Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts

P A Fedalen; Valentino Piacentino III; V Jeevanandam; C Fisher; J Greene; K B Margulies; S R Houser; S Furukawa; A K Singhal; B I Goldman

doi:10.1016/S1053-2498(02)01237-8

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Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts

Journal article

Peer reviewed

Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts

P A Fedalen, Valentino Piacentino III, V Jeevanandam, C Fisher, J Greene, K B Margulies, S R Houser, S Furukawa, A K Singhal and B I Goldman

The Journal of heart and lung transplantation, Vol.22(11), pp.1234-1244

11/2003

DOI: 10.1016/S1053-2498(02)01237-8

PMID: 14585385

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Abstract

Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals. Hearts from Yorkshire pigs (100 kg) were studied in 3 groups. Group 1 (control) hearts were surgically removed while beating. Group 2 hearts were harvested from animals made hypoxic by discontinuing mechanical ventilation for 30 minutes. Group 3 hearts were hypoxic as in Group 2, but these animals received adenosine (40 mg) and cariporide (400 mg) 10 minutes before stopping ventilation. Cardiac function in all groups was assessed ex vivo in a working heart apparatus in which pressure and flow measurements were made over 3 hours. Controlled reperfusion in Group 3 hearts used leukocyte-depleted blood perfusate containing free radical scavengers. Myocardial injury was assessed on the basis of perfusate creatine phosphokinase activity and histopathologically determined injury score. Groups 1 and 3 hearts could be resuscitated to perform work equivalently during the entire reperfusion period and showed positive responses to increases in pre-load and norepinephrine. Group 2 hearts could not perform work. After 3 hours, Group 2 hearts showed significantly higher creatine phosphokinase and histopathologic injury scores compared to with Groups 1 and 3, which were not significantly different from each other. Pharmacologic pre-conditioning and controlled reperfusion effectively protect non-beating porcine hearts from injury after 30 minutes of hypoxia/ischemia in situ.

Heart - physiopathology

Sulfones - therapeutic use

Vasodilator Agents - therapeutic use

Myocardium - pathology

Anti-Arrhythmia Agents - therapeutic use

Myocardial Reperfusion Injury - enzymology

Hypoxia - metabolism

Myocardial Reperfusion Injury - pathology

Myocardium - enzymology

Animals

Swine

Adenosine - therapeutic use

Creatine Kinase - metabolism

Heart - drug effects

Ischemic Preconditioning, Myocardial - methods

Guanidines - therapeutic use

Myocardial Reperfusion Injury - prevention & control

Details

Title: Subtitle: Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts
Creators: P A Fedalen - Department of Surgery, Temple University Health Sciences Center, Philadelphia, Pennsylvania 19140, USA
Valentino Piacentino III
V Jeevanandam
C Fisher
J Greene
K B Margulies
S R Houser
S Furukawa
A K Singhal
B I Goldman
Resource Type: Journal article
Publication Details: The Journal of heart and lung transplantation, Vol.22(11), pp.1234-1244
Publisher: United States
DOI: 10.1016/S1053-2498(02)01237-8
PMID: 14585385
ISSN: 1053-2498
eISSN: 1557-3117
Grant note: HL39201 / NHLBI NIH HHS HL61495 / NHLBI NIH HHS AG17022 / NIA NIH HHS HL03560 / NHLBI NIH HHS IF32HL 10079-01 / NHLBI NIH HHS
Language: English
Date published: 11/2003
Academic Unit: Surgery; Cardiothoracic Surgery
Record Identifier: 9984051529802771

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