On the mode of cardioprotection produced by a new bradycardic agent, FR 76830, during ischaemia and after reperfusion in the isolated perfused rat heart: a 31P-NMR study.
OBJECTIVE
The aim was to investigate the effects of a newly synthesised bradycardiac agent, FR 76830, on cardiac mechanical function and metabolism during ischaemia and reperfusion.


METHODS
FR 76830 and diltiazem were infused during 15 min before ischaemia. Hearts were then subjected to ischaemia (40 min) followed by reperfusion (40 min). High energy phosphate compounds and myocardial pH were assessed by 31P-NMR. The effects of bradycardia induced by FR 76830 before induction of ischaemia on the metabolic derangement resulting from ischaemia and on functional and metabolic recovery after reperfusion were examined in comparison with diltiazem.


METHODS
Male Wistar rats (about 250 g) were used.


RESULTS
FR 76830 and diltiazem produced a dose dependent decrease in heart rate before ischaemia. However, the decrease in the double product (heart rate x left ventricular pressure) was observed only with diltiazem. Both FR 76830 and diltiazem attenuated the fall in myocardial pH during early ischaemia and improved the level of ATP during late ischaemia. Diltiazem also produced an improvement in myocardial acidosis during late ischaemia and in the level of ATP during early ischaemia.


CONCLUSIONS
The importance of bradycardia in protection of the myocardial cells during early ischaemia and in preservation of ATP content during late ischaemia and after reperfusion was shown. However, to produce an improvement in myocardial pH during late ischaemia a decrease in the double product is needed.
Ishibashi
T
T
Department of Pharmacology, Niigata University School of Medicine, Japan.
Matsubara
T
T
Nakazawa
M
M
Katsumata
N
N
Imai
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007511:Ischemia; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D009025:Morpholines; C069354:FR 76830; D009536:Niacinamide; D000255:Adenosine Triphosphate; D004110:Diltiazem