What question did this study set out to answer?

To separate cardiac output into heart rate and stroke volume within a systems pharmacology model and determine whether drug mechanisms of action can be identified using only heart rate and blood pressure.

June 24, 2014British Journal of PharmacologyOpen Access

Drug effects on the CVS in conscious rats: separating cardiac output into heart rate and stroke volume usingPKPDmodelling

View Full Paper

Ask AI

Bookmark

Population

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats

Design

Preclinical

Authors

NSNelleke SnelderPNO Consultants (Netherlands)BPBart A. PloegerArbeitsgemeinschaft Gynäkologische Onkologie Studiengruppe OLOlivier LuttringerNovartis (Switzerland)

Discussion

Member takes

Implication

Limits use to preclinical research; extends systems pharmacology modeling but leaves open human translation.

Key Points

To separate cardiac output into heart rate and stroke volume within a systems pharmacology model and determine whether drug mechanisms of action can be identified using only heart rate and blood pressure.
Tested eight cardiovascular drugs across single-dose ranges in conscious spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Continuously recorded mean arterial pressure, heart rate, and cardiac output using ascending aortic flow probes and aortic catheters/radiotransmitters.
Analyzed hemodynamic data using mechanism-based pharmacokinetic-pharmacodynamic modeling incorporating drug concentration time courses.
The extended model successfully quantified drug-induced changes in total peripheral resistance, heart rate, and stroke volume regulated by mean arterial pressure feedback.
The modeling framework adequately described hemodynamic drug responses while accounting for baseline circadian rhythms and experimental handling effects.
The system accurately elucidated the mechanism of action for compounds with a single site of action using solely mean arterial pressure and heart rate measurements.

Structured PICO

Population

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats

Intervention

Single administrations of a range of doses of eight drugs with diverse mechanisms of action (amiloride, amlodipine, atropine, enalapril, fasudil, hydrochlorothiazide, prazosin and propranolol)

Outcome

Characterization of drug effects on the interrelationship between mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), heart rate (HR), and stroke volume (SV) using a PKPD modelsurrogate

A newly extended systems pharmacology model can elucidate the mechanism of action of novel cardiovascular compounds using only heart rate and mean arterial pressure measurements in rats.

Limitations

Whether the model can be applied for compounds with a more complex MoA remains to be established.

Cite This Study

Snelder et al. (2014) studied this question.

synapsesocial.com/papers/6a853a67b6c67ec53fcf2905 https://doi.org/10.1111/bph.12824

Topics

Hypertension management

View Full Paper

Ask AI

Bookmark

Drug effects on the CVS in conscious rats: separating cardiac output into heart rate and stroke volume usingPKPDmodelling

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Topics

Drug effects on the CVS in conscious rats: separating cardiac output into heart rate and stroke volume usingPKPDmodelling

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Also Consider

Topics

Also Consider