Preserved endothelium-dependent vasodilation at the vasospastic site in patients with variant angina.

Endothelial dysfunction has been implicated as a cause of coronary vasospasm in patients with variant angina. This study aimed to determine if endothelium-dependent vasodilation evoked with substance P (SP) was altered at the spastic site where vasospasm was induced by acetylcholine (ACH) in patients with variant angina. It has been shown that SP evokes endothelium-dependent vasodilation with no direct effect on vascular smooth muscle in excised human coronary arteries. SP and ACH were infused into the coronary arteries in nine patients with variant angina in whom coronary arteriograms showed normal or mild atherosclerotic lesions. The vasomotor responses of coronary arteries were assessed by quantitative arteriography. ACH at a high dose (100 micrograms/min) provoked coronary vasospasm associated with anginal attack in all patients. In contrast, SP at graded doses (13.5, 40, and 135 ng/min) caused the dose-dependent and comparable increases in the coronary diameter at the spastic and control sites. ACH at a low dose (10 micrograms/min) also caused comparable vasodilation at the spastic and control sites in patients with normal coronary arteries. Coronary vasodilating responses to SP were comparable in patients with variant angina and those with atypical chest pain. The results indicate that endothelium-dependent vasodilation evoked with SP and ACH at the low dose was present at the vasospastic site in patients with variant angina. These findings suggest that the ACH-induced coronary vasospasm in patients with variant angina results from hyperreactivity of vascular smooth muscle to ACH but not from endothelial dysfunction.

Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions.

We examined whether coronary risk factors and atherosclerotic lesions in the study artery were associated with impaired endothelium-dependent dilation of coronary resistance arteries. Acetylcholine (ACH) at graded doses (1, 3, 10 and 30 micrograms/min) and papaverine (10 mg) were selectively infused into the left anterior descending coronary artery of 28 patients, in whom the study artery was angiographically normal (n = 16) or with mild stenosis < or = 40% (n = 12). Coronary blood flow (CBF) was estimated from the product of mean CBF velocity measured by an intracoronary Doppler catheter and the arterial cross-sectional area of the study artery determined by quantitative arteriography. ACH increased CBF in a dose-dependent manner. However, the maximum CBF response to ACH varied widely among patients (from 50% to 660%). By multivariate analysis, the presence of atherosclerotic lesions in the study artery was an independent predictor for impaired CBF response to ACH (P < 0.01). Hypertension (P < 0.001), hypercholesterolemia (r = -0.52, P < 0.005), age > or = 50 yr (P < 0.01) and total number of coronary risk factors (r = -0.62, P < 0.001) were associated with the impaired increase in CBF with ACH by univariate analysis. The percent increase in CBF evoked with papaverine did not correlate with these risk factors. The results suggest that mild atherosclerotic lesions in the study artery and coronary risk factors are accompanied by impaired endothelium-dependent dilation of coronary resistance arteries evoked with ACH. Endothelial dysfunction of coronary resistance arteries may result in altered regulation of myocardial perfusion in patients with mild coronary atherosclerosis and coronary risk factors.

Correlation of basal coronary artery tone with constrictive response to ergonovine in patients with variant angina.

OBJECTIVES: This study was conducted to examine whether basal coronary artery tone is elevated at the spastic site in patients with variant angina and to determine the significance of basal artery tone in predicting provocation of coronary artery spasm. BACKGROUND: Previous data have been conflicting on whether basal coronary artery tone is elevated in patients with variant angina. METHODS: We assessed basal coronary artery tone by obtaining the percent increase in coronary artery diameter induced by nitroglycerin in 20 patients with variant angina and 24 control subjects. We also examined the correlation between basal coronary artery tone and the constrictive response to ergonovine. RESULTS: In the patients with variant angina in whom spasm was provoked by the lower doses (1 or 5 micrograms) of ergonovine, basal coronary artery tone was greater (p < 0.05) at the spastic site (54 +/- 15% or 36 +/- 16%, respectively) than at the nonspastic site (40 +/- 25% or 25 +/- 15%, respectively). Basal coronary tone at the nonspastic site in these patients was greater (p < 0.01) than that in control subjects (15 +/- 6%). In the patients with variant angina in whom spasm was provoked only by the higher doses (15 or 50 micrograms) of ergonovine, basal coronary artery tone was comparable at the spastic and nonspastic sites and was not different from that in control subjects. The diagnostic sensitivity and specificity of elevated basal coronary artery tone (> or = 40%) in predicting provocation of spasm were 26% and 98%, respectively. CONCLUSIONS: These results indicate that elevated basal coronary artery tone may be useful in predicting provocation of coronary spasm, but the normal level of basal coronary artery tone does not exclude such provocation.

[Pulmonary large cell carcinoma contiguous to bullae with massive bullous hematoma and hemoptysis; with special reference to 20 cases of Japanese reports].

A 50-year-old man with continuous hemosputa and large hematoma of left upper lobe contiguous to bilateral emphysematous bullous disease was admitted for surgery to stop hemorrhage and to resect left lung hematoma and multiple bullae. Bullectomy and neodymium yttrium aluminum garnet (Nd-YAG) laser irradiation to bullae of left upper lobe performed successfully with maximum preserved pulmonary function of it. Pathological examination, however, revealed anaplastic carcinoma inside bulla of S(1+2)c with minimal invasion into adhered parietal pleura (p 3). Left upper lobectomy was carried out with complete mediastinal lymph node dissection (ND 2 b). The final pathological diagnosis was large cell carcinoma of left S(1+2)c with the staging pT3N0M0 and stage II. The patient lives actively in daily life more than 7 years without any recurrence. Clinical analysis of Japanese 20 cases of lung carcinoma with initial signs of hemosputa and/or hemoptysis contiguous to emphysematous bullae elucidate following important facts. Hemosputa and hemoptysis play important role for early finding and diagnosis of lung cancer contiguous to bullous disease, especially in patients of early clinical stage with or without computed tomography (CT) exams and promise to better surgical prognosis and survivals as compared with non hemosputa ones.

Cross-reactive antibodies against human cultured B cells and bovine erythrocytes in human renal transplantation sera.

Sera of 58 recipients of renal allografts were studied for the presence of antibodies against cell cultures of human B lymphoid cell lines (B-LCL) and bovine erythrocytes (BRBC). Cytotoxic anti-B-LCL antibodies were found in 13% of the sera from recipients with the grafts and in 67% of the sera obtained after removal of the rejected grafts. Most of these sera also contained BRBC lysins of high titers. Absorption studies showed that the anti-B-LCL antibodies are directed against antigens shared by BRBC and that they can be absorbed with corresponding graft tissues. The specificity of BRBC lysins found in some of the transplantation sera was shown to be similar to that of Hanutziu-Deicher antibodies.

Effects of intracoronary infusion of atrial natriuretic peptide on pacing-induced myocardial ischemia in patients with effort angina pectoris.

BACKGROUND: Atrial natriuretic peptide (ANP) has been shown to dilate the coronary artery. The aim of this study was to determine whether, in patients with effort angina pectoris, intracoronary infusion of ANP attenuates pacing-induced myocardial ischemia either by dilating the stenotic lesion in a large coronary artery or by dilating collateral vessels. METHODS: We studied six patients who had total or subtotal occlusion in one coronary artery and well-developed, angiographically visible collateral vessels (group A) and five patients who had a significant stenosis in a large coronary artery with no visible collateral vessels (group B). Their heart rate was increased by atrial pacing both before and after intracoronary infusion of ANP (0.03 microgram/kg/min for 15 min) into the donor artery of collateral vessels in group A or into the stenotic artery in group B. RESULTS: Before ANP infusion, all patients of both groups developed an ischemic ST-segment depression (> or = 0.1 mV) and angina-like chest pain from pacing tachycardia. After ANP infusion, significant ST-segment depression was induced by rapid pacing in only one out of six patients of group A, whereas it was noted in all patients of group B (P < 0.01). After ANP infusion, chest pain developed in one out of six patients in group A, whereas it appeared in four out of five patients in group B (P < 0.05). ANP significantly dilated the angiographically normal segment of the epicardial coronary artery, but it did not significantly change the severity of the stenotic lesion in either group. ANP did not change the basal arterial pressure or heart rate, nor did it change their response to pacing tachycardia. CONCLUSION: Infusing ANP into the donor artery of collateral vessels, but not into the artery with culprit stenotic lesion, attenuated pacing-induced myocardial ischemia. Therefore, the beneficial effects of ANP in reducing pacing-induced myocardial ischemia may result from the increase in myocardial perfusion to the ischemic area caused by dilating the collateral vessels.

Early changes of bone histology and circulating markers of bone turnover after parathyroidectomy in hemodialysis patients with severe hyperparathyroidism.

AIMS: There have so far been no reports on the changes in bone histology in the early period after parathyroidectomy and autografting (PTX-AG). We investigated the effects of PTX-AG on bone histology during the initial 12 weeks after undergoing these surgical procedures. MATERIALS AND METHODS: We performed bone histomorphometry 3 times (before as well as 4 and 12 weeks after PTX-AG) in 6 patients and 2 times (before and 4 weeks after PTX-AG) in 3 hemodialysis patients. In addition, the circulating parameters of bone metabolism were also assessed before and after PTX-AG in all 9 patients. The changes in the histomorphometric (static) parameters between pre-surgery and 4 weeks after surgery and those between 4 weeks and 12 weeks after surgery were assessed by the t-test while changes in the circulating parameters of bone metabolism were analyzed by Friedman's test. RESULTS: Bone formation parameters including carboxy terminal propeptide of human type I procollagen (PICP), alkaline phosphatase (ALP) and intact osteocalcin (i-OC) were all extremely high before surgery. These parameters initially increased after PTX-AG and thereafter gradually declined. In contrast, the circulating bone resorption parameters including tartrate-resistant acid phosphatase (TRAP) and deoxypyridinoline (Dpyr) were also extremely high at baseline but markedly declined after operation. Osteoid-related parameters including osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th) all initially increased at 4 weeks after PTX-AG. In contrast, osteoblast surface (Ob.S/BS), osteoclast surface (Oc.S/BS), eroded surface (ES/BS), and fibrosis volume (Fb.V/TV) all decreased at 4 weeks after surgery, while Ob.S/BS decreased further at 12 weeks in cases 1-6. Although bone mineralization was ongoing at 4 weeks after surgery, both the mineral apposition rate (MAR) and bone formation rate (BFR) remained below the mean for normal individuals. CONCLUSIONS: The circulating bone formation parameters and osteoid-related parameters showed an initial increase after PTX-AG. The concomitant decline in the circulating bone resorption parameters reflected the reduction in bone resorption. BFR decreased, but bone mineralization did not stop after PTX-AG.

[Quantification of myocardial infarct size by technetium-99m pyrophosphate single photon emission computed tomography].

Myocardial infarct size in 41 patients with the first attack of acute transmural myocardial infarction (MI) was assessed by technetium-99m pyrophosphate single photon emission computed tomography (99mTcPYP-SPECT). A ratio of the number of voxels of 99mTcPYP uptake into the infarct area to that into the thorax was calculated as a parameter of MI size. The ratio was positively correlated with both peak CPK activity (r = 0.53, p less than 0.005, n = 24) and extent score in 201TI-SPECT (r = 0.70, p less than 0.005, n = 14) significantly in patients with anterior MI but not in patients with inferior MI. There was also significant negative correlation between the ratio and the left ventricular ejection fraction (LVEF) measured by RI angiography in both acute (r = -0.67, p less than 0.005, n = 18) and chronic (r = -0.75, p less than 0.005, n = 25) phases in patients with anterior MI. Recovery in LVEF at chronic phase was noted in patients with small anterior MI but not with large anterior MI. 8 of 14 patients with inferior MI had right ventricular MI, that might have affected evaluation of MI size and resulted in no correlation between variables. It was suggested that 99mTcPYP-SPECT was a useful method to evaluate MI size and to predict prognosis of cardiac function in patients with anterior MI but not in patients with inferior MI.

[A case of lupus erythematosus preceded by right heart failure due to pulmonary hypertension].

A 40-year-old woman was admitted because of increasing exertional dyspnea. Right heart failure was suggested by the presence of hepatomegaly, pretibial edema and also echocardiographic findings. Physical examination and echocardiography showed no evidence of valvular disease or congenital heart disease except for right ventricular dilatation and tricuspid regurgitation. The ventricular septum deviated toward the left ventricle throughout the cardiac cycle, but left ventricular function was preserved. Severe pulmonary hypertension averaging 44 mmHg was revealed by cardiac catheterization. Digital subtraction angiography and pulmonary blood flow scintigraphy showed no evidence of pulmonary artery embolism, and no interstitial pulmonary lesions that might have caused pulmonary hypertension were recognized. Hypergammaglobulinemia suggested an autoimmune disorder, and signs of systemic lupus erythematosus (SLE), such as pleural effusion, proteinuria, lymphocytopenia, LE cell phenomenon and antinuclear antibodies were present. Several autoimmune diseases are known to be causative factors of pulmonary hypertension. However, only ten cases of SLE complicated by pulmonary hypertension have been reported the present one. These cases were characterized by a high incidence of Raynaud's phenomenon and positivity for anti-RNP antibody. In our present case, SLE activity was suppressed using prednisolone, but pulmonary hypertension persisted and the patient eventually died due to right cardiac failure. Judging from the clinical course of the ten reported cases of SLE-pulmonary hypertension, there seems to be no hope of improving the pulmonary hypertension once it has become established. Therefore it is important to detect and cure pulmonary hypertension as early as possible.

Efficacy and effect on plasma B-type natriuretic peptide concentration of losartan-hydrochlorothiazide for hypertension uncontrolled by losartan-based therapy: subanalysis of a Multicentre Prospective Observational Study.

Many patients with hypertension have difficulty achieving their target blood pressure (BP). Therefore combination therapy, for example with an angiotensin II receptor blocker (ARB) and a diuretic, may be recommended. We previously evaluated the efficacy and safety of losartan (LOS) 50 mg - hydrochlorothiazide (HCTZ) 12.5 mg, as well as its effect on the plasma concentration of B-type natriuretic peptide (BNP, a prognostic marker for cardiovascular events), in patients with hypertension uncontrolled by ≥3 months of ARB-based therapy. The present subanalysis used data from patients who received LOS-based therapy before switching to LOS-HCTZ. Efficacy, safety, and changes in blood biochemical variables including BNP were evaluated. After excluding 4 patients with protocol violations, data from 35 patients (aged 36-79 years, mean 63 years; 66% male) were used in the safety analysis. The efficacy analysis used data from the 30 patients who were followed up for 12 months. Systolic/diastolic BP decreased from 156±12/87±11 mmHg at baseline to 125±11/73±10 mmHg at 12 months (p<0.001). After 12 months, half of the patients achieved their target BP as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2004. In 12 patients with baseline plasma BNP concentration ≥20 pg/mL, BNP decreased from 78.3±18.8 pg/mL to 57.3±17.7 pg/mL (p<0.01). 3 patients experienced adverse events, one of which was cardiovascular. LOS-HCTZ is efficacious, has a good safety profile, and decreases plasma BNP concentration.