Hidekazu Irie

Carbon Dioxide–Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System

Background—Carbon dioxide–rich water bathing has the effect of vasodilatation, whereas it remains undetermined whether this therapy exerts an angiogenic action associated with new vessel formation. Methods and Results—Unilateral hindlimb ischemia was induced by resecting the femoral arteries of C57BL/J mice. Lower limbs were immersed in CO2-enriched water (CO2 concentration, 1000 to 1200 mg/L) or freshwater (control) at 37°C for 10 minutes once a day. Laser Doppler imaging revealed increased blood perfusion in ischemic limbs of CO2 bathing (38% increase at day 28, P<0.001), whereas NG-nitro-l-arginine methyl ester treatment abolished this effect. Angiography or immunohistochemistry revealed that collateral vessel formation and capillary densities were increased (4.1-fold and 3.7-fold, P<0.001, respectively). Plasma vascular endothelial growth factor (VEGF) levels were elevated at day 14 (18%, P<0.05). VEGF mRNA levels, phosphorylation of NO synthase, and cGMP accumulation in the CO2-bathed hindlimb muscles were increased (2.7-fold, 2.4-fold, and 3.4-fold, respectively) but not in forelimb muscles. The number of circulating Lin−/Flk-1+/CD34− endothelial-lineage progenitor cells was markedly increased by CO2 bathing (24-fold at day 14, P<0.001). The Lin−/Flk-1+/CD34− cells express other endothelial antigens (endoglin and VE-cadherin) and incorporated acetylated LDL. Conclusions—Our present study demonstrates that CO2 bathing of ischemic hindlimb causes the induction of local VEGF synthesis, resulting in an NO-dependent neocapillary formation associated with mobilization of endothelial progenitor cells.

Prognostic impact of systolic blood pressure at admission on in-hospital outcome after primary percutaneous coronary intervention for acute myocardial infarction

BACKGROUND Data regarding the relationship between systolic blood pressure (SBP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking in Japan. METHODS AND RESULTS A total of 1475 primary PCI-treated AMI patients were classified into quintiles based on admission SBP (<105 mmHg, n=300; 105-125 mmHg, n=294; 126-140 mmHg, n=306; 141-158 mmHg, n=286; and ≥159 mmHg n=289). The patients with SBP<105 mmHg tended to have higher age, previous myocardial infarction, chronic kidney disease (CKD), Killip class≥3 at admission, right coronary artery, left main trunk (LMT), or multivessels as culprit lesions, larger number of diseased vessels, lower Thrombolysis In Myocardial Infarction (TIMI) grade in the infarct-related artery before primary PCI, and higher value of peak creatine phosphokinase concentration. Patients with SBP<105 mmHg had a significantly higher mortality, while mortality was not significantly different among the other quintiles: 24.3% (<105 mmHg), 4.8% (105-125 mmHg), 4.9% (126-140 mmHg), 2.8% (141-158 mmHg), and 5.2% (≥159 mmHg) (p<0.001). On multivariate analysis, Killip class≥3 at admission, LMT or multivessels as culprit lesions, admission SBP<105 mmHg, CKD, and age were the independent positive predictors of in-hospital mortality, whereas admission SBP 141-158 mmHg and TIMI 3 flow after PCI were the negative ones, but admission SBP 105-125 mmHg, admission SBP 126-140 mmHg, and admission SBP≥159 mmHg were not. CONCLUSIONS These results suggest that admission SBP 141-158 mmHg might be correlated with better in-hospital prognosis, whereas admission SBP<105 mmHg was associated with in-hospital death in Japanese AMI patients undergoing primary PCI.

Prognostic impact of pulse pressure at admission on in-hospital outcome after primary percutaneous coronary intervention for acute myocardial infarction

Data regarding relationship between pulse pressure (PP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking. A total of 1413 primary PCI-treated AMI patients were classified into quintiles based on admission PP (<40, n = 280; 40–48, n = 276; 49–57, n = 288; 58–70, n = 288; and ≥71 mmHg, n = 281). The patients with PP < 40 mmHg tended to have higher prevalence of male, smoking, and Killip class ≥3 at admission; right coronary artery, left main trunk (LMT), or multivessels as culprit lesions; larger number of diseased vessels; lower Thrombolysis in Myocardial Infarction (TIMI) grade in the infarct-related artery before/after primary PCI; and higher value of peak creatine phosphokinase concentration. Patients with PP < 40 mmHg had highest mortality, while patients with PP 49–57 mmHg had the lowest: 11.8 % (<40), 7.2 % (40–48), 2.8 % (49–57), 5.9 % (58–70), and 6.0 % (≥71 mmHg). On multivariate analysis, Killip class ≥3 at admission, LMT or multivessels as culprit lesions, chronic kidney disease, and age were the independent positive predictors of the in-hospital mortality, whereas admission PP 49–57 mmHg, hypercholesterolemia, and TIMI 3 flow before/after PCI were the negative ones, but admission PP < 40 mmHg was not. These results suggest that admission PP 49–57 mmHg might be correlated with better in-hospital prognosis in Japanese AMI patients undergoing primary PCI.

Primary percutaneous coronary intervention and intravascular ultrasound imaging for coronary thrombosis after cisplatin-based chemotherapy

Although cisplatin is indispensable for the chemotherapy treatment of many malignancies, cisplatin-associated thrombosis is attracting increasing attention. However, experience of primary percutaneous coronary intervention (PCI) and intravascular ultrasound imaging (IVUS) for coronary thrombosis, possibly due to cisplatin-based chemotherapy, has been limited. Case 1 with postoperative gastric cancer developed acute myocardial infarction (AMI) on the sixth day of the second chemotherapy course with conventional doses of cisplatin and tegafur gimeracil oteracil potassium. Emergency coronary angiography (CAG) showed a filling defect in the proximal left anterior descending coronary artery (LAD) concomitant with no reflow in the distal LAD. Case 2 with advanced lung cancer and brain metastasis suffered AMI on the fifth day of the first chemotherapy course with conventional doses of cisplatin and gemcitabine. Emergency CAG delineated a total occlusion in the proximal right coronary artery. In both cases, thrombectomy using aspiration catheter alone obtained optimal angiographic results and subsequent IVUS revealed no definite atherosclerotic plaque, while slow flow still remained even after selective intra-coronary infusion of vasodilator in the case 1. These cases suggest that primary PCI using thrombus-aspiration catheter might be safe and effective for coronary thrombosis due to cisplatin-based chemotherapy.

Systolic blood pressure at admission, clinical manifestations, and in-hospital outcomes in patients with acute myocardial infarction

BACKGROUND Several clinical studies have demonstrated an inverse relationship between systolic blood pressure (SBP) at admission and in-hospital mortality in patients hospitalized for acute myocardial infarction (AMI). However, data on the relation between admission SBP and in-hospital prognosis in AMI patients are still lacking in Japan. METHODS AND RESULTS A total of 1211 AMI patients were classified into quintiles based on SBP at hospital admission (<106 mmHg, n = 241; 106-125 mmHg, n = 239; 126-140 mmHg, n = 244; 141-159 mmHg, n = 238; and ≥ 160 mmHg, n = 249). The patients with SBP < 106 mmHg tended to have higher age, Killip class ≥ 3 at admission, right coronary artery, left main trunk, or multivessels as culprit lesions, larger number of diseased vessels, lower Thrombolysis In Myocardial Infarction grade in the infarct-related artery before primary percutaneous coronary intervention (PCI), and higher value of peak creatine phosphokinase concentration. Patients with SBP <106 mmHg had a significantly higher mortality, while mortality was not significantly different among the other quintiles: 25.7% (<106 mmHg), 5.4% (106-125 mmHg), 5.7% (126-140 mmHg), 2.5% (141-159 mmHg), and 5.6% (≥ 160 mmHg) (p<0.001). On multivariate analysis, Killip class ≥ 3 at admission, admission SBP <106 mmHg, and age were the independent positive predictors of in-hospital mortality, whereas admission SBP 141-159 mmHg and primary PCI were the negative ones, but admission SBP 106-125 mmHg, admission SBP 126-140 mmHg, and admission SBP ≥ 160 mmHg were not. CONCLUSIONS These results suggest that admission SBP 141-159 mmHg might be correlated with better in-hospital prognosis, whereas admission SBP <106 mmHg was associated with in-hospital death in Japanese patients hospitalized for AMI.

WITHDRAWN: Cardio‐cerebrovascular protective effects of valsartan in high-risk hypertensive patients with overweight/obesity: A post-hoc analysis of the KYOTO HEART Study

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Zilver stent implantation through 4.5 French guiding sheath in iliac vein compression syndrome complicated with acute deep vein thrombosis

Background Downsized devices for less invasive endovascular treatment are gaining more attention. Case report An 82-year-old woman was admitted to our hospital with pain and swelling in left lower extremity. Ultrasonography showed much thrombus at the left common femoral, superficial femoral, and popliteal veins, confirming a diagnosis of acute deep vein thrombosis (DVT). For lack of therapeutic effect of systemically administered anticoagulative and thrombolytic agents, we performed catheter intervention against DVT. After insertion of a 4.5 French guiding sheath (Parent Plus, Medikit, Tokyo, Japan) into left popliteal vein, venography showed a total occlusion of the common femoral vein. Even after thrombectomy by aspiration catheter, balloon dilation, and catheter-induced thrombolysis, severe stenosis at the proximal site of the left common iliac vein remained. After confirming the presence of iliac vein compression syndrome (IVCS) by intravascular ultrasound imaging, we successfully implanted a Zilver® stent (Cook Inc., Bloomington, IN, USA) in the common-external iliac vein through a 4.5 French guiding sheath, leading to an optimal venous-return flow. Conclusions The present case suggests that in addition to thrombus aspiration, Zilver stent implantation using a 4.5 French guiding sheath has the potential to serve as a minimally invasive strategy for the treatment of IVCS complicated with iliofemoral DVT.<Learning objective: During the interventional treatment of deep vein thrombosis, we should pay attention to procedure-related venous valve dysfunction in addition to bleeding complications and pulmonary embolism. From the point of view, downsized catheter devices might have some advantage with lesser prevalence of those complications.>.