To characterize uremic cardiac autonomic neuropathy, we measured plasma catecholamines, analyzed the 24-hour heart rate variability (HRV), and acquired serial images with ¹²³I-metaiodobenzylguanidine (MIBG) in 44 patients with chronic renal failure on hemodialysis and in 14 controls. Time-domain measures were calculated using the Marquette HRV program. MIBG clearance rates from the heart and lung were evaluated on planar images, and the regional MIBG uptake in the left ventricular myocardium was evaluated with single-photon emission computed tomography. Compared with controls, plasma dopamine and norepinephrine levels were elevated (p < 0.001 and p = 0.03, respectively), and all the time-domain measures of HRV were reduced in the patients (p < 0.001). The MIBG clearance rate from the heart was higher (p < 0.001), that from the lung was lower (p < 0.001), and the myocardial MIBG distribution was more heterogeneous in patients than in controls (total uptake score p ≤ 0.03). These variables were similar between 26 patients without and 18 patients with hypertension. Uremic cardiac autonomic neuropathy may be characterized by high plasma levels of dopamine and norepinephrine, reduced HRV, and abnormal MIBG kinetics in the heart with heterogeneous myocardial MIBG distribution, suggesting cardiac sympathetic overactivity and parasympathetic deterioration. In addition, abnormal MIBG kinetics in the lung may imply pulmonary sympathetic nervous dysfunction and/or endothelial dysfunction in uremic patients.

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Hepatocyte growth factor (HGF) is a multifunctional protein implicated in tissue regeneration, wound healing, and angiogenesis. We measured serum HGF concentrations in 37 patients with peripheral arterial occlusive disease (PAOD). Among them, 36 patients underwent arteriography. Serum HGF concentrations were also measured in 40 control subjects who remained free of vascular, liver, kidney, or lung disease. Patients with PAOD showed elevated serum HGF concentrations compared with control subjects (0.40+/-0.02 vs. 0.19+/-0.01 ng/mL; P<0.001). Serum HGF concentrations were significantly higher in smokers compared with nonsmokers (0.45+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.003). The serum HGF concentrations in patients with collaterals tended to be higher than those in patients without collaterals (0.43+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.06). Moreover, in patients who underwent bypass surgery or angioplasty, serum HGF concentrations decreased from 0.41+/-0.03 to 0.21+/-0.04 ng/mL after treatment (P<0.001). Serum HGF may be an useful marker for the diagnosis of PAOD. HGF may play an important role in angiogenesis and collateral vessel growth in PAOD.

Objectives-To evaluate the eYcacy of cilostazol, a new synthetic inhibitor of phosphodiesterase, in preventing stent thrombosis after successful implantation. Design-Preliminary prospective study. Setting-A single coronary care unit in Japan. Patients-Elective, bailout, or primary stents were implanted in 85 consecutive patients with 93 lesions. Primary stent implantation was performed in 18 patients with acute myocardial infarction. Patients received 200 mg cilostazol and 243 mg aspirin after stenting. Main outcome measures-Stent thrombosis, major and minor complications, and side eVects were assessed in the six months after stenting. Results-Gianturco-Roubin stents were implanted in 37 lesions, Wiktor stents in 55, and Palmaz-Schatz stents in 27. Multiple stents were used in 26 lesions. There was no mortality, stent thrombosis related Q wave myocardial infarction, emergency bypass surgery, repeat intervention, or vascular complications in the six months of follow up. Acute or subacute closure did not occur after stenting. There were no serious side eVects such as leucopenia and/or abnormal liver function for three months. Cilostazol was withdrawn in one patient because of skin rash. Patients who underwent primary stenting had no clinical events, such as acute or subacute thrombosis, or side eVects. Conclusions-Cilostazol is an eVective antiplatelet agent with minimum side eVects after elective, bailout, or primary stent implantation. (Heart 1998;80:393-396)

The progress of diabetic cardiac parasympathetic dysfunction may parallel the sympathetic one.

Background Stent implantation in coronary angioplasty has reduced the rate of restenosis, but many patients still undergo follow-up coronary angiography (CAG). The present study was a multi-center retrospective analysis of the usefulness of stress single photon emission computed tomography (SPECT) compared with follow-up CAG in stent-implanted patients who remained asymptomatic during the follow-up period. Methods and ResultsThe study group of 103 patients underwent both SPECT and CAG at 4-9 months after stent implantation. Restenosis occurred in 20 (19%) of 106 vessel territories, and a reversible perfusion defect was found in 32 (30%) territories. Sensitivity, specificity, positive and negative predictive values, and accuracy of SPECT were 65%, 78%, 41%, 91%, and 76%, respectively. The accuracy was lower in territories with a prior myocardial infarction (71%), in the left circumflex artery (58%), and in cases with three-vessel disease (63%). The negative predictive value was high, but 7 false negative cases included 4 cases with prior myocardial infarction, and 2 cases with reversible defects in other vessel territories. Conclusions Stress SPECT imaging is a useful tool for following up patients with coronary stent implantation, and follow-up CAG could be omitted in patients with negative SPECT imaging, no prior myocardial infarction, one-or two-vessel disease, and sufficient stress loading. (Circ J 2004; 68: 462 -466)

Some electrocardiographic variables, including the degree of maximal ST-segment depression (STD), may not necessarily indicate the severity of exercise-induced myocardial ischemia. The present study examined whether maximal STD correlates with the severity and extent of exercise-induced myocardial ischemia, as assessed by thallium-201 (201Tl) imaging, and which parameter of exercise testing reflects scintigraphic severity and extent in 270 patients who had a 1 mm or greater horizontal or down-sloping STD on exercise 201Tl imaging. The scintigraphic severity and extent of exercise-induced ischemia was assessed and correlated with maximal STD, number of positive leads, workload, peak heart rate, peak systolic blood pressure (SBP), rate-pressure product, chest pain and the Duke treadmill score. Most of the scintigraphic markers of the severity and extent of ischemia had significant but weak correlation with all of those parameters. Multivariate analysis demonstrated that peak SBP and the Duke treadmill score (chest pain in only simple variables model) correlated independently with scintigraphic severity and extent of ischemia. Furthermore, most of the patients with a peak SBP of 200 mmHg or more had milder and less extensive ischemia. In patients with exercise-induced STD, the scintigraphic severity and extent of ischemia may be estimated by peak SBP and the Duke treadmill score.

The negative charges of dextran-sulfate (DS) used for low-density lipoprotein (LDL) apheresis activates the intrinsic coagulation pathway, in which plasma kallikrein acts on high-molecular-weight kininogen (HMWK) to produce large amounts of bradykinin. This study was undertaken to see whether bradykinin generated during DS LDL apheresis has some physiologic effects in vivo. The plasma levels of bradykinin and nitric oxide derivatives (NOx) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity, this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the marked increase in bradykinin levels (before apheresis, 18 +/- 3 (mean +/- SE, n = 5) pg/ml; after apheresis 470 +/- 140, p < 0.01) was associated with the increase in NOx (before apheresis 50 +/- 11 pg/ml; after apheresis 66 +/- 15). Interestingly, these changes in bradykinin and NOx levels were suppressed during apheresis using NM. The changes in plasma NOx levels were negatively correlated with those in blood pressures. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects by means of activation of endothelium-derived relaxant factor (EDRF). Our results support the view that bradykinin produced during DS LDL apheresis has physiologic significance.