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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We can summarize the results of our studies as follows (Fig. 15). The critical cellular factors involved in the loss of reversibility following ischemia appear to be the mechanisms involved in the membrane function of energy transduction. Irreversibility appears to correlate with an irrepairable defect in energy transduction. This could involve both the mitochondrial energy transduction functions and those in the plasma membrane. The mechanisms involved in this transition are not presently clear but they are associated with increased leakiness or permeability of these membranes accompanied by changes in lipid content, alterations in membrane proteins, and presumably in lipid-protein interactions. There are two prominent theories to explain energy transduction. These are the "proton pump" hypothesis of Mitchell (1972) and the "paired moving charge" hypothesis of Blondin and Green (1975). Both of these hypotheses require integrated function of membrane components, i.e., lipid and protein. The hypothesis of Blondin and Green, however, can work even with discontinuous membrane sheets because it involves the concept of ribbons of protein embedded in the protein-lipid membrane matrix. The characteristic finding of our studies following ischemic injury, namely, the continuous electron flow well into the irreversible phase while the energy transduction is impaired, could be explained by both hypotheses. What do these observations have to say about theories of energy conservation? We have observed that the vectorial nature of the proton separation is stopped. Charge separation may not occur at this time across the membrane since proton gradient and possible membrane potential are abolished. Electron transport, however, continues indicating the generation of protons. Since the decline of P/O ratio, decline of proton gradient and the cellular "point-of-no-return" coincide, these observations point toward the important membrane defects acquired at that particular time. The "paired moving charge" model which involves moving ions encapsulated in endogenous ionophores such as lecithin and maintenance of magnesium is favpred by the observation that phosphatidyl choline and phosphatidyl ethanolamine are lost in correlation with irreversibility. Furthermore, the decrease in magnesium content of cells is closely associated with the loss of viability following ischemia. The "paired moving charge" hypothesis has the attractive feature in that it involves antagonistic effects of calcium and magnesium. During reflow, calcium may inhibit magnesium mediated transport of inorganic phosphate by lecithin. Also, according to this theory fatty acids or their cyclic anions which act as uncouplers may foster the loss of phosphorylation capacity.
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PMID:Recent studies on the pathophysiology of ischemic cell injury. 79 Dec 45

The ventrolateral medullary surface (VMS) has been shown to have chemosensitive areas that can alter blood pressure and respiration. It has also been shown that lesions near the VMS can affect the intensity of the cerebral ischemic response (CIR). To determine which regions of the central chemosensitive areas of the ventral medullary surface contribute to the pressor response caused by cerebral ischemia, we used focal cooling of the caudal Loescheke's (CL), intermediate Schlaefke's (IS), and rostral Mitchell's (RM) areas of VMS during ischemia of the brain. Experiments were performed on 17 pentobarbital sodium-anesthetized, paralyzed, and artificially ventilated cats after denervation of the vagi and sinoaortic nerves. Bilateral occlusion of the external carotid and vertebral arteries resulted in a significant increase of arterial pressure (from 129 +/- 4 to 174 +/- 8 mmHg, P less than 0.01) and an increase in splanchnic sympathetic activity. However, heart rate and cervical sympathetic activities were not appreciably affected by cerebral ischemia. Bilateral cooling of the IS area to as low as 10 degrees C led to a decrease or disappearance of phrenic activity but failed to affect the magnitude of the pressor response. Also cooling of the CL and RM areas and application of Gelfoam pledgets soaked in lidocaine (4%) to these areas did not affect the CIR. However, covering the whole VMS with 0.2 ml of 4% lidocaine or cold cerebrospinal fluid (10 degrees C) abolished the ischemic reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of focal cooling of central chemosensitive areas on cerebral ischemic response. 287 45

We have reported that cardiac preconditioning against ischemia-reperfusion (IR) can be induced by transient ischemia (TI) and alpha 1-adrenoreceptor stimulation, both mediated by protein kinase C (PKC) (Mitchell, M., X. Meng, C. Parker, E. Brew, A. Harken, and A. Banerjee. Circ. Res. 76: 73-81, 1995). Our study objective was to explore the mechanism of endogenous preconditioning and address the role of PKC activation in bradykinin-mediated cardiac functional protection. Isolated rat heart was used to assess the effects of exogenous bradykinin, TI, selective B2-receptor blocker, and PKC antagonism on cardiac functional recovery after a global IR injury. Final recovery of developed pressure was improved in hearts treated with bradykinin and TI compared with controls. Bradykinin- and TI-mediated preconditioning was eliminated with coinfusion of the B2-receptor antagonist. Further evaluation of bradykinin-mediated preconditioning revealed that PKC blockade also eliminated functional protection. Immunofluorescent stains of bradykinin-treated hearts demonstrated translocation and activation of specific PKC isoforms in the preconditioned heart. We conclude that TI-mediated preconditioning involves intrinsic cardiac bradykinin receptor stimulation. Bradykinin, through the B2 receptor, initiates a series of intracellular events culminating in the activation of PKC.
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PMID:Role of bradykinin in cardiac functional protection after global ischemia-reperfusion in rat heart. 748 70

Fifty consecutive patients with thrombocythemia (35 men and 15 women) were diagnosed as primary thrombocythemia (PT) in 30 and thrombocythemia associated with polycythemia vera (PV) in 20. The symptoms were platelet-mediated erythromelalgia in 16 PT and 15 PV, coronary artery disease in 3 PT and 2 PV, atypical cerebral ischemic attacks in 8 PT and 3 PV, paradoxical thrombosis and bleeding in 3 PT and 2 PV and hemorrhages alone in 6 PT and 2 PV patients. Erythromelalgia was localized in the forefoot sole and toes in 28, the fingertips in 9, the handpalm in 2. Untreated erythromelalgia progressed to acrocyanosis or peripheral ischemia with necrosis in a toe or fingertip in 14 cases. Painful red, warm and indurated erythromelalgic hot spots in the skin of the upper legs were misdiagnosed as superficial thrombophelebitis in 5 PT and 2 PV patients. Erythromelalgia in thrombocythemia already occurred at slightly increased platelet counts above 400 x 10(9)/l. The curative effect of aspirin on erythromelalgia in thrombocythemia was consistently accompanied by a significant increase of platelet counts. Erythromelalgia and bleeding paradoxically occurred in 5 patients at platelet counts between 1000 and 2000 x 10(9)/l. In this situation aspirin prevents erythromelalgic and microcirculatory circulation disturbances, but further increases the risk of serious bleeding complications. Presenting hemorrhagic manifestations in thrombocythemia were observed at platelet counts in excess of 1000 x 10(9)/l in 9 PT and 4 PV patients as severe epistaxis in 5, atypical ecchymoses in 3, gastrointestinal bleeding in 2 and secondary bleeding in 3. The concept of platelet-mediated erythromelalgia, thrombosis and hemorrhages in thrombocythemia is discussed.
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PMID:Erythromelalgic, thrombotic and hemorrhagic manifestations in 50 cases of thrombocythemia. 895 72

Bleeding and thrombosis are major causes of morbidity and mortality in patients with chronic myeloproliferative disorders. We retrospectively evaluated 101 consecutive patients affected by primary thrombocytosis (46 male, 55 female, aged 18-84 years; mean +/- SD 61 +/- 15) followed for a period ranging from 6 months up to 10 years (median 5 years) at our hematological unit. At the time of diagnosis 48 patients were asymptomatic; 26 had clinical evidence of atherothrombosis (cerebral ischemic attacks, ischemic heart disease, peripheral occlusive arterial disease), ten had venous thrombosis, four experienced major hemorrhages, 23 presented microvascular ischemic manifestations namely erythromelalgia, paresthesias, acrocyanosis and dizziness. At presentation 51.2% of the patients had elevated serum lactic dehydrogenase, 34.5% hyperuricemia, and 23.4% serum creatinine > 1.2 mg/dL. Color Doppler ultrasound provided evidence of vascular stenosis or medium-intimal hyperplasia of epiaortic vessels in 48.9% of patients studied, and similar alterations of lower limb arteries in 23.8% of cases. Therapy modality included an antiplatelet agent (picotamide 300 mg/bid); a cytoreductive agent (busulphan, hydroxyurea, pipobroman or melphalan) was used when platelet count was > 800000/microL. Symptoms due to microvascular ischemia promptly regressed after picotamide and cytoreductive therapy. During follow-up. nine patients suffered from atherothrombotic events (transient ischemic attacks, ischemic stroke, unstable angina pectoris) and five developed deep vein thrombosis or superficial thrombophlebitis. Five patients experienced major hemorrhages (two melena, two hematuria, one perioperative bleeding); the two gastrointestinal hemorrhages occurred in patients self-medicated with non steroidal anti-inflammatory drugs, and the two episodes of hematuria occurred on oral anticoagulant therapy and aspirin respectively. No major bleeding occurred in patients on continuative therapy with picotamide, even in the presence of upper digestive tract disorders. Seven patients died: mortality resulted from one sudden coronary death, three solid neoplasia, one blast crisis, one anile, and one massive hemorrhage due to abdominal aortic prosthesis tearing. Our study suggests that a long-term antithrombotic prophylaxis with picotamide may be of benefit in patients affected by primary thrombocytosis; a controlled clinical trial is warranted to assess whether picotamide can ameliorate the natural history of the disease.
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PMID:Thrombotic and hemorrhagic complications in chronic myeloproliferative disorders. 895 59

Neurologic and visual symptoms frequently occurred in 56 reported patients with essential thrombocythemia (ET). They may either precede or follow the well-known microcirculatory complications of ET of acroparesthesias, erythromelalgia, and acrocyanosis or ischemia of one or more toes. In comparison with transient ischemic attacks in patients with vascular risk factors, the usual neurologic presentation of ET consists of brief attacks of sudden cerebral or visual dysfunction, which can be either well localized or diffuse and entirely nonspecific. A dull and throbby headache usually lasting for several hours frequently accompanies the neurologic symptoms. Visual symptoms are less frequent and include transient monocular blindness and global symptoms such as scintillating scotomas and attacks of blurred vision. Neurologic and visual symptoms may leave minor sequelae but are generally nondisabling. The striking similarity to migraine, together with the absence of vascular risk factors and the striking efficacy of aspirin treatment supports the hypothesis that the ischemic neurologic and visual symptoms in ET are caused by shear rate-induced intravascular activation and aggregation of platelets with subsequent transient sludging or occlusion of the cerebral arterial microvasculature. Available data show that both the erythromelalgic distress and the ischemic neurologic attacks in ET are completely abolished by control of platelet function with low dose aspirin alone or reduction of platelet counts to normal as well as by the combination of platelet reducing therapy and low-dose aspirin. Early recognition and appropriate treatment of neurologic symptoms in patients with ET is therefore of great clinical relevance.
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PMID:Neurologic and visual symptoms in essential thrombocythemia: efficacy of low-dose aspirin. 926 53

The vascular complications in patients with polycythemia vera are microvascular circulatory disturbances typical of thrombocythemia including erythromelalgia, peripheral ischemia, atypical cerebral ischemic attacks, and major arterial and venous thrombotic events. These are positively related to hematocrits due to the increased red cell mass and its concomitant increased whole blood viscosity. Phlebotomy does not prevent the aspirin-responsive microcirculatory circulation disturbances in polycythemia vera because thrombocythemia (platelet count > 400 x 10(9)/L) persists. The risk of major vascular ischemic episodes in poorly controlled polycythemia vera at hematocrits between 0.45 and 0.50 is rather high. The risk of vascular complications in polycythemia vera is best controlled by maintaining the hematocrit at less than 0.45 and the platelet count below 400 x 10(9)/L. The microvascular syndrome associated with thrombocythemia in early stage polycythemia vera in remission by phlebotomy is easily and best controlled by low-dose aspirin (50 to 100 mg) or by selective reduction of platelet count to normal with low-dose myelosuppressive agents. The potential leukemogenic myelosuppressive agents busulfan and hydroxyurea and the nonleukemogenic cytosine interferon-alpha have proven to be effective in the control of the proliferative phase of polycythemia vera. However, data on the natural history of polycythemia vera and the best treatment modality of the various stages of myeloproliferative disease are still lacking.
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PMID:Erythromelalgia and vascular complications in polycythemia vera. 938 3

Patients with polycethemia vera (PV) or essential thrombocythemia (ET) are at increased risk of arterial and venous thromboembolic events. Arterial ischemic complications occur in 24 to 43% of these patients, particularly those with cardiovascular risk factors (especially cigarette smoking). Non-atheromatous arterial thrombosis concerns all large and medium-sized vessels, particularly cerebral, limb, coronary and digestive arteries. Extensive complications have been described in patients with lower limb occlusive arteriopathy, particularly stent or bypass thrombosis, critical ischemia. Juvenile myocardial infarction or rapid postangioplasty coronary thrombosis may reveal certain myeloproliferative disorders, particularly ET. Venous thrombosis is more frequent in PV than in ET; superficial or deep venous thromboses are seen. Thromboembolic events occur in about 25-30% of the patients and account for one-third of the deaths. Mesenteric vein thrombosis, portal thrombosis, or suprahepatic vein thrombosis may occur in all myeloproliferative disorders, but the pathogenesis is not fully understood. Pulmonary hypertension may be the consequence of local thrombosis in the pulmonary vasculature or may be due to the high blood flow in the right heart cavities. Microvascular circulatory disturbance includes erythromelalgia, Raynaud's phenomenon, digital ischemia, acrocyanosis, blue toe syndrome, livedo reticularis, cutaneous ulcers or necrotic purpura. All these manifestations may precede the myeloproliferative disorder by several months.
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PMID:[What vascular events suggest a myeloproliferative disorder?]. 1114 2

Erythromelalgia is the main, pathognomonic and presenting symptom in patients with essential thrombocythemia and thrombocythemia associated with polycythemia vera. Complete relief from erythromelalgic and acrocyanotic pain is obtained with the cyclooxygenase inhibitors aspirin and indomethacin, but not with sodiumsalicylate, dipyridamol, sulfinpyrozone and ticlopedine. Thus, cyclooxygenase metabolites are necessary for erythromelalgia to develop. Local platelet consumption in erythromelalgic areas became evident by the demonstration of arteriolar fibromuscular intimal proliferation and occlusions by platelet-rich thrombi in skin biopsies, by the findings of shortened platelet survival times, significant higher levels of platelet activation markers beta-thromboglobulin, thrombomoduline and increased urinary thromboxane B2 excretion in thrombocythemia patients suffering from erythromelalgia. Aspirin treatment of erythromelalgia in thrombocythemia patients resulted in the disappearance of the erythromelalgic, thrombotic signs and symptoms, correction of the shortened platelet survival times, and a significant reduction of the increased levels of beta-TG, PF4, TM and urinary TxB2 excretion to normal. Erythromelalgia is frequently preceded or followed by atypical transient neurologic, ocular or coronary ischemic symptoms, which specifically respond to low-dose aspirin or reduction of platelet counts to normal. The broad spectrum of acropareshesias, erythromelalgia and acrocyanotic ischemia together with the episodic and transient atypical TIAs and ocular or coronary ischemic symptoms are caused by spontaneous activation and aggregation of hypersensitive platelets in the end-arterial microvasculature involving the peripheral, cerebral and coronary circulation of thrombocythemia patients. These microvascular circulation ischemic disturbances in thrombocythemia vera already occur at platelet counts in excess of 400 x 10(9) l(-1). Low-dose aspirin is highly effective and safe in the cure and prevention of thrombotic and ischemic events and does not elicit bleedings at platelet counts below 1000 x 10(9) l(-1). Spontaneous hemorrhages usually occur at very high platelet counts far in excess of 1000 x 10(9) l(-1) (HT) due to an acquired von Willebrand factor deficiency at increasing platelet counts. At platelet counts between 1000 and 2000 x 10(9) l(-1), thrombosis and bleeding (ETT and HT) frequently occur in sequence or paradoxically and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count to below 1000 x 10(9) l(-1) by platelet lowering agents usually results in the disappearance of the bleeding tendency and improvement of the von Willebrand syndrome, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal.
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PMID:Platelet-mediated microvascular inflammation and thrombosis in thrombocythemia vera: a distinct aspirin-responsive arterial thrombophilia, which transforms into a bleeding diathesis at increasing platelet counts. 1278 99

Potassium transport plays three distinct roles in mitochondria. Volume homeostasis to prevent excess matrix swelling is a housekeeping function that is essential for maintaining the structural integrity of the organelle. This function is mediated by the K(+)/H(+) antiporter and was first proposed by Peter Mitchell. Volume homeostasis to prevent excess matrix contraction is a recently discovered function that maintains a fully expanded matrix when diffusive K(+) influx declines due to membrane depolarization caused by high rates of electron transport. Maintaining matrix volume under these conditions is important because matrix contraction inhibits electron transport and also perturbs the structure-function of the intermembrane space (IMS). This volume regulation is mediated by the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)). Cell signaling functions to protect the cell from ischemia-reperfusion injury and also to trigger transcription of genes required for cell growth. This function depends on the ability of mitoK(ATP) opening to trigger increased mitochondrial production of reactive oxygen species (ROS). This review discusses the properties of the mitochondrial K(+) cycle that help to understand the basis of these diverse effects.
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PMID:Mitochondrial potassium transport: the K(+) cycle. 1450 25


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