Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

Mini-, Micro-, and Conventional Electrodes: An in Vivo Electrophysiology and Ex Vivo Histology Head-to-Head Comparison.

OBJECTIVES: This study sought to assess the relative effect of catheter, tissue, and catheter-tissue parameters, on the ability to determine the amount of viable myocardium in vivo. BACKGROUND: Although multiple variables impact bipolar voltages (BVs), electrode size, interelectrode spacing, and directional dependency are of particular interest with the development of catheters incorporating mini and microelectrodes. METHODS: Nine swine with early reperfusion myocardial infarctions were mapped using the QDot catheter and then remapped using a Pentaray catheter. All QDot points were matched with Pentaray points within 5 mm. The swine were sacrificed, and mapping data projected onto the heart. Transmural biopsies corresponding to mapping points were obtained, allowing a comparison of electrograms recorded by mini, micro-, and conventional electrodes with histology. RESULTS: The conventional BV of 2,322 QDot points was 1.9 ± 1.3 mV. The largest of the 3 microelectrode BVs (BVµMax) average 4.8 ± 3.1 mV. The difference between the largest (BVµMax) and smallest (BVµMin) at a given location was 53.7 ± 18.1%. The relationships between both BVµMax and BVµMin and between the conventional BV and BVµMax were positively related but with a significant spread in data, which was more pronounced for the latter. Pentaray points positively related to the BVµMax with poor fit. On histology, increasing viable myocardium increased voltage, but both the slope coefficient and fit were best for BVµMax. CONCLUSIONS: Using histology, we could demonstrate that BVµMax is superior to identify viable myocardium compared with BVC and BV using the Pentaray catheter. The ability to simultaneously record 3 BVµs with different orientations, for the same beat, with controllable contact and selecting BVµMax for local BV may partially compensate for wave front direction.

Multisize Electrodes for Substrate Identification in Ischemic Cardiomyopathy: Validation by Integration of Whole Heart Histology.

OBJECTIVES: This study sought to evaluate the value of combined electrogram (EGM) information provided by simultaneous mapping using micro- and conventional electrodes in the identification of post-myocardial infarction ventricular tachycardia substrate. BACKGROUND: Ventricular tachycardias after myocardial infarction are related to scars with complex geometry. Scar delineation and ventricular tachycardia substrate identification relies on bipolar voltages (BV) and EGM characteristics. Early reperfusion therapy results in small, nontransmural scars, the details of which may not be delineated using 3.5 mm tip catheters. METHODS: Nine swine with early reperfusion myocardial infarction were mapped using Biosense Webster's QDOT Micro catheter, incorporating 3 microelectrodes at the tip of the standard 3.5 mm electrode. Analysis of EGM during sinus rhythm, right ventricular pacing, and short-coupled right ventricular extrastimuli was performed. The swine were sacrificed and mapping data were projected onto the heart. Transmural biopsies (n = 196) corresponding to mapping points were obtained, allowing a head-to-head comparison of EGM recorded by micro- and conventional electrodes with histology. RESULTS: To identify scar areas using standard electrodes, unique cutoff values of unipolar voltage <5.44 mV, BV <1.27 mV (conventional), and BV <2.84 mV (microelectrode) were identified. Combining the information provided by unipolar voltage and BV mapping, the sensitivity of scar identification was increased to 93%. Micro-EGM were better able to distinguish small near-fields corresponding to a layer of viable subendocardium than conventional EGM were. CONCLUSIONS: The combined information provided by multisize electrode mapping increases the sensitivity with which areas of scar are identified. EGM from microelectrodes, with narrower spacing, allow identification of near-fields arising from thin subendocardial layer and layers activated with short delay obscured in EGM from conventional mapping catheter.

Radiofrequency ablation lesions in low-, intermediate-, and normal-voltage myocardium: an in vivo study in a porcine heart model.

AIMS: Contact force (CF) between radiofrequency (RF) ablation catheter and myocardium and ablation index (AI) correlates with RF lesion depth and width in normal-voltage (>1.5 mV) myocardium (NVM). We investigate the impact of CF on RF lesion depth and width in low (<0.5 mV) (LVM) and intermediate-voltage (0.5-1.5 mV) myocardium (IVM) following myocardial infarction. Correlation between RF lesion depth and width evaluated by native contrast magnetic resonance imaging (ncMRI) and gross anatomical evaluation was investigated. METHODS AND RESULTS: Twelve weeks after myocardial infarction, 10 pigs underwent electroanatomical mapping and endocardial RF ablations were deployed in NVM, IVM, and LVM myocardium. In vivo ncMRI was performed before the heart was excised and subjected to gross anatomical evaluation. Ninety (82%) RF lesions were evaluated. Radiofrequency lesion depth and width were smaller in IVM and LVM compared with NVM (P < 0.001). Radiofrequency lesion depth and width correlated with CF, AI, and impedance drop in NVM (CF and AI P < 0.001) and IVM (CF and AI depths P < 0.001; CF and AI widths P < 0.05). Native contrast magnetic resonance imaging evaluated RF lesion depth and width correlated with gross anatomical depth and width (NVM and IVM P < 0.001; LVM P < 0.05). CONCLUSIONS: Radiofrequency lesions deployed by similar duration, power and CF are smaller in IVM and LVM than in NVM. Radiofrequency lesion depth and width correlated with CF, AI, and impedance drop in NVM and IVM but not in LVM. Native contrast magnetic resonance imaging may be useful to assess RF lesion depth and width in NVM, IVM, and LVM.

Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats.

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4-5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P < 0.05 vs. Cx), whole body insulin resistance (P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser(473) phosphorylation. The ESC treatment normalized corticosterone secretion (P < 0.05 vs. LBW), whole body insulin sensitivity (P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P < 0.05), and red muscle PKB Ser(473) phosphorylation (P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

Cardioprotection by L-glutamate during postischaemic reperfusion: reduced infarct size and enhanced glycogen resynthesis in a rat insulin-free heart model.

1. Previously, we found that administration of high-dose L-glutamate during postischaemic reperfusion improves haemodynamic recovery and enhances glycogen resynthesis. In the present study, we investigated whether the same effect occurs in an insulin-free model and whether glutamate administration reduces infarct size. Further, we studied whether the cardioprotective effect of glutamate depends on preserved glutamate transamination and K(ATP) channel activity. 2. In a rat isolated, insulin-free, perfused heart model, we compared the effects of administration of L-glutamate (10 mmol/L) during either 45 min no-flow regional ischaemia plus 120 min reperfusion or reperfusion alone on infarct size and left ventricular (LV) recovery. The effect of glutamate on glycogen metabolism was studied in a model of 30 min global no-flow ischaemia and 60 min reperfusion. In both models, the effects of inhibition of glutamate transamination and K(ATP) channel activity were examined by adding amino-oxyacetate (an aminotransferase inhibitor; 0.1 mmol/L) and glibenclamide (a K(ATP) blocker; 10 mmol/L), respectively. 3. Administration of L-glutamate reduced infarct size by 60% (P < 0.01) and improved postischaemic LV function (developed pressure and rate pressure product; P < 0.05). L-Glutamate increased glycogen content after 60 min reperfusion by 65% (P < 0.01). Amino-oxyacetate, as well as glibenclamide, abolished the glutamate-mediated reduction in infarct size, haemodynamic improvement and glycogen resynthesis during reperfusion. 4. In conclusion, L-glutamate administration from the start of postischaemic reperfusion exerts cardioprotective effects, including reduced infarct size, improved haemodynamic recovery and enhanced glycogen resynthesis. These effects depend on preserved transamination of glutamate and K(ATP) channel activity, but not on insulin administration.

L-glutamate and glutamine improve haemodynamic function and restore myocardial glycogen content during postischaemic reperfusion: A radioactive tracer study in the rat isolated heart.

1. L-Glutamate and glutamine have been suggested to have cardioprotective effects. However, the issue is controversial and the metabolic mechanisms underlying a beneficial effect are not well understood. 2. In the present study we investigated the effects of L-glutamate and glutamine on haemodynamic recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake during postischaemic reperfusion. 3. Hearts from male Wistar rats (250-300 g) were divided into three groups as follows: (i) control (n = 12); (ii) L-glutamate (n = 12); and (iii) glutamine (n = 12). Hearts were mounted in a Langendorff preparation and perfused with oxygenated Krebs'-Henseleit solution at 80 mmHg and 37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during which L-glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]-glucose and myocardial glucose uptake using D-[2-3H]-glucose were measured. 4. L-Glutamate and glutamine increased postischaemic LVDP (P < 0.01 vs control hearts for both). L-Glutamate and glutamine increased de novo glycogen synthesis by 78% (P < 0.001) and 55% (P < 0.01), respectively. At the end of reperfusion, total myocardial glycogen content was increased by both L-glutamate and glutamine (5.7 +/- 0.3 and 6.2 +/- 0.7 micromol/g wet weight, respectively; P < 0.05 and 0.01, respectively) compared with that in control hearts (3.6 +/- 0.4 micromol/g wet weight). Neither L-glutamate nor glutamine affected myocardial glucose uptake during reperfusion. 5. Improved postischaemic haemodynamic recovery after L-glutamate and glutamine supplementation during reperfusion is associated with increased de novo glycogen synthesis, suggesting a favourable modulation of intracellular myocardial carbohydrate metabolism.

Effects of L-glutamate supplementation mimic effects of fasting in the ischemic heart.

Endogenous glycogen stores are essential to maintain cell functions during myocardial ischemia.. Fasting and L-glutamate improve left ventricular function after an ischemic episode. We studied their effects on myocardial glycogen depletion during ischemia and on left ventricular function and glycogen resynthesis during reperfusion. We allocated 185 Wistar rats to 4 groups: 1) Control, 2) Fasting, 16-20 hours (Fast) 3) L-glutamate supplementation [100 mM] (Glt) or 4) Fasting + L-glutamate supplementation [100 mM]. n = 8-10 in each group. Hearts were mounted in an isolated perfused rat hearts model for 20 min stabilisation, 10/20/30 min ischemia and 60 min reperfusion. At each time point hearts were frozen in liquid nitrogen (-196 degrees C) within 2 seconds and myocardial contents of glycogen, lactate, alanine and glutamate were determined. Left ventricular pressure was measured continuously. Fasting and L-glutamate supplementation improved LV function after ischemia (Fast: p < 0.05, Glt: p < 0.01) and delayed myocardial glycogen depletion (Fast: p < 0.05, Glt: p < 0.01) compared to control. Decreased lactate accumulation and increased alanine content during ischemia were found in fasted (lactate: p < 0.05, alanine: p < 0.05) and L-glutamate supplemented (lactate: p < 0.01, alanine: p < 0.01) hearts compared to control. We did not find any additive effects of fasting and L-glutamate supplementation. In conclusion fasting and L-glutamate supplementation improve left ventricular function during reperfusion and delay myocardial glycogen depletion during ischemia. There were no additive effects of Fasting and L-glutamate supplementation. These finding suggest common metabolic pathways underlying the effects of L-glutamate supplementation and fasting.

Validation of myocardial acceleration during isovolumic contraction as a novel noninvasive index of right ventricular contractility: comparison with ventricular pressure-volume relations in an animal model.

BACKGROUND: We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of left ventricular contractile function. In this study, we assessed the utility of IVA to measure right ventricular (RV) contractile function. METHODS AND RESULTS: We examined 8 pigs by using tissue Doppler imaging of the RV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (e(max)), preload recruitable stroke work, and dP/dt(max) by conductance catheterization. Animals were paced in the right atrium at a rate of 130 beats per minute (bpm). IVA was compared with elastance during contractility modulation by esmolol and dobutamine and during preload reduction and afterload increase by transient balloon occlusion of the inferior vena cava and pulmonary artery, respectively. Data were also obtained during incremental atrial pacing from 110 to 210 bpm. Esmolol led to a decrease in IVA and dP/dt(max). During dobutamine infusion, IVA, dP/dt(max), preload recruitable stroke work, and e(max) all increased significantly. During preload reduction and afterload increase, IVA remained constant up to a reduction of RV volume by 54% and an RV systolic pressure increase of 58%. Pacing up to a rate of 190 bpm led to a stepwise increase in IVA and dP/dt(max), with a subsequent fall at a pacing rate of 210 bpm. CONCLUSIONS: IVA is a measurement of RV contractile function that is unaffected by preload and afterload changes in a physiological range and is able to measure the force-frequency relation. This novel index may be ideally suited to the assessment of acute changes of RV function in clinical studies.