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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When the heart contracts, it compresses its own arteries, so that blood flow in the coronary circulation comes to a standstill during systole. The heart must be supplied with blood from an auxiliary supply during diastole. The auxiliary pump is the aorta and its branches. When the stroke volume is injected into the aorta, it is overfilled and distended, storing energy in stretched elastic tissues. During diastole the contraction of these tissues maintains diastolic pressure. The hardest working organ in the body, the heart, therefore is supplied with blood only intermittently and only at diastolic pressure. In addition a layer of calcium tends to accumulate in the aorta, deteriorating its elasticity. It is suggested that this auxiliary pump is the weakest link in the circulatory system. If it fails, the heart dies of ischaemia. The calcium requirements of the body vary greatly in various age groups; 99% of the calcium content of the adult body is in the skeleton, which is complete by the age of 32 years. After that calcium requirements decrease. Catering for such varying calcium needs the gut to be impermeable to calcium. A special substance, 1,25,-dihydroxycholecalciferol, secreted by the liver and kidneys is needed to transfer calcium through the intestinal wall. When calcium needs are satisfied, the synthesis of cholecalciferol is discontinued, and the calcium in food in the intestines is excreted. To cater for the other extreme, when the calcification of the infant skeleton needs much calcium, nature produces a special nutrient, milk, not only rich in calcium, but containing a substance promoting its transference through the intestinal wall. The human habit of consuming the milk of another species is harmful because it invalidates the natural expedient of limiting calcium intake when it is not needed. The calcium excess resulting from milk consumption tends to calcify the aorta, deteriorating its elasticity, resulting in lower diastolic pressure. When that becomes inadequate, the heart dies of ischaemia.
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PMID:Ischaemic heart failure: a new explanation of its cause and preventability. 1241 64

The structure and function of the pharyngeal jaw apparatus (PJA) and postpharyngeal alimentary tract of Arrhamphus sclerolepis krefftii, an herbivorous hemiramphid, were investigated by dissection, light and scanning electron microscopy, and X-ray analysis of live specimens. A simple model of PJA operation is proposed, consisting of an adductive power stroke of the third pharyngobranchial that draws it posteriorly while the fifth ceratobranchial is adducted, and a return stroke in which the third pharyngobranchial bone is drawn anteriorly during abduction of the fifth ceratobranchial. Teeth in the posteromedial region of the PJA are eroded into an occlusion zone where the teeth of the third pharyngobranchial are spatulate incisiform and face posteriorly in opposition to the rostrally oriented spatulate incisiform teeth in the wear zone of the fifth ceratobranchial. The shape of the teeth and their pedestals (bone of attachment) is consistent with the model and with the forces likely to operate on the elements of the PJA during mastication. The role of pharyngeal tooth replacement in maintaining the occlusal surfaces in the PJA during growth is described. The postpharyngeal alimentary tract of A. sclerolepis krefftii comprises a stomachless cylinder that attenuates gradually as it passes straight to the anus, interrupted only by a rectal valve. The ratio of gut length to standard length is about 0.5. Despite superficial similarities to the cichlid PJA (Stiassny and Jensen [1987] Bull Mus Comp Zool 151:269-319), the hemiramphid PJA differs in the fusion of the third pharyngobranchial bones, teeth in the second pharyngobranchials and the fifth ceratobranchial face anteriorly, the presence of a slide-like diarthroses between the heads of the fourth epibranchials and the third pharyngobranchial, the occlusion zone of constantly wearing teeth, and the unusual form of the muscularis craniopharyngobranchialis. The functional relationship between these structures is explained and the consequence for the fish of a complex PJA and a simple gut is discussed.
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PMID:Anatomy of a hemiramphid pharyngeal mill with reference to Arrhamphus sclerolepis krefftii (Steindachner) (Teleostei: Hemiramphidae). 1247 68

Activation of the poly(ADP-ribose)polymerase (PARP), a highly energy-consuming DNA-repairing enzyme, plays a crucial role in the pathogenesis of multiorgan failure. Most results, however, were derived from experiments with hypodynamic shock states characterized by a markedly decreased cardiac output (CO) and/or using a pretreatment approach. Therefore, we investigated the effects of the novel potent and selective PARP-1 inhibitor PJ34 in a posttreatment model of long-term, volume-resuscitated porcine endotoxemia. Anesthetized, mechanically ventilated and instrumented pigs received continuous intravenous (i.v.) lipopolysaccharide (LPS) over 24 h. Hydroxyethyl starch was administered to maintain a mean arterial pressure > 65 mmHg. After 12 h of LPS infusion, the animals were randomized to receive either vehicle (Control, n = 9) or i.v. PJ34 (n = 6; 10 mg/kg over 1 h followed by 2 mg/kg/h until the end of the experiment). Measurements were performed before as well as at 12, 18, and 24 h of LPS infusion. In all animals CO increased because of reduced systemic vascular resistance (SVR) and fluid resuscitation. PJ34 further raised CO (P < 0.05 vs. control group) as the result of a higher stroke volume indicating its positive inotropic effect. In addition, it diminished the rise in the ileal mucosal-arterial PCO2 gap, which returned to baseline levels at 24 h of LPS, and improved the gut lactate balance (P = 0.093 PJ34 vs. control) together with significantly lower portal venous lactate/pyruvate ratios. By contrast, it failed to influence the LPS-induced derangements of liver metabolism. Incomplete PARP inhibition because of dilutional effects and/or an only partial efficacy when used in post-treatment approaches may account for this finding.
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PMID:Systemic and hepatosplanchnic hemodynamic and metabolic effects of the PARP inhibitor PJ34 during hyperdynamic porcine endotoxemia. 1274 83

The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been the focus of considerable research over the past 25 years. These "gut peptides" or "reproductive hormones" have been localized within nuclei responsible for the relay of visceral afferent information to the forebrain. The presence of peptides and hormones along the gut- or heart-brain continuum suggests that these neurochemicals do more than modulate the visceral processes of digestion and reproduction respectively. Numerous studies have shown that the exogenous administration of these neurochemicals directly into visceral afferent nuclei significantly alters blood pressure, heart rate, autonomic tone and the sensitivity of the baroreceptor reflex (an index of sympatho-vagal balance). A strong inverse correlation has been demonstrated between the sensitivity of the baroreceptor reflex and susceptibility to lethal cardiac arrhythmias which lead ultimately to sudden cardiac death. The differential effects of various neurochemicals on the sensitivity of the baroreceptor reflex suggests that some neurochemicals may act as preventatives while others may actually contribute to the pathogenesis of neurogenic cardiac arrhythmias. Hormones such as estrogen, in addition to their neuroprotective properties, may also play a role in modulating the cardiovascular consequences to neurogenic pathologies including stroke and epilepsy. This review will summarize the evidence available which suggests that neuropeptides and neurohormones can alter both neurogenic as well as visceral pathology-induced changes in autonomic function resulting in an increased risk of sudden cardiac death.
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PMID:The role of neuropeptides and neurohormones in neurogenic cardiac arrhythmias. 1287 Oct 42

Barotrauma is pressure-induced injury. The application of direct pressure to the body may cause trauma, including positive pressure from artificial ventilation. Trauma may also be caused by the effects of pressure changes on gas-containing body spaces, not in communication with the environment. This can include the external ear, the middle ear (and, indirectly, the inner ear), the para-nasal sinuses, the lungs, the gut, and abscess cavities (for example, in the teeth). Gas may penetrate tissues adjoining the affected space (such as the anterior cranial fossa, via the ethmoid sinus), or may embolise via the blood stream. The most severe expression of this is cerebral arterial gas embolism, which may present as a stroke. The management of these problems includes prevention, the use of pressure-equalizing techniques, vasoconstrictor drugs, surgery, and hyperbaric oxygen therapy.
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PMID:Barotrauma. 1503 70

In recent years, VIP/PACAP/secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP(1)), GLP(2), gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous system (CNS) and in various peripheral tissues. The family members that are released into blood from periphery, especially gut, circulate the brain and they can cross the blood brain barrier. On the other hand, some of the members of this family that present in the brain, can cross from brain to blood and reach the peripheral targets. VIP, secretin, GLP(1), and PACAP 27 are transported into the brain by transmembrane diffusion, a non-saturable mechanism. However, uptake of PACAP 38 into the brain is saturable mechanism. While there is no report for the passage of GIP, GLP(2), and PHM, there is only one report that shows, glucagon and GHRH can cross the BBB. The passage of VIP/PACAP/secretin family members opens up new horizon for understanding of CNS effects of peripherally administrated peptides. There is much hope that those peptides may prove to be useful in the treatment of serious neurological diseases such as Alzheimer's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS related neuropathy, diabetic neuropathy, autism, stroke and nerve injury. Their benefits in various pathophysiologic conditions undoubtly motivate the development of a novel drug design for future therapeutics.
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PMID:Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. 1513 84

Celiac disease is associated with a diversity of central nervous system manifestations although an association with stroke has not been documented. This case report describes a child who presented with a recurrent transient hemiplegia. Magnetic resonance imaging of the brain confirmed infarction; transcranial Doppler studies and magnetic resonance angiography were abnormal. Although there were virtually no gastrointestinal symptoms and the child was thriving, celiac disease serology was strongly positive and a duodenal biopsy confirmed the disease. Tissue transglutaminase is the major autoantigen in celiac disease and is thought to maintain vascular endothelial integrity. Antiendomysial immunoglobulin A antibodies, demonstrated to be the same autoantibody as antitransglutaminase, react with cerebral vasculature, suggesting an autoimmune mechanism for celiac disease associated vasculopathy. Because celiac disease is a potentially treatable cause of cerebral vasculopathy, serology-specifically antitissue transglutaminase antibodies-should be included in the evaluation for cryptogenic stroke in childhood, even in the absence of typical gut symptoms.
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PMID:Celiac disease and childhood stroke. 1530 36

Heat stroke is a life-threatening condition that can be fatal if not appropriately managed. Although heat stroke has been recognised as a medical condition for centuries, a universally accepted definition of heat stroke is lacking and the pathology of heat stroke is not fully understood. Information derived from autopsy reports and the clinical presentation of patients with heat stroke indicates that hyperthermia, septicaemia, central nervous system impairment and cardiovascular failure play important roles in the pathology of heat stroke. The current models of heat stroke advocate that heat stroke is triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers the systemic inflammatory response, which can lead to systemic coagulation and haemorrhage, necrosis, cell death and multi-organ failure. However, the current heat stroke models cannot fully explain the discrepancies in high core temperature (Tc) as a trigger of heat stroke within and between individuals. Research on the concept of critical Tc as a limitation to endurance exercise implies that a high Tc may function as a signal to trigger the protective mechanisms against heat stroke. Athletes undergoing a period of intense training are subjected to a variety of immune and gastrointestinal (GI) disturbances. The immune disturbances include the suppression of immune cells and their functions, suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS), suppression of anti-LPS antibodies, increased macrophage activity due to muscle tissue damage, and increased concentration of circulating inflammatory and pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase gut-related LPS translocation. This article discusses the current evidence that supports the argument that these exercise-induced immune and GI disturbances may contribute to the development of endotoxaemia and heat stroke. When endotoxaemia can be tolerated or prevented, continuing exercise and heat exposure will elevate Tc to a higher level (>42 degrees C), where heat stroke may occur through the direct thermal effects of heat on organ tissues and cells. We also discuss the evidence suggesting that heat stroke may occur through endotoxaemia (heat sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary pathway of heat stroke. The existence of these two pathways of heat stroke and the contribution of exercise-induced immune and GI disturbances in the primary pathway of heat stroke are illustrated in the dual pathway model of heat stroke. This model of heat stroke suggests that prolonged intense exercise suppresses anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the pathway of heat stroke.
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PMID:The roles of exercise-induced immune system disturbances in the pathology of heat stroke : the dual pathway model of heat stroke. 1644 10

Due to its high spatial, temporal, and dynamic resolution, noninvasive Doppler ultrasound can be used to determine the distribution of phasic cardiac output in humans. The effects of ageing and various common physical stresses on combined human major central and regional blood flows have not been reported. We tested the hypothesis that there are no significant age-related differences in steady-state human central and regional hemodynamics during leg exercise, hypoxia, eating, and standing. We used noninvasive, image-guided Doppler flowmetry (approximately 7% linearity, approximately 11% accuracy) to measure absolute values and percent changes (%C) in phasic blood flows in the following major arteries: ascending aorta (CO, cardiac output), common carotid (CQ, brain), subclavian (SQ, arm), renal (RQ, kidney), superior mesenteric (MQ, gut), and common femoral (FQ, leg). Mean arm cuff blood pressure (BP), heart rate (HR), stroke volume (SV), and total peripheral resistance (PR) were also determined. We studied 16 young (Y, 24/3 years, 8 males) and 16 elderly (E, 73/2 years, 7 males) healthy, lean adults during separate experiments of: 50% submaximal leg exercise; 12% oxygen breathing; ~700 calorie meal; and 70 degrees upright tilt. Exercise results (X/SD) are given as Y(%C) then E(%C) where (+) represents p<0.05 vs resting, fasting control: HR: 78/8+,66/7+; BP: 6/5,8/6; SV: - 15/5+,21/4+; CO: 96/11+,87/9+; PR: -83/13+,- 76/10+; CQ: 16/8+,14/6+; SQ: -6/8,-12/8; MQ: -21/11+,-15/11; RQ: -14/8/-12/7; FQ: 919/88+,898/74 Importantly, there were no significant (p<0.05) age-related differences in the percentage changes in any of these hemodynamic variables. Similar results were found during hypoxia, eating, and standing. We conclude that although physical stresses significantly (p<0.05) affects various central and regional hemodynamics, there are no significant age-related differences in these variables between healthy, successfully aged, 20 and 70 year old cohorts. These data suggest that given an appropriate genetic template and behavior free of significant trauma and disease states, cardiovascular control mechanisms and the distributions of cardiac output during common, daily, physical stresses are maintained with age through 70 years of life.
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PMID:Doppler ultrasound determination of the distribution of human cardiac output: effects of age and physical stresses. 1727 Oct 98

The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and traditionally used in the treatment of angina pectoris, acute myocardial infarct, hyperlipidemia and stroke in China and other Asian countries. In this study, we have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption of tanshinone IIA (TSA), a major active constituent of Danshen, using several in vitro and in vivo models. The oral bioavailability of TSA was about 2.9-3.4% in rats, with non-linear pharmacokinetics when its dosage increased. In a single pass rat intestinal perfusion model, the permeability coefficients (P(app)) based on TSA disappearance from the luminal perfusates (P(lumen)) were 6.2- to 7.2-fold higher (P < 0.01) than those based on drug appearance in mesenteric venous blood (P(blood)). The P(blood), but not P(lumen), was significantly increased when co-perfused with verapamil, or quinidine (both P-gp inhibitors). The uptake and efflux of TSA in confluent Caco-2 cells were significantly altered in the presence of verapamil, quinidine, MK-571, or probenecid. The transport of TSA across Caco-2 monolayers was pH-, temperature- and ATP-dependent. Furthermore, the transport from the apical (AP) to basolateral (BL) side of the Caco-2 monolayers was 3.3- to 8.5-fold lower than that from the BL to AP side, but such a polarized transport was attenuated by co-incubated verapamil or quinidine. A polarized transport was also observed in the control MDCKII cells and more apparent in MDR1-MDCKII monolayers, with the P(app) values of TSA in the BL-AP direction being 7- to 9-fold higher in MDR1-MDCKII monolayers than those in the control MDCKII cells. Moreover, TSA significantly inhibited P-gp-mediated transport of digoxin in P-gp-overexpressing membrane vesicles with an IC(50) of 2.6 microM, but stimulated vanadate-sensitive P-gp ATPase activity with estimated K(m) and V(max) values of 10.70 +/- 0.69 microM and 67.65 +/- 1.31 nmol/min/mg protein, respectively. TSA was extensively metabolized to tanshinone IIB (TSB), and two other oxidative metabolites in rat liver microsomes, but the formation rate of TSB in rat intestinal microsomes was only about 1/10 of that in liver microsomes. These findings indicate that TSA is a substrate and reversing agent for P-gp; and P-gp-mediated efflux of TSA into the gut lumen and the first-pass metabolism contribute to the low oral bioavailability. Further studies are needed to explore the role of other drug transporters and first-pass metabolism in the low bioavailability of TSA.
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PMID:Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge. 1750 22


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