An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Sophora tonkinensis and active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency in myocardial ischemia mice through regulating the vesicle-mediated transport pathway.

Ancient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1ß, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI.

The ß-adrenoceptor agonist isoproterenol rescues acetaminophen-injured livers through increasing progenitor numbers by Wnt in mice.

UNLABELLED: Acetaminophen (APAP)-induced acute liver injury (AILI) is a major health problem. Accumulating evidence suggests that the sympathetic nervous system (SNS) regulates neuronal and hematopoietic progenitors. SNS signaling affects hepatic progenitor/oval cells (HPCs) and ß-adrenoceptor agonism will expand HPCs to reduce AILI. Dopamine ß-hydroxylase-deficient mice (Dbh-/-), lacking catecholamine SNS neurotransmitters, isolated HPCs, and immature ductular 603B cells were initially used to investigate SNS involvement in HPC physiology. Subsequently, control mice were treated with APAP (350 mg/kg) followed by the ß-adrenoceptor agonist, isoproterenol (ISO), or the ß-adrenoceptor antagonist, propranolol. Mechanistic studies examined effects of non-SNS HPC expansion on AILI, involvement of the canonical Wnt/ß-catenin pathway (CWP) in the action of ISO on HPC expansion and comparison of ISO with the current standard of care, N-acetylcysteine (NAC). Dbh-/- mice lacking catecholamines had low HPC numbers, reconstituted by ISO. In vitro, ISO-induced proliferation of 603B cells was CWP dependent. In control mice, AILI raised HPC numbers, further increased by ISO, with attenuation of liver injury. Delayed administration of NAC did not, but delayed ISO did, reverse AILI. Propranolol worsened AILI. AILI activated the CWP, and ISO enhanced Wnt-ligand production. HPCs were the major source of Wnt ligands. Recombinant Wnt3a and ISO-603B-conditioned media, but not ISO alone, protected isolated hepatocytes from death, reversed by DKK1-a Wnt antagonist. Additionally, tumor-associated weak inducer of apoptosis expanded HPCs and protected against AILI. Furthermore, allotransplantation of HPCs from APAP+ISO-treated mice to other APAP-injured mice improved AILI, an effect antagonized by DKK1. CONCLUSION: SNS catecholamines expand HPCs, which are both targets and sources of Wnt ligands. Hepatoprotection by ISO is mediated by para- and autocrine effects of Wnt signaling. ISO represents novel pharmacotherapy for AILI.

Synergistic restoring effects of isoproterenol and magnesium on KCNQ1-inhibited bradycardia cell models cultured in microelectrode array.

OBJECTIVES: Bradycardia is caused by loss-of-function mutations in potassium channels that regulate phase 3 repolarization of the cardiac action potential. The purpose of this study is to monitor the effects of potassium channel (KCNQ1) inhibition and to evaluate the effects of isoproterenol (ISO) and MgSO4 in restoring sinus rhythm in atrial cells. METHODS: Microelectrode array was used to analyze conduction velocity, voltage amplitude and cycle length of atrial cells (HL-1). A combination of ISO and MgSO4 was used to restore sinus rhythm in these cells. RESULTS: mRNA expression levels of KCNQ1 (42.2 vs. 100%, p < 0.0001), connexin 43 (29.6 vs. 100%, p = 0.0033), atrial natriuretic peptide (31.0 vs. 100%, p = 0.0030), cardiac actin (38.2 vs. 100%, p < 0.0001) and α-myosin heavy chain (31.2 vs. 100%, p = 0.00254) were significantly lower in the KCNQ1 gene-inhibited group compared to the control group. When treated with MgSO4 (1 mM) and ISO (10 µM), conduction velocity (0.0208 ± 0.0036 vs. 0.0086 ± 0.0014 m/s, p = 0.0004) and voltage amplitude (1,210.78 ± 65.81 vs. 124.1 ± 13.30 µV, p < 0.0001) were higher, and cycle length (431.55 ± 2.05 vs. 1,015.15 ± 4.31 ms, p < 0.0001) was shorter than in the gene-inhibited group. CONCLUSION: Inhibition of sinus rhythm in the bradycardia cell model was recovered by treatment with ISO and MgSO4, demonstrating the potency of combination therapy in the treatment of bradycardia.

[Ablation of premature ventricular contractions originating in the right ventricular outflow tract using non-contact mapping]. / Ablación de extrasistolia ventricular del tracto de salida ventricular derecho con sistema de cartografía sin contacto.

Premature ventricular contractions originating in the right ventricular outflow tract may respond poorly to pharmacological treatment, and ablation using conventional fluoroscopically-guided systems may be complicated by the difficulty in inducing arrhythmias. We describe the use of a non-contact mapping system to ablate difficult-to-induce premature ventricular contractions originating in the right ventricular outflow tract. Five premature ventricular contractions sites in the right ventricular outflow tract were ablated in a prospective series of 4 patients. Patients had a poor quality of life and had not responded to antiarrhythmic drugs. A mean of 3 radiofrequency pulses per site was applied and mean application time was 113±15s. We achieved a 100% acute success rate and there were no complications. Patients were asymptomatic without drug therapy after a mean of 30±16 months of follow-up. The noncontact mapping system is highly effective in eliminating difficult to induce, isolated premature ventricular contractions.

Re-evaluating the efficacy of beta-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling.

AIMS: Long QT syndrome (LQTS) is a heterogeneous collection of inherited cardiac ion channelopathies characterized by a prolonged electrocardiogram QT interval and increased risk of sudden cardiac death. Beta-adrenergic blockers are the mainstay of treatment for LQTS. While their efficacy has been demonstrated in LQTS patients harbouring potassium channel mutations, studies of beta-blockers in subtype 3 (LQT3), which is caused by sodium channel mutations, have produced ambiguous results. In this modelling study, we explore the effects of beta-adrenergic drugs on the LQT3 phenotype. METHODS AND RESULTS: In order to investigate the effects of beta-adrenergic activity and to identify sources of ambiguity in earlier studies, we developed a computational model incorporating the effects of beta-agonists and beta-blockers into an LQT3 mutant guinea pig ventricular myocyte model. Beta-activation suppressed two arrhythmogenic phenomena, transmural dispersion of repolarization and early after depolarizations, in a dose-dependent manner. However, the ability of beta-activation to prevent cardiac conduction block was pacing-rate-dependent. Low-dose beta-blockade by propranolol reversed the beneficial effects of beta-activation, while high dose (which has off-target sodium channel effects) decreased arrhythmia susceptibility. CONCLUSION: These results demonstrate that beta-activation may be protective in LQT3 and help to reconcile seemingly conflicting results from different experimental models. They also highlight the need for well-controlled clinical investigations re-evaluating the use of beta-blockers in LQT3 patients.

Clinical and electrophysiological characteristics, and relatively benign outcome, of typical atrioventricular nodal reentrant tachycardia in children and adolescents.

BACKGROUND: Atrioventricular nodal re-entrant tachycardia is an uncommon arrhythmia in children. The natural history of this disturbance is poorly known in young patients. METHODS: We analyzed the clinical and electrophysiological features, and the final outcome, in 19 children affected by typical atrioventricular nodal re-entrant tachycardia diagnosed by a transoesophageal electrophysiological study. RESULTS: Of the cohort, 12 patients were female and 7 male, with a mean age of 11 years. Dual atrioventricular nodal physiology was demonstrated in 14 children (73%). The mean length of the tachycardia cycle was 297 milliseconds, with periods of 2 to 1 atrioventricular block during tachycardia noted in 5 children (26%). The mean cycle length was significantly shorter in the children who presented episodes of 2 to 1 atrioventricular block than in those who did not. After diagnosis, 12 children were not treated, 6 were treated with medical therapy, and 1 was submitted to radiofrequency transcatheter ablation. During a mean follow-up period of 41 months, 2 children with rare, but sustained, episodes of tachycardia that initially had not been treated were submitted to radiofrequency transcatheter ablation. Among children treated pharmacologically, 1 teenager was submitted to radiofrequency transcatheter ablation on the basis of parental choice, 3 children have discontinued medical therapy recording only sporadic episodes of tachycardia, and 2 children are still treated with antiarrhythmic drugs. At the last follow-up visit, 13 children (68%) were without any treatment, 4 had been successfully ablated, and 2 were still on medical treatment. CONCLUSIONS: Our data indicates a relatively benign outcome in this group of children and adolescents with atrioventricular nodal re-entrant tachycardia.

Autonomic and pharmacological responses of idiopathic ventricular tachycardia arising from the left ventricular outflow tract.

BACKGROUND: It is well recognized that the mechanism of idiopathic ventricular tachycardia (VT) arising from the right ventricular outflow tract (RVOT) is mostly due to cyclic AMP-mediated triggered activity. The mechanism of VT arising from the left ventricular outflow tract (LVOT) has not been well clarified whether it is the same as VT of RVOT. METHODS: We studied autonomic modulations and pharmacological interventions on VT/premature ventricular contractions (PVCs) from LVOT to explore its possible mechanism in six patients (age: 49 +/- 14, three males). None of them had structural heart diseases. RESULTS: Isoproterenol application easily induced VT and/or PVCs from LVOT. Valsalva maneuvers suppressed isoproterenol-induced VT in two and PVCs in two, and carotid sinus massage (CSM) suppressed PVCs in one patient. Adenosine triphosphate inhibited both VT and PVCs in all six patients. Propranolol, lidocaine, and procainamide eliminated VT/PVCs in four, three, and four patients, respectively. Verapamil terminated VT in one and PVCs in another one patient, but aggravated PVCs to VT in one patient. CONCLUSION: The results suggest that the mechanism of VT from LVOT is mostly due to cAMP-mediated triggered activity as similar to that in VT from RVOT.

Effects of cardioactive medications on retrograde conduction: continuing relevance for current devices.

INTRODUCTION: Retroconduction (ventriculo-atrial conduction) remains a problem for patients with implanted cardiac rhythm devices. Pacemaker algorithms can detect and terminate endless loop tachycardia (ELT), but actual prevention of ELT may require anti-arrhythmic drugs (AADs). Similarly, AADs can affect ICD rhythm discrimination algorithms that depend on atrio-ventricular ratios. There is concern whether these drugs remain effective during stress situations. METHODS: Electrophysiologic studies that included retroconduction testing using slow ramp pacing were done in 1332 patients. The presence or absence of retroconduction at baseline and with drug was recorded, as was the rate at block. As a stress surrogate, isoproterenol was used to test retroconduction and reversal of drug-induced block. RESULTS: Procainamide, mexiletine, phenytoin, disopyramide, quinidine, beta-blockers, encainide, and amiodarone caused complete retrograde block or decreased the rate at which block occurred (mean 76% of patients, p < 0.008), whereas digoxin, lidocaine, diltiazem, and verapamil did not. Isoproterenol (in the absence of AADs) increased the rate at block in 82% of 404 patients with retroconduction at baseline (p < 0.005). Of 319 patients without retroconduction at baseline, 134 (42%) developed retroconduction after isoproterenol. Isoproterenol reversed retrograde block in 39% of patients with block on an AAD. Amiodarone, digoxin, and the combination of digoxin plus a beta-blocker were most effective at resisting this reversal of ventriculo-atrial block (80%, 68%, and 75% respectively). CONCLUSION: Most of the AADs reviewed increase the cycle length at block or abolish retroconduction, while isoproterenol has the opposite effect. Anti-arrhythmic medications, particularly amiodarone, digoxin, and the combination of digoxin plus a beta-blocker may be considered for a patient with multiple ELT episodes or certain ICD detection problems.

[Insertion of catheter for temporary transvenous ventricular pacing at prehospital scene after sudden malfunction of pacemaker]. / Pose d'une sonde d'entraînement électrosystolique endocavitaire en préhospitalier suite à un dysfonctionnement de stimulateur cardiaque.

A 70-year-old patient who had been fitted with a pacemaker for 27 years consulted his cardiologist to check the latest device, which had been changed in 1998. During the examination there was a sudden malfunction of the pacemaker, which became uncontrollable, resulting in an escape rhythm of 15 beats/min and circulatory insufficiency. Attempted treatment by isoprénaline and external transcutaneous systolic stimulation failed, and an intraventricular catheter was therefore positioned successfully as an emergency prehospital manoeuvre. This produced good haemodynamic stability, allowing the transfer of the patient to hospital where his pacemaker was changed.

Dual AV nodal pathways and conduction during atrial fibrillation.

OBJECTIVE: AV node modification reduces ventricular rate during atrial fibrillation (AF). We induced AF in patients with dual AV nodal pathways before and after radiofrequency ablation (RFA) of AV nodal reentry tachycardia (AVNRT) and examined the role of the two pathways in the transmission of impulses during AF. DESIGN AND RESULTS: AF was induced in 30 patients before and after slow pathway ablation. Before RFA mean (AF CLmean) and shortest (AF CLshort) ventricular cycle lengths correlated significantly to ERPf, ERPs, and antegrade Wenckebach block (r = 0.53-0.67). Ablation eliminated slow pathway conduction completely in 10 patients (group A), whereas in 20 patients some slow pathway conduction was still present (group B). After RFA there was a 10% increase in AF CLmean (20%, p < 0.05 in A and 5%, p = NS in B) and 7% in AF CLshort (11%, p = NS in A and 6%, p = NS in B). During isoproterenol infusion after RFA AF CLmean increased 8% (p < 0.05) (14% in A and 6% in B; p < 0.05 in both groups). The effects of RFA were mainly confined to patients with ERPs less than the median value (13% vs 3% in those above median, respectively; p < 0.05). CONCLUSION: The refractory periods of the AV nodal pathways are the main determinants of ventricular rate during induced AF. Slow pathway ablation reduces ventricular rate during AF. This effect was greatest when slow pathway conduction was completely eliminated. A short ERPs predicted a greater reduction in ventricular rate.

Reversal of atrial mechanical stunning after cardioversion of atrial arrhythmias: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy.

BACKGROUND: Atrial mechanical stunning develops on termination of chronic atrial arrhythmias and is implicated in the genesis of thromboembolic complications after cardioversion. The mechanisms responsible for atrial mechanical stunning are unknown. The effects of atrial rate, isoproterenol, and calcium on atrial mechanical function in patients with atrial stunning have not been evaluated, and it is not known if atrial stunning can be reversed. METHODS AND RESULTS: Thirty-five patients with chronic atrial flutter (AFL) undergoing radiofrequency ablation were studied. Fifteen patients in sinus rhythm undergoing ablation for paroxysmal AFL were studied as control for effects of the procedure. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AFL, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol or calcium. With termination of AFL, LAAEV decreased from 59.0+/-3.7 cm/s to 18.8+/-1.4 cm/s (P<0.0001) and LASEC grade increased from 0.9+/-0.1 to 2.2+/-0.2 (P<0.0001). Pacing increased LAAEV to a maximum of 38.4+/-3.2 cm/s (P<0.0001) and reduced LASEC grade to 1.9+/-0.2 (P=0.005). Isoproterenol and calcium reversed atrial mechanical stunning with LAAEV increasing to 89.3+/-12.6 cm/s (P=0.0007) and 50.2+/-10.5 cm/s (P=0.005), respectively, and LASEC grade decreasing to 0.2+/-0.1 (P=0.001) and 1.4+/-0.2 (P=0.01), respectively. The postpacing pause increased LAAEV to 69.3+/-3.7 cm/s (P<0.0001). No change in LAAEV was observed in the paroxysmal AFL group. CONCLUSION: Atrial mechanical stunning can be reversed by pacing at increased rates and through the administration of isoproterenol or calcium. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium as a result of chronic atrial flutter.

Treatment of pulmonary air embolism with hyperbaric oxygen and isoproterenol in rats.

BACKGROUND: Pulmonary air embolism (PAE) occurs in inappropriate decompressions or clinical complications. Sudden lodging of air bubbles in the pulmonary circulation results in pulmonary hypertension, pulmonary edema, and deficiency in cardiopulmonary functions, which are often fatal without timely intervention. In this study, we investigated the effectiveness of hyperbaric oxygen (HBO2) therapy on the acute lung injury induced by venous air infusion in rats. METHODS: Systemic and pulmonary arterial pressures were monitered through catheters in the femoral artery and pulmonary artery, respectively. PAE was induced by venous infusion of air at the rate of 25 microL x min(-1). Wet/dry weight ratio of the lung and protein concentration and LDH activity in the bronchoalveolar lavage (BAL) fluid were measured at the end of the experiment. RESULTS: Air infusion raised the mean pulmonary arterial pressure (MPAP) within 10 min to a plateau that was 208% above the baseline value. The wet/dry ratio of lungs were 4.83 +/- 0.28, 4.98 +/- 0.39, and 5.20 +/- 0.38 in the groups receiving 0.13, 0.50, and 1.0 ml of air infusion, respectively, which were significantly higher than the control group that averaged 4.47 +/- 0.24. The protein concentration (mg x L(-1)) and the LDH activity (mAbs x min(-1)) in BAL fluid increased from 291 +/- 78 and 21.6 +/- 4.8 in the control group to 1491 +/- 402 and 83.3 +/- 15.4, 1432 +/- 278 and 75.2 +/- 35.4, and 1809 +/- 493 and 59.6 +/- 23.3 in the lungs receiving air infusion for 5, 20, and 40 min, respectively. Treatment with hyperbaric oxygen at 3 ATA or 6 ATA, or with isoproterenol reduced neither the increased wet/dry weight ratio nor the protein concentration and LDH activity in the BAL fluid. CONCLUSION: Our results demonstrated that venous air infusion induced acute lung injury in rats and suggested that neither HBO2 therapy nor isoproterenol treatment could not effectively reverse the PAE-induced lung injury.

Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia.

BACKGROUND: Radiofrequency ablation of the "slow pathway" in atrioventricular nodal reentrant tachycardia (AVNRT) relies on tachycardia non-inducibility after ablation as success criterion. However, AVNRT is frequently non-inducible at baseline. Thus, autonomic enhancement using either atropine or isoproterenol is frequently used for arrhythmia induction before ablation. METHODS: 80 patients (57 women, 23 men, age 50+/-14 years) undergoing slow pathway ablation for recurrent AVNRT were randomized to receive either 0.01 mg/kg atropine or 0.5-1.0 microg/kg/min isoproterenol before ablation after baseline assessment of AV conduction. The effects of either drug on ante- and retrograde conduction was assessed by measuring sinus cycle length, PR and AH interval, antegrade and retrograde Wenckebach cycle length (WBCL), antegrade effective refractory period (ERP) of slow and fast pathway and maximal stimulus-to-H interval during slow and fast pathway conduction. RESULTS: Inducibility of AVNRT at baseline was not different between patients randomized to atropine (73%) and isoproterenol (58%) but was reduced after atropine (45%) compared to isoproterenol (93%, P<0.001). Of the 28 patients non-inducible at baseline isoproterenol rendered AVNRT inducible in 21, atropine in 4 patients. Dual AV nodal pathway physiology was present in 88% before and 50% after atropine compared to 83% before and 73% after isoproterenol. Whereas both drugs exerted similar effects on ante- and retrograde fast pathway conduction maximal SH interval during slow pathway conduction was significantly shorter after isoproterenol (300+/-48 ms vs. 374+/-113 ms, P=0.012). CONCLUSION: Isoproterenol yields higher AVNRT inducibility than atropine in patients non-inducible at baseline. This may be caused by a more pronounced effect on antegrade slow pathway conduction.

Effects of alpha - and beta -adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock.

OBJECTIVE: To examine the effects of adrenergic stimulation on hepatosplanchnic perfusion, oxygen extraction, and tumor necrosis factor-alpha production during endotoxic shock. DESIGN: In vivo, prospective, randomized, controlled, repeated-measures, experimental study. SETTING: Experimental physiology laboratory in a university teaching hospital. SUBJECTS: Twenty-one anesthetized and mechanically ventilated dogs. INTERVENTIONS: An intrapericardial catheter was positioned. Catheters for blood sampling were inserted into the right femoral artery, hepatic vein, portal vein, and pulmonary artery. Ultrasonic flow probes were placed around the portal vein, the hepatic artery, the mesenteric artery, the left renal artery, and the left femoral artery. Animals received 2 mg/kg of Escherichia coli endotoxin, followed by fluid resuscitation. Seven dogs received intravenous isoproterenol (0.1 microg/kg x min(-1)), seven received phenylephrine (1 microg/kg x min(-1)), and seven served as controls. Thirty minutes later, cardiac tamponade was introduced to study organ perfusion and tissue oxygen extraction capabilities. MAIN RESULTS: The isoproterenol group had a higher cardiac index and stroke index and lower systemic vascular resistance than the other groups. The phenylephrine group had a higher arterial pressure but a lower cardiac index than the isoproterenol group. The isoproterenol group had a higher hepatic artery blood flow than the other groups and a higher portal and mesenteric flow than the control group. Liver and gut mucosal blood flow was greater in the isoproterenol than in the phenylephrine group. The isoproterenol group had a lower global critical oxygen delivery than the other groups (8.8 +/- 1.3 vs. 13.1 +/- 2.0 (control) and 11.8 +/- 3.3 mL/kg x min(-1) (phenylephrine); both p < .05) and a higher liver critical oxygen extraction ratio than the control group. Isoproterenol tended to attenuate, but phenylephrine significantly increased, blood tumor necrosis factor levels. CONCLUSIONS: During endotoxic shock, beta-stimulation can improve hepatosplanchnic perfusion and enhance tissue oxygen extraction capabilities, whereas alpha-stimulation does not. In addition, alpha-adrenergic stimulation can increase tumor necrosis factor levels.

[An original method of demolition of re-entry tachycardia of atrioventricular node]. / Original'nyi sposob ustraneniia rientri takhikardii predserdno-zheludochkovogo uzla.

In 75 patients with reentry tachycardia of atrioventricular node the dotted applications were performed on the ishtmus of coronal sinus level, right from the tricuspid valve ring deep to the atrium. The ratio of amplitudes of atrial and ventricular commissures was in limits of 1:10-11:10. After each application the possibility of tachycardia occurrence was tested. It took one procedure to perform to climinate tachycardia in all the patients. The applications quantity had constituted 5.5 +/- 3.8 at average. Roentgenexposition time had constituted--(10.2 +/- 3.8) min. The atrioventricular conduction disorder was not observed. Recurrency of arrhythmia was not noted in 5 months--4 years follow-up.

Differential alteration of cardiotonic effects of EMD 57033 and beta-adrenoceptor agonists in volume-overload rabbit ventricular myocytes.

BACKGROUND: We investigated the effects of EMD 57033, a prototype Ca2+ sensitizer, and beta-adrenoceptor agonists in ventricular myocytes isolated from the volume-overload (V-O) heart failure model of the rabbit. METHODS AND RESULTS: V-O cardiac hypertrophy was induced in rabbits by the formation of an arterio-venous shunt between the carotid artery and jugular vein 12 to 15 weeks after the operation. Ventricular myocytes were enzymically isolated from normal and V-O rabbit hearts. The myocyte was loaded with a fluorescence Ca2+ dye, indo-1, and Ca2+ transients, and cell lengths were measured simultaneously. V-O myocytes were significantly larger than control myocytes. Duration of Ca2+ transients and cell shortening was significantly longer in the V-O myocytes than in control myocytes. Effects of cardiotonic interventions, including EMD 57033, isoproterenol, and dobutamine, on Ca2+ transients and cell shortening in V-O myocytes were compared with those in control rabbit myocytes. Isoproterenol and dobutamine increased the systolic cell shortening and peak Ca2+ transients and abbreviated the duration of cell shortening and Ca2+ transients. These responses were markedly attenuated in V-O myocytes. By contrast, the response of cell shortening to EMD 57033 was unaltered, and the Ca2+ sensitizing effect of EMD 57033 was rather enhanced in V-O myocytes. CONCLUSION: Our results indicate that the effectiveness of Ca2+ sensitizers is maintained in the V-O rabbit hypertrophy and heart failure model in contrast to the blunted response to beta-adrenoceptor agonists, which provides an insight on therapeutic strategy with Ca2+ sensitizers for the treatment of contractile dysfunction in congestive heart failure.

Post-rest contraction amplitude in myocytes from failing human ventricle.

It has been reported that the balance between the two main Ca2+ removal systems in the cardiac cells, the sarcoplasmic reticulum (SR) and Na+/Ca2+ exchanger, is altered in failing human heart. We have studied post-rest contraction behaviour as a non-invasive probe of the amount of Ca2+ stored in the SR in myocytes from failing and non-failing human ventricle. The first beat following a rest interval, as a percentage of the preceding steady state (B1/SS), was larger and more variable in cells from failing heart, indicating some accumulation of Ca2+ in the SR during rest. This could be mimicked by treatment of myocytes with digoxigenin, a compound which increases intracellular Na+, suggesting that alterations in the Na+ balance of the cell might contribute to the effect. Isoprenaline, which stimulates Ca2+ uptake by the SR while the myocyte is beating, prevented SR Ca2+ accumulation during rest in susceptible myocytes. We hypothesize that loss of SR function in the failing heart is partially compensated for by increased Ca2+ extrusion via the Na+/Ca2+ exchange in the contracting myocyte, leading to increased intracellular Na+ during activity. This Na+ is lost at rest, predisposing the cells to accumulate Ca2+ in the SR. Experiments to test this hypothesis are proposed.