Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria.

Acute intermittent porphyria (AIP) is a human disease resulting from a dominantly inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen deaminase (PBGD). The frequency of the trait for AIP is 1/10,000 in most populations, but may be markedly higher (1/500) in psychiatric patients. The clinical expression of the disease is characterized by acute, life-threatening attacks of 'porphyric neuropathy' that include abdominal pain, motor and sensory neurological deficits and psychiatric symptoms. Attacks are frequently precipitated by drugs, alcohol and low caloric intake. Identical symptoms occur in other hepatic porphyrias. To study the pathogenesis of the neurologic symptoms of AIP we have generated Pbgd-deficient mice by gene targeting. These mice exhibit the typical biochemical characteristics of human AIP, notably, decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity and massively increased urinary excretion of the heme precursor, delta-aminolevulinic acid after treatment with drugs such as phenobarbital. Behavioural tests reveal decreased motor function and histopathological findings include axonal neuropathy and neurologic muscle atrophy.

The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells.

In mature B lymphocytes, the zinc finger transcription factor early growth response 1 (Egr-1) is one of the many immediate-early genes induced upon B cell antigen receptor engagement. However, its role during earlier stages of lymphopoiesis has remained unclear. By examining bone marrow B cell subsets, we found Egr-1 transcripts in pro/pre-B and immature B lymphocytes, and Egr-1 protein in pro/pre-B-I cells cultivated on stroma cells in the presence of interleukin (IL)-7. In recombinase-activating gene (RAG)-2-deficient mice overexpressing an Egr-1 transgene in the B lymphocyte lineage, pro/pre-B-I cells could differentiate past a developmental block at the B220(low) BP-1(-) stage to the stage of B220(low) BP-1(+) pre-B-I cells, but not further to the B220(low) BP-1(+) CD25(+) stage of pre-B-II cells. Therefore, during early B lymphopoiesis progression from the B220(low) BP-1(-) IL-2R- pro/pre-B-I stage to the B220(low) BP-1(+) IL-2R+ pre-B-II stage seems to occur in at least two distinct steps, and the first step to the stage of B220(low) BP-1(+) pre-B-I cells can be promoted by the overexpression of Egr-1 alone. Wild-type mice expressing an Egr-1 transgene had increased proportions of mature immunoglobulin (Ig)M+ B220(high) and decreased proportions of immature IgM+ B220(low) bone marrow B cells. Since transgenic and control precursor B cells show comparable proliferation patterns, overexpression of Egr-1 seems also to promote entry into the mature B cell stage. Analysis of changes in the expression pattern of potential Egr-1 target genes revealed that Egr-1 enhances the expression of the aminopeptidase BP-1/6C3 in pre-B and immature B cells and upregulates expression of the orphan nuclear receptor nur77 in IgM+ B cells.

IL-4-deficient Balb/c mice resist infection with Leishmania major.

Mice with a genetically engineered deficiency for either IL-4 or IFN-gamma R1 (single mutants), and IL-4/IFN-gamma R1 (double mutants) on the Balb/c and 129Sv background were used to study the course of infection with Leishmania major. In contrast to genetically resistant 129Sv wildtype mice, IL-4/IFN-gamma R1 double mutant mice developed fetal disease with parasite dissemination to visceral organs similar to mice lacking IFN-gamma R1 only. Balb/c mice, which are exquisitely susceptible to L. major, were rendered resistant to infection by disruption of the IL-4 gene. As compared to homozygous IL-4+/- mice, heterozygous IL-4+/- mice, heterozygous IL-4+/- animals consistently developed smaller lesions with less ulceration and necrosis, indicating the likelihood of gene-dosage effects. This implicates that the magnitude of the IL-4 response determines the severity of disease. CD4+ T cells of IL-4-deficient mice showed impaired Th2 cell development, as assessed by quantitative RT-PCR of characteristic cytokines. Development of resistance is not explained by default Th1 development, because this was observed only at very late stages of infection. Moreover, the induction of inflammatory cytokines (e.g., IL-1 alpha, IL-1 beta, TNF-alpha, IL-12) together with iNOS in the lesion and draining lymph nodes was not altered in the absence of IL-4.

Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart.

Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a constituent of the cytoplasmic plaque of desmosomes as well as of other adhering cell junctions, and is involved in anchorage of cytoskeletal filaments to specific cadherins. We have generated a null mutation of the plakoglobin gene in mice. Homozygous -/- mutant animals die between days 12-16 of embryogenesis due to defects in heart function. Often, heart ventricles burst and blood floods the pericard. This tissue instability correlates with the absence of desmosomes in heart, but not in epithelia organs. Instead, extended adherens junctions are formed in the heart, which contain desmosomal proteins, i.e., desmoplakin. Thus, plakoglobin is an essential component of myocardiac desmosomes and seems to play a crucial role in the sorting out of desmosomal and adherens junction components, and consequently in the architecture of intercalated discs and the stabilization of heart tissue.

Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6.

Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize lesions in this critical anabolic process. To test this possibility, we conditionally deleted the gene encoding 40S ribosomal protein S6 in the liver of adult mice. Unexpectedly, livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. These results imply that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.

Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity.

Two molecular mechanisms of T cell-mediated cytotoxicity, one perforin-based, the other Fas-based, have been demonstrated. To determine the extent of their contribution to T cell-mediated cytotoxicity, a range of effector cells from normal control or perforin-deficient mice were tested against a panel of target cells with various levels of Fas expression. All cytotoxicity observed was due to either of these mechanisms, and no third mechanism was detected. Thus, the perforin- and Fas-based mechanisms may account for all T cell-mediated cytotoxicity in short-term in vitro assays.

Resistance of Fc receptor- deficient mice to fatal glomerulonephritis.

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.

Trophoblast cell-specific carcinoembryonic antigen cell adhesion molecule 9 is not required for placental development or a positive outcome of allotypic pregnancies.

The carcinoembryonic antigen (CEA) family consists of a large group of evolutionarily divergent glycoproteins. The secreted pregnancy-specific glycoproteins constitute a subgroup within the CEA family. They are predominantly expressed in trophoblast cells throughout placental development and are essential for a positive outcome of pregnancy, possibly by protecting the semiallotypic fetus from the maternal immune system. The murine CEA gene family member CEA cell adhesion molecule 9 (Ceacam9) also exhibits a trophoblast-specific expression pattern. However, its mRNA is found only in certain populations of trophoblast giant cells during early stages of placental development. It is exceptionally well conserved in the rat (over 90% identity on the amino acid level) but is absent from humans. To determine its role during murine development, Ceacam9 was inactivated by homologous recombination. Ceacam9(-/-) mice on both BALB/c and 129/Sv backgrounds developed indistinguishably from heterozygous or wild-type littermates with respect to sex ratio, weight gain, and fertility. Furthermore, the placental morphology and the expression pattern of trophoblast marker genes in the placentae of Ceacam9(-/-) females exhibited no differences. Both backcross analyses and transfer of BALB/c Ceacam9(-/-) blastocysts into pseudopregnant C57BL/6 foster mothers indicated that Ceacam9 is not needed for the protection of the embryo in a semiallogeneic or allogeneic situation. Taken together, Ceacam9 is dispensable for murine placental and embryonic development despite being highly conserved within rodents.

[Diagnostic and prognostic significance of CK-MB, troponins, CRP, BNP and/or NT-proBNP in coronary angioplasty. Elevation mechanisms and clinical implications]. / Intérêt diagnostique et pronostique des marqueurs biologiques dans l'angioplastie coronaire en cas d'angor stable et de syndrome coronaire aigu ST-. Quelle stratégie biologique en routine?

The recommendations from respected bodies concerning the treatment and follow up of patients undergoing coronary angioplasty for stable angina or acute coronary syndrome (ACS) are essential for reducing the risks related to the procedure, and for preventing the occurrence of long term complications. Measuring the levels of troponin and CK-MB is part of the diagnostic and prognostic strategy during the coronary angioplasty procedure. In this context, the frequent elevation of markers following uncomplicated angioplasty is a sign of minor irreversible myocardial damage, the prognostic significance of which remains under discussion. Recent data suggest that only a basal troponin elevation (more so than CK-MB) prior to angioplasty has a long term prognostic value in ACS ST- patients, and that troponin elevation occurring after the procedure in the presence of normal basal concentrations, is only associated with in-hospital complications. Determining the basal level of troponin would appear to be essential for interpreting any elevation in concentrations following angioplasty. The recommendations should integrate this fundamental point, if it is confirmed. On the other hand, the question has been raised whether other markers (CRP, BNP and/or NT-proBNP) should be systematically measured as a routine prior to angioplasty. An elevation of CRP before and/or after angioplasty is an unfavourable short and long term prognostic factor. Elevation of NT-proBNP before angioplasty is also an unfavourable long term prognostic factor. Recommending a multi-marker strategy might represent a future direction for identifying at risk patients prior to coronary angioplasty, thus enabling specific treatment to be proposed.

Assessment of peak skin dose in interventional cardiology: A comparison between Gafchromic film and dosimetric software em.dose.

OBJECTIVE: To compare the use of a dose mapping software to Gafchromic film measurement for a simplified peak skin dose (PSD) estimation in interventional cardiology procedure. METHODS: The study was conducted on a total of 40 cardiac procedures (20 complex coronary angioplasty of chronic total occlusion (CTO) and 20 coronary angiography and coronary angioplasty (CA-PTCA)) conducted between January 2014 to December 2015. PSD measurement (PSDFilm) was obtained by placing XR-RV3 Gafchromic under the patient's back for each procedure. PSD (PSDem.dose) was computed with the software em.dose©. The calculation was performed on the dose metrics collected from the private dose report of each procedure. Two calculation methods (method A: fluoroscopic kerma equally spread on cine acquisition and B: fluoroscopic kerma is added to one air Kerma cine acquisition that contributes to the PSD) were used to calculate the fluoroscopic dose contribution as fluoroscopic data were not recorded in our interventional room. Statistical analyses were carried out to compare PSDFilm and PSDem.dose. RESULTS: The PSDFilm median (1st quartile; 3rd quartile) was 0.251(0.190;0.336)Gy for CA-PTCA and 1.453(0.767;2.011)Gy for CTO. For method-A, the PSDem.dose was 0.248(0.182;0.369)Gy for CA-PTCA and 1.601(0.892;2.178)Gy for CTO, and 0.267(0.223;0.446)Gy and 1.75 (0.912;2.584)Gy for method-B, respectively. For the two methods, the correlation between PSDFilm and PSDem.dose was strong. For all cardiology procedures investigated, the mean deviation between PSDFilm and PSDem.dose was 3.4±21.1% for method-A and 17.3%±23.9% for method-B. CONCLUSION: The dose mapping software is convenient to calculate peak skin dose in interventional cardiology.

Assessment of Patient's Peak Skin Dose Using Gafchromic Films During Interventional Cardiology Procedures: Routine Experience Feedback.

To assess the interest of Gafchromic films in detection of patient's peak skin dose (PSD) in interventional cardiology. A prospective study of 112 patients was conducted (July-December 2015). Three diagnostic and therapeutic procedures were evaluated: coronary angiography (CA), coronary angiography and coronary angioplasty for one or two vessels disease (CA-PTCA) and coronary angioplasty of complex chronic total occlusion (CTO). Dosimetric indicators (DIs) were collected and PSD were measured with Gafchromic films. Dose distribution was evaluated within 10 'Thorax Body-zone' defined by the system. Correlations between PSD and DI or dose distribution were computed. Delivered dose increased in complex procedures. The PSD were 0.121 ± 0.063 Gy for CA, 0.256 ± 0.142 Gy for CA-PTCA and 1.116 ± 0.721 Gy for CTO. High correlations were observed for PSD and DI as well for dose distribution within the 'Thorax Body-zone'. Film dosimetry is suggested for CTO procedures since the threshold of 2 Gy for skin injuries is likely to be exceeded.

Impact of the calibration conditions of XR-RV3 films on peak skin dose measurements in interventional radiology.

In this study, the impact of radiochromic films' (XR-RV3) calibration on PSD measurements was investigated under various peak kilovoltage (kVp) and additional filtration conditions. Films were calibrated free-in-air for six beam qualities with Allura Xper FD20 system (Philips). Six calibration curves (CCs) were constructed. Each beam quality was characterized in terms of mean energy (ME) in the air, with table, with table and water phantom using Monte Carlo simulations. A cohort of 155 patient films from cardiology (37) and vascular (118) procedures were read with each CC. Routine calibration beam quality was taken as reference (DoseNorm). Overall, it was observed that for a wider ME difference between the exposed film and the CC used, a larger deviation (from -28% to +41%) was observed. The choice of beam quality for the calibration is a key point when additional filtration and kVp are automatically controlled in clinical conditions.

[What is the place of bioresorbable vascular scaffolds in setting of ST-segment elevation myocardial infarction?]. / Quelle place pour les stents biorésorbables dans la prise en charge du syndrome coronarien aigu avec sus-décalage du segment ST ?

A 50-year-old woman was admitted for an inferior ST-segment elevation myocardial infarction; immediate coronary angiogram revealed a subocclusive stenosis of the right coronary artery. After optimal antithrombotic treatment, the type of stent could be discussed. The latest generation of drug-eluting stents showed excellent efficacy and safety in the long-term but has limitations such as potential chronic inflammation of the arterial wall and no recovery of vasoactive function. Bioresorbable vascular scaffolds, with complete resorption within several months, may reduce these limitations. Implantation of bioresorbable scaffold in the context of myocardial infarction may be interesting. However, very few studies are currently available in this setting. Preliminary results and perspectives are presented in this review.

Efficient generation of transgenic BALB/c mice using BALB/c embryonic stem cells.

BALB/c is one of the most widely used and best characterized mouse strains in immunology. For various applications, it is necessary to generate BALB/c transgenic mice. However, using the conventional microinjection technique it is extremely inefficient to produce transgenic BALB/c mice since the one-cell stage BALB/c embryos are highly vulnerable to pronuclear DNA microinjection. To overcome this problem, we have investigated the generation of Egr-1 (early growth response gene) transgenic mice via the transfection of BALB/c embryonic stem cells. Transfectants carrying Egr-1 constructs comprising either the immunoglobulin heavy chain or the MHC class II promoter/enhancer system were injected into C57BL/6 host blastocysts resulting in chimeric mice. For both type of expression vectors, transgenic offspring of the germline chimeras expressed recombinant Egr-1 in lymphoid tissues containing B cells. This demonstrates the successful generation of Egr-1 transgenic BALB/c mice using transfected ES cell.

Relation of minor cardiac troponin I elevation to late cardiac events after uncomplicated elective successful percutaneous transluminal coronary angioplasty for angina pectoris.

There is little information about the relation between mild cardiac troponin I (cTn-I) increase after coronary interventions and late outcome. We therefore focused on the long-term outcome and the clinical, morphologic, and procedural correlates of elevation of cTn-I compared with cardiac troponin T, creatine kinase (CK), CK-MB activity and mass, and myoglobin in 105 patients with successful elective percutaneous transluminal coronary angioplasty (PTCA) for stable or unstable angina. Patients with myocardial infarction and those with unstable angina who had a detectable increase in serum markers before PTCA were excluded. Markers were measured before and after the procedure and for 2 days. Patients were followed up to record recurrent angina, myocardial infarction, cardiac death, repeat PTCA, or elective coronary artery bypass graft surgery. Procedure success was achieved in all cases. Elevation in cTn-I (> or =0.1 microg/L) was observed in 23 of 105 patients (22%) (median peak: 0.25 microg/L); 18% had cardiac troponin T (cTn-T) release (> or = 0.1 microg/L, median peak 0.21); 11.4% CK-MB mass (> or =5 microg/L), and 7.6% myoglobin (> or =90 microg/L) release. Five and 2 patients had elevated CK and CK-MB activity, respectively. Fourteen of 18 patients with cTn-T elevation had a corresponding elevation in cTn-I (kappa 0.68; p = 0.001). Patients positive for cTn-I had more unstable angina (p = 0.042) and heparin before PTCA (p = 0.046), and had longest total time (p = 0.004) and single inflation (p = 0.01). By multivariate logistic regression, predictors of postprocedure cTnI elevation were maximum time of each inflation (odds ratio 9.2; p = 0.0012), type B lesions (odds ratio 6.6; p = 0.013), unstable angina (p = 0.041), and age > or =60 years (p = 0.032). Clinical follow-up was available in 103 patients (98%) (mean 19+/-10 months). Kaplan-Meier survival analysis showed that cTn-I elevation was not an important correlate of cardiac events (p = 0.34, by log-rank analysis). The incidence of recurrent angina, myocardial infarction, cardiac death, and repeat revascularization after 12 months was not different in patients positive or negative for cTn-I. We conclude that cTn-I elevation after successful PTCA is not associated with significantly worse late clinical outcome. Levels of cTn-I allow a much higher diagnostic accuracy in detecting minor myocardial injury after PTCA compared with other markers, but there is no association with periprocedural myocardial cell injury and late outcome when cTn-I and other markers are considered.

Release kinetics of serum cardiac troponin I in ischemic myocardial injury.

OBJECTIVES: The study was undertaken to evaluate the release kinetics of cardiac troponin I (cTn-I) in ischemic myocardial injury. DESIGN AND METHODS: The reference range for cTn-I was established by determination of cTn-I in sera and plasma obtained from 622 healthy volunteers (Group 1). cTn-I was compared to: (a) Creatine kinase (CK) MB mass and myoglobin in 12 patients with severe skeletal muscle damage (Group 2); (b) CK-MB activity in 48 patients with myocardial infarction (MI) receiving intravenous thrombolysis (Group 3) (in this group, an additional 43 patients with MI were analyzed separately to characterize cTn-I patterns in thrombolyzed and nonthrombolyzed populations): and in 44 patients with unstable angina (Group 4). RESULTS: In Groups 1 and 2, no positive results (> or = 0.1 microgram/L) were obtained. In Group 3, the time-courses of cTn-I were mostly monophasic in form. A pathologic increase occurred earlier in cTn-I than in CK-MB activity (p = 0.0002); the period with increased cTn-I was longer (p = 0.001), the overall sensitivity of cTn-I (93.9%) was higher than that of CK-MB activity (p = 0.00001). cTn-I was more sensitive at admission (p = 0.0004). In additional patients, the cTn-I peak occurred and cTn-I disappeared significantly later in nonthrombolyzed than in the thrombolyzed group. In Group 4, positive tests results were detected in 45% of patients for cTn-I, 16% for CK-MB activity, and 32% for CK-MB mass. CONCLUSIONS: The cTn-I assay appears to be ideally suited for the detection of ischemic myocardial injury in complex clinical situations because of its high specificity; cTn-I indicates myocardial tissue damage in patients with unstable angina and is superior to CK-MB activity and mass in this respect.

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats.

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

[Traumatic tricuspid insufficiency. Apropos of 2 cases]. / Insuffisance tricuspide traumatique. A propos de 2 observations.

The authors report two cases of tricuspid regurgitation by a ruptured anterior papillary muscle secondary to non-penetrating thoracic trauma. In the presence of suggestive clinical and electrocardiographic abnormalities (systolic murmur, right heart failure, right bundle branch block), echocardiography confirmed the tricuspid regurgitation, showed its mechanism and excluded any other intracardiac lesions. Tricuspid annuloplasty was performed in both cases because of the persistence of failure or degradation of the patient's clinical condition. Peroperative echocardiography was used to judge the quality of the surgical repair in both cases. Traumatic tricuspid regurgitation is a rare condition and the diagnosis is often delayed. Echocardiography is the investigation of choice and guides treatment which is essentially valvular repair in symptomatic patients.

[Prognostic significance of early raised cardiac troponine I in unstable angina. Contribution to the identification of a high-risk sub-group]. / Signification pronostique de l'élévation précoce de la troponine I cardiaque chez les patients en angor instable. Contribution à l'identification d'un sous-groupe à haut-risque.

The authors compared the clinical and angiographic characteristics of 44 patients with unstable angina according to cardiac Troponine I concentrations (TnIc) during early blood sampling and then tried to determine a threshold value to predic the occurrence of cardiac events during the hospital period and after 12 months. Tnlc, creatinine-kinase (CK), CK-MB activity and CK-MB mass were sampled over 48 hours. Forty-five per cent of patients had TnIc > or = 0.1 microgram/L; CK-MB activity and CK-MB mass were detected in 16 and 32% of patients. Age, gender, classification and recurrence of angina, previous cardiac history, risk factors, coronary angiographic appearances were comparable in patients with and without raised TnIc. No major cardiac events occurred during the hospital period in either group. The number of angioplasties and coronary bypass procedures was also comparable. At one year, the incidence of myocardial infarction (N = 4) and death (N = 5) was significantly different in patients with raised Tnlc (33% versus 0% in patients without increased TnIc). However, betablocker therapy was less prescribed in the group with the poorest outcomes and left ventricular dysfunction was also significantly more common in this group. Early elevation of Tnlc could contribute to the identification of a high risk subgroup of patients with unstable angina.

[Is it necessary to rehabilitate coronary artery disease patients based on ventilatory threshold?]. / Faut-il rééduquer les coronariens au seuil ventilatoire ?

PURPOSE: To compare the efficiency of two programs of exercise-based rehabilitation that are different for heart rate (HR) training in patients with coronary artery disease: heart rate (HR) according to Karvonen formula (HR training =70% (max HR -rest HR) +rest HR) or HR recorded at the gas exchange ventilatory threshold (VT). TYPE: Controlled randomised clinical trial. SETTING: Cardiovascular rehabilitation unit. METHOD: Twenty-four male patients (54 +/-9.5 years old) with coronary artery disease were allocated at random to one of the two groups: KHR group (n =13) according to Karvonen formula (n =11), and VTHR group according to VT determined by exertion test (n =13). The exercised-based program was similar for all the patients, differing only in HR training (five daily sessions a week for four weeks). Assessment tests were performed at D1 and D28 and included: - an exercise test with measure of HR and double product (HR x blood pressure) at rest, submaximal and maximal intensity, with measure of oxygen consumption and gas exchanges at rest and at maximum exercise; - specific functional tests based on daily life activities; - dyspnea assessment at maximal intensity; - quality of life measurement by SF36. It was taken notice of the drugs taken by the patients, specially betablockers. RESULTS: At inclusion, the two groups were not different for parametric (age, body mass index) and non parametric values (medical or surgical treatment, comorbidity). Even though HR training was significantly different (p <10(-6)), at the end of the program there was a significant increase of power and oxygen consumption at VT (+42.6%, p <10(-6); +18.6%, p <10(-5)) and at maximal intensity (+18.7 %, p <10(-6); 14.2 %, p <10(-5)), but differences between the two groups were not significant; double product was significantly lower at rest (-13.9 %, p <10(-5)) and at submaximal exertion (-10.6 %, p < 10(-3)). Yet, the two groups differed in HR, and HR increased in VTHR group and decreased in KHR, the difference being significant at VT (p =0.05), at submaximal (p =0.037) and maximal exercise (p = 0.05). Dyspnea at maximal intensity was higher in VTHR but SF36 values were not different. DISCUSSION AND CONCLUSION: These results confirm the efficiency of cardiac training program according to Karvonen formula as to ventilatory threshold. However, there is a negative chronotropic effect of cardiac training according to Karvonen formula with a higher intensity, which corresponds to a less cardiac work for a same activity.