Ambulatory Electrocardiographic Monitoring and Ectopic Beat Detection in Conscious Mice.

Ambulatory electrocardiography (AECG) is a primary diagnostic tool in patients with potential arrhythmic disorders. To study the pathophysiological mechanisms of arrhythmic disorders, mouse models are widely implemented. The use of a technique similar to AECG for mice is thus of great relevance. We have optimized a protocol which allows qualitative, long-term ECG data recording in conscious, freely moving mice. Automated algorithms were developed to efficiently process the large amount of data and calculate the average heart rate (HR), the mean peak-to-peak interval and heart rate variability (HRV) based on peak detection. Ectopic beats are automatically detected based on aberrant peak intervals. As we have incorporated a multiple lead configuration in our ECG set-up, the nature and origin of the suggested ectopic beats can be analyzed in detail. The protocol and analysis tools presented here are promising tools for studies which require detailed, long-term ECG characterization in mouse models with potential arrhythmic disorders.

Spontaneous Right Ventricular Pseudoaneurysms and Increased Arrhythmogenicity in a Mouse Model of Marfan Syndrome.

Patients with Marfan syndrome (MFS), a connective tissue disorder caused by pathogenic variants in the gene encoding the extracellular matrix protein fibrillin-1, have an increased prevalence of primary cardiomyopathy, arrhythmias, and sudden cardiac death. We have performed an in-depth in vivo and ex vivo study of the cardiac phenotype of Fbn1mgR/mgR mice, an established mouse model of MFS with a severely reduced expression of fibrillin-1. Using ultrasound measurements, we confirmed the presence of aortic dilatation and observed cardiac diastolic dysfunction in male Fbn1mgR/mgR mice. Upon post-mortem examination, we discovered that the mutant mice consistently presented myocardial lesions at the level of the right ventricular free wall, which we characterized as spontaneous pseudoaneurysms. Histological investigation demonstrated a decrease in myocardial compaction in the MFS mouse model. Furthermore, continuous 24 h electrocardiographic analysis showed a decreased heart rate variability and an increased prevalence of extrasystolic arrhythmic events in Fbn1mgR/mgR mice compared to wild-type littermates. Taken together, in this paper we document a previously unreported cardiac phenotype in the Fbn1mgR/mgR MFS mouse model and provide a detailed characterization of the cardiac dysfunction and rhythm disorders which are caused by fibrillin-1 deficiency. These findings highlight the wide spectrum of cardiac manifestations of MFS, which might have implications for patient care.

Human Plasmacytoid and Monocyte-Derived Dendritic Cells Display Distinct Metabolic Profile Upon RIG-I Activation.

Recent advances reveal that metabolic reprogramming is required for adequate antiviral responses of dendritic cells (DCs) that possess the capacity to initiate innate and adaptive immune responses. Several reports indicate that Toll-like receptor (TLR) stimulation of DCs is accompanied by a rapid induction of glycolysis; however, the metabolic requirements of retinoic-acid inducible gene I (RIG-I)-like receptor (RLR) activation have not defined either in conventional DCs (cDCs) or in plasmacytoid DCs (pDCs) that are the major producers of type I interferons (IFN) upon viral infections. To sense viruses and trigger an early type I IFN response, pDCs rely on endosomal TLRs, whereas cDCs employ cytosolic RIG-I, which is constitutively present in their cytoplasm. We previously found that RIG-I is upregulated in pDCs upon endosomal TLR activation and contributes to the late phase of type I IFN responses. Here we report that TLR9-driven activation of human pDCs leads to a metabolic transition to glycolysis supporting the production of type I IFNs, whereas RIG-I-mediated antiviral responses of pDCs do not require glycolysis and rather rely on oxidative phosphorylation (OXPHOS) activity. In particular, TLR9-activated pDCs show increased extracellular acidification rate (ECAR), lactate production, and upregulation of key glycolytic genes indicating an elevation in glycolytic flux. Furthermore, administration of 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, significantly impairs the TLR9-induced secretion of type I IFNs by human pDCs. In contrast, RIG-I stimulation of pDCs does not result in any alterations of ECAR, and type I IFN production is not inhibited but rather promoted by 2-DG treatment. Moreover, pDCs activated via TLR9 but not RIG-I in the presence of 2-DG are impaired in their capacity to prime allogeneic naïve CD8+ T cell proliferation. Interestingly, human monocyte-derived DCs (moDC) triggered via RIG-I show a commitment to glycolysis to promote type I IFN production and T cell priming in contrast to pDCs. Our findings reveal for the first time, that pDCs display a unique metabolic profile; TLR9-driven but not RIG-I-mediated activation of pDCs requires glycolytic reprogramming. Nevertheless, the metabolic signature of RIG-I-stimulated moDCs is characterized by glycolysis suggesting that RIG-I-induced metabolic alterations are rather cell type-specific and not receptor-specific.

Modulation by enkephalin analogues and neuroleptics of apomorphine-induced stereotypy and turning behaviour in rats.

The aim of the present investigation was to examine which areas of the brain might mediate the anti-apomorphine action of some opioids, which were found previously to be active upon subcutaneous application. As the first step, the substances were injected intracerebroventricularly or into the nucleus accumbens, a mesolimbic region which is rich in dopamine, and the inhibition of stereotypy induced by apomorphine was quantified. In a separate group of animals (rats with unilateral lesion of the nigra) the antagonism of turning behaviour elicited by apomorphine was measured. Substances examined were morphine, a mu-selective opiate; D-Ala2,Nle5-enkephalin sulphonic acid (ES), a delta-selective opioid peptide; D-Met2,Pro5-enkephalinamide (EA), a highly potent but non-selective opioid; and two dopamine receptor blockers, haloperidol and chlorpromazine, for comparison. Examining the antagonism of turning behaviour induced by apomorphine, the order of potency was EA greater than haloperidol greater than morphine greater than ES approximately equal to chlorpromazine if injections of the substances were intracerebroventricular and EA greater than morphine much greater than haloperidol approximately equal to ES much greater than chlorpromazine when administered into the nucleus accumbens. The order of potency for the suppression of stereotypy induced by apomorphine was EA much greater than haloperidol greater than morphine greater than ES greater than chlorpromazine upon intracerebroventricular application and EA much greater than haloperidol greater than morphine ES greater than chlorpromazine if injected into the nucleus accumbens. The data indicate that endogenous opioids might inhibit the activity of dopamine in brain through the nucleus accumbens.

Vectorcardiograms in severe aortic insufficiency. Clockwise rotation of QRS loop in the horizontal plane.

In La Paz Hospital, Madrid, recently, vectorcardiograms (VCGs) were performed on 74 patients with aortic insufficiency. These cases presenting electrocardiographic and radiologic signs of left ventricular hypertrophy, were divided into three groups. In 25 patients (Group 1) the QRS loop in the horizontal plane (HP) showed counterclockwise rotation; 43 patients (Group 2) showed clockwise rotation; and 6 patients (Group 3) showed a pattern of left bundle branch block (LBBB). In Group 2, 31 of the 43 patients (group 2-A) had a Qloop of normal orientation and generally increased voltage, and in the remaining 12 patients (group 2-B) the Q loop was absent. All of the patients in Group 2 had severe aortic insufficiency. Thus, that group's valuation of the left ventricular hypertrophy using maximum QRS vector voltage in the HP, was higher than in Group 1 mean 3.75mV in Group 2 versus mean 2.71mV in Group 1 (p less than 0.01). Postoperative VCGs were performed in 12 patients of group 2-A, showing in all of them a clockwise to counterclockwise rotation change of the QRS loop in the HP. On the other hand, this fact was observed in only two of the eight patients in group 2-B. The clockwise rotation of the QRS loop in the HP is an important datum in our report, particularly in the diagnosis of severe aortic insufficiency. Conversely, a clockwise to counterclockwise rotation change would be a positive sign of good post operative evolution. Finally, two reasons are given to explain this anomalous rotation in the horizontal plane: dilatation and fibrosis.

Vectocardiography in tetralogy of Fallot before and after operation (palliative and corrective surgery).

Vectorcardiograms from 55 patients with diagnosed tetralogy of Fallot were studied and divided into the following three groups: A, 35 nonoperated cases; B, 23 with systemic-pulmonary shunt (nine studied preoperatively and also in A); and C, ten after total correction. In group A, two different types of QRS loop occurred in the horizontal plane (HP); 23 clinically and hemodynamically severe cases had right anterior position with clockwise (C) rotation, and 12 less severe cases had right posterior position with counterclockwise (CC) rotation or figure-8 morphology. In the frontal plane the QRS loop was located inferiorly and to the right, with C rotation (80 percent); two cases had the left anterior hemiblock (LAHB) pattern, and another two severe cases had CC rotation and right superior position. Group B had an evident increase of left ventricular forces in the HP, compared with group A; group-B rotation was preferentially CC or figure-8 morphology. Group C had a pattern of right bundle-branch block in nine cases (classic in one and uncharacteristic in eight); four cases also had LAHB.

Fascicular block within the His bundle.

The findings in a patient with complete atrioventricular block and normal morphology and duration of the QRS complex are presented. A His bundle electrogram was obtained, which led to the location of the atrioventricular block within the His bundle. A careful review of the electrocardiograms obtained during the seven years preceding the onset of complete atrioventricular block showed a QRS complex with the features of left anterior hemiblock and a progressive impairment of atrioventricular conduction. From these data, we inferred that the different degrees of atrioventricular block and the left anterior hemiblock were caused by lesions within the His bundle involving the fibers destined for the left anterior division of the left branch. After the onset of complete atrioventricular block, with the subsidiary pacemaker located in the His bundle distal to the lesions, the QRS complex became normal, indicating the integrity of the bundle branches and fasciculi. The atrial and proximal His potential intervals and those between distal His and ventricular potentials were normal.

Anterograde and retrograde bradycardiac block in the His-Purkinje system. Finding in a patient with acute myocardial infarction.

A patient with an acute inferior myocardial infarction developed a complete atrioventricular block and intermitent periods of atrioventricular conduction with QRS complexes showing right bundle branch block associated with left anterior hemiblock. Recordings of the His bundle electrogram showed that the atrioventricular block was infrahisian and that in periods of resumed atrioventricular conduction, the His-ventricle (H-V) interval was long. Ventricular escape beats showed concealed conduction to the atrioventricular node. Anterograde atrioventricular conduction was always resumed through the left posterior division when the preceding division when the preceding intervals between ventricular escape beats and the atrium (V-A intervals) were shorter than 580 msec. The same phenomenon occurred with right ventricular pacing. A retrograde His potential could be observed. Retrograde conduction of ventricular escape beats and ventricular paced beats was blocked if the H-V interval and the interval between the His bundle and the ventricular paced beat (H-V interval) were long (more than 600 msec and 550 msec, respectively). The existence of an intermittent anterograde and retrograde bradycardiac infrahisian block was inferred from the previously mentioned data; a fixed retrograde atrial nodal block was also present.

Successful treatment of prosthetic aortic valve mucormycosis.

Mucor endocarditis after cardiovascular surgery is rare and usually fatal. We report the first known case of prosthetic aortic valve mucormycosis in a patient without predisposing risk factors who was successfully treated using a combination of early antifungal drug therapy and surgical removal of infected material.

Myocardial involvement in systemic lupus erythematosus. A noninvasive study of left ventricular function.

A relatively high incidence of heart failure is noted among patients with systemic lupus erythematosus (SLE) without clearly defined clinical causes. To evaluate left ventricular performance in patients with SLE without evidence of cardiovascular disease, noninvasive measurement of the systolic time intervals was carried out. Simultaneous recording of the electrocardiogram, phonocardiogram and carotid arterial pulsation were obtained in 25 patients with systemic lupus erythematosus and compared with 22 normal subjects. The patients with SLE had a shorter left ventricular ejection time (P less than 0.05), a longer pre-ejection period (P less than 0.02) and an increased ratio of pre-ejection period/left ventricular ejection time (P less than 0.005). These abnormalities on ventricular function were independent of age, duration of the disease, hypertension, renal involvement, anemia, immunologic activity and corticosteroid treatment. Several etiologic possibilities are discussed and the clinical usefulness of this method to detect and follow-up the cardiac dysfunction in systemic lupus erythematosus is emphasized.

Atrioventricular nodal dysfunction in patients with atrial septal defect. Abnormalities of conduction and reciprocal rhythms.

Electrophysiologic studies were performed in 17 unselected patients (mean age, 20 years) with atrial septal defect (ASD) of the ostium secundum type. In nine (52.9 percent) signs were found of atrioventricular (A-V) nodal dysfunction, in seven (41.1 percent) prolonged A-H interval, and in three (17.6 percent) prolonged effective refractory period of A-V node and in five (29.4 percent) A-V nodal tachycardia and reentry. Three of the four cases showed anterograde conduction (Ae-H interval) faster than retrograde conduction (H-A3 interval) during the tachycardia. In one patient with reentry a similar phenomenon was observed. In the remaining patient the conduction time was reversed (Ae-H longer than H-Ae). In two patients infrahisian and intrahisian block (first and second degree) with persistence of the tachycardia was observed. Patent or latent abnormalities in A-V node function are a frequent finding in patients with ASD. In the sinus node, any kind of significant abnormality can be found.

Apparent antinociceptive and anti-inflammatory effects of GYKI 52466.

GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine) was examined in a battery of analgesia and anti-inflammatory tests in rats and mice, respectively. Its 3-N-acetyl (GYKI 53773) and 3-N-methylcarbamoyl (GYKI 53784) derivatives were also examined in some assays. These 2,3-benzodiazepines, known as prototypic non-competitive antagonists of AMPA receptors, showed a peculiar profile in some routinely used antinociceptive tests. They were found fairly potent in rat tail flick and mouse phenylquinone writhing assays but the dose-response curves were rather shallow as compared to that of morphine. Their action is stereoselective, i.e., the (+) isomers were found inactive, in agreement with the previous in vitro studies. Their antinociceptive effect could not be reversed by naloxone and the GYKI compounds did not potentiate significantly the morphine-induced analgesia. In the mouse hot plate assay the 2,3-benzodiazepines were active only in doses inducing visible motor incapacitation. In rats, GYKI 52466 weakly reduced the hypersensitivity accompanying acute carrageenan edema. However, it potently inhibited the hyperalgesia during Freund adjuvant-induced chronic arthritis. In the latter assay GYKI 52466 also attenuated the body weight loss without altering the paw edema. The present findings confirm reports in the literature which indicate AMPA receptors may contribute to certain forms of pathological hyperalgesia, e.g., to that detectable in inflamed tissues.

Selective interaction of homophtalazine derivatives with morphine.

Homophtalazines show specific binding sites in the nigrostriatal system and to find their target of action the interactions between these derivatives, nerisopam and girisopam, and chlorpromazine, chlordiazepoxide and morphine were assessed. The compounds did not influence the chlorpromazine induced decrease in motility and catalepsy, nor did they alter the antiaggressive and anticonvulsive action of chlordiazepoxide. However, nerisopam and girisopam augmented the agonist potency of morphine to induce catalepsy or analgesia; they also altered the opioid antagonist potency of naloxone. The naloxone-induced decrease in sucrose consumption in drinking water was augmented by nerisopam and girisopam. It is suggested that a possible target of action of homophtalazines is the opioid signal transduction.

Phrenic nerve conduction study in demyelinating neuropathies and open-heart surgery.

OBJECTIVES: The aim of this study was to determine normal values of phrenic nerve conduction (PNC) in healthy individuals; to evaluate the subclinical extent of phrenic nerve involvement in Guillain-Barré syndrome (G-B) and hereditary motor and sensory neuropathy-I (HMSN-I), and to evaluate phrenic nerve damage after cardiac surgery. MATERIALS AND METHODS: PNC was performed by transcutaneous stimulation in the neck and recording the diaphragmatic potential from surface electrodes placed at the seventh and eight intercostal spaces. PNC was performed bilaterally in 25 healthy volunteers and 25 patients before and after open-heart surgery. Right PNC was also performed in 5 cases with G-B and 5 patients with HMNS-I. RESULTS: Latency and amplitude of the diaphragmatic potential were the same in controls and in patients with cardiac disease before surgery. After surgery, 28% of patients had left phrenic nerve inexcitability, and 8% had reduced amplitude of the response. These 9 patients demonstrated elevation of the left hemidiaphragm on chest radiography. Left PNC performed 1 year after the operation showed improvement in latency and amplitude of the responses in all except one patient. PNC was prolonged in 4 out of 5 cases with G-B and in all patients with HMNS-I. CONCLUSIONS: PNC is an easy and reliable method in evaluating phrenic nerve damage due to hypothermia or primary stretch injury in patients after cardiac surgery. PNC may be helpful in detecting diaphragmatic involvement before clinical ventilatory insufficiency in demyelinating neuropathies such as G-B and HMNS-I.

Delayed papillary muscle rupture following mild chest trauma.

A case of delayed papillary muscle rupture is reported, which developed 24 hours following a mild chest trauma. Transthoracic echocardiography established the diagnosis; immediate mitral valve replacement was carried out. The postoperative course was uneventful.

[Atrioventricular block at the nodal level and block of an accessory pathway during percutaneous mitral valvuloplasty]. / Bloqueo auriculoventricular a nivel del nodo y de una vía accesoria durante una valvuloplastia mitral percutánea.

We describe the simultaneous occurrence of a temporal complete atrioventricular block and a persistent disappearance of preexcitation, in a patient with rheumatic mitral stenosis and a ventricular preexcitation, after an effective percutaneous mitral valvuloplasty. These conduction disturbances were attributed to atrioventricular node and paraseptal atrioventricular pathway trauma, due to transseptal manipulation during the mitral valvuloplasty.

[Combination of quinidine and verapamil in auricular fibrillation]. / Combinación de quinidina y verapamil en la fibrilación auricular.

The efficacy of the association of verapamil plus quinidine in 70 patients with atrial fibrillation, 64 of them after having cardiac surgery, was assessed. Oral dosage ranged from 825 mg to 1,100 mg for quinidine polygalacturonate and 240 mg to 320 mg for verapamil. All patients but two reached a good control of heart rate (mean heart rate less than 110 beats/min) while arrhythmia persisted. Sixty patients (85.7%) reverted to normal sinus rhythm in a period of 2.4 +/- 1.5 days (mean +/- SD). According to the atrial fibrillation duration three subsets of patients with different conversion rates to sinus rhythm were established (p less than 0.01): group A (lasting from 1 day to 3 months) 31/39 (96%); group B (lasting 3 to 6 months) 18/21 (85.7%) and group C (lasting 6 to 12 months) 5/10 (50%) (p less than 0.01). Plasma quinidine levels were maintained at either near to or therapeutic range (2.6 +/- 0.94 micrograms/ml). Adverse effects comprised one ventricular arrhythmia-induced syncope (quinidine syncope) and two cases of systemic hypotension. Quinidine-verapamil association is a good alternative in the treatment of atrial fibrillation, particularly in those of recent onset, according to the high rates of conversion to normal sinus rhythm, affording control of heart rate while atrial fibrillation persists. Adverse reactions did not differ in severity from those observed with quinidine monotherapy.

[Indications and surgical techniques in the acute phase of infective endocarditis]. / Indicaciones y técnicas quirúrgicas en la fase aguda de la endocarditis infecciosa.

Infectious endocarditis is increasingly resistant to antibiotic therapy, due to the increasing number of patient with cardiovascular prostheses or those who are severely immunosuppressed. Frequently, this syndrome and its complications can only be solved with surgery. In this article, which is based on the international literature plus own observations in 77 patients, the indications for surgery and the different technical approaches during the acute phase of infectious endocarditis are reviewed. Surgery to control infectious endocarditis is indicated when there is one of the following situations: a) persistence of infection despite an adequate antibiotic treatment, usually due to a specific pathogen (Staphylococcus aureus, fungus, etc.) or to a low antibiotic penetration into the infected issues (abscess); b) progressive hemodynamic deterioration due to tissular destruction and development of valvular incompetence or fistulous communications or c) development of other complications (repetitive embolism, cardiovascular aneurysms, conduction blocks, etc.). Hemodynamic deterioration due to heart failure refractory to medical treatment is the most frequent indication for cardiovascular surgery, and this was present in 61% of our patients. The timing for surgery is still controversial, although scheduling it at an early stage is generally preferred. The specific surgical technique is chosen according to the degree of tissular destruction and is aimed to remove the infected tissue and to repair the damaged structures or, if this is not feasible, to implant cardiovascular prosthesis.

[Massive thrombosis of the left atrium. Surgical experience with a series of 117 patients]. / Trombosis masiva de aurícula izquierda. Experiencia quirúrgica en una serie de 117 pacientes.

From 1975 to 1988 we have operated 117 patients with left arterial thrombosis associated with rheumatic mitral valve disease. Seventy-seven were female and 40 male, with ages ranging from 22 to 69 years. In 75 cases (64.1%) the valvular lesion was mitral stenosis. Embolic antecedents were present in 38 cases (32.4%) and 95 patients (81.1%) were in class III or IV of the NYHA functional classification. In 48 cases we performed a mitral commissurotomy and in 51 cases mitral valve replacement, associated to left artrial thrombectomy. In the remaining 18 patients we made other valve procedures. The hospital mortality was 15 cases (12.8%), eight because low cardiac output, four because severe brain injury and three because posterior atrioventricular sulcus disruption. In 41.1% of the survivors there was serious hospital complications, standing out the incidence of 8 cases of transient neurologic accidents. We have followed 98 of the 102 hospital survivors between 10 and 140 months (mean 57 months). Three patients died in the follow-up, two of them during a reintervention because bioprosthesis disfunction and the third one during a reintervention because prosthetic infective endocarditis. Nine additional patients were reoperated because recidivant valvular lesions or because prosthetic disfunction, and two patients suffered embolic events during the follow-up. The antithrombotic therapy was abandoned in 19.6% of patients. At present 73.6% are in functional class I and 26.3% in class II. The association of left atrial thrombosis with with mitral valve disease induce a surgical morbimortality greater than usual for isolated valvular lesions, being mandatory a watchfull surgical technic.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lipomatous hypertrophy of the interauricular septum, fibrosis of the bundle of His and calcification of the mitral annulus associated with multiple rhythm and conduction disorders. The anatomicoclinical correlations]. / Hipertrofia lipomatosa del septo interauricular, fibrosis del haz de His y calcificación del anillo mitral asociadas a múltiples trastornos del ritmo y de la conducción. Correlaciones anatomoclínicas.

We present the case of a 72 years old female with multiple episodes of atrial fibrillation, interatrial block and different degrees of atrioventricular block, that died because of stroke. Postmortem pathologic examination showed a lipomatous hypertrophy of the interatrial septum (previously suspected on echocardiogram), his bundle and right branch degeneration as well as mitral annular calcification extended to conduction system. According to these pathologic findings, rhythm and conduction disturbances are correlated with the two levels (atrial and atrioventricular) where anatomic abnormalities were found.