Prognostic factors of the results of cardiopulmonary resuscitation in a cardiology hospital.

OBJECTIVE: To analyze the early and late results of cardiopulmonary resuscitation in a cardiology hospital and to try to detect prognostic determinants of both short- and long-term survival. METHODS: A series of 557 patients who suffered cardiorespiratory arrest (CRA) at the Dante Pazzanese Cardiology Institute over a period of 5 years was analyzed to examine factors predicting successful resuscitation and long-term survival. RESULTS: Ressuscitation maneuvers were tried in 536 patients; 281 patients (52.4%) died immediately, and 164 patients (30.6%) survived for than 24 hours. The 87 patients who survived for more than 1 month after CRA were compared with nonsurvivors. Coronary disease, cardiomyopathy, and valvular disease had a better prognosis. Primary arrhythmia occurred in 73.5% of the >1-month survivor group and heart failure occurred in 12.6% of this group. In those patients in whom the initial mechanism of CRA was ventricular fibrillation, 33.3% survived for more than 1 month, but of those with ventricular asystole only 4.3% survived. None of the 10 patients with electromechanical dissociation survived. There was worse prognosis in patients included in the extreme age groups (zero to 10 years and 70 years or more). The best results occurred when the cardiac arrest took place in the catheterization laboratories. The worst results occurred in the intensive care unit and the hemodialysis room. CONCLUSION: The results in our series may serve as a helpful guide to physicians with the difficult task of deciding when not to resuscitate or when to stop resuscitation efforts.

Trends in the risk of mortality due to cardiovascular diseases in five Brazilian geographic regions from 1979 to 1996.

OBJECTIVE - To analyze the trends in risk of death due to cardiovascular diseases in the northern, northeastern, southern, southeastern, and central western Brazilian geographic regions from 1979 to 1996. METHODS - Data on mortality due to cardiovascular, cardiac ischemic, and cerebrovascular diseases in 5 Brazilian geographic regions were obtained from the Ministry of Health. Population estimates for the time period from 1978 to 1996 in the 5 Brazilian geographic regions were calculated by interpolation with the Lagrange method, based on the census data from 1970, 1980, 1991, and the population count of 1996, for each age bracket and sex. Trends were analyzed with the multiple linear regression model. RESULTS - Cardiovascular diseases showed a declining trend in the southern, southeastern, and northern Brazilian geographic regions in all age brackets and for both sexes. In the northeastern and central western regions, an increasing trend in the risk of death due to cardiovascular diseases occurred, except for the age bracket from 30 to 39 years, which showed a slight reduction. This resulted from the trends of cardiac ischemic and cerebrovascular diseases. The analysis of the trend in the northeastern and northern regions was impaired by the great proportion of poorly defined causes of death. CONCLUSION - The risk of death due to cardiovascular, cerebrovascular, and cardiac ischemic diseases decreased in the southern and southeastern regions, which are the most developed regions in the country, and increased in the least developed regions, mainly in the central western region.

The TETAMI trial: the safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and of tirofiban versus placebo in the treatment of acute myocardial infarction for patients not thrombolyzed: methods and design.

Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non-Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.

PANDORA - Survey of Brazilian cardiologists about cholesterol reduction.

OBJECTIVE: To report about a group of physicians' understanding of the recommendations of the II Brazilian Guidelines Conference on Dyslipidemias, and about the state of the art of primary and secondary prevention of atherosclerosis. METHODS: Through the use of a questionnaire on dyslipidemia, atherosclerosis prevention, and recommendations for lipid targets established by the II Brazilian Guidelines Conference on Dyslipidemias, 746 physicians, 98% cardiologists, were evaluated. RESULTS: Eighty-seven percent of the respondents stated that the treatment of dyslipidemia changes the natural history of coronary disease. Although most of the participants followed the total cholesterol recommendations (<200mg/dL for atherosclerosis prevention), only 55.8% would adopt the target of LDL-C <100 mg/dL for secondary prevention. Between 30.5 and 36.7% answered, in different questions, that the recommended level for HDL-C should be <35mg/dL. Only 32.7% would treat their patients indefinitely with lipid- lowering drugs. If the drug treatment did not reach the proposed target, only 35.5% would increase the dosage, and 29.4% would change the medication. Participants did not know the targets proposed for diabetics. CONCLUSION: Although the participating physicians valued the role played by lipids in the prevention of atherosclerosis, serious deficiencies exist in their knowledge of the recommendations given during the II Brazilian Guidelines Conference on Dyslipidemias.

FK-binding protein is associated with the ryanodine receptor of skeletal muscle in vertebrate animals.

The ryanodine receptor/calcium release channel (RyR1) of sarcoplasmic reticulum from rabbit skeletal muscle terminal cisternae (TC) contains four tightly associated FK506-binding proteins (FKBP12). Dissociation and reconstitution studies have shown that RyR1 can be modulated by FKBP12, which helps to maintain the channel in the quiescent state. In this study, we found that the association of FKBP with RyR1 of skeletal muscle is common to each of the five classes of vertebrates. TC from skeletal muscle representing animals from different vertebrates, i.e. mammals (rabbit), birds (chicken), reptiles (turtle), fish (salmon and rainbow trout), and amphibians (frog), were isolated. For each, we find the following: 1) FKBP12 is localized to the TC (there are four FKBP binding sites/ryanodine receptor); 2) soluble FKBP exchanges with the bound form on RyR1 of TC; 3) release of FKBP from terminal cisternae by drug (FK590) treatment leads to a significant reduction in the net calcium loading rate, consistent with channel activation (the calcium loading rate is restored to the control value by reconstitution with FKBP12); and 4) RyR1 of skeletal muscle TC can bind to and exchange with either FKBP12 or FKBP12.6 (FKBP12.6 is the novel FKBP isoform found selectively associated with RyR2 of dog cardiac sarcoplasmic reticulum). We conclude that FKBP is an integral part of the RyR1 of skeletal muscle in each of the classes of vertebrate animals. The studies are consistent with a role for FKBP in skeletal muscle excitation-contraction coupling.

Choque cardiogênico / Cardiogenic shock

Choque cardiogênico pós-infarto agudo do miocárdio ocorre em cerca de 8 "por cento" dos pacientes acometidos por infarto do miocárdio. Somente com o tratamento farmacológico, apresenta altas taxas de mortalidade. Medidas agressivas, intervencionistas, devem ser instituídas täo logo o diagnóstico seja feito. A reperfusäo pelo infarto, como terapêutica de primeira linha, promove expressiva reduçäo das taxas de mortalidade. Os métodos mais eficazes para se revascularizar o miocárdio säo angioplastia coronariana, uso de agentes trombolíticos e cirurgia para correçäo de complicaçöes mecânicas (comunicaçäo interventricular, insuficiência mitral). A estratégia de tratamento deve ser iniciada o mais precocemente possível com agentes farmacológicos, além da instalaçäo do baläo intra-aórtico, seguida de terapêutica definitiva (angioplastia ou trombolítico). Essa estratégia reduz as elevadas taxas de mortalidade hospitalar desses pacientes.

Consenso Latino-Americano sobre infecçöes em bronquite crônica / Guidelines for the role of antibiotics in acute exacerbations of chronic bronchitis in Latin America

Infecçöes bacterianas crônicas ou de repetiçäo däo início e perpetuam o ciclo vicioso de lesäo das vias aéreas através da estimulaçäo dos mecanismos inflamatórios, desencadeada pelos produtos bacterianos e pela invasäo bacteriana recorrente. As exacerbaçöes agudas de bronquite crônica(EABC) säo caracterizadas por quadro abrupto de tosse,aumento da dispnéia e aumento no volume de escarro produzido. Em dois terços ou mais dos casos típicos de EABC säo isolados patógenos bacterianos. O patógeno predominante é o H. influenzae, o qual se encontra nitidamente associado ao círculo vicioso de inflamaçäo e infecçäo de repetiçäo. Entre outros patógenos comumente encontrados se incluem Moraxella catarrhalis, muitas das quais resistentes às aminopenicilinas devido à produçäo de ß-lactamase e, também, Streptococcus pneumoniae, em relaçäo aos quais se tem observado aumento no número de cepas resistentes à penicilina e macrolídeos, em âmbito mundial...

Selective binding of FKBP12.6 by the cardiac ryanodine receptor.

The calcium release channels (CRC)/ryanodine receptors of skeletal (Sk) and cardiac (C) muscle sarcoplasmic reticulum (SR) are hetero-oligomeric complexes with the structural formulas (ryanodine recepter (RyR)1 protomer)4(FKBP12)4 and (RyR2 protomer)4(FKBP12.6)4, respectively, where FKBP12 and FKBP12.6 are isoforms of the 12-kDa receptor for the immunosuppressant drug FK506. The sequence similarity between the RyR protomers and FKBP12 isoforms is 63 and 85%, respectively. Using 35S-labeled FKBP12 and 35S-labeled FKBP12.6 as probes to study the interaction with CRC, we find that: 1) analogous to its action in skeletal muscle sarcoplasmic reticulum (SkMSR), FK506 (or analog FK590) dissociates FKBP12.6 from CSR; 2) both FKBP isoforms bind to FKBP-stripped SkMSR and exchange with endogenously bound FKBP12 of SkMSR; and 3) by contrast, only FKBP12. 6 exchanges with endogenously bound FKBP12.6 or rebinds to FKBP-stripped CSR. This selective binding appears to explain why the cardiac CRC is isolated as a complex with FKBP12.6, whereas the skeletal muscle CRC is isolated as a complex with FKBP12, although only FKBP12 is detectable in the myoplasm of both muscle types. Also, in contrast to the activation of the channel by removal of FKBP from skeletal muscle, no activation is detected in CRC activity in FKBP-stripped CSR. This differential action of FKBP may reflect a fundamental difference in the modulation of excitation-contraction coupling in heart versus skeletal muscle.

A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor.

FK506, an immunosuppressant that prolongs allograft survival, is a co-drug with its intracellular receptor, FKBP12. The FKBP12.FK506 complex inhibits calcineurin, a critical signaling molecule during T-cell activation. FKBP12 was, until recently, the sole FKBP known to mediate calcineurin inhibition at clinically relevant FK506 concentrations. The best characterized cellular function of FKBP12 is the modulation of ryanodine receptor isoform-1, a component of the calcium release channel of skeletal muscle sarcoplasmic reticulum. Recently, a novel protein, FKBP12.6, was found to inhibit calcineurin at clinically relevant FK506 concentrations. We have cloned the cDNA encoding human FKBP12.6 and characterized the protein. In transfected Jurkat cells, FKBP12.6 is equivalent to FKBP12 at mediating the inhibitory effects of FK506. Upon binding rapamycin, FKBP12.6 complexes with the 288-kDa mammalian target of rapamycin. In contrast to FKBP12, FKBP12.6 is not associated with ryanodine receptor isoform-1 but with the distinct ryanodine receptor isoform-2 in cardiac muscle sarcoplasmic reticulum. Our results suggest that FKBP12.6 has both a unique physiological role in excitation-contraction coupling in cardiac muscle and the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin.

Affinity purification of the ryanodine receptor/calcium release channel from fast twitch skeletal muscle based on its tight association with FKBP12.

The ryanodine receptor (RyR)/calcium release channel isolated from skeletal muscle terminal cisternae (TC) of sarcoplasmic reticulum (SR) is tightly associated with FK506 binding protein of 12.0 kDa (FKBP12) (Jayaraman et al., (1992) J.Biol.Chem. 267, 9474-9477). In this study, we describe a new method of affinity chromatography for purifying the RyR from skeletal muscle SR based on: 1) its tight association with FKBP12; and 2) the finding that bound FKBP on the RyR can be exchanged with soluble FKBP12 (Timerman et al., (1995) J.Biol.Chem. 270, 2451-2459). Soluble glutathione S-transferase/FKBP12 (GST/FKBP12) fusion protein was first exchanged with bound FKBP12 on the RyR of TC. The TC were then solubilized with CHAPS and the complex of RyR.GST/FKBP12 was specifically adsorbed by glutathione Sepharose 4B and then eluted with glutathione. The RyR, purified by this method, has similar characteristics by SDS-PAGE, radioligand binding and immuno-reactivity as the RyR purified by multiple sequential column chromatography.