Usefulness of Novel Atherogenic Lipid Indices for the Evaluation of Metabolic Status Leading to Coronary Heart Disease in a Real-World Survey of the Japanese Population.

We evaluated the usefulness of two novel cholesterol-triglyceride subgroup (CTS) indices, CTSqlt and CTSqnt, that potentially reflect the metabolic status regarding risk of coronary heart disease (CHD) using a retrospective longitudinal study of the Japanese general population. We recruited 12,373 individuals from the annual users of our healthcare center. Among them, the first onset of CHD was recorded in 131 individuals between April 2014 and March 2020. The multivariate Cox proportional hazards regression analyses for all normalized lipid indices revealed that the CTSqnt index showed a comparable hazard ratio for the CHD outcome to non-high-density lipoprotein cholesterol (nonHDL-c) and triglycerides. The HR of the CTSqlt index was significantly lower than for CTSqnt, but still comparable to that for low-density lipoprotein cholesterol (LDL-c). In comparison with the other indices, CTSqlt is more sensitive to risk increment while the index value increases. Linear regression analyses for the CTS indices and previously known lipid indices suggest that the CTSqnt and CTSqlt indices reflect the quantity of atherogenic lipoproteins and particle size (quality) of smaller and denser LDLs, respectively. Furthermore, the CTSqnt/HDL-c index can be used as a comprehensive risk indicator that may represent the status of lipid metabolism determined by the CTSqlt and CTSqnt indices and thus may be useful for screening. The CTS indices can be used to evaluate the metabolic status of individuals, which may increase the risk of future CHD.

Transarterial Embolization With Complementary Surgical Ligation of Gastroduodenal Artery for Ruptured Pancreaticoduodenal Artery Aneurysm.

The association between pancreaticoduodenal artery aneurysm (PDAA) and local hemodynamic changes in pancreaticoduodenal arcades is well established. However, there are few case reports of PDAA associated with acute aortic dissection. In this article, we outline and discuss the case of a 61-year-old man diagnosed with a type A acute aortic dissection who underwent emergency surgery and developed sudden-onset severe abdominal pain and shock 10 days later. Contrast-enhanced computed tomography showed a ruptured PDAA with feeding vessels from the gastroduodenal and superior mesenteric arteries, with evidence that the celiac artery was diverged from a false lumen. Transarterial embolization via the superior mesenteric artery alone was not expected to achieve hemostasis, so we performed a hybrid procedure involving transarterial embolization cannulated from superior mesenteric artery with complementary surgical ligation of the gastroduodenal artery. The postoperative course was uneventful, and follow-up contrast-enhanced computed tomography showed no persistence of the aneurysm 8 days after the second operation. This case proposed that visceral arterial malperfusion due to acute aortic dissection can cause PDAA in the early postoperative period. Although previous reports suggest that endovascular treatment is preferable, it may not always be feasible. Since ruptured PDAAs are often not detected during surgery, surgical treatment can be overly invasive. Whereas, transarterial embolization with complementary clamping or ligation of the gastroduodenal artery for ruptured PDAA is less invasive and can control hemorrhage, especially when cannulation to the celiac artery is impossible. Notably, the technique did not cause organ ischemia, presumably because the small collateral vessels of the pancreaticoduodenal arcades permitted sufficient blood flow. If endovascular treatment is unable to achieve rapid hemostasis, this technique may be a useful option for ruptured PDAA.

In vitro assessment of six aspiration catheters using a distal protection filter.

BACKGROUND: We assessed performance of 6 aspiration catheters for distal embolization using a distal protection filter in an in vitro experiment. In acute myocardial infarction, a distal protection filter is used for lesions likely to induce a distal embolism. Which aspiration cathether is most effective when used with a distal protection filter remains still unclear. METHODS: A 0.5-cm3 bolus of gelatin as a model of stagnant pools of coronary plaque debris was captured in the distal protection filter and aspirated by 6 aspiration catheters. We measured and compared the length of the suspended embolus matter. RESULTS: Among the 6 catheters evaluated, the use of the Export Advance catheter (Medtronic) resulted in significantly shorter lengths of the suspended embolus matter compared to the use of the TVAC II (Nipro), Thrombuster III SL (Kaneka), and Rebirth Pro (Goodman) catheters (p < 0.01). The residual embolus matter in all cases had drained distally to the distal protection filter when the filter was retrieved. CONCLUSIONS: The use of the Export Advance catheter showed better performance using a distal protection filter in this in vitro experiment, and its use might be more effective in preventing distal embolisms in combination with a distal protection filter.

Norepinephrine spillover during exercise as a novel parameter to evaluate the severity of heart failure.

BACKGROUND: The washout rate (WR) of (123)I-metaiodobenzylguanidine (MIBG) is now widely used for assessing the severity of heart failure. Although the WR of MIBG is usually measured at rest, the assessment of WR of MIBG during exercise might have a different clinical relevance. In this study, we measured the WR rate of MIBG during low-grade exercise and studied the clinical importance of this novel index. METHODS: Twenty-four patients with dilated cardiomyopathy (DCM) were enrolled in this study. Planar images were obtained 20 minutes after MIBG injection (first image) and after 270 minutes (second image); the third image was obtained after 15 minutes of low-grade (10 W) bicycle ergometer exercise (300 minutes after MIBG injection). The decay of the specific counts was calculated from the first two images. The estimated third counts were calculated from the resting decay and were compared with the actual third counts. RESULTS: In the receiver operating characteristic (ROC) curve analysis, we set a 10% decrease from the estimated counts as a cut-off value for severe heart failure (New York Heart Association [NYHA] Class IIm or worse). In 15 patients, the actual third count value was within 10% of the estimated count (N-group). In nine patients, the WR during exercise was high, and the actual third count values showed more than a 10% decrease from the estimated count value (H-group). In the H-group, 78% of the patients were in NYHA class IIm or III. In contrast, in the N-group, no patient had NYHA class III, and only 20% of the patients were in class IIm. The brain natriuretic peptide (BNP) level was significantly higher in the H-group than in the N-group (525 ± 263 pg/mL vs 176 ± 144 pg/mL; P < .01). No significant differences were observed in heart/mediastinal (H/M) activity ratio, the regular WR, and left ventricular ejection fraction values between the two groups. CONCLUSIONS: The WR of MIBG during exercise may be an independent prediction variable, with a clinical relevance different from that of the WR at rest. This measurement could be used as a new index for assessing the severity of heart failure.

Retrovirally introduced prostaglandin D2 synthase suppresses lung injury induced by bleomycin.

Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme to produce prostaglandin (PG) D and J series. These PGs are involved in inflammation and immune system. The PGDS complementary DNA (cDNA)-expressing retrovirally transfected fibroblasts were introduced in vivo, and effect of the expression on lung injury induced by bleomycin was investigated in mice. Intravenous injection of PGDS cDNA-expressing fibroblasts significantly reduced lung edema, leukocyte infiltration in bronchoalveolar lavage (BAL) fluid, and pulmonary collagen content at 4 wk after instillation of bleomycin. Survival rate in mice instilled with the PGDS-expressing fibroblasts was higher than that in mice that received the mock transfection. Administration of 15-deoxy-Delta 12,14-PGJ2, which is a nonenzymatic metabolite of PGD2, also attenuated the lung injury, suggesting mediation of PGs produced by PGDS for the attenuation. Introduction of PGDS cDNA-expressing fibroblasts suppressed expression of basic fibroblast growth factor, connective tissue growth factor, and collagen messenger RNAs in the lungs, as well as the levels of total proteins and hemoglobin in BAL fluid. These data suggest that the suppressive effect of PGDS on the lung injury could be partly mediated by edema formation and inhibition of genes involved in the fibrotic change.

Nitric oxide released from iNOS in polymorphonuclear leukocytes makes them deformable in an autocrine manner.

The objective of this study was to determine whether endogenous nitric oxide (NO) derived from reaction catalyzed by the inducible isoform of NO synthase (iNOS: NOS II) in polymorphonuclear leukocytes (PMNs) makes the PMNs deformable. Previous studies have shown that NO increases the deformability of PMNs and decreases the sequestration of PMNs in the lungs. However, there was little information regarding the effect of PMN-derived NO on the cells' deformability. In the present study PMNs were isolated from the blood of rats 24h after ip injection of saline (control) or lipopolysaccharide (LPS), and expression of iNOS in the PMNs of the LPS group was confirmed by immunocytochemistry. PMN deformability was evaluated by measuring the pressure generated during their passage through a microfilter at a constant flow rate. The nitrite/nitrate content of the solution in which the isolated PMNs were incubated was measured by the Griess method. In the control group, no iNOS was detectable in the PMNs, and the nitrite/nitrate level in the PMN incubation solution was low. Deformability was unchanged after incubation with specific iNOS inhibitor aminoguanidine, but decreased after incubation with N-formyl-methionyl-leucyl-phenyl-alanine. In the LPS group, PMN deformability was decreased compared to that of the control group. iNOS was detectable in the PMNs, and the deformability further decreased after incubation with aminoguanidine. These results suggest that endogenous NO generated during reactions catalyzed by iNOS in PMNs makes them deformable in an autocrine manner.

Dietary cholesterol-oxidation products accumulate in serum and liver in apolipoprotein E-deficient mice, but do not accelerate atherosclerosis.

There are conflicting reports regarding the effect of dietary cholesterol-oxidation products (oxysterols) on the development of atherosclerosis in experimental animals. To address this issue, apolipoprotein (Apo) E-deficient mice were fed a purified diet (AIN-93) or the same purified diet containing 0.2 g cholesterol or 0.2 g oxysterols/kg. The dietary oxysterols had no significant effect on the serum lipid levels. Although all of the diet-derived oxysterols (cholest-5-en-3beta,7alpha-diol, cholest-5-en-3beta,7beta-diol, cholestan-5alpha,6alpha-epoxy-3beta-ol, cholestan-5beta,6beta-epoxy-3beta-ol, cholestan-3beta, 5alpha, 6beta-triol, cholest-5-en-3beta-ol-7-one and cholest-5-en-3beta, 25-diol) accumulated in the serum and liver, only cholest-5-en-3beta-ol-7-one and cholestan-3beta, 5alpha, 6beta-triol accumulated significantly (P<0.05) in the aorta. The oxysterol diet did not result in elevation of the aortic cholesterol level or the lesion volume in the aortic valve. These present results indicate that exogenous oxysterols do not promote the development of atherosclerosis in ApoE-deficient mice.