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

The aim of this study was to demonstrate the macrovascular disease in streptozotocin-induced diabetic rats and assess any possible differences between the histopatholological changes of the coronaries and cerebral arteries. Hearts and brains were obtained after 4 weeks (short-term experimental diabetes, 10 rats) and 12 weeks (long-term experimental diabetes, 10 rats) of streptozotocin injection. Sham injected, control rats were studied in parallel. Muscular-type arteries of 0.10-0.15 mm were examined and semiquantitatively classified either as normal, or slightly, or moderately, or severely thickened by light microscopy: While the arterial wall appeared normal in all sham-injected rats, a varying degree of hyperplasia of the muscular layer and deposition of fibrinoid material resulting in arterial stenosis was prominent in streptozotocin-injected rats. In the group of short-term diabetes there was a slight thickening of the cerebral arteries in the majority of the rats (8/10 rats), while thickening of the coronaries was moderate (9/10 rats). Further progression of arterial wall thickening in both cerebral and coronary arteries was observed in the long-term diabetic group. The mean severity of lesions was significantly higher in the coronaries than in cerebral arteries, both in the short-term (p < 0.0005) and long-term diabetes (p < 0.02). Moreover, by paired statistics within individual animals, we confirmed that wall thickening was significantly more severe in coronaries than cerebral arteries in both groups. These findings suggest an accelerated progress of macrovascular disease in the heart as compared to the brain in the streptozotocin-induced diabetic rat. Although histopathological changes in humans do not always mirror clinical severity, the differences in the macrovascular disease between heart and brain in experimental diabetes may be relevant to the higher relative risk of myocardial infarction compared to stroke for people with diabetes, as compared to people without diabetes.
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PMID:Macrovascular disease of coronaries and cerebral arteries in streptozotocin-induced diabetic rats. A controlled, comparative study. 951 57

In human heart transplantation limited myocardial ischemia duration remains one of the most restricting factors. A new approach towards prolongation of this duration is the combination of cardioplegic arrest and continuous Coronary Oxygen Persufflation (COP) with gaseous oxygen. This technique, which is based on former experiments, was applied in pig hearts which we transplanted orthotopically after a hypothermic preservation time of 14 hours. For cardioplegic arrest we used either Euro-Flush glutathion solution (EFG; n=5), University of Wisconsin solution (UW; n=5), modified Bretschneider HTK cardioplegic solution (mHTK; n=6). In preliminary experiments all three solutions had shown equal cardioprotective qualities. Hearts of the mHTK group were submitted to continuous COP during storage (mHTK+COP). After 14 hours of preservation and orthotopic transplantation the mHTK+COP hearts showed significantly improved cardiac functional recovery compared to hearts preserved by simple cold storage techniques. Hemodynamics measured after 3 hours reperfusion were significantly better in the mHTK+COP group compared to EFG and UW: dp/dtmax in % of baseline+/-standard deviation (SD): 85+/-22, 65+/-26, 36+/-15, CO in % of baseline: 68+/-13, 35+/-8, 39+/-8. Postoperative preload recruitable stroke work in the mHTK+COP hearts was: 51.4+/-23.1 mmHg compared to preoperative: 57.3+/-17.2. ATP of left-ventricular myocardium in the mHTK+COP group: 14.7+2.1 micromol/g dry weight was significantly higher compared to EFG: 10.3+/-4.5 and UW: 5.9+/-3.2. CK-MB in percent of CK in all groups showed no increase during postoperative reperfusion. This study suggests that COP may present an effective complement to cold storage techniques currently used in heart transplantation. Prior to clinical application further investigations regarding long-term survival and endothelial function are required.
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PMID:Coronary oxygen persufflation for long-term myocardial protection. 982 85

Troglitazone is a thiazolidinedione used for the treatment of NIDDM and potentially for other insulin-resistant disease states. Troglitazone has recently been shown to increase cardiac output and stroke volume in human subjects. These actions are thought to be mediated by the reduction of peripheral resistance, but a potential direct effect on cardiac function has not been studied. Therefore, we investigated the direct cardiac hemodynamic effects of troglitazone in isolated perfused rat hearts. Five groups of hearts were studied. Hearts were tested under isovolumetric contraction with a constant coronary flow, and troglitazone (0.2, 0.5, and 1.0 micromol) was administered by bolus injection. Peak isovolumetric left ventricular pressure (LVPmax), peak rate of rise of LVP (dP/dt(max)), and peak rate of fall of LVP (dP/dt(min)) were significantly increased 1 min after troglitazone administration in a dose-dependent manner, while the heart rate (HR) and coronary perfusion pressure (CPP) were significantly decreased (P < 0.05). HR was then fixed by pacing and/or CPP was fixed with nitroprusside to eliminate any effect of the two variables on the action of troglitazone. With constant HR and/or constant CPP, the effect of troglitazone on LVPmax, dP/dt(max), and dP/dt(min) was still unchanged. In addition, the positive inotropic, positive lusitropic, and negative chronotropic actions of troglitazone were not influenced even when hearts were pretreated with prazosin, propranolol, or nifedipine. In conclusion, troglitazone has direct positive inotropic, positive lusitropic, negative chronotropic, and coronary artery dilating effects. The inotropic and chronotropic actions of troglitazone are not mediated via adrenergic receptors or calcium channels. These findings have important clinical implications for diabetic patients with congestive heart failure.
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PMID:Hemodynamic basis for the acute cardiac effects of troglitazone in isolated perfused rat hearts. 1007 64

Electrical pacing at physiological rate induces myocardial remodeling associated with regional changes in workload, blood flow and oxygen consumption. However, to what extent energy-producing pathways are also modified within the paced heart remains to be investigated. Pacing could particularly affect glycogen metabolism since hypertrophy stimulates glycolysis and increased workload favors glucose over fat oxidation. In order to test this hypothesis, we used the embryonic chick heart model in which ventricular pacing rapidly resulted in thinning of the ventricle wall and thickening of the atrial wall. Hearts of stage 22HH chick embryos were submitted in ovo to asynchronous and intermittent ventricular pacing delivered at physiological rate during 24 h. The resulting alterations of glycogen content were determined in atrium, ventricle and conotruncus of paced and sham-operated hearts. Hemodynamic parameters of the paced and spontaneously beating hearts were derived from computerized image analysis of video recordings. With respect to sham, paced hearts showed a significant decrease in glycogen content (nmoles glucose units/microg protein; mean+/-S.D.) only in atrium (1.48+/-0.40 v 0.84+/-0.34, n=8) and conotruncus (0.75+/-0.28 v 0.42+/-0.23, n=8). Pacing decreased the end diastolic and stroke volumes by 34 and 44%, respectively. Thus, the rapid glycogen depletion in regions remote from the stimulation site appears to be associated with regional changes in workload and remodeling. These findings underscore the importance of the coupling mechanisms between metabolic pathways and myocardial remodeling in the ectopically paced heart.
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PMID:Pacing redistributes glycogen within the developing myocardium. 1118 Oct 19

Studies with mammals and birds clearly demonstrate that brief preexposure to oxygen deprivation can protect the myocardium from damage normally associated with a subsequent prolonged hypoxic/ischemic episode. However, is not known whether this potent mechanism of myocardial protection, termed preconditioning, exists in other vertebrates including fishes. In this study, we used an in situ trout (Oncorhynchus mykiss) working heart preparation at 10 degrees C to examine whether prior exposure to 5 min of anoxia (PO(2) < or = 5 mmHg) could reduce or eliminate the myocardial dysfunction that normally follows 15 min of anoxic exposure. Hearts were exposed either to a control treatment (oxygenated perfusion) or to one of three anoxic treatments: 1) anoxia with low P(out) [15 min of anoxia at an output pressure (P(out)) of 10 cmH(2)O]; 2) anoxia with high P(out) [10 min of anoxia at a P(out) of 10 cmH(2)O, followed by 5 min of anoxia at P(out) = 50 cmH(2)O]; and 3) preconditioning [5 min of anoxia at P(out) = 10 cmH(2)O, followed after 20 min of oxygenated perfusion by the protocol described for the anoxia with high P(out) group]. Changes in maximum cardiac function, measured before and after anoxic exposure, were used to assess myocardial damage. Maximum cardiac performance of the control group was unaffected by the experimental protocol, whereas 15 min of anoxia at low P(out) decreased maximum stroke volume (V(s max)) by 15% and maximum cardiac output (Q(max)) by 23%. When the anoxic workload was increased by raising P(out) to 50 cmH(2)O, these parameters were decreased further (by 23 and 38%, respectively). Preconditioning with anoxia completely prevented the reductions in V(s max) and Q(max) that were observed in the anoxia with high P(out) group and any anoxia-related increases in the input pressure (P(in)) required to maintain resting Q (16 ml. min(-1). kg(-1)). Myocardial levels of glycogen and lactate were not affected by any of the experimental treatments; however, lactate efflux was sevenfold higher in the preconditioned hearts. These data strongly suggest that 1) a preconditioning-like mechanism exists in the rainbow trout heart, 2) increased anaerobic glycolysis, fueled by exogenous glucose, was associated with anoxic preconditioning, and 3) preconditioning represents a fundamental mechanism of cardioprotection that appeared early in the evolution of vertebrates.
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PMID:Recovery of trout myocardial function following anoxia: preconditioning in a non-mammalian model. 1170 58

One possible way to expand the human heart donor pool is to include non-heart-beating human donors. To begin validating this approach, we developed an ex vivo cardiac perfusion circuit to support large mammalian hearts in Langendorff mode and beating-ejecting mode and to assess and improve their ischemic tolerance. In vivo hemodynamic data and heparinized blood (4.0 +/- 0.5 L) were collected from 6 anesthetized pigs. Hearts were isolated and connected to a recirculating perfusion circuit primed with autologous buffered blood (pH, 7.40). After retrograde aortic perfusion in Langendorff mode, the left atrium was gravity-filled at 10-20 mmHg, and the left ventricle began to eject against a compliance chamber in series with a systemic reservoir set to a hydraulic afterload of 100-120 mmHg. Left ventricular function was restored and maintained in all 6 hearts for 30 min. Cardiac output, myocardial oxygen consumption, stroke work, aortic pressure, left atrial pressure, and heart rate were measured. The mean myocardial oxygen consumption was 4.8 +/- 2.7 mL/min/100 g (95.8% of in vivo value); and mean stroke work, 5.3 +/- 1.1 g x m/100 g (58.95% of in vivo value). One resuscitated heart was exposed to 30 min of normothermic ischemic arrest, then flushed with Celsior and re-resuscitated. The ex vivo perfusion method described herein restored left ventricular ejection function and allowed assessment of ischemic tolerance in large mammalian hearts, potentially a 1st step toward including non-heart-beating human donors in the human donor pool.
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PMID:Ex vivo resuscitation of adult pig hearts. 1280 53

Reducing disability and dependency after a stroke is an important clinical objective. We examine what is known about the use of dexamphetamine in patients recovering from an acute stroke, and consider whether further clinical studies should be undertaken. Dexamphetamine has repeatedly been shown to enhance recovery after experimental brain injury in animals, the best effects being seen when dexamphetamine is combined with lesion-specific motor training or sensory stimulation. Postulated mechanisms for these beneficial effects in animals are in keeping with contemporary theories of neurophysiological rehabilitation in man. There have been few clinical studies of dexamphetamine during rehabilitation after an acute stroke. Four controlled trials demonstrated a tendency to an improved outcome when dexamphetamine was paired with therapy and administered 3-30 days after an ischaemic stroke. However, clinical studies to date have been small, included only highly selected patients, and have not addressed possible confounding effects of the drug on mood and untreated depression. Dexamphetamine has previously been used under supervision in medically ill patients and appears to be safe and well-tolerated. There is a need for well-designed studies to assess further the safety and efficacy of dexamphetamine in rehabilitation after stroke.
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PMID:Dexamphetamine treatment in stroke. 1292 23

In humans, cytoskeletal dystrophin and muscle LIM protein (MLP) gene mutations can cause dilated cardiomyopathy, yet these mutations may have different effects in mice, owing to increased accumulation of other, compensatory cytoskeletal proteins. Consequently, we characterized left-ventricular (LV) morphology and function in vivo using high-resolution cine-magnetic resonance imaging (MRI) in 2- to 3-month old dystrophin-deficient (mdx) and MLP-null mice, and their respective controls. LV passive stiffness was assessed in isolated, perfused hearts, and cytoskeletal protein levels were determined using Western blot analyses. In mdx mouse hearts, LV-to-body weight ratio, cavity volume, ejection fraction, stroke volume, and cardiac output were normal. However, MLP-null mouse hearts had 1.2-fold higher LV-to-body weight ratios (P<0.01), 1.5-fold higher end-diastolic volumes (P<0.01), and decreased ejection fraction compared with controls (25% vs. 66%, respectively, P<0.01), indicating dilated cardiomyopathy and heart failure. In both models, isolated, perfused heart end-diastolic pressure-volume relationships and passive left-ventricular stiffness were normal. Hearts from both models accumulated desmin and beta-tubulin, mdx mouse hearts accumulated utrophin and MLP, and MLP-null mouse hearts accumulated dystrophin and syncoilin. Although the increase in MLP and utrophin in the mdx mouse heart was able to compensate for the loss of dystrophin, accumulation of desmin, syncoilin and dystrophin were unable to compensate for the loss of MLP, resulting in heart failure.
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PMID:Dystrophin- and MLP-deficient mouse hearts: marked differences in morphology and function, but similar accumulation of cytoskeletal proteins. 1549 47

Impairment of language function (aphasia) is one of the most common neurological symptoms after stroke. Approximately one in every three patients who have an acute stroke will suffer from aphasia. The estimated incidence and prevalence of stroke in Western Europe is 140 and 800 per 100,000 of the population. Aphasia often results in significant disability and handicap. It is a major obstacle for patients to live independently in the community. When recovery from aphasia occurs, it is usually incomplete and patients are rarely able to return to full employment and other social activities. Currently, the main treatment for aphasia is conventional speech and language therapy. However, the effectiveness of this intervention has not been conclusively demonstrated and empirical observations suggest that spontaneous biological recovery may explain most of the improvement in language function that occurs in aphasics. The generally poor prognosis of the severe forms of poststroke language impairment (Broca, Wernicke and global aphasia), coupled with the limited effectiveness of conventional speech and language therapy has stimulated the search for other treatments that may be used in conjunction with speech and language therapy, including the use of various drugs. Dopamine agonists, piracetam (Nootropil), amphetamines, and more recently donepezil (Aricept), have been used in the treatment of aphasia in both the acute and chronic phase. The justification for the use of drugs in the treatment of aphasia is based on two types of evidence. Some drugs, such as dextroamphetamine (Dexedrine), improve attention span and enhance learning and memory. Learning is an essential mechanism for the acquisition of new motor and cognitive skills, and hence, for recovery from aphasia. Second, laboratory and clinical data suggest that drug treatment may partially restore the metabolic function in the ischemic zone that surrounds the brain lesion and also has a neuroprotective effect following acute brain damage. An example of this is the nootropic agent piracetam. Extensive animal studies have demonstrated the beneficial effects of this and other drugs on neural plasticity, but data on humans are still sparse. This review provides a critical analysis of the current evidence of the effectiveness of these drugs in the treatment of acute and chronic aphasia.
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PMID:Drug treatment of poststroke aphasia. 1585 62

Ranolazine is an inhibitor of the late sodium current and, via this mechanism, decreases sodium-dependent intracellular calcium overload during ischemia and reperfusion. Ranolazine reduces angina, but there is little information on its effects in acute myocardial infarction. The aim of this study was to test the effects of ranolazine on left ventricular (LV) function and myocardial infarct size after ischemia/reperfusion in rabbits. Ten minutes before coronary artery occlusion (CAO), anesthetized rabbits were assigned to vehicle (n=15) or ranolazine (2 mg/kg i.v. bolus plus 60 microg/kg/min i.v. infusion; n=15). Hearts received 60 min of CAO and 3 h of reperfusion. CAO caused LV dysfunction associated with necrosis. However, at the end of reperfusion, rabbits treated with ranolazine had better global LV ejection fraction (0.42+/-0.02 versus 0.33+/-0.02; p<0.007) and stroke volume (1.05+/-0.08 versus 0.78+/-0.07 ml; p<0.01) compared with vehicle. The fraction of the LV wall that was akinetic or dyskinetic was significantly less in the ranolazine group at 0.23+/-0.03 versus 0.34+/-0.03 in vehicle-treated group; p<0.02. The ischemic risk region was similar in both groups; however, infarct size was significantly smaller in the treated group (44+/-5 versus 57+/-4% vehicle; p<0.04). There were no significant differences among groups in heart rate, arterial pressure, LV end-diastolic pressure, or maximum-positive or -negative first time derivative of LV pressure (dP/dt). In conclusion, the results of this study show that ranolazine provides protection during acute myocardial infarction in this rabbit model of ischemia/reperfusion. Ranolazine treatment led to better ejection fraction, stroke volume and less wall motion abnormality after reperfusion, and less myocardial necrosis.
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PMID:Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel. 1661 68


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