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Tyrosine hydroxylase and choline acetyltransferase activities in ischemic canine heart
Insights
Following coronary artery occlusion in dogs, tyrosine hydroxylase (TH) activity decreased early in ischemic heart tissue, while choline acetyltransferase (CAT) activity decreased later. These findings reveal differential effects of infarction on sympathetic and parasympathetic nerve markers.
Area of Science:
- Cardiovascular Physiology
- Neurochemistry
- Myocardial Infarction Research
Background:
- Coronary artery occlusion can impact cardiac neurotransmitter synthesis enzymes.
- Sympathetic and parasympathetic nervous system enzyme activities may respond differently to ischemic events.
Purpose of the Study:
- To investigate the differential changes in tyrosine hydroxylase (TH) and choline acetyltransferase (CAT) activity in canine hearts after coronary artery occlusion.
- To correlate enzyme activity changes with regional myocardial blood flow deficits.
Main Methods:
- Induction of coronary artery occlusion (LAD ligation) or sham procedure in dogs.
- Measurement of myocardial blood flow using the microsphere technique.
- Assay of tyrosine hydroxylase (TH) and choline acetyltransferase (CAT) activity in normal and ischemic cardiac tissues at various time points.
Main Results:
- Early (5 hours post-ligation) heterogeneous decreases in TH activity were observed in the ischemic zone, correlating with blood flow deficits.
- Insignificant changes in CAT activity were noted at 2.5 and 5 hours post-ligation.
- Progressive and significant decreases in CAT activity occurred later, at 25 and 170 hours post-ligation, also showing heterogeneity.
Conclusions:
- Myocardial infarction induces early, heterogeneous reductions in TH activity, linked to perfusion deficits.
- Decreases in CAT activity are also heterogeneous but manifest later than TH changes.
- These results highlight distinct temporal and biochemical responses of sympathetic and parasympathetic indices to cardiac infarction.
Abstract:
After coronary artery occlusion, enzymes involved in the synthesis of sympathetic and parasympathetic neurotransmitters may change disparately. We investigated this in the canine heart by measuring the activity of tyrosine hydroxylase (TH) and choline acetyltransferase (CAT) in normal and ischemic tissue. Myocardial blood flow in selected regions was measured by the microsphere technique. Dogs had either ligation of the anterior descending coronary artery (LAD) or sham ligation (S). In the ischemic zone 5 h after LAD ligation, TH activity was lower than in corresponding anterior apical zones of S dogs (5.1 +/- 1.7 vs. 13.5 +/- 2.3 nmol.g-1.h-1) (P less than 0.05) with a tendency for greater decreases in endocardium than in epicardium. In contrast, there were insignificant changes in CAT activity 2.5 and 5 h after LAD ligation. Thereafter, progressive and significant (P less than 0.05) decreases occurred in CAT activity at 25 and 170 h after LAD ligation. Thus there are early heterogeneous decreases in TH activity that correlate directly with heterogeneous deficits in blood flow. Although decreases in CAT are also heterogeneous and correlate with deficits in perfusion, these changes occur later. These results indicate differences in the effects of infarction on these biochemical indices of sympathetic and parasympathetic innervation in canine heart.