Avio Maria Perna

High-dose aprotinin: hemostatic effects in open heart operations.

Two groups of patients were prospectively studied to evaluate the hemostatic effects of high-dose aprotinin in open heart operations. Group A patients (n = 22) received aprotinin during the entire surgical procedure. Group B patients (n = 12) served as controls. The groups were homogeneous for base variables and for cardiopulmonary bypass duration. Postoperative bleeding was lower in group A (mean, 486 mL) than in group B (830 mL) (p less than 0.01). The need for banked blood decreased by approximately half in the aprotinin patients (mean: group A, 213 mL; group B, 409 mL). Hemoglobin levels were similar in the two groups (postoperative day 7: group A, 11.29 g/100 mL; group B, 11.26 g/100 mL; NS). Platelet count decreased at the end of operation in both groups (99,000 and 95,000/mL, respectively; NS) and then increased beyond baseline levels before discharge. No complications were observed that could be attributed to aprotinin. In conclusion, we believe that the use of high-dose aprotinin is safe and effective. It decreases blood loss and reduces the need for banked blood in cardiac operations, particularly in select groups of patients (eg, those undergoing reoperation, Jehovahs Witnesses, those with renal failure).

Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload

Abstract—Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (n=15) and in sham-operated animals (n=15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, P <0.05), and significant increase of myocyte length (+29% at 3 months, P <0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (+117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.

Beneficial Effects of Poly (ADP-ribose) Polymerase Inhibition Against the Reperfusion Injury in Heart Transplantation

We investigated the effect of 3-aminobenzamide (3-AB), an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP), against early ischemia/reperfusion (IR) injury in heart transplantation. In our experimental model, rat heart subjected to heterotopic transplantation, low temperature global ischemia (2 h) was followed by an in vivo reperfusion (60 min). In these conditions, and in the absence of 3-AB treatment, clear signs of oxidative stress, such as lipid peroxidation, increase in protein carbonyls and DNA strand breaks, were evident; PARP was markedly activated in concomitance with a significant NAD + and ATP depletion. The results of microscopic observations (nuclear clearings, plasma membrane discontinuity), and the observed rise in the serum levels of heart damage markers, suggested the development of necrotic processes while, conversely, no typical sign of apoptosis was evident. Compared to the effects observed in untreated IR heart, the administration of 3-AB (10 mg/kg to the donor and to the recipient animal), but not that of its inactive analogue 3-aminobenzoic acid, significantly modified the above parameters: the levels of oxidative stress markers were significantly reduced; PARP activation was markedly inhibited and this matched a significant rise in NAD + and ATP levels. PARP inhibition also caused a reduced release of the cardiospecific damage markers and attenuated morphological cardiomyocyte alterations, save that, in this condition, we noted the appearance of typical apoptotic markers: activation of caspase-3, oligonucleosomal DNA fragmentation, ISEL positive nuclei. Possible mechanisms for these effects are discussed, in any case the present results indicate that PARP inhibition has an overall beneficial effect against myocardial reperfusion injury, mainly due to prevention of energy depletion. In this context, the signs of apoptosis observed under 3-AB treatment might be ascribed to the maintenance of sufficient intracellular energy levels. These latter allow irreversible damages triggered during the ischemic phase to proceed towards apoptosis instead of towards necrosis, as it appears to happen when the energetic pools are depleted by high PARP activity.

Are macrophages involved in early myocardial reperfusion injury

BACKGROUND Neutrophils are the predominant phagocytes in the early stages of myocardial ischemia-reperfusion response and are also implicated in the development of tissue damage. This study examined the role of recruited macrophages in the evolution of this tissue injury. METHODS Farm pigs were subjected to 30 minutes of myocardial ischemia followed by 30 minutes of reperfusion. Biopsy samples were taken from the control, ischemic, and ischemic-reperfused left ventricle wall and processed for both morphologic and biochemical analyses. In situ production of tumor necrosis factor-alpha was evaluated by Western blot and immunofluorescence. A full hemodynamic evaluation was also performed. RESULTS Myocardial ischemia and early reperfusion caused marked neutrophil and macrophage tissue accumulation and tumor necrosis factor-alpha production by the injured tissue. Immunofluorescence studies allowed us to localize tumor necrosis factor-alpha predominantly in tissue-infiltrating macrophages. No depression in the global myocardial contractile function was observed, either during ischemia or after reperfusion. CONCLUSIONS These data suggest that the newly recruited macrophages within the ischemic and early post-ischemic myocardium may play a role in promoting neutrophil tissue infiltration and subsequent neutrophil-induced tissue dysfunction by producing tumor necrosis factor-alpha.

Poly(ADP-ribose) Polymerase Activation and Cell Injury in the Course of Rat Heart Heterotopic Transplantation

Free radicals and other reactive species generated during reperfusion of ischemic tissues may cause DNA damage and, consequently, the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP). An excessive PARP activation may result in a depletion of intracellular NAD + and ATP, hence cell suffering and, ultimately, cell death. The present study is aimed at clarifying the role of PARP in a heart transplantation procedure and the contribution of myocyte necrosis and/or apoptosis to this process. In our experimental model, rat heart subjected to heterotopic transplantation, low temperature global ischemia (2 h) was followed by an in vivo reperfusion (30 or 60 u min). Under these conditions clear signs of oxidative stress, such as lipoperoxidation and DNA strand breaks, were evident. In addition to a marked activation, accompanied by a significant NAD + and ATP depletion, PARP protein levels significantly increased after 60 u min of reperfusion. Ultrastructural analysis showed nuclear clearings, intracellular oedema and plasma membrane discontinuity. Other relevant observations were the absence of typical signs of apoptosis like caspase-3 activation and PARP cleavage, random DNA fragmentation, rise in serum levels of heart damage markers. Our results suggest that during heart transplantation, the activation of PARP, causing energy depletion, results in myocardial cell injury whose dominant feature, at least in our experimental model, is necrosis rather than apoptosis.

Clinically relevant cognitive impairment after cardiac surgery: a 6-month follow-up study

BACKGROUND AND PURPOSE The majority of studies on neuropsychological complications after cardiac surgery used the raw variation of selective tests scores to define the occurrence of cognitive decline. We prospectively estimated the frequency of cognitive impairment after cardiac surgery, with a particular emphasis on persistent and clinically relevant cognitive decline. Possible baseline and operative predictors were also evaluated. METHODS An extensive neuropsychological battery was administered to 110 patients (mean age 64.1+/-9.4 years; 70.9% males) undergoing cardiac surgery before and 6 months after the operation. After evaluating the variations in the cognitive performances, two independent neuropsychologists ranked the patients as unchanged-improved, mildly-moderately deteriorated, or severely deteriorated, using a global and functionally oriented judgement. The degree of the impairment was determined in relation to its impact on everyday life activities. RESULTS Ten patients (9.1%) were ranked as severely deteriorated, 22 (20%) as mildly-moderately deteriorated, and 78 (70.9%) as unchanged-improved. Cognitively impaired patients were older (p=0.031), more often females (p=0.005), with a low education level (p=0.013). At multivariate analysis, female gender (odds ratio (OR) 6.14, 95% confidence interval (95% CI) 2.16-17.50), baseline use of beta-blockers (OR 4.55, 95% CI 1.30-15.92), and PaO2 at arrival in intensive care unit (OR for 1 mm Hg increment 1.012, 95% CI 1.004-1.020) were significant predictors of cognitive impairment of any degree. Positive predictors of severe cognitive impairment were history of hypertension (OR 5.33, 95% CI 1.03-27.64) and PaO2 at arrival intensive care unit (OR for 1 mm Hg increment 1.020, 95% CI 1.006-1.035), while education was protective (OR per year of increment 0.53, 95% CI 0.31-0.90). CONCLUSIONS A considerable proportion of cardiac surgery patients may undergo clinically relevant cognitive impairment. The knowledge of variables influencing cognitive outcome is essential for the adoption of preventive measures.

Endothelin receptors in adult human and swine isolated ventricular cardiomyocytes

The present study aimed to investigate endothelin-1 (ET-1) receptors in human and swine cardiomyocytes with binding studies using ET(A) and ET(B) selective receptor antagonists (BMS-182874 and BQ-788, respectively). Cell distribution of mRNA expression for ET(A) and ET(B) subtypes was investigated by in situ hybridization using specific cDNA probes. The 1251-ET-1 binding, which reached equilibrium in about 120 min (Kobs = 0.051+/-0.003 min(-1)), was only partially displaceable by the addition of a large excess of ET-1 (about 15% with a half-life of 20 min). In equilibrium binding studies, 125I-ET-1 had a Kd of 0.43+/-0.08 nM and a maximum binding (Bmax) of 42.8+/-6.6 fmol/mg protein. ET(A) and ET(B) receptors are represented in human and swine cardiomyocytes with an 85:15 ratio as indicated by the biphasic pattern of competition of both BMS-182874 and BQ-788. In situ hybridization studies confirmed that myocytes mainly expressed mRNA for ET(A), whereas expression of mRNA for the ET(B) subtype was documented in non-myocyte cells. These results showed that ET-1 binds with high affinity and poor reversibility to specific receptors, in both human and swine isolated ventricular cardiomyocytes, without significant species differences.

Intramural hematoma of the aorta: diagnosis and treatment

OBJECTIVE Increasing use of modern high-resolution imaging techniques yields to describe very early stages of aortic pathology which, if left untreated, may lead to overt aortic dissection. One typical example is aortic intramural hematoma (IMH) with a limited number of cases described in the literature and uncertainties still existing about the most appropriate treatment. Purpose of our study is to report our experience in the evaluation and treatment of IMHs. METHODS From 1991 to 1999 175 patients were conveyed to our centre for aortic dissection; in nine of them diagnosis of acute IMH was performed. RESULTS Diagnosis was obtained by means of conventional CT scan of the chest. All the patients underwent surgery, one patient died (11%). At the follow-up (mean 31 months) eight patients were alive and well and did not require any other cardiac surgery. CONCLUSIONS The possibility to progress to overt aortic dissection may explain the need to an early diagnosis in the treatment of acute IMHs. Immediate surgical treatment is, in our experience, the preferred therapeutic option.

Totally endoscopic subxiphoid pericardioscopy: early steps with a new surgical tool

BackgroundPericardial pathology still has challenging diagnostic and treating issues. To reduce surgical trauma and pain for the patient, the authors developed a totally endoscopic echo-guided approach for both diagnostic and operative pericardioscopy.MethodsThree steps moved from animal model (8 pigs) through concomitant open-chest interventions (7 patients) to closed-chest interventions for 10 patients with a diagnosis of severe pericardial effusion.ResultsA lesion of the right ventricle in one patient (10%) due to imperfect preoperative pericardial visualization needed sternotomy for repair. All the patients, except the aforementioned one, underwent surgery with local anesthesia or mild sedation. No method-related mortality was reported.ConclusionThe closed-chest nonintrapleural approach to the pericardium may represent an evolution, with a positive impact on the treatment of this pathology. Therapeutic maneuvers with rigid instruments in nonintubated patients are possible. Accurate patient selection and technical refinement should increase the safety and effectiveness of the method.

Revascularization of the right ischemic kidney by gastroduodenal artery

Hepatorenal bypass can successfully accomplish revascularization of the right renal artery when the aorta or the iliac vessels cannot be used for a standard renal bypass or renal autotransplantation. The use of the hepatic circulation can be increased by the gastroduodenal to renal artery bypass procedure. Herein we report a clinical case of severe hypertension in a patient with a solitary functional kidney and an extensive atheromatous alteration of the aortoiliac segment. It has been corrected by means of a gastroduodenal end-to-side renal saphenous vein bypass graft.