Megalin - a facultative marker of obesity-related glomerulopathy in children.

Obesity-related glomerulopathy (ORG) is an increasingly detected syndrome present in children with obesity. Megalin, a constitutive proximal tubule cell protein, when present in urine, can be considered as a biomarker indicating renal injury in these children.

Role of macrophages in the pathogenesis of atherosclerosis and aortocoronary graft disease.

Atherosclerosis and disease of graft implanted to bypass occluded coronary or peripheral arteries are similar processes. Patency of implanted grafts is of paramount importance in respect to long-term outcomes. Although few cell types participate in atherosclerotic plaque formation, macrophages play a crucial role. In this article we review the fate of monocytes that infiltrate vessel wall following endothelium damage, and then undergo transformation to macrophages (identified as CD68 positive cells) and eventually lead to severe stenosis of vessel. Opposing biological activity of two subpopulations of macrophages and their impact on plaque instability and its calcification is also presented. At the end of this paper, a possible clinical significance of pre-existing, CD68 positive cell infiltration of vessel wall, applied as aortocoronary grafts, is discussed.

Gender and age-related variability of macrophage representation in the internal thoracic artery wall: does it matter?

Some recent reports suggested that elderly and female patients did not benefit from implantation of the second internal thoracic artery (ITA) during coronary artery bypass surgery (CABG). Macrophages, among other cells, were described to be involved in both atherosclerosis and aortocoronary grafts failure. The aim of the study was to examine the age and gender association with different distribution of CD68+ cells within the layers of ITA wall. This study involved 158 consecutive patients (95 male and 63 female), with the mean age of 64.5±9.5 years, who underwent elective CABG procedures. During surgery, the surplus distal segments of ITA were harvested for immunohistochemical analysis. The number and distribution of CD68+ cells was calculated and plotted against the age and gender of the study participants. CD68+ cells were present in all of the harvested ITA fragments (median 44), more in women (55) than in men (42) (p less than 0.001). However, this difference was of statistical significance exclusively in the tunica intima. Approximately 70% of macrophages were found in the tunica adventitia. The total number of CD68+ cells the in arterial wall as well as in the tunica intima and adventitia correlated positively with the age of patients (r=0.544, r=501 and r=0.462, respectively). The lack of significant advantages of the use of two thoracic arteries, in elderly patients and women, might have resulted from the larger population of CD68+ cells in their walls, especially the tunica intima. However, this result from immunohistochemical analysis needs validation in long-term clinical research on a larger cohort of patients.

Cardiac tamponade - unusual clinical manifestation of undiagnosed malignant neoplasm.

Cardiac tamponade may be the first or predominant symptom of some pathologies but its etiology is not uncommonly unknown on admission to hospital. The purpose of this study was to evaluate the predominant causes of cardiac tamponade in previously healthy patients treated emergently in a single cardiac surgical center. The study involved 81 patients with the mean age of 58.1±16.0 years who underwent emergent subxyphoid pericardiotomy due to cardiac tamponade. Pericardial effusion was analyzed macro- and microscopically. Examinations done in the cardiac surgical department revealed pericarditis secondary to infection (n=17) or autoimmunologic processes (n=2) and malignancy in 18 patients (predominantly of the lungs (n=11)). Pericardial effusion obtained from patients with viral and autoimmunologic-induced pericarditis was straw-color and odorless while with bacterial infections dark yellow, iridescent and usually malodorous. Additional workup in the regional hospitals enabled to reveal malignant tumors in 29 patients, leukemia or lymphoma in 5 subjects. In all but one of the neoplastic cases, pericardial fluid was turbid and dark red or plummy. In 10 patients etiology of tamponade remained unknown. In conclusion, cardiac tamponade in previously healthy patients may be occasionally the predominant symptom of cancer, especially of the lungs. Macroscopic intraoperative appearance of pericardial fluid may be helpful in identification of causative condition of cardiac tamponade.

"Extracorporeal Membrane Oxygenation for Greater Poland" Program: How to Save Lives and Develop Organ Donation?

The "ECMO for Greater Poland" program takes full advantage of the extracorporeal membrane oxygenation (ECMO) perfusion therapy opportunities to promote the health of the 3.5 million inhabitants in the region. The main implementation areas are treatment of patients with hypothermia; severe reversible respiratory failure (RRF); critical states resulting in heart failure, that is, cardiac arrest, cardiogenic shock, or acute intoxication; and promotion of the donor after circulatory death (DCD) strategy in selected organ donor cases, after unsuccessful life-saving treatment, to achieve organ recovery. This organizational model is complex and expensive, so we used advanced high-fidelity medical simulation tests to prepare for real-life experience. Over the course of 4 months we performed scenarios including "ECMO for DCD," "ECMO for extended cardiopulmonary resuscitation," "ECMO for RRF," and "ECMO in hypothermia." Soon after these simulations, Maastricht category II DCD procedures were performed involving real patients and resulting in 2 successful double kidney transplantations for the first time in Poland. One month later we treated 2 hypothermia patients (7 adult patients with heart failure and 5 patients with reversible respiratory failure) with ECMO for the first time in the region. Fortunately, we have discovered an important new role of medical simulation. It can be used not only for skills testing but also as a tool to create non-existing procedures and unavailable algorithms. The result of these program activities will promote the care and treatment of patients in critical condition with ECMO therapy as well as increase the potential organ pool from DCDs in the Greater Poland region of Poland.

Are stentless aortic heterografts suitable for right ventricular outflow tract reconstruction? An experimental study in juvenile sheep.

Allograft valved conduits are used routinely for reconstruction of the right ventricular outflow tract in children with congenital heart disease; however, allografts are scarce. The purpose of this study was to evaluate two stentless aortic valves that might be suitable alternatives for right ventricular outflow tract reconstruction. Twelve juvenile sheep underwent implantation of stentless aortic heterografts as an interposition in the pulmonary artery: six porcine aortic valves (Freestyle) and six fully pericardial valves (Pericarbon stentless). In each series, three valves were explanted after 3 months, the other three after 6 months. Valves were analyzed by gross inspection, radiography, and light microscopy. The porcine aortic stentless valve (Freestyle) showed extensive calcification of its aortic wall portion, with perfectly functioning, pliable cusps without calcification or fibrous overgrowth up to 6 months. The pericardial valves (Pericarbon stentless) showed extensive fibrous sheathing, causing progressive retraction of the leaflets and severe regurgitation. After 3 months, minimal calcification was seen in the pericardial wall. Calcification was more pronounced after 6 months, sometimes causing complete calcification of pericardial wall and leaflets, leading to a significant stenosis. We conclude that the pericardial stentless valve becomes rapidly dysfunctional after right-sided implantation as a result of fibrous sheathing and severe calcification. The porcine aortic stentless valve remains functional, but severe calcification of the aortic wall portion is problematic.

Results of surgical repair of ostium primum atrial septal defect in adult patients.

BACKGROUND AND AIM OF THE STUDY: Ostium primum atrial septal defect (ASD I) is very rarely observed in the adults. Although ASD I was first corrected surgically almost 50 years ago, the efficacy of surgical treatment in adults has not been well documented. Thus, the long-term outcome of patients aged over 20 years and having surgical repair of ASD I was examined. METHODS: Fifteen patients (10 males, five females; mean age 31.4+/-13.1 years; range: 20 to 56 years) who had surgical repair of ASD I between 1982 and 2000 were followed. All patients were examined physically and underwent chest radiography, ECG and echocardiography (cross-sectional and Doppler) before and after surgery. Autologous pericardium was used to close the defect in 14 patients, and a direct suture was used in one patient. Mitral valvuloplasty (repair of the cleft) was performed in 12 patients, and De Vega annuloplasty in eight. RESULTS: There were no hospital deaths. In one case a pacemaker was implanted five days after surgery because of complete heart block. Preoperatively, nine patients (60%) were in NYHA classes III and IV; at the end of follow up, 14 (93.3%) were in classes I and II. Preoperatively, 13 patients had sinus rhythm, and one each had atrial fibrillation (AF) and rhythm from the atrioventricular sinus. During follow up, three patients developed AF which was treated successfully with electrical cardioversion. The preoperative mean cardiac volume index of 695 +/- 216 ml/m(2) was reduced significantly after repair to 523 +/- 108 ml/m(2) (p < 0.05). Before surgery, mitral regurgitation was observed (severe in five cases, moderate in seven, mild in three). Postoperatively, a residual intracardiac shunt was identified in one case. Postoperative mitral regurgitation was noted in six patients (moderate in two, mild in four). The right ventricular dimension was decreased significantly, from 5.0 +/- 1.5 mm before surgery to 3.2 +/- 0.6 mm after repair (p < 0.001). CONCLUSION: Patients aged over 20 years with ASD I benefit from surgical repair of the defect.

Results of repair of partial anomalous pulmonary venous connection and sinus venosus atrial septal defect in adults.

BACKGROUND AND AIMS OF THE STUDY: This retrospective study evaluated late results of surgical treatment of partial anomalous pulmonary venous connection (PAPVC) concomitant with sinus venosus-type atrial septal defect (ASD) with the use of pericardial patch technique. METHODS: Between 1981 and 1995, 25 consecutive patients (18 females, seven males) underwent surgical repair of PAVPC with ASD. Mean age at surgery was 37.8 +/- 13.0 (range: 16 to 62 years). All patients underwent the procedure of covering both defect and vein with pericardial patch to direct blood flow from anomalous pulmonary veins through the ASD into the left atrium. Mean follow up was 7.8 +/- 4.0 years (range: 2 to 16 years). No patients were lost to follow up. RESULTS: There were no early deaths. One patient died 11 months after surgery from progressive heart failure. At follow up, 10 (42.7%) patients were clinically asymptomatic. One patient had clinical signs of superior vena cava (SVC) obstruction. Electrocardiography showed no abnormalities in seven (29.2%) patients. Chest radiography revealed normal pulmonary vascularity in 22 (91.7%) patients and no residual shunts were found in the SVC. CONCLUSION: The patch method of repair of PAPVC with sinus venosus ASD in adults with use of autologous pericardium is a safe and effective procedure.

The influence of stenting on the behavior of amino-oleic acid-treated, glutaraldehyde-fixed porcine aortic valves in a sheep model.

BACKGROUND AND AIM OF THE STUDY: The durability of freehand-sewn aortic valve homografts used for valve replacement in humans is greater than for stented aortic homografts. In analogy with this, it is expected that the durability of a stentless heterograft will be superior to that of its stented counterpart. Our objective was to investigate the influence of stenting on amino-oleic acid (AOA)-treated, glutaraldehyde-fixed porcine aortic valve bioprostheses. METHODS: Twelve young sheep underwent implantation of porcine aortic valves in the pulmonary artery: six porcine aortic stentless valves (Freestyle) and six porcine aortic stented valves (Mosaic). In each series, three valves were explanted after three months, and three after six months. Valves were analyzed by gross inspection, radiography, histology, and transmission electron microscopy. Quantitative determination of calcium content was made with atomic absorption spectrometry. RESULTS: The porcine aortic stentless valve showed extensive calcification of its aortic wall portion, but had perfectly functioning, pliable cusps without calcification up to six months. The cusps of porcine aortic stented valves were also pliable and functioning without calcification up to six months. Only minimal calcification was seen in the aortic wall of the stented valves. At six months after implantation the cusps of stentless valves contained significantly less calcium than those of stented valves (2.7+/-1.2 microg/mg and 7.9+/-2.3 microg/mg, respectively; p = 0.011). However, the aortic wall from stentless valves contained significantly more calcium than that of stented valves (three-month explants: 39.2+/-14.4 versus 7.2+/-2.8 microg/mg; p <0.05; six-month explants: 49.3+/-14.0 versus 14.1+/-5.9 microg/mg; p <0.05). CONCLUSION: These data suggest that stenting does influence cuspal calcification of AOA-treated, glutaraldehyde-fixed porcine aortic valves.

Micropumps to support the heart during CABG.

OBJECTIVE: To show the effect of myocardial support by micropumps during beating heart CABG for triple vessel disease. METHODS: In 12 sheep, three coronary arteries (LAD, intermediate branch and circumflex) were consecutively occluded for 10 min. The animals were divided in two groups: group 1 without support (n=6) and group 2 with biventricular support of intravascular micropumps. The pumps (diameter 6.4 mm) were placed through peripheral access (femoral artery and jugular vein) and advanced under fluoroscopic guidance. The hemodynamic evolution was analyzed during the procedure and 2 h of reperfusion. Myocardial flow was assessed by colored microspheres. Differences between groups were analyzed by ANOVA for repeated measurements and post-hoc testing in case of significance. RESULTS: All of the pump-supported animals survived the procedure, 1 of the control animals died of resistant ventricular fibrillation. At the end of the reperfusion period, the hemodynamic performance and myocardial contractility was significantly better in the pump-supported group (cardiac output: 2.4+/-0.9 vs. 3.3+/-0.9 l/min, P=0.0192; mean arterial blood pressure: 51+/-23 vs. 73+/-9 mmHg, P=0. 036; first derivative of the left ventricular pressure: 561+/-271 vs. 947+/-316 mmHg/s, P=0.0074). After the procedure, subendocardial blood flow was significantly better in all areas of the left ventricle in group 2 (0.935+/-0.427 ml/min per g vs. 0.409+/-0.183 ml/min per g in group 1; P=0.0366). CONCLUSION: The supported heart is more resistant to repetitive local ischemia. Support by microaxial pumps can make beating heart surgery safer and applicable for more complex cases.

Calcification characteristics of porcine stentless valves in juvenile sheep.

OBJECTIVE: To compare calcification characteristics of two porcine stentless valves (Toronto SPV and Freestyle) with different designs, fixation and antimineralization techniques using a juvenile sheep model of valve implantation inside the circulation. METHODS: The stentless valves (n = 2 x 6) were implanted in juvenile sheep in the pulmonary artery as an interposition, while the circulation was maintained with a right ventricular assist device. The model was validated by the implantation of, clinically well-known, porcine (Hancock II) and pericardial (Pericarbon) valves. Half of the valves were explanted after 3 months, the rest after 6 months. Valves were examined macroscopically, by X-ray, light microscopy (HE, Masson, Von Giesson, Von Kossa, PTAH stains), and transmission electron microscopy. Quantitative determination of the calcium content of the cusps was performed with atomic absorption spectrometry. RESULTS: After 3 months, the Freestyle had an extensively calcified aortic wall, most prominent at the outflow side of the porcine valve. After 6 months, calcification increased transmurally, but the valve cusps were free of calcification, and the inflow side was only slightly calcified. The Toronto SPV valve also started to calcify at the inflow side of the valve after 3 months with increased calcification after 6 months. The base of the Toronto SPV valve cusps showed slight calcification after 6 months of implantation. CONCLUSIONS: The pattern of calcification of the porcine aortic wall differs between the two studied stentless valves, with calcification located predominantly at the outflow side in the Freestyle valve, but also at the inflow side in the Toronto SPV valve. The cusps of the Freestyle valve were less prone to calcification than those from the Toronto SPV valve.

Chronic heart failure model induced by coronary embolization in sheep.

OBJECTIVE: To create a model of chronic heart failure in a large animal. METHODS: Heart failure was induced in sheep by single intracoronary injection of polymer macrobeads, which were administered into left main coronary artery (n=3) or selectively into left anterior descending (n=4) or left circumflex (n=5) coronary artery. The animals were followed by echocardigraphy for 20 weeks. Measurements comprised fractional area change (FAC), and diastolic ventricular area (EDVA) and regional wall-thickening fraction (WT%). RESULTS: EDVA increased from 14.2+/-2.1 cm2 prior to embolization to 16.9+/-3.1 cm2 on day 1 (p<0.05), and remained significantly increased until completion of the follow-up period. FAC dropped from 47.9+/-4.6% at baseline to 29.3+/-4.4% on day 1 (p<0.001) and remained significantly depressed until 20 weeks later. In 9 selectively embolized animals WT% of the embolized area decreased from 33.8+/-8.0% at baseline to 5.3+/-2.6% on day 1 and remained significantly decreased. CONCLUSIONS: A simple model of chronic heart failure was developed. It shows relatively high stability over time and may prove beneficial in experimental work on ventricular assist devices.

[Results of coronary artery bypass grafting in patients with impaired left ventricular systolic function]. / Wyniki chirurgicznego leczenia choroby wiencowej u chorych z uposledzona funkcja skurczowa lewej komory.

The purpose of this study was to examine the early and late results of CABG in patients with left ventricular ejection fraction (LVEF) lower than 40%. This study comprised 128 patients (114 male and 14 female) at age from 41 to 75 years (mean 58.3 +/- 7.9). Before operation 115 patients (89.8%) were in CCS class III or IV. Before operation in all patients coronary arteriography with left-sided ventriculography were performed. In 12 patients myocardial perfusion in SPECT with Tc-99m-MIBI was assessed. Perioperative mortality in whole group was 12.5% (16 patients). The lowest (9.2%) was in subgroup with LVEF from 0.31 to 0.4 and the highest (27.3%) in patients with LVEF below 0.2. In 8 patients death was caused by low cardiac output, in 4 by ventricular fibrillation, in the others by renal failure or cerebral stroke (2 patients in each). In 45 patients (35.2%) postoperative low cardiac output was observed. In 41 patients was treated with the use of intraaortic balloon pumping (IABP). Twenty seven (65.9%) patients with IABP survived. During follow-up died 5 pts. 24-months probability of survival calculated from Kaplan-Meier method was 82.4%. In follow-up 80.9% of patients were in CCS class I and II. In SPECT, four months after CABG significantly more segments of left ventricle with normal perfusion (45% vs 53%; p < 0.05) were observed. Patients with LVEF < 40% are at higher operative risk because of often postoperative low output syndrome. Low output syndrome can by successfully treated with IABP. CABG significantly improves circulatory sufficiency in patients with LVEF < 40%.

[Coronary artery bypass grafting in patients over 70 years of age]. / Bezposrednia rewaskularyzacja miesnia sercowego u chorych powyzej 70. roku zycia.

The purpose of this study was to assess the risk of coronary artery bypass grafting (CABG) in the group of patients (pts) over 70 years of age and to examine results of surgical treatment in these pts. Between January 1993 to December 1999 1276 pts underwent CABG. From this group 114 consecutive pts at the age over 70 were retrospectively studied. The average age of the pts was 71.8 +/- 2.2 years (range, 70 to 79 years). Eighty nine male (78.1%) and 25 female (21.9%) pts were operated. One or more myocardial infarction had occurred in 64.0% of pts preoperatively. All the pts underwent left cardiac catheterization. The indication for surgery was significant stenosis of the left main trunk in 35 (30.7%) pts and three vessels disease in 54 (47.4%) pts. The total number of peripheral anastomoses was 274 (average 2.4 +/- 0.9 grafts per pts). In 29 cases left internal mammary artery (to left anterior descending artery) and in 245 reversed saphenous vein grafts were used. The early postoperative mortality in the group of pts at the age over 70 (10 pts--8.8%) was significantly higher than in the group of younger pts (41 of 1162 pts). The cause of death in septuagenarians was: low cardiac output syndrome (5 pts), respiratory failure (2 pts), renal insufficiency (2 pts) and cerebral stroke (1 pt). In early postoperative course the incidence of any organ insufficiency (cardiac, respiratory, renal and neurological) was higher in the group of pts over 70 years of age than in the younger pts. Seven-year probability of survival calculated from Kaplan-Meier method was 66 +/- 4%. After operation 84.5% of pts were asymptomatic, while only 5 pts were in III and IV CCS functional class. CABG in pts at the age over 70 is associated with higher operative risk and higher rate of perioperative organ failure. After surgery most pts enjoy improvement in life quality.

Do patients over 40 years of age benefit from surgical closure of atrial septal defects?

OBJECTIVE: To determine the value of surgical closure of atrial septal defects in patients over 40 years of age. METHODS: Retrospective analysis of 76 patients (63 women, 13 men), age range 40-62 years (mean (SD) 45.8 (5.1) years), who underwent surgical repair of atrial septal defect. Pre- and postoperative clinical status (New York Heart Association (NYHA) functional class) was assessed, and ECG, x ray, and echocardiographic investigations performed. Follow up was between 1 and 17 years. RESULTS: One operative and one late death occurred during the study period. Before operation, 47 patients (61.8%) were in NYHA functional classes III and IV. After operation, 61 patients (82.4%) were in classes I and II. Four patients had atrial fibrillation before surgery versus nine after surgery. Before operation, 52 patients had intensified pulmonary vascularity compared with only seven after operation. Echocardiographic examination showed a significant reduction in right ventricular dimension (4.10 (0.91) v 2.95 (0.36) cm, p < 0.001). No residual intracardiac shunts were identified on echocardiographic follow up. CONCLUSIONS: Surgical closure of atrial septal defects in patients over 40 years old can improve their clinical status and prevent right ventricular dilatation and insufficiency.

The effect of sudden failure of a rotary blood pump on left ventricular performance in normal and failing hearts.

We investigated the hemodynamic effect of regurgitation (or back-flow) due to sudden failure of a rotary blood pump (diagonal pump). Seven healthy sheep (Group C) and 7 with chronic heart failure (Group F) were studied. Chronic heart failure was obtained by intracoronary injection of microspheres several weeks earlier. Left ventricular function and ventricular efficacy were assessed by the pressure-volume relationship. The back-flow through the stopped pump was significantly lower in Group F (2.3 +/- 0.34 L/min) than in Group C (2.8 +/- 0.33 L/min). Mean aortic blood pressure dropped significantly from 68.3 +/- 9.65 to 61.9 +/- 9.75 mm Hg in Group C and from 62.5 +/- 9.12 to 51.5 +/- 9.08 in Group F but remained stable during the 15 min period of pump stop. Parameters of left ventricular contractility (preload recruitable stroke work) dropped significantly in both groups, remained stable during the pump stop, and returned to baseline values 30 min after the end of back-flow. The ventricular efficacy (in terms of energy transfer) was tolerant against this acute volume overload even in the failing hearts. Sudden pump failure of a rotary blood pump leads to an acute depression of the hemodynamic state and myocardial contractility. However, this depression remained stable over 15 min, did not lead to further deterioration of the animals, and was completely reversible.