Clinically observed phenomena on cardiac energetics in heart failure emerge from simulations of cardiac metabolism

15 mins 26 secs, 77.16 MB, WebM 450x360, 25.0 fps, 44100 Hz, 682.56 kbits/sec

Share this media item:

Embed this media item:

<iframe width="_width_" height="_height_" src="https://sms.cam.ac.uk/media/649645/embed" frameborder="0" scrolling="no" allowfullscreen></iframe>

Choose size:

About this item

Available Formats

About this item

Description:	Beard, D (Medical College of Wisconsin) Monday 20 July 2009, 12:15-12:30

Created:

2009-07-22 16:53

Collection:

Cardiac Physiome Project

Publisher:

Isaac Newton Institute

Beard, D (Medical College of Wisconsin)

Language:

eng (English)

Credits:

Author:

Beard, D


Abstract:	The failing heart is hypothesized to suffer from energy supply inadequate for supporting normal cardiac function. We analyzed data from a canine left ventricular hypertrophy (LVH) model to determine how the energy state evolves due to changes in key metabolic pools. Our findings¡Xconfirmed by in vivo 31P-magnetic resonance spectroscopy (31P-MRS)¡Xindicate that the transition between the clinically observed early compensatory phase and heart failure and the critical point at which the transition occurs are emergent properties of cardiac energy metabolism. Specifically, analysis reveals a phenomenon in which low and moderate reductions in metabolite pools have no major negative impact on oxidative capacity while reductions beyond a critical tipping point lead to a severely compromised energy state. Furthermore, our analysis reveals: (1.) the predicted metabolic tipping point coincides with the transition to severe cardiac dysfunction; (2.) the tipping point is associated with a ~30% reduction of TAN reduction corresponds to the reduction observed in humans in heart failure [Circ Res 95:135-145]; (3.), the predicted cytoplasmic AMP at the tipping point is approximately 1.6 mM and equal to the apparent AMP concentration at half-maximal activation of cardiac AMP-activated protein kinase; (4.) oxidative stress in the myocardium is predicted to progressively increase as the metabolic pools are diminished; and (5.) at given values of TAN and TEP during hypertrophic remodeling, CRtot attains a value that is associated with optimal ƒ´GATPase. Thus, both increases and decreases to the creatine pool are predicted to result in diminished energetic state unless accompanied by appropriate simultaneous changes in the other pools.

Abstract:

The failing heart is hypothesized to suffer from energy supply inadequate for supporting normal cardiac function. We analyzed data from a canine left ventricular hypertrophy (LVH) model to determine how the energy state evolves due to changes in key metabolic pools. Our findings¡Xconfirmed by in vivo 31P-magnetic resonance spectroscopy (31P-MRS)¡Xindicate that the transition between the clinically observed early compensatory phase and heart failure and the critical point at which the transition occurs are emergent properties of cardiac energy metabolism. Specifically, analysis reveals a phenomenon in which low and moderate reductions in metabolite pools have no major negative impact on oxidative capacity while reductions beyond a critical tipping point lead to a severely compromised energy state. Furthermore, our analysis reveals: (1.) the predicted metabolic tipping point coincides with the transition to severe cardiac dysfunction; (2.) the tipping point is associated with a ~30% reduction of TAN reduction corresponds to the reduction observed in humans in heart failure [Circ Res 95:135-145]; (3.), the predicted cytoplasmic AMP at the tipping point is approximately 1.6 mM and equal to the apparent AMP concentration at half-maximal activation of cardiac AMP-activated protein kinase; (4.) oxidative stress in the myocardium is predicted to progressively increase as the metabolic pools are diminished; and (5.) at given values of TAN and TEP during hypertrophic remodeling, CRtot attains a value that is associated with optimal ƒ´GATPase. Thus, both increases and decreases to the creatine pool are predicted to result in diminished energetic state unless accompanied by appropriate simultaneous changes in the other pools.

Available Formats

Format	Quality	Bitrate	Size
MPEG-4 Video	480x360	1.82 Mbits/sec	213.49 MB	View	Download
WebM *	450x360	682.56 kbits/sec	77.16 MB	View	Download
Flash Video	480x360	803.31 kbits/sec	91.20 MB	View	Download
iPod Video	320x240	504.61 kbits/sec	57.29 MB	View	Download
QuickTime	480x360	506.77 kbits/sec	57.53 MB	View	Download
MP3	44100 Hz	125.0 kbits/sec	13.99 MB	Listen	Download
Windows Media Video		477.66 kbits/sec	54.23 MB	View	Download
Auto	(Allows browser to choose a format it supports)