L.S. De Santo

Role of Sildenafil in Acute Posttransplant Right Ventricular Dysfunction: Successful Experience in 13 Consecutive Patients

BACKGROUND Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. METHODS Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. RESULTS Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. CONCLUSION Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.

Coronary artery bypass grafting in patients with severe left ventricular dysfunction: A prospective randomized study on the timing of perioperative intraaortic balloon pump support

In this prospective trial the results of preoperative and intraoperative IABP in coronary artery bypass graft (CABG) patients with low left ventricular ejection fraction (LVEF) were compared. Sixty CABG patients with preoperative LVEF ≤0.30 were enrolled: in group A patients (n=30) IABP was started within 2 hours preoperatively; in group B (n=30) it was instituted intraoperatively before weaning from cardiopulmonary bypass. Cardiac performance was assessed through Swan-Ganz catheter monitoring and daily echocardiography. Hospital survival, length of IABP support, intubation, ICU and hospital stay, need for postoperative inotropic drugs and incidence of myocardial infarction were compared between the two groups. Survival in group A patients proved significantly higher (P=0.047). Cardiac performance after myocardial revascularization improved in both groups with significantly better outcomes in group A patients (p<0.001). Doses of inotropic drugs (dobutamine, enoximone) were lower in group A (P=0.001; P=0.004) and duration shorter (p<0.001; p<0.001). No major IABP-related complication was observed.

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 Nε-(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.

Basal lamina structural alterations in human asymmetric aneurismatic aorta

Basal lamina (BL) is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation. We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens. We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study. We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RT-PCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin alpha2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type IV is more evident in the concavity and Tenascin in the convexity.

Berengario da Carpi

Berengario da Carpi was magister of anatomy and surgery at the University of Bologna from 1502 to 1527. Eustachio and Falloppia defined him as ‘the restaurator of anatomy’. He was a great surgeon, anatomist and physician of illustrious patients including Lorenzo II dei Medici, Giovanni dalle Bande Nere, Galeazzo Pallavicini, Cardinal Colonna, and Alessandro Soderini. He had strong links to the intellectuals of his time (Forni, Bonamici, Manuzio, Pomponazzi) as well as with the Medici family. He was respected by the Popes Julius II, Leo X and Clement VII. His main contributions are the Isogogae Breves, De Fractura calvae sive cranei, and the illustrated Commentaria on the Anatomy of Mondino de Liucci, a textbook utilized for more than 200 years, which Berengario aimed to restore to its initial text. The Commentaria constitutes the material for the last part of this paper which concludes with a personal translation of some passages on ‘The kidney’, where the author gives poignant examples of experimental ingenuity.

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 + 0.75mg/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±52×103/μl versus 131±70×103/μl; P=0.045). The amount of postoperative bleeding was 525ml versus 680ml at 24hrs (p <0.001), 819ml versus 1102ml at 48hrs, (p <0.001), 963ml versus 1294ml at 72hrs, (p <0.045) (group A versus group B respectively). Crystalloid priming with low-dose albumin reduces postoperative bleeding.

Renal Reserve Is Normal in Patients with Dilative Cardiomyopathy Waiting for Heart Transplantation

Renal reserve was explored by means of an oral protein load (2 g/kg body weight) under the form of cooked red meat in a group of 9 patients with end-stage heart failure (ESHF), class III of the New York Heart Association receiving loop diuretics and angiotensin-converting enzyme (ACE) inhibitors, and in a group of 18 healthy controls (HC) matched for age, gender, and height under an identical dietary regimen providing 40 cal/kg per day, 1 g/kg body weight of protein per day, Na 120 mmol/day, and K 50 mmol/day. Baseline glomerular filtration rate averaged 109.5±9.89 ml/min×1.73 m2 in HC and 71.9±8.8 ml/min×1.73 m2 in ESHF. Renal plasma flow averaged 540±27 ml/min×1.73 m2 in HC and 235±47 ml/min×1.73 m2 in ESHF. The filtration fraction was significantly higher in ESHF (p<0.01). Renal reserve averaged 26.03±3.28 ml/min×1.73 m2 in HC and 27.2±7.12 ml/min×1.73 m2 (not significant). Renal reserve averaged 123.9±2.9% in HC and 137.3±6.68% in ESHF (not significant). The filtration capacity was significantly higher in HC (p<0.001). The data point to a normalcy of renal reserve in ESHF which may depend on the chronic use of ACE inhibitors.

Long term clinical and echocardiographic results of isolated aortic valve replacement in elderly patients

Results after isolated aortic valve replacement with bileaflet prostheses in patients over 70 years old were reviewed. One-hundred-twenty-eight elderly patients were operated on between January 1988 and January 2000. Patients with associated heart disease were excluded from the study. Preoperative data, early and late postoperative mortality, all valve related complications and data concerning anticoagulation status were recorded. Hospital mortality was 9.3%. Mean follow-up time was 60.98±2.23 months. Twelve-year actuarial survival was 69.6±0.08%. Valve related and anticoagulation related complication rates (0.8% and 1.6% respectively) and actuarial freedom (99±0.009 both) were low, as well as the mean interval between consecutive INR checks (18.39±1.90 days) and the mean INR value (2.17±0.135). Late echocardiographic results showed low postoperative mean transprosthetic gradients (15.48±0.94). Bileaftlet prostheses in the elderly can achieve excellent results with a low incidence of anticoagulation related complications and low risk of reoperation. Older age can no longer be considered a contraindication to bileaftlet prosthesis implant.

Bioelectrical impedance analysis before and after Novacor implantation.

In this study Bioelectrical Impedance Analysis was performed in 5 patients with end stage heart failure in whom a left ventricular assist device (Novacor) was successfully implanted. Whole body measurements of bioelectrical indices resistance and reactance were taken before surgery and 3, 7, 12, and 15 days after it. After surgery there was a significant decrease in reactance, indicating a shift of body fluids from intra- to extra-cellular space.