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

The direct effects of cocaine on myocardial contractility and isovolumetric relaxation were investigated in conscious dogs (n = 8) chronically instrumented for measurement of hemodynamics, including left ventricular pressure (LVP) and subendocardial segment length. Experiments were performed in the presence of pharmacologic blockade of beta-adrenergic, cholinergic, and ganglionic receptors because cocaine indirectly produces significant alterations in systemic hemodynamics through central and peripheral sympathomimetic actions. Myocardial contractility was quantitated using the preload recruitable stroke work (PRSW) versus end-diastolic segment length (EDL) relationship. LVP-segment length loops were generated in the unsedated control state and after cocaine administration with use of preload reduction by abrupt inferior vena caval constriction, and PRSW versus EDL slope (Mw) and length intercept (Lw) were calculated. In addition, regional preload recruitable work area (PRWA) and stroke work at constant EDL (SWEDL) were also determined. Ventricular relaxation was assessed using a time constant of isovolumetric relaxation assuming a nonzero asymptote of LVP decay. Systemic hemodynamics, myocardial contractility, and isovolumetric relaxation were recorded and calculated before and 1, 3, 5, and 10 min after cocaine administration (2 mg/kg intravenously, i.v.). Mw was significantly (p less than 0.05) reduced by cocaine (63 +/- 8 during control to 45 +/- 8 mm Hg at 1 min after drug administration). PRWA also reflected significant decreases in myocardial contractility after cocaine administration (1,800 +/- 260 during control to 1,200 +/- 220 mm Hg.mm2 at 1 min after drug administration). Similar results were observed with SWEDL (469 +/- 60 during control to 317 +/- 52 mm Hg.mm at 1 min after cocaine administration). All three indexes of contractile state demonstrated complete recovery of contractile function by 10 min after cocaine administration. The time constant of isovolumetric relaxation was prolonged by cocaine (35 +/- 2 during control to 46 +/- 3 ms at 3 min after drug administration), indicating impairment of diastolic function. Ventricular relaxation returned to control levels within 5 min after cocaine administration. No cocaine-induced alterations in coronary blood flow (CBF) or changes in calculated pressure work index (PWI, an indicator of myocardial O2 consumption) were observed. The present results suggest that cocaine produces direct negative inotropic and lusitropic effects independent of changes in myocardial O2 supply and demand and autonomic nervous system activity in conscious chronically instrumented dogs.
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PMID:Cocaine depresses myocardial contractility and prolongs isovolumetric relaxation in conscious dogs with partial autonomic nervous system blockade. 138 28

We examined the effects of levosimendan, a new myofilament Ca2+ sensitizer with phosphodiesterase (PDE)-inhibiting properties, on systemic and coronary hemodynamics and left ventricular (LV) systolic and diastolic function in conscious dogs with intact and blocked autonomic nervous system (ANS) reflexes. Twenty experiments were conducted in 10 dogs chronically instrumented for measurement of aortic and LV pressure, the peak rate of increase and decrease in LV pressure (+dP/dtmax and -dP/dtmin), subendocardial segment length, diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated by -dP/dtmin, a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity during rapid ventricular filling (dL/dtmax), and a regional chamber stiffness constant (Kp). Dogs were randomly assigned to receive levosimendan (0.5, 1.0, 2.0, and 4.0 micrograms.kg-1.min-1) with or without ANS blockade. On separate experimental days, systemic and coronary hemodynamics and LV pressure-segment length diagrams and waveforms were recorded after 10-min equilibration at each dose in the conscious ANS-intact or ANS-blocked state. Levosimendan increased heart rate (HR), CO, mean and diastolic CBF velocity, and pressure-work index (PWI, an estimate of myocardial oxygen consumption) and decreased LV end-diastolic pressure (EDP), systemic vascular resistance (SVR), end-systolic and end-diastolic segment length, and mean and diastolic coronary vascular resistance (CVR) in dogs with intact ANS function. Levosimendan-induced increases in HR and PWI and decreases in SVR were attenuated by ANS blockade. Levosimendan caused equivalent dose-dependent increases in Mw in ANS-intact and ANS-blocked dogs, consistent with a positive inotropic effect independent of ANS activity. Levosimendan decreased tau (e.g., 35 +/- 1 ms during control to 29 +/- 1 ms at the high dose) and increased the magnitude of LV -dP/dtmin in dogs with intact but not blocked ANS reflexes, suggesting that relaxation was enhanced by favorable changes in systemic hemodynamics or ANS activation and direct effects of this drug on lusitropic state. Levosimendan also increased dL/dtmax to a greater degree in ANS-intact dogs, indicating that improvement of rapid ventricular filling was also partially dependent on ANS tone. No changes in Kp were observed in either experimental group. The results indicate that levosimendan decreases preload and afterload and has positive inotropic and lusitropic properties. The actions of levosimendan on diastolic function are largely mediated by the ANS.
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PMID:Systemic and coronary hemodynamic actions and left ventricular functional effects of levosimendan in conscious dogs. 747 41

The cardiovascular and left ventricular (LV) functional effects of levosimendan were examined (LSM; 0.5, 1.0, 2.0 and 4.0 micrograms.kg-1.min-1) in conscious, chronically instrumented dogs (n = 8) in the presence and absence of heart rate control with zatebradine (ZAT) or ZAT alone (0.25, 0.5 and 1.0 mg.kg-1). LSM increased heart rate (HR) cardiac output (CO), diastolic coronary blood flow velocity (DCBFV) and pressure-work index (PWI; calculated myocardial oxygen consumption) and decreased mean arterial, LV systolic and end-diastolic pressures, systemic vascular resistance and diastolic coronary vascular resistance (DCVR). ZAT alone decreased HR and PWI and increased stroke volume. LSM-induced increases in HR and PWI were attenuated by ZAT. Increases in DCBFV and decreases in DCVR occurred without changes in PWI in the presence of ZAT. LSM increased preload recruitable stroke work slope (Mw, 68 +/- 6 to 159 +/- 13 mm Hg) and +dP/dt. These positive inotropic effects were partially attenuated by ZAT. LSM alone decreased the time constant of isovolumic relaxation (tau, 36 +/- 2 to 29 +/- 2 ms). LSM-induced decreases in tau were blunted by ZAT, indicating that changes in tau were partially dependent on heart rate. LSM increased the maximal rate of segment lengthening to a similar degree in ZAT-treated versus -untreated dogs. ZAT alone had minimal effects on LV function. Control of LSM-induced tachycardia with ZAT decreases myocardial oxygen consumption but also partially attenuates the positive inotropic and lusitropic effects of LSM.
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PMID:Zatebradine, a specific bradycardic agent, alters the hemodynamic and left ventricular mechanical actions of levosimendan, a new myofilament calcium sensitizer, in conscious dogs. 756 40

We examined and compared the effects of levosimendan, a new myofilament calcium sensitizer with phosphodiesterase inhibiting activity, pimobendan, and milrinone on left ventricular-arterial coupling and mechanical efficiency in 21 experiments performed in open-chest, barbiturate-anesthetized dogs instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), +dP/dt, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of differentially loaded LV pressure-volume diagrams. LV-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. Levosimendan (0.75, 1.5, and 3.0 micrograms.kg-1.min-1) significantly (p < 0.05) increased heart rate, +dP/dt, and ejection fraction (EF) and decreased mean arterial pressure (MAP), pressure-work index (PWI; an estimate of myocardial-oxygen consumption), and LV systolic and end-diastolic pressures (LVSP and LVEDP) and volumes (EDV and ESV). Levosimendan-induced augmentation of myocardial contractility (Ees, Msw and +dP/dt) and reductions in LV afterload (Ea) caused increases in the Ees/Ea ratio (0.61 +/- 0.10 during control to 3.3 +/- 0.7 during the high dose) consistent with enhancement of LV-arterial coupling. Levosimendan increased SW/PVA (0.48 +/- 0.05 during control to 0.84 +/- 0.04 during the high dose), indicating this drug improves the transfer of myocardial potential energy to external work. Levosimendan also increased the ratio of SW to PWI (109 +/- 18 during control to 255 +/- 50 mmHg.min.100g during the high dose), suggesting that myocardial metabolic efficiency was improved as well. Like levosimendan, pimobendan and milrinone (10, 20, and 40 and 1.0, 2.0, and 4.0 micrograms.kg-1.min-1, respectively) increased HR, +dP/dt, EF, Ees, and Msw and decreased MAP, LVSP, LVEDP, EDV, ESV, and Ea. In contrast to levosimendan, neither agent reduced PWI. Pimobendan and milrinone caused dose-related increases in Ees/Ea, SW/PVA, and SW/PWI. The results indicate that levosimendan, pimobendan, and milrinone augment myocardial contractility, produce venous and arteriolar vasodilation, and enhance LV-arterial coupling and mechanical efficiency in open-chest, barbiturate-anesthetized dogs.
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PMID:Comparison of the effects of levosimendan, pimobendan, and milrinone on canine left ventricular-arterial coupling and mechanical efficiency. 887 79

Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2 (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). Diffusion-weighted imaging, T2WI, and PWI were performed before, during, and after embolization from 1 hour to 7 days. After embolization in both rt-PA-treated and control animals, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) in the ischemic region significantly declined from the preischemic control values (P < 0.001). However, mean CBF and ADCw in the rt-PA-treated group was elevated early after administration of rt-PA compared with the untreated control group, and significant differences between the two groups were detected in CBF (24 hours after embolization, P < 0.05) and ADCw (3, 4, and 24 hours after embolization, P < 0.05). T2 values maximized at 24 (control group, P < 0.001) or 48 hours (treated group, P < 0.01) after embolization. The increase in T2 in the control group was significantly higher at 24 hours and 168 hours than in the rt-PA-treated group (P < 0.05). Significant correlations (r > or = 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADCw obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADCw and T2 data maps, indicated a significant reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADCw obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the increase of T2, and a reduction of the ischemic lesion size measured using MRI cluster analysis.
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PMID:Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of middle cerebral artery embolic stroke and recombinant tissue plasminogen activator intervention in the rat. 966 6

Combined NMR imaging and spectroscopy have been applied to mouse brain during focal cerebral ischemia. The present study evaluated the feasibility of NMR measurements on mice in order to fine-tune the sequences and experimental setup for systematic investigations on stroke including future studies on transgenic animals. The acquisition of high quality diffusion-weighted, perfusion-weighted, and T2-weighted images (DWI, PWI, T2-WI, respectively) is demonstrated and complemented by measurements of 1H volume-selective spectroscopy and spectroscopic imaging (SI). Despite the small volume of the mouse brain, a satisfactory signal-to-noise ratio can be achieved with reasonably short measurement times. C57black/6J mice with an average body weight of 25 g were studied using state-of-the-art NMR sequences at 4.7 T. After induction of focal cerebral ischemia, the lesion was found clearly distinguishable in all imaging techniques. The apparent diffusion coefficient (ADC) was reduced in the ischemic region, and an expansion of the affected volume was observed with ongoing ischemia time. In the H spectra of ischemic animals a distinct change in the concentrations of NAA and lactate was visible. This is the first report on both SI data and perfusion-weighted imaging on mouse brain. It is demonstrated that the perfusion deficit during ischemia can be well demarcated. The spatial resolution of changes in metabolite concentrations allows the clear differentiation of elevated lactate levels in ischemic brain tissue.
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PMID:High resolution MRI and MRS: a feasibility study for the investigation of focal cerebral ischemia in mice. 1022 85

A prospective longitudinal diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia-induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.
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PMID:Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: evolution of lesion volume and correlation with clinical outcome. 1051 90

The aim of this study was to evaluate the differences in cerebral perfusion seen on mean transit time (MTT) and cerebral blood volume (CBV) maps and to assess the subsequent prognostic value of the MTT-DWI (diffusion-weighted MRI) and CBV-DWI mismatch in the first three days of stroke on lesion enlargement and clinical outcome. In 38 patients, imaged 1-46 h after onset of symptoms, lesion volumes on proton-density (PD)-weighted MRI, DWI and PWI (both MTT and CBV maps) were compared with lesion volumes on follow-up PD-weighted scans, and to clinical outcome (National Institutes of Health Stroke Scale, Barthel index, and Rankin scale). The MTT-CBV, MTT-DWI and CBV-DWI mismatches were compared with change in lesion volume between initial and follow-up PD-weighted scans. Lesion volume on both DWI and PWI correlated significantly with clinical outcome parameters (p < 0.001) with strongest correlation for lesion volume on CBV. Perfusion-diffusion mismatches were found for both CBV and MTT and correlated significantly with lesion enlargement on PDweighted imaging with strongest correlation for the CBV-DWI mismatch. The CBV-DWI mismatch has the highest accuracy in predicting lesion size on follow-up imaging and in predicting clinical outcome. Lesion volume measurements on CBV maps have a higher specificity than on PD-weighted, MTT or DWI images in predicting clinical follow-up imaging and in predicting clinical outcome.
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PMID:Prognostic value of perfusion- and diffusion-weighted MR imaging in first 3 days of stroke. 1099 32

The progress in the technical procedures of stenting in the ICA and the growing expertise in this field need primary multidisciplinary efforts for improving both, indication and periinvasive management of stroke patients. From a neurological point of view in the acute stroke there is an indication on the single case basis, only, e.g. in crescendo-TIA and given TEA-indication but without operability given in the patient. Later on, the stenting should be taken into account only after complex neurovascular workup, incl. CMRT with DWI and PWI, interdisciplinary definitive indication and qualified periinvasive management, i.e., apparative monitoring and neurological examination, e.g., on a stroke unit. Some indications emerge from the present expertise: re-stenosis after TEA, radiogenic stenosis, given indication for TEA, but no operability for technical reasons, e.g. distal ICA-stenosis, or class III or IV risk patients. The contraindications remain to be clarified.
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PMID:[Carotid stenting--stratification of the acute phase, indications in secondary prevention from the neurological viewpoint]]. 1114 93

The recent reports confirm the idea that the selection of cerebral stroke patients for thrombolysis should be performed by MRI. These studies suggested that DWI/PWI/MRA may be able to identify patients who are most likely to benefit from thrombolytics, and that the PWI>DWI pattern in particular is associated with an improved outcome from thrombolytic therapy. However, many questions remain unanswered and a lot of work is necessary before MRI guided thrombolysis in acute cerebral stroke becomes a part of the standard care.
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PMID:Actual trends in diagnosis/thrombolytic therapy of acute cerebral stroke. 1128 62


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