Abstract Body: Objective: Phenylephrine (PE) is known to act as an alpha-1 adrenergic receptor agonist with negligible beta-adrenergic activity. In the systemic circulation, it raises BP by inducing vasoconstriction. Its role in cardiac preload is still highly debated. PE predominantly acts on vascular smooth muscle cells without causing stimulation of cardiomyocytes. Clinically, an intravenous bolus is used to elevate BP during hypovolemia in septic or cardiogenic shock. We used different doses to inquire about venous preload induction comparing its afterload action to transient mechanical occlusion of carotid artery (CAO).

Methods: The systemic pressure (SBP, DBP), jugular vein pressure (JVP), jugular vein and carotid artery blood flow (JVF and ABF) were measured in healthy rats (n=5) at rest and during the PE administration (15, and 30ug/kg) or CAO. The CAO was measured by transient ceasing of blood flow measured by a flowmeter on internal CA. Calculation of vascular resistances were used to generate the initial quality assessment of afterload/preload (baseline vs. elevated AL).

Results: During CAO the mean JVP has not changed as compared to baseline (5.01±0.71 vs. 4.99±0.74 mmHg; p=0.7), however, the JV blood flow has significantly dropped to about 50 % of the initial value (6.01± 1.72 vs. 3.2±0.9 ml/min; p<0.05), which significantly increased venous resistance (1.96±0.28 vs. 0.97±0.14 mmHg*min/l; p<0.05). This increase of preload resistance was not observed during doses of PE (0.74±0.14 and 0.81±0.16 mmHg*min/l), where in contrast both JVP and JV blood flow has increased, effectively canceling the resistance to preload (p=0.97 and 0.89, resp.).
Compared to CAO, both PE 15 and 30 elicited a greater rise in SBP, DBP, from the same baseline conditions. In case of SBP 15 and 30 vs. CAO (149.1±10.8 vs. 162.3±8.7 vs. 106.9±2.89 mmHg; p<0.05; and p<0.001); DBP (93.8±10.6 vs. 108.4±8 vs. 60.5±2.72 mmHg; p<0.05 and p<0.001).

Conclusions: Compared to CAO, doses of PE elicited greater dose-dependent preload response. This observation confirms the beneficial nature of PE during hypovolemic conditions in septic, or cardiogenic shock. Findings also highlight importance titrating PE to balance its afterload/ preload properties while monitoring venous system response.