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Effects of calcium antagonists and β-blockers on the ischemia-reperfusion induced changes in myocardial cation contents and adenine nucleotides
e i~bito~ effect of BA 1 cmol/l, on isolated working rabbit hearts was not seen, but showed the protective on myocardial ischemic reperfused injury in this experiments (Table I), e present study also showed that the coronary flow, cardiac output, cardiac index, left cardiac work and heart rate ouly restcned to 52 65,66,&i and 79% (P < 0.05) of the preischemia values respectively at 20 min after reperfusion in the control hezrts, while the above parameters already restored to the preischemia level (P > 0.05) in IO min of apron in the B&treated hearts. The results of present study demonstrated that BA could prevent the myocardial ischemic reperfused damages and accelarate the recoveries of cardiac functions in isolated working rabbit hearts. It has been proved that BA inhibits calcium influx into the cell as Ver, this may be one of the mechanisms of the direct protective effects of BA on myocardial ischemic reperfused damages. ef
n
Kawada, T., Yoshida, &pwtmentof Phmwcology,
Niigata
fn
Y., Sakurai, H. and Imai, S.
University School
ofMeScine,
757? Asahimachi-dori
at
Niiguta, 951, Japan
Effects of calcium ~tago~sts, diltiazem (Dil) and felodipine (Fel) and @blockers, propr~olol (Prop), atenolol (Car), on the ischemia-reperfusion induced change in myocardial cation contents and adenine nucleotides were studied in isolated perfused rat heart. The intracellular contents of Ca*, K’ and Ca’+ were analyzed using cobaltic EDTA (Bridge, 1982) as a marker of the extracellular space. These ions were extracted with the method of Sparrow and Johnston (1964) and measured either with a flamephotometric method or with an atomic absorption spectrophotometric method. The determination of the myocardial adenine nucleotides was conducted with the method developed by Khym (1973). As a measure of the myocardial rn~ha~~ fu~c~on ~MMF), the product of the left ventricular pressure and the heart rate was calculated. Perfusion with a solution containing Dil (lob7 or 3 x lW7), Fe1 (IO”‘or 3 x 10m7) and Prop (3 X lo-“, lo-’ or 3 x 10v5) for 10 miu prior to induction of global ischcmia resulted in a dose-dependent reduction of MMF. However, the reduction of MMF by Car (3 x lo-’ IOv6 or 3 X 10m6) and Ate (low4 or 3 X IOe4) was either slight or minimal. Beperfusion of 40 min after global ischemia of 40 min resulted in a decrease in myocardial K+ and ATP content, ATPflflADP ratio and energy charge (EC) and an increase in Na+ and Ca” content. Both doses of Dil si~i~ca~~tly prevented the reduction of K’ and the increase in Ca 2* . There was a tendency for the increase in Na+ to be prevented. Fe1 tended to prevent the increase in Ca2+ and Na* and the reduction of K+ although the effects were not significantly greater than that of ethanol, the vehicle of Fel. The higher dose of Dil and Fe1 significantly prevented the reduction of ATP and ATp/ADP ratio and tended to prevent the reduction of EC. The higher dose of Prop and Car silently prevented the reduction of ATP, ATP/ADP ratio and EC and tended to prevent the a~umulation of Na’ and the reduction of K+. Only the lowest dose of Prop prevented CaZC accumulation. Higher doses of Prop and Car produced a better recovery of MMF after 40 min reperfusion. Car inhibited the elevation of end-diastolic pressure after 40 min reperfusion. However, Ate did not prevent the developement of myocardial injury. These findings suggest that the protective effects of calcium antagonists and Prop on myocardial injury are due to the reduction of MMF before induction of ischemia. Both Car and Ate showed protective effects without producing reduc&i of MMF- Car is a non-selective B-blocker with a potent ar-blocking activity and the myocardial protective effects of Car may be ascribed to its potent ar-blocking activity. Inhibition by a-blockers of the myocardisl injury induced by ischemia-reperfnsion was demonstrated by several investigators. (Ate) and ca~edilol
EWg, sparrow,
U-US.
et al., Am. J. PE-tysiol., 242: I-%71-H676,
W-P. and
1982.
Johnston@,B.M., B&him. Biophys. Acta, 90: 425-426.1964.
#Rym, J.X., Clin.Chem., 21:1245-1252.1975.
n
Kawada, T., Yoshida, &pwtmentof Phmwcology,
Niigata
fn
Y., Sakurai, H. and Imai, S.
University School
ofMeScine,
757? Asahimachi-dori
at
Niiguta, 951, Japan
Effects of calcium ~tago~sts, diltiazem (Dil) and felodipine (Fel) and @blockers, propr~olol (Prop), atenolol (Car), on the ischemia-reperfusion induced change in myocardial cation contents and adenine nucleotides were studied in isolated perfused rat heart. The intracellular contents of Ca*, K’ and Ca’+ were analyzed using cobaltic EDTA (Bridge, 1982) as a marker of the extracellular space. These ions were extracted with the method of Sparrow and Johnston (1964) and measured either with a flamephotometric method or with an atomic absorption spectrophotometric method. The determination of the myocardial adenine nucleotides was conducted with the method developed by Khym (1973). As a measure of the myocardial rn~ha~~ fu~c~on ~MMF), the product of the left ventricular pressure and the heart rate was calculated. Perfusion with a solution containing Dil (lob7 or 3 x lW7), Fe1 (IO”‘or 3 x 10m7) and Prop (3 X lo-“, lo-’ or 3 x 10v5) for 10 miu prior to induction of global ischcmia resulted in a dose-dependent reduction of MMF. However, the reduction of MMF by Car (3 x lo-’ IOv6 or 3 X 10m6) and Ate (low4 or 3 X IOe4) was either slight or minimal. Beperfusion of 40 min after global ischemia of 40 min resulted in a decrease in myocardial K+ and ATP content, ATPflflADP ratio and energy charge (EC) and an increase in Na+ and Ca” content. Both doses of Dil si~i~ca~~tly prevented the reduction of K’ and the increase in Ca 2* . There was a tendency for the increase in Na+ to be prevented. Fe1 tended to prevent the increase in Ca2+ and Na* and the reduction of K+ although the effects were not significantly greater than that of ethanol, the vehicle of Fel. The higher dose of Dil and Fe1 significantly prevented the reduction of ATP and ATp/ADP ratio and tended to prevent the reduction of EC. The higher dose of Prop and Car silently prevented the reduction of ATP, ATP/ADP ratio and EC and tended to prevent the a~umulation of Na’ and the reduction of K+. Only the lowest dose of Prop prevented CaZC accumulation. Higher doses of Prop and Car produced a better recovery of MMF after 40 min reperfusion. Car inhibited the elevation of end-diastolic pressure after 40 min reperfusion. However, Ate did not prevent the developement of myocardial injury. These findings suggest that the protective effects of calcium antagonists and Prop on myocardial injury are due to the reduction of MMF before induction of ischemia. Both Car and Ate showed protective effects without producing reduc&i of MMF- Car is a non-selective B-blocker with a potent ar-blocking activity and the myocardial protective effects of Car may be ascribed to its potent ar-blocking activity. Inhibition by a-blockers of the myocardisl injury induced by ischemia-reperfnsion was demonstrated by several investigators. (Ate) and ca~edilol
EWg, sparrow,
U-US.
et al., Am. J. PE-tysiol., 242: I-%71-H676,
W-P. and
1982.
Johnston@,B.M., B&him. Biophys. Acta, 90: 425-426.1964.
#Rym, J.X., Clin.Chem., 21:1245-1252.1975.