurement of serial releases of creatine kinase (CK) in effluents and by cellular morphology. The results show that progressive hypothermia to 22 C during calcium-free perfusion periods produced a progressive reduction of CK release and morphologic evidence of injury due to anoxia, caffeine, or DNP, which closely paralleled protection of hearts from the calcium paradox. Protection from injury in all experimental groups was associated with preservation of sarcolemmal membrane integrity and prevention of cell separations at intercalated disk junctions. It is proposed that weakening of intercalated disks occurs during calcium-free perfusions and may be a cause of mechanical fragility of the sarcolemma. Hypothermia may protect hearts from contracture-associated injury by preserving the integrity of intercalated disk junctions during periods of extracellular calcium depletion.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (4.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
icon of scanned page 94
94
icon of scanned page 95
95
icon of scanned page 96
96
icon of scanned page 97
97
icon of scanned page 98
98
icon of scanned page 99
99
icon of scanned page 100
100
icon of scanned page 101
101
icon of scanned page 102
102
icon of scanned page 103
103
icon of scanned page 104
104
icon of scanned page 105
105
icon of scanned page 106
106

Images in this article

Figure 4
Figure 4
on p.98
Figure 5
Figure 5
on p.100
Figure 6
Figure 6
on p.102
Figure 7
Figure 7
on p.102
Figure 8
Figure 8
on p.103
Figure 9
Figure 9
on p.103
Figure 10
Figure 10
on p.104
Figure 11
Figure 11
on p.104
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hearse DJ, Humphrey SM, Bullock GR. The oxygen paradox and the calcium paradox: two facets of the same problem? J Mol Cell Cardiol. 1978 Jul;10(7):641–668. [PubMed] [Google Scholar]
  • Yates JC, Dhalla NS. Structural and functional changes associated with failure and recovery of hearts after perfusion with Ca2+-free medium. J Mol Cell Cardiol. 1975 Feb;7(2):91–103. [PubMed] [Google Scholar]
  • Grinwald PM, Nayler WG. Calcium entry in the calcium paradox. J Mol Cell Cardiol. 1981 Oct;13(10):867–880. [PubMed] [Google Scholar]
  • Ganote CE, Liu SY, Safavi S, Kaltenbach JP. Anoxia, calcium and contracture as mediators of myocardial enzyme release. J Mol Cell Cardiol. 1981 Jan;13(1):93–106. [PubMed] [Google Scholar]
  • Ganote CE, Sims MA. Physical stress-mediated enzyme release from calcium-deficient hearts. J Mol Cell Cardiol. 1983 Jul;15(7):421–429. [PubMed] [Google Scholar]
  • Ganote CE. Contraction band necrosis and irreversible myocardial injury. J Mol Cell Cardiol. 1983 Feb;15(2):67–73. [PubMed] [Google Scholar]
  • Holland CE, Jr, Olson RE. Prevention by hypothermia of paradoxical calcium necrosis in cardiac muscle. J Mol Cell Cardiol. 1975 Dec;7(12):917–928. [PubMed] [Google Scholar]
  • Rich TL, Langer GA. Calcium depletion in rabbit myocardium. Calcium paradox protection by hypothermia and cation substitution. Circ Res. 1982 Aug;51(2):131–141. [PubMed] [Google Scholar]
  • Baker JE, Bullock GR, Hearse DJ. The temperature dependence of the calcium paradox: enzymatic, functional and morphological correlates of cellular injury. J Mol Cell Cardiol. 1983 Jun;15(6):393–411. [PubMed] [Google Scholar]
  • Maunsbach AB. The influence of different fixatives and fixation methods on the ultrastructure of rat kidney proximal tubule cells. I. Comparison of different perfusion fixation methods and of glutaraldehyde, formaldehyde and osmium tetroxide fixatives. J Ultrastruct Res. 1966 Jun;15(3):242–282. [PubMed] [Google Scholar]
  • Ashraf M. Correlative studies on sarcolemmal ultrastructure, permeability, and loss of intracellular enzymes in the isolated heart perfused with calcium-free medium. Am J Pathol. 1979 Nov;97(2):411–432.[PMC free article] [PubMed] [Google Scholar]
  • Frank JS, Rich TL, Beydler S, Kreman M. Calcium depletion in rabbit myocardium. Ultrastructure of the sarcolemma and correlation with the calcium paradox. Circ Res. 1982 Aug;51(2):117–130. [PubMed] [Google Scholar]
  • Carlson EC, Grosso DS, Romero SA, Frangakis CJ, Byus CV, Bressler R. Ultrastructural studies of metabolically active isolated adult rat heart myocytes. J Mol Cell Cardiol. 1978 May;10(5):449–459. [PubMed] [Google Scholar]
  • Altschuld R, Gibb L, Ansel A, Hohl C, Kruger FA, Brierley GP. Calcium tolerance of isolated rat heart cells. J Mol Cell Cardiol. 1980 Dec;12(12):1383–1395. [PubMed] [Google Scholar]
  • Burt JM. Electrical and contractile consequences of Na+ or Ca2+ gradient reduction in cultured heart cells. J Mol Cell Cardiol. 1982 Feb;14(2):99–110. [PubMed] [Google Scholar]
  • Haworth RA, Hunter DR, Berkoff HA. The isolation of Ca2+-resistant myocytes from the adult rat. J Mol Cell Cardiol. 1980 Jul;12(7):715–723. [PubMed] [Google Scholar]
  • Muir AR. The effects of divalent cations on the ultrastructure of the perfused rat heart. J Anat. 1967 Apr;101(Pt 2):239–261.[PMC free article] [PubMed] [Google Scholar]
  • De Leiris J, Feuvray D. Factors affecting the release of lactate dehydrogenase from isolated rat heart after calcium and magnesium free perfusions. Cardiovasc Res. 1973 May;7(3):383–390. [PubMed] [Google Scholar]
  • Bulkley BH, Nunnally RL, Hollis DP. "Calcium paradox" and the effect of varied temperature on its development: a phosphorus nuclear magnetic resonance and morphologic study. Lab Invest. 1978 Aug;39(2):133–140. [PubMed] [Google Scholar]
  • Boink AB, Ruigrok TJ, de Moes D, Maas AH, Zimmerman AN. The effect of hypothermia on the occurrence of the calcium paradox. Pflugers Arch. 1980 May;385(2):105–109. [PubMed] [Google Scholar]
  • Hunter DR, Haworth RA, Berkoff HA. Cellular calcium turnover in the perfused rat heart: modulation by caffeine and procaine. Circ Res. 1982 Sep;51(3):363–370. [PubMed] [Google Scholar]
  • Reuter H, Seitz N. The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol. 1968 Mar;195(2):451–470.[PMC free article] [PubMed] [Google Scholar]
  • Alto LE, Dhalla NS. Myocardial cation contents during induction of calcium paradox. Am J Physiol. 1979 Dec;237(6):H713–H719. [PubMed] [Google Scholar]
Copyright notice
Abstract
Hypothermia during calcium-free perfusion of hearts protects them from injury caused by subsequent calcium repletion at 37 C (calcium paradox). Injury to calcium-free hearts is also associated with contracture caused by anoxia, 2,4-dinitrophenol (DNP), or caffeine. This study was done for the purpose of determining whether hypothermia during calcium-free perfusions protects hearts from contracture-associated injury. Langendorff-perfused rat hearts were studied in four experimental groups: I) Anoxia: Thirty minutes of anoxic perfusion at 37 C was followed by thirty minutes of anoxic calcium-free perfusion at 37-18 C. II) Calcium paradox: Five minutes of calcium-free perfusion at 37-18 C was followed by calcium repletion at 37 C. III, IVa) Caffeine or DNP: Five minutes of calcium-free perfusion at 37-18 C was followed by addition of 10 mM caffeine or 1 mM DNP in calcium-free medium at 37 C or, IVb) 1 mM DNP in calcium-free medium at 22 C. Injury was assessed by measurement of serial releases of creatine kinase (CK) in effluents and by cellular morphology. The results show that progressive hypothermia to 22 C during calcium-free perfusion periods produced a progressive reduction of CK release and morphologic evidence of injury due to anoxia, caffeine, or DNP, which closely paralleled protection of hearts from the calcium paradox. Protection from injury in all experimental groups was associated with preservation of sarcolemmal membrane integrity and prevention of cell separations at intercalated disk junctions. It is proposed that weakening of intercalated disks occurs during calcium-free perfusions and may be a cause of mechanical fragility of the sarcolemma. Hypothermia may protect hearts from contracture-associated injury by preserving the integrity of intercalated disk junctions during periods of extracellular calcium depletion.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.