Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) may cause an increase in the inflammatory status and oxidative stress as well as sympathetic nervous system overactivity, even in the absence of any other organic heart disease. We investigated the effect of perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of systemic inflammation and oxidative stress in normotensive patients with type 2 DM. We also examined the effect of the drug on the disturbances of left ventricular myocardial adrenergic innervation that may be seen in these patients. We studied 62 normotensive patients with type 2 DM, who were randomized to receive perindopril (n=32) or placebo (n=30). At the start of the study and after 6 months' therapy blood samples were taken to evaluate total peroxides (TP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy study. ACE-i caused a significant reduction in levels of cytokines and TP (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h was improved (P<0.001 for both). No significant alterations were observed in the placebo group. Our data indicate that the addition of ACE-i to the medication of normotensive diabetic type 2 patients may improve the disturbed myocardial adrenergic innervation, the systemic inflammatory status and oxidative stress. Our findings indicate the cardioprotective action of ACE-i and suggest that earlier treatment might be appropriate in those patients.

Assessment of myocardial adrenergic innervation in patients with sick sinus syndrome: effect of asynchronous ventricular activation from ventricular apical stimulation.

OBJECTIVE: To investigate ventricular sympathetic innervation in patients with sick sinus syndrome and to detect regional deterioration of adrenergic innervation caused by asynchronous ventricular activation from right ventricular pacing. DESIGN: Prospective controlled study. SETTING: Tertiary cardiac referral centre. PATIENTS: 22 patients with sick sinus syndrome and indications for permanent dual chamber pacing; 20 healthy individuals as controls. INTERVENTIONS: All patients underwent myocardial imaging with planar and single photon emission computed tomography (SPECT) after an intravenous infusion of 5 mCi 123I-meta-iodobenzylguanidine (123I-MIBG) before and after pacemaker implantation. A SPECT thallium201 myocardial study was done during the same week as the 123I-MIBG study in all patients. MAIN OUTCOME MEASURES: The heart to mediastinum (H/M) ratio and washout rate were calculated during the 123I-MIBG study to assess the global cardiac sympathetic activity; the aim of the SPECT study was to investigate the regional distribution of adrenergic innervation. RESULTS: The H/M ratio was significantly smaller in the patients with sick sinus syndrome than in the controls (p < 0.001). In sick sinus syndrome there were regional adrenergic innervation defects, mostly in the inferior and apical walls. After a medium term pacing period, a redistribution of 123I-MIBG uptake was detected, with deterioration of adrenergic innervation in the inferior, apical, and posterior walls. The thallium201 myocardial perfusion study showed no change after three months of permanent pacing. CONCLUSIONS: Patients with sick sinus syndrome have global and regional disturbances of the adrenergic innervation of the left ventricular myocardium. These seem to deteriorate as a result of asynchronous electrical activation. The clinical significance of this finding requires further investigation.

Effects of asynchronous ventricular activation on myocardial adrenergic innervation in patients with permanent dual-chamber pacemakers; an I(123)-metaiodobenzylguanidine cardiac scintigraphic study.

AIMS: To evaluate myocardial sympathetic innervation abnormalities in patients with DDD pacemakers for complete heart block. METHODS: We studied 39 patients, chronically paced in DDD mode because of complete atrioventricular block. Twenty-three healthy individuals served as a control group. All patients underwent planar and single-photon emission computed tomography (SPECT) myocardial imaging 4 h after intravenous infusion of 185 MBq I(123)-MIBG. The heart to mediastinum ratio was calculated to quantify cardiac I(123)-MIBG accumulation, while the SPECT study was performed to investigate the regional distribution of adrenergic innervation. All patients underwent a SPECT thallium(201)myocardial study during the same week as the I(123)-MIBG study. RESULTS: The heart to mediastinum ratio was significantly smaller in paced patients than in the controls (P<0.001). 89.7% of paced patients had regional abnormalities of I(123)-MIBG uptake, mainly in the inferior (92.3%) and apical (38.5%) wall. 46.2% of paced patients had regional perfusion defects, also mainly in the inferior (46.2%) and apical (10.3%) wall. Neither the I(123)-MIBG abnormalities nor the perfusion defects were related to the duration of pacing. CONCLUSIONS: Stimulation from the apex of the right ventricle leads to regional disturbances of the adrenergic innervation of the left ventricular myocardium, as assessed by I(123)-MIBG activity.

Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries.

OBJECTIVES: The purposes of this study were to test the specificity of dipyridamole myocardial perfusion scintigraphy in patients with permanent ventricular pacing (PVP) and to evaluate coronary blood flow and reserve in these patients. BACKGROUND: Permanent ventricular pacing is associated with exercise perfusion defects on myocardial scintigraphy in the absence of coronary artery disease (CAD). On the basis of studies in patients with left bundle brunch block, coronary vasodilation with dipyridamole has been proposed as an alternative to exercise testing for detecting CAD in paced patients, but this approach has never been tested. METHODS: Fourteen patients with a PVP and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In these patients and in eight control subjects, coronary flow velocities were measured in the left anterior descending coronary artery (LAD) and in the dominant coronary artery before and after adenosine administration. RESULTS: In the paced patients, coronary flow velocities in the LAD and in the dominant coronary artery were significantly lower than those in the control subjects. In addition, seven patients showed perfusion defects on dipyridamole thallium-201 single-photon emission computed tomography, with a specificity of 50% for this test. The defect-related artery in these patients had lower coronary flow reserve (2.6 +/- 0.5) as compared with those without perfusion defects (3.9 +/- 1.0, p < 0.05) or the control group (3.5 +/- 0.5, p < 0.05). CONCLUSIONS: Permanent ventricular pacing is associated with alterations in regional myocardial perfusion. Furthermore, abnormalities of microvascular flow, as indicated by reduced coronary flow reserve in the defect-related artery, are at least partially responsible for the uncertain specificity of dipyridamole myocardial perfusion scintigraphy.

Phasic coronary flow pattern and flow reserve in patients with left bundle branch block and normal coronary arteries.

OBJECTIVES: The purpose of this study was to determine whether scintigraphic myocardial perfusion defects in patients with left bundle branch block (LBBB) and normal coronary arteries are related to abnormalities in coronary flow velocity pattern and/or coronary flow reserve. BACKGROUND: Septal or anteroseptal defects on exercise myocardial perfusion scintigraphy are common in patients with LBBB and normal coronary arteries. METHODS: Thirteen patients (7 men, age 61+/-8 years) with LBBB and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In all patients and in 11 control subjects coronary blood flow parameters were calculated from Doppler measurements of flow velocity in the left anterior descending coronary artery (LAD) before and after adenosine administration. RESULTS: The time to maximum peak diastolic flow velocity was significantly longer both for the seven patients with (134+/-19 ms) and for the six without (136+/-7 ms) exercise perfusion defects than for controls (105+/-12 ms, p < 0.05), whereas the acceleration was slower (170+/-54, 186+/-42 and 279+/-96 cm/s2, respectively, p < 0.05). Coronary flow reserve in the patients with exercise perfusion defects (2.7+/-0.3) was significantly lower than in those without (3.7+/-0.5, p < 0.05) or in the control group (3.4+/-0.5, p < 0.05). CONCLUSIONS: Patients with LBBB have an impairment of early diastolic blood flow in the LAD due to an increase in early diastolic compressive resistance resulting from delayed ventricular relaxation. Furthermore, exercise scintigraphic perfusion defects in these patients are associated with a reduced coronary flow reserve, indicating abnormalities of microvascular function in the same vascular territory.