Cardiac sympathetic nerve function assessed by [131I]metaiodobenzylguanidine after ischemia and reperfusion in anesthetized dogs

Takatsu, Hisato; Duncker, Carlos Martínez; Arai, M.; Becker, Lewis C.

doi:10.1016/s1071-3581(97)90047-7

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Although these changes are similar to those reported in viable myocardium after transmural infarction, [13][14][15] subendocardium. This raises the possibility that inhomogeneity of sympathetic innervation arising from reversible ischemia may contribute to the increased risk of sudden cardiac death when hibernating myocardium cannot be revascularized.…”

Section: Discussionsupporting

confidence: 86%

“…The remainder is nonspecific uptake and not affected by denervation. 15 Although controversy exists as to whether acute reductions in MIBG uptake reflect the uptake-1 mechanism after acute infarction, 13-15 ␤-adrenergic-mediated changes in myocardial function 5 and ␣-adrenergic coronary vasoconstriction 6 in response to sympathetic nerve stimulation are immediately attenuated after brief reversible episodes of transmural ischemia. In addition, animal models have shown that reductions in MIBG activity are associated with reductions in tissue norepinephrine content and sympathetic nerve density, which supports the use of MIBG as an index of sympathetic nerve function in the chronic setting.…”

Section: Discussionmentioning

confidence: 99%

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Spatial Inhomogeneity of Sympathetic Nerve Function in Hibernating Myocardium

et al. 2002

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Background-Although humans and swine with hibernating myocardium have an increased risk of sudden death, the contribution of chronic alterations in sympathetic nerve function is unknown. Acute transmural ischemia causes inhomogeneity in sympathetic innervation that may lead to lethal arrhythmias, but it is unclear whether similar abnormalities develop in response to chronic reversible ischemia. Methods and Results-Swine were chronically instrumented with a left anterior descending coronary artery (LAD) stenosis that produced hibernating myocardium after 3 months. Resting subendocardial flow (LAD 0.75Ϯ0.14 versus 1.19Ϯ0.14 mL · min Ϫ1 · g Ϫ1 , PϽ0.05) and wall thickening (LAD 15Ϯ3% versus 40Ϯ2%, PϽ0.05) were reduced compared with normal remote regions, without triphenyltetrazolium chloride evidence of necrosis.131 I-metaiodobenzylguanidine (MIBG) was used to assess integrity of the norepinephrine uptake-1 mechanism, and the spatial and transmural distributions were quantified by ex vivo counting. In hibernating myocardium, MIBG deposition was decreased in each layer, with the greatest reduction in the subendocardium (LAD subendocardium 0.28Ϯ0.02 versus 0.42Ϯ0.04 mL · g Ϫ1 · min Ϫ1 in normal, PϽ0.05; LAD subepicardium 0.31Ϯ0.03 versus 0.38Ϯ0.04 mL · g Ϫ1 · min Ϫ1 in normal, PϽ0.05). In contrast, there were no spatial alterations of MIBG deposition in sham-instrumented animals. Conclusions-The sympathetic norepinephrine uptake-1 mechanism is impaired in hibernating myocardium. These findings raise the possibility that chronic alterations in sympathetic innervation contribute to the excess mortality seen in the setting of hibernating myocardium. Key Words: hibernation Ⅲ myocardial stunning Ⅲ nervous system, sympathetic Ⅲ death, sudden Ⅲ ischemia S patial variations in regional sympathetic innervation lead to inhomogeneity in cardiac repolarization and may increase the risk of arrhythmic sudden death. 1-3 Regional denervation occurs after myocardial infarction, and lethal arrhythmias may be related to nerve sprouting during reinnervation. 4 Functional denervation has also been observed after brief coronary occlusions, 5,6 as well as in viable risk areas of reperfused myocardial infarcts, 7 which supports the view that sympathetic nerve function is exquisitely sensitive to ischemia.Although transmural ischemia causes cardiac denervation, it is uncertain whether reversible subendocardial ischemia could chronically affect sympathetic nerve function and contribute to the risk of sudden death in patients with chronic ischemic heart disease. In support of this, clinical studies have demonstrated an increased mortality when patients with hibernating myocardium are not revascularized, and the excess risk is largely related to sudden death. 8 This increased mortality is also seen in animal studies of chronic hibernating myocardium, in which the cumulative incidence of sudden death approaches 50% over 5 months. 9 We hypothesized that hibernating myocardium exhibits regional inhomogeneity in sympathetic innervation that arise...

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Spatial Inhomogeneity of Sympathetic Nerve Function in Hibernating Myocardium

et al. 2002

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“…Some amount of MIBG injected may be taken up by nonneuronal tissue in the heart. Takatsu et al (39) reported that the reduced MIBG accumulation in the infarcted region after coronary occlusion followed by the reperfusion might result from a deficit in nonneuronal accumulation. The influence of the nonneuronal accumulation in the present results was not evaluated, although the present study was performed without the reperfusion after the coronary occlusion.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous cardiac sympathetic innervation in heart failure after myocardial infarction of rats

Igawa

Nozawa

Yoshida

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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We examined cardiac neuronal function and beta-receptor with a dual-tracer method of [(131)I]meta-iodobenzylguanidine (MIBG) and [(125)I]iodocyanopindolol (ICYP) in rat heart failure after myocardial infarction (MI). In rats with MI, left ventricular (LV) systolic function decreased, and LV dimension and right ventricular (RV) mass increased gradually. MIBG accumulations of the noninfarcted LV (remote region) and RV decreased by 15% at 1 wk compared with sham-operated rats, and these accumulations were restored by 71% and 56%, respectively, at 24 wk compared with age-matched sham rats despite sustained depletion of myocardial norepinephrine contents in these regions. ICYP accumulation of the remote region and of the RV did not decrease at any stages. Myocardial MIBG distribution was heterogeneous at 1 wk when it was lower in the peri-infarcted region than in the remote region, associated with reduced ICYP accumulation in the peri-infarcted region. The heterogeneous distribution of both isotopes disappeared at 12 wk. Thus cardiac sympathetic neuronal alteration was coupled with downregulation of beta-receptors in rat heart failure after MI. The abnormal adrenergic signaling occurred heterogeneously in terms of ventricular distribution and time course after MI.

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“…Subtraction of the area of perfusion defect at rest detected by perfusion study from the entire extent of defect detected by the new test at rest should allow detection of the reversible ischaemic territory. It has been shown that the uptake of iodine-123 metaiodobenzylguanidine (MIBG) is significantly reduced in the areas of myocardial infarction [9,10,11], and also in areas of acute and chronic ischaemia in canine experiments [12,13]. A decrease in MIBG uptake represents the loss of integrity of post-ganglionic, presynaptic neurones.…”

Section: Introductionmentioning

confidence: 99%

Concordance between rest MIBG and exercise tetrofosmin defects: possible use of rest MIBG imaging as a marker of reversible ischaemia

et al. 2001

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Perfusion imaging combined with pharmacological stress is the study of choice in patients with ischaemic heart disease who are incapable of exercising. Some medical conditions, however, can preclude the use of pharmacological stress. In these particular situations, availability of a diagnostic test which allows for the assessment of ischaemic territory at rest would be desirable. With the purpose of providing a marker of reversible ischaemia, we evaluated myocardial iodine-123 metaiodobenzylguanidine (MIBG) uptake in regions with fixed and reversible defects defined by exercise/rest perfusion study. Fifty-four male patients with ischaemic heart disease and previous myocardial infarction were studied by means of exercise/rest tetrofosmin and MIBG single-photon emission tomography (SPET). Regional tracer uptake was quantified and expressed as a percentage of maximum peak activity. Areas with denervated but perfused myocardium and areas with ischaemic myocardium were calculated. Regions with<75% of peak activity in the exercise perfusion study were divided into two groups according to whether the increase in peak activity in the respective rest study was >10% (reversible regional defect) or <10% (fixed regional defect). These percentages were compared with the percentages of the innervation study. The area of the innervation defect was significantly larger when the perfusion defect was reversible than when it was fixed. In regions with reversible perfusion defects, the size of the area of denervated but perfused myocardium was similar to the size of the area of ischaemic myocardium. In regions with reversible defects, the percentage of myocardial MIBG uptake was not significantly different from the percentage of tetrofosmin uptake at exercise, while it was significantly lower than the percentage of tetrofosmin uptake at rest. In regions with fixed defects, the percentage of myocardial MIBG uptake was significantly lower than the percentage of tetrofosmin uptake at exercise and at rest. In patients who developed angina during exercise test, the area of denervated but perfused myocardium was significantly larger than in patients without angina (4.1+/-2.4 vs 3.4+/-2.5, P=0.02). The same trend was observed with regard to the size of the innervation defect (8.6+/-2.4 vs 5.7+/-2.2, P=0.02). It is concluded that when the use of pharmacological stress is not possible in patients incapable of exercising, rest studies with MIBG combined with rest myocardial perfusion studies may be useful as a marker of reversible ischaemia.

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Cardiac sympathetic nerve function assessed by [131I]metaiodobenzylguanidine after ischemia and reperfusion in anesthetized dogs

Cited by 9 publications

References 28 publications

Spatial Inhomogeneity of Sympathetic Nerve Function in Hibernating Myocardium

Spatial Inhomogeneity of Sympathetic Nerve Function in Hibernating Myocardium

Heterogeneous cardiac sympathetic innervation in heart failure after myocardial infarction of rats

Concordance between rest MIBG and exercise tetrofosmin defects: possible use of rest MIBG imaging as a marker of reversible ischaemia

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