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Biomedical subjects

M Ranucci

Publications and source records attributed to M Ranucci.

At least 19 recordsLinked to original sources

The endothelial function in cardiac surgery.

Cardiac operations with cardiopulmonary bypass exerts many different actions which modify the natural function of endothelial cells. The main determinant is the activation of the coagulation system both through the intrinsic and extrinsic pathways, leading to an overwhelming thrombin formation. To counteract the coagulant effects of thrombin, heparin is used in large doses. As a result, the endothelium is asked to promote all its anticoagulant properties, basically through the AT release from the surface, the tissue factor pathway inhibitor release, and the activation of the protein C protein S system. At the end of cardiac operations, all these systems are depleted, and low levels of antithrombin, tissue factor pathway inhibitor, protein C are available for further anticoagulant effects. There is the evidence that levels of antithrombin activity below 50% at the end of cardiac operations with cardiopulmonary bypass are associated to bad outcomes in terms of surgical revision rate, thromboembolic events, and neurological events. Exogenous antithrombin administration has a well defined action in limiting thrombin formation during cardiac operations; however, we are still lacking an evidence-based information about the clinical impact of this and others possible preventive strategies based on exogenous administration of antithrombin before or during cardiac operations.

Cardiac Surgical Procedures↗

Reduced systemic heparin dose with phosphorylcholine coated closed circuit in coronary operations.

In this prospective cohort study we addressed the clinical impact of a reduced anticoagulation protocol on the hospital outcome of patients undergoing coronary revascularization with cardiopulmonary bypass. 364 consecutive low to moderate risk patients scheduled for elective isolated coronary operations were admitted to the study. 184 patients (Control Group) received conventional open circuits and full systemic anticoagulation (target activated clotting time 480 seconds); 180 patients (Intraoperative ECMO group) received closed, phosphorylcholine coated circuits and a reduced systemic heparin dose (target activated clotting time 320 seconds). Patients of the Intraoperative ECMO group had less requirement for allogeneic blood products (odds ratio 0.55, 95% confidence interval 0.34-0.92, p = 0.02), a significant containment of blood loss (374 +/- 278 mL vs. 463 +/- 321 mL in Control group, p = 0.005) a lower postoperative peak serum creatinine levels (1.19 +/- 0.48 mg/dL vs. 1.41 +/- 0.94 mg/dL in Control group, p = 0.048), and a significant lower rate of severe morbidity (odds ratio 0.27, 95% confidence interval 0.09-0.81, p = 0.02). A reduction of systemic anticoagulation is feasible with a non-heparin-bonded, closed biocompatible circuit, and results in a significant improvement of the outcome of low to moderate risk coronary patients.

Aged↗

Unsteady flow through in-vitro models of the glottis.

The unsteady two-dimensional flow through fixed rigid in vitro models of the glottis is studied in some detail to validate a more accurate model based on the prediction of boundary-layer separation. The study is restricted to the flow phenomena occurring within the glottis and does not include effects of vocal-fold movement on the flow. Pressure measurements have been carried out for a transient flow through a rigid scale model of the glottis. The rigid model with a fixed geometry driven by an unsteady pressure is used in order to achieve a high accuracy in the specification of the geometry of the glottis. The experimental study is focused on flow phenomena as they might occur in the glottis, such as the asymmetry of the flow due to the Coanda effect and the transition to turbulent flow. It was found that both effects need a relatively long time to establish themselves and are therefore unlikely to occur during the production of normal voiced speech when the glottis closes completely during part of the oscillation cycle. It is shown that when the flow is still laminar and symmetric the prediction of the boundary-layer model and the measurement of the pressure drop from the throat of the glottis to the exit of the glottis agree within 40%. Results of the boundary-layer model are compared with a two-dimensional vortex-blob method for viscous flow. The difference between the results of the simpiflied boundary-layer model and the experimental results is explained by an additional pressure difference between the separation point and the far field within the jet downstream of the separation point. The influence of the movement of the vocal folds on our conclusions is still unclear.

Air Pressure↗

Ischemic mitral regurgitation: intraventricular papillary muscle imbrication without mitral ring during left ventricular restoration.

OBJECTIVES: Functional mitral regurgitation in ischemic cardiomyopathy carries a poor prognosis, and its surgical management remains problematic and controversial. The aim of this study was to report the results of our surgical approach to patients who have had myocardial infarctions and have ventricular dilatation, mitral regurgitation, reduced pump function, pulmonary hypertension and coronary artery disease. This surgical approach consists of endoventricular mitral repair without prosthetic ring, ventricular reconstruction with or without patch, and coronary artery bypass grafting. PATIENTS: Forty-six patients (aged 64 +/- 10 years) with previous anterior transmural myocardial infarction and mitral regurgitation comprised the study group. Indication for surgery was heart failure in 93% of cases; 25 patients were in New York Heart Association functional class IV and 17 were in class III. Mitral regurgitation was moderate to severe in 32 cases (69%). RESULTS: All patients underwent coronary artery bypass grafting, with a mean of 3.2 +/- 1.3 grafts. Associated aortic valve replacement was performed in 4 cases. Global operative mortality rate was 15.2%. End-diastolic and end-systolic volumes significantly decreased after surgery (from 140 +/- 40 to 98 +/- 36 mL/m(2) and from 98 +/- 32 to 63 +/- 22 mL/m(2), respectively, P =.001). Systolic pulmonary pressure decreased significantly (from 55 +/- 13 to 43 +/- 16 mm Hg, P =.001). Ejection fraction did not change significantly. Postoperative mitral regurgitation was absent or minimal in 84% of cases; 1 patient had severe mitral regurgitation necessitating valve replacement. New York Heart Association functional class significantly improved. The mean preoperative functional class was 3.4 +/- 0.6 (median 3, range 2-4); after the operation, this decreased to 1.9 +/- 0.7 (median 2, range 1-3, P <.001). Cumulative survival at a 30-month follow-up was 63%. CONCLUSIONS: Our aggressive, combined surgical approach is aimed at correcting the three components of ischemic cardiomyopathy: relieving ischemia, reducing left ventricular wall tension by decreasing left ventricular volumes, and reducing volume overload and pulmonary hypertension by repairing the mitral valve. Despite a relatively high perioperative mortality rate, surviving patients benefitted from the operation, with improved clinical functional class and thus quality of life.

Adult↗

Closed, phosphorylcholine-coated circuit and reduction of systemic heparinization for cardiopulmonary bypass: the intraoperative ECMO concept.

Cardiopulmonary bypass with heparin-bonded circuits reduces systemic heparinization which is associated to a better clinical outcome in cardiac operations. In the present study, a novel biocompatible treatment, based on a phosphorylcholine coating without heparin, has been used to reduce systemic heparinization during cardiopulmonary bypass. Sixty patients underwent coronary revascularization with a fully phosphorylcholine-coated circuit. The circuit was entirely closed; suctions from the field were separated during the cardiopulmonary bypass time. A low systemic heparinization protocol based on half the loading dose of heparin (150 IU/kg) and a target activated clotting time of 320 seconds was applied. No thrombus formation inside the extracorporeal circulation circuit occurred; in-hospital mortality was absent. One patient (1.6%) had a postoperative myocardial infarction and 2 (3.3%) were surgically revised due to bleeding. Homologous blood transfusion rate was 11.6%, postoperative bleeding was 310 +/- 136 ml. If compared to patients treated with heparin-coated circuits and low systemic heparinization, these patients have better platelet count preservation and lower postoperative bleeding. The low thrombogenicity of phosphorylcholine-treated surfaces, despite the absence of surface-immobilized heparin, allows a safe reduction of systemic heparinization in the setting of an ECMO-like intraoperative cardiopulmonary - bypass. This intraoperative ECMO approach offers promising results in terms of clinical outcome after coronary revascularization operations.

Anticoagulants↗

Angioplasty in severe heart attack. Anesthesia and general management.

BACKGROUND: Percutaneous transluminal coronary angioplasty is more and more widely applied for the treatment of acute coronary syndromes. Both if primary employed or following an unsuccessful thrombolytic treatment (rescue angioplasty), it improves the early and late outcome of acute myocardial infarction patients. Anyway, in about 10% of the cases, it fails and must be followed by a coronary artery bypass graft operation. In this case, the patients reach the operating theater with a risk profile that differs from the usual one due to the higher rate of cardiogenic shock (4.5 vs 0.4%), need for intra-aortic balloon pumping (14 vs 0.8%), use of antiaggregants and heparin. METHODS: 3,296 patients who underwent coronary artery bypass graft operation over the last two years were analysed. RESULTS: Despite this, in our population of coronary patients undergone surgical revascularization (3,296 consecutive patients in the last two years), we could not find a worsened outcome in patients being operated after a failed primary percutaneous transluminal coronary angioplasty. CONCLUSIONS: The role of GPIIb-IIIa inhibitors in determining an excessive postoperative bleeding still remains to be defined, but probably mainly depends on the type of drug, its dose, and the time between its administration and the operation.

Acute Disease↗

Antithrombin III. Key factor in extracorporeal circulation.

Antithrombin III plays many different roles during cardiac operations with cardiopulmonary bypass. Basically, it acts as the natural inhibitor of thrombin, which, in presence of heparin, blocks the thrombin action and avoids gross thrombus formation inside the extracorporeal circulation circuit. By acting as a "suicide substrate", antithrombin III is consumed during cardiopulmonary bypass; at the same time, thrombin is extensively formed during and after cardiopulmonary bypass. As a result, at the end of the operation there is a potential imbalance in the antithrombin III-thrombin interaction, leading to a prothrombotic status. Moreover, patients pre-treated with heparin reach the operating theater with reduced levels of circulating antithrombin III; this may lead to the heparin resistance phenomenon and may further increase the risk for postoperative thrombotic complications. Finally, the anti-inflammatory properties of antithrombin III in the setting of the "whole body inflammatory reaction" induced by the cardiopulmonary bypass represents a new and unexplored field of research.

Anticoagulants↗

Risk factors for fatal myocardial infarction after coronary bypass graft surgery.

BACKGROUND AND OBJECTIVE: The incidence and clinical impact of perioperative myocardial infarction during coronary artery bypass graft surgery vary greatly depending upon the diagnostic criteria applied. Fatal perioperative myocardial infarction has a less arguable diagnosis and clinical impact. The aim of this paper is to find out the risk factors for fatal myocardial infarction after coronary surgery. METHODS: Data from 1561 consecutive patients, who underwent coronary revascularization during a 10-month period, have been retrospectively analysed. After an univariate analysis for pre- and intraoperative risk factors, a multivariate model (logistic regression analysis) was settled. RESULTS: Preoperative use of subcutaneous/intravenous heparin, a heparin sensitivity index < 1.3 and need for a thromboendarterectomy of the left anterior descending coronary artery are independent risk factors for fatal myocardial infarction. The relative risk for fatal myocardial infarction was about 2 in the case of preoperative heparin use or heparin sensitivity index < 1.3 and 5.5 in the case of thromboendarterectomy of the left anterior descending coronary artery. CONCLUSIONS: In patients undergoing coronary artery bypass surgery, preoperative anticoagulation management with heparin may represent a risk factor for fatal myocardial infarction. Patterns of heparin resistance, whether or not due to heparin pretreatment, seem to be closely related to fatal myocardial infarction.

Aged↗

Trillium biopassive surface: a new biocompatible treatment for extracorporeal circulation circuits.

139 patients undergoing cardiac surgery were included in a prospective, randomized trial. Patients were randomly allocated to receive cardiopulmonary bypass (CPB) with Trillium Biopassive Surface (TBS Group) coated oxygenators or conventional circuits (control group). 112 patients were studied with respect to postoperative biochemical profile; a subgroup of 27 patients was studied with respect to perioperative complement (C3a) activation. Patients in the TBS group demonstrated a significantly lower white blood cell count at the end of the operation (p=0.036) and a significantly higher platelet count the day after the operation (p=0.023) when compared to the control group. C3a was significantly higher (p=0.02) in the TBS group after 30 minutes of CPB, but the C3a increase after protamine administration was significantly less pronounced in the TBS group vs. the control group. Further studies involving platelet and leukocyte activation are required to better elucidate the action of this new coating in the setting of routine CPB.

Biocompatible Materials↗

Diabetes and complications after cardiac surgery: comparison with a non-diabetic population.

Diabetes is a well-recognized independent risk factor for mortality due to coronary artery disease. When diabetic patients need cardiac surgery, either coronary-aortic by-pass (CABP) or valve operations (VO), the presence of diabetes represents an additional risk factor for these major surgical procedures. Because of controversial data on mortality rates and post-operative complications in diabetic patients, probably due to not exactly comparable groups of patients, this retrospective study aimed to compare two homogeneous populations, which were different only for the presence or absence of diabetes. We studied 700 patients undergoing cardiac surgery: 350 with and 350 without diabetes, mean age 62 +/- 9 years (67% males); 441 underwent CABP and 259 VO. Apart from the diabetes, the two groups were strictly matched for age, body mass index, concomitant pathologies and smoking habits, except for previous neurological injuries (more frequent in diabetic patients), and for a slightly lower ejection fraction in the diabetic group. Intra- and post-operative complications or events were evaluated carefully: death, number staying in post-operative intensive care unit (ICU), renal, hepatic and respiratory complications, necessity for reoperation and hemotransfusions. Anesthesia and surgical procedures (including extra-corporeal circulation techniques) remained substantially unchanged over the period of recruitment of patients (1996-1998) and applied equally to both groups of patients. All diabetic patients were treated with insulin by using standard procedures in order to optimize metabolic control. Diabetic patients in our study, did not show higher rates of mortality in comparison with non-diabetic patients, but had more total neurological complications, more renal complications, a higher re-opening rate, more prolonged ICU stay, and they needed more blood transfusions. Diabetes remains an independent risk factor for these events even in a multivariate logistic regression model analysis. In the subgroup of diabetic patients who underwent CABP a higher rate of renal dysfunction, re-opening, need for hemotransfusions and prolonged ICU stay were confirmed. In the subgroup of diabetic patients undergoing VO we found a higher rate of renal dysfunction, reopening, prolonged ICU stay and major lung complications. In conclusion, diabetes does not seem to increase the mortality rates of cardiac surgery, but diabetic patients undergoing CABP have, on the basis of the relative risk evaluation, a 5-fold risk for renal complications, a 3.5-fold risk for neurological dysfunction, a double risk of being hemotransfused, reoperated or being kept 3 or more days in the ICU in comparison with non-diabetic patients. Moreover, diabetic patients undergoing VO have a 5-fold risk of being affected by major lung complications.

Coronary Artery Bypass↗

Heparin-coated circuits for high-risk patients: a multicenter, prospective, randomized trial.

BACKGROUND: Heparin-coated circuits (HCCs) in low-risk cardiac patients who have coronary revascularization have a limited impact on postoperative outcome. In this prospective, randomized investigation, we studied high-risk patients who had cardiac operations with or without HCCs. METHODS: A total of 886 patients who had cardiac operations with cardiopulmonary bypass and at least one patient-related or procedure-related risk factor were enrolled in a multicenter study. They were randomly allocated to have cardiopulmonary bypass with Duraflo II HCCs (HCC group, n = 442) or conventional circuits (control group, n = 444). Postoperative outcome was investigated with respect to the occurrence of organ dysfunction. RESULTS: HCCs are associated with a shorter intensive care unit and postoperative hospital stay and with a lower rate of patients having a severely impaired clinical outcome (stay in intensive care unit for more than 5 days or death) (relative risk 0.66, p = 0.045). Lung dysfunction rate was significantly lower for the patients in HCC group affected by chronic obstructive pulmonary disease or who had mitral procedure (relative risk, respectively, 0.31, p = 0.018 and 0.05, p = 0.02). Renal dysfunction rate was significantly (p = 0.05) lower for diabetics in the HCC group (relative risk 0.28). CONCLUSIONS: When HCCs were used postoperative times decreased and they had a protective effect on lung and kidney function in high-risk patients.

Aged↗

Obesity and coronary artery surgery.

OBJECTIVE: To assess whether obesity is a risk factor for morbidity and mortality in patients undergoing elective coronary artery revascularization. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Three hundred forty-five consecutive patients who underwent elective coronary revascularization with cardiopulmonary bypass and without associated procedures. INTERVENTIONS: Patients were assigned to the obese group if their body mass index was greater than 30 for men and 28.6 for women, according to the World Health Organization indications. MEASUREMENTS AND MAIN RESULTS: Preoperative and intraoperative variables were collected and checked for homogeneity of the groups. Postoperative outcome was assessed on the basis of intubation time, intensive care unit (ICU) and postoperative hospital stay, mortality rate, and incidence of transfusions, reoperations, low-output syndrome, minor and major neurologic dysfunction, minor and major lung dysfunctions, renal dysfunction, and superficial and deep infections. The effect of obesity on postoperative outcome was tested with a multivariate logistic regression analysis. Obese and control patients had the same intubation time and ICU and postoperative hospital stay. Mortality and all major complications occurred with the same incidence in the two groups. Obese patients had a significantly (p < 0.05) greater rate of superficial infections and more (24.1% v 7.4%; p < 0.001) minor lung complications. Conversely, they had a significantly lower transfusion rate (27.5% v42.7%; p < 0.01). CONCLUSION: Obese patients had only minor complications after coronary artery surgery. The large body surface area because of obesity protects them against the hemodilution-related transfusion risk.

Adult↗

Gabexate mesilate and antithrombin III for intraoperative anticoagulation in heparin pretreated patients.

Thirty patients scheduled for elective myocardial revascularization and having undergone preoperative heparin treatment have been admitted to this prospective, randomized study. The aim of the study was to test two different strategies for preserving circulating antithrombin III (AT-III) during cardiopulmonary bypass. Patients in the control group (group C, n = 10) were treated with a standard heparinization (300 IU/kg). Patients in group A (n = 10) received the same management plus two doses of purified antithrombin III (1000 IU each). Patients in group GA received 200 IU/kg heparin and a continuous infusion of heparin (100 IU/kg/h) and gabexate mesilate (2 mg/kg/h) plus the same dose of antithrombin III as group A. Both group A and group GA demonstrated a preservation of circulating AT-III when compared to group C; this effect was more pronounced in group GA. The total heparin dosage was less in group GA than in groups A and C. Purified AT-III administration is recommended in heparin pretreated patients; the addition of gabexate mesilate to this protocol decreases the heparin requirement and increases the AT-III preservation.

Aged↗

Predictors for heparin resistance in patients undergoing coronary artery bypass grafting.

Heparin resistance (HR) is a common event in cardiac operations. At present, no clear recognition of the risk factors for HR has been reached. The aim of this study was to determine a predictive model for HR, based on the preoperative patient's profile. Two hundred consecutive patients scheduled for elective coronary artery bypass operations were enrolled in a prospective trial. Demographics, type of preoperative anticoagulation therapy and preoperative coagulation profile were collected and statistically analysed with respect to the evidence of a HR. Heparin resistance was defined as at least one activated clotting time < 400 s after heparinization and/or the need for purified antithrombin III (AT-III) administration. With a multivariate analysis we could identify five predictors for HR: AT-III < or = 60%; preoperative subcutaneous heparin therapy; intravenous heparin therapy; platelet count > or = 300000 cells/mm3; age > or = 65 years. We conclude that HR is a predictable event. In the presence of all the risk factors, the likelihood of HR is 99%; in the absence of all of them, it is 10%. Predicting HR allows us to apply many possible therapeutic strategies.

Aged↗

Postoperative analgesia for early extubation after cardiac surgery. A prospective, randomized trial.

BACKGROUND: Early extubation after cardiac surgery is a procedure recently gaining interest due to its ability to shorten intensive care unit and hospital stay and to limit the operation-related costs. Its use, however, raised new problems in terms of pain control in the early postoperative course, due to the need for limiting opioid analgesia. This study deals with non-opioid pain control after cardiac surgery and early extubation. METHODS: Prospective, randomized trial aimed to investigate the effectiveness of three intravenous analgesic drugs (ketorolac, 60 mg i.v.; propacetamol, 2 g i.v.; tramadol, 200 mg i.v.) for the management of postoperative pain in early extubated cardiac surgical patients. Each treatment group comprised 20 patients. RESULTS: The pain assessment (5-item verbal scale) demonstrated a significant (p < 0.05) lower value in patients treated with ketorolac vs propacetamol, while patients treated with tramadol did not significantly differ from the other two groups. There was a significantly (p < 0.05) higher rate of patients with severe pain in propacetamol group. Patients treated with tramadol had a significantly (p < 0.01) higher PaCO2 (48 +/- 6 mmHg) versus patients treated with ketorolac (43.4 +/- 3.7 mmHg) or propacetamol (42.9 +/- 3.4 mmHg). CONCLUSIONS: Tramadol and ketorolac seem to be the best options for treating postoperative pain in the specific setting of early extubation after cardiac surgery; high doses of tramadol may result in a significant even if clinically not relevant respiratory depression.

Analgesics↗