Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

Abstract

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.

Multiparametric Molecular Imaging Provides Mechanistic Insights into Sympathetic Innervation Impairment in the Viable Infarct Border Zone

“…Using volumetric sampling of the last frame of the perfusion study, we defined myocardial radioactivity in 460 left ventricular (LV) sectors and depicted the radioactivity in a polar map (19). For reproducible and comparable quantitative analysis, the so-defined cardiac long-axis and myocardial segments were automatically transferred to dynamic series of all other tracers, and time-activity curves were obtained, as previously established (20,21). Additionally, for each tracer, arterial input function was defined by a small region of interest in the LV cavity.…”

Abnormal Myocardial Energy-Production State in Mitochondrial Cardiomyopathy and Acute Response to L-Arginine Infusion - C-11 Acetate Kinetics Revealed by Positron Emission Tomography -

“…15, 16 Efficiency can be precisely quantified using invasive measurement of ventricular stroke work and myocardial oxygen consumption. 15 This concept has been used successfully to assess the effects of medical therapy on the heart.…”

“…15 This concept has been used successfully to assess the effects of medical therapy on the heart. 16 To evaluate myocardial efficiency non-invasively, an index known as the "work metabolic index" is usually used. 17 However, to measure the work metabolic index, simultaneous measurement of kmono and stroke volume (SV) is required.…”

Clinical Determinants of Ventricular Sympathetic Reinnervation After Orthotopic Heart Transplantation

“…PET was performed as described previously 6,9,10,12 with an ECAT 951, EXACT, or EXACT HRϩ scanner (CTI/Siemens). Briefly, after acquisition of a transmission scan and qualitative assessment of myocardial perfusion with [ 13 N]-ammonia or [ 11 C]acetate, 600 MBq of the catecholamine analogue [ 11 C]hydroxyephedrine (HED) was injected intravenously, and a dynamic imaging sequence was acquired.…”

“…The occurrence of subsequent partial reinnervation of the left ventricle has been demonstrated in various studies, [1][2][3][4][5][6] and the physiological importance of this phenomenon has been supported by description of beneficial effects on regulation of myocardial blood flow, 7 metabolism, 8,9 and exercise performance. 10,11 Because of the increasing evidence that restoration of sympathetic innervation is advantageous for transplant recipients, approaches to support reinnervation are of interest, and a more detailed understanding of clinical determinants of reinnervation is desirable.…”