Coronary artery stent dislodgement and aortic dissection in a patient with a severely calcified lesion in the proximal right coronary artery.

In atherosclerosis progression, calcium deposition may have an impact on the natural history of coronary atherosclerosis, and the amount of calcium may affect the success rate of percutaneous coronary intervention (PCI). Coronary stent dislodgement does not commonly occur in the modern PCI era; however, it may lead to fatal death. If it occurs, retrieval of a dislodged stent can be performed either surgically or percutaneously using a variety of retrieval techniques, including inflating a catheter balloon distal to the undeployed stent, twirling 2 wires around the stent, a loop snare, or forceps. Here, we report a rare case that coronary artery stent dislodgement and aortic dissection simultaneously occurred during PCI for a severely calcified lesion in the proximal right coronary artery with shepherd's crook morphology. The situation was successfully rectified by using balloons to deploy the stent, as well as by applying an additional stent and minimizing the contrast used to treat aortic dissection. Learning objective: During percutaneous coronary intervention (PCI), stent dislodgement and aortic dissection are extremely rare, but life-threatening complications. In this rare case of simultaneous stent dislodgement in the coronary artery and aortic dissection during PCI for a severely calcified lesion in the right coronary artery with shepherd's crook morphology, the situation was successfully rectified by using balloons to retrieve and deploy the stent, as well as by applying an additional stent and minimizing the contrast used to treat aortic dissection.

Acute Pulmonary Embolism due to Paget-Schroetter Syndrome.

A 17-year-old Japanese male athlete presented to the emergency department at our hospital with a chief complaint of exertional dyspnea. Although there were no significant findings in the right and left upper extremities on a physical examination, a chest computed tomography scan showed bilateral multiple thrombosis in the pulmonary arteries, indicating pulmonary thromboembolism, and deep vein thrombosis in the left subclavian vein. Upper limb venography showed interruption of the left subclavian vein (so-called Paget-Schroetter syndrome; PSS). We herein report this rare case of PSS that led to pulmonary thromboembolism in a young, male field athlete.

Effect of autologous bone-marrow cell transplantation on ischemic ulcer in patients with Buerger's disease.

BACKGROUND: Thromboangiitis obliterans, also known as Buerger's disease, is characterized by peripheral occlusive changes in the arteries of the upper and lower limbs and treatment is often ineffective. Intramuscular transplantation of autologous bone marrow-mononuclear cells (BM-MNC) has been recently reported as improving the symptoms and clinical manifestations in patients with severely ischemic limbs, mostly caused by arteriosclerosis obliterans. The present study focused on the patients with Buerger's disease presenting with rest pain and/or skin ulcer uncontrolled by conventional treatments. METHODS AND RESULTS: Fourteen patients with Buerger's disease (Fontaine III: n=2, Fontaine IV: n=12) underwent transplantation of autologous BM-MNC into ischemic skeletal muscles of either the upper or lower limb. After 4 weeks, rest pain was significantly reduced. In 19 skin ulcers of 9 patients, 8 ulcers were healed and 8 were diminished in the size. These improvements were maintained for 24 weeks without complications. CONCLUSIONS: In patients with Buerger's disease, intramuscular transplantation of autologous BM-MNC improved symptoms and clinical manifestations, especially skin ulcer.

Prediction of coronary artery disease in patients undergoing carotid endarterectomy.

OBJECT: The authors determined the factors that predict the coexistence of coronary artery disease (CAD) in patients who undergo carotid endarterectomy (CEA). METHODS: Data from 200 consecutive Japanese patients who underwent CEA for extracranial carotid artery stenosis were studied. Among 73 patients with CAD, 35 (48%) had three-vessel or left main CAD (that is, severe CAD). Peripheral artery disease was an independent predictor of CAD (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.08-6.3). In addition, diabetes mellitus ([DM]; OR 2.8, 95% CI 1.24-6.32) and peripheral artery disease (PAD) (OR 2.83, 95% CI 1.05-7.57) were independent predictors of severe CAD in the 200 patients. The percentage of patients with CAD as well as those with the severe form of the disease increased stepwise as the number of major coronary risk factors in patients increased. Asymptomatic CAD was newly detected during the pre-CEA assessment in 18 (25%) of the 73 patients in whom CAD was eventually diagnosed. Diabetes mellitus was an independent predictor of occult CAD among the 200 patients (OR 4.83, 95% CI 1.53-15.2). CONCLUSIONS: In patients with DM, PAD, or multiple major coronary risk factors who have been scheduled for CEA, one should carefully search for concomitant CAD, especially severe CAD, even when the patient has had no previous episode of angina.

Recurrent embolic stroke originating from an internal carotid aneurysm in a young adult.

An unruptured intracranial aneurysm is an uncommon but possible embolic source to the brain. We report a young patient who developed recurrent ischemic strokes occurring mainly in the left internal carotid arterial territory within a short interval; the first stroke occurred midway through a long-distance race, and the second stroke occurred immediately following a bowel movement. The angiographical contrast deficit indicated a thrombus in the left anterior cerebral artery as a result of the embolism. A saccular aneurysm of the left distal internal carotid artery was the only detectable potential embolic source. Initially anticoagulant therapy was given, and then surgical clipping of the aneurysm was performed. The patient has been free from stroke recurrence. As a cause of ischemic stroke in young adults, a carotid saccular aneurysm should be considered. Hard exercise and a Valsalva maneuver may be important triggers of thrombus detachment from the aneurysm.

Improved healing of small-caliber, long-fibril expanded polytetrafluoroethylene vascular grafts by covalent bonding of fibronectin.

PURPOSE: To evaluate the intermediate performance of small-caliber, long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts pretreated with covalent bonding of fibronectin in dogs. METHODS: Small-caliber (4 mm), long-fibril (60 microm), ePTFE vascular grafts, 10 cm in length, were pretreated by covalent bonding of fibronectin. Bilateral iliac grafting was done in dogs using a fibronectin-bonded graft on one side and a nonbonded control graft on the other side. The grafts were retrieved 12 weeks after implantation, and subjected to histomorphometric analysis. RESULTS: Although the patency rates of the fibronectin-bonded and control grafts were the same (3/7, 43%), the fibronectin-bonded grafts showed almost complete neointimal healing, whereas the nonbonded control grafts showed only partial neointimal healing, proximally and distally. CONCLUSIONS: Small-caliber, long-fibril ePTFE vascular grafts with covalent bonding of fibronectin achieved almost complete neointimal healing by the time of retrieval at 12 weeks. This indicates that, with further modifications, our new technique for covalent bonding of fibronectin has great potential in the development of small-caliber arterial prosthetic grafts.

Recurrent small-artery disease in hyperhomocysteinemia: widowers' stroke syndrome?

Hyperhomocysteinemia is thought to cause ischemic strokes. We report two middle-aged widowers with frequent recurrences of small-artery strokes, two capsular infarcts and a thalamic hemorrhage in one patient, and two thalamic and pontine infarcts in the other. Blood tests following the final stroke showed hyperhomocysteinemia and methylenetetrahydrofolate reductase C677T gene mutation, with low concentration of vitamin B6. Multivitamin supplementation normalized plasma homocysteine levels in both patients. Hyperhomocysteinemia is treatable; therefore, serum homocysteine should be measured as a potential risk factor for stroke recurrence in relatively young patients with recurrent small-artery infarctions or hemorrhage, especially those with insufficient lifestyle factors.

Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization.

OBJECTIVES: We sought to investigate the role of endogenous monocyte chemoattractant protein (MCP)-1 in ischemia-induced neovascularization. BACKGROUND: Roles of inflammatory changes including macrophage infiltration are suggested in ischemic neovascularization. METHODS: Unilateral hindlimb ischemia was induced by excising surgically the entire femoral artery and vein in mice. Immediately after operation, plasmid deoxyribonucleic acid encoding a dominant negative mutant of MCP-1 (7ND) or the empty plasmid (mock) was injected into the ipsilateral thigh adductor muscle. RESULTS: In mock-treated mice, MCP-1 was upregulated transiently in ischemic hindlimb peaking at day 3. Serial laser Doppler blood flow (LDBF) analysis showed an abrupt decrease in blood flow, followed by a recovery to the near-normal levels in mock-treated mice; 7ND treatment had no effects on the initial decrease in LDBF but deteriorated the recovery. At day 3, macrophage infiltration and inductions of tumor necrosis factor (TNF)-alpha and vascular endothelial growth factor (VEGF) were prominent in the ischemic adductor muscle in mock-treated mice; 7ND treatment significantly reduced macrophage infiltration and suppressed TNF-alpha and VEGF inductions in response to ischemia. At day 21, postmortem angiography and anti-CD31 immunohistostaining revealed well-developed collateral vessels and capillary formation, respectively, in the ischemic muscle of mock-treated mice; 7ND overexpression remarkably suppressed the collateral vessel formation and capillary formation. CONCLUSIONS: Endogenous MCP-1 may play a role in ischemia-induced neovascularization by recruiting macrophages that activate TNF-alpha and VEGF inductions.

Relationship between fibril length and tissue ingrowth in the healing of expanded polytetrafluoroethylene grafts.

PURPOSE: To determine whether fibril length is correlated with graft healing as well as cellular and capillary ingrowth in a canine carotid implantation model. METHODS: Expanded polytetrafluoroethylene (ePTFE) vascular grafts with three different fibril lengths (30, 60, and 90 microm) were implanted into the carotid artery in dogs. They were retrieved 4 weeks later, and subjected to histomorphometric analysis. RESULTS: Endothelial healing was best in the 60-microm grafts. Not only cellular ingrowth but also capillary ingrowth was most evident in the 60-microm grafts, followed by the 90-microm grafts and then the 30-microm grafts. CONCLUSION: Better endothelial healing of ePTFE vascular grafts is correlated with more cellular and capillary ingrowth, but more cellular and capillary ingrowth is not correlated with longer fibril length or higher air porosity.

Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse.

BACKGROUND: The effects of aging on angiogenesis (vascular sprouting) and vasculogenesis (endothelial precursor cell [EPC] incorporation into vessels) are not well known. We examined whether ischemia-induced angiogenesis/vasculogenesis is altered in klotho (kl) mutant mice, an animal model of typical aging. METHODS AND RESULTS: After unilateral hindlimb ischemia, laser Doppler blood-flow (LDBF) analysis revealed a decreased ischemic-normal LDBF ratio in kl mice. Tissue capillary density was also suppressed in kl mice (+/+>+/kl>kl/kl). Aortic-ring culture assay showed impaired angiogenesis in kl/kl mice, accompanied by reduced endothelium-derived nitric oxide release. Moreover, the rate of transplanted homologous bone marrow cells incorporated into capillaries in ischemic tissues (vasculogenesis) was lower in kl/kl mice than in wild-type (+/+) mice, which was associated with a decrease in the number of c-Kit+CD31+ EPC-like mononuclear cells in bone marrow and in peripheral blood. Finally, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin restored the impaired neovascularization in kl/kl mice, accompanied by an increase in c-Kit+CD31+ cells in bone marrow and peripheral blood, and enhanced angiogenesis in the aortic-ring culture. CONCLUSIONS: Angiogenesis and vasculogenesis are impaired in kl mutant mice, a model of typical aging. Moreover, the age-associated impairment of neovascularization might be a new target of statin therapy.

Reversible posterior leukoencephalopathy syndrome in a postpartum woman without eclampsia.

We report a patient who developed reversible posterior leukoencephalopathy syndrome (RPLS) in puerperium without preeclampsia-eclampsia or chronic hypertension. The woman suddenly complained of visual loss and headache 10 days after delivery caused by edematous lesions mainly distributed in the bilateral occipital lobe. Apparent diffusion coefficient map was useful for distinction of this vasogenic edema from cytotoxic edema due to brain infarction. Under the diagnosis of RPLS, we successfully treated her disease using a trinitroglycerin as an antihypertensive, a hyperosmolar agent, methylprednisolone, and a free radical scavenger. Postpartum women may have the risk of development of RPLS even without preeclampsia-eclampsia. Vascular endothelial dysfunction may trigger RPLS, in addition to acute and modest increase in systemic pressure.

Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth.

Although the renin angiotensin system (RAS) is a major regulator of vascular homeostasis, the role of the RAS in tumor angiogenesis is little understood. Here we show that host angiotensin II (ATII) type 1 (AT1) receptor plays an important role in angiogenesis and growth of tumor cells engrafted in mice. Subcutaneous B16-F1 melanoma-induced angiogenesis as assessed by tissue capillary density and microangiography was prominent in WT mice but was reduced in AT1a receptor-deficient (AT1a-/-) mice. Consequently, tumor growth rate was significantly slower, and the mouse survival rate was greater, in AT1a-/- mice than in WT mice. Tumor growth was also reduced in WT mice treated with TCV-116, a selective blocker of AT1 receptor. Because the beta-galactosidase gene was inserted into the AT1a gene locus in AT1a-/- mice, the site of beta-galactosidase expression represents the AT1a receptor expression in these mutant mice. In tumor-implanted AT1a-/- mice, the major site of the beta-galactosidase expression was macrophages in tissues surrounding tumors. Moreover, the number of infiltrated macrophages was significantly lower in AT1a-/- mice than in WT mice, and double-immunofluorescence staining revealed that these macrophages expressed VEGF protein intensively. Therefore, the host ATII-AT1 receptor pathway supports tumor-associated macrophage infiltration, which results in enhanced tissue VEGF protein levels. The host ATII-AT1 receptor pathway thereby plays important roles in tumor-related angiogenesis and growth in vivo.

Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation.

OBJECTIVES: We examined whether oral folate supplementation would rescue a hypercholesterolemia (HC)-related impairment of ischemia-induced angiogenesis. BACKGROUND: Folate protects against endothelial dysfunction, but the effect of folate supplementation on angiogenesis is little known. METHODS: Sprague-Dawley rats were divided into four groups. Control rats were fed a normal diet (n = 18); HC rats (n = 18) were fed 2% cholesterol diet; and HC + folate (HC+F) rats were fed an HC diet with oral folate (0.003% in water). The left femoral artery and vein were surgically excised, and angiogenesis in the ischemic limb was evaluated. We also examined the effects of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on angiogenesis in the HC+F state. RESULTS: Laser Doppler blood flow (LDBF) analysis showed lower ischemic/normal LDBF ratio in the HC group than in the control group. Angiographic and histologic analyses on day 14 revealed a smaller angiographic score (p < 0.001) and capillary density (p < 0.001) in the HC group than in controls, which were associated with reduced tissue NOx and cyclic guanosine monophosphate (cGMP) levels. The LDBF ratio, angiographic score, and capillary density were significantly restored in the HC+F group (p < 0.01 vs. HC), which were associated with increased serum folate and tissue NOx and cGMP levels. Finally, L-NAME treatment abolished the beneficial action of folate on angiogenesis in the HC state. CONCLUSIONS: Ischemia-induced angiogenesis was inhibited by HC, which was rescued by oral folate supplementation, at least in part, via an NO-dependent manner.

Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization.

A subset of human peripheral blood mononuclear cells (PB-MNCs) differentiate into endothelial progenitor cells (EPCs) that participate in postnatal neovascularization. Although tissue ischemia can mobilize EPCs from bone marrow, the effects of hypoxia on differentiation and angiogenic function of EPCs are little known. We examined whether hypoxic conditioning would modulate differentiation and function of human PB-MNC-derived EPCs. A subset of PB-MNCs gave rise to EPC-like attaching (AT) cells under either normoxic or hypoxic conditions. However, hypoxia much enhanced the differentiation of AT cells from PB-MNCs compared with normoxia. AT cells released vascular endothelial growth factor (VEGF) protein and expressed CD31 and kinase insert domain receptor/VEGFR-2, endothelial lineage markers, on their surface, which were also enhanced by hypoxia. Both a neutralizing anti-VEGF mAb and a KDR-specific receptor tyrosine kinase inhibitor, SU1498, suppressed PB-MNC differentiation into EPC-like AT cells in a dose-dependent manner. Migration of AT cells in response to VEGF as examined by a modified Boyden chamber apparatus was also enhanced by hypoxia. Finally, in vivo neovascularization efficacy was significantly enhanced by in vitro hypoxic conditioning of AT cells when cells were transplanted into the ischemic hindlimb of immunodeficient nude rats. In conclusion, hypoxia directly stimulated differentiation of EPC-like AT cells from human PB-MNC culture. Moreover, hypoxic preconditioning of AT cells before in vivo transplantation is a useful means to enhance therapeutic vasculogenesis.

Bacteremic and leukopenic pneumococcal pneumonia: successful treatment with antibiotics, pulse steroid, and continuous hemodiafiltration.

We describe a case of bacteremic, leukopenic pneumococcal pneumonia with respiratory failure, accompanied by diabetic ketoacidosis and hypothermia. Pulmonary leukostasis may play a role in the pathogenesis of the acute respiratory distress syndrome (ARDS) in pneumococcal pneumonia. The patient recovered with mechanical ventilation, intravenous antibiotics, pulse-steroid therapy, and continuous hemodiafiltration (CHDF). In particular, administration of steroid and the use of CHDF may improve the status of pulmonary leukostasis in leukopenic pneumococcal infection.

Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis.

The role of the renin-angiotensin system (RAS) in angiogenesis is little known. Here, we show that the angiotensin II (ATII) type 1 (AT1) receptor plays an important role in ischemia-induced angiogenesis. Well-developed collateral vessels and angiogenesis were observed in wild-type (WT) mice in response to hindlimb ischemia, whereas these responses were reduced in ATII type 1a receptor knockout (AT1a(-/-)) mice. Ischemia-induced angiogenesis was also impaired in WT mice treated with the AT1 receptor blocker TCV-116. These effects were not due to reduced systemic blood pressure (SBP), because hydralazine treatment preserved angiogenesis in WT mice although it reduced SBP to a level similar to that of AT1a(-/-) mice. Infiltration of inflammatory mononuclear cells (MNCs), including macrophages and T lymphocytes, was suppressed in the ischemic tissues of AT1a(-/-) mice compared with WT mice. Double immunofluorescence staining revealed that infiltrated macrophages and T lymphocytes expressed VEGF, and the expression of VEGF and monocyte chemoattractant protein-1 was also decreased in AT1a(-/-). Finally, the impaired angiogenesis in AT1a(-/-) mice was rescued by intramuscular transplantation of MNCs obtained from WT mice, further indicating the importance of MNC infiltration in ischemia-induced angiogenesis. Thus, the ATII--AT1 receptor pathway promotes early angiogenesis by supporting inflammatory cell infiltration and angiogenic cytokine expression.