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Effects of prostacyclin analogue on function and metabolism in the ischemic working rat heart
.J Mel Ccll(:ardiol23
(Supplement 11) (19911
19
EFFECTS CF VERAPAMIL ANLi PROPRANOLUL ON CHANGES IN EXTSACELLULAR r:+ A&L ~:C‘vT&1C’;il,l:‘!’ ZLJ!tING JF,ADE3 CORONARY FLOW 3EDUCTLiiN IN THE PI!:. I. Watanabe, S. Saitc, V. 37iawi. 71. ia tano. The Second >epartmerlt $71‘ yiediclne, Nlhon University Schs:ol o:‘ !*le~<~.:1r1c~. Tne beta adrenergic and calciur-. channel blocking agents are know t:) re~tucc, We used a low-flow model of ischPmla il. UU~‘I.‘. heart rate and alter contractility. Blood was shunted from carotid artery to the left anterior descending coronary z:..t+‘~, ta; assess tne threshold flow for the rise in extracellular potassilim ;iK*Je, associated with ischemia during control and following the adminlstration i,!’ proprarwlol (Pl=O.Jmg/kg: P2=1-&g/kg! or verapamil (C.Z’mg/kg). ‘We also 1,.l?as1,l-i’-: the changein contractlllty associated with graded flow reductions. We :‘, un8! t,:!:. when heart rate is held constant: 1) Verapamil and F; shift the threnhol.: t.l:,. for [R*]e rise, but Pl dose not; 2;~ Verapamil reduces afterload awl select ! vcih.iepresses contractility in the ischemic zone: 3) High dose of propracolo! ~11~1 ‘I(~ t affect 2fterload and depresses contractility in both 1schemic and non-ischeml :? 8%~: even in the settin? ,>: VZI’,~’ 4) Verapamil reduces ischemia-induced [K+] e releare low ,cor2nary flow (O-gml/minj, whereas hi&h Jose of propranobl dons II< t r?ii ((‘+ lschem:?-induced [K’]e release when the regional wall rrnti?u become a:iyst.ii+ : dys:
20
EFFECTS OF PROSTACYCLIN ANALOGUE ON FUNCTION AND METABOLISM IN THE ISCHEMIC WORKING RAT HEART. T. Oguchi, S. Kashimoto, T. Nakamura. T. Yamanashi Medical College. KtlmaZ?awa. Department of Anesthesiology. Yamanashi, Japan. Prostacyclin has several biological activities that include prevention of platelet aggregation, coronary vasodilation, stabilization of and inhibition of thromboxane generation. The aim lysosomal membranes. (PG- I a : of this study was to determine whether prostacyclin analogue isolated op-2507) could reduce myocardial damage against ischemia in rat hearts. The hearts were perfused by a working rat heart model with and whole heart ischemia was Krebs-Henseleit bicarbonate (KHB) buffer. induced by one-way aortic valve for 15 min followed by reperfusion for administered to KHB buffer from the 30 min. PG-Ia, 20 “g/ml. was Coronary flow in the PG-la group beginning to the end of experiment. in the control during ischemia increased significantly more than that group. The incidence of ventricular fibrillation during reperfusion was 100% and 25% in the control and PG-la groups, respectively. Myom cardial ATP content in the PG-la group was significantly greater than These results suggest that PG-la protected that in the control group. the heart against ischemia and possessed an anti-arrhythmic effect
21
DEFEROXAMINE GUINEA-PIG
DELAYED
HO
-INDUCED
ELECTROPHYSIOLOGICAL
CHANGES
IN
SINGLE
VENTRICULAR '&OCYTES. K.Yasui, S.Kato, J.Toyama. The Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. radicals have been implicated in the genesis of Oxygen free reperfusion injury and arrythmia. The formation of the highly reactive hydroxyl radical requires the presence of metal ions, most importantly iron. We examined the effects of Hz02 on action potentials and membrane currents of single guinea-pig ventricular myoctes and assessed the action iron chelator deferoxamine(DFX) against Hz0 -induced of electrophysiological changes, using patch clamp technique. DFH(300 vM) to myocytes by intracellular perfusion. was given H202(100 I'MI superfusion, in the presence and absence of DFX, shortened progressively action potential duration(APD) resulting in inexcitability without resting potential. significant depolarization of Current-voltage revealed a large relations obtained after cells became inexcitable, potential. The mean outward current reversing near the K equilibrium time to inexcitability for all cells exposed to H202 was significantly longer in DFX-loaded cells (18.123.7 min, n=7) than in control cells (10.253.3 min, n=7). (pqO.01; non-paired t-test). These results suggest that DFX decelerates H202-induced cellular damage possibly through the inhibition of Fenton reaction.
S.23
(Supplement 11) (19911
19
EFFECTS CF VERAPAMIL ANLi PROPRANOLUL ON CHANGES IN EXTSACELLULAR r:+ A&L ~:C‘vT&1C’;il,l:‘!’ ZLJ!tING JF,ADE3 CORONARY FLOW 3EDUCTLiiN IN THE PI!:. I. Watanabe, S. Saitc, V. 37iawi. 71. ia tano. The Second >epartmerlt $71‘ yiediclne, Nlhon University Schs:ol o:‘ !*le~<~.:1r1c~. Tne beta adrenergic and calciur-. channel blocking agents are know t:) re~tucc, We used a low-flow model of ischPmla il. UU~‘I.‘. heart rate and alter contractility. Blood was shunted from carotid artery to the left anterior descending coronary z:..t+‘~, ta; assess tne threshold flow for the rise in extracellular potassilim ;iK*Je, associated with ischemia during control and following the adminlstration i,!’ proprarwlol (Pl=O.Jmg/kg: P2=1-&g/kg! or verapamil (C.Z’mg/kg). ‘We also 1,.l?as1,l-i’-: the changein contractlllty associated with graded flow reductions. We :‘, un8! t,:!:. when heart rate is held constant: 1) Verapamil and F; shift the threnhol.: t.l:,. for [R*]e rise, but Pl dose not; 2;~ Verapamil reduces afterload awl select ! vcih.iepresses contractility in the ischemic zone: 3) High dose of propracolo! ~11~1 ‘I(~ t affect 2fterload and depresses contractility in both 1schemic and non-ischeml :? 8%~: even in the settin? ,>: VZI’,~’ 4) Verapamil reduces ischemia-induced [K+] e releare low ,cor2nary flow (O-gml/minj, whereas hi&h Jose of propranobl dons II< t r?ii ((‘+ lschem:?-induced [K’]e release when the regional wall rrnti?u become a:iyst.ii+ : dys:
20
EFFECTS OF PROSTACYCLIN ANALOGUE ON FUNCTION AND METABOLISM IN THE ISCHEMIC WORKING RAT HEART. T. Oguchi, S. Kashimoto, T. Nakamura. T. Yamanashi Medical College. KtlmaZ?awa. Department of Anesthesiology. Yamanashi, Japan. Prostacyclin has several biological activities that include prevention of platelet aggregation, coronary vasodilation, stabilization of and inhibition of thromboxane generation. The aim lysosomal membranes. (PG- I a : of this study was to determine whether prostacyclin analogue isolated op-2507) could reduce myocardial damage against ischemia in rat hearts. The hearts were perfused by a working rat heart model with and whole heart ischemia was Krebs-Henseleit bicarbonate (KHB) buffer. induced by one-way aortic valve for 15 min followed by reperfusion for administered to KHB buffer from the 30 min. PG-Ia, 20 “g/ml. was Coronary flow in the PG-la group beginning to the end of experiment. in the control during ischemia increased significantly more than that group. The incidence of ventricular fibrillation during reperfusion was 100% and 25% in the control and PG-la groups, respectively. Myom cardial ATP content in the PG-la group was significantly greater than These results suggest that PG-la protected that in the control group. the heart against ischemia and possessed an anti-arrhythmic effect
21
DEFEROXAMINE GUINEA-PIG
DELAYED
HO
-INDUCED
ELECTROPHYSIOLOGICAL
CHANGES
IN
SINGLE
VENTRICULAR '&OCYTES. K.Yasui, S.Kato, J.Toyama. The Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. radicals have been implicated in the genesis of Oxygen free reperfusion injury and arrythmia. The formation of the highly reactive hydroxyl radical requires the presence of metal ions, most importantly iron. We examined the effects of Hz02 on action potentials and membrane currents of single guinea-pig ventricular myoctes and assessed the action iron chelator deferoxamine(DFX) against Hz0 -induced of electrophysiological changes, using patch clamp technique. DFH(300 vM) to myocytes by intracellular perfusion. was given H202(100 I'MI superfusion, in the presence and absence of DFX, shortened progressively action potential duration(APD) resulting in inexcitability without resting potential. significant depolarization of Current-voltage revealed a large relations obtained after cells became inexcitable, potential. The mean outward current reversing near the K equilibrium time to inexcitability for all cells exposed to H202 was significantly longer in DFX-loaded cells (18.123.7 min, n=7) than in control cells (10.253.3 min, n=7). (pqO.01; non-paired t-test). These results suggest that DFX decelerates H202-induced cellular damage possibly through the inhibition of Fenton reaction.
S.23