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Biomedical subjects

M Cotrufo

Publications and source records attributed to M Cotrufo.

At least 19 recordsLinked to original sources

Perioperative optic neuropathy following off-pump coronary artery bypass grafting.

Visual loss from ischemic perioperative optic neuropathy (PON) rarely occurs during the postoperative period of patients undergoing cardiac surgery. Since the first description, PON has been associated with cardiopulmonary bypass (CPB), being some CPB-related complications and epiphenomena considered the causes of such terrible complication. In particular, the risk for micro-embolization during aortic cannulation and clamping, the CPB-related inflammatory response, the hemodilution and the hypothermia during CPB could be responsible of PON. However, some cases of PON still remain idiopathic. We report here a very rare case of PON following off-pump surgery in a patient with severe coronary disease and multiorgan comorbidities. The case reported opens the debate on the potential mechanisms underlying PON, other than cardiopulmonary bypass.

Aged↗

The risk of stroke following CABG: one possible strategy to reduce it?

OBJECTIVE: Stroke remains a devastating complication of coronary artery bypass grafting (CABG): we evaluated whether a more aggressive diagnostic and therapeutic approach can reduce its incidence. METHODS: Between January 1998 and January 2002, 1388 consecutive patients underwent isolated on pump CABG with blood cardioplegia. Among the first 627 patients (Group A), Echo-Doppler study (DS) was performed only in selected patients (58) with history of cerebrovascular disease (CVD) and/or carotid bruit; in 761 patients (Group B), DS was performed routinely. Carotid endarterectomy (CEA) was performed in 45 patients in Group A associated to CABG during cardiopulmonary bypass (CPB) and in 90 patients in Group B under local anaesthesia before CABG. Brain CT scan was performed in all cases with postoperative neurological symptoms. RESULTS: The two groups were homogeneous for age, sex, associated diseases, history of CVD, number of graft and CPB time. There were no differences in terms of hospital mortality between Group A (22/627: 3.5%) and Group B (21/761: 2.75%); p=0.5. Postoperative stroke was observed in 24/627 (3.82%) patients of Group A and in 2/761 (0.26%) of Group B (p<0.001). Hospital mortality for stroke was higher in Group A (12/627: 1.91%) than in Group B (0/761; p<0.001) as well as the incidence of non-fatal stroke (Group A 12/627: 1.91% versus Group B 2/761: 0.26% p=0.006). CONCLUSIONS: Preoperative DS, performed in all cases of CABG, followed by CEA under local anaesthesia in patients with critical carotid stenosis reduces the incidence of postoperative stroke.

Aged↗

Myocardial protection in diabetics with left main stem disease: which is the best strategy?

AIM: Diabetes mellitus is a well known risk factor for extensive coronary disease. The optimal route for cardioplegia administration in patients with severe ischaemic heart disease undergone surgery, especially with left main stem disease (LMSD) is still under debate. Aim of the study is to compare 2 different strategies of myocardial protection in diabetics with LMSD. METHODS: Between January 2000 and June 2003 90 consecutive patients with type II diabetes mellitus and LMSD undergoing isolated myocardial revascularization were divided into 2 groups according to the route of cardioplegia delivery: antegrade in 45 patients (group A), antegrade followed by intermittent retrograde in 45 (group B). ECG, Troponin I, MB-CPK, MB-CPK mass were performed at 12, 24, 48, and 72 hours postoperatively. Echocardiography was performed preoperatively and before hospital discharge. RESULTS: Groups were homogeneous in preoperative and intraoperative variables, apart from higher incidence of unstable angina and longer cardiopulmonary bypass time in Group B and hypertension in Group A. Hospital deaths, in intensive care units (ITU) stay, perioperative acute myocardial infarction, intra-aortic balloon pump support, postoperative recovery of left ventricle ejection fraction and wall motion score index were similar in both groups. In hospital stay proved shorter in group B (p=0.002), whereas postoperative atrial fibrillation was higher in group A (p<0.001), as postoperative inotropic support (p=0.006). Troponin I proved significantly higher in group A from the 12 degrees to the 72 degrees postoperative hour (p<0.0001). CONCLUSIONS: Despite major in hospital end-points did not differ with strategy of cardioplegia administration, combined route of intermittent blood cardioplegia allows better biochemical and perioperative results in diabetics with LMSD.

Angina, Unstable↗

Myocardial protection with insulin cardioplegia: who can really benefit?

AIM: The aim of the study was to evaluate the effects on myocardial protection of insulin-enriched warm blood cardioplegia (IWBC) in coronary artery bypass grafting (CABG) and in subgroups of patients with associated cardiac co-morbidities. METHODS: Between May 2000 and December 2002, 268 consecutive patients underwent CABG with warm blood cardioplegia (group A) or IWBC (10 UI/L) (group B). Hospital outcome, ECG, echocardiography and biochemical markers of ischemia were compared. Differences between subgroups of patients with unstable angina (UA), ventricular hypertrophy (VH) and diabetes were assessed. RESULTS: Hospital mortality, incidence of postoperative myocardial infarction and low output syndrome, IABP requirement, postoperative atrial fibrillation, in-hospital and in-ITU stay, postoperative recovery of left ventricular function and enzyme leakage did not show differences between the 2 groups; inotropic support was lower in IWBC. Moreover, patients with UA and IWBC showed a lower troponin I (TnI) (12 h: 0.82+/-0.57 ng/mL vs 2.56+/-1.18, P < 0.0001; 24 h: 0.71+/-0.64 vs 2.16+/-1.52, P < 0.0001; 48 h: 0.69+/-1.13 vs 1.79+/-1.43, P = 0.001; 72 h: 0.44+/-0.83 vs 1.01+/-1.02, P = 0.001), lower incidence of atrial fibrillation (4.2% versus 60.6%; P < 0.0001) and intraoperative defibrillation (0% versus 27.3%; P = 0.007). Furthermore, patients with VH treated with IWBC showed lower level of TnI (12 h: 0.41+/-0.32 ng/mL vs 2.93+/-0.67, P < 0.0001; 24 h: 0.37+/-0.45 vs 2.40+/-1.28, P < 0.0001; 48 h: 0.22+/-0.18 vs 1.95+/-1.33, P < 0.0001; 72 h: 0.12+/-0.12 vs 1.31+/-1.56, P < 0.0001), lower atrial fibrillation (6.5% vs 48%, P < 0.0001) and ventricular defibrillation (0% vs 20%, P = 0.011). CONCLUSIONS: Insulin addiction to blood cardioplegia does not show any benefit in the global population and in diabetics; nevertheless, better myocardial protection can be demonstrated in patients with unstable angina and left ventricular hypertrophy.

Aged↗

Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure.

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.

Cardiomyopathy, Dilated↗

Evolving practice patterns in heart transplantation: a single-center experience over 15 years.

This analysis is a retrospective characterization of evolving patterns in donor and recipient risk factors for early and late outcomes (survival and freedom from rejection) along with determinants of hospital and 1-year mortality after heart transplantation over a 15-year experience in a single center. Profiles and outcomes were evaluated for procedures performed between 1988 and 1995 (group A, n = 105) versus 1996 and 2003 (group B, n = 218). The following parameters were considered: pretransplant diagnosis, recipient age UNOS status, donor age, total postretrieval ischemic time, donor/recipient size match, and degree of myocardial necrosis at biopsy. Recipients in group B were significantly more compromised as demonstrated by UNOS status (11.4% vs 19.3%; P =.05) and pretransplant pulmonary vascular resistance (2.3 +/- 1.5 vs 3.1 +/- 1.5; P =.04). Marginal donors were more frequently used for group B procedures (21.9% vs 47.7%; P <.0001). Outcomes were significantly more favorable among group B patients in terms of hospital mortality (18.1% vs 10.6%; P =.046), and 1- and 5-year actuarial survival (72.4% vs 83.4%, 60% vs 73.3%, respectively; P =.006). Analysis of the causes of death disclosed a significant reduction in fatal events due to graft failure and acute rejection in group B. No difference emerged with regard to actual freedom from acute rejection. Determinants of hospital mortality were pretransplant diagnosis, UNOS status, donor age, and cardioplegic solution. Transplant era, recipient age, infectious episodes, and ischemic necrosis at biopsy were risk factors for 1-year mortality. We conclude that despite extensive usage of marginal donors and selection of worse candidates, significantly better outcomes were achieved due to improvements in global management strategies.

Cause of Death↗

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Adult↗

Efficacy and limitations of preemptive therapy against cytomegalovirus infections in heart transplant patients.

OBJECTIVES: Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. PATIENTS AND METHODS: We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value >/= 10 positive cells per 2 x 10(5) polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. RESULTS: Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P <.01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. CONCLUSIONS: Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.

Antigens, Viral↗

Right ventricular myocardial activation delay in adult patients with right bundle branch block late after repair of Tetralogy of Fallot.

Electromechanical interaction, with prolonged QRS duration due to right ventricular (RV) overload, has been described as a predictor of unfavorable outcome in patients late after correction of Tetralogy of Fallot (TOF). Aim of our study was to evaluate myocardial function and activation delay of both left and right ventricles in TOF patients. Doppler echo, treadmill test and pulsed Tissue Doppler (TD) were performed in 25 healthy subjects and in 30 adult patients who had undergone surgery for TOF, all with right bundle branch block on ECG. Exclusion criteria were evidence of residual pulmonary either stenosis or regurgitation. By use of TD, the level of both LV mitral and RV tricuspid annulus were measured: systolic (Sm), early- and late-diastolic (Em and Am) regional peak velocities. The indexes of myocardial systolic activation were calculated: precontraction time (PCTm) and interventricular activation delay (InterV-del) (difference of PCTm between RV and LV segments). The two groups were comparable for LV diameters and for Doppler indexes, while QRS duration was prolonged and RV end-diastolic diameter was increased in TOF. By TD analysis, only at the level of tricuspid annulus TOF patients had lower Sm and Em, and increased RV PCTm ( p<0.001 ) and InterV-del ( p<0.0001 ), even after adjustment for heart rate (HR) and QRS duration. By treadmill test, TOF showed reduced cardiac functional reserve. In seven patients non-sustained ventricular tachycardia was documented during physical effort. By multivariate analysis, RV Em ( p<0.001 ), and InterV-del ( p<0.01 ) were independently associated to maximal workload at peak effort. The same InterV-del was an independent determinant of risk of ventricular arrhythmias during effort ( p<0.01 ). A cut-off point of Em peak velocity of tricuspid annulus <0.13 m/s at rest showed a sensitivity of 91% and a specificity of 88% in identifying TOF patients with submaximal exercise test. A cut-off point of InterV-del >55 ms showed 87% sensitivity and 88% specificity to detect increased risk of ventricular arrhythmias during effort. In TOF patients, TD analysis at rest may be taken into account as a non-invasive and easy-repeatable tool to predict cardiac performance during physical effort, and to select subgroups of patients at increased risk of ventricular arrhythmias.

Adolescent↗

Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation.

OBJECTIVES: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated. METHODS AND RESULTS: Circulating N(epsilon)-(carboxymethyl)lysine (CML) and AGE associated fluorescence (AGE-Fl), lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross sectional study of 22 patients with advanced CHF, 30 heart transplant recipients, and 20 healthy controls. Compared with the controls, the CHF patients had decreased CML (mean (SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p < 0.01), AGE-Fl (mean (SEM) 302.2 (13.3) arbitrary units v 204.9 (15.7) arbitrary units, p < 0.01), and GFR (p < 0.01). CML was positively related to decreased total protein and serum albumin and negatively to body mass index (p < 0.01). In contrast, in the heart transplant group, impaired GFR was associated with a notable rise of both CML (mean (SEM) 876.1 (53.1) ng/ml, p < 0.01) and AGE-Fl (mean (SEM) 385.6 (26.1) arbitrary units, p < 0.01). A positive relation between CML and serum albumin (r = 0.394, p < 0.05) and lipofuscin (r = 0.651, p < 0.01) was found. CONCLUSIONS: The contrasting concentration of CML and AGE-Fl between patients with CHF and after heart transplantation in the presence of decreased GFR and oxidative stress are explained by lowered plasma proteins in CHF and higher concentrations in heart transplant recipients. In heart transplant recipients, in addition to myocardial inflammatory processes, immunosuppression may be important for enhanced formation of AGEs.

Adolescent↗

Risk factors for pacemaker implantation following aortic valve replacement: a single centre experience.

OBJECTIVE: To identify perioperative clinical predictors of permanent pacemaker implantation following aortic valve replacement. DESIGN AND PATIENTS: Prospective cohort study on 276 patients submitted for aortic valve replacement: 267 patients (mean (SD) age, 57.5 (14) years) with no conduction disturbances, and nine patients (67.7 (5) years) with severe conduction disturbances requiring permanent pacing; 65 perioperative variables (38 preoperative, eight intraoperative, and 19 postoperative) were considered. RESULTS: Nine patients (3.2%) had irreversible second or third degree atrioventricular (AV) block requiring permanent pacing. Risk factors for permanent pacing identified by univariate analysis were: preoperative: additional valvar disease, aortic regurgitation, myocardial infarction, pulmonary hypertension, anaemia, use of digitalis; intraoperative: cardiac arrest; postoperative: cardiac arrest, conduction disturbances, electrolytic imbalance, angiotensin converting enzyme inhibitor use. Multivariate logistic regression analysis identified preoperative aortic regurgitation (p < 0.005; odds ratio (OR) 6.6, 95% confidence interval (CI) 1.6 to 12.2), myocardial infarction (p < 0.0005; OR 15.2, 95% CI 6.3 to 19.9), pulmonary hypertension (p < 0.005; OR 12.5, 95% CI 3.2 to 18.3), and postoperative electrolyte imbalance (p < 0.01; OR 4.5, 95% CI 1.3 to 6.4). CONCLUSIONS: Irreversible AV block requiring permanent pacemaker implantation is an uncommon condition following aortic valve replacement. Previous aortic regurgitation, myocardial infarction, pulmonary hypertension, and postoperative electrolyte imbalance should be considered in order to identify patients at increased risk for advanced AV block.

Aged↗

Does priming implementation with low-dose albumin reduce postoperative bleeding following cardiopulmonary bypass?

This study aimed to assess whether low doses of albumin in the priming solution for cardiopulmonary bypass (CPB) reduce postoperative bleeding. Three-hundred and seventy-seven patients undergoing CPB were retrospectively assigned to group A (154 patients, CPB primed with 20 ml/kg Ringer Lactate solution + 0.75 mg/kg albumin 20%) and group B (223 patients with 20 ml/kg Ringer Lactate). A significant difference was found in terms of reoperations for bleeding (group A 0/154 versus group B 9/223; P=0.033). The mean number of blood derivatives transfused per patient was higher in group B than in group A (P<0.001). Platelet count after CPB was higher in group A than in group B (175 +/- 52x10(3)/microl versus 131 +/- 70x10(3)/microl; P=0.045). The amount of postoperative bleeding was 525 ml versus 680 ml at 24 hrs (P<0.001), 819 ml versus 1102 ml at 48 hrs, (P<0.001), 963 ml versus 1294 ml at 72 hrs, (P<0.045) (group A versus group B respectively). Crystalloid priming with low-dose albumin reduces postoperative bleeding.

Adult↗

Treatment strategies for postinfarction left ventricular free wall rupture: stabilization with peri-operative IABP and off-pump repair.

BACKGROUND: Perioperative management of post-infarction left ventricular free wall rupture (LVFWR) is not clearly standardized and surgical repair is the only therapeutic option. Role of off-pump surgery and stabilization with perioperative intraaortic balloon pumping (IABP) were here analysed. METHODS: Seven patients underwent surgery for LVFWR between 1990 and 2002. Clinical picture included electromechanical dissociation (3 patients) and sudden hypotension (4 patients). Except in one patient who was reanimated through femoro-femoral cardiopulmonary bypass, off-pump repair through on-lay patching technique was always performed. IABP was employed in the immediate postoperative period in five cases. RESULTS: A satisfactory hemodynamic state was restored in all cases and there were no reoperations for bleeding or rerupture. Hospital survival was 100%. One patient underwent successful surgical myocardial revascularization two months after LVFWR. Two patients died at follow-up. The survivors present with good NYHA and CCS functional classes. CONCLUSIONS: When the anatomy of the LVFWR is favourable, off-pump external patching repair proves a good choice. Postoperative IABP provides satisfactory hemodynamic support.

Aged↗

Pilot study on prevention of lung injury during surgery for type A acute aortic dissection: no evident improvements with celsior flushing through the pulmonary artery.

OBJECTIVE: Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection. Experimental evidence suggests that pulmonary artery perfusion using hypothermic protective solutions helps prevent lung injury. The aim of this pilot prospective study was to evaluate the effect of pulmonary artery flushing during selective cerebral perfusion (SCP) on lung function. METHODS: Twenty patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to two treatment groups. Pulmonary flushing was performed during SCP in group P (10 patients), while conventional Kazui technique was applied in group N (10 patients). Lung perfusion consisted of single-shot hypothermic pulmonary artery flush with Celsior. Lung function was evaluated by intubation time, scoring of chest radiograms at 12 hours after CPB, and PaO2/FiO2 assessed from immediately before surgery to 72 hours after termination of cardiopulmonary bypass. RESULTS: Incidence of pre, intra and post operative determinants of lung dysfunction proved homogeneous in both groups. Lung oxygenation function showed a marked post operative decline followed by a slow improvement in both groups. Analysis of respiratory ratios did not disclose significant differences even though the flushed group had a better performance in all study patients. The incidence of prolonged ventilator support (longer than 72 hours) (30% vs 20%, p = NS) and severity of x-ray pulmonary infiltrate score were comparable (mean score 1.7 +/- 0.71 vs 1.6 +/- 0.68, p = NS). CONCLUSIONS: Pulmonary artery flushing with Celsior solution does not seem to provide an effective preservation of lung function.

Aged↗

Initial clinical and hemodynamic experience with Edwards MIRA mechanical bileaflet valve.

AIM: An enhanced bileaflet valve, the Edwards MIRA feminine Mechanical Valve became available in 1998. Favorable hydrodynamic features and a redesigned sewing ring encouraged us to implant this device in indicated patients. Hemodynamics and clinical performance parameters were evaluated. METHODS: Between February 1998 and October 1999, 338 patients (171 males, 167 females) underwent native valve replacement with a MIRA prosthesis. Mean age 56.6+/-13.6 years, 320 patients were in NYHA class III/IV. Sixty-seven patients had echocardiographic examinations. Standard cardiopulmonary bypass was employed utilizing institutionally accepted implantation techniques. Aortic valve replacement was performed in 163 patients, mitral valve replacement in 134 patients, 35* double valve replacements and 1 triple valve replacement. RESULTS: Follow-up is 98% complete. Mean follow-up is 6.9+/-3.3 months (178.2 patient years). There were no operative deaths. Four early deaths were seen (1.18%). Late deaths reported in 12 patients. Linearized rate of late mortality was 6.7% per patient year (ppy). Overall actuarial survival at 13 months is 92.2%. Mean gradients and Effective Orifice Areas (EOA's) are comparable to other bileaflet valves. Linearized rates for valve-related complications was 4.49% ppy. Only 5 transient thromboembolic events (TE = 2.81% ppy) and 3 non-structural valve dysfunction events (NSVD = 1.68%) were seen. No reports of bleeding events, prosthetic endocarditis, valve thrombosis or structural valve deterioration. One patient required mitral valve reoperation for perivalvular leak. CONCLUSIONS: Short-term hemodynamic and clinical results are comparable to other bileaflet valves. The sewing ring is non-obstructive, compliant with smoother needle penetration. Early clinical results are encouraging, follow-up should be continued.

Adolescent↗

Medial degeneration does not involve uniformly the whole ascending aorta: morphological, biochemical and clinical correlations.

OBJECTIVE: To investigate whether and how the severity of medial degeneration (MD) lesions varies along the circumference of the dilated intrapericardial aorta. METHODS: Two groups of aortic wall specimens, respectively harvested 1cm distal to the non-coronary (NC) sinus (right postero-lateral wall) and to the right coronary sinus (anterior wall) in 22 patients undergoing surgery for dilatation of the intrapericardial aorta associated with aortic valve disease, were separately sent for pathology, morphometry and ultrastructural examination. MD lesions found at histology were classified into three degrees of severity. MD mean degree and morphometric findings in postero-lateral ('NC') and anterior ('coronary') specimens were compared by paired t-test. Correlation between degree of aortic dilatation at echocardiography and severity of MD was assessed separately for each of the two groups of specimens. After the preliminary results of the morphological study, we decided to send the specimens for biochemical investigation of protein electrophoretic patterns. This was performed in the last seven patients of this series. RESULTS: At histology, MD was found in all cases. A higher mean MD degree was found in the NC group (2.59+/-0.50 versus 1.59+/-0.67 in the coronary group; P<0.001). At morphometry, normal smooth muscle cells in the NC specimens were significantly reduced (P=0.012) and the length (P=0.011) and number (P=0.015) of elastic fibres reduced and increased, respectively. Correlation between aortic ratio and MD degree was significant in the NC specimens (P<0.001), not in the coronary ones (P=0.227). Quantitative differences between coronary and NC proteins from the same patient and between coronary proteins from different patients were found at electrophoresis. However, at this stage of the study, the sample was too small to allow for the identification of proteins involved in those differences. CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the right postero-lateral wall area, likely due to haemodynamic stress asymmetry.

Adult↗

Surgical injury of rat arteries: genetic control of the remodelling process.

OBJECTIVES: Remodelling and restenosis are complex biological processes responsible for bypass and percutaneous transluminal coronary angioplasty failures which are likely to affect many hundreds of genes. We evaluated the effectiveness of topically applied antisense oligonucleotides in reducing the translation of the messenger RNA for the transcription factor c-myc and in reducing stenosis. METHODS: Surgery was performed under sterile conditions; 60 Wistar-Kyoto male rats were anaesthetized by ketamine. The carotid arteries were isolated through a median incision in the anterior neck region. At the same point, 0.5 mm longitudinal incisions were performed. Haemostasis was obtained by an adventitial 8.0 stitch. Thirty animals were given 150 microg of c-myc antisense oligonucleotide (Group A) while the other 30 animals received 150 microg of c-myc control sense oligonucleotide (Group B). Oligo molecules were locally applied through 100 microl of 20% pluronic gel. Rats were sacrificed at 30 days; carotid arteries were explanted and stained. Qualitative histological analysis was performed in all cases; serial sections were made every 25 micro in seven consecutive rats for each group. Morphometric analysis was also performed, luminal and medial area values recorded and the ratio between the two areas calculated. Data from each animal were compared with the corresponding contralateral carotid artery and expressed as mean+/-standard deviation. Statistical comparison between the two groups was carried out by one-way ANOVA text. RESULTS: Qualitative histological analysis showed marked remodelling with complete disarray of vessel wall, neointima accumulation and evidence of elastic fibres in the adventitia of all animals of Group B versus Group A. Morphometric analysis showed a significant reduction in the lumen area in Group A animals together with increased values of the medial area versus Group B animals. In addition, the ratio between the lumen and medial area was significantly higher in Group A than in Group B (2.61+/-0.18 versus 1.14+/-0.33, P<0.0001). CONCLUSIONS: c-myc antisense oligonucleotides applied intraoperatively can reduce post-operative stenosis.

Analysis of Variance↗