Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Summary

Acute myocardial infarction in mice induces acute but incompletely characterized changes in left ventricular (LV) function. LV catheterization in mice undergoing coronary artery occlusion serves as a novel method for a real-time evaluation of LV function.

Abstract

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any potential therapeutic approach directed against acute left ventricular (LV) dysfunction. Current imaging modalities (e.g., echocardiography and magnetic resonance imaging) have several limitations since data on LV pressure cannot directly be measured. LV catheterization in mice undergoing coronary artery occlusion could serve as a novel method for a real-time evaluation of LV function.

At the beginning of the procedure, mice were anesthetized followed by endotracheal intubation. For LV catheterization, the right carotid artery was exposed via middle-neck incision. The catheter was introduced and placed into the LV cavity. Left thoracotomy was conducted and the left main coronary artery (LCA) was ligated. To induce reperfusion, the suture was released after 45 min. Pressure-volume data was recorded at all times.

Ligation of the LCA caused a decrease in LV systolic function as evidenced by a 30% reduction in stroke volume, LV ejection fraction (EF), and cardiac output. Maximum dP/dt as a parameter for LV contractility was also significantly reduced and diastolic function was severely impaired (minimum dP/dt -40%). Reperfusion over a period of 20 min did not lead to a complete recovery of LV function.

Real-time pressure-volume analysis served as a valid procedure for monitoring cardiac function during acute myocardial infarction in mice. Maintaining stable anesthesia and a standardized surgical approach was crucial to ensure valid results. As the early phase of acute myocardial infarction is critical for morbidity and mortality, the delineated method could be beneficial for preclinical evaluation of new strategies for cardioprotection.

Introduction

Cardiovascular disease is the most common cause of death in western civilization¹. Acute myocardial infarction is a critical event, which is associated with high acute and chronic mortality². Even if revascularization is achieved via emergency percutaneous coronary intervention (PCI), mortality remains high, particularly within the first 48 h after onset of symptoms in patients with acute myocardial infarction³. Cardiogenic shock caused by acute reduction in left ventricular (LV) function is a major cause for in-hospital mortality in these patients³. This early red....

Protocol

All experiments were completed in accordance and compliance with all relevant regulations (‘European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes’ (Directive 2010/63/EU) and animal care was in accordance with institutional guidelines. All experiments have been performed with male C57BL/6JRj mice at the age of 6 months.

1. Preparation

1. Prepare a surgical microscope and a heating pad as well as a rectal probe to monitor the body temperature. Clean and sterilize all surgical instruments.
2. Prepare 2 pieces of 10 cm 5-0 silk thread for vessel ligation....

Results

After LV catheterization, reversible LCA ligation was performed for 45 min followed by 10 min of reperfusion. PV data was recorded at all times (Figure 1).

Correct placement of the PV catheter was confirmed by obtaining the characteristic LV PV graph (Figure 2A). LV catheter placement showed the typical ventricular pressure range with a minimum of 0 - 20 mmHg whereas fa.......

Discussion

PV monitoring of LV hemodynamics in acute myocardial infarction serves as a novel method for real-time in vivo assessment of cardiogenic shock and impaired LV function in I/R injury. PV catheterization can provide a broad spectrum of parameters with regard to LV systolic and diastolic function. In addition to the LV volumetric parameters typically obtained by echocardiography or MRI (chamber volumes, EF, stroke volume, and cardiac output), PV analysis yields a more complete profile of LV function by simultaneous.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Betaisodona Loesung	Mundipharma	4162-1606/89x30mm	Povidon-Iod
Calibration cuvette	Millar instruments	910-1049	Calibration cuvette
Contura professional hair trimmer	Wella	HS-60	Small animal shaving system
Eclipse Needle 27G	BD	REF 305770	27G needle
Forceps	FST	11203-25, 11069-08, 11616-15, 11506-12, 11051-10	Surgical forceps
Forceps	Aesculap Braun	BN731R, BD 311R	Surgical forceps
Foris FS2434	Eizo	0FTD2033	Monitor
Hamilton Syringe 100 µl needle	Hamilton	80621	100µl syringe with needle
Heated Small animal OP table	Harvard Apparatus	15001	Heated OP table
Heparin-Natrium 25000	Ratiopharm	N68542.04	Heparin
Ketamin 10% 100 mg/ml	bela-pharm	FS1670041	Ketamin
Labchart Pro 8 + Pro modules	AD Instruments	MLS260/8	PV data analysis software
LAS EZ	Leica	LAS EZ	Microscope camera software
Leica IC80 HD	Leica	IC80 HD	Microscope camera
Leica M80	Leica	M80	Microscope
Micro-tip catheter transducer	Millar instruments	SPR-839	PV catheter
MiniVent	Harvard Apparatus	845	ventilation
MPVS Ultra	Millar instruments	PL3508B48/M	PV catheter data acquisition device
Octenisept	Schülke	20000832-A	disinfectant
Plastipak 1ml	PD	REF 303172	1ml syringe
PowerLab 8/35	AD Instruments	PL3508	analog/digital converter
Prolene 6-0	Ethicon	XNEH7814.P31	Polypropylene suture
Retraction Kit	FST	18200-20	retraction of surgical situs
Seraflex 5-0	Naila	IC108000	silk suture
Small and micro-scissors	FST Essen	14059-11, 15007-08, 14064-11	Surgical scissors
Small silicon tube	Reichelt Chemietechnik		tube for LCA occlusion
Sodium Chloride	Sigma-Aldrich	S7653	Sodium Chloride
testo 108	testo	5631080	rectal thermometer
Thinkcentre desktop computer	Lenovo	PC0EJS2V	Computer
Vasofix Safety 20G	Braun	4269110S-01	intubation catheter
Windows 10	Microsoft	KW9-00240	Operating system
Xylazin 2%	Ceva	6324464.00.00	Xylazine hydrochloride