These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Left ventricular pressure, contractility and dP/dt(max) in nonclinical drug safety assessment studies.
    Author: Sarazan RD, Kroehle JP, Main BW.
    Journal: J Pharmacol Toxicol Methods; 2012 Sep; 66(2):71-8. PubMed ID: 22659561.
    Abstract:
    Increasing or decreasing cardiac contractility is an undesirable property of drugs being developed for noncardiovascular 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, these nonclinical safety assessment studies can detect these effects if properly designed and conducted using appropriate instrumentation. Left ventricular dP/dt is the first derivative of left ventricular pressure, which is computed by software algorithms by using calculus. Its peak value, dP/dt(max), 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. For dogs, nonhuman primates, and normotensive rats, all important information in a left ventricular pressure signal can be captured with a system with a frequency response of 100 Hz. Although systems with much higher frequency response can be used to measure left ventricular pressure, 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 2× 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. This manuscript has been written for biologists who do not have advanced knowledge of physics and/or engineering and is therefore less technical and more simplified than what would be found in the engineering literature.
    [Abstract] [Full Text] [Related] [New Search]