Ischemic functional impairments

Hypersensitivity reactions While taking -blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. Renal/Hepatic function impairment Rarely, use of carvedilol in patients with CHF has resulted in deterioration of renal function. Patients at risk appear to be those with low blood pressure (systolic BP less than 100 mm Hg), ischemic heart disease. 

It is almost impossible to individualize the exact role of CSA-induced chronic nephrotoxicity in renal allograft outcomes. From the moment of implantation, the transplanted kidney will suffer from mechanical manipulation, ischemic injury and immunologic attack. Later on acute rejection, recurrent or de novo renal disease, hypertension, chronic viral infection, metabolic derangements (dyslipidemia, diabetes, and hyperuricemia), chronic rejection and aging may work in various combinations causing progressive structural damage and functional impairment. 

With modest impairment of blood flow, this mechanism allows for preservation of oxidative metabolism without alteration in electrical function. However, when CPP and therefore CBF are sufficiently low, OEF reaches a maximum and cannot increase further. Brain tissue ceases to function electrically, resulting in a neurologic deficit. Microvascular collapse occurs, and CBV falls. If the oxygen supply falls low enough, the tissue dies. Of critical clinical importance is the observation that the amount of time it takes for tissue to suffer irreversible damage is inversely related to the severity of the ischemic insult. Tissue that is completely deprived of blood will die within a few minutes, but less severely hypoperfused tissue may survive for many hours, and may be saved by timely thrombolysis that restores perfusion, or perhaps by another therapeutic intervention. 

Excellent biological arguments exist for a direct impact of fever specifically on neurological outcome. On a local level, fever produces increased levels of excitatory amino acids (e.g., glutamate and dopamine), free radicals, lactic acid, and pyr-uvate. There is an increase in cell depolarizations and BBB breakdown. Enzymatic function is impaired and cytoskeletal stability reduced. These events lead to increased cerebral edema, with a possible reduction in CPP as well as larger volumes of ischemic injury. " ... 

Risk factors for embolic cerebrovascular accidents include previous ischemic stroke, transient ischemic attacks (TIA), systemic embolism, age >75 yr, moderately or severely impaired left ventricular systolic function, hypertension, diabetes mellitus... 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

Normal coronary arteries can dilate in response to ischemia, increasing delivery of oxygen to the myocardium. This is mediated by nitric oxide, which acts upon smooth muscle cells of the arterial media. This function is impaired by atherogenic lipoproteins in several phenotypes of hyperlipidemia, aggravating ischemic manifestations of atherosclerosis. Reducing levels of atherogenic lipoproteins and inhibition of their oxidation helps restore endothelial function. 

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