Ca2+-dependent modulation of single human cardiac L-type calcium channels by the calcineurin inhibitor cyclosporine

OBJECTIVE: Activity of single L-type calcium channels (LTCC) is enhanced in human failing myocardium (Circulation 98 (1998) 969.), most likely due to impaired dephosphorylation. Protein phosphatase 2B (calcineurin) has recently been shown to be involved in heart failure pathophysiology. We now focus on the regulation of single LTCC by calcineurin that were prevented by Ca(2+)-free experimental conditions in our previous study. METHODS: Single LTCC currents were recorded in myocytes from human atrium and ventricle. Charge carriers were 70 mM Ba(2+), or a mixture of 30 mM Ca(2+) and 60 mM Ba(2+) to facilitate Ca(2+) permeation through recorded channels. The calcineurin inhibitor cyclosporine (10 microM) was used to reveal a putative role for calcineurin in regulation of LTCC. RESULTS: A mixture of Ca(2+) and Ba(2+) as charge carriers allowed for Ca(2+) permeation through recombinant human embryonic kidney cells and native (atrial and ventricular) human cardiac LTCC. With only Ba(2+) as the charge carrier, activities of both ventricular and atrial LTCC were strongly decreased by cyclosporine. In contrast, channel activity remained constant when Ca(2+) permeation was provided. In the presence of thapsigargin and (S)-BayK 8644, cyclosporine here even increased channel activity. CONCLUSIONS: We propose a dual cyclosporine effect on human cardiac LTCC. A non-specific inhibitory effect prevails with Ba(2+) permeation but can be compensated or overcome by a specific Ca(2+)-dependent stimulation with Ca(2+) permeation. More complete restoration of physiological Ca(2+) movements (e.g., Ca(2+) release from sarcoplasmic reticulum) will help to define even more precisely the involvement of calcineurin in regulation of human cardiac LTCC.     

Chronic inflammatory demyelinating polyradiculoneuropathy associated intracranial hypertension

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated demyelinating neuropathy. In this report, we detail the course of a 58-year-old male patient who had headache and double vision followed by progressive paresthesia and difficulty in walking. The patient had bilateral papilledema and mild leg weakness, absent ankle jerks and loss of sensation in distal parts of his lower and upper extremities. His electromyography (EMG) was concordant with CIDP and lumbar puncture revealed high opening pressure. The polyradiculoneuropathy as well as the papilledema and elevated cerebrospinal fluid (CSF) pressure improved under steroids. The improvement in intracranial hypertension (IHT) and papilledema under steroid treatment suggests that the IHT in this patient might be associated with CIDP.     

Catheter ablation of ventricular tachycardias using remote magnetic navigation: a consecutive case-control study

Remote Magnetic Navigation for VT Ablation. Background: This study aimed to compare acute and late outcomes of VT ablation using the magnetic navigation system (MNS) to manual techniques (MAN) in patients with (SHD) and without (NSHD) structural heart disease. Methods: Ablation data of 113 consecutive patients (43 SHD, 70 NSHD) with ventricular tachycardia treated with catheter ablation at our center were analyzed. Success rate, complications, procedure, fluoroscopy, and ablation times, and recurrence rates were systematically recorded for all patients. Results: A total of 72 patients were included in the MNS group and 41 patients were included in the MAN group. Patient age, gender, and right ventricular and left ventricular VT were equally distributed. Acute success was achieved in 59 patients in the MNS group (82%) versus 27 (66%) patients in the MAN group (P = 0.046). Overall procedural time (177 ± 79 vs 232 ± 99 minutes, P < 0.01) and mean patient fluoroscopy time (27 ± 19 vs 56 ± 32 minutes, P < 0.001) were all significantly lower using MNS. In NSHD pts, higher acute success was achieved with MNS (83,7% vs 61.9%, P = 0.049), with shorter procedure times (151 ± 57 vs 210 ± 96, P = 0.011), whereas in SHD‐VT these were not significantly different. No major complications occurred in the MNS group (0%) versus 1 cardiac tamponade and 1 significantly damaged ICD lead in the MAN group (4.9%, NS). After follow‐up (20 ± 11 vs 20 ± 10 months, NS), VT recurred in 14 pts (23.7%) in the MNS group versus 12 pts (44.4%) in the MAN group (P = 0.047). Conclusions: The use of MNS offers advantages for ablation of NSHD‐VT, while it offers similar efficacy for SHD‐VT. ((J Cardiovasc Electrophysiol, Vol. 23, pp. 948‐954, September 2012)     

Spectroscopic,antiproliferative and antiradical properties of Cu(II), Ni(II), and Zn(II) complexes with amino acid based Schiff bases

Novel six Cu(II), Ni(II), and Zn(II) complexes with Schiff bases derived from 4-aminobenzoic acid with terephtaldehyde and amino acids (glycine, β-alanine). Structures have been proposed from elemental analysis, UV–Vis, IR, NMR, TGA, DTA, and magnetic measurements. Spectroscopic studies suggest that coordination occurs through azomethine nitrogen, hydroxyl group, and carbonyl oxygen of the ligands to the metal ions. The elemental analyses of the complexes where L is Schiff base ligands, are confined to the stoichiometry of the type M₂L₂(CH₃COO)₂ [M = Cu(II)]; and M₂L(CH₃COO)₂ [M = Ni(II) and Zn(II)]. The cytotoxicity activities of the compounds against human breast carcinoma MCF-7 cell line have been studied. Ligands and their Zn(II) compounds inhibited cell proliferation of MCF-7 cancer cell lines in a dose- and time-dependent manner. The free radical scavenging activity was measured by 1,1-diphenyl-2-picryl-hydrazil. Our results show that the synthesized compounds induced oxidative damage by increasing the lipid peroxidation in yeast since MDA formation was increased, and it could be concluded that the synthesized compounds caused oxidative stress. In addition, the antioxidant activities of the synthesized compounds were very much lower than those of standard antioxidants.     

Coronary sinus venoarterial CO2 difference in different hemodynamic states

Myocardial metabolic rate and coronary flow are closely related limiting thus the diagnostic value of coronary sinus saturation monitoring as an indicator of flow. Regional venoarterial CO2 gradient was found elevated during low flow in various clinical and experimental conditions, in animals and humans. This study was undertaken to examine the impact of the variations of cardiac mechanical work on veno-arterial CO2 content and partial pressure difference (deltaPCO2) of the coronary sinus blood. Twenty-seven patients of either sex (m/f = 21/6), undergoing coronary artery bypass grafting under extracorporeal circulation, were studied. Monitoring included a Swan-Ganz catheter and a coronary sinus line. The correct position of the late was verified by the waveform displayed in the monitor. Immediately after cannulae placement, a hemodynamic profile was obtained and simultaneous arterial and coronary sinus sampling for blood gas analysis was done in an ABL 720 (Radiometer Copenhagen) analyzer. A second collection of the same data was obtained five minutes later with the patients in a slight "head-down" position. Conditions for exclusion was intersample variation of hemoglobin's concentration greater than 15% and sodium ion concentration difference greater than 10% of the greater value. Arteriovenous oxygen partial pressure difference (deltaP(a-cs)O2), veno-arterial carbon dioxide partial pressure difference (deltaP(cs-a)CO2), O2 & CO2 content difference and heart's respiratory quotient were calculated and correlated to cardiac output (CO) and the other hemodynamic parameters. Statistical analysis employed t-paired test and linear regression. No ischemia was detected during sampling. "Head-down" position had a significant impact to all hemodynamic parameters except heart rate. In both data rows, although CO ranged widely and altered significantly, coronary sinus oxygen saturation and arteriovenous O2 content difference were stable and showed insignificant correlations to all the hemodynamic parameters that were studied. Carbon dioxide content difference (coronary sinus-arterial) showed a trending of decrease with higher flow. DeltaP(cs-a)CO2 appeared stable and independent of flow. Finally, respiratory quotient decreased significantly from 0.91 +/- 0.4 to 0.86 +/- 0.4 (mean +/- SD; p < 0.05). The heart's high basal oxygen consumption and the almost near hemoglobin's desaturation transcoronary extraction of oxygen limits the value of coronary sinus saturation monitoring as indicator of coronary flow. Heart's little extraction reserve is faced with coronary flow reserve. In the physiologic range and under the conditions of anesthesia, elevated CO2 production is accompanied with increased coronary flow. Under these circumstances, deltaP(cs-a)CO2 appears stable and is not suitable for clinical decisions concerning heart's coronary flow.     

Left Atrial Deformation Parameters Predict Left Atrial Appendage Function and Thrombus in Patients in Sinus Rhythm with Suspected Cardioembolic Stroke: A Speckle Tracking and Transesophageal Echocardiography Study

The aim of this study was to evaluate left atrial deformations using speckle tracking echocardiography for predicting left atrial appendage (LAA) thrombus in patients with suspected cardioembolic stroke who were in normal sinus rhythm. A total of 153 ischemic stroke patients (89 males, 64 females) in sinus rhythm who were suspected of having cardioembolism were included in the study. The patients underwent conventional two‐dimensional (2D) echocardiogram and 2D speckle tracking echocardiogram of the left atrium. Left atrial peak strain (LA‐4C‐RES) and left atrial precontraction strain (LA‐4C‐PUMP) were measured. Patients were divided into 2 groups according to the presence of thrombus in the LAA in transesophageal echocardiography. Both LA‐4C‐RES and LA‐4C‐PUMP values were found to be significantly lower in patients with LAA thrombus (11.8 ± 1.4% vs. 33 ± 12%, P < 0.001 and 5.8 ± 1.3% vs. 14.2 ± 5.3%, P < 0.001, respectively). A good inverse correlation was present between LA‐4C‐RES values and LAA morphologic parameters (with LAA area: r = ?0.70, P < 0.001, with LAA length: r = ?0.60, P < 0.001), and a good positive correlation was present with LAA emptying velocity with pulse Doppler (r = 0.74, P < 0.001). The area under the receiver‐operating characteristic curve of the LA‐4C‐RES was 0.94 (0.90–0.98, P < 0.001), for the LA‐4C‐PUMP, the area was 0.92 (0.87–0.96, P < 0.001) to predict LAA thrombus. Left atrial deformation parameters measured by 2D speckle tracking method was found to predict impaired LAA functions and the presence of LAA thrombus in ischemic stroke patients with suspected cardioembolism, but who are in sinus rhythm.