Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Summary

Cardiac pressure-volume loop analysis is the most comprehensive way to measure cardiac function in the intact heart. We describe a technique to perform and analyze cardiac pressure volume loops, using conductance catheters.

Abstract

Cardiac pressure-volume loop analysis is the “gold-standard” in the assessment of load-dependent and load-independent measures of ventricular systolic and diastolic function. Measures of ventricular contractility and compliance are obtained through examination of cardiac response to changes in afterload and preload. These techniques were originally developed nearly three decades ago to measure cardiac function in large mammals and humans. The application of these analyses to small mammals, such as mice, has been accomplished through the optimization of microsurgical techniques and creation of conductance catheters. Conductance catheters allow for estimation of the blood pool by exploiting the relationship between electrical conductance and volume. When properly performed, these techniques allow for testing of cardiac function in genetic mutant mouse models or in drug treatment studies. The accuracy and precision of these studies are dependent on careful attention to the calibration of instruments, systematic conduct of hemodynamic measurements and data analyses. We will review the methods of conducting pressure-volume loop experiments using a conductance catheter in mice.

Introduction

Cardiac pressure volume loop analysis provides detailed information of cardiac function and are the gold standard for functional assessment ¹. While imaging techniques such as echocardiography or cardiac MRI provide functional measures, these measures are highly dependent on loading conditions. Load-independent measures of cardiac contractility and relaxation require dynamic measurements of the ventricular pressure and volume relation over a range of preload and afterload. This understanding of the pressure-volume relation arises from the groundbreaking work of Sagawa and colleagues ^2,3. They demonstrated in ex vivo perfused canine heart....

Protocol

1. Conductance Catheter Preparations and Pressure Calibration

1. Connect conductance catheter to the hemodynamic catheter module. Electronically calibrate pressure and volume measurements by recording preset pressure and volume set on the catheter module. Record a tracing of 0 mm Hg and 25 mm Hg (Figure 1A) and assign voltages to both pressure tracings (Figure 1B and 1C). Similarly, record a volume tracing of 5 RVU and 25 RVU (Figure 1D) and assign voltages to both volume tracings (1E and 1F).
2. Confirm the electronic pressure calibration with a manual pressure calibration, using a mercury column....

Results

Pressure-volume loop analysis can be used to measure cardiac function in genetically modified mice ^14,15 or mice undergoing drug studies¹⁶. Representative pressure volume loops are provided from previously published work ¹⁶ investigating the effect of ß-Arrestin biased AT1R ligand, TRV120023. To test whether TRV120023 affects cardiac function in vivo, pressure-volume loop analysis was performed on wild type mice receiving conventional and novel angiotensin receptor blockers. Intr.......

Discussion

We describe a method for perfoming pressure-volume loop analysis using a conductance catheter in mice, to derive comprehensive analyses of both cardiac contractility and relaxation. Suga, Sagawa and colleagues utilized pressure-volume loops to define measures of cardiac contractility, specifically the slope of the ESPVR, or the end-systolic elastance (E_es), and E_max. Elastance, defined by the ratio of pressure to volume (P/V), varies over the duration of systole. During each systole, the instantaneo.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
AnaSed (xylazine)	Lloyd Laboratories	NADA no. 139-236	Anesthetic
Ketaset (ketamine)	Pfizer	440842	Anesthetic
VIP3000	Matrx Medical Inc.		Anesthesia machine
Ventilator	Harvard Apparatus	Model 683	Surgical Equipment
Tubing kit	Harvard Apparatus	72-1049	Surgical Equipment
Homeothermic Blanket	Kaz Inc.	5628	Surgical Equipment
Stereo microscope	Carl Zeiss Optical Inc.	Stemi 2000	Surgical Equipment
Illuminator	Cole–Parmer	41720	Surgical Equipment
Dumont no. 55 Dumostar Forceps	Fine Science Tools Inc	11295-51	Surgical Instruments
Graefe forceps, curved	Fine Science Tools Inc	11052-10	Surgical Instruments
Moria MC31 forceps	Fine Science Tools Inc	11370-31	Surgical Instruments
Mayo scissors	Fine Science Tools Inc	14512-15	Surgical Instruments
Iris scissors	Fine Science Tools Inc	14041-10	Surgical Instruments
Halsey needle holder	Fine Science Tools Inc	12501-13	Surgical Instruments
Olsen–Hegar needle holder	Fine Science Tools Inc	12002-12	Surgical Instruments
spring scissors	Fine Science Tools Inc	15610-08	Surgical Instruments
disposable underpads	Kendall/Tyco Healthcare	1038	Surgical Supplies
Sterile gauze sponges, sterile	Dukal	62208	Surgical Supplies
Cotton-tipped applicators, sterile	Solon	368	Surgical Supplies
Surgical suture,  silk, 6-0	DemeTECH	FT-639-1	Surgical Supplies
1 cc Insulin syringes	Becton Dickenson	329412	Surgical Supplies
Access 9 Hemostasis Valve	Merit Medical	MAP111	Hemodynamic equipment
Sphygmomanometer	Baumanometer	320	Hemodynamic equipment
Millar PV system MPVS-300/400 or MPVS Ultra (includes calibration cuvette)	ADInstruments Inc		Hemodynamic equipment
1.4F conductance catheter	ADInstruments Inc	SPR-839	Hemodynamic equipment
PowerLab 4/30 with Chart Pro	ADInstruments Inc.	ML866/P	Hemodynamic software
animal clipper	Wahl	8787-450A	Miscellaneous
Intradermic tubing PE-10	Becton Dickenson	427401	Miscellaneous
Intradermic tubing PE-50	Becton Dickenson	427411	Miscellaneous
Needle assortment (18, 25 and 30 gauge; Thomas Scientific)			Miscellaneous
0.9% (wt/vol) sodium chloride injection, USP)	Hospira	NDC no. 0409-4888-50	Miscellaneous
Surgical tape			Miscellaneous
Alconox (Alconox Inc.) for catheter cleaning	ADInstruments Inc.		Miscellaneous