Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monitoring of ICP from the subarachnoid, intraparenchymal, or ventricular spaces can be accomplished easily and reliably. The risks and benefits of each approach should be considered when choosing the monitoring technique. The goal of ICP management is to prevent herniation and to optimize cerebral perfusion. Even transient episodes of post-traumatic cerebral ischemia due to inadequate CPP can quickly nullify all resuscitative efforts. The provision of sufficient CBF is complicated by the varying degree of disruption of pressure autoregulation commonly resulting from head trauma. Post-injury, there is a need to provide a CPP which is elevated to some extent with respect to that sufficient in uninjured brains. This generally requires a CPP of at least 70 mm Hg, which must be accomplished by maintaining an adequate MAP while controlling ICH. Although ICH can generally be controlled using methods commonly employed, the majority of these techniques have potential complications. Additionally, there is increasing evidence that significant variation exists in the pathologic processes driving ICH in individual patients. Therefore, goals such as the desired CPP and conditions such as the relative contribution of edema, cerebral hypervolemia, and ischemia to ICH should optimally be considered in a patient-specific fashion and allow a targeted approach to therapy.
 ...
PMID:Intracranial pressure. Monitoring and management. 782 72

The possibility of measuring cerebral blood flow by mobile bedside units with the intravenous 133-Xenon technique increased the interest to monitor haemodynamic changes after head injury and subarachnoid haemorrhage in intensive care. Time course of resting CBF after trauma is variable (reduced CBF, hyperemia) and there is no strong correlation to clinical outcome. Additional studies of CBF/CO2 reactivity show normal and impaired CO2 response in the acute stage after trauma (day 1-8). A permanently impaired CO2 reactivity correlates with severe brain damage and bad outcome (GOS 1,2). A normal or improving CO2 reactivity indicates a favourable outcome (GOS 3-5). There was no significant correlation between CBF and ICP, nor between CBF and CPP. A CPP of more than 70 mmHg did not guarantee a sufficient CBF in every case indicating the variability of the limits of autoregulation. As therapeutic hyperventilation may lead to ischemia, mannitol was preferred to reduce ICP and increased low CBF to normal values. This fact should be considered in the treatment of patients with low CBF and normal CO2 reactivity. Delayed ischemic neurological deficits ("vasospasm") are well-known as significant complications of the clinical course following SAH. Immediately postoperatively performed CBF measurements enable to detect ischemia and allow to start early antiischemic therapy. During "vasospasm" CBF showed a better correlation to the neurological status than blood flow velocity in the basal arteries measured by transcranial doppler sonography. Furthermore hyperemia after SAH could only be verified by CBF measurements.
 ...
PMID:Xenon 133--CBF measurements in severe head injury and subarachnoid haemorrhage. 790 78

Glutamate antagonists are the most powerful neuroprotective drugs in laboratory studies of focal cerebral ischemia. Because the majority of clinical conditions in which focal brain ischemia occurs are associated with high intracranial pressure (ICP), we have used the rat acute subdural hematoma model to evaluate the effects of three glutamate N-methyl-D-aspartate antagonists, MK-801, CGS 19755 (SELFOTEL), D-CPP-ene, and mannitol, upon ICP and also upon the volume of ischemic brain damage. Only mannitol produced a significant reduction in ICP and improved cerebral perfusion pressure. The three glutamate antagonists did not significantly affect ICP or cerebral perfusion pressure, but they were associated with a significantly smaller zone of focal brain damage, when compared to the mannitol and saline groups. N-methyl-D-aspartate antagonists do not increase ICP or jeopardize cerebral perfusion pressure when administered under anesthesia with a controlled PaCO2 level. Further studies in humans are indicated.
 ...
PMID:Effect of neuroprotective N-methyl-D-aspartate antagonists on increased intracranial pressure: studies in the rat acute subdural hematoma model. 793 30

In the past, physicians viewed ischemic injury as an irreversible event. Modern science has shown that this view is incorrect and that ischemic neuronal damage is an ongoing, active process that might be amenable to various therapies. Figure 2 illustrates some of the possible sites where these therapies might be active. Pending evidence of their effectiveness, cerebral protection can best be achieved by maintaining adequate CPP and CBF during periods when patients are at risk for cerebral ischemia, restoring perfusion after ischemia occurs, and optimizing the metabolic milieu of the ischemic penumbra.
 ...
PMID:Current concepts in cerebral protection. 813 75

Hemodilution has been shown to increase cerebral blood flow (CBF) and reduce lesion volume in models of occlusive cerebral ischemia, but it has not been evaluated in the setting of head trauma and shock in which ischemia is thought to play a role in the evolution of secondary injury. In a porcine model of brain injury and shock the authors compared hemodilution with diaspirin cross-linked hemoglobin (DCLHb) to a standard resuscitation regimen using Ringer's lactate solution and shed blood. After creation of a cryogenic brain injury followed by hemorrhage, the animals received a bolus of either 4 ml/kg of Ringer's lactate solution (Group 1, six animals) or DCLHb (Group 2, six animals), followed by infusion of Ringer's lactate solution to restore mean arterial pressure (MAP) to baseline. Group 1 received shed blood 1 hour after hemorrhage (R1) in the form of packed red blood cells. Group 2 received shed blood only for an Hb count of less than 5 g/dl. The animals were monitored for 24 hours. At R1, Group 2 had a significantly greater cerebral perfusion pressure ([CPP] 88 +/- 5.7 vs. 68 +/- 2.4 mm Hg, p < 0.05). By 3 hours after hemorrhage (R3) Group 2 had a significantly lower Hb concentration (8.5 +/- 0.4 vs. 12.1 +/- 0.3 g/dl, p < 0.05) and a significantly lower intracranial pressure ([ICP] 9 +/- 0.8 vs. 14 +/- 0.6 mm Hg, p < 0.05). The total 24-hour fluid requirement was significantly less in Group 2 (10,654 +/- 505 ml vs. 15,542 +/- 1094 ml, p < 0.05) There was no difference between the groups regarding levels of regional CBF in the injured hemisphere. Cerebral O2 delivery was not significantly different between groups at any time. Lesion volume as determined at postmortem examination was not significantly different between the groups. The increased MAP and CPP and lower ICP observed in the Group 2 animals indicate that hemodilution with DCLHb may be beneficial in the treatment of head injury and shock.
 ...
PMID:Effect of hemodilution with diaspirin cross-linked hemoglobin on intracranial pressure, cerebral perfusion pressure, and fluid requirements after head injury and shock. 898 91

The neuroprotective effects of drugs that act against excitotoxic damage, caused by glutamate, are well described in focal ischemia, but behavioral effects, and apparent failure in clinical trials of "first-generation" competitive N-methyl D-aspartate (NMDA) antagonists, such as Selfotel (CGS19755), has led to interest in evaluating newer NMDA antagonists with fewer behavioral effects. We have therefore evaluated the neuroprotective effect of a new forebrain-selective polyamine site NMDA antagonist, CP101,606 in a rat subdural hematoma (SDH) model. An SDH was produced by slow injection of 0.4 ml autologous blood into the parietal subdural space. Brain damage was assessed histologically at eight coronal planes, in animals sacrificed 4 h after induction of hematoma. The drug was infused 30 min after induction of SDH. The reductions of ischemic brain damage achieved by CP101,606, was 29% for the low dose and 37% for the high dose. This novel glutamate antagonist has shown a magnitude of neuroprotection which is comparable with that seen with "first-generation" NMDA antagonists such as MK801, D-CPP-ene and CGS19755, in this same model. This new agent is claimed to have fewer psychomotor and behavioral effects than MK801, D-CPP-ene, and CGS19755.
 ...
PMID:The neuroprotective effect of the forebrain-selective NMDA antagonist CP101,606 upon focal ischemic brain damage caused by acute subdural hematoma in the rat. 921 55

Time-related effects of hypothermia on intracranial pressure (ICP), brain (Tbr) and rectal temperature (Tc), cortical (LDF) and subcortical microcirculation (ti-pO2) were assessed following a unilateral balloon induced epidural focal mass lesion in rats. Results of injured but normothermia animals (Group A, n = 6) were compared with hypothermia animals (Group B, n = 6). Parameters were recorded during balloon expansion (BE) to an ICP of 60 mmHg followed by a period of sustained inflation (SI) of 30+/-2 min. Animals in Group B were then cooled to 31.7+/-0.4 degrees C (Tbr) during SI. After reperfusion animals were monitored 178+/-4 min. The study protocol concluded with a rewarming phase of the hypothermic animals. Balloon expansion led to a Cushing response and flattening of the EEG. In both groups Tbr decreased during inflation of the balloon 0.5-0.8 degrees C below Tc and during SI in Group A 1.7 degrees C below Tc. During SI and reperfusion Tbr decreased below Tc in Group A but remained above Tc in Group B (p < 0.003). During sustained inflation LDF decreased in group A to 21% and in Group B to 45% of baseline values. After 178+/-4 min of reperfusion LDF reached 68% of baseline values in Group A and 97% in Group B (p < 0.001). During sustained inflation ti-pO2 showed median values of 0.8 mmHg in Group A and 5.5 mmHg in Group B. After reperfusion ti-pO2 reached normal values in both groups (p < 0.3) but ti-pO2 showed 18% higher values before rewarming. After reperfusion the secondary increase of ICP was reduced (p < 0.006) and CPP was improved by 20% in Group B. EEG restored quicker in Group B than Group A (106+/-11 min vs. 188+/-25 min). Intra-ischemic hypothermia improved cerebral microcirculation, prevented a secondary increase of ICP and improved restoration of EEG after ischemia-reperfusion.
 ...
PMID:Hypothermia influences time course of intracranial pressure, brain temperature, EEG and microcirculation during ischemia-reperfusion. 958 26

The aim of our study was to characterize the temporal relationship of apoptosis to regional myocardial ischemia and reperfusion and we aimed to determine the effect of ischemia and reperfusion on the distribution of the pro-apoptotic cysteine protease caspase-3 (CPP 32, apopain, Yama) in an in vivo rat model. Male Sprague-Dawley rats (250-400 g) were anesthetized with sodium pentobarbital (65 mg/kg, i.p.), the left external carotid artery was isolated to monitor arterial pressure and a left thoracotomy was performed. Regional myocardial ischemia was induced by occluding the left main coronary artery for 45 min. The heart was reperfused for 0, 60, 120 or 180 min. TUNEL staining of formalin-fixed, paraffin-embedded left ventricle, and DNA fragmentation analysis, showed that apoptosis occurred during 45 min of ischemia alone, but further developed during the 3-h reperfusion period. Immunohistochemical analysis of ischemic/reperfused left ventricle showed caspase-3 levels were substantially elevated and localized in the ischemic/reperfused region, and that caspase-3 co-localized to TUNEL positive myocytes. Therefore, regional myocardial ischemia serves as a stimulus for myocyte apoptosis, and this form of cell death progresses time-dependently after the onset of reperfusion. Our studies implicate caspase-3 to be involved in apoptotic cell death in ischemic/reperfused rat heart.
 ...
PMID:Co-localization of the cysteine protease caspase-3 with apoptotic myocytes after in vivo myocardial ischemia and reperfusion in the rat. 960 22

The ability of hexarelin, a recently synthesized hexapeptide with a strong growth hormone (GH)-releasing activity, or of GH itself to display a protectant activity against postischemic ventricular dysfunction in senescent hearts was studied in 24-month-old male rats. Heart preparations from control (saline-treated) senescent rats, subjected to moderate ischemia, showed at reperfusion: (a) a low recovery of postischemic left ventricular developed pressure (LVDP; 37% of the preischemic values; from 90 +/- 5.7 to 33.5 +/- 3.8 mm Hg; p < 0.01; n = 10) coupled to a substantial increase in coronary perfusion pressure (CPP; 71% over baseline; from 68.3 +/- 5.2 to 116.8 +/- 4.6 mm Hg; p < 0.01; n = 10); (b) a marked increase of creatine kinase (CK) released in the perfusates (6.6-fold increase over preischemic values; from 45 +/- 4 to 298 +/- 25 mU/min/g wet tissue; p < 0.001; n = 10). In vivo administration of hexarelin (80 microg/kg, b.i.d., s.c.) for 21 days resulted in a striking heart protection against reperfusion stunning. In fact, the recovery of LVDP at reperfusion was almost complete (90% of the preischemic values; from 93 +/- 5.8 to 83.7 +/- 5.9 mm Hg; p > 0.05; n = 9), and the increase in coronary resistance was minimal (from 67 +/- 5.8 to 79.7 +/- 6.9 mm Hg; p > 0.05; n = 9). Furthermore, the concentration of CK in the perfusates was increased only twofold (from 45.8 +/- 5.5 to 90 +/- 7.2 mU/min/g wet tissue; p < 0.05; n = 9), with a gradual return toward basal values at the end of reperfusion. The protectant activity of hexarelin was divorced from any detectable alteration of the somatotropic function, as assessed by pituitary GH messenger RNA (mRNA) and plasma insulin-like growth factor I levels. In vivo administration of GH (400 microg/kg b.i.d., s.c.) for the same time lapse resulted in only a partial protectant activity: 55% of LVDP recovery (from 91.5 +/- 6.2 to 50 +/- 3.5 mm Hg; p < 0.01; n = 6); 65% increase of coronary resistance (from 68 +/- 4.3 to 112.2 +/- 5.2 mm Hg; p < 0.01; n = 6); 5.3-fold increase of CK concentrations in heart perfusates on reperfusion (from 43.8 +/- 3.8 to 232 +/- 16 mU/min/g wet tissue; p < 0.001; n = 6). Evaluation of the rate of release of 6-keto-prostaglandin F1alpha (PGF1alpha), the stable metabolite of prostacyclin, in heart perfusates, and assessment of the vasopressor activity of angiotensin II on the coronary vasculature, did not show any change in these parameters among the three experimental groups. Collectively these data indicate that hexarelin displays a strong heart-protectant activity against myocardial stunning in senescent rats. The protection afforded by the peptide is likely due to a direct cardiotropic action and is far greater than that of GH. Neither compound appears able to interfere with the endothelium-dependent relaxant mechanism.
 ...
PMID:Protectant activity of hexarelin or growth hormone against postischemic ventricular dysfunction in hearts from aged rats. 970 Sep 88

The injured brain may be damaged by primary impact, secondary injury from secondary damage due to initiation of destructive inflammatory and biochemical cascades by the primary injury or secondary ischemic injury following secondary insults that initiate or augment these immunological and biochemical cascades. Cerebral ischemia will arise whenever delivery of oxygen and substrates to the brain fall below metabolic needs. Many factors lead to the development of secondary insults to the injured brain during initial resuscitation, transport, surgery, and subsequent intensive care. Continuous monitoring of cerebral oxygenation (jugular oximetry, brain tissue PO2) and cerebral blood flow velocity (transcranial Doppler ultrasonography) in patients with brain trauma reveals multiple episodes of transient hypoperfusion with an adverse relationship between incidence and outcome. Secondary brain insults arise through systemic or intracranial mechanisms that reduce cerebral blood flow from compromised CPP, vascular distortion or cerebrovascular narrowing or lower oxygen delivery from hypoxemia associated with airway obstruction, pulmonary pathology, or anemia. Secondary brain ischemia remains a common pathway to secondary brain damage in most critically ill neurosurgical patients. In the future prevention of secondary brain injury may well hinge on giving a cocktail of novel agents that modify destructive biochemical and inflammatory pathways, each having a potential therapeutic window possibly in a subgroup of patients. To date, phase 3 clinical trials of several agents including PEGSOD and tyrilizad mesylate have failed to show relevant efficacy after brain trauma or subarachnoid hemorrhage. The therapeutic role of calcium channel blockers in traumatic subarachnoid hemorrhage is currently under investigation following the results of subgroup metaanalysis. Several phase 3, NMDA receptor antagonist studies are underway in brain trauma with results expected soon. Although we know that secondary insults promote excitotoxic secondary brain damage there is currently no pharmacological intervention with proven efficacy and, therefore, detection and correction of secondary insults appear to offer the best therapeutic strategy. After brain trauma, systemic hypotension, compromised CPP, raised ICP, elevated temperature, hypoxemia, and jugular bulb venous desaturation are associated with poor prognosis. Clinical trials of moderate hypothermia following brain trauma are ongoing. Following adult brain trauma maintenance of CPP above at least 65 mmHg (probably > 40 mmHg in children below 8 years) seems important to improve outcome indicating the need for continuous ICP monitoring during intensive care of brain-injured patients.
 ...
PMID:Mechanisms and prevention of secondary brain damage during intensive care. 970 38


<< Previous 1 2 3 4 Next >>