Cutaneous polyarteritis nodosa: therapy and clinical course in four cases.

Cutaneous polyarteritis nodosa (PN) has a benign and chronic course; relapses are frequently associated with steroid dependence. We have observed four cases of cutaneous PN in the past 15 years and followed up two of the four cases long-term for 13 and 10 years after diagnosis. There has been a marked contrast in the clinical courses of these two cases: one case has shown a complete remission for 12.5 years without treatment during the most recent 11 years; the other case had four relapses and has never experienced cessation of treatment. The only difference between the two cases was careful therapy with adequate prednisolone in the long-term remission case. The other two cases clinically showed erythema nodosum-like features, and they had antecedent sore throats and embedded chronic tonsillitis; one was associated with presumed streptococcal infection. These two cases may simply be an accelerated process of post-streptococcal erythema nodosum rather than typical cutaneous PN. We performed tonsillectomies as adjuvant therapy in these two cases. No relapse of the disease has been observed in these two cases, and the tonsillectomy allowed us to taper the dose of steroids, resulting in discontinuation of the treatment in one of the two cases. The duration of the remission as well as the adjuvant therapy was variable in each of our cutaneous PN cases. Tonsillectomy can be recommended as an adjuvant to steroids for PN cases with chronic tonsillitis and/or streptococcal infection.

Pseudoxanthoma elasticum with dipyridamole-induced coronary artery spasm: a case report.

In patients with pseudoxanthoma elasticum, severe organic coronary artery stenosis often occurs without coronary risk factors. However, this report presents the case of a 49-year-old woman with pseudoxanthoma elasticum who had coronary artery spasm with an angiographically normal coronary artery. In addition, coronary artery spasm was provoked with dipyridamole thallium-201 cardiac imaging.

Effects of amlodipine and cilnidipine on cardiac sympathetic nervous system and neurohormonal status in essential hypertension.

N-Type calcium channel antagonists may suppress sympathetic activity. The purpose of this study was to assess the effects of amlodipine and cilnidipine on the cardiac sympathetic nervous system and the neurohormonal status of essential hypertension. 123I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed and blood samples were taken to determine plasma renin activity and plasma norepinephrine concentration before and 3 months after drug administration in 47 patients with mild essential hypertension. Twenty-four of the patients were treated with 5 to 10 mg/d of amlodipine; the other 23 were treated with 10 to 20 mg/d of cilnidipine. For comparison, 12 normotensive subjects were also studied. No significant differences were found in the basal characteristics between the 2 hypertensive groups. In both hypertensive groups, both the systolic and diastolic blood pressures were significantly reduced to similar levels 3 months after drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower heart-to-mediastinum (H/M) ratio compared with the normotensive subjects. The H/M ratio significantly increased (P<0.05) in combination with a decreased washout rate (P<0.02) after drug treatment in the cilnidipine group. In the amlodipine group, a significant decrease in washout rate (P<0. 04) was noted, without an increase in the H/M ratio. However, no significant changes were found in plasma renin activity and plasma norepinephrine concentration in either group. Thus, in patients with essential hypertension, cilnidipine suppressed cardiac sympathetic overactivity and amlodipine had a little suppressive effect. Cilnidipine may provide a new strategy for treatment of cardiovascular diseases with sympathetic overactivity.

Differential effects of enalapril and nitrendipine on the fibrinolytic system in essential hypertension.

BACKGROUND: Impaired fibrinolysis is associated with thromboembolic complications in hypertensive patients. It has been reported that cardiovascular morbidity and mortality rates are high even after lowering the elevated blood pressure with antihypertensive drugs. The aim of this study was to assess the effect of clinically used dosages of enalapril and nitrendipine on the fibrinolytic system. METHODS: Tissue plasminogen activator antigen (tPA) and tissue plasminogen activator inhibitor-1 (PAI-1) activity were measured in 20 normotensive male subjects and 46 male patients with mild essential hypertension divided into 2 groups (22 patients treated with 5 to 10 mg enalapril once a day and 24 treated with 5 to 10 mg nitrendipine once a day) before and 3 months after drug administration. Plasma renin activity and norepinephrine concentration were also measured. RESULTS: There were no significant differences in basal characteristics between the 2 hypertensive groups. In both hypertensive groups, blood pressure was significantly reduced to a similar level after drug treatment. In the 2 hypertensive groups, plasma renin activity significantly increased after drug treatment; however, there were no significant changes in norepinephrine concentration. Before drug treatment, the 2 hypertensive groups had significantly higher tPA and higher PAI-1 activity than the normotensive subjects. In the enalapril group, there was no significant change in tPA although PAI-1 activity significantly decreased after drug treatment. In the nitrendipine group, there was no significant change in tPA although PAI-1 activity significantly increased after drug treatment. CONCLUSION: Thus enalapril improved impaired fibrinolysis but nitrendipine further aggravated fibrinolysis in essential hypertension. Considering the effect of antihypertensive drugs on the fibrinolytic system, more effective and beneficial treatment of hypertensives, especially at a high risk for thrombus formation might be selected.

Assessment of myocardial fatty acid metabolism in atrioventricular synchronous pacing: analysis of iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid SPECT.

BACKGROUND: We used beta-methyl iodophenyl pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) to evaluate fatty acid metabolism in patients who were candidates for permanent pacemaker implantation and in patients with atrioventricular (AV) synchronous pacing. METHODS AND RESULTS: We performed BMIPP SPECT studies in 66 patients with bradyarrhythmia, of whom 11 patients were candidates for permanent pacemaker implantation, 27 patients had atrial pacing (atrial sensing, inhibited mode, simple programmable [AAI]), and 28 patients had atrial synchronous ventricular inhibited pacing (ventricular pacing, 2-chamber sensing, atrial-triggered and ventricular-inhibited, multiprogrammable [VDD]) or atrial and ventricular pacing in sequence (atrial and ventricular sensing, atrial-inhibited and atrial-triggered, ventricular-inhibited, multiprogrammable [DDD]). A qualitative assessment revealed that the BMIPP uptake at the septal, inferior, and apical regions was significantly decreased in the patients with VDD/DDD compared with both the candidates for permanent pacemaker implantation and the patients with AAI. The total extent score (ES) and severity score (SS) were significantly higher in the patients with VDD/DDD than in the other 2 groups. Significant regional differences of both ES and SS values were observed at the septal and inferior regions in the patients with VDD/DDD compared with the other groups. No differences were found between the qualitative and quantitative measures of BMIPP uptake in the candidates for permanent pacemaker implantation and those in the patients with AAI. CONCLUSION: Our study suggests that AV synchronous right ventricular pacing resulting in the delayed conduction and depolarization of myocardial cells may directly interfere with regional cellular free fatty acid uptake and metabolism.

Cardiac sympathetic nervous system in early essential hypertension assessed by 123I-MIBG.

UNLABELLED: Sympathetic overactivity has been noted in various clinical stages of essential hypertension. The purpose of this study is to investigate 123I-metaiodobenzylguanidine (MIBG) uptake and washout in patients with borderline and mild hypertension. METHODS: To assess cardiac sympathetic function in essential hypertension, we performed 123I-MIBG cardiac imaging and echocardiography in 25 normotensive, 25 borderline hypertensive and 24 mildly hypertensive men. Age and body mass index were similar in the three groups. RESULTS: Regarding the echocardiographic variables, the left ventricular mass index (LVMI) was significantly higher in the mildly hypertensive group (125.6+/-28.6 g/m2) than in the normotensive (99.9+/-20.7 g/m2) and the borderline hypertensive (110.0+/-24.4 g/m2) groups (P < 0.001 and P < 0.05, respectively). Regarding the scintigraphic variables, the heart-to-mediastinum (H/M) ratio was significantly lower in the mildly hypertensive group (1.8+/-0.3) than in the normotensive (2.1+/-0.3) and the borderline hypertensive (2.1+/-0.2) groups. In contrast, the washout rate was significantly higher in the mildly hypertensive group (17.6%+/-10.8%) than in the normotensive (7.0%+/-4.9%) and the borderline (11.9%+/-8.9%) hypertensive groups (P< 0.001 and P< 0.02, respectively). In addition, the borderline hypertensive group had a significantly higher washout rate than the normotensive group (P < 0.05). MIBG washout rate had a strong positive correlation with LVMI (r = 0.77, P < 0.0001). In contrast, the H/M ratio had a weak negative correlation with LVMI (r = -0.40, P < 0.0006). CONCLUSION: During the course of establishment of essential hypertension, the washout rate becomes higher with the advance of hypertension and with the development of left ventricular hypertrophy. Thus, we suggest a strong relationship between cardiac sympathetic activity and the advance of hypertension at its early stages.

Physiological fluctuation of the human left ventricle sympathetic nervous system assessed by iodine-123-MIBG.

UNLABELLED: It has been proposed that sympathetic nervous system pathophysiology is involved in the development of cardiovascular disorders. Since cardiac adrenergic activity has been difficult to assess in humans, physiological changes in the sympathetic nervous system in the human left ventricle remain unclear. METHODS: To determine if age and gender influence the sympathetic nervous function of the left ventricle, 300 angiographically normal subjects (170 men, 130 women; age range 40-79 yr) had 123I-metaiodobenzylguanidine (MIBG) cardiac imaging. Regional quantitative analysis of MIBG uptake and washout rate was performed. RESULTS: Men and women had prominent age-related decreases in MIBG uptake in the inferior and lateral walls (r2 = 0.34, p <0.0001 for both). Both genders had a significant positive correlation between regional washout rate and age in each region. In contrast to men, women had strong positive correlations in all regions (r2 = 0.54, p <0.0001 in the anterior wall, r2 = 0.56, p <0.0001 in the lateral wall and r2 = 0.44, p <0.0001 in the inferior wall). According to the decade-by-decade analysis of washout rate, women had a significantly lower washout than men under 50 yr in every region and a significantly higher washout in the lateral wall than men over 70 yr. CONCLUSION: The sympathetic nervous system in the human left ventricle showed age- and gender-related regional changes. The findings suggested that men have high sympathetic nerve activity from a younger age, and women have a progressive increase in sympathetic nerve activity with aging. These changes may contribute to the age and gender differences in the incidence and development of cardiac disorders.

Comparison of effects of enalapril and nitrendipine on cardiac sympathetic nervous system in essential hypertension.

OBJECTIVES: The purpose of this study was to assess the effects of enalapril and nitrendipine on the cardiac sympathetic nervous system. BACKGROUND: Angiotensin-converting enzyme inhibitors and long-acting calcium channel blockers have been widely used in the treatment of cardiovascular diseases, in some of which sympathetic overactivity plays a major role in the pathophysiology and prognosis. However, little information is available on the effects of these drugs on the cardiac sympathetic nervous system. METHODS: 123I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed before and 3 months after drug administration in 46 patients with mild essential hypertension. Twenty-two patients were treated with 5 to 10 mg of enalapril once a day, and the other 24 with 5 to 10 mg of nitrendipine once a day. For comparison, 20 normotensive subjects were also studied. RESULTS: There were no significant differences between the basal characteristics in the 2 hypertensive groups. In both hypertensive groups, both systolic and diastolic blood pressures were significantly reduced to similar levels after the 3-month drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower MIBG uptake than the normotensive subjects. The heart-to-mediastinum ratio significantly increased (p < 0.0001), with decreased (p < 0.002) washout rate after drug treatment in the enalapril group, but with no significant changes in the nitrendipine group. CONCLUSION: Enalapril could suppress cardiac sympathetic activity and nitrendipine had no effect on it. The knowledge of antihypertensive drugs on the cardiac sympathetic nervous system appears to be helpful in selecting appropriate treatment in cardiovascular diseases.

Remnant-like particle cholesterol is a major risk factor for myocardial infarction in vasospastic angina with nearly normal coronary artery.

We investigated the association of remnant-like particle cholesterol (RLP-C), with vasospastic angina (VSA). We selected 66 subjects with nearly normal coronary artery as a control group, and 74 VSA with nearly normal coronary artery, of whom 19 had prior myocardial infarction (MI). Coronary risk factors, triglyceride, lipoproteins and apolipoproteins were evaluated using stepwise discriminant analysis, smoking was the only discriminator of the control group from VSA and RLP-C was the only discriminator of VSA with MI from VSA without MI. In comparison between VSA with and without MI, using stepwise logistic regression analysis, the only significant variable was RLP-C, and odds ratio of RLP-C for MI was 1.59. Thus, RLP-C is a major discriminator of VSA with MI and appears to be a major risk factor for MI in VSA.

Comparison of filled-in myocardial segments after early and late reinjection of thallium-201--influence of the timing of reinjection on fill-in.

Thallium-201 (201Tl) late reinjection after stress-redistribution imaging improves the detection of viable myocardium. Recently, early reinjection of 201Tl immediately after stress imaging was proposed as a new method for distinguishing ischemic myocardium, hibernating myocardium, and myocardial scar. However, there are no data on the influence of the timing of reinjection on "fill-in." This study was designed to assess whether the reinjection time influences "fill-in" in chronic coronary artery disease. Thirty-three patients with chronic coronary artery disease were studied. All patients underwent exercise 201Tl tomography. Immediately after stress imaging, 37 MBq of thallium was reinjected earlier than usual and early reinjection delayed image (ERDI) was acquired 3 h later. With the same protocol, all patients also underwent a second study involving late reinjection of 201Tl within 1 week. An additional 37 MBq of thallium was reinjected 3 h after stress imaging, and late reinjection delayed image (LRDI) was obtained 10 min later. All images were analyzed qualitatively using a 4-point grading uptake score. Of the 72 hypoperfused segments on stress images, 66 segments showed fill-in and 6 showed persistent defects on ERDI, and of the same 72 segments 55 segments displayed fill-in and the remaining 17 showed persistent defects on LRDI (p<0.05). The delta uptake score (the uptake score of the delayed image minus that of stress image) in early reinjection was 1.60+/-0.80, which was significantly higher than that in late reinjection (1.24+/-0.94, p<0.01). A small dose of thallium reinjected immediately after stress imaging with delayed images obtained 3 h later is convenient and might provide another technique for determining myocardial viability.

[A case of an expanding congenital left ventricular aneurysm].

Congenital ventricular aneurysm is rare. There have been only 17 case reports in Japan. Only 9 of them were treated surgically. In this paper, we report a case with a congenital left ventricular aneurysm successfully treated by surgery. A 42-year-old female was admitted to our hospital with chest pain and ECG abnormalities. Left ventriculography revealed aneurysmal formation of the left ventricle with normal coronary arteries. Surgical resection was performed because repeated echocardiography had showed its enlargement. Surgical treatment for congenital ventricular aneurysm seems to be indicated to those with worsening symptoms, volume enlargement or thrombus formation.

Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize vasospastic angina without significant coronary artery narrowing.

OBJECTIVES: We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG) imaging to identify and localize coronary spasm and determined the most useful method of MIBG analysis in vasospastic angina without significant coronary narrowing. BACKGROUND: Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in patients with sporadic attacks. MIBG imaging has recently been proposed as a useful tool for detecting vasospastic angina. METHODS: Normal limits of both visual and quantitative analysis of two-dimensional polar maps (bull's-eyes) for MIBG imaging were at first established in 59 normal subjects. For optimal criteria of visual analysis, we established regional differences in abnormal MIBG defect scores. An abnormal region of the bull's-eye was defined as an area > 2 SD below normal. An abnormal regional washout rate was defined as < 0%. Using these criteria, we prospectively evaluated 104 patients with suspected vasospastic angina. Visual, bull's-eye and regional washout rate analyses were compared for overall detection of the disease and for individual vessel involvement. RESULTS: Overall sensitivity by these methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a significantly higher sensitivity than the other two methods. Specificity was 78%, 72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary artery with washout rate analysis was 82% for the left anterior descending (LAD), 76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for bull's-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis showed a significantly higher sensitivity for LAD spasm than for the other two methods and a higher sensitivity for RCA and Cx spasms than for visual analysis. CONCLUSIONS: Regional washout rate analysis of MIBG imaging is a highly accurate technique for determining the presence and location of coronary artery spasm.

Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy.

With the use of iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy, this study evaluated regional sympathetic nerve activity in vasospastic angina. Twenty male patients with left anterior descending coronary artery spasm and 18 male patients with normal coronary arteries as a control group were studied. All patients underwent quantitative 123I-MIBG scintigraphy and atropine stress 123I-MIBG scintigraphy. Both groups showed a similar heterogeneous 123I-MIBG uptake in the left ventricle. However, the regional washout rate in patients with coronary artery spasm was significantly reduced in all three territories compared with that in the control group. In vasospastic angina, the regional washout rate in the left anterior descending coronary artery territory was significantly reduced as compared with the other two regions. After intravenous injection of 1 mg atropine, the regional washout rate in the three regions significantly increased in both groups, but the regional differences between the two groups disappeared. The current study demonstrated that cardiac sympathetic nerve activity in vasospastic angina was suppressed, especially in the territory of the spasm-induced coronary artery, probably because of the enhanced parasympathetic nerve activity.

Impaired fibrinolysis early after percutaneous transluminal coronary angioplasty is associated with restenosis.

This study examined the role of fibrinolytic components in the process of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Seventy-two patients with single-vessel disease who underwent successful PTCA were prospectively selected. Tissue plasminogen activator (TPA), free plasminogen activator inhibitor-1 (free PAI-1), TPA/PAI-1 complex, and total PAI-1 antigen levels were measured before, at 1 week after, and at 3 months after PTCA. Six months after PTCA, the study patients were divided into two groups: 41 patients without restenosis and 31 patients with restenosis. There were no significant differences with regard to sex, age, coronary risk factors, or morphologic changes in the target lesions between the two groups. There were no significant differences in plasma TPA, TPA/PAI-1 complex, or total PAI-1 levels at each sampling period, or in the time courses between the two groups, except for total PAI-1 levels at 1 week after PTCA. Although no significant differences in free PAI-1 levels before PTCA were observed, free PAI-1 levels after PTCA in the patients with restenosis were significantly higher than those in the patients without restenosis. In addition, each group had a significant change in the time course of free PAI-1 levels. The results suggest that impaired fibrinolysis early after PTCA might affect the repair process of vascular injury, which leads to restenosis, and also that serial determination of free PAI-1 levels could help predict restenosis.

Emergency coronary angioplasty for acute myocardial infarction: predictors of early occlusion of the infarct-related artery after balloon inflation.

THE FACTORS RESPONSIBLE FOR EARLY OCCLUSION OF THE INFARCT VESSEL AFTER emergency percutaneous transluminal coronary angioplasty (PTCA) were retrospectively examined in 191 patients with acute myocardial infarction. During the 24-hour period after the initial balloon inflation, 47 patients (25%) had occlusion of the vessel (occlusion group), whereas 144 did not (nonocclusion group). The former patients immediately underwent repeat PTCA, which was successful in 37. Univariate correlates of early occlusion were a shorter time interval between the onset of symptoms and PTCA (3.5 +/- 2.2 vs 4.5 +/- 2.9 hours, p = 0.025), right coronary artery involvement (53% vs 30%, p = 0.015), prior thrombolytic therapy (49% vs 32%, p = 0.035), and undersized inflation (43% vs 17%, p < 0.001). With multivariate analysis the three independent predictors were undersized inflation (p < 0.001), right coronary artery involvement (p = 0.004), and a shorter time interval until PTCA (p = 0.011). Thus patients undergoing early PTCA and having right coronary artery involvement appear to be at greater risk of having early occlusion. Thrombolytic agents and undersized inflation may also play an important role in its development.

HA-1077 suppress both proliferation of vascular smooth muscle cells and c-fos mRNA induction.

HA1077 is a newly synthesized vasodilator with unique intracellular calcium antagonistic action. In this study, its effect on the growth of vascular smooth muscle cells (VSMC) stimulated by fetal calf serum was examined. Both the proliferation and [3H]thymidine incorporation into DNA of the growth-arrested VSMC was dose-dependently inhibited by HA1077. The expression of a proto-oncogene, c-fos, which reached the maximum 30 min after addition of serum, was similarly inhibited by this agent in a dose-dependent manner. Thus, HA1077 is expected to be a useful vasodilator agent capable of suppressing the growth of VSMC which is thought to be an important underlying mechanism of atherosclerosis or restenosis after angioplasty.

Percutaneous transluminal coronary angioplasty for patients with unstable angina pectoris.

Percutaneous transluminal coronary angioplasty (PTCA) was successful in 91% of 76 patients with unstable angina pectoris refractory to pharmacological treatment. However, the rate of acute occlusion and reocclusion was rather high (95). Restenosis developed in 56.5% of successful cases after initial PTCA, and 29 patients underwent 2nd, and nine 3rd PTCA. Most refractory unstable angina can be controlled by PTCA, which may require repeating in some patients.

A new type of vasodilator, HA1077, an isoquinoline derivative, inhibits proliferation of bovine vascular smooth muscle cells in culture.

The effects of a newly developed vasodilator agent, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride], were investigated on the proliferation of cultured bovine aortic vascular smooth muscle cells (VSMC). HA1077 (10-100 microM) inhibited both fetal calf serum-induced proliferation and [3H]thymidine incorporation into DNA of the growth-arrested VSMC in a dose-dependent manner. When quiescent cells were stimulated with platelet-derived growth factor followed by insulin, HA1077 (1-30 microM), administered together with either stimulation, showed dose-dependent inhibition of [3H]thymidine incorporation. Further reduction of [3H]thymidine incorporation was observed when HA1077 was present at both stimulations, suggesting that HA1077 suppresses DNA synthesis acting in both competence and progression stages. After stimulation with fetal calf serum, quiescent VSMC started and ceased DNA synthesis in 15 to 18 hr and 24 hr, respectively. HA1077 inhibited [3H]thymidine incorporation when it was added either from 12 hr to 15 hr or from 21 hr to 24 hr after serum stimulation. In addition, when percent inhibition of [3H]thymidine incorporation by continuous exposure to HA1077 was examined as a function of the time it was added, reductions of the value were observed at 0 to 3 hr, 12 to 18 hr and 21 to 24 hr. Thus, we concluded that HA1077 suppresses DNA synthesis of bovine VSMC acting at the G0/G1 and the G1/S phase transitions and also in the S phase of the cell cycle. It is suggested that this agent may act as a potent inhibitor of VSMC proliferation as well as a vasodilator.