Data from: Effects of the selective stretch-activated channel blocker GsMtx4 on stretch-induced changes in refractoriness in isolated rat hearts and on ventricular premature beats and arrhythmias after coronary occlusion in swine

Mechanical factors may contribute to ischemic ventricular arrhythmias. GsMtx4 peptide, a selective stretch-activated channel blocker, inhibits stretch-induced atrial arrhythmias. We aimed to assess whether GsMtx4 protects against ventricular ectopy and arrhythmias following coronary occlusion in swine. First, the effects of 170-nM GsMtx4 on the changes in the effective refractory period (ERP) induced by left ventricular (LV) dilatation were assessed in 8 isolated rat hearts. Then, 44 anesthetized, open-chest pigs subjected to 50-min left anterior descending artery occlusion and 2-h reperfusion were blindly allocated to GsMtx4 (57 μg/kg iv. bolus and 3.8 μg/kg/min infusion, calculated to attain the above concentration in plasma) or saline, starting 5-min before occlusion and continuing until after reflow. In rat hearts, LV distension induced progressive reductions in ERP (35±2, 32±2, and 29±2 ms at 0, 20, and 40 mmHg of LV end-diastolic pressure, respectively, P<0.001) that were prevented by GsMTx4 (33±2, 33±2, and 32±2 ms, respectively, P=0.002 for the interaction with LV end-diastolic pressure). Pigs receiving GsMtx4 had similar number of ventricular premature beats during the ischemic period as control pigs (110±28 vs. 103±21, respectively, P=0.842). There were not significant differences among treated and untreated animals in the incidence of ventricular fibrillation (13.6 vs. 22.7%, respectively, P=0.696) or tachycardia (36.4 vs. 50.0%, P=0.361) or in the number of ventricular tachycardia episodes during the occlusion period (1.8±0.7 vs. 5.5±2.6, P=0.323). Thus, GsMtx4 administered under these conditions does not suppress ventricular ectopy following coronary occlusion in swine. Whether it might protect against malignant arrhythmias should be tested in studies powered for these outcomes

ERP in isolated rat hearts

SPSS data (.sav) file. It contains the effective refractory periods at different loading conditions (0, 20, 40mmHg LVEDP) and with and without GsMtx4 in isolated rat hearts

Data on experiments in pigs

SPSS data (.sav) file. It contains all data of the experiments in pigs. Description of the variables in the attached ReadMe file

Data on experiments in pigs

SPSS data (.sav) file. It contains all data of the experiments in pigs. Description of the variables in the attached ReadMe file

Whole number, distribution and co-expression of brn3 transcription factors in retinal ganglion cells of adult albino and pigmented rats.

The three members of the Pou4f family of transcription factors: Pou4f1, Pou4f2, Pou4f3 (Brn3a, Brn3b and Brn3c, respectively) play, during development, essential roles in the differentiation and survival of sensory neurons. The purpose of this work is to study the expression of the three Brn3 factors in the albino and pigmented adult rat. Animals were divided into these groups: i) untouched; ii) fluorogold (FG) tracing from both superior colliculli; iii) FG-tracing from one superior colliculus; iv) intraorbital optic nerve transection or crush. All retinas were dissected as flat-mounts and subjected to single, double or triple immunohistofluorescence The total number of FG-traced, Brn3a, Brn3b, Brn3c or Brn3 expressing RGCs was automatically quantified and their spatial distribution assessed using specific routines. Brn3 factors were studied in the general RGC population, and in the intrinsically photosensitive (ip-RGCs) and ipsilateral RGC sub-populations. Our results show that: i) 70% of RGCs co- express two or three Brn3s and the remaining 30% express only Brn3a (26%) or Brn3b; ii) the most abundant Brn3 member is Brn3a followed by Brn3b and finally Brn3c; iii) Brn3 a-, b- or c- expressing RGCs are similarly distributed in the retina; iv) The vast majority of ip-RGCs do not express Brn3; v) The main difference between both rat strains was found in the population of ipsilateral-RGCs, which accounts for 4.2% and 2.5% of the total RGC population in the pigmented and albino strain, respectively. However, more ipsilateral-RGCs express Brn3 factors in the albino than in the pigmented rat; vi) RGCs that express only Brn3b and RGCs that co-express the three Brn3 members have the biggest nuclei; vii) After axonal injury the level of Brn3a expression in the surviving RGCs decreases compared to control retinas. Finally, this work strengthens the validity of Brn3a as a marker to identify and quantify rat RGCs

Induced arrhythmias in rat hearts

SPSS data (.sav) file. It contains the number of TV runs (and the sum of ventricular beats in these runs) induced by programmed stimulation in isolated rat hearts at 0, 20, 40 mmHg LVEDP and with and without GsMtx4

Blood tests in anesthetized pigs.

<p>Values are means ± SE. P values reflect the effect of time and of GsMtx4 (interaction term, two-way repeated-measures analysis of variance).</p><p>Blood tests in anesthetized pigs.</p

Distribution of ventricular premature beats during the ischemic period in treated and untreated pigs.

<p>P values obtained with a linear mixed effect model after square-root transformation of data.</p

Distribution of episodes of ventricular tachycardia (rhombi) or fibrillation (circles) during ischemia and initial reperfusion in both groups.

<p>Each line represents an animal. In cases with a very high density of ventricular tachycardia episodes not all of them could be depicted. R = Reperfusion.</p

Summary of the main results of the experiments in isolated rat hearts.

<p>Top: Values of the ventricular effective refractory period in isolated rat hearts at different loading conditions and with or without GsMtx4 in the perfusate. Bottom: Number of runs of ventricular tachycardia induced by 5 stimulation protocols with coupling intervals 1 to 5 ms over the effective refractory period in isolated rat hearts. LVEDP = Left ventricular enddiastolic pressure; VT = Ventricular tachycardia.</p