The systemic and regional hemodynamic effects of phenylephrine in sheep under normal conditions and during early hyperdynamic sepsis.
ABSTRACT Phenylephrine treatment of hypotension in sepsis raises concern because it may decrease vital organ bloodflow. Accordingly, we investigated the effects of phenylephrine on systemic and regional bloodflow in normal and septic sheep.
Responses to phenylephrine or vehicle infusion for 6 hours were determined in conscious normal sheep and sheep with early sepsis induced by administration of live Escherichia coli. Cardiac output and coronary, mesenteric, and renal bloodflow were measured with implanted flow probes.
In normal sheep, phenylephrine decreased cardiac output and heart rate (HR) but increased stroke volume and mean arterial blood pressure (MAP) (84 ± 6 to 108 ± 6 mm Hg, magnitude of mean difference [diff.] 19 [22.6%]; 95% confidence intervals [CI], 17-21). There were significant decreases in regional conductance values with a transient decrease in mesenteric bloodflow, no change in coronary bloodflow, and increased renal bloodflow (222 ± 53 to 271 ± 55 mL/min; diff. 31 [13.9%]; 95% CI, 26-36). During hyperdynamic sepsis, vasodilatation and increased bloodflow occurred in all vascular beds. Phenylephrine restored MAP and stroke volume to baseline values, but HR, cardiac output, and total peripheral conductance progressively decreased. Phenylephrine decreased mesenteric and coronary conductance, with no sustained reduction in flows, but renal conductance was significantly decreased and overall renal bloodflow increased (293 ± 22 vs 347 ± 100 mL/min; diff. 55 [18.8%]; 95% CI, 47-65).
In sheep with early hyperdynamic sepsis, phenylephrine, at a dose that restored MAP, increased stroke volume and renal bloodflow while decreasing HR and coronary bloodflow but not mesenteric bloodflow. Similar responses were seen in normal animals.
- SourceAvailable from: Durk F Zandstra[show abstract] [hide abstract]
ABSTRACT: Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this microvascular network a heterogeneous process. Owing to an increased microcirculatory resistance, a maldistribution of blood flow occurs with a decreased systemic vascular resistance due to shunting phenomena. Therapy in shock is aimed at the optimization of cardiac function, arterial hemoglobin saturation and tissue perfusion. This will mean the correction of hypovolemia and the restoration of an evenly distributed microcirculatory flow and adequate oxygen transport. A practical clinical score for the definition of shock is proposed and a novel technique for bedside visualization of the capillary network is discussed, including its possible implications for the treatment of septic shock patients with vasodilators to open the microcirculation.Critical care (London, England) 01/2005; 8(6):462-8. · 4.72 Impact Factor
Article: Autoregulation of blood flow.Circulation Research 12/1986; 59(5):483-95. · 11.86 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: To study the effects of acute alterations in heart rate and systemic arterial pressure on the mean velocity of left ventricular circumferential fiber shortening (Vcf) and on mean posterior wall velocity (Vpw), we performed ultrasound studies in 25 normal human subjects between the ages of 21 and 29 years. When heart rate was augmented by the administration of intravenous atropine from 64 +/- 2.2 (SEM) to 98 +/- 2.7 beats/min, mean normalized Vcf increased from 1.22 +/- 0.05 to 1.38 +/- 0.06 circumferences (circ)/sec(P less than 0.001). Mean normalized Vpw increased from 0.76 +/- 0.03 to 0.89 +/- 0.04 sec-1 (P less than 0.001). Mean Vcf and mean Vpw uncorrected for end-diastolic diameter increased in a similar fashion (P less than 0.01). After atropine administration, systemic arterial pressure was augmented by means of a phenylephrine infusion in 23 subjects by an average of 39 mm Hg (range 20-50 mm Hg). During the phenylephrine infusion, average heart rate decreased from 96 +/- 2.6 to 91 +/- 3.1 beats/min (NS), while mean normalized Vcf declined from 1.38 +/- 0.06 to 1.09 +/- 0.05 circ/sec (P less than 0.001) and normalized Vpw from 0.89 +/- 0.04 to 0.65 +/- 0.04 sec-1 (P less than 0.001). Nonnormalized velocities exhibited similar alterations (P less than 0.01). We conclude that in the normal human subject mean Vcf and mean Vpw are sensitive to acute alterations in heart rate and systemic arterial pressure. Thus, when ultrasound measures are used for serial assessment of left ventricular performance, the level of heart rate and systemic arterial pressure at which studies are obtained must be considered. Further, the sequential use of atropine and phenylephrine, as described in this study, provides an experimental model for the evaluation of the effects of drug treatment and other interventions on left ventricular performance in man.Circulation 12/1975; 52(5):835-41. · 15.20 Impact Factor