Description of Selected Services

Tailcuff Measurement of Blood Pressure

The tailcuff technique can be used for low-cost, high throughput, serial measurements of blood pressure in conscious rats and mice. Kent Scientific system is available, which consists of an occluding tailcuff, blood pressure (BP) sensors , rodent holders, and a computer-controlled inflation pump. Measured parameters include systolic pressure, diastolic pressure, mean BP, and heart rate. There is good correlation between tailcuff and intra-arterial BP in anesthetized animals (Chen et al. Am J Resp Crit Care Med, 2005; 172:915). Nevertheless, tailcuff measurements in conscious animals may be more variable, and may be confounded by animal stress attributable to handling and heating.

Cardiovascular Measurements in Chronically Implanted Animals

Chronic implant technique permits cardiovascular phenotyping in conscious and freely-moving animals, without the confounding effects of anesthesia, acute surgery, and animal handling. Moreover, this technique provides continuous beat-to-beat measurements over a prolonged period (i.e., days for implanted fluid-filled catheters, weeks for implanted telemetry devices, and months for implanted flow probes). It can be used to measure the effects of circadian rhythms, for example, BP variability during dark (high activity) and light (low activity) periods. Finally, the technique offers opportunities for sequential experiment designs that can reduce the number of genetically engineered animals required.

The following procedures can be performed in SAPC:

• Chronic sampling of arterial and/or venous blood through implanted fluid-filled catheters;
• Arterial or venous pressure measurements through implanted fluid-filled catheters;
• Arterial or venous blood pressure (see Figures 1-3), ECG, EEG, EMG, locomotor activity and temperature, through implanted telemetry devices (Data Sciences International);
• Cardiac output and organ blood flow with implanted flow probes (Transonics Systems) (see Figures 1-3).

Cardiovascular Measurements in Anesthetized Animals

Invasive catheter-based approaches provide complimentary in vivo characterization of the cardiovascular phenotype. Under isoflurane anesthesia, high fidelity catheters (e.g., Millar Mikro-tip catheters) are used for measurement of arterial and central venous BP, and left and right ventricular pressure. Cardiac output is measured by either thermodilution technique (Cardiomax III from Columbus Instruments or Vigilance from Edwards Lifesciences) or by flow probe technique (Transonic System).

Major cardiovascular indices that can be measured include:

• Indices of Global Cardiovascular Function: BP, heart rate, and cardiac output

• Indices of Cardiac Load: central venous pressure, left and right ventricular end-diastolic pressures or volumes, total peripheral resistance

• Indices of Cardiac Contractility: left and right ventricular contraction rates (dP/dtmax), left ventricular fractional shortening

• Indices of Cardiac Relaxation: left and right ventricular relaxation rates (-dP/dtmax)

Ultrasound Biomicroscopy

Echocardiography is a leading method for imaging the cardiovascular system because it is non-invasive, versatile, high throughput, and well suited for serial measurements. Clinical echocardiographic systems, with frequencies of 8-12 MHz, provide low spatial resolution that preclude the study of the small and fast-beating mouse heart. Our VisualSonics Vevo 770 system offers high frequency (20 to 55 MHz) imaging and spatial resolution of ~30 microns. The system can produce images at near-microscopic resolution, and is therefore called ultrasound biomicroscopy.

The SAPC Vevo 770 system is used for in vivo observation of cardiac morphology and hemodynamics in mice and rats. For example, two-dimensionally (2D)- guided M-mode and Doppler echocardiography can be used to determine the geometry and blood velocity in the four heart chambers and large thoracic vessels (aorta, pulmonary artery/vein) (see Figures 4-7).

SAPC also provides SonoSite Elite ultrasound system equipped with comprehensive cardiac software and three transducers (2-10MHz). This portable system can be used for on-site echocardiography or other organ ultrasound from rats to large animals including pigs, monkeys and sheep.

Additional applications of the Vevo 770 system include:

• Developmental Studies: Detailed in vivo visualization of the same mouse from as early as embryonic day 5.5 through neonate to adulthood.
• Cancer Research: Measurement of tumor size (volume) and shape by high-resolution 3D visualization; measurement of blood flow in and around tumors with pulse-wave Doppler.
• Organ/tissue Perfusion: Untargeted micro-bubbles can significantly enhance image quality of organ and tissue blood pools.
• Molecular Imaging: Targeted contrast agents with appropriate ligands that bind to specific biomarkers can be used to quantify expression of these biomarkers (e.g., P-Selectin, an inflammatory marker, or VEGFR2, an angiogenic marker).
• Neurobiological Research: Ultrasound-guided needle injections and extractions, study of embryonic or neonatal brain development, study of cell lineage, and study of progressive neural degenerative diseases associated with mouse models.

Ex Vivo Heart Perfusion

The classic Langendorff perfusion and the working heart preparation are powerful model systems for studying cardiac function without such confounding factors as variation of loading conditions, changes in systemic neurohormonal activation, pericardial constraint, and cardiac-vascular interactions. The preparations enable the study of heart pacing rate, coronary flow or pressure, and temperature under controlled conditions.

Animal Models

Animal models that mimic human cardiovascular diseases are necessary for studying pathogenic mechanisms and the effects of intervention. Human diseases such as chronic heart failure are usually complex syndromes that include cardiac, hemodynamic, neurohumoral, and peripheral alterations. No animal models mimic all of these changes; nevertheless, well-designed animal models are applicable to specific pathogenic aspects of human diseases.

The following is a selected list of animal models that SAPC can provide:

• Acute myocardial ischemia, infarction, or ischemia and reperfusion: Coronary artery ligation
• Chronic myocardial ischemia and heart failure: Coronary artery ligation
• Pressure Overload: Aortic banding
• Volume Overload: Aortico-caval fistula; Aortic Insufficiency
• Toxic cardiomyopathy: Administration of cardiac toxins and other agents, such as monocrotaline, adriamycin, catecholamine, and aldosterone. The drugs can be delivered orally, subcutaneously, by gavage, or by chronically implanted osmotic minipumps.
• Hypoxia: Chronic sustained hypoxia; Chronic intermittent hypoxia.

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