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cases of irregularity projecting incisors are kept in their. The objective of all forms of stress testing in coronary artery disease . Dynamic exercise may be viewed as an indirect test of the CFR. This type of exercise may be performed on a treadmill or bicycle and increases flow demand ambien cause dry eyes which secondarily increases flow. Pharmacologic stress, as delivered by dobutamine, acts similarly to increase flow indirectly through an increase in flow demands. However, dipyridamole and adenosine act directly to increase the coronary flow. Indirect tests of the CFR, such as dynamic treadmill or bicycle exercise or dobutamine, seek to provoke ischemic perfusion and wall motion endpoints. Here, test sensitivity is influenced by, and directly related to, the ability of the intervention to augment demand. Direct tests of the CFR . In those who can exercise sufficiently to increase the heart rate enough to maximally augment flow demands, both exercise and vasodilator stress may maximally test the CFR. Exercise is not only preferred clinically but also preferred to vasodilator stress in these types of patients because of its occasionally increased sensitivity in 36 selected patients. They found that exercise was not equal to pharmacologic stress, as the former yielded much larger stress-induced defects than did the latter. Although vasodilator stress myocardial perfusion SPECT . Nonetheless, many patients who cannot exercise sufficiently to achieve the required threshold, for which exercise is insufficient to answer the clinical question, benefit from vasodilator stress testing. Pharmacologic stress testing is applied to evaluate the cause of symptoms, signs, or perceived risk from CAD in patients who cannot exercise or who cannot exercise sufficiently to perform an adequate diagnostic or prognostic exercise test. It is said that safety should not be an issue, and patients should not be studied with pharmacologic stress if it is not safe for them to exercise. However, the patients who undergo pharmacologic stress are more debilitated and limited and are likely, as a group, to be at higher risk than those who exercise. Some patients, such as those studied early after myocardial infarction, may indeed be safely studied with pharmacologic but not with exercise stress. The choice of the stress-testing method depends on the clinical question, or the test indication, not entirely on the patient's ability to exercise. For example, if an elderly woman experiences chest pain when pushing a shopping cart at a supermarket and we simply seek the cause of the pain, all that is required is an exercise test with an achieved workload similar to that of the activity that induced the symptom. Here, we would simply apply that stress, bring on the symptoms, monitor those symptoms, and observe. The specific heart rate and level of coronary flow demands achieved are not critical. However, if this same woman were to have high-risk vascular surgery, she would need a maximal assessment of coronary risk and CFR. If she could not exercise effectively or she was on treatment that blunted her rate-pressure product response, she would need effective pharmacologic stress testing in the form of coronary vasodilators. Because these methods evaluate the perfusion endpoint, they must be performed with imaging. Vasodilator stress imaging with MPI currently accounts for roughly 50% of all stress MPI. Shown are pathways of adenosine production transport, receptor activation, and metabolism. Patients should not have caffeine for 24–48 h before testing and should be safely withdrawn from β-blocker treatment before the study, if possible. Dipyridamole, given therapeutically as an oral agent to reduce platelet adhesiveness in patients with prior strokes or as an ingredient of Aggrenox , may pose a danger during adenosine infusion, prolonging drug action and requiring an aminophylline antidote at the end of the test. The direct coronary vasodilators adenosine and dipyridamole act directly on the coronary resistance vessels . The prognostic value of vasodilator stress imaging has generally been shown to be equal to that of maximal and optimal exercise stress imaging. Adenosine and dipyridamole—which are well able to induce abnormalities of the CFR, generally without inducing ischemia—are the most widely applied pharmacologic stress agents in the nuclear medicine laboratory. In the absence of an ultrasound contrast agent that can directly monitor perfusion, adenosine and dipyridamole find little application to echocardiography, in which induced wall motion abnormalities are sought as the indicator of true coronary ischemia. Because of its ability to augment the determinants of myocardial oxygen demand and test the CFR, dobutamine is applied as an ischemic stress agent. Dobutamine stress MPI has been shown to be more sensitive for CAD diagnosis than is dobutamine stress echocardiography. The agent is applied widely for pharmacologic stress in the echocardiography laboratory but infrequently in the nuclear laboratory because of the ability of scintigraphic methods to monitor the hyperemic response and the related ability to apply the safer, more accurate vasodilator agents . If dobutamine is ineffective in increasing myocardial oxygen demands, or if the patient develops intolerance early in the administration of dobutamine, its effect on the CFR is blunted. The ability of dobutamine to augment coronary flow and test the CFR is lower than that of adenosine, even when applied to maximal dose , and not infrequently the effects of the agent force premature test cessation. The use of dobutamine is prohibited in the setting of acute MI, acute coronary syndromes, uncontrolled hypertension, aortic stenosis, dissecting aneurysms, and other conditions that are aggravated by the effects of the agent. The 3-min stages of the incremental titration dobutamine stress protocol are modeled, for commercial reasons, after the 3-min stages of the standard exercise protocol. Its 2.4-min half-time indicates that the dobutamine dose would be better augmented at intervals of 10–15 min to permit the adequate buildup of drug levels and related effectiveness at each stage. However, commercially this interval would be unacceptable and too time-consuming for clinical application. Those who apply this 3-min interval must do so acknowledging the intrinsic loss of sensitivity early in the test and the potential dangers late in the test, when the earlier dose-related effects accumulate and manifest themselves unpredictably, where a higher dose is infused before the effects of earlier levels can occur. Although, in the absence of any alternative, dobutamine is applied widely by those who seek to use echocardiography as the stress-imaging modality, the agent need only rarely and grudgingly be applied in the nuclear laboratory in selected patients without contraindications, when adequate exercise testing is not possible and when the risk of vasodilators is prohibitive. Shown diagrammatically are clinical infusion protocols recommended for regadenoson and binodenoson. These are designed on the basis of pharmacokinetics of the agents and their necessary interaction with the imaging agent. Although the agent is FDA approved and will soon be available everywhere, there is much about regadenoson that we do not know as it approaches clinical application. What is not known about the regadenoson includes the use of the agent in patients with bronchospasm, the incidence of AV block, the effect of caffeine, the effect of β-blockers, the meaning of a test with a blunted hemodynamic and symptomatic response, the value of added exercise, the value of transient ischemic dilation, the effects of left bundle branch block, the ability to appreciate related ischemia, the frequency of related ischemia, the safety of the agent with renal insufficiency, the applicability of the agent to stress testing with PET and MRI, and the effects of the single-dose protocol .. as. far from the disturbances of mastication. The. to the consideration

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