Abstract
The purpose of this study was to investigate serial ultrasound imaging in rats as a fully non-invasive method to (1) quantify the diameters of splanchnic veins in real time as an indirect surrogate for the capacitance function of those veins, and (2) assess the effects of drugs on venous dimensions. A 21 MHz probe was used on anesthetized male Sprague–Dawley rats to collect images containing the portal vein (PV), superior mesenteric vein (SMV), abdominal inferior vena cava (IVC), and splenic vein (SpV; used as a landmark in timed studies) and the abdominal aorta (AA). Stable landmarks were established that allowed reproducible quantification of cross-sectional diameters within an animal. The average diameters of vessels measured every 5 min over 45 min remained within 0.75 ± 0.15% (PV), 0.2 ± 0.09% (SMV), 0.5 ± 0.12% (IVC), and 0.38 ± 0.06% (AA) of baseline (PV: 2.0 ± 0.12 mm; SMV: 1.7 ± 0.04 mm; IVC: 3.2 ± 0.1 mm; AA: 2.3 ± 0.14 mm). The maximal effects of the vasodilator sodium nitroprusside (SNP; 2 mg/kg, i.v. bolus) on venous diameters were determined 5 min post SNP bolus; the diameters of all noted veins were significantly increased by SNP, while mean arterial pressure (MAP) decreased 29 ± 4 mmHg. By contrast, administration of the venoconstrictor sarafotoxin (S6c; 5 ng/kg, i.v. bolus) significantly decreased PV and SpV, but not IVC, SMV, or AA, diameters 5 min post S6c bolus; MAP increased by 6 ± 2 mmHg. In order to determine if resting splanchnic vein diameters were stable over much longer periods of time, vessel diameters were measured every 2 weeks for 8 weeks. Measurements were found to be highly reproducible within animals over this time period. Finally, to evaluate the utility of vein imaging in a chronic condition, images were acquired from 4-week deoxycorticosterone acetate salt (DOCA-salt) hypertensive and normotensive (SHAM) control rats. All vessel diameters increased from baseline while MAP increased (67 ± 4 mmHg) in DOCA-salt rats compared to SHAM at 4 weeks after pellet implantation. Vessel diameters remained unchanged in SHAM animals. Together, these results support serial ultrasound imaging as a non-invasive, reliable technique able to measure acute and chronic changes in the diameter of splanchnic veins in intact rats.
Highlights
Dysregulation of venous capacitance is proposed to contribute to the etiology of heart failure, arterial hypertension, hepatic cirrhosis, preeclampsia, postural hypotension and shock (Safar and London, 1987; Reilly et al, 2001; Stewart et al, 2004; Aardenburg et al, 2005; Li et al, 2008; Burchell et al, 2013)
Because it was important to visualize the branching of the splenic vein (SpV) off the parent vessels and to include multiple vessels of interest within the same view, a transverse positioning of the ultrasound transducer as seen in Figure 1A was determined to provide the optimal views for measurements of the portal vein (PV), superior mesenteric vein (SMV), SpV, inferior vena cava (IVC), and AA diameters
We investigated several different vein segments (PV, SMV, IVC, and SpV) because multiple veins contribute to splanchnic vascular capacitance function, and each segment is unique in terms of structure and contractile regulation (Schmitt et al, 2002)
Summary
Dysregulation of venous capacitance (venous volume at a given transmural pressure) is proposed to contribute to the etiology of heart failure, arterial hypertension, hepatic cirrhosis, preeclampsia, postural hypotension and shock (Safar and London, 1987; Reilly et al, 2001; Stewart et al, 2004; Aardenburg et al, 2005; Li et al, 2008; Burchell et al, 2013). Splanchnic veins, located within the abdominal region, represent the largest blood volume reservoir within the human body (Gelman, 2009), and exhibit the largest degree of active capacitance response of all venous beds in the body (Tyberg, 2002). They play an important role in the regulation of the circulation by affecting cardiac preload, and cardiac output and blood pressure. Ultrasonographic assessment of the dimensions of large veins [ the inferior vena cava (IVC)] has been used to estimate venous capacitance as a measure of intravascular volume status in patients with septic shock (Schefold et al, 2010) and in patients on hemodialysis (Brennan et al, 2006)
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