Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy

Department of Internal Medicine, University of Michigan, Ann Arbor, USA. stevensm@umich.edu

OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS: Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.

This article has been cited by other articles:

				G. Karayannis, G. Giamouzis, E. Alexandridis, P. Kamvrogiannis, J. Butler, J. Skoularigis, and F. Triposkiadis Prevalence of impaired coronary flow reserve and its association with left ventricular diastolic function in asymptomatic individuals with major cardiovascular risk factors European Journal of Cardiovascular Prevention & Rehabilitation, April 1, 2011; 18(2): 326 - 333. [Abstract] [Full Text] [PDF]

				F. G. Hage and A. E. Iskandrian Cardiac Autonomic Denervation in Diabetes Mellitus Circ Cardiovasc Imaging, March 1, 2011; 4(2): 79 - 81. [Full Text] [PDF]

				M. C. Gerson, J. H. Caldwell, K. Ananthasubramaniam, I. P. Clements, M. J. Henzlova, A. Amanullah, and A. F. Jacobson Influence of Diabetes Mellitus on Prognostic Utility of Imaging of Myocardial Sympathetic Innervation in Heart Failure Patients Circ Cardiovasc Imaging, March 1, 2011; 4(2): 87 - 93. [Abstract] [Full Text] [PDF]

				A. Flotats and I. Carrio Is Cardiac Autonomic Neuropathy the Basis of Nonischemic Diabetic Cardiomyopathy? J. Am. Coll. Cardiol. Img., December 1, 2010; 3(12): 1216 - 1218. [Full Text] [PDF]

				G. N. Shivu, K. Abozguia, T. T. Phan, I. Ahmed, R. Weaver, P. Narendran, M. Stevens, and M. Frenneaux Increased Left Ventricular Torsion in Uncomplicated Type 1 Diabetic Patients: The role of coronary microvascular function Diabetes Care, September 1, 2009; 32(9): 1710 - 1712. [Abstract] [Full Text] [PDF]

				A. P. Kellogg, K. Converso, T. Wiggin, M. Stevens, and R. Pop-Busui Effects of cyclooxygenase-2 gene inactivation on cardiac autonomic and left ventricular function in experimental diabetes Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H453 - H461. [Abstract] [Full Text] [PDF]

				F. Cosentino, L. Ryden, P. Francia, and L. G. Mellbin CHAPTER 14 Diabetes Mellitus and Metabolic Syndrome ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				A. I. Vinik and D. Ziegler Diabetic Cardiovascular Autonomic Neuropathy Circulation, January 23, 2007; 115(3): 387 - 397. [Full Text] [PDF]

				B. D. Rosen, J. A.C. Lima, K. Nasir, T. Edvardsen, A. R. Folsom, S. Lai, D. A. Bluemke, and M. Jerosch-Herold Lower Myocardial Perfusion Reserve Is Associated With Decreased Regional Left Ventricular Function in Asymptomatic Participants of the Multi-Ethnic Study of Atherosclerosis Circulation, July 25, 2006; 114(4): 289 - 297. [Abstract] [Full Text] [PDF]

				G A Suarez, V M Clark, J E Norell, T E Kottke, M J Callahan, P C O'Brien, P A Low, and P J Dyck Sudden cardiac death in diabetes mellitus: risk factors in the Rochester diabetic neuropathy study J. Neurol. Neurosurg. Psychiatry, February 1, 2005; 76(2): 240 - 245. [Abstract] [Full Text] [PDF]

				R. Pop-Busui, I. Kirkwood, H. Schmid, V. Marinescu, J. Schroeder, D. Larkin, E. Yamada, D. M. Raffel, and M. J. Stevens Sympathetic dysfunction in type 1 diabetes: Association with impaired myocardial blood flow reserve and diastolic dysfunction J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2368 - 2374. [Abstract] [Full Text] [PDF]

				C. Freccero, H. Svensson, S. Bornmyr, P. Wollmer, and G. Sundkvist Sympathetic and Parasympathetic Neuropathy Are Frequent in Both Type 1 and Type 2 Diabetic Patients Diabetes Care, December 1, 2004; 27(12): 2936 - 2941. [Abstract] [Full Text] [PDF]

				Z. Y. Fang, J. B. Prins, and T. H. Marwick Diabetic Cardiomyopathy: Evidence, Mechanisms, and Therapeutic Implications Endocr. Rev., August 1, 2004; 25(4): 543 - 567. [Abstract] [Full Text] [PDF]

				M. Taskiran, T. Fritz-Hansen, V. Rasmussen, H. B. W. Larsson, and J. Hilsted Decreased Myocardial Perfusion Reserve in Diabetic Autonomic Neuropathy Diabetes, November 1, 2002; 51(11): 3306 - 3310. [Abstract] [Full Text] [PDF]

				M. Pietila, K. Malminiemi, R. Vesalainen, T. Jartti, M. Teras, K. Nagren, P. Lehikoinen, and L.-M. Voipio-Pulkki Exercise Training in Chronic Heart Failure: Beneficial Effects on Cardiac 11C-Hydroxyephedrine PET, Autonomic Nervous Control, and Ventricular Repolarization J. Nucl. Med., June 1, 2002; 43(6): 773 - 779. [Abstract] [Full Text] [PDF]

				M. F. Di Carli, D. Bianco-Batlles, M. E. Landa, A. Kazmers, H. Groehn, O. Muzik, and G. Grunberger Effects of Autonomic Neuropathy on Coronary Blood Flow in Patients With Diabetes Mellitus Circulation, August 24, 1999; 100(8): 813 - 819. [Abstract] [Full Text] [PDF]