Left Ventricular Pressure

The pressure generated in the ventricular chambers of the heart can be measured and used in a variety of ways to understand changes in cardiac function.  Left ventricular pressure (LVP) in conjunction with ventricular volume measurements has a long history of being used to characterize the pressure-volume relationship in the beating heart. In addition LVP is studied to ensure drugs developed do not negatively alter cardiac contractility.  

 

Increasing or decreasing cardiac contractility is an undesirable property of drugs being developed for non-cardiovascular indications.  The International Conference on Harmonization (ICH) Topic S7A and S7B guidelines only require the assessment of heart rate, blood pressure and the electrocardiogram in nonclinical in vivo safety pharmacology studies.  Assessment of drug effects on contractility is only suggested as an optional follow-up study.  However, early implementation of a measure of cardiac function can greatly reduce the risk of discovering alterations in cardiac performance in late stage drug development

 

Left ventricular dP/dt is the first derivative of LVP, which is computed  by software algorithms using calculus.  Its peak value, dP/dtmax, is a common, robust and sensitive indicator of changes in cardiac contractility if experimental parameters such as preload, afterload and heart rate are well controlled.  In order to ensure accuracy and avoid errors in the measurement of contractility in experimental animals, the frequency response of the pressure sensing system and the sample rate of the data acquisition system must be optimized for the signal. 

 

Cardiac contractility is an intrinsic property of heart muscle that affects the heart's performance and can be modified by the autonomic system, circulating hormones, drugs and disease.  Evaluation of a drug's effects on contractility is important in safety assessment studies since either an increase or a decrease may be harmful under certain clinical situations.  An increase in contractility dramatically increases the heart's energy consumption, which translates to increased oxygen consumption and increased coronary blood flow.  This can have serious consequences in the presence of heart disease and/or coronary insufficiency.  A decrease in contractility in an already diseased heart can exacerbate the symptoms and consequences of clinical heart failure.  

In order to accurately measure LVP dP/dtmax, the LVP measurement system must have a high signal to noise ratio and have adequate frequency response to faithfully acquire and store the important information in the signal.  Evidence proves that all important information in those signals occurs at frequencies below 100 Hz.  Therefore, the frequency response of the pressure measurement system must be at least 100 Hz. 

For dogs, nonhuman primates, and normotensive rats, all important information in a LVP signal can be captured with a system with a frequency of 100 Hz.  Although systems with much higher frequency response can be used to measure LVP, the output of these devices must be filtered to allow no frequencies to be acquired that are higher than one-half the sample rate of the acquisition system.  Stated conversely, the sample rate of the acquisition system must be at least 2X the highest frequency contained in the signal.  Failure to follow these principals can lead to incorrect results due to measurement artifacts from high frequency noise, which could be present but not detectable by the investigator.     

Parameters Most Commonly Measured with LVP

  • LVP
  • Diastolic Pressure
  • Heart Rate (HR)
  • Minimum Pressure
  • Peak Systolic Pressure (Sys)
  • LVP and End-Diastolic Pressure (LVEDP)
  • dP/dtmax (+dP/dt)
  • dP/dtmin (-dP/dt)

Small Animal System Set-Up
LVP can be measured in small animals using the HD-S21

  




Large Animal System Set-Up
LVP can be measured in large animals using the PhysioTel™ Digital L21 Implant

 









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