Hemodynamic Effects of Cardiovascular Medications in a Normovolemic and Hemorrhaged Yorkshire-cross Swine Model

Abstract

The Yorkshire-cross swine model is a valuable translational model commonly used to study cardiovascular physiology and response to insult. Although the effects of vasoactive medications have been well described in healthy swine, the effects of these medications during hemorrhagic shock are less studied. In this study, we sought to expand the utility of the swine model by characterizing the hemodynamic changes that occurred after the administration of commonly available vasoactive medications during euvolemic and hypovolemic states. To this end, we anesthetized and established femoral arterial, central venous, and pulmonary arterial access in 15 juvenile Yorkshire-cross pigs. The pigs then received a series of rapidly metabolized but highly vasoactive medications in a standard dosing sequence. After completion of this sequence, each pig underwent a 30-mL/kg hemorrhage over 10 min, and the standard dosing sequence was repeated. We then used standard sta- tistical techniques to compare the effects of these vasoactive medications on a variety of hemodynamic parameters between the euvolemic and hemorrhagic states. All subjects completed the study protocol. The responses in the hemorrhagic state were often attenuated or even opposite of those in the euvolemic state. For example, phenylephrine decreased the mean arterial blood pressure during the euvolemic state but increased it in the hemorrhagic state. These results clarify previously poorly defined responses to commonly used vasoactive agents during the hemorrhagic state in swine. Our findings also demonstrate the need to consider the complex and dynamic physiologic state of hemorrhage when anticipating the effects of vasoactive drugs and planning study protocols.

Figure 1.

Timing of study interventions.

Figure 2.

The effects of hemorrhage (30 mL/kg over 10 min) on investigated hemodynamic parameters. The values of these parameters were normalized to the value that was measured at the start of the hemorrhage, and these normalized values were then averaged over the 15 subject animals. The error bars represent 95% CI for each data point. (A) Heart rate. (B) Mean arterial pressure. (C) Stroke volume. (D) Cardiac output. (E) Systemic vascular resistance. (F) Plethysmography variability index. (G) Mean pulmonary artery pressure. (H) Central venous pressure.