Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing

Mechanical stretch of cardiac muscle modulates action potential propagation velocity, causing potentially arrhythmogenic conduction slowing. The mechanisms by which stretch alters cardiac conduction remain unknown, but previous studies suggest that stretch can affect the conformation of caveolae in myocytes and other cell types. We tested the hypothesis that slowing of action potential conduction due to cardiac myocyte stretch is dependent on caveolae. Cardiac action potential propagation velocities, measured by optical mapping in isolated mouse hearts and in micropatterned mouse cardiomyocyte cultures, decreased reversibly with volume loading or stretch, respectively (by 19±5% and 26±4%). Stretch-dependent conduction slowing was not altered by stretch-activated channel blockade with gadolinium or by GsMTx-4 peptide, but was inhibited when caveolae were disrupted via genetic deletion of caveolin-3 (Cav3 KO) or membrane cholesterol depletion by methyl-β-cyclodextrin. In wild-type mouse hearts, stretch coincided with recruitment of caveolae to the sarcolemma, as observed by electron microscopy. In myocytes from wild-type but not Cav3 KO mice, stretch significantly increased cell membrane capacitance (by 98±64%), electrical time constant (by 285±149%), and lipid recruitment to the bilayer (by 84±39%). Recruitment of caveolae to the sarcolemma during physiologic cardiomyocyte stretch slows ventricular action potential propagation by increasing cell membrane capacitance

Monte Carlo simulation of light propagation in adult brain: influence of tissue blood content and indocyanine green

Near-infrared spectroscopy (NIRS), applied to a human head, is a noninvasive method in neurointensive care to monitor cerebral hemodynamics and oxygenation. The method is particularly powerful when it is applied in combination with indocyanine green (ICG) as a tracer substance. In order to assess contributions to the measured optical density (OD) which are due to extracerebral circulation and disturb the clinically significant intracerebral signals, we simulated the light propagation in an anatomically representative model of the adult head derived from MRI measurements with the aid of Monte Carlo methods. Since the measured OD signal depends largely on the relative blood content in various transilluminated tissues, we weighted the calculated densities of the photon distribution under baseline conditions within the tissues with the changes and aberrations of the relative blood volumes which we expect to prevail under physiological conditions. Furthermore, the influence of the IGC dye as a tracer substance was assessed. We conclude that up to about different 70% of the measured OD signal may have its origin in the tissues of interest under optimal conditions, which is mainly due to the extrapolated high relative blood content of brain tissue along with the influence of ICG