Enzyme release during myocardial anoxia: A study of metabolic protection
| Autor: | S. M. Humphrey, D. J. Hearse |
|---|---|
| Rok vydání: | 1975 |
| Předmět: |
Male
medicine.medical_specialty Exacerbation Myocardial Infarction Adenylate kinase Coronary Disease Dehydrogenase Biology Pharmacology Methylprednisolone Antioxidants Hydroxybutyrate Dehydrogenase Oxygen Consumption Internal medicine medicine Animals Humans Aspartate Aminotransferases Creatine Kinase Molecular Biology chemistry.chemical_classification Myocardium Adenylate Kinase Hypoxia (medical) Rats Enzyme Activation Perfusion Glucose Endocrinology Enzyme chemistry Protective Agents Potassium biology.protein Creatine kinase medicine.symptom Cardiology and Cardiovascular Medicine Anaerobic exercise |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 7:463-482 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/0022-2828(75)90164-9 |
| Popis: | In studies with the isolated perfused anoxic rat heart, myocardial enzyme release was used as an index of cellular damage. Anoxic damage (with K+ arrest) was characterized by measuring the release of four enzymes (creatine phosphokinase, α-hydroxybutyrate dehydrogenase, glutamate oxaloacetate transaminase and adenylate kinase). The possibility of protecting the myocardium against anoxic damage by using potential metabolic protective agents was investigated. The inclusion of glucose as an anaerobic energy source in the perfusion fluid during the entire anoxic period afforded considerable metabolic protection, the period of anoxia that could be tolerated without significant enzyme release was extended and the overall release was reduced. In addition, glucose during anoxia was able to confer protection against the exacerbation of enzyme release induced by reoxygenation. The results with graded hypoxia were similar to those with glucose and the two were additive. An increasing availability of oxygen afforded an increasing degree of protection. The membrane stabilizing drug methyl prednisolone had a variable effect upon enzyme release but was unable to confer true protection with increased viability upon the myocardium. The exacerbation of enzyme release induced by reoxygenation was further investigated. Potential protective agents (glucose, methyl prednisolone and the anti-oxidant ascorbate) introduced at the time of reoxygenation had little protective effect. Stepwise reoxygenation studies revealed that the extent of exacerbation was determined by the concentration of O2 used in the reoxygenation process, the higher the O2 tension the greater the exacerbation of release. It is proposed that the onset of major myocardial enzyme release reflects the transition from reversible to irreversible cellular damage and that the action of metabolic protective agents is to prevent the deterioration of the cells to a point where they become susceptible to irreversible damage. Once the cells enter a state of irreversible damage and major enzyme release occurs then metabolic protection becomes ineffective. The results underline the importance of the need for the rapid introduction of protective agents to the anoxic myocardium. In this experimental model, protection must be initiated before the transition from reversible to irreversible cellular damage and this may possibly be best achieved either by reducing cellular energy demands or by maximizing cellular energy production. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|