Direct and indirect effects of calcium entry blocking agents on isovolumic left ventricular relaxation in conscious dogs. 1985

R A Walsh, and R A O'Rourke

To assess the direct and indirect effects of the commonly used calcium entry blockers (CEB) upon the major determinants of isovolumic left ventricular relaxation, we administered equidepressant intracoronary (IC, n = 7) and equihypotensive intravenous (n = 12) dosages of diltiazem (16 +/- 3 SE micrograms/kg IC and 63 +/- 9 micrograms/kg i.v.), verapamil (10 +/- 2 and 57 +/- 5 micrograms/kg), and nifedipine (1 +/- 0.1 and 8 +/- 0.3 micrograms/kg) to preinstrumented awake dogs with normal ventricular function. The time constant of left ventricle (LV) relaxation, analyzed by two methods (T1, from the linear relation of the natural logarithm of LV pressure and time; T2, from the linear relation of LV pressure and negative high fidelity LV pressure), was significantly and equivalently prolonged by IC diltiazem (T1 + 48%, P less than 0.02), verapamil (T1 + 43%, P less than 0.001), and nifedipine (T1 + 30%, P less than 0.03). Lesser amounts of each CEB that did not affect rate of LV pressure development or extent of shortening produced no change in T1 or T2. By contrast, intravenous calcium entry blockade either produced no significant change (diltiazem and verapamil) or shortened (nifedipine T1 - 18%, P less than 0.01) LV isovolumic relaxation. However, after beta adrenergic blockade with propranolol (2 mg/kg i.v., n = 6) no change in ventricular relaxation was observed during nifedipine and the time constant was significantly prolonged by verapamil (T1 + 15%, P less than 0.05). We conclude that calcium entry blockade directly impairs normal left ventricular relaxation: This effect is closely linked to the negative inotropic properties of these drugs. The prolongation of isovolumic relaxation produced by calcium blockade is attenuated or even reversed by reflex sympathetic stimulation and favorably altered loading conditions during systemic administration.

UI MeSH Term Description Entries
D007022 Hypotension Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients. Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D007263 Infusions, Parenteral The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping. Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D007269 Injections, Intra-Arterial Delivery of drugs into an artery. Injections, Intraarterial,Intra-Arterial Injections,Intraarterial Injections,Injection, Intra-Arterial,Injection, Intraarterial,Injections, Intra Arterial,Intra Arterial Injections,Intra-Arterial Injection,Intraarterial Injection
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D002306 Cardiac Volume The volume of the HEART, usually relating to the volume of BLOOD contained within it at various periods of the cardiac cycle. The amount of blood ejected from a ventricle at each beat is STROKE VOLUME. Heart Volume,Cardiac Volumes,Heart Volumes,Volume, Cardiac,Volume, Heart,Volumes, Cardiac,Volumes, Heart
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000319 Adrenergic beta-Antagonists Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Adrenergic beta-Antagonist,Adrenergic beta-Receptor Blockader,Adrenergic beta-Receptor Blockaders,beta-Adrenergic Antagonist,beta-Adrenergic Blocker,beta-Adrenergic Blocking Agent,beta-Adrenergic Blocking Agents,beta-Adrenergic Receptor Blockader,beta-Adrenergic Receptor Blockaders,beta-Adrenoceptor Antagonist,beta-Blockers, Adrenergic,beta-Adrenergic Antagonists,beta-Adrenergic Blockers,beta-Adrenoceptor Antagonists,Adrenergic beta Antagonist,Adrenergic beta Antagonists,Adrenergic beta Receptor Blockader,Adrenergic beta Receptor Blockaders,Adrenergic beta-Blockers,Agent, beta-Adrenergic Blocking,Agents, beta-Adrenergic Blocking,Antagonist, beta-Adrenergic,Antagonist, beta-Adrenoceptor,Antagonists, beta-Adrenergic,Antagonists, beta-Adrenoceptor,Blockader, Adrenergic beta-Receptor,Blockader, beta-Adrenergic Receptor,Blockaders, Adrenergic beta-Receptor,Blockaders, beta-Adrenergic Receptor,Blocker, beta-Adrenergic,Blockers, beta-Adrenergic,Blocking Agent, beta-Adrenergic,Blocking Agents, beta-Adrenergic,Receptor Blockader, beta-Adrenergic,Receptor Blockaders, beta-Adrenergic,beta Adrenergic Antagonist,beta Adrenergic Antagonists,beta Adrenergic Blocker,beta Adrenergic Blockers,beta Adrenergic Blocking Agent,beta Adrenergic Blocking Agents,beta Adrenergic Receptor Blockader,beta Adrenergic Receptor Blockaders,beta Adrenoceptor Antagonist,beta Adrenoceptor Antagonists,beta Blockers, Adrenergic,beta-Antagonist, Adrenergic,beta-Antagonists, Adrenergic,beta-Receptor Blockader, Adrenergic,beta-Receptor Blockaders, Adrenergic

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