PMID- 7532750
OWN - NLM
STAT- MEDLINE
DCOM- 19950330
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 24
IP  - 5
DP  - 1994 Nov
TI  - Hemodynamic, neurohumoral, and myocardial energetic effects of pimobendan, a 
      novel calcium-sensitizing compound, in patients with mild to moderate heart 
      failure.
PG  - 730-9
AB  - In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer 
      and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial 
      effects in heart failure. However, its effect on relaxation, myocardial 
      energetics and neurohormones are unknown. Twelve patients with heart failure, New 
      York Heart Association (NYHA) classification II-III, due to ischemic 
      cardiomyopathy, were studied for 1 h after they received 5 mg pimobendan 
      intravenously (i.v.). Pimobendan progressively reduced systemic resistance and 
      left ventricular end-diastolic pressure (LVEDP) (22 and 50%, respectively) and 
      improved isovolumetric contractility and relaxation parameters by 30% (all p < 
      0.05 vs. control). LV end-diastolic and end-systolic volumes (LVEDV, LVESV) 
      decreased significantly by 20 and 19%, respectively. Cardiac output (CO) 
      increased by 17% due to a simultaneous increase in heart rate (HR) from 75 +/- 3 
      to 86 +/- 5 beats/min (mean +/- SEM, p < 0.05). Pimobendan did not change 
      coronary hemodynamics, but myocardial O2 extraction and consumption were 
      decreased significantly by 18 and 20%, respectively. Catecholamines, angiotensin 
      II (AII), and aldosterone levels did not change significantly. In contrast, 
      arterial and coronary venous renin increased significantly from 57 +/- 17 and 53 
      +/- 14.7 microM/h at control to 69 +/- 20 and 69 +/- 20 microM/h, respectively, 
      60 min after pimobendan administration. Simultaneously, cardiac renin uptake at 
      baseline (0.449 +/- 0.185 mumol/min) changed to release (-0.071 +/- 0.145 
      mumol/min, p < 0.05). Serious side effects did not occur. Thus, pimobendan had 
      progressive positive inotropic and lusitropic effects, diminished preload and 
      afterload despite modest stimulation of plasma renin activity (PRA), and reduced 
      systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Remme, W J
AU  - Remme WJ
AD  - Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
FAU - Kruijssen, D A
AU  - Kruijssen DA
FAU - van Hoogenhuyze, D C
AU  - van Hoogenhuyze DC
FAU - Krauss, X H
AU  - Krauss XH
FAU - Bartels, G L
AU  - Bartels GL
FAU - Storm, C J
AU  - Storm CJ
FAU - de Leeuw, P W
AU  - de Leeuw PW
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Catecholamines)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyridazines)
RN  - 0 (Vasodilator Agents)
RN  - 34AP3BBP9T (pimobendan)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Pressure/drug effects
MH  - Cardiac Output/drug effects
MH  - Cardiotonic Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Catecholamines/blood
MH  - Coronary Angiography/drug effects
MH  - Electrocardiography/drug effects
MH  - Female
MH  - Heart Failure/*drug therapy
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Injections, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Muscle, Smooth, Vascular/drug effects
MH  - Myocardial Contraction/drug effects
MH  - Myocardial Ischemia/*drug therapy/pathology
MH  - Oxygen Consumption/drug effects
MH  - Phosphodiesterase Inhibitors/administration & dosage/pharmacology/therapeutic use
MH  - Pyridazines/administration & dosage/pharmacology/*therapeutic use
MH  - Vascular Resistance/drug effects
MH  - Vasodilator Agents/administration & dosage/pharmacology/*therapeutic use
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
AID - 10.1097/00005344-199424050-00007 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 1994 Nov;24(5):730-9. doi: 
      10.1097/00005344-199424050-00007.