Tracer norepinephrine kinetics in coronary circulation of patients with heart failure secondary to chronic pressure and volume overload.
Controversy exists over the nature of the abnormality in cardiac sympathetic nerves in heart failure. In the cardiomyopathy of the Syrian hamster, reduction in tissue stores and increased turnover of norepinephrine is clearly associated with excessive sympathetic stimulation but in animal models and humans with heart failure secondary to mechanical overload there is evidence for depression of neuronal uptake. Because norepinephrine is both released and taken up by sympathetic fibers it is impossible to assess norepinephrine kinetics in an intact heart without separating these two functions. A technique for doing so has recently been developed in normal dogs and we therefore acquired similar data in humans with heart failure secondary to chronic pressure and volume overload. The technique involves the combination of transient norepinephrine tracer coronary sinus outflow in relation to intravascular and interstitial references after simultaneous injection into the left coronary artery and the measurement of endogenous norepinephrine concentrations in artery and coronary sinus. We found a marked reduction in cardiac norepinephrine release and uptake in a group of patients with clinical left ventricular failure secondary to mechanical overload, relative to a group of patients with no failure. Norepinephrine balance and overflow across the heart were not significantly different. We conclude that there is hypofunction of the cardiac sympathetic nerves in heart failure secondary to mechanical overload and that traditional methods are inadequate in assessing cardiac norepinephrine kinetics when there are simultaneous changes in neuronal uptake and release.
D000328:Adult; D001794:Blood Pressure; D006328:Cardiac Catheterization; D003331:Coronary Vessels / Q000502:physiology; D006321:Heart / Q000294:innervation; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism
D013395:Sucrose; D009638:Norepinephrine