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Biomedical subjects

Stephen M Wildhirt

Publications and source records attributed to Stephen M Wildhirt.

12 recordsLinked to original sources

Graft function, histopathology and morphometry of radial arteries used as conduits for myocardial revascularization in patients beyond age 70.

BACKGROUND: Coronary artery bypass grafting (CABG) using radial arteries has become a standard procedure for younger patients in many centers. However, advanced atherosclerotic changes may limit its use in older patients. We studied the effects of age on morphologic and histopathologic findings in CABG patients aged 70 years and older. METHODS: In 31 consecutive patients aged 70-85 (mean 77+/-8 years) scheduled for elective CABG, the left or right radial artery (RA) was used to graft the second target vessel (first graft: LIMA-LAD). Preoperative Doppler flow and Allen's test were satisfactory. Intraoperatively the distal segment adjacent to the anastomosis site of the RA was collected for histologic evaluation. Intraoperative angiography, measurement of flow, and resistance index (PI) were performed to document graft quality. Histopathology and morphometry were used to measure intimal and medial areas (IA, MA; microm2), intimal thickening index (ITI), relation between intimal and medial width at maximum intimal thickness (IMR), and percentage of luminal narrowing (%LN). RESULTS: The RA showed no evidence for stenosis of the conduits or the anastomosis. In all grafts flow and PI were satisfactory (76+/-14 ml/min; PI: 2.2+/-0.9). Histopathology and morphometry showed atherosclerotic changes in all RA grafts: IA: 890+/-971 (range 286-5244), MA: 2751+/-818 (range 1357-4989), ITI: 0.26+/-0.09 (range 0.12-0.44), IMR: 0.59+/-0.28 (range 0.21-1.13) %LN: 38+/-5 (range 13.2-61.7). Age as well as classic risk factors including diabetes, hypertension, smoking, and hyperlipidemia did not correlate with RA atherosclerosis. CONCLUSIONS: Excellent macroscopic and angiographic results were obtained. All grafts used showed minor to moderate atherosclerotic changes without severely altered indices of intimal thickening or luminal narrowing. The radial artery must be used with caution; however, age should not be an exclusion criterion per se.

Age Factors↗

Severe superior vena cava syndrome after transvenous pacemaker implantation.

Superior vena cava syndrome is a rare complication after pacemaker implantation. The present report outlines how underestimation of clinically relevant symptoms of superior vena cava syndrome early after pacemaker implantation may result in severe complication with the need for major surgical intervention. Superior vena cava syndrome should be diagnosed early because immediate thrombolytic therapy is effective in the majority of patients and avoids the requirement for interventional or surgical efforts.

Bradycardia↗

Automatic patient registration for port placement in minimally invasive endoscopic surgery.

Optimal port placement is a delicate issue in minimally invasive endoscopic surgery, particularly in robotically assisted surgery. A good choice of the instruments' and endoscope's ports can avoid time-consuming consecutive new port placement. We present a novel method to intuitively and precisely plan the port placement. The patient is registered to its pre-operative CT by just moving the endoscope around fiducials, which are attached to the patient's thorax and are visible in its CT. Their 3D positions are automatically reconstructed. Without prior time-consuming segmentation, the pre-operative CT volume is directly rendered with respect to the endoscope or instruments. This enables the simulation of a camera flight through the patient's interior along the instruments' axes to easily validate possible ports.

Algorithms↗

Rest and exercise performance of the Medtronic Advantage bileaflet valve in the aortic position.

BACKGROUND: The aim of the study was to evaluate rest and exercise performance and left ventricular mass regression of the Medtronic Advantage (Medtronic, Inc, Minneapolis, MN) prosthesis in the aortic position at 1 year at a single center as part of a multicenter, prospective clinical trial. METHODS: Between May 2002 and June 2003, 63 consecutive patients underwent aortic valve replacement with a Medtronic Advantage prosthesis (84.1% male; mean age, 56.0 +/- 9.7 years; ejection fraction, 56.5 +/- 15.8%). Valve lesions were stenosis (n = 20), mixed (n = 34), and insufficiency (n = 9). Concomitant procedures were performed in 34.9%. Follow-up was 100% complete. Echocardiographic data were obtained early postoperatively and at 1 year, combined with stress echocardiography by treadmill. Mean pressure gradients, stroke volume, and left ventricular mass were determined by echocardiography. Data are presented as mean +/- standard deviation. RESULTS: Operative mortality was 0%. Valve-related complications were observed in 2 patients (endocarditis, n = 1; thromboembolic event, n = 1). There was no case of antithromboembolic hemorrhage, prosthesis-related explant, or reoperation. One patient showed moderate paravalvular regurgitation. Mean pressure gradients 1 year postoperatively ranged from 6.3 to 11.0 mm Hg across all valve sizes. Left ventricular mass regression at 1 year was 18.4% across all valve sizes (p < 0.001). No severe patient-prosthesis mismatch (effective orifice area index < or = 0.65 cm2/m2) could be observed. CONCLUSIONS: After 1 year, the Medtronic Advantage valve shows comparable transvalvular mean pressure gradients across the valve sizes used during rest and exercise. This is accompanied by a significant left ventricular mass regression, an important indicator for long-term survival.

Adult↗

Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study.

BACKGROUND: Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and their combination administered directly into the oxygenator on platelet function, platelet-leukocyte interactions, and postoperative blood loss in patients undergoing coronary artery bypass grafting. METHODS: Blood samples from 41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate were quantified by means of flow cytometry. Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry. RESULTS: Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin, microparticle formation, Mac-1 upregulation, and suppression of collagen-induced aggregation. Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia, microparticle formation, and P-selectin translocation. Moreover, this treatment preserved thrombin receptor-activating peptide-induced aggregation, which was not rescued by single treatments. Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss. CONCLUSIONS: Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass, such as thrombocytopenia, platelet activation, platelet-leukocyte aggregate formation, and suppression of platelet aggregative responses. The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass.

Aged↗

Persistently increased systemic, but not cardiac-specific, adhesion molecule expression and coronary endothelial dysfunction in human cardiac allografts.

BACKGROUND: Adhesion molecules are involved in inflammatory processes that alter endothelial function and lead to impairment of coronary vasomotor function. We studied a possible relationship between systemic expression, cardiac-specific expression, or both of P-selectin and intercellular adhesion molecule 1 and coronary vasomotor function both 1 and 12 months after heart transplantation in human subjects. METHODS: The expression of endomyocardial and soluble forms of P-selectin and intercellular adhesion molecule 1, as well as levels of tumor necrosis factor alpha, were determined in aortic and coronary sinus blood samples 1, 6, and 12 months after heart transplantation in 42 transplant recipients and 20 age-matched, nontransplanted control subjects. In addition, both endothelium-dependent (acetylcholine) and endothelium-independent (adenosine) coronary vasomotor function were assessed by using a Doppler flow wire and quantitative coronary angiography 1 and 12 months after heart transplantation. RESULTS: Adhesion molecules were highly expressed 1 month after heart transplantation and remained at high levels 12 months after heart transplantation when compared with levels in nontransplanted control subjects. No cardiac-specific expression or release of P-selectin or intercellular adhesion molecule 1 was observed. There was a significant inverse correlation between coronary vasomotor function and soluble adhesion molecule expression both 1 and 12 months after heart transplantation. CONCLUSION: Persistently high levels of circulating adhesion molecules are of systemic, but not cardiac-specific, origin and reflect a chronic inflammatory state throughout the first year after heart transplantation. This is associated with impairment of coronary vasomotor function, an early and potentially reversible step in the process of atherothrombosis and transplant coronary artery disease.

Coronary Vessels↗

Off-pump epicardial tissue sealing--a novel method for atrioventricular disruption complicating mitral valve procedures.

BACKGROUND: Atrioventricular disruption (AVD) is a rare (1%-2%) but fatal complication after mitral valve procedures; the intraoperative mortality is more than 50% despite the current standard procedure of surgical closure of the defect. We compared the outcome of 9 patients with intraoperative AV disruption, 4 being surgically treated on-pump and 5 receiving epicardial tissue sealing off-pump. METHODS: Between March 1998 and May 2002 a total of 9 patients presented with AV disruption intraoperative. The first 4 patients were treated with surgical repair on-pump by reconstruction of the defects with patch or buttressed suture. The second series of 5 patients were treated with a biodegradable collagen system with fibrinogen-based coating off-pump. Three to six layers were placed over the bleeding site with manual pressure for 30-60 minutes on the beating heart until bleeding was stopped. Cell saved blood was retransfused. RESULTS: In the on-pump surgical repair group 3 patients (75%) died within the first day after repair either because of persistent bleeding or cardiac tamponade. One patient survived at 30 days and 1 year. In the off-pump tissue sealing group 30 days and 1 year survival was 100%. Postoperative echocardiography showed normal left ventricular (LV) function with no regional wall motion abnormalities. CONCLUSIONS: Our data show that epicardial tissue sealing off-pump results in successful termination of bleeding from AVD and considerably improves survival when compared with the standard procedure. Because of this tremendous improvement in patient survival we now consider this technique as standard therapy for AV disruption in our center.

Aged↗

Invited commentary.

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Arteriosclerosis↗

Inhibition of inducible nitric oxide synthase and superoxide production reduces matrix metalloproteinase-9 activity and restores coronary vasomotor function in rat cardiac allografts.

OBJECTIVE: Oxidants such as nitric oxide (NO) and superoxide are involved in coronary endothelial dysfunction, an early event in the process of allograft coronary atherogenesis, possibly by activation of matrix metalloproteinases (MMPs) and extracellular matrix proteins. We investigated the contribution of inducible nitric oxide synthase (iNOS) derived NO and superoxide on (MMP)-9 activity and to changes in coronary vasomotor function in rat cardiac allografts. METHODS AND RESULTS: An allogenic (Brown Norway to Lewis rats) heterotopic cardiac transplantation model was used to study the effect of continuous treatment with a selective iNOS inhibitor; N-(3-(aminomethyl) benzyl) acetamidine (1400W), and polyethylene glycol conjugated superoxide dismutase (SOD) either alone or in combination on coronary vasomotor dysfunction. 1400W or SOD 24 h alone or their combination improved endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) coronary flow reserve and inhibited enhanced MMP-9 protein and activity. In addition, histopathological study revealed that either 1400W or SOD or their combination reduced superoxide production and nitrotyrosine protein. CONCLUSION: The present study demonstrates for the first time that selective iNOS inhibition or SOD treatment reduces enhanced MMP-9 protein and activity associated with improvement of both, endothelium-dependent and -independent coronary vasomotor function in rat cardiac allografts. This is accompanied by reduction of nitrotyrosine and superoxide production. This suggests that the proteolytic enzyme MMP-9 is an effector molecule of oxidant-mediated coronary vasomotor dysfunction.

Amidines↗

Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats.

Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O(2) consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca(2+)-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.

Animals↗

Effects of phospholipid-coated extracorporeal circuits on clinical outcome parameters and systemic inflammatory response in coronary artery bypass graft patients.

INTRODUCTION: The use of extracorporeal circulation (ECC) during coronary artery bypass graft (CABG) surgery is associated with a systemic inflammatory response due to the contact of blood with artificial surfaces. The clinical relevance of ECC-related systemic inflammation varies with the patient, and such inflammation may be accompanied by intermittent organ dysfunction and an increased catecholamine requirement. We investigated the effects of a new phospholipid coating system of ECC on systemic inflammatory response and clinical outcome following CABG. METHODS: Patients scheduled for CABG surgery were prospectively divided randomly into 2 patient groups: patients using noncoated ECC materials and patients using phospholipid-coated ECC materials. Clinical data measured perioperatively included hemodynamics, aortic clamp time, duration of bypass, time to extubation, catecholamine requirement, length of intensive care unit (ICU) stay, postoperative blood loss, and amount of blood transfused. In addition, blood samples were collected before cannulation and at 2, 24, and 48 hours postoperative. Cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin 10 [IL-10]) and P-selectin were measured with an enzyme-linked immunosorbent assay. Plasma nitrate/nitrite levels (NOx) were determined by the Griess reaction. RESULTS: A significant increase of TNF-a level was noted in the uncoated control group only. In the uncoated group, IL-10 levels significantly increased at 2 hours postoperative, whereas levels remained unchanged in the phospholipid coating group. P-selectin increased 2 hours postoperative in the uncoated group, and no significant changes were noted in the phospholipid coating group. At 24 hours postoperative, total plasma NOx production significantly increased in the phospholipid coating group but remained constant in the control group. No significant differences with respect to postoperative parameters (time to extubation, ICU stay, amount of bleeding, blood transfused, and catecholamine requirement) were observed. CONCLUSIONS: Phospholipid coating significantly reduces the systemic increase in proinflammatory and anti-inflammatory cytokines and P-selectin. Despite the comparable clinical outcomes in this study, the observed significant reduction in systemic inflammatory parameter values suggests an improved biocompatibility of ECC materials when they are coated with phospholipids.

Aged↗

A comparative analysis of outcome after heart transplantation in patients aged 60 years and older: the University of Alberta experience.

BACKGROUND: The Registry of the International Society for Heart and Lung Transplantation (ISHLT) 2001 Annual Report indicated that the vast majority of heart transplant recipients are between 50 and 64 years of age. However, patient age beyond 60 years may have higher long-term mortality compared to younger patients. The purpose of this study was to compare short- and intermediate-term results including rates of acute rejection, transplant coronary artery disease, infections, malignancy, and mortality in cardiac transplant recipients 60 years or older with those below the age of 60 years. METHODS: We retrospectively analyzed the results of 50 patients aged 60 years and older who underwent heart transplantation at the University of Alberta from January 1990 to December 2000 and compared them with the results of 225 younger patients undergoing heart transplantation in the same time period. RESULTS: The older and younger groups had similar rates for treated acute rejection episodes (20.0% vs. 12.6%), transplant coronary artery disease (4.0% vs. 1.1%), and mortality (10.5% vs. 14.3%), respectively. No differences were noted with regards to quality and quantity of infection or malignancy rates. Five-year actuarial survival between the older and younger patients was also comparable at 89.5% vs.86.9% (p > 0.05). CONCLUSIONS: Heart transplantation in patients 60 years of age and older can be performed as successfully as in younger patients (< 60 years) with comparable morbidity and mortality, suggesting that patient age per se should not be an exclusion criterion for heart transplantation.

Adult↗