The Potential Impact of Using Donations After Cardiac Death on the Liver Transplantation Program and Waiting List in the State of Sao Paulo, Brazil

Liver transplantation was first performed at the University of Sao Paulo School of Medicine in 1968. Since then, the patient waiting list for liver transplantation has increased at a rate of 150 new cases per month. Liver transplantation itself rose 1.84-fold (from 160 to 295) from 1988 to 2004. However, the number of patients on the liver waiting list jumped 2.71-fold (from 553 to 1500). Consequently, the number of deaths on the liver waiting list moved to a higher level, from 321 to 671, increasing 2.09-fold. We have applied a mathematical model to analyze the potential impact of using a donation after cardiac death (DCD) policy on our liver transplantation program and on the waiting list. Five thousand one hundred people died because of accidents and other violent causes in our state in 2004; of these, only 295 were donors of liver grafts that were transplanted. The model assumed that 5% of these grafts would have been DCD. We found a relative reduction of 27% in the size of the liver transplantation waiting list if DCD had been used by assuming that 248 additional liver transplants would have been performed annually. In conclusion, the use of DCD in our transplantation program would reduce the pressure on our liver transplantation waiting list, reducing it by at least 27%. On the basis of this model, the projected number of averted deaths is about 41,487 in the next 20 years. Liver Transpl 14:1732-1736, 2008. (C) 2008 AASLD.

Gender-Specific Differences in Fetal Cardiac Troponin T in Pregnancies Complicated by Placental Insufficiency

Background: Placental insufficiency and fetal growth restriction may lead to fetal hypoxia and acidemia, which result in fetal cardiac injury. Objective: The goal of this study was to compare the levels of fetal cardiac troponin T (cTnT) at birth and fetal Doppler parameters according to fetal gender in pregnancies complicated by placental insufficiency before 34 weeks` gestation. Methods: Between March 2007 and November 2010, singleton pregnancies with placental insufficiency characterized by abnormal umbilical artery Doppler results were prospectively studied. All the patients delivered by cesarean section, and Doppler examinations were performed up to 48 hours before birth. Immediately after delivery, umbilical artery blood samples were obtained for fetal cTnT measurements. Results: Fifty high-risk pregnant women met the study criteria. The study groups were as follows: group 1 consisted of 23 male fetuses (46%) and group 2 consisted of 27 female fetuses (54%). cTnT levels were significantly higher in the group of male fetuses (median, 0.14; range, 0.01-0.85) compared with the group of female fetuses (median, 0.05; range, 0.01-0.27) (P = 0.039). In the group of male fetuses, Doppler results of the ductus venosus assessment revealed values of pulsatility index for veins >= 1.0 in 15 male fetuses (65.2%) and 9 female fetuses (33.3%) (P = 0.032). Conclusions: Fetal gender was associated with cTnT level at birth in pregnancies complicated by placental insufficiency before 34 weeks` gestation, although the Doppler findings did not support gender differences. The fetal cardiac compromise and cardiac injury may be influenced by fetal gender, suggesting differences in the cardiovascular response to fetal hypoxia. (Gend Med. 2011;8:202-208) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.

Intracardiac Cavopulmonary Connection in Patients with Univentricular Heart Using Intra-atrial Lateral Tunnel and Intra-atrial Conduit Techniques

Background: In this study, we analyzed the time course of hemodynamic efficiency and follow-up in Fontan candidates who underwent the bidirectional Glenn procedure for staged intracardiac cavopulmonary connection (ICPC). Methods: Between 1991 and 2008, 52 patients with univentricular heart (mean age, 3.3 years; range, 2-8 years; 27 female patients [51.9%]) underwent ICPC. The cardiac malformations were as follows: tricuspid atresia, 25 cases (48.0%); common ventricle, 16 cases (30.7%); and pulmonary atresia with intact ventricular septum, 11 cases (21.1%). The intracardiac cavopulmonary procedure was indicated for all 52 cases. In 42 patients (80.7%), an intra-atrial lateral tunnel was constructed with a bovine pericardium patch. In the last 10 consecutive cases (19.3%), we performed a modified surgical technique in which we implanted an intra-atrial corrugated bovine pericardium tube sutured around the superior and inferior vena cava ostium. In all cases, a 4-mm fenestration was made to reduce the intratunnel pressure. All 52 patients had previously undergone a Glenn operation. Results: There were 2 hospital deaths (3.8%) and no recorded late deaths. During the follow-up, all patients were medicated with antiplatelet drugs. To evaluate the hemodynamic performance, we used Doppler echocardiography, computed tomography, and magnetic nuclear resonance studies. There were no prosthesis thromboses during this follow-up period. To evaluate cardiac arrhythmias, we conducted a Holter study. The last 10 patients with an intra-atrial conduit (IAC) presented with sinus rhythm and no arrhythmias during the last 4 years. The 50 surviving patients (96.1%) have been followed up for 6 to 204 months; all these patients are free of reoperation. Conclusion: The Glenn operation, which is performed at an early age, prepares the pulmonary bed to receive the ICPC. The midterm results of the intracardiac Fontan procedure seem to be good. The modified surgical procedure (IAC) can be a good alternative technique to the Fontan procedure in suitable patients.

Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N = 62), bipolar disorder (N = 26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.

CENTRAL N-ACETYLCYSTEINE EFFECTS ON BAROREFLEX IN JUVENILE SPONTANEOUSLY HYPERTENSIVE RATS

In this study, we evaluated the acute effects of central NAC administration on baroreflex in juvenile SHR and Wistar Kyoto (WKY) rats. Male SHR and WKY rats (8 10 weeks old) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. After basal MAP and HR recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 mu g/kg, bolus) and a depressor dose of sodium nitroprusside (SNP, 50 mu g/kg, bolus). Baroreflex was evaluated before, 5, 15, 30 and 60 minutes after NAC injection into the 4th V. Vehicle treatment did not change baroreflex responses in WKY and SHR. Central NAC slightly but significantly increased basal HR at 15 minutes and significantly reduced PHE-induced increase in MAP 30 and 60 minutes after NAC injection (p < 0.05) in WKY rats. In relation to SHR, NAC decreased HR range 15 and 30 minutes after its administration. In conclusion, acute NAC into the 4th V does not improve baroreflex in juvenile SHR.

Changes in plasma free fatty acid levels in septic patients are associated with cardiac damage and reduction in heart rate variability

Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. Thirty-one patients with sepsis were included. The patients were divided into two groups: survivors(n = 12) and nonsurvivors (n = 19). The following associations were investigated: (a) troponin I elevation and HRV reduction and (b) clinical evolution and HRV index, plasma troponin, and plasma FFA levels. Initial measurements of C-reactive protein and gravity Acute Physiology and Chronic Health Evaluation scores were similar in both groups. Overall, an increase in plasma troponin level was related to increased mortality risk. From the first day of study, the nonsurvivor group presented a reduced left ventricular stroke work systolic index and a reduced low frequency (LF) that is one of HRV indexes. The correlation coefficient for LF values and troponin was r(2) = 0.75 (P < 0.05). All patients presented elevated plasma FFA levels on the first day of the study (5.11 +/- 0.53 mg/mL), and this elevation was even greater in the nonsurvivor group compared with the survivors (6.88 +/- 0.13 vs. 3.85 +/- 0.48 mg/mL, respectively; P < 0.05). Cardiac damage was confirmed by measurement of plasma troponin I and histological analysis. Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: The MONICA/KORA Augsburg cohort study

Background and Aim: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. Methods and Results: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n = 833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n = 36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n = 21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). Conclusions: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes. (C) 2009 Elsevier B.V. All rights reserved.

Salt-Induced Cardiac Hypertrophy and Interstitial Fibrosis Are Due to a Blood Pressure-Independent Mechanism in Wistar Rats

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg.kg(-1).d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg.kg(-1).d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding. J. Nutr. 140: 1742-1751, 2010.

Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained beta-adrenergic hyperactivity

Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by beta-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor alpha, interleukin-6, interleukin-10 and transforming growth factor beta(1) (TGF-beta(1)) in the tissue. NF-kappa B expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor alpha and interleukin-6, as well as TGF-beta(1) mRNA, were increased. In addition, the NF-kappa B expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-beta(1) mRNA. Thus, exercise training in a model of beta-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance.

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

Background: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Results: Asymptomatic patients with normal myocardial scans (n = 57) had significantly fewer cardiac events (log-rank = 0.0002) and deaths (log-rank = 0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n = 76) and individuals with CAD (n = 34) documented angiographically. CAD increased the probability of events (HR = 2.27, % CI 1.007-5.11; p = 0.04). The incidence of cardiac events (log-rank = 0.349) and deaths (log-rank = 0.588) was similar among patients treated medically (n = 23) or by intervention (n = 11). Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support pre-emptive myocardial revascularization for renal transplant candidates.

Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI-36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals. Methods and Results: In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (similar to 9 mu M plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29-50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24-34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71-109) ms to 98 (86-121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811-1220) seconds to 621 (549-761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7-20.5) Hz to 7.6 (2.9-8.8) Hz (P = 0.02, n = 6). Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency-dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation. (J Cardiovasc Electrophysiol, Vol. 20, pp. 796-802, July 2009).

Cavopulmonary anastomosis improves left ventricular assist device support in acute biventricular failure

Objective: Right ventricular failure during left ventricular assist device (WAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on right ventricular loading and WAD performance in a model of severe biventricular failure. Methods: LVAD support was performed by means of centrifugal pump implantation in 14 anesthetized dogs (20-30 kg) with severe biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to classical cavopulmonary anastomosis (Glenn shunt) or to control group and were maintained under WAD support for 2 h. Left and right atrial, right ventricular and systemic pressures were monitored, white total pulmonary flow was simultaneously recorded by transonic flowmeters located on the superior vena cava and pulmonary trunk. Blood gas and venous lactate determinations were also obtained. Results: Ventricular fibrillation maintenance resulted in acute WAD performance impairment after 90 min in the control group, while animals with Glenn circuit maintained normal WAD pump flow (55 +/- 13 ml kg(-1) min(-1) vs 21 +/- 4 ml kg(-1) min(-1), p < 0.001) and better peripheral perfusion (blood lactate of 29 +/- 10 pg/ml vs 46 +/- 9 pg/ml, p < 0.001). Left and right atrial pressures did not change significantly, while right ventricular pressure was tower in animals with Glenn circuit (13 +/- 3 mmHg vs 22 +/- 8 mmHg, p = 0.005). Right ventricular unloading with Glenn shunt also resulted in superior total pulmonary flow (59 +/- 13 ml kg(-1) min(-1) vs 17 +/- 3 ml kg(-1) min(-1), p < 0.001). Conclusion: The concomitant use of cavopulmonary anastomosis during LVAD support in a model of severe biventricular failure limited right ventricular overloading and resulted in better hemodynamic performance. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Influence of ventilatory settings on static and functional haemodynamic parameters during experimental hypovolaemia

Background and objective The influence of ventilatory settings on static and functional haemodynamic parameters during mechanical ventilation is not completely known. The purpose of this study was to evaluate the effect of positive end-expiratory pressure, tidal volume and inspiratory to expiratory time ratio variations on haemodynamic parameters during haemorrhage and after transfusion of shed blood. Methods Ten anaesthetized pigs were instrumented and mechanically ventilated with a tidal volume of 8 ml kg(-1), a positive end-expiratory pressure of 5 cmH(2)O and an inspiratory to expiratory ratio of 1 : 2. Then, they were submitted in a random order to different ventilatory settings (tidal volume 16 ml kg(-1), positive end-expiratory pressure 15 cmH(2)O or inspiratory to expiratory time ratio 2: 1). Functional and static haemodynamic parameters (central venous pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume and pulse pressure variation) were evaluated at baseline, during hypovolaemia (withdrawal of 20% of estimated blood volume) and after an infusion of withdrawn blood (posttransfusion). Results During baseline, a positive end-expiratory pressure of 15cmH(2)O significantly increased pulmonary artery occlusion pressure from 14.6 +/- 1.6 mmHg to 17.4 +/- 1.7 mmHg (P<0.001) and pulse pressure variation from 15.8 +/- 8.5% to 25.3 +/- 9.5% (P<0.001). High tidal volume increased pulse pressure variation from 15.8 8.5% to 31.6 +/- 10.4% (P<0.001), and an inspiratory to expiratory time ratio of 2: 1 significantly increased only central venous pressure. During hypovolaemia, high positive end-expiratory pressure influenced all studied variables, and high tidal volume strongly increased pulse pressure variation (40.5 +/- 12.4% pre vs. 84.2 +/- 19.1 % post, P<0.001). The inversion of the inspiratory to expiratory time ratio only slightly increased filling pressures during hypovolaemia, without without affecting pulse pressure variation or right ventricle end-diastolic volume. Conclusion We concluded that pulse pressure variation measurement is influenced by cyclic variations in intrathoracic pressure, such as those caused by augmentations in tidal volume. The increase in mean airway pressure caused by positive end-expiratory pressure affects cardiac filling pressures and also pulse pressure variation, although to a lesser extent. Inversion of the inspiratory to expiratory time ratio does not induce significant changes in static and functional haemodynamic parameters. Eur J Anaesthesiol 26:66-72 (c) 2009 European Society of Anaesthesiology.

Fetal Cardiac Troponin T as a Marker of Poor Prognosis in Nonimmune Hydrops Fetalis

Objective: Severe fetal anemia and cardiac compromise are important causes of nonimmune hydrops fetalis, and fetal recovery also depends on the degree of fetal heart compromise. The aim of this study was to report the fetal cardiac troponin T (cTnT) levels in cases of nonimmune fetal hydrops. Methods: Fetal cTnT was analyzed on 7 occasions in 5 cases of nonimmune fetal hydrops ( twice in 2 cases). Results: In 3 of 4 fetuses in which intrauterine death occurred, fetal cTnT levels were increased. The only fetus that survived in this series showed decreased levels of cTnT before birth. Conclusion: Fetal cTnT levels may be a marker of fetal prognosis in cases of fetal hydrops. Copyright (C) 2009 S. Karger AG, Basel