Cardiac parameter

Human exposures with measured concentrations were limited to occupational reports. Symptoms of exposed workers ranged from no adverse health effects to mild discomfort to frank central nervous system effects. Repeated or chronic exposures have resulted in hypothyroidism. Inhalation studies resulting in sublethal effects, such as incapacitation, and changes in respiratory and cardiac parameters were described for the monkey, dog, rat, and mouse lethality studies were available for the rat, mouse, and rabbit. Exposure durations ranged from a few seconds to 24 hours (h). Regression analyses of the exposure duration-concentration relationships for both incapacitation and lethality for the monkey determined that the relationship is C2xt= k and that the relationship for lethality based on rat data is C2 6xt=k. 

In vivo Hemodynamic and cardiac parameters pressure (arterial, venous, ventricular, e.g., ventricular contractility, cardiac output), HR, peripheral resistance, ECG parameters, body temperature, flow Conscious (restrained or telemetry) and anesthetized Takahara et al. 97 Sato et al. 98 Nekooeian and Tabrizchi99... 

Frames corresponding to end diastole and end systole are identified from each cine sequence and regions-of-interest (ROI) drawn around the left ventricular (LV) epi- and endocardial borders using ParaVision software (Bruker). The area of the ROIs is summed and multiplied by the inter-slice distance (5 mm) to calculate the end diastolic and end systolic volumes (EDV and ESV) of the whole ventricle and lumen. Other cardiac parameters are calculated as follows ... 

Cohen H, Loewenthal U, Matar MA, Kotler M. Reversal of pathologic cardiac parameters after transition from clozapine to olanzapine treatment a case report. Clin Neuropharmacol 2001 24(2) 106-8. 

The cardiorespiratory effects of capsaicin have been studied following i.v. administration, which resulted in a triphasic effect on blood pressure and altered cardiac parameters. ° Capsaicin induces complex effects on the cardiovascular system consisting of tachypnea, hypotension (seen in the Bezold-Jarrish reflex), bradycardia, and apnea. 

Cardiac parameters related to blood pumping may also be optimized to reduce energy use. Model results appear to be consistent with an optimization hypothesis (Figure 6.14.7). 

Cenci MC, Soares DV, Spina LD, de Lima Oliveira Brasil RR, Lobo PM, Mansur VA, Gold J, Michmacher E, Vaisman M, Conceigao FL. Effects of 5 years of growth hormone (GH) replacement therapy on cardiac parameters and physical performance in adults with GH deficiency. Pituitary 2009 12 322-9. 

Neither steroid had an effect on mortality, lung oedema, or shunt fraction. However, some beneficial effects on cardiac parameters, e.g. stroke volume, left ventricular stroke work, were noted Steroids were neither beneficial nor detrimental in the treatment of phosgene induced lung injury... 

Mest HJ, Ponicke K, Heinroth I, Meissner N, Cheissler C. Relevance of mediators to cardiac parameters of isolated anaphylactic guinea-pig heart. Prostaglandins Leukot Essent Fatty Acids 1995 53 21 29. 

Monitoring the patient in shock requires vigilance on the part of the nurse The patient s heart rate, blood pressure, and ECG are monitored continuously. The urinary output is measured often (usually hourly), and an accurate intake and output is taken. Monitoring of central venous pressure via a central venous catheter will provide an estimation of the patient s fluid status. Sometimes additional hemodynamic monitoring is necessary with a pulmonary artery catheter. The use of a pulmonary artery catheter allows the nurse to monitor a number of parameters, such as cardiac output and peripheral vascular resistance The nurse adjusts therapy according to the primary health care provider s instructions. 

Physiologically Based Phamiacokinetic (PBPK) Model—Comprised of a series of compartments representing organs or tissue groups with realistic weights and blood flows. These models require a variety of physiological information tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry models. 

Modern representations of the virtual heart, therefore, describe structural aspects like fibre orientation in cardiac muscle, together with the distribution of various cell types, active and passive electrical and mechanical properties, as well as the coupling between cells. This then allows accurate reproduction of the spread of the electrical wave, subsequent contraction of the heart, and effects on blood pressure, coronary perfusion, etc. It is important to point out, here, that all these parameters are closely interrelated, and changes in any one of them influence the behaviour of all others. This makes for an exceedingly complex system. 

A basic grasp of normal cardiac function sets the stage for understanding the pathophysiologic processes leading to HF and selecting appropriate therapy for HF. Cardiac output is defined as the volume of blood ejected per unit of time (liters per minute) and is a major determinant of tissue perfusion. Cardiac output is the product of heart rate (HR) and stroke volume (SV) CO = HR x SV. The following describes how each parameter relates to CO. 

Upon stabilization, placement of a pulmonary artery (PA) catheter may be indicated based on the need for more extensive cardiovascular monitoring than is available from non-invasive measurements such as vital signs, cardiac rhythm, and urine output.9,10 Key measured parameters that can be obtained from a PA catheter are the pulmonary artery occlusion pressure, which is a measure of preload, and CO. From these values and simultaneous measurement of HR and blood pressure (BP), one can calculate the left ventricular SV and SVR.10 Placement of a PA catheter should be reserved for patients at high risk of death due to the severity of shock or preexisting medical conditions such as heart failure.11 Use of PA catheters in broad populations of critically ill patients is somewhat controversial because clinical trials have not shown consistent benefits with their use.12-14 However, critically ill patients with a high severity of illness may have improved outcomes from PA catheter placement. It is not clear why this was... 

The clinical scenario and the severity of the volume abnormality dictate monitoring parameters during fluid replacement therapy. These may include a subjective sense of thirst, mental status, skin turgor, orthostatic vital signs, pulse rate, weight changes, blood chemistries, fluid input and output, central venous pressure, pulmonary capillary wedge pressure, and cardiac output. Fluid replacement requires particular caution in patient populations at risk of fluid overload, such as those with renal failure, cardiac failure, hepatic failure, or the elderly. Other complications of IV fluid therapy include infiltration, infection, phlebitis, thrombophlebitis, and extravasation. 

Pulmonary artery catheter An invasive device used to measure hemodynamic parameters directly, including cardiac output and pulmonary artery occlusion pressure calculated parameters include stroke volume and systemic vascular resistance. 

Data adequacy The key study was well designed and conducted and documented a lack of effects on heart and lung parameters as well as clinical chemistry. Pharmacokinetic data were also collected. The compound was without adverse effects when tested as a component of metered-dose inhalers on patients with COPD. Animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The values are supported by a study with rats in which no effects were observed during a 4-h exposure to 81,000 ppm. Adjustment of the 81,000 ppm concentration by an interspecies and intraspecies uncertainty factors of 3 each, for a total of 10, results in essentially the same value (8,100 ppm) as that from the human study. ... 

The AEGL-1 value was based on the observation that exercising healthy human subjects could tolerate exposure to concentrations of 500 or 1,000 ppm for 4 h with no adverse effects on lung function, respiratory symptoms, sensory irritation, or cardiac symptoms (Utell et al. 1997). The exercise, which tripled the subjects minute ventilation, simulates an emergency situation and accelerates pulmonary uptake. Results of the exposure of two subjects for an additional 2 h to the 500-ppm concentration and the exposure of one subject to the 1,000-ppm concentration for an additional 2 h failed to elicit any clear alterations in neurobehavioral parameters. The 4- or 6-h 1,000-ppm concentration is a NOAEL in exercising individuals, there were no indications of response differences among tested subjects, and animal studies indicate that adverse effects occur only at considerably higher concentrations, so the 1,000-ppm value was adjusted by an uncertainty factor (UF) of 1. The intraspecies UF of 1 is supported by the lack of adverse effects in patients with severe... 

Studies to assess the effects of compound and any known metabolites on ECG and cardiac action potentials are recommended. Changes in action potential duration and other parameters measured are a functional consequence of effects on the ion channels which contribute to the action potential. This in vitro test is considered to provide a reliable risk assessment of the potential for a compound to prolong Q-T interval in humans. 

Endpoint. An indicator measured in a patient or biological sample to assess safety, efficacy, or another trial objective. Some endpoints are derived from primary endpoints (e.g., cardiac output is derived from stroke volume and heart rate). Synonyms include outcome, variable, parameter, marker, and measure. See surrogate endpoint in the text. Also defined as the final trial objective by some authors. 

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