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

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

Treatment of chronic heart failure with ACE-inhibitors has greatly improved the prognosis. In addition to ACE-inhibitors, diuretics seem to be necessary to decrease mortality, whereas the importance of cardiac glycosides has not been demonstrated unequivocally. Nevertheless, modern treatment of chronic heart failure in all stages should be a combination of diuretics, digitalis, and ACE-inhibitors rather than a stepwise addition of drugs depending on the severity of the disease. An increased heart rate leads to increased myocardial O2-consumption, decreased O2-supply, ischemia, and reduced contractility. Betablocker-induced reduction of heart rate does, however, not necessarily improve symptoms or hemodynamic conditions. The optimal heart rate in large failing hearts is not known yet. Probably, it is dependent on the type and severity of myocardial disease or impairment. In this respect, the sarcoplasmatic release and uptake of Ca2+ plays the most important role in the disordered force-frequency-relation in chronic heart failure.
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PMID:[Clinical aspects of differential drug therapy of chronic heart failure]. 129 Mar 10

Using Langendorff's perfusion model of isolated rat heart, the effect of period of ischemia, ischemia-reperfusion and changes in perfusate pH on the function of calcium uptake of cardiac sarcoplasmic reticulum (SR) was observed. The initial rate and capacity of calcium uptake by SR decreased significantly after 25 min ischemia, and were further worsened when ischemia was prolonged to 40 min. When hearts were subjected to 15 min reperfusion after 25 min ischemia, calcium uptake capacity and initial rate decreased even more in comparison with that of 40 min ischemia. In addition, the calcium dependent ATPase activity of SR was also markedly inhibited. Reperfusion with acid (pH 6.8) or alkaline (pH 8.0) made no significant difference on the aforementioned reperfusion induced changes. The results indicated that myocardial ischemia depressed the calcium transport activity of SR, and this depression was further aggravated with prolonging ischemia. Reperfusion after ischemia exacerbated the ischemic injury. Reperfusion with either acid or alkaline Krebs-Henseleit solution could not improve the calcium uptake function of SR, implying that the pH change does not seem to be an important factor in inducing the SR dysfunction during ischemia-reperfusion.
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PMID:[Alteration of calcium uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum in rat during ischemia-reperfusion]. 129 51

The effects of praeruptorin C (Pra-C, 15 mg/kg, bid x 3 d, ip) on global myocardial ischemia and reperfusion were investigated in the isolated working rat hearts. The results at 35 min after reperfusion showed that as compared with the values before ischemia, AP, LVSP, +dP/dtmax, -dP/dtmax, LVEDP and T were recovered up to 80 +/- 19%, 82 +/- 16%, 78 +/- 21%, 85 +/- 11%, 136 +/- 77% and 133 +/- 21%, respectively. The corresponding parameters of Nifedipine (Nif, 60 micrograms/kg, bid x 3 d, ip) were 80 +/- 16%, 97 +/- 30%, 102 +/- 24%, 106 +/- 32%, 129 +/- 41% and 145 +/- 46%, respectively. The CF, SV and HR were recovered by 81 +/- 11%, 104 +/- 20% and 78 +/- 7% when using Pra-C and 86 +/- 11%, 106 +/- 25% and 82 +/- 11%, respectively, when using Nif. Additionally, in comparison of Pra-C and Nif with the ischemia group, the levels of creatine kinase released from cardiac cells decreased by 30% and 40%; while calcium accumulation in myocardial mitochondria were 41% and 46%, respectively. The study suggests that the protective effects of Pra-C on myocardial cells in the isolated working rat heart during myocardial ischemia are similar to those Nif.
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PMID:[Protective effects of praeruptorin C and nifedipine on ischemia-reperfused injury in working rat hearts]. 129 18

Cortical mouse astrocytes in culture were impaled with two-channel microelectrodes. These mouse astrocytes have the same responses to different K+ concentrations, ouabain, and glutamate as cultured rat astrocytes, with the exception that a large barium-sensitive K+ conductance clamps the membrane potential at the K+ equilibrium potential. Glycolytic and mitochondrial inhibitors have little effect on the mouse astrocytes. Total blockade of energy metabolism leads to an irreversible, calcium-dependent depolarization, but only if applied for longer than 45 min. Increasing the extracellular K+ concentration to 60 mM increases the intracellular K+ concentration by 43 mM and the bicarbonate concentration by 22 mM and leads to a concomitant fast swelling. Together with the 20 mM increase in Cl- concentration reported in the literature this is a good indication for a Boyle- and Conway-mediated K(+)-anion influx with water. This influx is accomplished by the depolarization-induced opening of Cl- channels as reported in the literature. In conclusion, ischemia-like conditions have little direct, immediate impact on astrocytes. In contrast, ischemia-induced release of substances from neurones, such as K+, produces an immediate and fast response.
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PMID:Coupling of metabolism and electrical activity in cortical astrocytes. 129 68

The effects of nimodipine, a 1,4-dihydropyridine calcium channel blocker, on multiunit activity (MUA) of several brain structures were investigated in cats during 6 h immediately following acute global cerebral ischemia-anoxia induced by a 10 min cardiorespiratory arrest (CRA), as well as in cats exposed to sham procedures corresponding to CRA. Four groups of cats were studied: 1) CRA and continuous administration of nimodipine, 1 microgram/kg/min iv during 6 h; 2) CRA and continuous administration of vehicle; 3) sham and continuous administration of nimodipine as in group 1; 4) sham and vehicle as in group 2. MUA and electroencephalogram disappeared during ischemia-anoxia; their progressive recovery occurred throughout the hours following CRA, although 6 h after CRA MUA was still lower than its control prearrest values in all the recorded subcortical structures. Delta-like waves, isolated spikes, and bursts of fast EEG waves occurred during the recovery of EEG activity. Nimodipine inhibited the otherwise increasing MUA in mesencephalic reticular formation, hippocampus and putamen, but not in ventromedial hypothalamus, during the hours following acute global cerebral ischemia-anoxia. Absence of isolated spikes and bursts of fast EEG activity was noted in the EEG of CRA-, nimodipine-treated cats. Nimodipine significantly reduced MUA in hippocampus but not in other cerebral structures in cats of the sham treated group. The results suggest the involvement of 1,4 dihydropyridine sensitive calcium channels in the cellular mechanisms related to neuronal activity after cerebral ischemia-anoxia, and the possible relationship between the effects of nimodipine on MUA and better functional conditions of the central nervous system after acute global cerebral ischemia-anoxia.
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PMID:Effects of nimodipine on multiunit activity of several brain structures following acute global cerebral ischemia-anoxia in cats. 129 69

Nisoldipine represents a new attractive second generation calcium channel blocker of the dihydropyridine-class for the treatment of all types of coronary artery disease. The effect on chronic ischemia is comparable to long-acting nitrates, side-effects have been rarely observed. The advantages will be the high vascular selectivity with only slight negative inotropic effect as well as a long-lasting positive influence on the myocardial metabolism. Up to now, no studies have been reported which compare nisoldipine and long-acting nitrates directly, but this calcium antagonist appears to influence duration and intensity of symptomatic and silent episodes of ischemia similar to the nitrates.
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PMID:[Nisoldipine in comparison with long-term nitrates]. 129 42

Evidence obtained from experimental animals and man indicates that reentry is a major mechanism underlying arrhythmogenesis. However, focal or nonreentrant mechanisms also appear to be operative under a wide variety of pathophysiologic conditions. For example, results obtained using three-dimensional (3D) mapping from 232 simultaneous sites in the feline heart in vivo revealed that nonreentrant or focal mechanisms were prominent during both ischemia and reperfusion. During early ischemia, nonreentrant mechanisms were responsible for initiation of ventricular tachycardia (VT) in 25% of cases and, in cases where VT was initiated by reentry, it often could be maintained by a nonreentrant mechanism. During reperfusion of ischemic myocardium, nonreentrant mechanisms were responsible for initiation of VT in 75% of cases. Most importantly, the transition from VT to ventricular fibrillation in response to reperfusion was secondary to acceleration of a nonreentrant mechanism in either the subendocardium or subepicardium. Potential cellular mechanisms include: 1) sarcolemmal accumulation of amphiphiles such as long-chain acylcarnitines and lysophosphatidylcholine; 2) alpha- and beta-adrenergic mediated effects of catecholamines on the transient inward current (ITI) secondary to an increase in intracellular Ca2+; and 3) alpha-adrenergic receptor-induced decrease in IK mediated by activation of protein kinase C. Recent findings obtained using 3D intraoperative mapping in patients with refractory VT and a previous myocardial infarction also indicate that both reentrant and nonreentrant or focal mechanisms contribute. For example, in 13 selected patients, mapping was of a sufficient resolution to define the mechanisms of 10 runs of VT. Intraoperative mapping indicated that five runs of VT were initiated by intramural reentry, whereas five runs of VT were initiated by a focal or nonreentrant mechanism. The mechanisms underlying ventricular arrhythmias associated with ischemic cardiomyopathy have recently been delineated in dogs after multiple sequential intracoronary embolizations with microspheres (with a decrease in mean ejection fraction from 64% to 25%). Spontaneous VT initiated by focal mechanisms from the subendocardium in 82% and epicardium in 18%, with no evidence of macroreentry. Thus, in divergent pathophysiologic settings, nonreentrant mechanisms appear to contribute importantly to the genesis of lethal ventricular arrhythmias, suggesting that development of novel therapeutic approaches should be directed at inhibition of not only reentrant circuits, but also nonreentrant mechanisms, including triggered activity.
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PMID:The contribution of nonreentrant mechanisms to malignant ventricular arrhythmias. 129 6

Ca2+ ions are often invoked as potential initiators of cardiac arrhythmias in pathophysiological situations which are associated with an increase of free [Ca2+]i. It is well documented that elevated [Ca2+]i may produce SR release of Ca2+ and oscillations of membrane potential, thereby leading to triggered or spontaneous ectopic activity. The relation among elevated free [Ca2+]i, electrical cell-to-cell coupling, conduction slowing, and reentrant arrhythmias is more speculative. If Ca2+ (e.g. in mechanically injured cells) has direct access to the cellular interconnections (gap junctions), rapid uncoupling occurs at [Ca2+]i which is even within the range of a normal contractile cycle. If cellular integrity is preserved and changes of [Ca2+]i are imposed by extracellular interventions, the effect of [Ca2+]i is critically dependent on pHi. At normal pHi, transcellular conductance remains normal even if [Ca2+]i is increased to bring the cells into a hypercontractile state (> 1-2 microM). At decreased pHi, rapid uncoupling develops at low [Ca2+]i. Comparison of the conduction delay between two cells (or conduction velocity in a simulated conducting medium) with the [Ca2+]i-mediated increase in coupling resistance suggests that the transition from normal conduction velocity to conduction block (a key event in re-entrant arrhythmias) occurs within a relatively narrow range of [Ca2+]i or pHi, almost like a threshold phenomenon. Major efforts have been made in recent years to assess the changes of electrical cell-to-cell coupling and [Ca2+]i in myocardial ischemia. Therefore, the discussion of the role of [Ca2+]i as a modulator of electrical coupling is made in this pathophysiological setting. Comparison of several studies indicate that cell-to-cell resistance and [Ca2+]i in ischemia increase at the same time (10-15 min after perfusional arrest). Since other potential uncoupling processes (delta ATP, delta Mg2+, amphiphilic metabolites, delta pHi) show a similar time-course, it is difficult to attribute cell-to-cell uncoupling in ischemia solely to an increase in [Ca2+]i. Both an initial decrease of membrane excitability and subsequent electrical cell-to-cell uncoupling characterize the early phase of ischemia. The first mechanism is assumed to be more important for the generation of conduction block and re-entry. However, Ca(2+)-induced cell-to-cell uncoupling may partially contribute to the second phase of the early ischemic arrhythmias and mark the transition from reversible to irreversible ischemic damage.
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PMID:The potential role of Ca2+ for electrical cell-to-cell uncoupling and conduction block in myocardial tissue. 129 7

Anisodamine was used as an antishock (chiefly septic) drug beginning in the early 1960s in China. Its underlining mechanism was believed to be due to its vasodilative action. But in normal animals it only produces slight vasodilation. Our work during the recent 15 years proved that anisodamine is not only beneficial in the treatment for septic shock, but also for hemorrhagic, traumatic, and SMAO shock, and its mechanism of action are based on its following biological actions: (1) it has membrane stabilization and cell protection action, which was probably related to its calcium antagonist action; (2) it protects ischemia intestine from releasing shock factors; and (3) its inhibition of endotoxin binding to cells and tissue at the membrane level probably makes it an special antishock drug for septic shock.
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PMID:Cell protection mechanism of antishock action of anisodamine. 129 54


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