Functional Cardiovascular Characterization of the Common Marmoset (Callithrix jacchus)

**Background:** Cardiovascular diseases remain the leading cause of death worldwide, and appropriate animal models are critical for investigating genetic, molecular, and therapeutic approaches. The common marmoset (Callithrix jacchus), a small non-human primate (300–500 g), offers genetic proximity to humans, a short lifespan, and similarities in heart anatomy, collagen distribution, and age-related cardiovascular changes. However, a comprehensive functional characterization of its cardiovascular system, particularly invasive hemodynamic measurements, has been lacking. This study aimed to establish pressure–volume loop (PV loop) measurements in the common marmoset and compare the results with magnetic resonance imaging (MRI) and echocardiography to validate and classify the data.

**Methods:** Seven healthy, test-naive male common marmosets (mean age 32.83 ± 1.08 months, mean body weight 435 ± 11.55 g) were included. All animals underwent cardiac MRI at 9.4 Tesla using a navigator-based IntraGate-FLASH sequence to assess left and right ventricular volumes and function. After at least four weeks, PV loop measurements were performed via an open-chest abdominal approach using a 1.9F admittance catheter inserted into the left ventricle. Vena cava occlusions were performed to obtain load-independent parameters (e.g., end-systolic pressure–volume relationship [ESPVR], preload recruitable stroke work [PRSW]). In five animals, transthoracic echocardiography (Vevo 3100, 15–46 MHz) was performed immediately before PV loop measurements. For direct method comparison, only data from animals with all three datasets were analyzed (n=5). Anesthesia was standardized: induction with alfaxalone and benzodiazepine, maintenance with propofol and remifentanil, supplemented with sevoflurane (PV loop) or isoflurane (MRI). Statistical analysis used repeated-measures ANOVA with Bonferroni correction.

**Key Results:** PV loop measurements (n=6) yielded the following baseline values (mean ± SEM): heart rate (HR) 198 ± 14 bpm, end-diastolic volume (EDV) 315 ± 27 µL, end-systolic volume (ESV) 89 ± 21 µL, stroke volume (SV) 226 ± 25 µL, ejection fraction (EF) 72 ± 6%, cardiac output (CO) 44 ± 6 mL/min, stroke work 9191 ± 768 mmHg·µL, dP/dt max 1429 ± 166 mmHg/s, dP/dt min −1221 ± 142 mmHg/s, arterial elastance 0.23 ± 0.03 mmHg/µL, and Tau 19 ± 1 ms. Load-independent parameters from vena cava occlusions included: linear ESPVR slope (Ees) 0.467 ± 0.095 mmHg/µL, PRSW slope 40 ± 5 mmHg, linear EDPVR slope (dp/dV) 0.027 ± 0.009 mmHg/µL, and exponential EDPVR stiffness constant 0.013 ± 0.004 mmHg/µL. MRI (n=7) showed left ventricular EDV 956 ± 53 µL, ESV 365 ± 15 µL, SV 591 ± 46 µL, EF 61 ± 2%, and CO significantly higher than PV loop and echocardiography. Echocardiography (n=5) gave values similar to PV loop for EDV, ESV, SV, and CO (p > 0.05). Direct comparison of the five animals with all three methods revealed that MRI volumes were approximately three- to four-fold higher than PV loop and echocardiography, while EF was similar across methods. HR during MRI (225 ± 17 bpm) was slightly higher but not significantly different.

**Clinical Implications:** This study provides the first comprehensive invasive hemodynamic characterization of the common marmoset using PV loop measurements, establishing reference values for young adult males. The protocol enables assessment of load-independent contractility, compliance, and myocardial energetics, which are critical for detecting subtle cardiac dysfunction in disease models such as heart failure. The comparison with MRI and echocardiography highlights that while all three methods are feasible, absolute volumetric values differ significantly, likely due to technical factors (open-chest vs. closed-chest, calculation methods, anesthesia, and small chamber sizes). Researchers must carefully select the method based on study objectives: PV loops offer real-time, load-independent data ideal for mechanistic studies; MRI provides high-resolution, non-invasive volumetric assessment with lower variability; echocardiography is portable and allows repeated measures. These findings support the common marmoset as a valuable translational primate model for cardiovascular research, bridging the gap between rodent models and humans.