Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs.
1. The 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. 2. Haemodynamics and regional blood flow were determined before and during infusions of levosimendan (0.75, 1.5, and 3.0 micrograms kg-1 min-1), pimobendan (10, 20, and 40 micrograms kg-1 min-1), or milrinone (1.0, 2.0, and 4.0 micrograms kg-1 min-1). 3. All 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. 4. Levosimendan 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. 5. The results indicate that levosimendan, pimobendan, and milrinone cause subtlety different alterations in regional tissue perfusion while producing similar haemodynamic effects.
Pagel
P S
PS
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Hettrick
D A
DA
Warltier
D C
DC
D000758:Anesthesia; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D008297:Male; D020105:Milrinone; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D000077464:Simendan
D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D011728:Pyridones; D000077464:Simendan; C041648:pimobendan; D020105:Milrinone