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Open Access Publications from the University of California

Mechanisms of slow conductions during ventricular volume loading

  • Author(s): Mills, Robert W.
  • et al.

Several studies have linked increased myocardial strain (wall stretch) with atrial and ventricular arrhythmias. Although the precise mechanisms for these loading related rhythm disturbances remain unclear, the predominant mechanism underlying ventricular arrhythmias associated with mechanical dysfunction is reentrant conduction, which is promoted and sustained by slowed conduction. Passive ventricular volume loading in the Langendorff-perfused isolated rabbit heart has been shown to slow conduction. Optical mapping was used to image myocardial conduction. A phase-shifting filtering technique was previously developed to enhance optical maps of myocardial electrical activity. The improvements of the phase-shifting scheme were validated by processing a known data set taken from a modified FitzHugh-Nagumo model, to which comparable noise was added. Further improvements were made to the filtering and analysis routines to improve efficiency and accuracy. Conduction slowing in response to ventricular volume loading was validated by excluding several potentially confounding factors. Improved oxygen delivery with a synthetic oxygen carrier, indicated that the effect is not a result of global ischemia. Measurement of regional tissue perfusion with microspheres suggested that the load effect is not due to regional ischemia. Conduction slowing was not significantly attributable to a decrease in epicardial surface temperature during loading. Measurements with epicardial electrodes were performed without two reagents used during optical mapping: di-4- ANEPPS and 2,3-butanedione monoxime. These measurements indicated that incremental loading within a physiological range still led to incrementally longer activation times (slowed conduction). Several potential physiological mechanisms of conduction slowing during ventricular volume loading were investigated. Inclusion of the stretch- activated channel blocker gadolinium3+ in the perfusate attenuated the reversible increase in action potential duration during volume loading, but did not alter the reversible slowing of conduction. Volume loading reduced conduction despite changes in membrane excitability caused by varying perfusate potassium concentrations. Effective cross-fiber space and time constants, assessed by optical mapping of the tissue response to a cathodal-break point stimulus, increased significantly, indicating that loading may reduce intercellular resistance and increase effective membrane capacitance, resulting in a net slowing of conduction due to the greater sensitivity of conduction velocity to a change in capacitance

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