Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog

1 The haemodynamic profile of elgodipine (1–30 μg kg−1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1–30 μg kg−1, i.v.) in chloralose‐anaesthetized dogs. 2 Nicardipine produced dose‐related systemic, pulmonary and coronary vasodilatation acco...

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Veröffentlicht in:British journal of pharmacology 1994-01, Vol.111 (1), p.49-56
Hauptverfasser: Rochelle, C. Drieu, Grosset, A., O'Connor, S.E.
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container_title British journal of pharmacology
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creator Rochelle, C. Drieu
Grosset, A.
O'Connor, S.E.
description 1 The haemodynamic profile of elgodipine (1–30 μg kg−1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1–30 μg kg−1, i.v.) in chloralose‐anaesthetized dogs. 2 Nicardipine produced dose‐related systemic, pulmonary and coronary vasodilatation accompanied by reflex tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2). Elgodipine had similar vasodilator and hypotensive properties to nicardipine but produced less reflex inotropy, little or no reflex tachycardia and did not increase MVO2. 3 Both calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with propranolol (1 mg kg−1, i.v.) and atropine (0.3 mg kg−1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both elgodipine and nicardipine decreased heart rate and cardiac contractility and slowed atrio‐ventricular conduction. Elgodipine was approximately ten times more potent than nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration. Elgodipine, unlike nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of elgodipine, which was present throughout the dose‐range, appears to be largely responsible for the suppression of reflex tachycardia observed when the baroreflex is functional. 4 Elgodipine is a potent systemic and coronary vasodilator with more marked direct cardiac effects than nicardipine, particularly with respect to slowing of heart rate. The ability of elgodipine to increase coronary blood flow without significant reflex tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial oxygen supply/demand balance than nicardipine. The haemodynamic profile of elgodipine may be suitable for the treatment of angina.
doi_str_mv 10.1111/j.1476-5381.1994.tb14022.x
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Drieu ; Grosset, A. ; O'Connor, S.E.</creator><creatorcontrib>Rochelle, C. Drieu ; Grosset, A. ; O'Connor, S.E.</creatorcontrib><description>1 The haemodynamic profile of elgodipine (1–30 μg kg−1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1–30 μg kg−1, i.v.) in chloralose‐anaesthetized dogs. 2 Nicardipine produced dose‐related systemic, pulmonary and coronary vasodilatation accompanied by reflex tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2). Elgodipine had similar vasodilator and hypotensive properties to nicardipine but produced less reflex inotropy, little or no reflex tachycardia and did not increase MVO2. 3 Both calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with propranolol (1 mg kg−1, i.v.) and atropine (0.3 mg kg−1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both elgodipine and nicardipine decreased heart rate and cardiac contractility and slowed atrio‐ventricular conduction. Elgodipine was approximately ten times more potent than nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration. Elgodipine, unlike nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of elgodipine, which was present throughout the dose‐range, appears to be largely responsible for the suppression of reflex tachycardia observed when the baroreflex is functional. 4 Elgodipine is a potent systemic and coronary vasodilator with more marked direct cardiac effects than nicardipine, particularly with respect to slowing of heart rate. The ability of elgodipine to increase coronary blood flow without significant reflex tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial oxygen supply/demand balance than nicardipine. The haemodynamic profile of elgodipine may be suitable for the treatment of angina.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/j.1476-5381.1994.tb14022.x</identifier><identifier>PMID: 8012724</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>anaesthetized dog ; Animals ; Atropine - pharmacology ; Biological and medical sciences ; Blood Pressure - drug effects ; Calcium Channel Blockers - pharmacology ; Cardiac Output - drug effects ; Cardiovascular system ; dihydropyridine calcium antagonists ; Dihydropyridines - pharmacology ; Dogs ; Electrocardiography - drug effects ; Elgodipine ; Female ; Heart Conduction System - drug effects ; Heart Rate - drug effects ; Hemodynamics - drug effects ; Male ; Medical sciences ; Miscellaneous ; Myocardial Contraction - drug effects ; nicardipine ; Nicardipine - pharmacology ; Oxygen Consumption - drug effects ; Pharmacology. 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Drieu</creatorcontrib><creatorcontrib>Grosset, A.</creatorcontrib><creatorcontrib>O'Connor, S.E.</creatorcontrib><title>Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>1 The haemodynamic profile of elgodipine (1–30 μg kg−1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1–30 μg kg−1, i.v.) in chloralose‐anaesthetized dogs. 2 Nicardipine produced dose‐related systemic, pulmonary and coronary vasodilatation accompanied by reflex tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2). Elgodipine had similar vasodilator and hypotensive properties to nicardipine but produced less reflex inotropy, little or no reflex tachycardia and did not increase MVO2. 3 Both calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with propranolol (1 mg kg−1, i.v.) and atropine (0.3 mg kg−1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both elgodipine and nicardipine decreased heart rate and cardiac contractility and slowed atrio‐ventricular conduction. Elgodipine was approximately ten times more potent than nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration. Elgodipine, unlike nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of elgodipine, which was present throughout the dose‐range, appears to be largely responsible for the suppression of reflex tachycardia observed when the baroreflex is functional. 4 Elgodipine is a potent systemic and coronary vasodilator with more marked direct cardiac effects than nicardipine, particularly with respect to slowing of heart rate. The ability of elgodipine to increase coronary blood flow without significant reflex tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial oxygen supply/demand balance than nicardipine. The haemodynamic profile of elgodipine may be suitable for the treatment of angina.</description><subject>anaesthetized dog</subject><subject>Animals</subject><subject>Atropine - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cardiac Output - drug effects</subject><subject>Cardiovascular system</subject><subject>dihydropyridine calcium antagonists</subject><subject>Dihydropyridines - pharmacology</subject><subject>Dogs</subject><subject>Electrocardiography - drug effects</subject><subject>Elgodipine</subject><subject>Female</subject><subject>Heart Conduction System - drug effects</subject><subject>Heart Rate - drug effects</subject><subject>Hemodynamics - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Myocardial Contraction - drug effects</subject><subject>nicardipine</subject><subject>Nicardipine - pharmacology</subject><subject>Oxygen Consumption - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Propranolol - pharmacology</subject><subject>reflex tachycardia</subject><subject>Vascular Resistance - drug effects</subject><subject>vascular/cardiac selectivity</subject><subject>Vasodilation - drug effects</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkV-P1CAUxYnRrLOrH8GkMca3Vi6lpfhg1MnqmmyiD_oqofyZYdJChRnd8dNLd5qJPsoLl5xzDxd-CD0HXEFer3YVUNaWTd1BBZzTat8DxYRUdw_Q6iw9RCuMMSsBuu4xukxph3EWWXOBLjoMhBG6Qt_XYZxkdCn4IthivzXFVpox6KOXo1PFFIN1g0mzaIZN0G5y3hTS68I7JeNydv6-VXppUi727rfRhQ6bJ-iRlUMyT5f9Cn37cP11fVPefv74af3utlSUEFIa3ijeAq07TXqjcKPAKk4M71VjJfBOW8wotL0Bag1rGCbMNoxSom2bXfUVenPKnQ79aLQyfh_lIKboRhmPIkgn_lW824pN-CmAQ_4VyAEvl4AYfhzyI8TokjLDIL0JhyRY27SMkzobX5-MKoaUorHnSwCLmY7YiRmBmBGImY5Y6Ii73Pzs7zHPrQuOrL9YdJmUHGyUXrl0ttUcd10zD_v2ZPuV0Rz_YwDx_svNfVn_AdY4ryI</recordid><startdate>199401</startdate><enddate>199401</enddate><creator>Rochelle, C. Drieu</creator><creator>Grosset, A.</creator><creator>O'Connor, S.E.</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>199401</creationdate><title>Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog</title><author>Rochelle, C. Drieu ; Grosset, A. ; O'Connor, S.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4222-e95c961438d2bec05c1fc92e9bc5fa198df07416be14fe757027f57442df6e9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>anaesthetized dog</topic><topic>Animals</topic><topic>Atropine - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cardiac Output - drug effects</topic><topic>Cardiovascular system</topic><topic>dihydropyridine calcium antagonists</topic><topic>Dihydropyridines - pharmacology</topic><topic>Dogs</topic><topic>Electrocardiography - drug effects</topic><topic>Elgodipine</topic><topic>Female</topic><topic>Heart Conduction System - drug effects</topic><topic>Heart Rate - drug effects</topic><topic>Hemodynamics - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Myocardial Contraction - drug effects</topic><topic>nicardipine</topic><topic>Nicardipine - pharmacology</topic><topic>Oxygen Consumption - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Propranolol - pharmacology</topic><topic>reflex tachycardia</topic><topic>Vascular Resistance - drug effects</topic><topic>vascular/cardiac selectivity</topic><topic>Vasodilation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rochelle, C. Drieu</creatorcontrib><creatorcontrib>Grosset, A.</creatorcontrib><creatorcontrib>O'Connor, S.E.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rochelle, C. Drieu</au><au>Grosset, A.</au><au>O'Connor, S.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1994-01</date><risdate>1994</risdate><volume>111</volume><issue>1</issue><spage>49</spage><epage>56</epage><pages>49-56</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>1 The haemodynamic profile of elgodipine (1–30 μg kg−1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1–30 μg kg−1, i.v.) in chloralose‐anaesthetized dogs. 2 Nicardipine produced dose‐related systemic, pulmonary and coronary vasodilatation accompanied by reflex tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2). Elgodipine had similar vasodilator and hypotensive properties to nicardipine but produced less reflex inotropy, little or no reflex tachycardia and did not increase MVO2. 3 Both calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with propranolol (1 mg kg−1, i.v.) and atropine (0.3 mg kg−1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both elgodipine and nicardipine decreased heart rate and cardiac contractility and slowed atrio‐ventricular conduction. Elgodipine was approximately ten times more potent than nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration. Elgodipine, unlike nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of elgodipine, which was present throughout the dose‐range, appears to be largely responsible for the suppression of reflex tachycardia observed when the baroreflex is functional. 4 Elgodipine is a potent systemic and coronary vasodilator with more marked direct cardiac effects than nicardipine, particularly with respect to slowing of heart rate. The ability of elgodipine to increase coronary blood flow without significant reflex tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial oxygen supply/demand balance than nicardipine. The haemodynamic profile of elgodipine may be suitable for the treatment of angina.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>8012724</pmid><doi>10.1111/j.1476-5381.1994.tb14022.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects anaesthetized dog
Animals
Atropine - pharmacology
Biological and medical sciences
Blood Pressure - drug effects
Calcium Channel Blockers - pharmacology
Cardiac Output - drug effects
Cardiovascular system
dihydropyridine calcium antagonists
Dihydropyridines - pharmacology
Dogs
Electrocardiography - drug effects
Elgodipine
Female
Heart Conduction System - drug effects
Heart Rate - drug effects
Hemodynamics - drug effects
Male
Medical sciences
Miscellaneous
Myocardial Contraction - drug effects
nicardipine
Nicardipine - pharmacology
Oxygen Consumption - drug effects
Pharmacology. Drug treatments
Propranolol - pharmacology
reflex tachycardia
Vascular Resistance - drug effects
vascular/cardiac selectivity
Vasodilation - drug effects
title Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog
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