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Effect of clentiazem on the Syrian hamster hereditary cardiomyopathy
J Viol C:rll C:artiilll 97
23 (Supplrmrnt
IV)
(1991)
VARIATIONS OF ENDOTHELIN BLOOD LEVELS DURING PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY (PTA ). C.Jacob ,B.Dousset,J.Fays, P.Bours, L.Hennequin, MDousset. Services de Biochimie,Radiologie et Chirurgie B 2, Centre Hospitalier ROgional Universitaire .NANCY .FRANCE.
et
Endothelin (ET) is the most potent vascular smooth muscle constrictor released by mammalian endothelium. The production of ET is regulated by various stimuli such as hypoxia and mechanical stretch. Identical phenomena occur in dinical use of PTA. ET arterial levels were evaluated by specific radioimmunoassay (AMERSHAM ) in 12 PTA : 2 iliac , 4 renal , 6 femoropopliieal . Except for iliac PTA where results were shown discordant for unknown reasons, ET levels were always increased after PTA ( from 2Oi3 pmol/ I to 31f 4 pmol/ I ).The highest values were associated with recanalization difficulties and repeated inflations. As a transient rise was observed immediatly after PTA decrease of corresponding values was shown 15 minutes after PTA. bur data suggest that increase of ETconcentrations correlates with spasms described post PTA as visualized by angiograms
98
EFFECT OF CLENTIAZEM ON THE SYRIAN HAMSTER HEREDITARY CARDIOMYOPATHY. 6. Jasmin, L. Proschek, C. Tautu. Departement de pathologie. Universite de Montreal. Canada. Clentiazem (G-Chlorodiltiazem) is a potent calcium channel antagonist which has a long lasting hypotensive effect in various animal models of experimental Beside its vasodilating activity on coronary arteries and a weak hypertension. negative inotropic effect, the question arise whether this calcium channel blocker is also efficient in preventing myocardial necrotic changes as we were able to demonstrate with verapamil several years ago. Clentiazem dissolved in water or in a 1% carboxymethylcellulose solution was administered by different routes in daily doses varying between 3 and 40 mg/kg. Optimal results were obtained by using 0.25 ml osmotic minipumps (Alzet) inserted subcutaneously once a week and delivering a daily dose of 5.6 mg/kg. After a 4-week treatment in 30-day-old cardiomyopathic hamsters, the incidence of cardiac necrotic changes was reduced by 50% with a mean severity of 0.5 (scale O-3). While the cardioprotection was similar to that obtained with verapamil, the squelettal muscle necrotic lesions however were unchanged by this calcium antagonist. (Supported by grants from Fondation Hacdonald Stewart and by Laboratoires Nordic.).
99
CARDIAC OUTPUT (CO) AND REGIONAL BLOOD FLOWS (RBF) IN THE RAT : INFLUENCE OF DIETARY (n-3) AND (o-6) POLYUNSATURATED FATI’Y ACIDS (PUFA). A. Javouheyl>2, L. Rochette2, G. Rocquelinl. 1. INRA, Dijon, France. 2. Facult& de MCde&e et Pharmacie, Dijon, France. Dietary PUFA arc known to change membrane pbospholipid composition but the influence of these variations on peripheral circulation remained to bc determined. The aim of the study was to measure CO and RBF using the isotopclabeled microspheres technique in rats fed with equivalent intakes of 1813 n-3 or its two main metabolites (205 and 226 n-3). Three groups of 11 male Sprague Dawley rats were fed for 4 weeks one diet having 20% of the total FA as 18~2 n-6 (“24l%18:2”) and two diets (“10%18:3” and “IO%LCn-3”) with 10 % of total FA as l&2 n-6 and respectively 10% of total FA as 18~3 n-3 or Long Chain (n-3) PUFA (205 and 22~6 essentially). All diets contained 15% by weight of fats and had the same level of saturated FA (about 20% of total FA). At the end of the feeding period, rats weighing 340-390g were anesthetized with sodium pentobarbital (60 mg/kg). A catheter was placed in the right carotid artery and advanced to the left ventricle as assessed by the characteristic blood pressure changes. A suspension in 10% PVP of microspheres (diameter 15 2 Sp, labeled with 113 Tm) . was injected in the left ventricle. Measurement of arterial blood pressure (BP) and withdrawal of arterial blood sample during microsphere injection for CO determination were performed by femoral arteries cannulation. The animals were killed 5 minutes after the administration of microspheres. The activity of 113Trn in different tissues and organs was determined with a gamma spectrometer. No signScant differences in BP, heart rate and CO were observed (CO : 58.8 + 8.0, 50.9 f 7.7 and 59.0 + 8.0 ml/min with “20%18:2”, “10118~3” and “lO%LCn-3” diets respectively). Neither were differences between the 3 groups of animals for the distribution of CO (% of CO/organ or /gram of tissue) and for RBF (ml/min). The highest RBF recorded was for the kidneys (5 ml/min/g). To summarize, WC could not demonstrate any difference in cardiovascular parameters in our experimental conditions of diet. s.33
23 (Supplrmrnt
IV)
(1991)
VARIATIONS OF ENDOTHELIN BLOOD LEVELS DURING PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY (PTA ). C.Jacob ,B.Dousset,J.Fays, P.Bours, L.Hennequin, MDousset. Services de Biochimie,Radiologie et Chirurgie B 2, Centre Hospitalier ROgional Universitaire .NANCY .FRANCE.
et
Endothelin (ET) is the most potent vascular smooth muscle constrictor released by mammalian endothelium. The production of ET is regulated by various stimuli such as hypoxia and mechanical stretch. Identical phenomena occur in dinical use of PTA. ET arterial levels were evaluated by specific radioimmunoassay (AMERSHAM ) in 12 PTA : 2 iliac , 4 renal , 6 femoropopliieal . Except for iliac PTA where results were shown discordant for unknown reasons, ET levels were always increased after PTA ( from 2Oi3 pmol/ I to 31f 4 pmol/ I ).The highest values were associated with recanalization difficulties and repeated inflations. As a transient rise was observed immediatly after PTA decrease of corresponding values was shown 15 minutes after PTA. bur data suggest that increase of ETconcentrations correlates with spasms described post PTA as visualized by angiograms
98
EFFECT OF CLENTIAZEM ON THE SYRIAN HAMSTER HEREDITARY CARDIOMYOPATHY. 6. Jasmin, L. Proschek, C. Tautu. Departement de pathologie. Universite de Montreal. Canada. Clentiazem (G-Chlorodiltiazem) is a potent calcium channel antagonist which has a long lasting hypotensive effect in various animal models of experimental Beside its vasodilating activity on coronary arteries and a weak hypertension. negative inotropic effect, the question arise whether this calcium channel blocker is also efficient in preventing myocardial necrotic changes as we were able to demonstrate with verapamil several years ago. Clentiazem dissolved in water or in a 1% carboxymethylcellulose solution was administered by different routes in daily doses varying between 3 and 40 mg/kg. Optimal results were obtained by using 0.25 ml osmotic minipumps (Alzet) inserted subcutaneously once a week and delivering a daily dose of 5.6 mg/kg. After a 4-week treatment in 30-day-old cardiomyopathic hamsters, the incidence of cardiac necrotic changes was reduced by 50% with a mean severity of 0.5 (scale O-3). While the cardioprotection was similar to that obtained with verapamil, the squelettal muscle necrotic lesions however were unchanged by this calcium antagonist. (Supported by grants from Fondation Hacdonald Stewart and by Laboratoires Nordic.).
99
CARDIAC OUTPUT (CO) AND REGIONAL BLOOD FLOWS (RBF) IN THE RAT : INFLUENCE OF DIETARY (n-3) AND (o-6) POLYUNSATURATED FATI’Y ACIDS (PUFA). A. Javouheyl>2, L. Rochette2, G. Rocquelinl. 1. INRA, Dijon, France. 2. Facult& de MCde&e et Pharmacie, Dijon, France. Dietary PUFA arc known to change membrane pbospholipid composition but the influence of these variations on peripheral circulation remained to bc determined. The aim of the study was to measure CO and RBF using the isotopclabeled microspheres technique in rats fed with equivalent intakes of 1813 n-3 or its two main metabolites (205 and 226 n-3). Three groups of 11 male Sprague Dawley rats were fed for 4 weeks one diet having 20% of the total FA as 18~2 n-6 (“24l%18:2”) and two diets (“10%18:3” and “IO%LCn-3”) with 10 % of total FA as l&2 n-6 and respectively 10% of total FA as 18~3 n-3 or Long Chain (n-3) PUFA (205 and 22~6 essentially). All diets contained 15% by weight of fats and had the same level of saturated FA (about 20% of total FA). At the end of the feeding period, rats weighing 340-390g were anesthetized with sodium pentobarbital (60 mg/kg). A catheter was placed in the right carotid artery and advanced to the left ventricle as assessed by the characteristic blood pressure changes. A suspension in 10% PVP of microspheres (diameter 15 2 Sp, labeled with 113 Tm) . was injected in the left ventricle. Measurement of arterial blood pressure (BP) and withdrawal of arterial blood sample during microsphere injection for CO determination were performed by femoral arteries cannulation. The animals were killed 5 minutes after the administration of microspheres. The activity of 113Trn in different tissues and organs was determined with a gamma spectrometer. No signScant differences in BP, heart rate and CO were observed (CO : 58.8 + 8.0, 50.9 f 7.7 and 59.0 + 8.0 ml/min with “20%18:2”, “10118~3” and “lO%LCn-3” diets respectively). Neither were differences between the 3 groups of animals for the distribution of CO (% of CO/organ or /gram of tissue) and for RBF (ml/min). The highest RBF recorded was for the kidneys (5 ml/min/g). To summarize, WC could not demonstrate any difference in cardiovascular parameters in our experimental conditions of diet. s.33