Preclinical Research Models

Heart failure

• Myocardial infarction - This method will be done by permanent ligation of left anterior descending artery (LAD ligation). For mouse and rat intubation new rodent intubation system will be used, which allows us to intubate mouse with 100 % accurate in less than 20 seconds. Any drug we have in our protocol for anesthesia and analgesia will be discussed with costumers, so these drugs will not effect on data.

• Ischemia/Reperfusion - This method will be performed as described in the myocardial infarction method, but the LAD ligation will be removed after certain time of ischemia.

• Transaortic constriction (TAC) and De-banding - TAC will be performed by minimal invasive surgical technique. Animals will not be intubated during the surgery and minimal incision will be made on chest. One week after TAC, it is recommended to do echocardiography and to estimate the degree of the construction. Any mice having mild or low degree of constriction will be removed from the study and extra mice will be included in the study.

• Ascending Aortic Constriction (AAC) - For this surgery animals will be intubated and chest will be opened. Constriction will be placed in the ascending aortic area. One week after AAC recommended to have cardiac imaging for evaluation of degree of constriction.
• Neonatal Ascending aorta or trans-aortic constriction - Surgeries will be performed after weaning the pups. It will be in 19-21 days old mice. The constriction in this method will develop slowly.

• Renal Artery Constriction - By partially constricting left , right or both renal arteries). Using Transonic flow measurement technology we will measure % blood flow decrease after surgery.
• Pulmonary hypertension/right heart failure - for this surgery animal will be intubated and chest will be opened. Constriction will be placed in pulmonary artery.

Middle Cerebral Artery Occlusion ( MCAO)

• MCAO is performed by insertion of the monofilament (Suture) from the carotid artery an blocking the blood flow to the MCA ( Middle cerebral artery). The figure shows the schematic of the surgery.

Systemic Blood Pressure Measurements

• Systolic blood pressure(SBP), diastolic blood pressure ( SBP) and mean blood pressure (MBP), heart rate (HR) measurements will be done by using solid state pressure recording catheter (Transonic Scisense). Power lab will be used for data collection and lab char for data analysis. This method can be done as terminal measurement and for chronic monitoring (by using telemetric system).

Intracardiac Pressure Measure (close chest & open chest)

• For Close Chests Left Ventricular (LV) pressure measurements solid state pressure recording catheter (Transonic Scisense) will be inserted into left ventricle (LV) through right carotid artery ( echo guided). Jugular vein catheterization will also perform for drug delivery.
• For Open Chest LV pressure measurements the thoracic cavity will be opened and the catheter will be inserted from the apex of the heart into the LV
• Left Ventricular (LV) end-diastolic and end-systolic pressure, dP/dt, and heart rate will be measured and dat will be recorder by PowerLab (AdInstruments)

Carotid or Femoral Artery Endothelial Damage

• Carotid Artery Endothelial damage - The spring wire will be inserted into common carotid artery from external carotid artery. External carotid artery will be closed after the surgery. Blood flow to the brain from internal carotid artery will not be altered.

• Femoral Artery Endothelial Damage - The spring wire will be inserted from the muscular branch o the femoral artery. Blood flow will be restored to the femoral arter after endothelial denudation.

Intravenous (IV) and Intraarterial (IA) Chronic Catheterization for Drug Administration and Blood Collection

• Jugular vein, femoral artery or carotid artery will be catheterized chronically for drug administration. The catheter can be connected to the mini-osmotic pump or will be exposed out of the cage (by using metal spring tedder, which will be placed at the back of the animals between the scapula)

Treatment of animals with pharmacological agents

• IV- Intravenous
• IA-Intraartreial
• IP-Intraperitonel
• IM-Intramsular
• SQ- sub cutaneouse
• Oral gavage
• Intracardiac
• Implantation of alzet mini osmotic pumps
• Food
• Drinking water

Euthanasia and tissue collection

• We will collect and store any tissues in liquid nitrogen, store in-80 freezer. We will ship tissue samples to our customers (with dry ice or liquid nitrogen)

Custom designed research projects.

• We are happy to discuss any surgeries which are not listed here. Dr. Raffi Gurunluoghlu, plastic surgeon and Dr. Vahe Fahradyan from the Cleveland Clinic, along with Dr. Vahagn Ohanyan will discuss all possible surgical and research methods we can perform.