Cardiac Tropism

Cardiac Tropism describes the effects of cardiac drugs on various heart muscle properties with a brief focus on anesthetics

1. CARDIAC TROPISM By Mehdi hadavi Anesthesiologist

2. Properties of the Cardiac cells=> Automaticity: capability of contract even in the absence of neural control Rhythmicity: heart beats are extremely regular Contractibility: cardiac muscle contracts in response to a stimulus Excitability: ability of the cardiac muscle to respond to different stimuli Conductivity: impulses produced in the SA node is conducted by the specialized conducting pathway Distensibility : occurs due to compliance of the cardiac muscle Functional syncytium: due to the presence of numerous gap junctions

3. CardioTropy based on cardiac muscle properties Chronotropic (Heart rate) Inotropic (Contractility) Dromotropic (Conduction velocity) Bathmotropic (Excitability) Lusitropic (Relaxation)

4. Chronotropy From chrono -, meaning time . Chronotrope Affects heart rate.

5. Chronotropy Negative Chronotropes : -Beta-blockers such as Metoprolol -Acetylcholine -Digoxin -The non- dihydropyridine calcium channel blockers diltiazem and verapamil   Positive Chronotropes : -Atropine -Dopamine - Dobutamine -Epinephrine -Isoproterenol

6. Inotropy From Greek in-, meaning fibre or sinew. An inotrope is an agent that alters the force or energy of muscular contractions positive inotropy : increase contractile force of heart --> ventricles empty more completely --> cardiac output improved negative inotropy : weaken/decrease the force of myocardial contraction

7. Inotropy Positive Inotropes: - Dgoxine - Bipyridine derivatives -Calcium and Ca sensitizing agents - Cathecolamines -Eicosanoids - Phosphodiesterase inhibitors -Glucagon Negative Inotropes: -Beta blockers -Calcium channel blockers -Class 1A antiarrhythmic drugs -Class 1C antiarrhythmic drugs

8. Inotropy

9. Dromotropy from the Greek word " Dromos ", meaning running, a course, a race Dromotrope Affects Atrioventricular node (AV node) conduction Agents that are dromotropic are often (but not always) inotropic and chronotropic

10. Positive dromotropic : -Isoproterenol -Phenytoin Negative dromotropic : -Verapamil -Adenosine Dromotropy

11. Bathmotropy From the Greek word " Bathmos ," meaning step or threshold Bathmotrope Refers to modification of the degree of excitability, (threshold of excitation), of musculature in general, and of heart musculature specifically Positive Bathmotropic effects increase the response of muscle to stimulation N egative Bathmotropic effects decrease the response of muscle to stimulation

12. Bathmotropy Positive Bathmotropes : -Norepinephrine and sympathetic stimulation in general -Digitalis - Converts the normal Purkinje action potential of heart muscle to the automaticity type, which increases myocardial irritability. -Adrenaline - Hypocalcemia -Mild to Moderate Hyperkalemia -Mild hypoxia - Ischaemia Negative Bathmotropes : - Propanolol -Quinidine and other Class A Antiarrhythmic Agents -Calcium Channel Blockers -Parasympathetic stimulation (only of atrial muscle cells) - Hyponatremia - decreases external sodium concentration -Marked Hyperkalemia -Hypokalemia - Hypercalcemia - Hyponatremia -Acetylcholine -Marked Hypoxia

13. Lusitropy from Gr .  lusis , variant of  lysis Lusiotrope Describes myocardial relaxation . The increase in calcium uptake by cardiomyocytes leads to increased myocardial contractility (positive inotropic effect), but the myocardial relaxation, or lusitropy , decreases Increased catecholamine levels promote positive lusitropy , enabling the heart to relax more rapidly

14. Lusitropy Positive L usitropy : -Beta adrenergic agonists phosphorylate phospholamban via cAMP , reducing calcium available for binding with troponin. Phospholamban is antagonist of SERCA in the non phosphorylated state Negative Lusitropy : -High calcium - Reduced rate of calcium removal from myocyte through pumps -Impaired sarcoplasmic reticulum calcium ATPase ( SERCA) -Increase affinity of troponin C -Alkalosis that increases calcium sensitivity

15. Vascular effects of some Inotrope drug

16. Inotrope effects on bp and co

17. Hemodynamic effects of inotropes

18. Inotrope effects, mechanisms and dosage in sock situations

19. DOSE-DEPENDENT ACTIONS OF INOTROPES AND CHRONOTROPES Miller:

20. Cardiotrpic effect of volatile Volatile anesthetics exert profound effects on the cardiovascular system by altering the inotropic, chronotropic , dromotropic , and lusitropic state of the heart Volatile anesthetics produce dose-related prolongation of LV isovolumic relaxation in vivo. This delay of isovolumic relaxation is associated with declines in early LV filling but is not of sufficient magnitude to affect LV chamber stiffness. Coronary blood flow is elevated during isovolumic relaxation, and delays in relaxation produced by volatile anesthetics contribute to impairment of coronary flow during early diastole. Prolongation of LV relaxation probably occurs as a result of simultaneous depression of myocardial contractility and not because of a direct negative lusitropic effect. In fact, volatile anesthetics modestly enhanced the rate of relaxation of isolated myocardium in vitro. Volatile anesthetics also cause concentration-related decreases in the rate and extent of early LV filling concomitant with negative inotropic effects . Further , volatile anesthetics reduced LV filling during atrial systole .

21. Cardiotrpic effect of volatile  inhalation anesthetics have direct inhibitory effects on sinoatrial node activity, which would decrease heart rate in the absence of other compensatory mechanisms Rapid increases in the inhaled concentrations of desflurane , and to a lesser extent those of isoflurane , may cause marked increases in heart rate due to sympathetic nervous system activation. Sevoflurane , in contrast, has minimal effects on heart rate Isoflurane , desflurane , and sevoflurane did not alter invasively derived indices of regional myocardial or chamber stiffness, indicating that LV distensibility was unaffected by these volatile anesthetics. favorable reduction in myocardial O2 demand (reductions in ischemic burden) concomitant with preservation of energy-dependent vital cellular processes because volatile anesthetics cause direct negative inotropic, lusitropic , and chronotropic effects and are vasodilators . N 2 O has been demonstrated to depress various measures of LV contractile function, although to a lesser extent than potent inhaled agents do N 2 O increases heart rate through stimulation of the sympathetic nervous system

22. Cardiotropic effect of hypnotics, sedative and opioids High concentrations of propofol abolish the inotropic effect of α- but not β- adrenoreceptor stimulation, and enhance the lusitropic (relaxation) effect of β- adrenoreceptor stimulation Systolic shortening can be impaired by propofol , especially at high doses but sedative concentrations of propofol (0.65 to 2.6 g/mL) produce significant vasodilation and hemodynamic disturbances but not direct negative inotropic effects. Increases in plasma histamine after morphine administration cause dilatation of terminal arterioles and direct positive cardiac chronotropic and inotropic actions Combinations of vecuronium and high doses of opioids may produce negative chronotropic and inotropic effects

23. Cardiotropic effect of hypnotics, sedative and opioids Diazepam and midazolam exert a direct myocardial depressant effect . Negative inotropic effects of benzodiazepines have also been reported in isolated organ preparations, although debate exists . In vivo  human studies of benzodiazepine effects, which also reflect central and local reflex compensatory changes after drug administration, do not indicate that these negative inotropic actions are problematic or very significant.  The dose-dependent negative inotropic actions of barbiturates are greater than those produced by benzodiazepines, etomidate , or ketamine but probably not as great as the depression that can be produced by potent inhaled anesthetics . The inotropic effects of etomidate are slight; the drug itself has mild positive inotropic actions  in vitro , but propylene glycol, the solvent that is used for the preparation of etomidate , may produce a slight negative inotropic effect

24. Cardiotropic effect of hypnotics, sedative and opioids Ketamine c ardiovascular stimulation probably results from central nervous system-mediated effects and sympathoneural and systemic release of norepinephrine. Ketamine also produces direct positive inotropic actions secondary to increased myocardial calcium influx

25. Cardiotropic effect of Neuromuscular Blocking Drugs Important cardiovascular effects mediated by muscarinic stimulation are primarily related to parasympathetic cardiac actions Succinylcholine:low doses=>negative inotropic and chronotropic Large doses=> effects may become positive Pancuronium ,  d - tubocurarine , and, to a lesser extent, rapacuronium , rocuronium , and metocurine produce increases in heart rate due to muscarinic blockade  a positive chronotropic effect that places emphasis on the vagolytic mechanism of pancuronium has not been found in humans tachycardia seen with benzylisoquinolinium compounds is the result of histamine release

26. Chronotropic /inotropic ACTIONS OF HORMONES Miller: