Peroxide paralysis of creating kinase and glycolysjs underlies reperfusion injury

Lewis Kaplan, Charles Belkms, Glenn Whitman

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: This study examines whether reperfusion (RP) inactivates creatine Id n use (CK) in a specific compartment; increased catalase (CAT) activity protects against RP injury; peroxide fPER) infusion creates injury similar to RP; substrate supplementation confers tolerance to PER infusion. Methods: Isolated perfused hearts were divided into 5 groups (n=6/gp): control i CTRL), myrigtic acid pretherapy (MA), PER infusion, and PER infusion with pyruvate (PYR) supplementation. Left ventricle (LV) developed pressure (DP) and 31P NMR spectra were recorded. Baseline CK and CAT cytoplasmictcyto) and mitochondrial(mito) activity were assayed in all groups. CK was assayed after 25 minutes of global ischemia and at 40 minutes RP in CTRL and MA groups. PER hearts were infused with 0.07/on/gm bw PER followed by 40 minutes of PER free perfusate; CK was assayed at end infusion. Additional PER hearts (n=4) underwent glycolytic product extraction. PYR hearts were infused with 0.14/on PER/gm bw followed by 40 minutes of PER free perfusion with PYR perfusate. Significance (p<05) was determined by paired and unpaired i-test Regulte: All groups were identical at baseline (DP, PCr/ATP, CK and CAT mito/cyto activity). MA hearts evidenced higher CATcyto (29±1 v. 20±2 U/mg protein, p<.05) and CKcyto activity (990±35 v. 849±44 U/gm LV, p<.05) than CTRL, higher DP (62±7 v. 31±4 mmHg, p<.05), and lower PCr/ATP ratios (2.14±.09 v. 2.81±. 17, p<.05)at 40 min. RP. CATmito and CKmito activités were unchanged throughout. PER infusion lowered DP (46±5 v. 108±5mm Hg, p<.05 ) and PCr/ATP (1.01±.12 v. 1.97±.08, p<05) from baseline, but DP returned to baseline (88±6 nun Hg p=.09) by 8 minutes of PER free perfusion; PCr/ATP normalized by 40 minutes (2.58±.22, p=.08). PER infusion also decreased CKcyto (1171±42 v. 1316±42 U/gm LV; p<.05) from CTRL. All extracted glycolytic products were proximal to the glyceraldehyde-3-phosphate dehydrogenase step. PYR hearts had a lower DP(60±2 v. 83±5 mm Hg, p<.05) and increased PCr/ATP (2.53±. 13 v. 2.14±.06, p<.05) from baseUne after PER infuaion. After 5 minutes of PER free perfusion, both DP (83±6) and PCr/ATP were normal (2.1±.08, p>.06). Conclusion: RP and PER infusion injury selectively inactivate CKcyto. Enhanced CATcyto stores protects mechanical and bioenergetic function following RP. PER infusion mimics RP injury, and blocks glycolysis. Pyruvate supplementation confers tolerance to PER infusion injury.

Original languageEnglish (US)
Pages (from-to)A121
JournalCritical care medicine
Volume26
Issue number1 SUPPL.
StatePublished - Dec 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Fingerprint

Dive into the research topics of 'Peroxide paralysis of creating kinase and glycolysjs underlies reperfusion injury'. Together they form a unique fingerprint.

Cite this