Influence of the new inotropic agent DPI 201-106 on the total capacitance vasculature in dogs

L. Bell, D. L. Rutlen

Research output: Contribution to journalArticlepeer-review

Abstract

Recent investigations have demonstrated that the piperazinyl-indole DPI 201-106 (DPI) acts to increase contractility independent of increases in cAMP or inhibition of Na+, K+-ATPase. Since associated changes in the capacitance vasculature would also be expected to influence ventricular performance, the influence of DPI on total intravascular volume (IV) was examined. In eight anesthetized dogs undergoing prior sinoaortic baroreceptor denervation and bilateral cervical vagotomy, blood from the venae cavae was drained to an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in IV could be recorded as reciprocal changes in reservoir volume. Racemic DPI at 50 υg/kg/min for 20 min was associated with a 65 ± 7 ml (P < 0.0001) decrease in total IV and a decrease in mean arterial pressure from 80 ± 7 to 74 ± 5 mmHg (P < 0.0001). DPI administration was associated with a 67 ± 9 ml (P < 0.05) decrease in IV after beta adrenergic blockade and a 68 ± 11 ml (P < 0.05) decrease in IV after alpha and beta adrenergic blockade. Abdominal evisceration abolished the IV decrement due to DPI. Radionuclide imaging studies demonstrated that decreases in hepatic and splenic IV contributed to the decrease in splanchnic IV. Thus, DPI acts to decrease total IV. The IV decrement is due entirely to a decrease in splanchnic IV and is not mediated by baroreceptor stimulation or by adrenergic receptor stimulation. In the animal with an intact circulation, the total IV decrement would be expected to increase venous return and thereby act to maintain ventricular end diastolic pressure.

Original languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalCirculatory Shock
Volume31
Issue number4
StatePublished - 1990
Externally publishedYes

Keywords

  • cardiogenic shock
  • intravascular volume
  • radionuclide imaging
  • splanchnic vasculature
  • venous return

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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