Coronary distribution

A total of 79 patients with chronic stable angina was enrolled into the AGENT trial. Patients could exercise for > 3 min in an exercise treadmill test (ETT) using the modified Balke protocol. The adenovirus vector was infused over 90 seconds through subselective catheters into all major patent coronary arteries and grafts (40% into the right coronary distribution and 60% into the left coronary distribution). Repeat ETTs were performed at 4 and 12 weeks after treatment [13]. 

SIDEMAN We have seen here two models related to the coronary distribution, one by yourself and one by Professor Heethaar. Your model does not go deeply into the muscle. So my question is more related to Dr. Heethaar. It is logical that whatever the distribution of the ventricles, they should be almost evenly, homogenously, distributed. Why do you have to check the directions Ultimately, the blood goes everywhere and comes back. So what is the point in measuring the direction. What would you gain that you don t know by assuming an even distribution ... 

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. 

The endogenous release of the potent vasoconstrictor neuropeptide Y (NPY) is increased during sepsis and the highest levels are detected in patients with shock (A8). NPY is a 36-amino-acid peptide belonging to the pancreatic polypeptide family of neuroendocrine peptides (T2). It is one of the most abundant peptides present in the brain and is widely expressed by neurons in the central and peripheral nervous systems as well as the adrenal medulla (A3). NPY coexists with norepinephrine in peripheral sympathetic nerves and is released together with norepinephrine (LI9, W14). NPY causes direct vasoconstriction of cerebral, coronary, and mesenteric arteries and also potentiates norepinephrine-induced vasoconstriction in these arterial beds (T8). It appears that vasoconstriction caused by NPY does not counterbalance the vasodilatator effects of substance P in patients with sepsis. The properties of vasodilatation and smooth muscle contraction of substance P are well known (14), but because of the morphological distribution and the neuroendocrine effects a possible stress hormone function for substance P was also advocated (J7). Substance P, which is a potent vasodilatator agent and has an innervation pathway similar to that of NPY, shows a low plasma concentration in septic patients with and without shock (A8). 

Familial hypercholesterolemia (FH) is an autosomal dominantly inherited disease caused by mutations in the gene for the LDL receptor. Up to now more than 680 distinct mutations, distributed over the entire gene, have been described [42]. Heterozygous FH individuals express only half the number of functional LDL-r and, therefore, have a markedly raised plasma cholesterol and usually present with premature coronary artery disease. Homozygous FH individuals are more severely affected and may succumb before the age of maturity. The prevalence of heterozygous FH is approximately 1 in 500 in Caucasians. 

Cardiovascular anatomy and physiology Ventricular performance Electrophysiology Coronary artery distribution Human skin... 

Fig. 11. Distribution of Lp(a) lys+ (A) and lys- (B) levels in plasma of male patients with moderate coronary artery disease (MCAD) and serious coronary artery disease (SCAD). [With permission of Karmansky et al. (K8).]...

Figure 2.1 illustrates normal myocardial perfusion by PET using Rubidium ( Rb) at rest and after dipyridamole stress in 3D views. A coronary arterial map is overlaid on the perfusion image or alternatively an arterial distribution map as a precise perfusion atlas of the coronary artery tree and all its secondary and tertiary branches [25]. 

Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis. Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol 1974 33 87-94... 

Hou D, Youssef EA, Brinton TJ, Zhang P, Rogers P, Price ET, Yeung AC, Johnstone BH, Yock PG, March KL. Radiolabeled cell distribution after intramyocar-dial, intracoronary, and interstitial retrograde coronary venous delivery implications for current chnical trials. Circulation 2005 112(9 Suppl) I150-156. 

Pharmacokinetics According to the product label, the pharmacokinetics of eptihbatide are linear and dose proportional. Plasma elimination half-life is approximately 2.5 hours. The extent of eptihbatide binding to human plasma protein is about 25% its mean volume of distribution is 185mPkg. Clearance in patients with coronary artery disease is 55-58 ml/kg per hour. Clinical studies have included 2418 patients with serum creatinine between 1.0 and 2.0mg/dl without dose adjustment. No data are available in patients with more severe degrees of renal impairment, but plasma eptihbatide levels are expected to be higher in such patients. Patients in clinical studies were older than the subjects in clinical pharmacology studies, and they had lower total body eptihbatide clearance and higher eptihbatide plasma levels. Men and women showed no important differences in the pharmacokinetics of eptihbatide. 

This break-out of values is much more informative to the vast majority of patients than the all-patient average. Variable dosing, which occurred as well in the placebo group, though with a somewhat different distribution than in the active group, had no evident effect on the two main endpoints of the LRC-CPPT, cholesterol reduction and coronary risk reduction (Lipid Research Clinics Coronary Primary Prevention Trial, 1984). 

Excess fat can be located in the central abdominal area (android, upper body obesity). This fat is associated with a greater risk for hypertension, insulin resistance, diabetes, dyslipidemia, and coronary heart disease. That distributed in the lower extremities (gynoid, lower body obesity) is relatively benign, healthwise. 

The observed associations between folate, antioxidant vitamins, and cardiovascular disease may be confounded by other substances in fruits and vegetables, as the following examples of studies show Flavonoids (see Chapter 31) are naturally occurring, water-soluble antioxidants found widely distributed in vegetables, fruits, tea, and wine. There is an inverse relationship between flavonoids and decreased risk of coronary heart disease. Lycopene, the key antioxidant in tomatoes, shows an inverse association with myocardial infarctions. There is an inverse association between folate and cardiovascular disease. 

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