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Coronary flow rate dependent enzyme release rate from normoxic and anoxic rat hearts in vitro
Insights
Low coronary flow rate (CFR) impacts enzyme release from rat hearts. Reduced CFR during normoxic or anoxic ischemia initially increases, then decreases, lactate dehydrogenase (LDH) release, indicating heterogeneous perfusion and enzyme leakage inhibition.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Ischemia Research
Background:
- Understanding enzyme release during cardiac ischemia is crucial for diagnosing myocardial injury.
- Coronary flow rate (CFR) is a key determinant of myocardial oxygen supply and metabolic function.
- Lactate dehydrogenase (LDH) is a common biomarker for cardiac cell damage.
Purpose of the Study:
- To investigate the relationship between coronary flow rate (CFR) and lactate dehydrogenase (LDH) enzyme release in isolated perfused rat hearts under normoxic and anoxic ischemic conditions.
- To determine how varying CFR influences myocardial perfusion homogeneity and subsequent enzyme leakage.
Main Methods:
- Isolated rat hearts were subjected to either normoxic or anoxic ischemia for 3 hours.
- Coronary flow rate (CFR) and total lactate dehydrogenase (LDH) activity released into the perfusate were measured.
- Coronary vascular resistance (CVR) and percentage of unperfused myocardium were assessed.
Main Results:
- LDH release showed a positive correlation with CFR during anoxic ischemia (0-17 ml x min⁻¹).
- During normoxic ischemia, LDH release correlated positively with CFR up to 7 ml x min⁻¹, then negatively at higher CFRs.
- Mean CFR was negatively correlated with CVR, and CVR positively correlated with unperfused myocardium in normoxic ischemia.
Conclusions:
- Low CFR leads to heterogeneous myocardial perfusion, which paradoxically inhibits enzyme leakage from myocytes.
- The relationship between CFR and LDH release is complex and depends on the ischemic condition (normoxic vs. anoxic).
- Myocardial perfusion heterogeneity, influenced by CFR, plays a significant role in modulating enzyme release during ischemia.
Abstract:
To study the relation between coronary flow rate (CFR) and the rate of enzyme release from isolated perfused rat hearts which were either normoxic or anoxic, we measured the total activity of lactate dehydrogenase (LDH) released from the heart during a 3 h test period and mean CFR during that period. The test period consisted of (under)perfusion in the presence of oxygen and sodium pyruvate (normoxic ischaemia) or (under)perfusion in the absence of oxygen and metabolic substrates (anoxic ischaemia). Activity of LDH released during the 3 h test period correlated positively with mean CFR during anoxic ischaemia for the whole range of CFR from 0 to 17 ml X min-1, and during normoxic ischaemia when CFR was in the range 0 to 7 ml X min-1. At a CFR higher than 7 ml X min-1, the activity of LDH released during 3 h of normoxic ischaemia correlated negatively with CFR. Mean CFR was negatively correlated with coronary vascular resistance at the end of the 3 h period of perfusion. In the hearts subjected to normoxic ischaemia, coronary vascular resistance correlated positively with the percentage of myocardium unperfused. This study shows that a low CFR leads to unhomogeneous myocardial perfusion, which inhibits leakage of enzymes from myocytes into the perfusate.