Recommended
More Related Content
Similar to Cardiac sensitization- A fatal Phenomenon
Similar to Cardiac sensitization- A fatal Phenomenon (20)
Recently uploaded
Recently uploaded (20)
Cardiac sensitization- A fatal Phenomenon
- 1. Cardiac Sensitization: A Fatal Phenomenon - Alex Thomas September 09, 2017
- 2. Background Information • Levy and Lewis (1911-1912) and Levy (1913) • 1960s and early 1970s • Bass (1970) reported 110 cases of sudden death (Toluene, benzene, gasoline, 1,1,1-trichloroethane, chlorofluo rocarbon aerosol propellants such as CFC-12 and CFC-11) • NIOSH, 1989 and Kaufman et al, 1994 (CFC-113) 2
- 3. 3 Fight-or-Flight Response • Hyperarousal, or the acute stress response • Walter Bradford Cannon (1871-1945) • The adrenal medulla produces a hormonal cascade that results in the secretion of catecholamines, especially nor epinepehrine and epinephrine.
- 4. 4 Director: Anand Shankar Release date: 8 September, 2016
- 5. Epinephrine (Greek) ; Adrenaline (Latin) 5 1857-1938 1854-1922 John Jacob Abel Jokichi Takamine Parke, Davis & Co
- 6. Effects of adrenaline in the body Organ Effects Heart Increases heart rate; contractility; conduction across AV node Lungs Increases respiratory rate; bronchodilation Systemic Vasoconstriction (?)and vasodilation (?) Liver Stimulates glycogenolysis Systemic Triggers lipolysis Systemic Muscle contraction 6
- 7. In resting adults : less than 10 ng/L Exercise : Increase by 10-fold Stress : Increase by 50-fold or more Endogenous plasma epinephrine concentrations 7
- 10. Sensitization often is characterized by an enhancement of response to a whole class of stimuli in addition to the one that is repeated. Sensitization Day 1 Day 365 10
- 11. Cardiac Sensization An increased sensitivity of the heart to catecholamines. Cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. 11
- 14. Cardiac Sensitization studies 14 Ionic mechanism of repolarisation differs Reproducible results
- 15. Standard Test Method for Cardiac Sensitization Study on Dogs: Summary Number of Dogs: 6 Step 1 Each dog is evaluated to select an appropriate dose of Adrenaline required for a cardiac response 15
- 16. 16 Step 2- Testing protocol 0 min-Start of ECG recording 2 min-Administration of adrenaline (cephalic vein) 7 min-Start of inhalation of vapor (test item) 12 min- administration of a challenge injection of adrenaline. 17 min- stop the vapor inhalation and the ECG recording.
- 17. Step 3 2.5 % concentration of the test iteml the first day 5 % on the next test day. If necessary, the dogs are exposed successively to 10 %, 15 %, and 20 % as needed. As soon as ventricular tachycardia is evidenced, the testing is stopped. No appearance of ventricular arrhythmia at the highest concentration! No other deleterious events! No cardiac sensitization. 17
- 18. Summary 18 Fight or Flight Response Adrenaline Cardiac Sensitization Walter Bradford Cannon John Jacob Abel Jokichi Takamine Parke, Davis & Co.
- 19. References • Reinhardt, C. F., Azar, A., Maxfield, M. E., Smith, P. E. Jr., and Mullin, L. S. 1971. Cardiac Arrhythmias and Aerosol Sniffing, Archives of Environmental Health. 22:265–279. • Meek, W. J., Hathaway, H. R., and Orth, O. S. 1937. The Effects of Ether, Chloroform and Cyclopropane on Cardiac Automaticity, Journal of Pharmacology and Experimental Therapy. 61:240–252. • Reinhardt, C.F., L.S. Mullin, and M.E. Maxfield. 1973. Epinephrine-induced cardiac arrhythmia potential of some common industrial solvents. Journal of Occupational Medicine. 15:953-955. 19
- 20. Leo Tolstoy (1828-1910) Russian writer Born: 9 September, 1828 We lost because we told ourselves we lost. -Leo Tolstoy
Editor's Notes
- The phenomenon now referred to as cardiac sensitisation was first described by Levy and Lewis (1911-1912) and Levy (1913) when they demonstrated in cats that adrenaline and chloroform (≈ 0.5 - 1.0% [5,000 - 10,000 ppm; 24,400 - 48,800 mg/m3] a), when administered separately, did not produce serious heart arrhythmias but, when administered together, could produce fatal ventricular fibrillation. They found that the arrhythmias sometimes advanced to ventricular fibrillation when a dose of 65 μg of adrenaline was given intravenously during the administration of chloroform. Based on these studies, Levy and Lewis were of the opinion that many of the sudden deaths that occurred during chloroform anaesthesia were caused by chloroform increasing the irritability of the heart muscle, making it more sensitive to adrenaline, thus resulting in the development of fatal arrhythmias, especially during light anaesthesia In the late 1960s and early 1970s, numerous sudden deaths were reported in teenagers who inhaled (“sniffed”) various products to achieve a chemically induced euphoria. Bass (1970) reported 110 cases of sudden death, mostly in teenagers. The chemicals involved included toluene, benzene, gasoline, 1,1,1-trichloroethane and chlorofluorocarbon aerosol propellants such as dichlorodifluoromethane (CFC-12) and trichlorofluoromethane (CFC-11) a. The solvent trichlorotrifluoroethane (CFC-113) was also reported to cause sudden deaths in situations whereworkers were accidentally exposed to very high concentrations (NIOSH, 1989; Kaufman et al, 1994). Ventricular fibrillation (v-fib for short) is the most serious cardiac rhythm disturbance. The lower chambers quiver and the heart can't pump any blood, causing cardiac arrest.
- A catecholamine (/kætəˈkoʊləmi/) (CA) is a monoamine, an organic compound that has a catechol (benzene with two hydroxylside groups at carbons 1 and 2) and a side-chaina free molecule or a substituent of a larger molecule, where it represents a 1,2-dihydroxybenzene group.Catecholamines are derived from the amino acid tyrosine, which is derived from dietary sources as well as synthesis from phenylalanine. Catecholamines are water-soluble and are 50%-bound to plasma proteins in circulation.Included among catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. Release of the hormones epinephrine and norepinephrine from the adrenal medulla of the adrenal glands is part of the fight-or-flight response. Walter Bradford Cannon was an American physiologist, professor and chairman of the Department of Physiology at Harvard Medical School. He coined the term fight or flight response, and he expanded on Claude Bernard's concept of homeostasis.
- One example of this overlap is norepinephrine which can be released into the bloodstream by the adrenal glands as a hormone or can be released by sympathetic nerve endings as a neurotransmitter. Neurotransmitters belong to the nervous system, whereas hormones belong to the endocrine system
- The term epinephrine was coined by the pharmacologist John Abel (from the Greek for "on top of the kidneys"), who used the name to describe the extracts he prepared from the adrenal glands as early as 1897. In 1901, Jokichi Takamine patented a purified adrenal extract, and called it "adrenalin" (from the Latin for "on top of the kidneys"), which was trademarked by Parke, Davis & Co in the U.S.[57] In the belief that Abel's extract was the same as Takamine's, a belief since disputed, epinephrine became the generic name in the U.S.[57] The British Approved Name and European Pharmacopoeia term for this drug is adrenaline and is indeed now one of the few differences between the INN and BAN systems of names. Among American health professionals and scientists, the term epinephrine is used over adrenaline. However, pharmaceuticals that mimic the effects of epinephrine are often called adrenergics, and receptors for epinephrine are called adrenergic receptors or adrenoceptors. John Jacob Abel (19 May 1857 – 26 May 1938) was an American biochemist and pharmacologist. He established the pharmacology department at Johns Hopkins University School of Medicine in 1893, and then became America's first full-time professor of pharmacology.[2] During his time at Hopkins, he made several important medical advancements, especially in the field of hormone extraction. In addition to his laboratory work, he founded several significant scientific journals such as the Journal of Biological Chemistry and the Journal of Pharmacology and Experimental Therapeutics.[3] Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once America's oldest and largest drug maker,[1] and played an important role in medical history. Parke-Davis was acquired by Warner–Lambert in 1970, which in turn was bought by Pfizer in 2000. Takamine was born in Takaoka, Toyama Prefecture, in November 1854.[2] His father was a doctor; his mother a member of a family of sake brewers. He spent his childhood in Kanazawa, capital of present-day Ishikawa Prefecture in central Honshū, and was educated in Osaka, Kyoto, and Tokyo, graduating from the Tokyo Imperial University in 1879. He did postgraduate work at University of Glasgowand Anderson College in Scotland. He returned to Japan in 1883 and joined the division of chemistry at the newly established Department of Agriculture and Commerce. He learned English as a child from a Dutch family in Nagasaki and so always spoke English with a Dutch accent.[3]
- "Epinephrine acts on alpha receptors causing vasoconstriction and on beta receptors causing vasodilation. The affinity of epinephrine for beta receptors is somewhat greater than its affinity for alpha receptors. When given in low doses, or by slow IV infusion in humans, the beta effects of epinephrine may predominate. When given in a large IV bolus dose, as here, the alpha effects (vasoconstriction) predominate when the concentration of epinephrine is high, and the beta effects (vasodilation) may sometimes be seen as the concentration is falling. From these facts you may be able to infer the relative affinity of epinephrine for alpha receptors on the one hand, and beta receptors on the other hand.The fact that vasoconstriction predominates when both alpha and beta receptors are activated shows that the capacity for vasoconstriction mediated by alpha receptors is very great, whereas the capacity for vasodilation mediated by beta receptors is somewhat limited."
- the state or quality of being sensitive; often used to denote a state of abnormal responsiveness to stimulation, or of responding quickly and acutely.
- Arrhythmias, tagged atrial fibrillation, ECG, junctional fibrillation, mechanim of irregularity in af, rr interval irregular RR interval in Atrial fibrillation is irregular cause . . .The Atria fires irregularlyAV node conducts irregularly Atria confuses the AV node with its random firing and varying penetration * The ventricle just reflects irregular response of atria .
- .
- The ionic mechanisms of repolarisation in rats and mice differ significantly from larger species, including humans. The primary ionic current controlling repolarisation in the rat and mouse is the transient outward current Ito, whereas the rapid and/or slow delayed rectifier, IKr and IKs, dominates repolarisation in the larger species. Therefore, as is noted in the ICH guidelines, the use of rodents to study cardiotoxic effects is not considered appropriate.
- Ventricular tachycardia (V-tach or VT) is a type of regular and fast heart rate that arises from improper electrical activity in the ventricles of the heart. Ventricular arrhythmias are abnormal heart rhythms that originate in the bottom chambers of the heart called the ventricles. These rhythms can occur as a result of damage to the heart muscle from a heart attack or cardiomyopathy – or can occur in patients with hearts that seem structurally normal.