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.

Influence of Suture on Peripheral Nerve Regeneration and Collagen Production at the Site of Neurorrhaphy: An Experimental Study

BACKGROUND: Restoration of nerve continuity and effective maintenance of coaptation are considered fundamental principles of end-to-end peripheral nerve repair. OBJECTIVE: To evaluate the influence of the number of stitches on axonal regeneration and collagen production after neurorrhaphy. METHODS: Thirty male Wistar rats were equally divided into 3 groups and were all operated on with the right sciatic nerve exposed. In 2 groups, the nerve was sectioned and repaired by means of 3 (group B) or 6 (group C) epineurium sutures with 100 monofilament nylon. One group (group A) was used as a control. Each animal from groups B and C underwent electrophysiological evaluation with motor action potential recordings before nerve section and again at an 8-week interval after neurorrhaphy. Nerve biopsy specimens were used for histomorphometric assessment of axonal regeneration and quantification of collagen at the repair site. RESULTS: Animals from group C had significantly lower motor action potential conduction velocities compared with control animals (P = .02), and no significant difference was seen between groups B and C. Parameters obtained from morphometric evaluation were not significantly different between these 2 groups. Type I collagen and III collagen in the epineurium were significantly higher in group C than in either the control group (P = .001 and P = .003) or group B (P = .01 and P = .02). No differences were identified for collagen I and III in the endoneurium. CONCLUSION: Using 6 sutures for nerve repair is associated with worse electrophysiological outcomes and higher amounts of type I and III collagen in the epineurium compared with control. Neurorraphy with 6 stitches is also related to a significant increase in epineurium collagen I and III compared with 3-stitch neurorraphy.

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.

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.

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.

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.

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

Exercise Training Reduces Sympathetic Modulation on Cardiovascular System and Cardiac Oxidative Stress in Spontaneously Hypertensive Rats

BACKGROUND Spontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether ET alters cardiac sympathetic modulation on cardiovascular system and whether a correlation exists between cardiac oxidative stress and hypertrophy. METHODS Male SHRs (15-weeks old) were divided into sedentary hypertensive (SHR, n = 7) and exercise-trained hypertensive rats (SHR-T, n = 7). Moderate ET was performed on a treadmill (5 days/week, 60 min, 10 weeks). After ET, cardiopulmonary reflex responses were assessed by bolus injections of 5-HT. Autoregressive spectral estimation was performed for systolic arterial pressure (SAP) with oscillatory components quantified as low (LF: 0.2-0.75 Hz) and high (HF:0.75-4.0 Hz) frequency ranges. Cardiac NE concentration, lipid peroxidation, antioxidant enzymes activities, and total nitrates/nitrites were determined. RESULTS ET reduced mean arterial pressure, SAP variability (SAP var), LIF of SAP, and cardiac hypertrophy and increased cardiopulmonary reflex responses. Cardiac lipid peroxidation was decreased in trained SHRs and positively correlated with NE concentrations (r= 0.89, P < 0.01) and heart weight/body weight ratio (r= 0.72, P < 0.01), and inversely correlated with total nitrates/nitrites (r= -0.79, P < 0.01). Moreover, in trained SHR, cardiac total nitrates/nitrites were inversely correlated with NE concentrations (r= -0.82, P < 0.01). CONCLUSIONS ET attenuates cardiac sympathetic modulation and cardiac hypertrophy, which were associated with reduced oxidative stress and increased nitric oxide (NO) bioavailability. Am J Hypertens 2008;21:1138-1193 (C) 2008 American Journal of Hypertension, Ltd.

Comparative effects of wavelengths of low-power laser in regeneration of sciatic nerve in rats following crushing lesion

Peripheral nerves are structures that, when damaged, can result in significant motor and sensory disabilities. Several studies have used therapeutic resources with the aim of promoting early nerve regeneration, such as the use of low-power laser. However, this laser therapy does not represent a consensus regarding the methodology, thus yielding controversial conclusions. The objective of our study was to investigate, by functional evaluation, the comparative effects of low-power laser (660 nm and 830 nm) on sciatic nerve regeneration following crushing injuries. Twenty-seven Wistar rats subjected to sciatic nerve injury were divided into three groups: group sham, consisting of rats undergoing simulated irradiation; a group consisting of rats subjected to gallium-aluminum-arsenide (GaAlAs) laser at 660 nm (10 J/cm(2), 30 mW and 0.06 cm(2) beam), and another one consisting of rats subjected to GaAlAs laser at 830 nm (10 J/cm(2), 30 mW and 0.116 cm(2)). Laser was applied to the lesion for 21 days. A sciatic functional index (SFI) was used for functional evaluation prior to surgery and on days 7, 14, and 21 after surgery. Differences in SFI were found between group 660 nm and the other ones at the 14th day. One can observe that laser application at 660 nm with the parameters and methods utilised was effective in promoting early functional recovery, as indicated by the SFI, over the period evaluated.

LOCAL LOW POWER LASER IRRADIATION ACCELERATES THE REGENERATION OF THE FIBULAR NERVE IN RATS

Objective: To study the influence of low power GaAsAl laser irradiation on the regeneration of a peripheral nerve, following a controlled crush injury. Material and methods: The right common fibular nerve of 30 Wistar rats was submitted to a crush injury with an adjustable load forceps (5 000 g, 10 minutes of application). The animals were divided into three groups (n=10), according to the postoperative procedure (no irradiation; sham irradiation; effective irradiation). Laser irradiation (830 nm wave-length; 100 mW emission power; continuous mode; 140 J/cm(2)) was started on the first postoperative day and continued over 21 consecutive days. Body mass, time spent on the walking track and functional peroneal index (PFI) were analyzed based on the hind footprints, both preoperatively and on the 21st postoperative day. Results: Walking time and PFI significantly improved in the group that received effective laser irradiation, despite the significant gain in body mass between the pre- and post-operative periods. Conclusion: Low Power GaAsAl laser irradiation, with the parameters used in our study, accelerated and improved fibular nerve regeneration in rats.

INFLUENCE OF LASER RADIATION IN NERVE REGENERATION IN DIFFERENT TREATMENT SITES

Objective: This study seeks to determine, through functional gait assessment in different irradiation sites, the influence of a low-intensity GaAsAl laser beam on an injury caused by crushing the peroneal nerve in rats. Methods: 53 rats were used, which were divided into six groups: normal, injured and untreated, injured and treated using placebo, injured and treated in the bone marrow, injured and treated in the nerve, and injured and treated in both (nerve and bone marrow). The peroneal nerve was crushed using a pair of tweezers, and subsequently treated with laser for 28 consecutive days. The functional gait evaluation analyzed the footprints, which were recorded with a video camera on an acrylic bridge in the preoperative period, and on postoperative days 14, 21 and 28, and assessed using PFI formula software. Results: In the functional gait evaluation, significant differences were found only on postoperative day 14. Conclusion: Based on the functional gait evaluation, low-intensity GaAs AI irradiation was able to accelerate and reinforce the process of peripheral nerve regeneration in rats on postoperative day 14, both in the bone marrow- and in the nerve-treated groups.

Effect of the duration of daily aerobic physical training on cardiac autonomic adaptations

The present study has investigated in conscious rats the influence of the duration of physical training sessions on cardiac autonomic adaptations by using different approaches; 1) double blockade with methylatropine and propranolol; 2) the baroreflex sensitivity evaluated by alternating bolus injections of phenylephrine and sodium nitroprusside; and 3) the autonomic modulation of HRV in the frequency domain by means of spectral analysis. The animals were divided into four groups: one sedentary group and three training groups submitted to physical exercise (swimming) for 15, 30, and 60 min a day during 10 weeks. All training groups showed similar reduction in intrinsic heart rate (IHR) after double blockade with methylatropine and propranolol. However, only 30-min and 60-min physical training presented an increase in the vagal autonomic component for determination of basal heart rate (HR) in relation to group sedentary. Spectral analysis of HR showed that the 30-min and 60-min physical training presented the reduction in low-frequency oscillations (LF = 0.20-0.75 Hz) and the increase in high-frequency oscillations (HF = 0.75-2.5 Hz) in normalized units. These both groups only showed an increased baroreflex sensitivity to tachycardiac responses in relation to group sedentary, however when compared, the physical training of 30-min exhibited a greater gain. In conclusion, cardiac autonomic adaptations, characterised by the increased predominance of the vagal autonomic component, were not proportional to the duration of daily physical training sessions. In fact, 30-minute training sessions provided similar cardiac autonomic adaptations, or even more enhanced ones, as in the case of baroreflex sensitivity compared to 60-minute training sessions. (C) 2010 Elsevier B.V. All rights reserved.

Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms

Familial hypertrophic cardiomyopathy (FHC) is frequently caused by cardiac myosin-binding protein C (cMyBP-C) gene mutations, which should result in C-terminal truncated mutants. However, truncated mutants were not detected in myocardial tissue of FHC patients and were rapidly degraded by the ubiquitin-proteasome system (UPS) after gene transfer in cardiac myocytes. Since the diversity and specificity of UPS regulation lie in E3 ubiquitin ligases, we investigated whether the muscle-specific E3 ligases atrogin-1 or muscle ring finger protein-1 (MuRF1) mediate degradation of truncated cMyBP-C. Human wild-type (WT) and truncated (M7t, resulting from a human mutation) cMyBP-C species were co-immunoprecipitated with atrogin-1 after adenoviral overexpression in cardiac myocytes, and WT-cMyBP-C was identified as an interaction partner of MuRF1 by yeast two-hybrid screens. Overexpression of atrogin-1 in cardiac myocytes decreased the protein level of M7t-cMyBP-C by 80% and left WT-cMyBP-C level unaffected. This was rescued by proteasome inhibition. In contrast, overexpression of MuRF1 in cardiac myocytes not only reduced the protein level of WT- and M7t-cMyBP-C by > 60%, but also the level of myosin heavy chains (MHCs) by > 40%, which were not rescued by proteasome inhibition. Both exogenous cMyBP-C and endogenous MHC mRNA levels were markedly reduced by MuRF1 overexpression. Similar to cardiac myocytes, MuRF1-overexpressing (TG) mice exhibited 40% lower levels of MHC mRNAs and proteins. Protein levels of cMyBP-C were 29% higher in MuRF1 knockout and 34% lower in TG than in WT, without a corresponding change in mRNA levels. These data suggest that atrogin-1 specifically targets truncated M7t-cMyBP-C, but not WT-cMyBP-C, for proteasomal degradation and that MuRF1 indirectly reduces cMyBP-C levels by regulating the transcription of MHC.