Blood flow aging

Montciro-Riviere, N. A., Banks, Y. B., and Bimhaum, L, S. (1991), La,ser Doppler measurements of cutaneous blood flow ageing in mice. Toxicol. Lett. 57,329-338. 

The success of thrombus lysis depends mainly on how large the thrombus is and whether any blood flow stiU remains. The outcome is better the larger the surface of the entire thrombus exposed to the thrombolytic agent. As the clot ages, the polymerization of fibria cross-linking and other blood materials iacreases and it becomes more resistant to lysis. Therefore, the eadier the thrombolysis therapy starts, the higher the frequency of clot dissolution. Thrombolytic agents available are Hsted ia Table 7 (261—276). 

Cardioembolism Cardioembolism accounts for approximately 30% of all stroke and 25-30% of strokes in the young (age <45 years)." AF accounts for a large proportion of these strokes (15-25%). Symptoms may be suggestive, but they are not diagnostic. Repetitive, stereotyped, transient ischemic attacks (TIAs) are unusual in embolic stroke. The classic presentation for cardioembolism is the sudden onset of maximal symptoms. The size of the embolic material determines, in part, the course of the embolic material. Small emboli can cause retinal ischemic or lacunar symptoms. Posterior cerebral artery territory infarcts, in particular, are often due to cardiac embolism. This predilection is not completely consistent across the various cardiac structural abnormalities that predispose to stroke, and may be due to patterns of blood flow associated with specific cardiac pathologies. 

PBPK and classical pharmacokinetic models both have valid applications in lead risk assessment. Both approaches can incorporate capacity-limited or nonlinear kinetic behavior in parameter estimates. An advantage of classical pharmacokinetic models is that, because the kinetic characteristics of the compartments of which they are composed are not constrained, a best possible fit to empirical data can be arrived at by varying the values of the parameters (O Flaherty 1987). However, such models are not readily extrapolated to other species because the parameters do not have precise physiological correlates. Compartmental models developed to date also do not simulate changes in bone metabolism, tissue volumes, blood flow rates, and enzyme activities associated with pregnancy, adverse nutritional states, aging, or osteoporotic diseases. Therefore, extrapolation of classical compartmental model simulations... 

While these models simulate the transfer of lead between many of the same physiological compartments, they use different methodologies to quantify lead exposure as well as the kinetics of lead transfer among the compartments. As described earlier, in contrast to PBPK models, classical pharmacokinetic models are calibrated to experimental data using transfer coefficients that may not have any physiological correlates. Examples of lead models that use PBPK and classical pharmacokinetic approaches are discussed in the following section, with a focus on the basis for model parameters, including age-specific blood flow rates and volumes for multiple body compartments, kinetic rate constants, tissue dosimetry,... 

Kety SS (1956). Human cerebral blood flow and oxygen consumption as related to aging. Journal of Chronic Disease, 3, 478-486. 

Lassen NA and Ingvar DH (1980). Blood flow studies in the aging normal brain and in senile dementia. Aging of the brain and dementia. Aging, 13, 91-98. 

Cerebral metabolic rate declines from developmental levels and plateaus after maturation. Reliable quantitative data on the changes in cerebral circulation and metabolism in humans from the middle of the first decade of life to old age have been reported [2,39,44]. By 6 years of age, cerebral blood flow and oxygen consumption already have attained high rates, and they decline thereafter to the rates of normal young adulthood [45]. Oxygen is utilized in the brain almost entirely for the oxidation of carbohydrates [46]. The equation for the complete oxidation of glucose is ... 

Blood pressure lowering drugs reduce risk of stroke (and myocardial infarction and death) in middle aged patients and even better in the elderly (NNT 86 vs 29 over 5 years) (Pearce 1998). However in the elderly the dysfunction in the autoregulation of brain blood flow, salt and fluids, and increased sensitivity to adverse effects and symptoms may change the picture. 

Senile dementia is another type of mental disease for which physical and chemical causes, aside from aging itself, are known. Cerebral arteriosclerosis is a every common accompaniment, and this is known to decrease the cerebral blood flow and the total metabolism of the brain. 11 This itself is enough to account for the deranged metabolism and the accompanying deranged mental functions. 

Maiese K, Holloway HH, Larson DM, SoncrantTT. (1994). Effect of acute and chronic arecoline treatment on cerebral metabolism and blood flow in the conscious rat. Brain Res. 641(1) 65-75. Malloy MH, Kleinman JC, Land GH, Schramm WF. (1988). The association of maternal smoking with age and cause of infant death. Am J Epidemiol. 128(1) 46-55. 

Gitelman DR, Prohovnik I. (1992). Muscarinic and nicotinic contributions to cognitive function and cortical blood flow. Neurobiol Aging. 13(2) 313-18. 

Clearance of nicotine is decreased in the elderly (age >65) compared to adults (Molander et al. 2001). Total clearance was lower by 23%, and renal clearance lower by 49% in the elderly compared to yonng adults. Lower nicotine metabolism in the elderly may be contribnted to by rednced liver blood flow, since no decrease in CYP2A6 protein levels or nicotine metabolism in liver microsomes due to age has been detected (Messina et al. 1997). No differences in steady-state nicotine plasma levels or estimated plasma clearance valnes were detected in three age gronps (18-39, 40-59, and 60-69 years) nsing patches with the same nicotine content (Gonrlay and Benowitz 1996). The volnme of distribntion of nicotine is lower in older snbjects due to a decrease in lean body mass (Molander et al. 2001). 

Renal development is also immature in both the premature and the full-term baby. At birth overall renal function is approximately 20% of the adult value, but increases rapidly up to around one year of age when it is usually the same as that of an adult (when adjusted for body size). Glomerular filtration rate in particular may increase four-fold over the first week of life. As renal blood flow, glomerular filtration rate and tubular secretion of drugs are all low in the neonate, drugs cleared by the kidney need to be given in reduced dose - particularly if the drug has a narrow therapeutic window , and the potential to produce toxicity if Cp rises too greatly. 

Even if a medication is available in multiple formulations and dosage forms, the prescriber must consider the absorption and distribution differences between adult and pediatric patients. Blood supply at injection or infusion site, available blood supply for unit muscle mass, and skeletal muscle mass relative to body mass vary with patient age and size, causing drug absorption to vary, as well. A rapid intravenous bolus in a pediatric patient might result in acute toxicity a slow intravenous infusion, often required in neonates, can cause erratic, unreliable drug delivery in an older child. In addition, the volume of fluid tolerated for intravenous delivery varies significantly with the age and size of the patient. The blood supply and blood flow to and from the injection site are of prime importance since a gradual decrease in blood supply per unit muscle mass is seen with maturation. In addition, the skeletal muscle mass relative to... 

In developed countries endocarditis is present in 1/1000 hospital admissions or 1-2 cases per million population. An increasing number of endocarditis cases are associated with intravascular device infections and the placement of prosthetic valves thus, endocarditis can be acquired during hospital stay. Men are afflicted more often than females, and most patients are >50 years of age. Pre-existing heart lesions predispose to bacterial endocarditis if they are accompanied by (thrombotic) alterations of the endocardial surface or blood flow such that bacteria... 

Renal elimination of foreign compounds may change dramatically with increasing age by factors such as reduced renal blood flow, reduced glomerular filtration rate, reduced tubular secretory activity, and a reduction in the number of functional nephrons. It has been estimated that in humans, beginning at age 20 years, renal function declines by about 10% for each decade of life. This decline in renal excretion is particularly important for drugs such as penicillin and digoxin, which are eliminated primarily by the kidney. 

Absorption Decreased absorptive surface Decreased splanchnic blood flow Increased gastric pH Altered gastrointestinal motility Little change in absorption with age... 

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