Determinants of left ventricular systolic function recovery after an acute coronary syndrome.

INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western societies. However, the factors that may influence left ventricular function (LVF) recovery after an acute coronary syndrome (ACS) are still unclear. OBJECTIVE: To identify variables that may influence LVF evolution one year after ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002 and with systolic dysfunction--defined as an echocardiographic ejection fraction (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program (FUP) or a general cardiology clinic (GC); patients from both groups were also randomly referred to a structured cardiac rehabilitation program (CRP). EF was re-assessed at one year. We compared differences between patients who recovered left ventricular function (EF > 45%; group 1) and those who did not (group 2). RESULTS: One year after discharge, 44.2% of the patients had recovered function. There were no significant differences between the groups in gender (77.7 vs. 76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking habits or family history. A previous history of cardiovascular events was more frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p = NS); no differences were found in coronary anatomy between the two groups. Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There were no differences in the use of angiotensin-converting enzyme inhibitors (83.3% vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There was no significant difference in LVF recovery between patients randomized to FUP or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at one year compared to 32.7% of patients not referred to the program (p = 0.009). Although EF improved in both groups, this improvement was greater in patients who completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular event and completion of a CRP were the only variables that influenced LVF recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an important therapeutic measure in patients with systolic dysfunction after ACS; our data suggest that these programs should be more widely used.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Tumour necrosis factor β gene polymorphisms in myasthenia gravis

Genetic analyses indicate that genes within the major histocompatibility complex (MHC) can be involved in susceptibility to autoimmune disease. To investigate the role of the tumour necrosis factor beta (TNFB) gene in myasthenia gravis (MG) susceptibility, we analysed an NcoI polymorphism within the TNFB gene in 63 MG patients and 93 healthy individuals. When patients were subdivided according to thymic pathology, we found differences between MG patients with thymic hyperplasia and thymoma versus controls. In MG patients with thymic hyperplasia we found a positive association with the TNFB*1 allele [Relative risk (RR): 2.6; P<0.001] and phenotype (RR: 1.8; P<0.005) and a negative association with the TNFB*2/2 genotype (RR: 0.2; P<0.001) when compared to the controls. On the other hand, in MG patients with thymoma we found a positive association with the TNFB*2/2 genotype (RR: 5.6; P<0.01) and a negative association with the TNFB*1 allele (RR: 0.3; P<0.05) and *1/2 genotype (RR: 0.2; P<0.01). These data suggest that the two different forms of MG can have different pathogenesis and that the TNFB gene could influence susceptibility to MG.     

Course and treatment of myasthenia gravis during pregnancy

OBJECTIVE: To evaluate the influence of myasthenia gravis (MG) on pregnancy and potential treatment risks for infants and mothers. BACKGROUND: MG frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Knowledge of the potential effects of 1) pregnancy on the course of MG and 2) the use of immunosuppressive drugs during pregnancy is limited, rendering decision-making difficult for both patient and physician. METHODS: We studied 47 women who became pregnant after the onset of MG. Immunosuppressive drugs were administered when MG symptoms were not controlled with anticholinesterases. Sixty-four pregnancies resulted in 55 children and 10 abortions. RESULTS: During pregnancy, MG relapsed in 4 of 23 (17%) asymptomatic patients who were not on therapy before conception; in patients taking therapy, MG symptoms improved in 12 of 31 pregnancies (39%), remained unchanged in 13 (42%), and deteriorated in 6 (19%). MG symptoms worsened after delivery in 15 of 54 (28%) pregnancies. Anti-acetylcholine receptor antibody (anti-AChR ab) was positive in 40 of 47 mothers and was assayed in 30 of 55 newborns; 13 were positive and 5 of 55 (9%) showed signs of neonatal MG (NMG). All affected babies were seropositive. CONCLUSIONS: Pregnancy does not worsen the long-term outcome of MG. The course of the disease is highly variable and unpredictable during gestation and can change in subsequent pregnancies. The occurrence of NMG does not correlate with either maternal disease severity or anti-AChR antibody titer. Immunosuppressive therapy, plasmapheresis, and i.v. human immunoglobulins can be administered safely if needed.     

The role of spontaneous portosystemic shunts in the course of orthotopic liver transplantation

Spontaneous portosystemic shunts are commonly found in cirrhotic patients. Not yet established is their role after orthotopic liver transplantation (OLTx), especially when an increase in portal pressure develops, as during early acute rejection. In this study, 34 cirrhotic patients in a series of 70 OLTx are considered. Each patient had preoperative angiographic assessment, and, in 21 (62%), large spontaneous portosystemic shunts were evident. In 12 cases the shunts were not affected by the surgical procedure and were present during the postoperative period; in 9 the hepatectomy itself involved interruption of the shunts. The patient population was divided into two groups: patients with postoperative shunts (n=12) and those without (n=22). The two groups were similar in age, sex, Child's stage, transplantation variables, and number and grade of rejection episodes. However, mean transaminases (AST) values in the first 2 weeks were significantly higher levels in shunt versus nonshunt patients (421±335 vs 183±126; P<0.025), and this was even more evident when rejection occurred (626±375 vs 195±129; P<0.001). Furthermore, during an acute rejection reaction, three cases showed a true steal phenomenon through the large reopened shunts with ischemic damage to the grafts. The data indicate a possible detrimental effect of the spontaneous shunts on graft perfusion and suggest the prophylactic surgical interruption of the residual shunts during the transplantation.     

Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice

Ethnopharmacological relevance

Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America.

Aim of the study

To investigate the neuropharmacological properties on experimental animals.

Materials and methods

The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200 mg/kg.

Results

All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant.

Conclusion

Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.     

Anti-inflammatory effect of low-intensity laser on the healing of third-degree burn wounds in rats

Third-degree burn wounds are considered severe injuries because they destroy all the skin layers and may affect subcutaneous tissues, fasciae, muscles, and bones. To favor the healing process of the injured tissues, it is very useful to diminish the occurrence of the inflammatory process. The present study was aimed at comparing the effect of different energetic densities of AlGaInP laser on the inflammatory process and in the healing of third-degree burn wounds in Wistar rats. This study was approved by the Ethics Committee, in which 36 adult male rats were selected and suffered the induction of third-degree burn injury. These rats were divided as follows: group 1—control (treated with silver sulfadiazine), group 2—received energy density of 3 J/cm², and group 3—received energy density of 6 J/cm². All animals daily received an occlusive bandage with silver sulfadiazine and 8 % papain. The laser therapy was performed alternatively three times a week. The animals were evaluated on the 3rd, 7th, 14th, and 21st days after the initial lesion and euthanized for the macroscopic, histologic, and morphometric analysis. A higher production of collagen was observed at 7 days and a greater re-epithelialization at 21 days in group 3 (6 J/cm²). Furthermore, the latter when compared to the other groups presented macroscopically a better aspect of the scar at 21 days with more granulation tissue and fibrosis. We conclude that the AlGaInP laser used in dosages of 3 and 6 J/cm² favors the healing of third-degree burn wounds induced in rats.     

Cirurgia cardíaca na estenose aórtica severa: o que mudou com o advento do tratamento percutâneo?

Introduction and objectiveTranscatheter aortic valve implantation (TAVI) is an alternative therapeutic approach to patients not considered suitable for surgical aortic valve replacement (SAVR) due to their high operative risk. We sought to assess the impact of TAVI on the profile and operative results of patients with severe aortic stenosis undergoing SAVR.MethodsA total of 214 patients were included, of whom 103 consecutive patients underwent isolated SAVR in 2005 and 111 in 2009. Patients’ demographic and operative data were collected retrospectively. Operative and one-year mortality and morbidity were analyzed.ResultsPatients’ mean age was 70 years, and 56% were female. Following the introduction of a TAVI program, patients undergoing conventional surgery were older, with more comorbidities. Overall 30-day and one-year mortality were 2.8% and 7.0%, respectively. After the introduction of TAVI, the observed mortality rate for SAVR decreased, but not significantly (operative mortality: 3.9% before TAVI vs. 1.8% after TAVI, p=NS; one-year mortality: 10% vs. 4.5%, p=NS). Striking differences were observed in morbidity (operative morbidity: 23.3% before TAVI vs. 13.5% after TAVI, p=0.047, and one-year morbidity: 20.4% vs. 9.9%, p=0.032).ConclusionsSince the introduction of a TAVI program at our center, the number of patients undergoing SAVR has increased, with a slight rise in surgical risk, but without worsening the final operative results. The implementation of a TAVI program has thus had a positive impact on the volume of procedures, patient selection and outcomes in SAVR.