Although a reduction in myocardial norepinephrine stores in cardiac hypertrophy and congestive failure is well documented, norepinephrine turnover has been inadequately studied in such hearts. We compared norepinephrine turnover in control and cardiomyopathic hamsters by following the decline in specific activity of myocardial norepinephrine after labeling with an intraperitoneal tracer dose of 3 H-norepinephrine. Adult myocardial norepinephrine concentrations were not attained until 4 weeks of age in both strains. There was no difference in the rate constant (K) for myocardial norepinephrine turnover (0.107 ± 0.004 hours" 1 vs. 0.100 ± 0.005 hours" 1 ) in the two strains of hamsters during the neonatal period. In young control hamsters, K fell to 0.064 ± 0.004 hours" 1 , but that for age-matched hamsters with mild cardiac hypertrophy was 0.102 ± 0.001 hours" 1 (P < 0.001). There was little change in K as control hamsters aged. With the development of more severe hypertrophy in cardiomyopathic hamsters, cardiac norepinephrine decreased and resting K rapidly increased to approach the value obtained when hamsters were subjected to immobilization stress (0.302 ± 0.013 hours" 1 ). The maximum achievable K remained the same for both control and dystrophic hamsters even during terminal disease. Prolonged immobilization led to a reduction in cardiac norepinephrine in both strains. Ganglionic blockade of failing hamsters completely restored the levels of both cardiac norepinephrine and K to control values. Splenic noradrenergic nerves showed no change in K, norepinephrine content, or maximum K during cardiac decompensation. We conclude that, in the late stages of hamster cardiomyopathy, there is a progressive and possibly specific increase in cardiac sympathetic tone which leads to a concomitant decrease in cardiac norepinephrine. With the loss of sympathetic reserve, congestive failure supervenes.• The normal heart is richly supplied with noradrenergic sympathetic nerves. This innervation contributes little to intrinsic myocardial function (1) but is a most important mechanism for the elevation of cardiac output in response to a physiological stress such as exercise (2). In the absence of a catecholamine stimulus, cardiac output can be increased solely by the Frank-Starling mechanism (3). Dilated or noncompliant hearts, however, cannot take further advantage of the length-tension relationship and thus depend on sympathetic support to maintain cardiac output (4). This paper won the Young Investigators' Award given by the Canadian Cardiovascular Society.Dr. Sole was a Hunter Fellow of the Ontario Heart Foundation.Please address reprint requests to Dr. Michael J. Sole, Clinical Sciences Division, Medical Sciences Building, University of Toronto, Toronto, Canada M5S 1A8.Received May 1, 1975. Accepted for publication October 2, 1975.Circulation Research, Vol. 37, December 1975 There is considerable evidence for sympathetic dysfunction in the hearts of humans with congestive heart failure and animals with experime...

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