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Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure
Insights
In congestive heart failure, myocardial norepinephrine levels are not uniformly low, contrary to previous hypotheses. Further research is needed to understand factors regulating cardiac catecholamine concentration in these patients.
Area of Science:
- Cardiology
- Neuropharmacology
- Heart Failure Research
Background:
- Congestive heart failure (CHF) is often associated with altered myocardial catecholamine levels.
- Previous hypotheses suggested a uniform depletion of norepinephrine and increase in dopamine in CHF due to a rate-limiting step in norepinephrine synthesis.
Purpose of the Study:
- To investigate the hypothesis that myocardial norepinephrine is depleted and dopamine is increased in patients with CHF.
- To analyze left ventricular catecholamine and plasma norepinephrine levels in patients undergoing cardiac transplantation.
Main Methods:
- Assayed left ventricular catecholamine (norepinephrine and dopamine) and plasma norepinephrine levels in 39 patients with CHF undergoing cardiac transplantation.
- Correlated cardiac norepinephrine levels with peripheral vascular resistance and other clinical variables.
Main Results:
- Plasma norepinephrine was elevated in all patients.
- Myocardial norepinephrine levels showed significant variability, not uniformly depleted.
- Observed different patterns of myocardial norepinephrine and dopamine, including normal levels, low levels of both, and preserved norepinephrine with high dopamine.
Conclusions:
- Myocardial norepinephrine concentration is not uniformly reduced in patients with severe CHF.
- The factors regulating myocardial catecholamine concentration and adrenergic function in CHF require further investigation.
Abstract:
Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 +/- 472 micrograms/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 +/- 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 +/- 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p less than 0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.