Ali A. Youssef

Level and Value of Circulating Endothelial Progenitor Cells in Patients After Acute Ischemic Stroke

Background and Purpose— Endothelial progenitor cells (EPCs) migrate from bone marrow to systemic circulation in response to tissue ischemia where they differentiate into mature endothelial cells for angiogenesis in situ. This study tested the hypothesis that the level of circulating EPCs is substantially increased and predictive of prognostic outcomes after acute ischemic stroke (IS). Methods— The level of circulating EPCs (staining markers: CD31/CD34 [E1], CD62E/CD34 [E2], and KDR/CD34 [E3]) were examined using flow cytometry at 48 hours after acute IS in 138 consecutive patients. The EPC level was also evaluated once in 20 healthy volunteers and in 40 at-risk control subjects. Results— Level of circulating EPCs (E1–3) was significantly higher in patients with IS than in at-risk control subjects (P<0.05). Additionally, EPC (E1–3) level was significantly lower in patients with severe neurological impairment (defined as a score ≥12 on the National Institutes of Health Stroke Scale) than in patients with less severe impairment (National Institutes of Health Stroke Scale < score 12) at 48 hours after IS (P<0.0001). Moreover, the EPC (E3) level was strongly correlated with improved National Institutes of Health Stroke Scale ≥4 on day 21 after IS (P=0.0004). Furthermore, low circulating EPC level was independently predictive of severe neurological impairment (National Institutes of Health Stroke Scale ≥12) at 48 hours (E1–3) and combined major adverse clinical outcomes (defined as recurrent IS, any cause of death, or National Institutes of Health Stroke Scale of ≥12) on day 90 (E1) after IS (P<0.001). Conclusions— Level of circulating EPCs is independently predictive of prognosis after IS.

Autologous transplantation of bone marrow-derived endothelial progenitor cells attenuates monocrotaline-induced pulmonary arterial hypertension in rats

Objectives:Bone marrow–derived endothelial progenitor cells have been shown to circulate to damaged vascular endothelium and differentiate into mature endothelial cells. This study investigated whether bone marrow–derived endothelial progenitor cell therapy ameliorates monocrotaline (MCT)-induced pulmonary arterial hypertension in a rat model. Design:Male Sprague-Dawley rats were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus autologous bone marrow–derived endothelial progenitor cell (1.2 × 106 cells) transplantation (group 2), and saline injection only (group 3). Mononuclear cells were obtained from femoral bone marrow of group 2 rats and isolated by Ficoll gradient centrifugation. The cells were cultured for 21 days in endothelial culture medium. Setting:An animal research laboratory at Kaohsiung Chang Gung Memorial Hospital. Measurements:Hemodynamics, ventricular weight, expressions of connexin43, endothelial nitric oxide synthase messenger RNA gene, Bcl-2, and number of alveolar sacs and small lung arterioles were measured. Results:Hemodynamic measurements on day 28 after MCT treatment revealed the development of significantly increased pulmonary arterial hypertension in MCT-treated groups (p < .0001). The bone marrow–derived endothelial progenitor cells were intravenously transplanted in group 2 on day 28 after MCT-induced pulmonary arterial hypertension. By day 90 after MCT treatment, the right ventricular systolic blood pressure and right ventricular hypertrophy were significantly increased in group 1 compared with groups 2 and 3 (all p values <.01). In addition, connexin43 and endothelial nitric oxide synthase messenger RNA gene expressions of lung and right ventricle and Bcl-2 protein expression of right ventricle were significantly lower in group 1 than in groups 2 and 3 (all p values <.01). Furthermore, the number of alveolar sacs and small lung arterioles were significantly lower in group 1 than in groups 2 and 3 (all p values <.01). Conclusions:Autologous bone marrow–derived endothelial progenitor cell transplantation effectively ameliorates MCT-induced pulmonary arterial hypertension.

Transradial and Transbrachial Arterial Approach for Simultaneous Carotid Angiographic Examination and Stenting Using Catheter Looping and Retrograde Engagement Technique

BACKGROUND The purpose of this study was to introduce a novel and safe technique with high procedural success for carotid artery stenting (CAS). METHODS From April 2004 to May 2009, 161 patients underwent CAS using either a high transradial arterial approach (TRA, defined as 10 cm above styloid process) or a transbrachial arterial approach (TBA) with a 7F arterial sheath. Selective carotid angiography was performed using a 6F Kimny guiding catheter and Teflon wire (260 cm in length) by Catheter Looping And Retrograde Engagement Technique (CLARET) with the guiding catheter seated on the right coronary cusp and its tip engaged into the common carotid artery (CCA). Teflon wire was introduced into the CCA again after the diagnostic procedure, followed by replacement of the 6F Kimny guiding catheter by a 7F Kimny catheter for CAS using one of the following techniques: (1) direct-engagement method, i.e., from right innominate artery into the right CCA; (2) looping method plus double-wire technique (utilized two Teflon wires to provide an adequate support) for both the right and left CCA; and (3) looping method plus a PercuSurge balloon anchoring at the external carotid artery. RESULTS This distinctive technique offered 100% diagnostic success and 99.4% CAS success. Two patients (1.2%) experienced major ischemic stroke after CAS and two (1.2%) died during hospitalization. CONCLUSION The results of the present study showed that high TRA/TBA using CLARET for CAS in patients with severe carotid artery stenosis is safe and technically feasible with an extremely high success rate.

Autologous bone marrow cell implantation attenuates left ventricular remodeling and improves heart function in porcine myocardial infarction: An echocardiographic, six-month angiographic, and molecular-cellular study

BACKGROUND We investigated the potential benefits and the underlying mechanisms of autologous bone marrow-derived mononuclear cell (BMDMNC) implantation in a porcine model of acute anterior wall myocardial infarction (AAWMI) by studying 6-month left ventricular (LV) function and LV remodeling. METHODS After being aspirated from the iliac crest and cultured for 1 week, BMDMNCs were implanted immediately after AAWMI induction through the left anterior descending artery ligation. Thirty male mini-pigs (16-18 kg) were equally divided into group 1 [AAWMI plus saline injection into infarct-ischemia area (IA)], group 2 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into non-IA), group 3 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into IA), group 4 (sham control plus 3.0 × 10⁷ BMDMNC transplantation into LV myocardium), and group 5 (normal control). RESULTS By day 90, echocardiography demonstrated an increased LV end-diastolic and end-systolic dimensions but reduced LV ejection fraction (LVEF) in groups 1 and 2 than in other groups (all p < 0.01). Six-month angiographic study showed a lower LVEF and wall motion score but a higher mitral regurgitation in groups 1 and 2 than in other groups (all p < 0.01). In IA and peri-infarct area, the number of small vessels and mRNA expressions of endothelial nitric oxide synthase, Bcl-2, interleukin (IL)-10, and peroxisome proliferator-activated receptor-γ coactivator-1α were lower, whereas the number of apoptotic nuclei, caspase-3, Bax, endothelin-1, IL-8, and matrix metalloproteinase was higher in groups 1 and 2 than in other groups (all p < 0.01). CONCLUSIONS Autologous BMDMNC transplantation into IA rather non-IA improves LV function and reduces LV remodeling via eliciting a broad-spectrum of molecular-cellular defensive mechanisms.

Level and value of circulating endothelial progenitor cells in patients with acute myocardial infarction undergoing primary coronary angioplasty: in vivo and in vitro studies

Levels of circulating endothelial progenitor cells (EPCs) in acute ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI) were investigated in this study. Flow cytometric analysis of the circulating EPC level (CD31/CD34 [E(1)], CD62E/CD34 [E(2)], and KDR/CD34 [E(3)]) was determined from blood samples of 161 consecutive patients with STEMI undergoing primary PCI. Angiogenesis was evaluated using mononuclear cell-derived EPCs on Matrigel. The EPC number (E(1-3)) was lower in STEMI patients than in normal subjects (n = 25) (P < 0.005). Patients with high EPCs (E(1-3)) (≥1.2%) had a lower left ventricular ejection fraction, elevated white blood cell count and creatinine level, advanced Killip score (≥class 3), more advanced congestive heart failure (CHF) (≥class 3), and increased 30-day mortality than those with a low EPC (E(1-3)) level (<1.2%) (P < 0.0001). Angiogenesis was lower in patients with a high EPC level than those with a low EPC level and normal controls (P < 0.001). Both the advanced Killip score and the CHF were independent predictors of increased EPC levels (P < 0.05). Multivariate analysis identified a high EPC (E(3)) level to be the most important predictor of increased 30-day major adverse clinical outcome (MACO) (P < 0.0001). In conclusion, the circulating EPC level is a major independent predictor of 30-day MACO in patients with STEMI undergoing primary PCI.

Link between Interleukin-10 Level and Outcome after Ischemic Stroke

Objectives: The prognostic value of interleukin (IL)-10 in patients after acute ischemic stroke (IS) is not well understood. This study tested the hypothesis that serum levels of IL-10 are substantially increased after IS and predictive of IS outcome. Methods: Serum IL-10 levels were examined 48 h after acute IS in 135 consecutive patients, and in 20 healthy and 30 at-risk controls. Results: Mean serum IL-10 was significantly higher in IS patients than in both control groups (p < 0.0001, respectively). Additionally, serum IL-10 was significantly higher in patients with severe neurological impairment [defined as a score ≧12 on the National Institute of Health Stroke Scale (NIHSS)] than in patients with less severe neurological impairment (NIHSS score <12) 48 h after IS (p < 0.0001). Furthermore, higher serum IL-10 was strongly and independently correlated with severe neurological impairment (NIHSS ≧12) 48 h after acute IS (p < 0.0001), and independently predictive of combined major adverse clinical outcomes (defined as recurrent IS, any cause of death or NIHSS ≧12) on day 90 following IS (p < 0.0001). Conclusions: Serum IL-10 is an independent prognosticator of IS outcome.

Feasibility and Safety of Transradial Arterial Approach for Simultaneous Right and Left Vertebral Artery Angiographic Studies and Stenting

ObjectivesThis study investigated whether the transradial artery (TRA) approach using a 6-French (F) Kimny guiding catheter for right vertebral artery (VA) angiographic study and stenting is safe and effective for patients with significant VA stenosis.BackgroundThe TRA approach is commonly performed worldwide for both diagnostic cardiac catheterization and catheter-based coronary intervention. However, to our knowledge, the safety and feasibility of left and right VA angiographic study and stenting, in the same procedure, using the TRA approach for patients with brain ischemia have not been reported.MethodsThe study included 24 consecutive patients (22 male,2 female; age, 63–78 years). Indications for VA angiographic study and stenting were (1) prior stroke or symptoms related to vertebrobasilar ischemia and (2) an asymptomatic but vertebral angiographic finding of severe stenosis (>70%). A combination of the ipsilateral and retrograde-engagement technique, which involved a looping 6-F Kimny guiding catheter, was utilized for VA angiographic study. For VA stenting, an ipsilateral TRA approach with either a Kimny guiding catheter or a left internal mammary artery guiding catheter was utilized in 22 patients and retrograde-engagement technique in 2 patients.ResultsA technically successful procedure was achieved in all patients, including left VA stenting in 15 patients and right VA stenting in 9 patients. The mean time for stenting (from engagement to stent deployment) was 12.7 min. There were no vascular complications or mortality. However, one patient suffered from a transient ischemic attack that resolved within 3 h.ConclusionWe conclude that TRA access for both VA angiographic study and VA stenting is safe and effective, and provides a simple and useful clinical tool for patients unsuited for femoral arterial access.

Comparison of 30-day mortality between anterior-wall versus inferior-wall ST-segment elevation myocardial infarction complicated by cardiogenic shock in patients undergoing primary coronary angioplasty.

Objectives: In this study, 30-day mortality from cardiogenic shock caused by left anterior descending artery (LAD) occlusion was compared with that caused by left circumflex (LCX) or right coronary artery (RCA) occlusion after primary percutaneous coronary intervention (PCI). Methods: Between May 2001 and December 2009, 212 consecutive patients with anterior-wall ST-elevation myocardial infarction complicated by cardiogenic shock due to LAD (n = 97) occlusion (group 1) and LCX or RCA (n = 115) occlusion (group 2) undergoing primary PCI were enrolled. Results: The results showed a higher mean peak level of creatine phosphokinase and incidence of extracorporeal membrane oxygenation in group 1 than group 2 (all p < 0.01). However, no significant difference was noted in the achievement of normal blood flow in the infarct-related artery (p = 0.461) and 30-day morality (p = 0.338). Univariate analysis demonstrated a significant association of 30-day morality with age, lower left-ventricular ejection fraction, advanced congestive heart failure and unsuccessful reperfusion (all p < 0.02). Multivariate analysis revealed unsuccessful reperfusion as the most independent predictor of 30-day mortality (p = 0.002). Conclusion: No significant difference was noted in 30-day mortality between patients with acute myocardial infarction and cardiogenic shock caused by LAD occlusion and by either RCA or LCX occlusion undergoing primary PCI.

Time Courses of Subcellular Signal Transduction and Cellular Apoptosis in Remote Viable Myocardium of Rat Left Ventricles Following Acute Myocardial Infarction: Role of Pharmacomodulation

We tested hypothesis that acute myocardial infarction (AMI) induces cellular apoptosis and serial changes of protein kinase C epsilon (PKC-e) and p38 mitogen-activated protein kinase (p38 MAPK), and tested cardio-protective effect of losartan in this condition. The rats were assigned to group A (sacrificed on day 2), group B (sacrificed on day 5), and group C (sacrificed on day 14). Rats in each group were further randomized into the following groups: AMI (ligation of left coronary artery) without losartan (AMI-L0); AMI with losartan 20 mg/ kg/d (AMI-L1); and sham groups (L0 and L1). The PKC-e expression in membrane compartment was increased in AMI-L1 group than in other groups on day 5 and in AMI groups than in sham groups on day 14 (P < .01). Phosphorylated form of cytosolic p38 MAPK level was increased in AMI-L1 than in other groups on day 14 (P < .05). Furthermore, 14-day left ventricular ejection fraction was higher and cellular apoptosis was lower in AMI-L1 group than in AMI-L0 group (P < .0001).

Polygamy and Risk of Coronary Artery Disease in Men Undergoing Angiography: An Observational Study

Epidemiologic evidence suggests a link between psychosocial risk factors such as marital status and coronary artery disease (CAD). Polygamy (multiple concurrent wives) is a distinct marital status practiced in many countries in Asia and the Middle East, but its association with CAD is not well defined. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period from April 1, 2013, to March 30, 2014. Of 1,068 enrolled patients, 687 were married men. Polygamy was reported in 32% of married men (1 wife: 68%, 2 wives: 19%, 3 wives: 10%, and 4 wives: 3%). When stratified by number of wives, significant baseline differences were observed in age, type of community (rural versus urban), prior coronary artery bypass grafting (CABG), and household income. After adjusting for baseline differences, there was a significant association between polygamy and CAD (adjusted OR 4.6 [95% CI 2.5, 8.3]), multivessel disease (MVD) (adjusted OR 2.6 [95% CI 1.8, 3.7]), and left main disease (LMD) (adjusted OR 3.5 [95% CI 2.1, 5.9]). Findings were consistent when the number of wives was analyzed as a continuous variable. In conclusion, among married men undergoing coronary angiography for clinical indications, polygamy is associated with the presence of significant CAD, MVD, and LMD.