Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs
Article first published online: 19 JUL 2012
1996 British Pharmacological Society
British Journal of Pharmacology
Volume 119, Issue 3, pages 609–615, October 1996
How to Cite
Pagel, P. S., Hettrick, D. A. and Warltier, D. C. (1996), Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs. British Journal of Pharmacology, 119: 609–615. doi: 10.1111/j.1476-5381.1996.tb15716.x
- Issue published online: 19 JUL 2012
- Article first published online: 19 JUL 2012
- Received February 26, 1996 Revised June 19, 1996 Accepted July 3, 1996
- Systemic and coronary blood flow;
- myofilament calcium sensitizer;
- troponin C;
- 1The distribution of cardiac output during administration of levosimendan, a new myofilament calcium sensitizer, is unknown. We examined and compared the effects of levosimendan, pimobendan, and milrinone on regional tissue perfusion by use of the radioactive microsphere technique in barbiturate-anaesthetized dogs.
- 2Haemodynamics and regional blood flow were determined before and during infusions of levosimendan (0.75, 1.5, and 3.0 μg kg−1 min−1), pimobendan (10, 20, and 40 μg kg−1 min−1), or milrinone (1.0, 2.0, and 4.0 μg kg−1 min−1).
- 3All three drugs caused similar increases in heart rate, cardiac output, and left ventricular + dP/dt and decreases in end-diastolic pressure and systemic vascular resistance. No changes in subendocardial, midmyocardial, and subepicardial blood flow occurred during administration of levosimendan. However, a redistribution of blood flow from subendocardium to subepicardium was observed. Pimobendan increased midmyocardial and subepicardial blood flow and reduced the endo/epi ratio to a greater degree than levosimendan. Milrinone did not affect myocardial perfusion.
- 4Levosimendan increased blood flow to the renal medulla and decreased renal medullary and cortical vascular resistance. Levosimendan increased blood flow to the small intestine and liver and reduced vascular resistance in these organs. Pimobendan increased hepatic blood flow to a greater degree than levosimendan but did not alter small intestinal perfusion. All three drugs decreased splenic blood flow to similar degrees. Levosimendan and pimobendan reduced cerebral vascular resistance. Levosimendan and milrinone reduced skeletal muscle vascular resistance.
- 5The results indicate that levosimendan, pimobendan, and milrinone cause subtlety different alterations in regional tissue perfusion while producing similar haemodynamic effects.