Paweł Rudziński

Calcium-Dependent NOX5 Nicotinamide Adenine Dinucleotide Phosphate Oxidase Contributes to Vascular Oxidative Stress in Human Coronary Artery Disease

OBJECTIVES This study sought to examine the expression and activity of the calcium-dependent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in human atherosclerotic coronary arteries. BACKGROUND The NOX-based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several NOX homologues have been identified, but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels. METHODS Coronary arteries from patients undergoing cardiac transplantation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction. Calcium-dependent NADPH oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic resonance. RESULTS Both Western blotting and quantitative real-time polymerase chain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CAD versus non-CAD vessels. Calcium-dependent NADPH-driven production of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlated significantly with NOX5 mRNA levels among subjects. Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced coronary lesions. CONCLUSIONS These studies identify NOX5 as a novel, calcium-dependent source of ROS in atherosclerosis.

Systemic Regulation of Vascular NAD(P)H Oxidase Activity and Nox Isoform Expression in Human Arteries and Veins

Objective—Impaired endothelial function, characterized by nitric oxide scavenging by increased superoxide production, is a hallmark of vascular disease states. However, molecular mechanisms regulating superoxide production in human blood vessels remain poorly defined. Methods and Results—We compared endothelial function, vascular superoxide production, and the expression of NAD(P)H oxidase subunits in arteries and veins from patients undergoing coronary bypass surgery (n=86). Superoxide release was similar in arteries and veins. Inhibitor studies revealed that the NAD(P)H oxidase system was a quantitatively and proportionately greater source of superoxide in veins, whereas xanthine oxidase also contributed significantly to superoxide production in arteries. Moreover, NAD(P)H oxidase molecular composition differed in veins and arteries; veins expressed more nox2 and p22phox, whereas the relative expression of nox4 was greater in arteries. However, there were strong correlations between p22phox and nox4 expression and between superoxide production, NAD(P)H oxidase activity, and endothelial function in arteries and veins from the same patient. Conclusions—In individuals with coronary artery disease, changes in vascular superoxide production, endothelial function, and NAD(P)H oxidase activity and expression are related in veins and arteries. These findings highlight the importance of systemic effects on the molecular regulation of the NAD(P)H oxidases in human vascular disease.

Reoperation after fresh homograft replacement: 23 years’ experience with 655 patients

OBJECTIVE Through a retrospective study on the use of fresh homografts in 655 aortic valve replacement patients over a period of 23 years, we aimed to assess the reasons for eventual reoperation and causes of valve dysfunction. METHODS Between January 1980 and December 2002, 655 patients received fresh homografts. All homografts were antibiotic sterilized and stored at 4 degrees C. During this time, 139 patients (116 male and 23 female) with a mean age of 46.7 years (range 18-72) required reoperation. RESULTS The 30-day hospital overall mortality was 2.87%. The mean durability for all homografts was 12.4+/-4.54 years (1 month to 23 years). The cumulative rates for freedom from reoperation for any cause were 94.09+/-2% at 5 years and 87.9%+/-4% at 10 years, 76.6 at 15 years, 49.55 at 20 years. The major cause of valve dysfunction and indication for reoperation was degeneration in 111 patients (79.8%). Predominant aortic valve insufficiency in 87 patients (62.5%) and predominant stenosis in 24 patients (17.26%). Endocarditis occurred in 21 patients (15.1%). Early endocarditis was diagnosed in five patients (3.59%), late endocarditis in 16 patients (11.5%). Additional causes for reoperation included ascending aortic aneurysm, mitral valve insufficiency and congestive cardiomyopathy. Seventeen patients (12.2%) required concomitant procedures. Coronary artery bypass grafting was performed in six cases (4.3%), mitral valve replacement in five cases (3.59%), mitral valve annuloplasty in six (4.3%). The primary reoperative procedure was artificial/mechanical aortic valve implantation. In five cases, St. Jude Medical conduit grafts were implanted due to ascending aortic aneurysms. Homograft reimplantation was performed in four cases. One patient underwent mitral valve replacement and one patient received a heart transplant. CONCLUSION The results of the study suggest that reoperation in patients with aortic homografts is a low-risk procedure as compared to alternative therapies. Primary allograft aortic valve replacement can give acceptable results for up to 23 years. The major cause of valve dysfunction and indication for reoperation was degeneration. Cumulative rates for freedom from reoperation for any cause in age groups suggest careful selection and indications in homograft implantation in the younger patients. Young age is a risk factor for an early homograft structural deterioration (degeneration).

The combined use of transmyocardial laser revascularisation and intramyocardial injection of bone-marrow derived stem cells in patients with end-stage coronary artery disease: one year follow-up

BACKGROUND There are a growing number of patients with end-stage coronary artery disease (CAD) and refractory angina. Angiogenesis may be induced by intramyocardial injection of autologous bone marrow stem cells, intensified by inflammation around channels performed by laser. AIM To assess the effect of a combined treatment consisting of transmyocardial laser revascularisation (TLMR) and intramyocardial injection of bone-marrow derived stem cells (bone marrow laser revascularisation, BMLR) in patients with refractory angina one year after the procedure. METHODS Five male patients (age 49-78 years) with end-stage diffuse CAD, severe angina (CCS III/IV) despite intensive medical therapy and disqualified from prior coronary artery bypass grafting (CABG) or percutaneous coronary intervention were included. After heart exposure, at sites where CABG was impossible, TMLR was performed with the Holmium: YAG laser combined with injection of 1 mL of bone marrow concentrate into the border zone of a laser channel using a Phoenix handpiece. RESULTS No deaths in the follow-up period were observed. All patients were in I CCS Class. One year after the procedure,left ventricular (LV) segments treated by BMLR tended to demonstrate stronger myocardial thickening compared to baseline(53.0 ± 7.5% vs. 45.0 ± 9.5%; p = 0.06). Using late gadolinium-enhanced imaging, new myocardial infarction was found after one year only in one LV segment treated by BMLR. The BMLR treated regions in the remaining subjects, as well as regions subtended by left internal thoracic artery in two subjects, did not show new myocardial infarction areas. In contrast,all subjects who underwent only BMLR procedure revealed new and/or more extensive myocardial infarct in regions not treated by BMLR. CONCLUSIONS Intramyocardial delivery of bone marrow stem-cells together with laser therapy is a safe procedure, with improvement in quality of life during follow-up. One year after the procedure, myocardial regions where BMLR was performed tended to demonstrate stronger myocardial thickening observed in cardiac magnetic resonance imaging.

Clinical outcome of arterial myocardial revascularization using bilateral internal thoracic arteries in diabetic patients: a single centre experience.

OBJECTIVES The use of bilateral internal thoracic arteries (BITAs) grafting has been documented to be advantageous over left internal thoracic artery (LITA) grafting. It has been shown to significantly improve clinical outcomes and increase long-term survival in patients with diabetes. However, harvesting BITAs may result in a greater risk of superficial wound infection (SWI) or deep sternal wound infection (DSWI) and cardiovascular complications (major adverse cardiac and cerebrovascular events; MACCE) in such a patient group. The objective of this study was to compare the incidence of SWI or DSWI and cardiovascular events in a series of isolated coronary artery bypass grafting (CABG) patients who underwent BITA grafting vs LITA grafting. METHODS A total of 147 patients with coronary artery disease and diabetes underwent isolated CABG at John Paul II Hospital. Of these, 38 procedures were performed using BITA grafting and 109 with LITA-saphenous vein grafting. RESULTS MACCE were similar in bilateral groups (7.9%--BITA group and 9.2%--LITA group). No significant difference was found in mortality and length of stay between bilateral groups. The MACCE risk factor was age. The incidence of SWI and DSWI and sternal re-fixation did not differ between the BITA or LITA groups (5.2 vs 9.1%, 5.2 vs 7.3% and 5.2 vs 6.4%). The risk factors for DSWI were age (odds ratio 3.47, P = 0.032 for every 10 years) and body mass index >30 kg/m(2). CONCLUSIONS Perioperative complications do not increase with the use of BITAs in this group of diabetic patients. There are no statistically significant differences in the number of superficial or deep wound infections or number of sternal resuturing between the BITA and LITA groups.

Changes in myocardial perfusion after transmyocardial laser revascularization in patients with end-stage angina pectoris.

The purpose of the present study was to analyze the effects of transmyocardial laser revascularization (TMLR) on myocardial perfusion. The value of 99mTc-MIBI scintigraphy in the detection of changes in perfusion of the lased and nonlased segments was assessed as well. In 15 patients before TMLR and then 3 and 6 months afterwards, MIBI scintigraphy and a stress test were carried out. At the beginning of the study, all patients were classified as having angina pectoris class III or IV (according to the criteria of the Canadian Cardiac Society); their ejection fraction was >30%. The parameters of the stress test increased significantly in 70% of the patients. Cardiac scintigraphy revealed improved perfusion of 33.7% of the transient defects within 3 months after TMLR which persisted at 6 months with a clear trend towards further improvement in the lased segments. TMLR has been found to be particularly beneficial in patients in whom other invasive methods of treatment cannot be applied.