Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization in a porcine model.

BACKGROUND AND PURPOSE: Emboli and proinflammatory mediators are suspected of generating cerebral edema after coronary surgery. In contrast to cardiopulmonary bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli count and proinflammatory mediator release but carries the risk of hemodynamic instability. A microaxial blood pump can augment cardiac output. METHODS: Coronary bypasses were constructed in pigs with CPB and cardioplegia (n=9), OPCAB (n=9), or blood-pump support CAB (n=9). Nine animals underwent sham operation. Embolus count was monitored and regional cerebral blood flow was assessed with microspheres in 21 brain specimens per animal (n=189 per group). Interleukins 6 and 8 and tumor necrosis factor-alpha concentrations were determined. These variables were studied before, during, and for 4 hours after surgery. Finally, cerebral water content was determined. RESULTS: During CPB and blood-pump CAB, a significant number of emboli were counted in contrast to OPCAB and controls (P<0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and showed reactive hyperemia except in 10 specimens after aortic cross-clamp release. This impairment persisted in 20 specimens. During and after OPCAB, regional cerebral blood flow remained nearly unchanged but showed low flow during (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in proinflammatory mediators was observed only in the CPB group. CPB and blood-pump CAB significantly increased cerebral water content (P<0.05). A strong correlation between embolic load and cerebral water content was observed in all groups. No correlation between proinflammatory mediator release and cerebral water content was detected. CONCLUSIONS: Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization.

Neutrophil adherence to activated saphenous vein and mammary endothelium after graft preparation.

BACKGROUND: Interaction of circulating leukocytes and vascular endothelium plays an important role in vasoconstriction, endothelial dysfunction, and vascular injury. Dilation procedures of grafts before coronary artery bypass graft surgery might lead to vascular injury and subsequent bypass graft disease. METHODS: We analyzed in vitro the adherence of fluorescence-labeled polymorphonuclear neutrophils (PMNs) to endothelium of human saphenous vein grafts or internal mammary artery grafts after stimulation with thrombin (0.5 to 2 U/mL) or dilating procedures. Furthermore, we investigated endothelial function of prepared grafts. RESULTS: Thrombin stimulation resulted in a dose-dependent increase of PMN adherence to the endothelium of saphenous vein and internal mammary artery, which was attenuated by the selectin-blocking carbohydrate fucoidin or anti-P-selectin monoclonal antibody. Mechanical dilation of saphenous vein or internal mammary artery led to a marked increase in PMN adherence (65 +/- 5 versus 5 +/- 3 PMN/mm2; p < 0.01), which was significantly attenuated by fucoidin or anti-P-selectin monoclonal antibodies. Treatment of internal mammary artery with the vasodilator papaverine led to a marked increase of PMN adherence (59 +/- 8 versus 12 +/- 4 PMN/mm2; p < 0.01) when papaverine was administered directly into the vessel. However, external treatment with papaverine did not affect PMN adhesion. Endothelial dysfunction was observed in dilated venous grafts and in arterial grafts internally treated with papaverine; in contrast, external treatment did not affect endothelial function. CONCLUSIONS: This study showed that mechanical or pharmacologic dilation of venous or arterial coronary grafts, usually performed before anastomosis of aortocoronary bypass grafts, led to increased selectin-mediated PMN adhesion on vascular endothelium and subsequent endothelial dysfunction.

Aortic valve papillary fibroelastoma.

Cardiac papillary fibroelastoma (CPF) is a rare primary benign cardiac tumor. Before the use of echocardiography, the lesion was identified at autopsy or incidentally during cardiac surgery. CPF is the third most common primary cardiac tumor after atrial myxoma and lipoma, and is the most common tumor of the valvular endothelium. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) permit diagnosis of the tumor in living patients. CPF may be the cause of cerebrovascular or cardiac ischemia due to embolization or occlusion of the vascular ostia. Embolic material may arise from fragments of the tumor itself, or from surrounding thrombus. The case is reported of a patient with CPF of the aortic valve in whom TEE diagnosis was conducted and the tumor removed surgically.

Comparison of cardiac troponin I versus T and creatine kinase MB after coronary artery bypass grafting in patients with and without perioperative myocardial infarction.

BACKGROUND AND PURPOSE: Cardiac troponins have shown to be specific markers of myocardial injury. The aim of this prospective study was to compare patterns and kinetics of troponin I and T after coronary artery bypass grafting (CABG) with or without perioperative myocardial infarction (PMI). PATIENTS AND METHODS: 119 patients (male/female: 96/23, age 64 +/- 10 years) underwent first time elective CABG. Preoperative mean ejection fraction was 55.8% +/- 15.6%. The mean number of grafts was 3.1 +/- 1.1/patient, in 85.7% the internal mammary artery was used. Cardiac troponin I (cTnI) and T (cTnT) levels, total serum activities of creatine kinase (CK) and creatine kinase isoenzyme MB (CK-MB) were measured before operation, at arrival on the intensive care unit (ICU), and 6, 12, 24, 48, and 120 h after unclamping of the aorta. Twelve lead electrocardiograms (ECGs) were recorded preoperatively and at days 1, 2, and 5. Perioperative data and postoperative cTnI and cTnT levels were correlated statistically. RESULTS: Two patients died due to refractory myocardial failure in the early postoperative period. For further evaluation, patients were divided in two groups according to postoperative ECG changes (group I: patients without PMI, n = 107; group II: patients with PMI, n = 10: six of them with Q-wave and four of them with non-Q-wave PMI). Calculated best cutoff values for cTnI and cTnT were 8.35 microg/l and 0.768 microg/l in ROC (receiver-operator characteristic) analysis. Serum concentrations of cTnI, and cTnT were in the normal range preoperatively and increased significantly after surgery in both groups. In both groups, cTnI reached its medium peak level after 24 h (group I: 2.7 microg/l, 95% confidence interval [CI]: [2.1,3.2]); group II: 70.5 microg/l). CTnT reached its medium peak level in group I without PMI after 48 h (0.298 microg/l, 95% CI: [0.254,0.354]), in group II with PMI not until 120 h (3.0 microg/l) postoperatively. In group II serum level of both troponins remained considerably high at 120 h (cTnI median = 10.75 microg/l, cTnT median = 3 microg/l). CONCLUSION: Release patterns of cTnI and cTnT after CABG are different: cTnI reaches its postoperative peak value earlier and declines more quickly than cTnT. After uncomplicated CABG, serum levels of both cardiac troponins remain continuously low. Elevated concentrations reflect perioperative myocardial ischemia or infarction. CTnT shows a different release pattern in patients with or without myocardial infarction.

Ultrathin polymer monolayers for promotion of cell growth on bioprosthetic materials -- evolution of a new concept to improve long term performance of biologic heart vales.

Reoperation of aldehyde tanned bioprotheses due to calcific degeneration remains their major drawback. Based on experiments studying mechanisms and factors that influence the time phase, extent and progression of calcification and evaluating the efficiency of anticalcification treatments and the effects of surface seeding with vital cells a new concept to avoid calcification emerged: masking aldehyde-residues with a covalently bound polymer that supports surface cell seeding. Different covalently bound polymers were tested for their suitability to grow cells. Dense cell growth was achieved on some polymers but without correlation to physico-chemical properties. Ultrathin coating of biological materials appears a promising approach to achieve lining with vital cells.

Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy.

BACKGROUND: In primary pulmonary hypertension, aerosolized prostanoids selectively reduce pulmonary vascular resistance and improve right ventricular function. In this study, hemodynamic effects of inhaled iloprost, a stable prostacyclin analogue, were evaluated in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and early after pulmonary thromboendarterctomy (PTE). METHODS: Ten patients (mean age 49 years old [32 to 70 years old], New York Heart Association functional class III and IV) received a dose of 33 micro g aerosolized iloprost immediately before surgery (T1), after intensive care unit admission (T2), and 12-hours postoperatively (T3). Effects on pulmonary and systemic hemodynamics and gas exchange were recorded and compared with preinhalation baseline values. RESULTS: Preoperatively, inhaled iloprost did not significantly change mean pulmonary artery pressure (mPAP), cardiac index (CI), or pulmonary vascular resistance (PVR). Postoperatively, inhaled iloprost induced a significant reduction of mPAP and PVR and a significant increase of CI at T2 and T3. Preinhalation versus postinhalation PVR was as follows: at T1, 847 versus 729 dynes. s. cm(-5), p = 0.45; at T2, 502 versus 316 dynes. s. cm(-5), p = 0.008; and at T3, 299 versus 227 dynes. s. cm(-5), p = 0.004. CONCLUSIONS: In patients with CTEPH, inhalation of iloprost elicits no significant pulmonary vasodilation before surgery, and may have detrimental effects on systemic hemodynamics. Postoperatively, it significantly reduces mPAP and PVR, and enhances CI. Following PTE, inhalation of iloprost is useful to improve early postoperative hemodynamics.

Aprotinin inhibits leukocyte-endothelial cell interactions after hemorrhage and reperfusion.

BACKGROUND: The serine protease inhibitor aprotinin has been successfully used to reduce blood loss in patients undergoing cardiac operations. We studied aprotinin for its ability to modulate leukocyte-endothelial cell interactions after ischemia and reperfusion. METHODS: The effects of aprotinin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation and immunohistochemical analysis. The inflammatory cascade (leukocyte rolling, firm adherence, and transmigration) was studied after thrombin stimulation and after hemorrhage and reperfusion. RESULTS: Intravenous bolus administration of aprotinin treatment (20,000 U/kg) significantly reduced leukocyte rolling from 55 +/- 8 to 17 +/- 3 cells/min (p < 0.01) and adherent cells from 12 +/- 2 to 7 +/- 1.4 cells (p < 0.05) along the venous endothelium of the rat mesentery after thrombin activation. In addition, aprotinin pretreatment significantly inhibited transmigration of leukocytes from 11.3 +/- 1.2 to 6.0 +/- 1.1 cells (p < 0.05) through the microvascular endothelial wall. Similarly, aprotinin decreased leukocyte-endothelium interaction after hemorrhagic shock. Moreover, immunohistochemistry demonstrated that aprotinin significantly attenuated P-selectin expression by the intestinal vascular endothelium. CONCLUSIONS. Our data demonstrate that aprotinin potently inhibits recruitment of leukocytes in the microvasculature by interfering with endothelial cell-polymorphonuclear neutrophil interaction, and is a potent endothelial protective agent in clinically relevant doses. Thus, aprotinin pretreatment may be useful for primary prevention of inflammatory tissue injury mediated by ischemia-reperfusion injury such as shock, trauma, open heart operation, or other extensive vascular surgical procedures.

Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart.

OBJECTIVE: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. METHODS: The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by means of measurement of creatine kinase and myeloperoxidase activity within the myocardium, as well as histochemical analysis. RESULTS: Aprotinin (20,000 U/kg) administrated 2 minutes before reperfusion significantly attenuated myocardial injury expressed as creatine kinase washout compared with that seen in vehicle-treated rats (65 +/- 25 vs 585 +/- 98 creatine kinase difference in units per 100 mg, P <.01). Administration of 5000 U/kg of the protease inhibitor resulted in partial inhibition of myocardial reperfusion injury. Moreover, cardiac myeloperoxidase activity in the ischemic myocardium, a marker of neutrophil accumulation, was significantly reduced after aprotinin treatment. Histologic analysis of the reperfused myocardium demonstrated reduced polymorphonuclear leukocyte infiltration and reduced tissue injury. Furthermore, aprotinin treatment resulted in decreased induction of cardiac myocyte apoptosis compared with that seen in vehicle-treated rats. CONCLUSIONS: Inhibition of serine proteases with aprotinin appears to be an effective means of preserving ischemic myocardium from reperfusion injury, even after 24 hours of reperfusion. Aprotinin might exert cardioprotection through inhibition of polymorphonuclear leukocyte-induced myocardial injury and inhibition of reperfusion-induced apoptosis of cardiac myocytes.

Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin.

BACKGROUND: Simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, has been shown to lower serum cholesterol levels in clinical use. Moreover, statins exert beneficial effects in vascular diseases by inhibition of leukocyte rolling, adherence, and transmigration. The aim of this study was to determine if pretreatment with simvastatin attenuates Staphylococcus aureus alpha-toxin-induced increase in leukocyte-endothelial interactions during exotoxemia. METHODS AND RESULTS: The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation. Simvastatin (50 or 100 microg/kg) was administered 18 hours before the study. Activation of microcirculation was induced by bolus administration of 40 microg/kg S aureus alpha-toxin. Exotoxemia resulted in a significant and time-dependent increase in leukocyte rolling, adherence, and transmigration of leukocytes as well as P-selectin expression on the intestinal vascular endothelium. Pretreatment with simvastatin significantly inhibited exotoxin-induced leukocyte rolling from 71+/-10 to 14+/-4.7 cells/min (P<0.01) and adherence from 14+/-3.5 to 0.4+/-0.2 cells (P<0.01). In addition, simvastatin pretreatment significantly inhibited transmigration of leukocytes from 10.5+/-1.2 to 4.2+/-0.9 (P<0.05) cells. Immunohistochemical detection of endothelial cell adhesion molecule P-selectin showed a 50% decrease in endothelial cell surface expression after simvastatin treatment. Furthermore, simvastatin treatment resulted in enhanced expression of endothelial cell NO synthase III in the intestinal microcirculation. CONCLUSIONS: These results demonstrate that simvastatin interferes with exotoxin-induced leukocyte-endothelial cell interactions, which may be relevant in various infectious diseases. Statin treatment may offer a new therapeutic strategy for these clinical conditions.

Magnetic resonance angiography unmasks reliable target vessels for pedal bypass grafting in patients with diabetes mellitus.

OBJECTIVE: The purpose of this study was to evaluate the performance of pedal bypass grafts to foot vessels detected by magnetic resonance angiography (MRA) that were occult in conventional angiography in patients with diabetes mellitus and severe arterial occlusive disease. METHODS: Vascular surgery and radiology registries were reviewed for patients with pedal bypass grafts to arteries that were not detected with digital subtraction angiography but unmasked with MRA. From December 1997 to March 1999, 15 patients (mean age, 73 +/- 8 years) were identified and analyzed retrospectively. All the patients were diabetic, with 60% being insulin-dependent. Advanced tissue loss was the operative indication in all the cases. Distal anastomosis was performed to the dorsalis pedis artery in 10 cases and to the plantar artery in five cases, with ipsilateral greater saphenous vein as graft material in all the cases. RESULTS: The perioperative mortality rate was 7% (1 of 15 cases). One graft occlusion resulted in a secondary patency rate of 93.1%. During a mean follow-up examination period of 22 months, no graft occlusions and one major amputation were noted, which resulted in a secondary patency rate of 93.1% and a limb salvage rate of 89.5% at 36 months. CONCLUSION: Foot vessels that were occult in conventional angiography but could be detected with MRA were shown to be suitable target vessels for pedal bypass grafting with promising results.

[Endovascular aneurysm therapy--long-term treatment outcomes after 7 years]. / Endovaskuläre Aneurysmatherapie--Langzeitergebnisse nach 7 Jahren.

BACKGROUND: Stentgrafts for endovascular treatment of abdominal aortic aneurysms (AAA) have been commercially available since 1994, with now large numbers of implantations all over the world. PATIENTS AND METHODS: From 1994-2001, 115 patients were treated with Stentor, Vanguard and Talent stentgrafts in our institution. RESULTS: Late complications of the first- and second-generation stentgrafts as radiologic or surgical interventions to maintain complete exclusion of the aneurysm amounted to 30% with an additional 22% for observed endoleaks and configuration changes of the stentgraft. Third-generation stentgrafts had a lower complication rate of 12.2% for interventions and 18.3% for late endoleaks and graft changes. CONCLUSION: High costs of the devices, a pretty high late complication rate, and the uncertain maintenance of stentgraft function to prevent aneurysm rupture currently limit the widespread application of this new technology, leaving conventional aneurysmectomy the standard for aneurysm treatment and reserving the endovascular method for selected patients.

[Pedal bypass surgery in diabetic foot syndrome: indications, technique and outcome]. / Pedale Bypasschirurgie beim diabetischen Fusssyndrom: Indikation, Technik und Ergebnisse.

Peripheral arterial occlusive disease in the diabetic patients is characterized predominantly by long segmental occlusion of the tibial arteries with patent segments of pedal arteries. Neuropathy and high susceptibility for foot infection explain the dramatically increased risk of major amputation. The pattern of arteriosclerotic disease allows construction of pedal bypasses especially by the use of short autologous vein grafts employing distal origin of the bypass. Indication and performance of the bypass procedure rely on a complete angiographic evaluation of the arterial system of the diseased limb. Besides the dorsalis pedis artery with its major branches as preferentially used recipient vessel, the posterior tibial artery and its plantar branches may be anastomosed. Thus, improved foot perfusion will allow necessary minor amputations with safe wound healing. The use of autologous vein grafts is associated with a high late patency rate of more than 70% and a late limb salvage rate of more than 80%. Pedal artery bypass grafting should routinely be part of the therapeutic strategies in advanced diabetic foot syndrome with critical limb ischemia and impending limb loss.

Assessment of cardiac performance using Tei indices in patients undergoing pulmonary thromboendarterectomy.

BACKGROUND: This study was designed to evaluate left and right ventricular performance using Tei indices in patients with severe chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy (PTE). The Doppler-derived indices are easily measurable indicators of ventricular function based on nongeometric assessment, which helps overcome some of the difficulties entailed in the geometric assessment of left ventricular (LV) and right ventricular (RV) function in pulmonary hypertension. METHODS: The indices were derived for 24 patients (aged 54+/-14 years) before and after PTE. Calculation of these indices was based on the duration of two time intervals using the formula (A - B)/B, where A is the interval between cessation and onset of mitral inflow (or tricuspid inflow) and B is LV or RV ejection time. In addition, LV and RV end-diastolic and end-systolic chamber areas were determined using two-dimensional echocardiography, and systolic function was calculated. Mean pulmonary artery pressure was determined invasively. RESULTS: PTE led to a significant reduction of mean pulmonary artery pressure (46+/-10 versus 25+/-6 mm Hg; p < 0.05). LV and RV indices were abnormally high before surgery, declined significantly afterwards, and then almost matched normal values (0.61+/-0.26 versus 0.37+/-0.18; p < 0.05 and 0.55+/-0.22 versus 0.37+/-0.13; p < 0.05). Geometric assessment of the left and right ventricle also showed impaired systolic function before PTE, with significant improvement after surgery. CONCLUSIONS: LV and RV Tei indices allow a quantitative assessment of ventricular function in patients undergoing PTE. Lower indices after surgery reflect an improvement of the previously impaired cardiac function. Our results emphasize the value of PTE in the treatment of chronic thromboembolic pulmonary hypertension.

Improved Assessment of Pathological Regurgitation in Patients with Prosthetic Heart Valves by Multiplane Transesophageal Echocardiography.

The aim of this study was to evaluate the diagnostic increment of individually optimized axes in the assessment of pathological prosthetic valve regurgitation. Forty-two patients with pathologically regurgitant prostheses in the aortic (n = 21), mitral (n = 15), and tricuspid (n = 6) positions were examined by multiplane transesophageal echocardiography. The investigation was performed utilizing the transverse axis first, the longitudinal axis second, and the intermediate axes afterwards. The presence of regurgitation, the differentiation between trans- and perivalvular origin, and the localization of perivalvular leakages at the sewing ring were evaluated. Findings in the biplane and intermediate axes were compared to surgery or autopsy in all patients. There was slightly higher detection rate for aortic prosthetic regurgitation using the intermediate axes than the biplane axes. The intermediate axes revealed significantly fewer differences to the morphological control than the biplane axes with regard to the differentiation of peri- and transprosthetic aortic regurgitation and to the localization of a periprosthetic aortic regurgitant origin. The intermediate axes provided significantly better agreement to surgery/autopsy than the biplane axes regarding the localization of the origin of mitral periprosthetic regurgitation. Morphological visualization of the perivalvular gap adds important information on the precise localization of the regurgitant origin. The pathological gap was visualized significantly more often using the intermediate than the biplane axes in all types of prostheses. The data in this study therefore suggest that multiplane transesophageal echocardiography is superior to biplane transesophageal echocardiography in the assessment of pathologic prosthetic regurgitation.