Cardiac responses

Avakian, E.V., and Manneh, V.A. Cardiac responsivity to epinephrine following chronic cocaine administration. Proc West Pharmacol Soc 30 281-284, 1987. 

Although it is an optimized model, the end point of cardiac sensitization is relevant as humans exposed at high concentrations of some halocarbons may develop cardiac arrhythmias. The concentration of 80,000 ppm along with intravenous epinephrine, which induced a marked cardiac response in the dog, was used as the basis for the AEGL-3 values. Because the dog heart is considered an appropriate model for the human heart, an interspecies UF of 1 was applied. Because the cardiac sensitization test is a conservative test, the 80,000 ppm concentration was adjusted by an intraspecies UF of 3 to protect potentially susceptible individuals. Blood concentrations were close to equi... 

The AEGL-3 value was based on a concentration of 9,000 ppm, the highest value that resulted in mild to marked cardiac responses but did not cause death in a cardiac-sensitization study with the dog (Hardy et al. 1989a). Because the dog heart is a reliable model for that of the human, an interspecies UF of 1 was applied. The cardiac sensitization test is highly sensitive as the response to exogenous epinephrine is optimized, so a single intraspecies UF of 3 was applied. Cardiac sensitization is concentration dependent duration... 

Testing for cardiac sensitization consists of establishing a background (control) response to an injection of epinephrine followed by a second injection during exposure to the chemical of concern (Reinhardt et al. 1971). The dose of epinephrine chosen is the maximum dose that does not cause a serious arrhythmia (NRC 1996). Because a second injection of epinephrine during air exposure often induces a mild cardiac response, Reinhardt et al. (1971) con... 

Time scaling may not be applicable to halogenated hydrocarbons as blood concentrations of these chemicals do not increase as exposure time is increased beyond 5-10 min (Bakshi et al. 1998). In the Utell et al. (1997) study with human volunteers exposed to HCFC-141b, the relationship between exposure concentration and blood level was linear and reached equilibrium at 250 ppm within 145 min. Graphical representation of the exposure time-blood concentration indicated that at the higher concentrations, equilibrium was approached at 225 min, and at 55 min concentrations were within 80% of the 225 min concentration. Furthermore, the circulating HCFC-141b concentration, rather than duration of exposure, defines whether or not a cardiac response will occur. 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

Respiratory and cardiovascular effects of maitotoxin have been studied in pentobarbital anaesthetized cats (21). Sublethal doses of maitotoxin induced an important hyperventilation phase, hypertension and a transitory tachycardia followed by slight bradycardia. Higher dosage caused respiratory depression, cardiac arrhythmias and tachycardia leading to cardiac failure. Artificial respiration did not modify the cardiac responses. 

Shapiro, W., Narahara, K., and Taubert, K., Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man. Circulation 42, 1065-1072 (1970). 

A. Both sets of responses to isoproterenol are mediated by p-adrenoceptors, and all the choices are p-antagonists. However, drug X is more effective in antagonizing cardiac responses to isoproterenol than it is the bronchiolar responses. Drug X is therefore a cardioselective p-blocker, that is, selective for Pi over P2 receptors. Metoprolol is the only pi-selective antagonist among the choices. 

Since propranolol crosses the placenta and enters the fetal circulation, fetal cardiac responses to the stresses of labor and delivery will be blocked. Additionally, propranolol crosses the blood-brain barrier and is associated with mood changes and depression. School difficulties are commonly associated with its use in children. Propranolol may also cause hypoglycemia in infants. 

By attenuating the cardiac response to exercise, propranolol and other (3-blockers increase the amount of exercise that can be performed before angina develops. Although propranolol does not change the point of imbalance between oxygen supply and demand at which angina occurs, it does slow the rate at which the imbalance point is reached. 

Doses of 2-PAM larger than 40 mg/kg, as well as TMB-4 and toxogonin, produced a temporary block of the cardiac response to vagal stimulation and of the nictitating membrane response to preganglionic, but not postganglionic, stimulation. There was transient hypotension due to block of ganglionic transmission.9,63,71... 

In cats anesthetized with sodium pentobarbital, an intravenous dose of III at 25 mg/kg was found to be able to block almost comletely the cardiac response to stimulation of the peripheral right vagus nerve.121 Small doses (2-8 mg/kg) did not inhibit peristaltic activity in... 

Etomidate is a carboxylated imidazole that can be used for induction of anesthesia in patients with limited cardiovascular reserve. Its major advantage over other intravenous anesthetics is that it causes minimal cardiovascular and respiratory depression. Etomidate produces a rapid loss of consciousness, with minimal hypotension even in elderly patients with poor cardiovascular reserve. The heart rate is usually unchanged, and the incidence of apnea is low. The drug has no analgesic effects, and coadministration of opioid analgesics is required to decrease cardiac responses during tracheal intubation and to lessen spontaneous muscle movements. Following an induction dose, initial recovery from etomidate is less rapid (< 10 minutes) compared with recovery from propofol. 

Problem/lnfluence of Medication. Propranolol and the other beta blockers are successful in reducing various supraventricular arrhythmias. These drugs, however, also attenuate the cardiac response to exercise. Heart rate and cardiac output are lower at any absolute workload, and maximal heart rate and cardiac output are attenuated by beta blockade. Consequently, the exercise response of a patient taking a beta blocker will be less than if the patient is not tak-... 

Another cardiac response to catecholamine release is Increased vulnerability to ventricular fibrillation. Recent studies (13) have shown that bromocriptine produced an increase of 50% in the ventricular fibrillation threshold In anesthetized dogs, and that pretreatment with the peripheral D-2 dopamine antagonist domperidone abolished this effect. This suggests that adrenergic induced cardiac arrhythmia may be inhibited by peripheral presynaptic dopamine agonists. 

Thompson, D., and M.A. Fedak (1989). Comparison of dive behaviour and cardiac responses of free ranging harbor and grey seals. Tenth Biennial Conf. Biol. Marine Mammals A106. 

Edwards RP, Miller RD, Roizen MF, Ham J, Way WL, Lake CR, Roderick L. Cardiac responses to imipramine and pancuronium during anesthesia with halothane or enflurane. Anesthesiology 1979 50(5) 421-5. 

Cheshire WP Jr., Saper CB (2006). The insular cortex and cardiac response to stroke. Neurology 66 1296-1297... 

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