Heart rate catecholamines effect

Enflurane produces a dose-related decrease in systemic arterial blood pressure secondary to reductions in cardiac output and systemic vascular resistance. There is evidence that cardiac output is partially maintained by a compensatory increase in heart rate. This effect seems dependent on a degree of hypercardia and does not occur during controlled ventilation. Enflurane and halothane depress myocardial contractility to a similar extent and less than isoflurane. Enflurane does not sensitise the heart to the effects of catecholamines to any significant extent and adrenaline (epinephrine) may be given subcutaneously for control of bleeding. 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

At low doses, ketamine may result in impairment of attention, learning ability, and memory, and at high doses it has been associated with delirium, amnesia, impaired motor function, hypertension, depression, and respiratory depression (Krystal et al. 1994). Another mechanism of action appears to be a blocking of the reuptake of catecholamines. This effect leads to an increase in heart rate and blood pressure (Reich and Silvay 1989). 

The second factor that exerts control on heart rate is the release of the catecholamines, epinephrine and norepinephrine, from the adrenal medulla. Circulating catecholamines have the same effect on heart rate as direct sympathetic stimulation, which is to increase heart rate. In fact, in the intact heart, the effect of the catecholamines serves to supplement this direct effect. In a denervated heart, circulating catecholamines serve to replace the effect of direct sympathetic stimulation. In this way, patients who have had a heart transplant may still increase their heart rate during exercise. 

One of the few examples of decreased susceptibility among elderly is the effect of catecholamines on the heart. There is a down-regulation of beta-adrenergic receptors and a reduced response to beta-adrenergic stimulation (Turnheim 1998). This results in decreased effect of betablockers on heart rate and stroke volume. In the elderly betablockers may be less effective than other drugs against hypertension and they should not be considered appropriate for first-line therapy of uncomplicated hypertension in the elderly (Grossman and Messerli 2002). 

Its most important pharmacological effects are dilation of veins and capillaries, increased permeability of capillaries, increased heart rate, contraction of nonvascular smooth musculature (constriction of bronchi, gastrointestinal tract peristalsis), stimulation of gastric juice secretion, and release of catecholamines from adrenal glands. 

SA node and A-V fibers become dominant. Activation of M2 receptors increases the potassium permeability and reduces cAMP levels, slowing the rate of depolarization and decreasing the excitability of SA node and A-V fiber cells. This results in marked bradycardia and a slowing of A-V conduction that can override the stimulation of the heart by catecholamines released during sympathetic stimulation. In fact, very high doses of a muscarinic agonist can produce lethal bradycardia and A-V block. Choline esters have relatively minor direct effects on ventricular function, but they can produce negative inotropy of the atria. 

The myocardial response to exercise includes an increase in heart rate and myocardial contractility. These effects are mediated in part by the sympathetic nervous system. Propranolol and other p-adrenoceptor blockers antagonize the actions of catecholamines on the heart... 

Mechanism of Action An antihypertensive that depletes stores of catecholamines and 5-hydroxytryptamine in many organs, including the brain and adrenal medulla. Depression of sympathetic nerve function results in a decreased heart rate and a lowering of arterial blood pressure. Depletion of catecholamines and 5-hydrox-ytryptamine from the brain is thought to be the mechanism of the sedative and tran-quilizing properties. Therapeutic Effects Decreases blood pressure and heart rate sedation. 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

The effects of sympathomimetic drugs on blood pressure can be explained on the basis of their effects on heart rate, myocardial function, peripheral vascular resistance, and venous return (see Figure 6-7 and Table 9-4). The endogenous catecholamines, norepinephrine and epinephrine have complex cardiovascular effects because they activate both and 13 receptors. It is easier to understand these actions by first describing the cardiovascular effect of sympathomimetics that are selective for a given adrenoreceptor. 

Direct effects on the heart are determined largely by Bi receptors, although B2 and to a lesser extent a receptors are also involved, especially in heart failure. Beta-receptor activation results in increased calcium influx in cardiac cells. This has both electrical and mechanical consequences. Pacemaker activity—both normal (sinoatrial node) and abnormal (eg, Purkinje fibers)—is increased (positive chronotropic effect). Conduction velocity in the atrioventricular node is increased (positive dromotropic effect), and the refractory period is decreased. Intrinsic contractility is increased (positive inotropic effect), and relaxation is accelerated. As a result, the twitch response of isolated cardiac muscle is increased in tension but abbreviated in duration. In the intact heart, intraventricular pressure rises and falls more rapidly, and ejection time is decreased. These direct effects are easily demonstrated in the absence of reflexes evoked by changes in blood pressure, eg, in isolated myocardial preparations and in patients with ganglionic blockade. In the presence of normal reflex activity, the direct effects on heart rate may be dominated by a reflex response to blood pressure changes. Physiologic stimulation of the heart by catecholamines tends to increase coronary blood flow. 

Trials of 3-blocker therapy in patients with heart failure are based on the hypothesis that excessive tachycardia and adverse effects of high catecholamine levels on the heart contribute to the downward course of heart failure patients. The results clearly indicate that such therapy is beneficial if initiated very cautiously at low doses, even though acutely blocking the supportive effects of catecholamines can worsen heart failure. Several months of therapy may be required before improvement is noted this usually consists of a slight rise in ejection fraction, slower heart rate, and reduction in symptoms. As noted above, not all 3 blockers have proved useful, but bisoprolol, carvedilol, and metoprolol have been shown to reduce mortality. Trials are underway with the newer 13 blocker, nebivolol. 

Inhaled anesthetics change heart rate either directly by altering the rate of sinus node depolarization or indirectly by shifting the balance of autonomic nervous system activity. Bradycardia can be seen with halothane, probably because of direct vagal stimulation. In contrast, enflurane, and sevoflurane have little effect, and both desflurane and isoflurane increase heart rate. In the case of desflurane, transient sympathetic activation with elevations in catecholamine levels can lead to marked increases in heart rate and blood pressure when high inspired gas concentrations are administered. 

Indapamidc has been shown to possess diuretic and independent vasodilators- effects. It lowers the elevated blood pressure and reduces inial peripheral resistance without an increase in heart rate. Indapamidc antagonizes die vasoconsiriciing effects of the catecholamines and angiotensin II. a property not shared by other thiazidc-lype diuretics. Tripumide is also reported to have direct vasodilators- effects. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

When injected intravenously, kinins produce a rapid fall in blood pressure that is due to their arteriolar vasodilator action. The hypotensive response to bradykinin is of very brief duration. Intravenous infusions of the peptide fail to produce a sustained decrease in blood pressure prolonged hypotension can only be produced by progressively increasing the rate of infusion. The rapid reversibility of the hypotensive response to kinins is due primarily to reflex increases in heart rate, myocardial contractility, and cardiac output. In some species, bradykinin produces a biphasic change in blood pressure—an initial hypotensive response followed by an increase above the preinjection level. The increase in blood pressure may be due to a reflex activation of the sympathetic nervous system, but under some conditions, bradykinin can directly release catecholamines from the adrenal medulla and stimulate sympathetic ganglia. Bradykinin also increases blood pressure when injected into the central nervous system, but the physiologic significance of this effect is not clear, since it is unlikely that kinins cross the blood-brain barrier. 

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