Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs.
1. The ability of the cardioselective beta-adrenoceptor antagonist bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropyl-amino -2-propanol hemifumarate, EMD 33512) to suppress isoprenaline-induced increases in heart rate and maximal rate of rise in left ventricular pressure (LVdP/dtmax) was studied in 6 anaesthetized pigs given 4 cumulative doses (16, 64, 256 and 1024 micrograms kg-1). Bisoprolol was about 2 times more effective in suppressing isoprenaline-induced increases in LVdP/dtmax than those in heart rate. 2. In 8 animals which had a partial stenosis of the left anterior descending coronary artery (LADCA), the effects of 3 consecutive doses (50, 200 and 750 micrograms kg-1) of bisoprolol were studied on systemic haemodynamics, regional myocardial perfusion and function. The effects of the drug were compared with those obtained in a group of 9 animals with LADCA stenosis which did not receive any treatment. 3. The lowest dose of bisoprolol (50 micrograms kg-1) increased perfusion of the ischaemic myocardium (which had been reduced from 123 +/- 20 ml min-1 100 g-1 to 42 +/- 11 ml min-1 100 g-1) by 21 +/- 10 ml min-1 100 g-1 (P less than 0.05). In particular the subendocardial layers, which were most severely affected by the stenosis (a decrease from 128 +/- 19 ml min-1 100 g-1 to 20 +/- 6 ml min-1 100 g-1) benefited from the administration of the drug (an increase of 30 +/- 10 ml min-1 100 g-1). Perfusion of the subepicardium was not significantly affected. With the higher dose only a minor additional improvement in perfusion of the ischaemic myocardium was observed. 4. The negative chronotropic response is the most likely factor leading to the improvement in perfusion. 5. Myocardial wall thickening, which decreased from 41 +/- 2% to 9 +/- 4% (P less than 0.05) due to the hypoperfusion, did not improve after administration of the drug. This lack of improvement may possibly be due to the duration of ischaemia before and the magnitude of the flow deficit after bisoprolol administration. 6. Between 15 and 60 min of ischaemia, 5 of the 9 untreated animals had an episode of ventricular fibrillation compared with only 1 of the 8 animals treated with bisoprolol, in spite of an initially larger flow reduction in the treated animals. The more homogeneous flow distribution after bisoprolol might account for the lower incidence of arrhythmias in this group. 7. It was demonstrated that bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs even at doses (50.pgkg-1) that only moderately antagonize isoprenaline-induced cardiostimulatory effects.
Sassen
L M
LM
Laboratory for Experimental Cardiology (Thoraxcenter), Erasmus University Rotterdam, The Netherlands.
den Boer
M O
MO
Rensen
R J
RJ
Saxena
P R
PR
Verdouw
P D
PD
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D017298:Bisoprolol; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D013552:Swine
D011412:Propanolamines; D006859:Hydrogen; D007545:Isoproterenol; D017298:Bisoprolol