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The effect of orotic acid on the response of the recently infarcted rat heart to hypothermic cardioplegia.
- Source :
-
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery [Eur J Cardiothorac Surg] 1991; Vol. 5 (2), pp. 82-92; discussion 93. - Publication Year :
- 1991
-
Abstract
- Patients with a recent myocardial infarction have a higher morbidity and mortality than comparable patients with chronic myocardial ischaemia. We postulated that this might be due to a reduced overall tolerance of the heart to cardioplegic arrest in the presence of a recent infarct. We postulated that orotic acid, a pyrimidine precursor which augments the rate of protein synthesis, might improve the response of the recently infarcted heart to cardioplegic arrest. Myocardial infarction was produced in rats by coronary ligation. The rats were then divided into two groups according to whether they were treated with oral orotic acid (10 mg/kg per day) or untreated. A sham-operated (non-infarcted) group served as normal controls. After 2 days, the hearts (n = 12 per group) underwent 1 h of cardioplegic arrest at 23 degrees C on the isolated working heart apparatus. Before arrest, maximum cardiac function in the untreated infarct group was lower than in the normal group (P less than 0.05), whereas in the treated group, function was similar to the normal group. After arrest there was severe depression of cardiac function in the untreated infarct group: only 57% recovery of the pre-arrest value compared with 86% in the normal group (P less than 0.001). In the orotic acid treated group, recovery (90%) was significantly greater than in the untreated group (P less than 0.001) and equivalent to the normal group. Oxygen utilisation, when corrected for external work, was higher in both infarct groups than in the normal group before and after arrest (P less than 0.05 in both cases). Total uridine nucleotide content of the infarcted and non-infarcted zones of the heart was increased. Treatment with orotic acid produced a further upward trend in uridine nucleotide levels. We conclude that an established, recent infarct reduces the overall tolerance of the heart to hypothermic cardioplegia. Treatment with orotic acid improves the function of the infarcted heart following cardioplegic arrest, and may therefore improve the results of urgent cardiac surgery in patients with myocardial infarction.
- Subjects :
- Animals
Blood Pressure drug effects
Blood Pressure physiology
Cardiac Output drug effects
Cardiac Output physiology
Heart drug effects
Heart physiopathology
Ischemia physiopathology
Male
Myocardial Infarction pathology
Myocardium chemistry
Myocardium metabolism
Orotic Acid administration & dosage
Oxygen Consumption drug effects
Oxygen Consumption physiology
Rats
Rats, Inbred Strains
Uracil Nucleotides analysis
Heart Arrest, Induced
Myocardial Infarction physiopathology
Orotic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1010-7940
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 2018659
- Full Text :
- https://doi.org/10.1016/1010-7940(91)90005-5