Tohru Ohtake

Reduced Myocardial Flow Reserve in Non–Insulin-Dependent Diabetes Mellitus

OBJECTIVES We analyzed myocardial flow reserve (MFR) in patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM) without symptoms and signs of ischemia. BACKGROUND Diminished MFR in diabetes has been suggested. However, it remains controversial whether MFR is related to glycemic control, mode of therapy or gender in NIDDM. METHODS Myocardial blood flow (MBF) was measured at baseline and during dipyridamole loading in 25 asymptomatic, normotensive, normocholesterolemic patients with NIDDM and 12 age-matched control subjects by means of positron emission tomography and nitrogen-13 ammonia, after which MFR was calculated. RESULTS Baseline MBF in patients with NIDDM ([mean +/- SD] 74.0 +/- 24.0 ml/min per 100 g body weight) was comparable to that in control subjects (73.0 +/- 17.0 ml/min per 100 g). However, MBF during dipyridamole loading was significantly lower in patients with NIDDM (184 +/- 99.0 ml/min per 100 g, p < 0.01) than in control subjects (262 +/- 120 ml/min per 100 g), as was MFR (NIDDM: 2.77 +/- 0.85; control subjects: 3.8 +/- 1.0, p < 0.01). A significantly decreased MFR was seen in men (2.35 +/- 0.84) compared with women with NIDDM (3.18 +/- 0.79, p < 0.05); however, no significant differences were found in terms of age, hemoglobin a1c and baseline MBF. MFR was comparable between the diet (2.78 +/- 0.80) and medication therapy groups (2.76 +/- 0.77) and was inversely correlated with average hemoglobin A1c for 5 years (r = -0.55, p < 0.01) and fasting plasma glucose concentration (r = -0.57, p < 0.01) but not age or lipid fractions. CONCLUSIONS Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.

Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis.

BACKGROUND Reduced coronary flow reserve (CFR) in hypercholesterolemic patients without evidence of ischemia has been reported. However, it remains uncertain whether this abnormality occurs without overt coronary atherosclerosis. This study aimed to clarify whether CFR is impaired even in anatomically normal coronary arteries in hypercholesterolemic patients and to compare CFR between familial hypercholesterolemic (FH) patients and secondary hypercholesterolemic (SH) patients. METHODS AND RESULTS Twenty-two patients with hypercholesterolemia (11 FH, 11 SH) and 11 control subjects were studied. Baseline myocardial blood flow (MBF) and MBF during dipyridamole loading were measured in segments perfused by angiographically normal coronary arteries with the use of positron emission tomography and 13N-ammonia, and CFR was calculated. Baseline MBF (mL/min per 100 g heart wt) in FH (81.3 +/- 31.4) and SH (70.0 +/- 20.7) patients was not different from that in control subjects (75.0 +/- 34.9). However, MBF during dipyridamole loading was significantly lower in FH patients (129 +/- 19.1) than in control subjects (322 +/- 174, P < .01) and SH patients (210 +/- 71.2, P < .01). CFR in FH patients (1.59 +/- 0.41) was also significantly lower compared with both control subjects (4.22 +/- 1.42, P < .01) and SH patients (3.00 +/- 0.96, P < .01). CFR in SH patients was also significantly lower than that in control subjects (P < .05). CFR correlated significantly with both plasma total cholesterol (r = .67, P < .01) and LDL cholesterol concentrations (r = .69, P < .01). CONCLUSIONS CFR was decreased even in anatomically normal coronary arteries in hypercholesterolemic patients. This abnormality was more prominent in FH patients.

Hyperglycemia Rather Than Insulin Resistance Is Related to Reduced Coronary Flow Reserve in NIDDM

To clarify if coronary flow reserve (CFR) is related to insulin resistance or hyperglycemia in normotensive NIDDM, myocardial blood flow (MBF) at baseline and during dipyridamole loading were measured with 13N-ammonia positron-emission tomography. CFR was significantly reduced in NIDDM patients compared with agematched control subjects. CFR in patients with well-controlled NIDDM was significantly higher than in those with poorly controlled NIDDM, whereas insulin resistance was comparable between the two groups. CFR in NIDDM patients was not related to the degree of insulin resistance. CFR correlated significantly with average fasting glucose concentration and average HbA1c, but not with insulin resistance, age, lipid parameters, or blood pressure. In conclusion, control of blood glucose concentration rather than insulin resistance is most likely related to the reduced CFR in NIDDM.

Improvement of Impaired Myocardial Vasodilatation Due to Diffuse Coronary Atherosclerosis in Hypercholesterolemics After Lipid-Lowering Therapy

BACKGROUND Diminished myocardial vasodilatation (MVD) in hypercholesterolemics without overt coronary stenosis has been reported. However, whether the diminished MVD of angiographically normal coronary arteries in hypercholesterolemics can be reversed after lipid-lowering therapy is not known. METHODS AND RESULTS A total of 27 hypercholesterolemics and 16 age-matched controls were studied. All patients had >1 normal coronary artery, and those segments that were perfused by anatomically normal coronary arteries were studied. Myocardial blood flow (MBF) was measured during dipyridamole loading and at baseline using positron emission tomography and 13N-ammonia, after which MVD was calculated before and after lipid-lowering therapy. Total cholesterol was significantly higher in hypercholesterolemics (263+/-33.8) than in controls (195+/-16.6), and it normalized after lipid-lowering therapy (197+/-19.9). Baseline MBF (ml. min-1. 100 g-1) was comparable among hypercholesterolemics (both before and after therapy) and controls. MBF during dipyridamole loading was significantly lower in hypercholesterolemics before therapy (189+/-75.4) than in controls (299+/-162, P<0.01). However, MBF during dipyridamole loading significantly increased after therapy (226+/-84.7; P<0.01). MVD significantly improved after therapy in hypercholesterolemics (2.77+/-1.35 after treatment [P<0.05] versus 2. 02+/-0.68 before treatment [P<0.01]), but it remained significantly higher in controls (3.69+/-1.13, P<0.01). There was a significant relationship between the percent change of total cholesterol and the percent change of MVD before and after lipid-lowering therapy (r=-0. 61, P<0.05). CONCLUSIONS Diminished MVD of anatomically normal coronary arteries in hypercholesterolemics can be reversed after lipid-lowering therapy.

Scintigraphic manifestation of fibrous dysplasia

Scintigraphic manifestations of fibrous dysplasia were analyzed in 59 lesions of 26 patients (12 monostotic, 14 polystotic). Bone imaging with Tc-99m MDP revealed a high percentage of increased uptake of radioisotope in the lesions of fibrous dysplasia. Four (14%) of 29 cystic lesions and two (7%) of 30 lesions with the appearance of ground glass showed no increase in radioisotope uptake, although roentgenograms showed marked changes. Therefore, care must be taken in the diagnosis of fibrous dysplasia with bone imaging alone. Nuclear methods, however, are indispensable in evaluating the dynamic aspects of bone mineral behavior and in demonstrating disease where none was suspected, or in visualizing polyostotic involvement in those cases where only monostotic disease was suspected clinically. It is concluded that both scintigrams and roentgenograms are complementary procedures in the diagnosis of fibrous dysplasia.

Role of insulin resistance in heart and skeletal muscle F-18 fluorodeoxyglucose uptake in patients with non-insulin-dependent diabetes mellitus.

BackgroundAltered heart and skeletal glucose usage has been reported in patients with non-insulin-dependent diabetes mellitus (NIDDM). Although elevations in plasma free fatty acid (FFA) concentrations have been implicated in reduced myocardial 18fluorine-fluoro-2-deoxy-d-glucose uptake (MFU), the specific role of whole-body insulin resistance in MFU in patients with NIDDM compared with skeletal muscle metabolism remains controversial.PurposeMFU and skeletal muscle 18fluorine-fluoro-2-deoxy-d-glucose uptake (SMFU) were compared with positron emission tomography and the whole-body glucose disposal rate (GDR) during hyperinsulinemic euglycemic clamping in 26 normotensive asymptomatic patients with NIDDM who were not taking medication. These factors were also compared in 12 age-matched control subjects to increase the knowledge of the influence of whole-body insulin resistance on MFU. In addition, independent factors for both SMFU and MFU were investigated.ResultsGDR in control subjects (10.0±2.97 mg/min per kilogram) was significantly higher than in patients with NIDDM (4.05±2.37 mg/min per kilogram, P<.01). SMFU in patients with NIDDM (0.826 +-0.604 mg/min per 100g) was significantly lower than that in control subjects (1.86±1.06 mg/min per 100g, P<.01). MFU in patients with NIDDM (5.35±2.10 mg/min per 100 g) was also significantly lower than that of control subjects (7.05±1.66 mg/min per 100 g, P =.0182). SMFU significantly correlated with GDR (r=.727, P<.01) and FFA (r=-.52, P <.01) in patients with NIDDM. MFU also correlated with GDR (r=.778, P<.01) and FFA (r=-.72, P<.01) in patients with NIDDM. Multivariate stepwise regression analysis showed that GDR (F=36.8) was independently related to MFU (r=.85, P<.01) whereas FFA was not (F=1.763), where F is the value for statistical analysis of multivariate stepwise regression analysis.ConclusionInsulin resistance is the most essential factor for both heart and skeletal muscle FDG uptake in patients with NIDDM.

Altered Myocardial Vasodilatation in Patients With Hypertriglyceridemia in Anatomically Normal Coronary Arteries

Reduced myocardial vasodilatation (MVD) in hypercholesterolemics without overt coronary stenosis has been reported. However, the status of MVD in hypertriglyceridemics has not yet been clarified. The aim of this study was to investigate whether MVD is impaired in patients with hypertriglyceridemia without overt coronary stenosis. Twenty-three hypertriglyceridemics (10 normocholesterolemic hypertriglyceridemics [HTGs] and 13 mixed combined hyperlipidemics [MCHLs]) and 13 age-matched controls were studied. All patients were proven to have more than one normal coronary artery, as diagnosed by coronary angiography, and those segments that were perfused by anatomically normal coronary arteries were used in the study. Myocardial blood flow (MBF) during dipyridamole (DP) loading and baseline MBF were measured by using positron emission tomography and [13N]ammonia, after which MVD was calculated. Baseline MBF (mL.min(-1).100 g(-1)) was comparable among HTG (76.0+/-26.1), MCHL (77.0+/-26.1), and controls (80.3+/-38.5). However, MBF during DP loading was significantly lower in MCHL (159+/-52.5) than in control subjects (292+/-166, P<.01), while it was comparable in HTG (202+/-104) and controls. MVD was significantly reduced in both HTG (2.70+/-1.09, P<.05) and MCHL (2.07+/-.70, P<.01) compared with controls (3.73+/-1.14). MVD in MCHLs tended to be reduced compared with that in HTGs, but the difference was statistically insignificant (P=.08). There was a significant relationship between MVD and both plasma triglycerides (r=-.47, P<.01) and plasma total cholesterol (r=-.55, P<.01). When controls and HTGs were combined, the relationship between MVD and plasma total triglycerides became more prominent (r=-.55, P<.05), and the significant relationship between cholesterol level and MVD disappeared. Multivariate regression analysis has revealed that the triglyceride level (F=5.2, P<.05) was independently related to MVD (r=.69, P<.01). In conclusion, MVD was reduced in hypertriglyceridemics in anatomically normal coronary arteries. Hypertriglyceridemia is an independent factor for this abnormality.

Hemodynamic and Endocrine Responsiveness to Mental Arithmetic Task and Mirror Drawing Test in Patients With Essential Hypertension

To evaluate the reactivity to psychological stress in patients with essential hypertension we investigated hemodynamic and endocrinologic changes during a mental arithmetic task (MAT) and a mirror drawing test (MDT) in 10 hypertensive subjects. Hemodynamic changes were assessed continuously using an ambulatory radionuclide cardiac detector. There were significant increases in systolic blood pressure (deltaSBP: +37.8 +/- 11.1 and +41.0 +/- 9.4 mm Hg during MAT and MDT, respectively, P < .01) and diastolic blood pressure (deltaDBP: +17.5 +/- 3.1 and +21.2 +/- 3.9 mm Hg, P < .01) and in heart rate (deltaHR: +17.1 +/- 5.3 and +12.5 +/- 2.9 beats/min, P < .01) during both tasks in association with an increase in cardiac output (CO). The plasma levels of norepinephrine and epinephrine increased during both the MAT (deltaNE: +0.074 +/- 0.022 ng/mL, P < .01; deltaEP: +0.068 +/- 0.025 ng/mL, P < .01) and the MDT (deltaNE: +0.067 +/- 0.034 ng/mL, P < .01; deltaEP: +0.030 +/- 0.011 ng/mL, .05 < P < .1). Although the deltaNE was similar in response to the MAT and MDT, the deltaEP during the MDT tended to be less than half the deltaEP during the MAT (.05 < P < .10). The deltaEP was positively correlated with the deltaDBP and the deltaCO during both tasks and with the deltaSBP and the deltaHR during the MAT. These findings suggest that MAT- and MDT-induced increases in BP were attributable mainly to an increase in CO, possibly as the result of stimulation of the sympathoadrenomedullary system. However, the sympathoadrenomedullary system appeared to be more closely associated with the hemodynamic responses during the MAT than during the MDT.

Impaired Myocardial Vasodilation During Hyperemic Stress With Dipyridamole in Hypertriglyceridemia

OBJECTIVES This study sought to investigate the specific role of hypertriglyceridemia in the myocardial hyperemic stress with dipyridamole/rest flow ratio (MDR). BACKGROUND Reduced MDR has been reported in hypercholesterolemic patients without evidence of ischemia. However, the specific role of hypertriglyceridemia in MDR has not been studied. METHODS Fifteen nondiabetic normocholesterolemic hypertriglyceridemic patients and 13 age-matched control subjects were studied. Myocardial blood flow (MBF) during dipyridamole administration and baseline MBF in hypertriglyceridemic patients and control subjects were measured using positron emission tomography and nitrogen-13 ammonia, after which the MDR was calculated. RESULTS Baseline MBF (ml/min per 100 g heart weight) in hypertriglyceridemic patients (mean +/- SD 73.6 +/- 24.1) did not differ significantly from that in control subjects (81.6 +/- 37.2). MBF during dipyridamole loading in hypertriglyceridemic patients (198 +/- 106) was significantly reduced compared with that in control subjects (313 +/- 176, p < 0.05), as was the MDR (2.71 +/- 1.07 vs. 3.73 +/- 1.14, respectively, p < 0.05). Spearman rank-order correlation analysis showed a significant relation between plasma triglyceride concentration and MDR (r = -0.466, asymptotic SE 0.157, p = 0.0125); however, no such significant relation was seen between total plasma cholesterol concentration and MDR (r = -0.369, asymptotic SE 0.130, p = 0.059). CONCLUSIONS Impaired myocardial vasodilation was suggested in hypertriglyceridemic patients without symptoms and signs of ischemia.

Flow characteristics of soft-tissue vascular anomalies evaluated by direct puncture scintigraphy

Soft-tissue vascular anomalies such as haemangioma and vascular malformation are treated by surgical resection, arterial embolization or sclerotherapy. Because the effect of sclerotherapy, i.e. the percutaneous injection of sclerosing agents, depends on intralesional haemodynamics, estimation of flow characteristics of soft-tissue vascular anomalies is essential when determining appropriate patient management. However, lesions are at present divided into only two groups: high flow and low flow. We have developed a new method, direct puncture scintigraphy, to evaluate in detail the haemodynamics of vascular anomalies under conditions simulating sclerotherapy. Twenty-six soft-tissue vascular anomalies in 21 patients were studied. After 30 MBq of technetium-99m Sn colloid was injected percutaneously into the intravascular space of the lesion, dynamic imaging was performed for 5 min. A time-activity curve for the lesion was generated, with the infiltrated activity on injection subtracted. A monoexponential curve was fitted to the declining phase of the time-activity curve, and mean vascular transit time (MTT) was obtained. The lesions were classified into high-flow and low-flow lesions based on radionuclide angiography with intravenous injection of99mTc-labelled red blood cells, and estimates of MTT in the two groups were compared. The imaging procedures were carried out with no major complications, and broad intralesional diffusion of99mTc-Sn colloid was achieved in most lesions. The high-flow lesions (six lesions) had a short MTT, ranging from 1.6 to 3.4 s, while the low-flow lesions (20 lesions) had a longer MTT, with no overlap between the groups. MTT showed a wide range in low-flow lesions: it was less than 30 s in six lesions and more than 10 min in five other lesions. Direct puncture scintigraphy provides a quantitative indicator of the flow characteristics of soft-tissue vascular anomalies, and may aid in determining treatment strategies for patients with vascular anomalies.