Cardiac Norepinephrine Stores in Experimental Heart Failure in the Dog*

Chidsey, Charles A.; Kaiser, Gerard A.; Sonnenblick, Edmund H.; Spann, James F.; Braunwald, Eugene

doi:10.1172/jci105113

Cited by 188 publications

(45 citation statements)

References 32 publications

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“…13 [25][26][27][28][29] In either case, in patients with severe left ventricular failure, plasma catecholamines fail to increase and may even decrease with vasodilators;"'' 30 this is consistent with our observations that patients with a markedly reduced CI manifested little change or even decreases in HR despite significant decreases in systemic pressures during therapy and demonstrated mild rebound changes. Patients in our study with a mildly reduced CI, however, manifested reactions similar to those of normal and hypertensive subjects, which is consistent with experimental evidence that baroreceptor reflexes are only mildly attenuated in subjects in whom ventricular function is only mildly impaired.…”

Section: Discussionsupporting

confidence: 78%

Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.

Packer¹,

Meller²,

Medina³

et al. 1981

Circulation

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SUMMARY Vasodilator drugs activate neurohumoral forces that produce peripheral vasoconstriction and tachycardia and probably cause the rebound events observed upon abrupt withdrawal of therapy. To determine their role in limiting therapeutic vasodilator responses, these reactive forces were measured in 40 patients with severe chronic heart failure by quantifying the magnitude of rebound change (MRC) after nitroprusside withdrawal. Group 1 patients (n = 22), who had minimal reactive vasoconstriction (MRC 27%), showed marked hemodynamic effects with nitroprusside (4.5 ,g/kg/min) and isosorbide dinitrate (40 mg orally), associated with significant decreases in heart rate with both drugs (p < 0.001). Despite administration of the same doses of both drugs, group 2 patients (n = 18), who had marked rebound changes (MRC > 27%), showed significantly smaller changes in cardiac index, systemic vascular resistance and mean arterial pressure (p < 0.001), associated with no change or increases in heart rate. Rebound events were attenuated and the responses to nitroprusside and nitrates were enhanced in four patients in whom these drugs were readministered after pretreatment with i.v. phentolamine (0.3 mg/min). We conclude that activation of neurohumoral forces can limit the hemodynamic responses to vasodilator administration; this supports the use of combination therapy of direct-acting vasodilators and neurohumoral antagonists in selected patients with severe chronic heart failure.

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Section: Discussionsupporting

confidence: 78%

Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.

Packer¹,

Meller²,

Medina³

et al. 1981

Circulation

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“…[8][9][10] Unfortunately, a noninvasive method to detect and characterize these abnormalities has not been described. Early studies with MIBG have suggested the potential of this radiopharmaceutical as a myocardial imaging agent with kinetic and distribution properties that might reflect the integrity of myocardial sympathetic innervation.5 Myocardial norepinephrine kinetics involve three major compartments: transport into the neuronal axoplasm, transport into the terminal storage vesicles, and transport in the extraneuronal myocardial tissues.…”

Section: Discussionmentioning

confidence: 99%

Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy.

et al. 1988

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1-123 metaiodobenzylguanidine (MIBG) is a new radiopharmaceutical with properties that allow the characterization of the sympathetic innervation of several organ systems. In this study, we used MIBG with tomographic imaging to evaluate noninvasively the differences in myocardial sympathetic innervation in 14 healthy volunteers and 16 patients with severe dilated cardiomyopathy (CM). Initial (15-minute) images demonstrated no significant differences in MIBG concentration in the hearts of patients with CM and of healthy volunteers. However, the myocardial retention of MIBG was significantly reduced in the patients with CM. Expressed as the percent washout from 15 to 85 minutes, the patients with CM had a 28 ± 12% washout rate compared with 6 8% in the controls (p

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“…It is interesting to note that most circumstances which are associated with an increased release of norepinephrine such as hemorrhage (15) and cardiac failure (16), are most frequently associated with a diminution, rather than an increase, in renal water excretion. Thus, the diuretic effect of intravenous norepinephrine (1-6) has heretofore seemed rather paradoxical.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Suppression of Vasopressin during Alpha-Adrenergic Stimulation with Norepinephrine

Berl¹,

Cadnapaphornchai²,

Harbottle³

et al. 1974

J. Clin. Invest.

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A B S T R A C T Recent studies have demonstrated that the water diuresis associated with intravenous infusion of norepinephrine is mediated primarly by suppression of antidiuretic hormone (ADH) release. To investigate whether the increase in cerebral perfusion pressure with intravenous norepinephrine (0.5 jg/kg/min) is directly responsible for suppression of ADH release, the carotid circulation of dogs was pump-perfused bilaterally to selectively increase cerebral perfusion pressure. In six experiments cerebral perfusion pressure was increased from a mean of 125 to 151 mm Hg and then returned to 120 mm Hg. This maneuver was not associated with a reversible increase in renal water excretion. The possibility was also examined that norepinephrine exerts a direct central effect to suppress ADH release. In 12 experiments norepinephrine was infused into the carotid artery in a subpressor dose (0.12 ,tg/kg/min) estimated to equal the amount of the catecholamine reaching the cerebral circulation with intravenous norepinephrine. The urinary osmolality (Uosm) was not significantly altered with intracarotid norepinephrine (932 to 959 mosmol/kg H20. The possibility was also examined that changes in autonomic neural tone from arterial baroreceptors is responsible for suppression of ADH release with intravenous norepinephrine. In sham-operated animals intravenous norepinephrine diminished Uosm from 1,034 to 205 mosmol/kg H20 (P < 0.001) whereas in animals with denervated arterial baroreceptors intravenous norepinephrine was not associated with a significant alteration in Uosm (1,233 to 1,232 mosmol/kg) H20. These different effects on urinary osmolality occurred in the absence of differences in plasma osmolality and volume status. The results therefore indicate that norepinephrine primarily suppresses ADH release by altering autonomic baroreceptor tone rather than by a diReceived for publication 9 July 1973 and in revised form 29 August 1973. rect central or pressor effect of the catecholamine. This same mechanism may be the primary pathway for other nonosmotic influences on ADH release. INTRODUCTIONThe effect of intravenous norepinephrine to increase renal water excretion has been well documented in both humans (1-3) and animals (4, 5). Recent experimental evidence has demonstrated that this effect of norepinephrine is primarily related to its alpha adrenergic-stimulating properties (4,5). Moreover, studies from our laboratory have shown that this effect of norepinephrine on -renal water excretion is mediated primarily by suppression of vasopressin release rather than a direct effect

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Cardiac Norepinephrine Stores in Experimental Heart Failure in the Dog*

Cited by 188 publications

References 32 publications

Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.

Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.

Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy.

Mechanism of Suppression of Vasopressin during Alpha-Adrenergic Stimulation with Norepinephrine

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