Aortic Constriction Model

Indication and Application:

Efficacy screening of anti-heart failure and anti-hypertrophic therapeutics, evaluation of anti-fibrotic pharmacological interventions, research on molecular pathways governing pathological cardiac remodeling, and validation of ventricular assist devices or advanced cardiovascular technologies.

Modeling Method:

• Transverse Aortic Constriction (TAC - Thoracic): Under mechanical ventilation and aseptic conditions, a partial ligation of the aortic arch is performed between the brachiocephalic trunk and the left common carotid artery against a calibrated needle (e.g., 27G for mice, 22G for rats). The needle is promptly removed, leaving a uniform, highly reproducible luminal constriction.

• Abdominal Aortic Constriction (AAC): The abdominal aorta above the renal arteries is surgically isolated and constricted utilizing a similar calibrated needle technique, providing a robust model for renal-associated systemic hypertension and concentric ventricular remodeling.

Clinical Relevance:

• Pathological Fidelity: The mechanical constriction of the aorta forces the left ventricle to pump blood against elevated resistance, successfully driving the transition from compensated concentric cardiac hypertrophy to decompensated, dilated heart failure, mimicking human hypertensive cardiomyopathy.

• Translational Reliability: The synchronized development of myocardial fibrosis, endothelial dysfunction, and progressive ventricular dilation in this model provides a highly rigorous testing ground for novel compounds targeting chronic heart failure before moving into clinical trials.

Key Evaluation Endpoints:

1. In Vivo / Surgical / Imaging:

• High-Resolution Echocardiography (Vevo System): Non-invasive longitudinal monitoring of Left Ventricular Ejection Fraction (LVEF), Fractional Shortening (FS), Left Ventricular Internal Diameter (LVIDd/LVIDs), and Anterior/Posterior Wall Thickness to track hypertrophy progression.

• Doppler Velocity Profiling: Measurement of the peak systolic pressure gradient across the constriction site to verify the surgical consistency and success of the constriction.

• Hemodynamic Catheterization (Millar Catheter): Invasive left ventricular pressure-volume (P-V) loop analysis to quantify end-systolic/end-diastolic pressure, dP/dt max, and dP/dt min.

2. Histopathology:

• Morphometry (Gold Standard): Gross heart morphology, Heart Weight to Body Weight (HW/BW) ratio, and Heart Weight to Tibia Length (HW/TL) ratio calculation.

• Myocyte Cross-Sectional Area: H&E or Wheat Germ Agglutinin (WGA) staining to quantify the exact physical hypertrophy of individual cardiomyocytes.

• Myocardial Fibrosis Quantification: Masson's Trichrome or Sirius Red staining to assess interstitial and perivascular collagen deposition.

• IHC/IF: Profiling of capillary density (CD31) and local inflammatory cell infiltration (CD68, MAC-2).

3. Molecular:

• Heart Failure Biomarkers: Quantification of fetal gene re-activation markers, including Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP), and beta-Myosin Heavy Chain (beta-MHC) via RT-qPCR or Western Blot.

• Fibrotic Pathways: Expression analysis of TGF-beta, Collagen I/III, and Matrix Metalloproteinases (MMPs) to evaluate pharmaceutical compound efficacy.

Regulatory-Grade Data Package (OECD GLP, AAALAC, CMA, CNAS):

As an established preclinical CRO, all cardiovascular and heart failure studies at HuaTeng Biotechnology are executed in full alignment with international quality standards. Our expert surgical teams utilize strictly calibrated suture and needle specifications to minimize operator-dependent variability, ensuring tightly grouped pressure gradients and highly reproducible data packages designed to accelerate global IND and regulatory submissions.