We demonstrated the presence of 11 mechanotransduction channels in the TM and in isolated TM cells at protein level. Demonstration of these channels as proteins at tissue and cellular level will pave the way for further experimentation.
Increasing evidence suggests that trabecular meshwork (TM) cells participate in the regulation of intraocular pressure by controlling the rate of filtration of the aqueous humor. Ionic conductances that regulate cell volume and shape have been suggested to play an important role in TM cell volume regulation. Here we compared ionic currents from TM cells derived from a normal subject (CTM) and from an individual affected by glaucoma (GTM). We found that while the ionic currents types are similar, the current amplitudes and percentage of cells endowed with specific current at baseline are different in the two cell lines. Thus, we found that the majority of CTM cells are endowed with a swelling-activated Cl− current at baseline, whereas in the majority of GTM cells this current is not active at baseline and becomes activated only after perfusion with a hypotonic solution. An inward rectifier K+ current is also more prevalent in CTM than in GTM cells. Our work suggests that disregulation of one or more of these ionic currents may be at the basis of TM cells participation in the development of glaucoma.
Background:
Radiofrequency ablation depth can be inadequate to reach intramural or epicardial substrate, and energy delivery in the pericardium is limited by penetration through epicardial fat and coronary anatomy. We hypothesized that open irrigated microwave catheter ablation can create deep myocardial lesions endocardially and epicardially though fat while acutely sparing nearby the coronary arteries.
Methods:
In-house designed and constructed irrigated microwave catheters were tested in in vitro phantom models and in 15 sheep. Endocardial ablations were performed at 140 to 180 W for 4 minutes; epicardial ablations via subxiphoid access were performed at 90 to 100 W for 4 minutes at sites near coronary arteries.
Results:
Epicardial ablations at 90 to 100 W produced mean lesion depth of 10±4 mm, width 18±10 mm, and length 29±8 mm through median epicardial fat thickness of 1.2 mm. Endocardial ablations at 180 W reached depths of 10.7±3.3 mm, width of 16.6±5 mm, and length of 20±5 mm. Acute coronary occlusion or spasm was not observed at a median separation distance of 2.7 mm (IQR, 1.2–3.4 mm). Saline electrodes recorded unipolar and bipolar electrograms; microwave ablation caused reductions in voltage and changes in electrogram morphology with loss of pace-capture. In vitro models demonstrated the heat sink effect of coronary flow, as well as preferential microwave coupling to myocardium and blood as opposed to lung and epicardial fat phantoms.
Conclusions:
Irrigated microwave catheter ablation may be an effective ablation modality for deep ventricular lesion creation with capacity for fat penetration and sparing of nearby coronary arteries because of cooling endoluminal flow. Clinical translation could improve the treatment of ventricular tachycardia arising from mid myocardial or epicardial substrates.
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