Cardiovascular function testing

Traditionally, safety pharmacology screens for cardiovascular fimction have been performed in the anesthetized dog or rat. In the rat, diastolic, systolic, and mean arterial blood pressures (DAP, SAP, MAP) are recorded via direct cannulation of a major artery (e.g., femoral or carotid), and the test article is injected directly into a vein while the animal remains anesthetized. Heart rate is determined electronically from the pressure signal, and other physiological parameters may be monitored, such as body temperature, respiration rate, and ECG. Often, an escalating dose strategy is employed to determine the minimum dose necessary to see any changes in cardiovascular function. 

Radiotelemetry devices are also subject to interference from other nearby electronic instruments, and they have a tendency to display a baseline drift over time. Careful attention to the study setup and design as well as improved sensor design can minimize these problems. To compensate for drift one may need to periodically calibrate the animal and telemetry system with responses to known agents, but this is not desirable when testing an xmknown compound. Lastly, maintenance of a telemetry-instrumented colony can be expensive. Many researchers find that the cost of telemetry implants is not feasible for short-term evaluations. In spite of these drawbacks, radiotelemetry may produce the most accurate picture of the effects of a novel compound on cardiovascular function. 

Magnetic resonance imaging (MRl) relies mainly on the detection of hydrogen nuclei in water and fat to construct high-resolution images. The contrast in these images results from different tissue environments. MRl 

In the present studies, the parameters measured varied because of differences in hearf size, anatomy, species movement artifacts, and equipment used. However, certain parameters are constant across the studies, and these are used for comparative purposes. Two of these parameters (or surrogate) are also those used in the Common Terminology Criteria for Adverse Events (CTCAE), version 3 (v3), an adverse event rating, which is used for assessing adverse evenfs during clinical trials. These parameters include an assessment of left ventricular ejection fraction and fractional shortening of the left ventricle. 

Results with studies suggest that the use of ECHO can demonsfrate changes in cardiac function af lower doses fhat can predict more significant changes at higher doses. 

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KC706 stabilizes the inactive conformation of the mitogen-activated protein kinase p38a, a protein kinase involved in inflammatory reactions and cardiovascular functions. KC706 therefore holds the potential to treat conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease and cardiovascular disease. This compound is currently being tested in phase II clinical trials with patients suffering from rheumatoid arthritis. 

During tiie ongoing assessment, tiie nurse assesses the respiratory status every 4 hours and whenever tiie drug is administered. The nurse notes the respiratory rate, lung sounds, and use of accessory muscles in breathing, hi addition, tiie nurse keeps a careful record of the intake and output and reports any imbalance, which may indicate a fluid overload or excessive diuresis. It is important to monitor any patient with a history of cardiovascular problems for chest pain and changes in the electrocardiogram. The primary health care provider may order periodic pulmonary function tests, particularly for patients with emphysema or bronchitis, to help monitor respiratory status. 

Evidence-based pharmacotherapy provides a succinct appreciation of the benefits of a drug, but rarely takes into account the patient s quality of life. Eor instance, intensive statin therapy is recommended because it reduces the incidence of cardiovascular death (odds ratio 0.86), myocardial infarction (odds ratio 0.84), and stroke (odds ratio 0.82) however, the increased risks for any adverse event (odds ratio 1.44), for abnormalities on liver function testing (odds ratio 4.48), for elevations in CK (odds ratio 9.97) and for adverse events requiring discontinuation of therapy (odds ratio 1.28) are less often taken into account by the prescriber. This example emphasises that individualisation is of the utmost importance to keep an acceptable benefit/risk ratio (Clin Ther 2007 29 253-60). The benefits of evidence-based pharmacotherapy may be obtained whenever concordance/compliance of the patient is adequate. However, concordance rate is slightly higher than 30% for chronic conditions, such as hypertension (Curr Hypertens Rep 2007 9 184-9), indicating that the patient has to be educated about the use of drugs, and therapy has to be individualised. 

Medical history and a physical examination should be completed for every patient. Given the physiological changes during ECT, the physical examination should include assessment of the airway, cardiovascular, pulmonary, and central nervous systems. Eaboratory examinations may include a blood count, liver and thyroid function tests, urine analysis, and electrocardiogram (EKG). Other investigations such as skeletal X-ray, completed tomographic (CT) scan of the... 

Oral glucose tolerance test Total cholesterol level Phospholipids B level Body composition by DEXA Regional fat depot assessment by gCT Weekly body weight Tissue glycogen level Cardiovascular function... 

Mr JJ should be monitored regularly for efficacy. If there is no significant improvement in the condition, as determined by laboratory measurements of liver function (ALT test) and viral DNA load, then treatment with interferon alfa should be discontinued. In addition, white blood cell counts should be monitored, as should cardiovascular function. Fluid replacement may be required to correct hypotension. 

Acute hepatocellular necrosis. This reaction varies from a transient disturbance of liver function tests to acute hepatitis. It can be induced by several drugs including general anaesthetics (halothane), antiepileptics (carbamazepine, phenytoin, sodium valproate, phenobarbital), antidepressants (MAO inhibitors), antiinflammatory drugs (indomethacin, ibuprofen), antimicrobials (isoniazid, sulphonamides, nitrofurantoin) and cardiovascular drugs (methyldopa, hydralazine). 

Nuclear imaging techniques have demonstrated equal sensitivity and specificity to many of the invasive gold standard testing modalities. The major limitations of nuclear cardiology are the availability of suitable radionuclides and correlation of nuclear images with cardiovascular function. 

The initial visit of a perimenopausal or postmenopausal woman is the most appropriate time to obtain a complete medical history, perform a physical examination, and educate the patient. Medical history should include determination of a personal or family history of thrombotic problems. The physical examination should include a complete cardiovascular examination, clinical assessment of thyroid status, and breast and pelvic examinations. Papanicolaou cervical cytologic examination and screening mammography negative for malignancy are required before initiating hormone therapy. Thyroid function tests and lipoprotein lipid profile also should be performed at the discretion of the clinician. 

Nausea and vomiting (may be dose-limiting) diarrhea cardiovascular lowers arterial circulation ischemic heart disease patients with CHE may develop increased symptoms of heart failure thromboembolic events gynecomastia, nipple tenderness increased liver function tests... 

Volpino P, Tomei F, La Valle C, Tomao E, Rosati MV, Ciarrocca M, De Sio S, Cangemi B, Vigliarolo R, Fedele F (2004) Respiratoiy and cardiovascular function at rest and during exercise testing in a healthy working population effects of outdoor traffic air pollution. Occup Med (Lond) 54 475-482... 

Ruiz-Garcia J, Alegria-Barrero E (2016) Cardiovascular safety in drug development a role for endothehal function tests. J Cardiovasc Pharmacol Ther [Epub ahead of print]... 

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