Effects of Cardiac Sympathetic Innervation on Coronary Blood Flow

Carli, Marcelo F. Di; Tobes, Michael C.; Mangner, Thomas J.; Levine, Arlene B.; Muzik, Otto; Chakroborty, Praloy; Levine, T. Barry

doi:10.1056/nejm199704243361703

Cited by 211 publications

(158 citation statements)

References 38 publications

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“…Previous work has shown that sympathetic reinnervation contributes to partial restoration of exercise capacity 29 and plays a role for regulation of myocardial blood flow and metabolism. 30,31 In the present study, however, cardiac work, oxygen consumption, and efficiency at rest were not different between reinnervated and denervated transplant recipients. Additionally, there was no regional difference for contractile performance or oxygen consumption in reinnervated and denervated territories.…”

Section: Discussioncontrasting

confidence: 67%

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

et al. 2001

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Background-The lack of cardiac catecholamine uptake and storage caused by sympathetic denervation may influence performance of the transplanted heart. Reinnervation, occurring late after transplantation, may partially resolve these effects. In this study, oxidative metabolism and its relation to cardiac work were compared in allografts and normal and failing hearts, and the effects of sympathetic reinnervation were evaluated. Methods and Results-Twenty-seven nonrejecting, symptom-free transplant recipients, 11 healthy control subjects, and 10 patients with severe dilated cardiomyopathy underwent PET with 11 C acetate for assessment of oxidative metabolism by the clearance constant k(mono) and radionuclide angiography or MRI for measurement of ventricular function, geometry, and work. Efficiency was estimated noninvasively by a work-metabolic index [WMIϭ(stroke volumeϫheart rateϫsystolic pressure)/k(mono)]. In 14 of 27 transplants, presence of regional reinnervation was identified with PET and the catecholamine analogue 11 C hydroxyephedrine (extent, 24Ϯ14% of left ventricle). The WMI was comparable in normal subjects and reinnervated and denervated transplants (6.2Ϯ2.3 versus 4.9Ϯ2.0 versus 4.9Ϯ1.2 ⅐ 10 6 mm Hg · mL; PϭNS) and significantly lower in cardiomyopathy patients (3.0Ϯ1.3 ⅐ 10 6 mm Hg ⅐ mL; PϽ0.001). For normal subjects and transplant recipients, the WMI was significantly correlated with afterload (peripheral vascular resistance; rϭϪ0.65, PϽ0.01), preload (end-diastolic volume; rϭ0.78, PϽ0.01), and stroke volume (rϭ0.81, PϽ0.01) but not with hydroxyephedrine retention (transplants only; rϭ0.09, PϭNS). Conclusions-After transplantation, cardiac efficiency is improved compared with failing hearts and comparable to normal hearts. Differences between denervated and reinnervated allografts were not surveyed. Additionally, the dependency on loading conditions and contractility was preserved, suggesting that normal regulatory interactions for efficiency are intact and that sympathetic tone does not play a role under resting conditions.

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Section: Discussioncontrasting

confidence: 67%

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

et al. 2001

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“…2,16 Whereas the exact mechanism by which this mixed humoral-nervous sympathetic stimulation mediates coronary vasodilation is unknown, activation of both ␤ 2 -adrenergic receptors on coronary smooth muscle cells and ␣ 2 -adrenergic receptors on endothelial cells with subsequent nitric oxide release has been suggested. 21,22 In our patients with ischemic heart disease, myocardial blood flow during sympathetic stimulation remained unchanged in the face of a 65% increase in cardiac work estimated by the rate-pressure product, and an increase in the coronary vascular resistance was recorded.…”

Section: Discussionmentioning

confidence: 99%

“…1 Impaired myocardial sympathetic innervation as in diabetic autonomic neuropathy or in the transplanted heart is associated with a reduced coronary vasodilatory response to sympathetic stimulation, whereas sympathetic reinnervation of the transplanted heart is associated with a normal coronary vasodilatory response. 2,3 In patients with coronary atherosclerosis and endothelial dysfunction, an abnormally augmented response to coronary ␣-adrenergic activation has been shown to result in a reduced coronary blood flow response during sympathetic stimulation. 4 -6 This phenomenon is believed to reflect a disturbance of the balance between coronary endothelial vasodilatory function and vasoconstrictor effects of myocardial sympathetic tone.…”

mentioning

confidence: 99%

Effects of High Thoracic Epidural Analgesia on Myocardial Blood Flow in Patients With Ischemic Heart Disease

et al. 2005

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Background-In patients with ischemic heart disease, high thoracic epidural analgesia (TEA) has been proposed to improve abnormalities of coronary function by inhibiting cardiac sympathetic tone. We evaluated the effect of TEA on myocardial blood flow in patients with ischemic heart disease. Methods and Results-Twenty male patients with multivessel ischemic heart disease were studied. An epidural catheter was inserted between the second and third thoracic vertebral interspace (Th2 to Th3). Analgesia was induced by epidural injection of bupivacaine 0.5%, and a sensory block from the sixth cervical (C6 to C7) to Th10 (Th8 to Th11) vertebral interspace was achieved. Myocardial blood flow was measured with dynamic 13 N-ammonia PET with and without TEA at rest, during pharmacological vasodilation with dipyridamole, and during sympathetic stimulation with the cold pressor test. Myocardial blood flow during dipyridamole increased similarly, regardless of TEA, in all regions except in myocardium subtended by collateral arteries in which blood flow increased more with than without TEA (PϽ0.05). Without TEA, myocardial blood flow during the cold pressor test remained unchanged compared with myocardial blood flow at rest. In contrast, with TEA, myocardial blood flow increased in all vascular territories. Coronary vascular resistance increased during the cold pressor test without TEA, whereas with TEA, coronary resistance decreased in myocardium subtended by nonstenotic and stenotic coronary vessels and remained unchanged in myocardium subtended by occluded vessels. Conclusions-In patients with multivessel ischemic heart disease, TEA partly normalizes the myocardial blood flow response to sympathetic stimulation.

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“…In normal subjects, physiological hyperinsulinaemia can modulate central neural control directed to the heart by inducing vagal withdrawal paralleled by a slight sympathetic activation [26,27,28]. This dual action on the regional autonomic control could explain the overall increase of MBF, and the predominance of sympathetic innervation in the antero-septal ventricular wall [29] could account for the preferential increase of MBF in this region. Of interest, recent radionuclide studies have shown that signs of autonomic neuropathy are present at a very early stage in the heart of patients with diabetes, when microvascular complications are not yet clinically detectable [30].…”

Section: Discussionmentioning

confidence: 99%

Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type II diabetes

et al. 2002

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Aims/hypothesis. We investigated the effect of physiological hyperinsulinaemia on global and regional myocardial blood flow and glucose uptake in five patients with Type II (non-insulin-dependent) diabetes mellitus and seven healthy control subjects. Methods. Myocardial blood flow was assessed by positron emission tomography with oxygen-15 labelled water (H 2 15 O) either before or after 1 h of euglycaemic hyperinsulinaemia. Myocardial glucose uptake was assessed by positron emission tomography and fluorine-18 labelled fluorodeoxyglucose ( 18 FDG). Results. During hyperinsulinaemia, myocardial blood flow increased from 0.91±0.03 to 1.00±0.03 ml . min -1 . g -1 in control subjects (p<0.005) and from 0.81±0.02 to 0.95±0.04 ml . min -1. g -1 in diabetic patients (p<0.0005). Corresponding glucose uptakes were 0.56±0.01 and 0.36±0.02 µmol . min -1. g -1 (p<0.0001), respectively. During hyperinsulinaemia, the regional distribution of myocardial blood flow and glucose uptake showed higher values in the septum and anterolateral wall (short axis) and in the mid-ventricle (long axis) in control subjects, and insulin action was circumscribed to these regions. In diabetic patients, the regional distribution of glucose uptake was similar; however, insulin-induced increase of myocardial blood flow was mainly directed to the postero-inferior areas (short axis) and to the base (long axis) of the heart, thus cancelling the predominance of the anterior wall observed before insulin administration. Conclusion/interpretation. These results provide evidence that insulin-mediated regulation of global myocardial blood flow is preserved in Type II diabetic patients. In contrast, the regional re-distribution of myocardial blood flow induced by insulin is directed to different target areas when compared with healthy subjects, thereby resulting in a mismatch between blood flow and glucose metabolism. [Diabetologia (2002[Diabetologia ( ) 45:1404[Diabetologia ( -1409 Keywords Insulin, diabetes, myocardial glucose metabolism, myocardial perfusion, positron emission tomography. The availability of non-invasive quantification of myocardial blood flow (MBF) with positron emission tomography (PET) has re-opened the long debated issue concerning the role of insulin in the regulation of myocardial perfusion. A better understanding of this issue carries important pathophysiological implications on the relation between insulin resistance and enhanced cardiovascular risk. In previous studies [1,2,3,4,5,6], the use of invasive techniques and/or anaesthesia could have introduced confounding factors, such as variable degrees of sympathetic activation and circulating NEFA concentrations. Using PET and oxygen-15 labelled water, we have shown that in healthy

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Effects of Cardiac Sympathetic Innervation on Coronary Blood Flow

Abstract: Increases in coronary blood flow in response to sympathetic stimulation correlated with the regional norepinephrine content in the cardiac sympathetic-nerve terminals. These findings suggest that cardiac adrenergic signals play an important part in regulating myocardial blood flow.

Cited by 211 publications

References 38 publications

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

Effects of High Thoracic Epidural Analgesia on Myocardial Blood Flow in Patients With Ischemic Heart Disease

Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type II diabetes

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