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

A number of cardioplegic solutions have been described for the reduction of cellular damage during ischemic cardiac arrest. Using an isolated working rat heart model, we have attempted to precise some of the factors affecting the post-ischemic recovery of myocardial tissue after a 30-min period of total ischemia at 37 degrees C. The results indicate that procaine (1 mM) is able to afford some protective against normothermic ischemia while this protective effect remains consistently lower than that of the St. Thomas' Hospital solution (procaine + high K+ + high Mg2+; JYNGE et al., 1977). On the other hand, hearts from rats of the Wistar strain consistently exhibit a significantly better degree of recovery than do hearts from rats of the Shermann strain. When hearts were perfused at different levels of preload (1 or 2 kPa) and afterload (8 or 10 kPa), post-ischemic recovery was better in hearts with lower levels of cardiac work. Glucose, insulin and DL-propranolol which have been shown to exert a protective effect in isolated rat hearts with regional ischemia failed to protect the heart in the present experimental conditions. No clear correlation does exist between the post-ischemic recovery and the enzymatic assessment of myocardial cell damage.
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PMID:[Factors affecting the post-ischemic recuperation of isolated perfused rat heart]. 615 59

Glucose, insulin, potassium (GIK: 300 g glucose + 50 U insulin + 80 mEq KC1/L) was administered to anesthetized dogs as a 30-ml bolus followed by 1.5 ml/kg/h for 2 h. Five populations were studied: control (C, n = 6); 60 min hypothermic arrest both without (I, n = 6) and with pretreatment (I + GIK, n = 6); 60 min hypothermic arrest followed by reperfusion without (R, n = 6) and with pretreatment (R + GIK, n = 6). Glycogen content declined during the ischemic and reperfusion periods whether or not GIK pretreatment was utilized. Glycogen values did not differ significantly among the four groups. GIK pretreatment significantly protected sarcoplasmic reticulum (SR) calcium uptake rates. SR Ca2+ + Mg2+ adenosine triphosphatase (ATPase) activity was unaffected in the I group, depressed in the R group, but protected by GIK pretreatment. Myofibrillar pCa-ATPase activity was significantly depressed in the I group and unaffected by GIK pretreatment. In the R + GIK group, myofibrillar pCa-ATPase activity was identical to controls at all calcium concentrations except for Vmax. In vitro, generation of the superoxide anion by a xanthine-xanthine oxidase system at pH 7.0 significantly depressed both SR calcium uptake and ATPase activity, and this depression was partially reversible by glucose. Generation of the hydroxyl free radical and pH 6.4 significantly depressed calcium uptake but not ATPase activity, and this depression was reversible with glucose + superoxide dismutase. GIK pretreatment exerts a protective effect on the excitation-contraction coupling system during hypothermic global ischemia and reperfusion. Glycogen augmentation after short-term GIK infusion was not significantly different. It is hypothesized that an additional mechanism by which GIK may protect subcellular function is by serving as a scavenger of free radicals generated during the ischemic/reperfusion process.
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PMID:Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: a new proposed mechanism by the scavenging of free radicals. 618 57

Considerable experimental as well as clinical evidence has now accumulated to indicate that Mg2+ and K+ deficiencies have probably been overlooked as important causal factors in the etiology of hypertensive disease. Mg2+ ions are important for the regulation of Na+ and K+ transport across cell membranes, including those found in cardiac and vascular smooth muscle cells. Mg2+ activates a Na+-K+-ATPase pump which in turn plays a major role in regulating Na+-K+ transport. Loss of cellular Mg2+ results in the loss of critically important phosphagens: Mg ATP and creatine phosphate. Thus, under conditions where cellular Mg2+ is depleted (e.g. hypoxia, anoxia, ischemia, Mg deficiency, errors in Mg metabolism and/or binding, and transport), the Na+-K+ pump and phosphagen stores will be compromised, leading to alterations in resting membranes (e.g. membrane depolarization). Cellular Mg2+ depletion has been found to result in concomitant depletion of K+ in a number of cells, including cardiac and vascular muscles. Myocardial and vascular injury thus results in an uptake of Na+ and Ca2+, Mg2+ and K+ being lost first. The available evidence indicates that Mg2+ is important in the control of arteriolar tone and blood pressure, primarily via the regulation of vascular membrane Mg2+-Ca2+ exchange sites. A reduction in extracellular Mg2+ (or K+) can produce hypertension, vasospasm and potentiation of vasoconstrictor agents by allowing excess entry of Ca2+, concomitantly the potency of vasodilators is reduced. Alterations in vascular membrane Mg2+ result in 'leaky' arterial and arteriolar membranes thus contributing to the cellular reduction in K+ and the gain of Ca2+ and Na+. These factors seem all-important in the production and etiology of hypertension. Both clinical and experimental forms of hypertension are associated with tissue and plasma deficits of Mg2+. The arterial blood pressure elevation appears to be inversely related to the level of ionized intracellular and plasma Mg2+.
Magnesium 1984
PMID:Interactions of Mg and K on blood vessels--aspects in view of hypertension. Review of present status and new findings. 639 41

Considerable experimental evidence has accumulated to indicate that brain ischemia or stroke-like events will lead to rapid losses of brain potassium, magnesium, ATP, creatine phosphate and glucose. These events are usually followed by an uptake of sodium and calcium ions. Increased uptake or excess Ca2+ uptake in neuronal cells is thought to be the prime cause of neuronal death in the brain. Mg2+ deficiency is known to produce a host of neurological disturbances in man; experimentally, Mg2+ deficiency leads to excess uptake of Ca2+ in the brain. Strokes and transient ischemic attacks also are known to be associated with neurological disturbances and ionic changes in the brain. Stroke patients have been reported to exhibit deficits in serum and CSF [Mg]. Acute Mg or K deficiency can produce cerebrovasospasm, at least experimentally. The lower the extracellular concentration of either Mg2+ or K+, the greater the magnitude of cerebral arterial contraction. These cerebrovascular contractions induced by lowering either the [Mg2+]0 or [K+]0 cannot be antagonized or attenuated by known pharmacologic antagonists. The cerebrovasospasms produced upon lowering [Mg2+]0 can be modulated by [K+]0 and vice versa; e.g. the lower the [K+]0, the greater the degree of vasospasm upon withdrawal of [Mg2+]0 and vice versa. Lowering [Mg2+]0 in situ and in vitro results in increased uptake of Ca2+ in the brain and the cerebral arteries. Cerebrovasospasms induced by substances that are known to be released in the brain on injury, such as prostanoids and serotonin, are relaxed dramatically by addition of [Mg2+]0. Infusions of MgSO4 into the brain via the internal carotid artery produces dose-dependent lowering of systolic and diastolic blood pressure as well as dose-dependent vasodilatation of arterioles (17-30 micron) and venules (18-40 micron) in the cerebral microcirculation, as observed by direct in situ high-resolution TV image-intensification microscopy. In clinical studies, infusion of MgSO4 has been reported to alleviate cerebrovasospasms. Epidemiological evidence is accumulating to suggest that consumption of fruit and vegetables (foodstuffs relatively high in K and Mg, and low in Na) is associated in certain geographic regions with a lower than normal incidence of strokes, particularly that of cerebral hemorrhage. On the basis of such data, and the findings reported herein, we believe one must consider that certain types of cerebrovascular accidents, transient ischemic attacks and 'classical' migraine attacks may be associated with a 'true' Mg deficiency and altered fluxes of K+ ions in the brain and CSF.(ABSTRACT TRUNCATED AT 400 WORDS)
Magnesium 1984
PMID:Interactions of Mg and K on cerebral vessels--aspects in view of stroke. Review of present status and new findings. 639 42

Recovery of brain mitochondrial function was studied following forebrain ischemia induced in rats by common carotid artery occlusion in combination with hypotension caused by bleeding. A reversible insult was induced by 15-min ischemia in fasted animals (hypoglycemic ischemia), and an irreversible one by 30-min ischemia in fed animals (normoglycemic ischemia), the latter procedure causing exaggerated lactic acidosis as well. Mitochondrial function recovered during a 30-min recirculation period after 15-min hypoglycemic ischemia, although a small amount of Ca2+ accumulated during recirculation. Thirty-minute normoglycemic ischemia induced irreversible mitochondrial damage that was not associated with Ca2+ accumulation during recirculation. Ischemia of 15 and 30 min caused a loss of mitochondrial Mg2+ (approximately 25%) that persisted during recirculation but did not influence recovery. Based on our earlier data obtained on isolated brain mitochondria in vitro, it is suggested that the lack of full recovery following 30 min of normoglycemic ischemia was due to the profound lactic acidosis during this insult.
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PMID:Mitochondrial response to transient forebrain ischemia and recirculation in the rat. 647 58

Chronic implantation of surface coils on the skull has been developed to record 31P NMR spectra of the brain in unanesthetized rats. Intraperitoneal sublethal potassium cyanide doses induce strong and reversible changes in high-energy phosphate compounds in the brain, similar in part to those induced by ischemia. These effects are dose-dependent as far as phosphocreatine, inorganic orthophosphates and pH are concerned; ATP does not seem to be altered by KCN doses ranging from 3 to 5 mg/kg but starts decreasing at a dose of 6 mg/kg. The fraction of Mg2+ complexed ATP which could be estimated as about 90% was not affected by KCN intoxication. For high doses (6 mg/kg) a new peak, appearing on the upfield side of the inorganic phosphate peak, may correspond to an acidic compartment, the significance of which is discussed.
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PMID:Analysis of brain metabolism changes induced by acute potassium cyanide intoxication by 31P NMR in vivo using chronically implanted surface coils. 670 16

These studies were designed to test the efficacy and possible mechanisms of the prevention of mitochondrial functional deterioration in renal ischemia by the slow-channel calcium blocker verapamil. Renal ischemia was induced in guinea pigs by a unilateral ligation of the renal artery for 30 or 60 min. In the pretreated animals verapamil was given twice a day over a 5-d period prior to the induction of ischemia. Sham-operated animals were used as normal controls. After 30 and 60 minutes, the kidneys were removed and used for mitochondrial isolation and analyses, total tissue Ca2+ and Mg2+ determinations, or for electron microscopy. Verapamil pretreatment completely blocked the decrease of mitochondrial Ca2+ uptake rate induced by 30 or 60 min of ischemia. The pretreatment delayed by 30 min the ischemic decrease of state 3 respiratory activity. Total tissue Ca2+ concentration was not altered by ischemia or verapamil pretreatment. Total tissue Mg2+ concentration, however, was significantly reduced in the ischemic kidney at 60 min. This reduction was prevented completely by verapamil pretreatment. These data suggest that the mitochondrial functional deterioration induced by 30 min of ischemia is a primary cellular insult secondarily leading to loss of tissue Mg2+. The point of irreversibility in the ischemic cell injury might be initiated by lowered tissue Mg2+/Ca2+ ratios.
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PMID:Verapamil pretreatment preserves mitochondrial function and tissue magnesium in the ischemic kidney. 672 97

The effects of verapamil (1 mg/liter, 2 x 10(-6) mol/liter), quiescence, and cardioplegia (K+ 16 mmol/liter, Mg2+ 16 mmol/liter) on calcium exchange and mechanical function during ischemia and reperfusion have been investigated in the rabbit interventricular septum at 32 degrees C. Calcium influx and efflux were recorded continuously with 47Ca2+ and 45Ca2+. After 60 minutes of total ischemia and reperfusion for 30 minutes, there was a net calcium gain of 4.9 mmol/kg dry tissue. Verapamil given before total ischemia reduced net calcium gain to 1.5 mmol/kg dry tissue (n = 5, P less than 0.03). When given only on reperfusion after total ischemia, or 10 minutes before reperfusion during low flow ischemia, verapamil did not affect calcium exchange. Cardioplegia begun 10 minutes before total ischemia reduced net calcium gain to 1.0 +/- 0.26 mmol/kg dry tissue (n = 6, P less than 0.001). Cardioplegia during the first 10 minutes of reperfusion, or lack of electrical stimulation during reperfusion, did not reduce calcium gain. Net calcium gain correlated with the maximum rise in resting tension and with the recovery of developed tension. In control experiments neither verapamil nor cardioplegia altered influx or efflux of slowly exchanging calcium. The cardioprotective effects of cardioplegia and the calcium channel blocker verapamil appear to be due to a reduction of myocardial work rather than to any specific direct action on calcium fluxes across the myocardial cell membrane.
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PMID:The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium. 706 Feb 32

The importance of metals in normal and pathologic cardiovascular function has been recognized. Significant derangements in myocardial Ca2+, Mg2+, and Cu2+ have been reported in ischemic heart injury. We studied 3 groups of hearts: 1) fifteen specimens obtained from patients who had no heart disease, 2) nine specimens from patients who had expired from cyanotic congenital heart disease, and 3) ten specimens from patients who had expired from acute rheumatic heart disease with carditis and severe heart failure. None of the patients had undergone cardiac surgery. Left ventricular lateral wall Mg2+, Ca2+, Cu2+, and Zn2+ contents were measured by atomic absorption spectrometry. The results showed a significant decrease in myocardial Mg2- (Group I 177.06 +/- 32.71; Group II 155.66 +/- 14.79; Group III 149.00 +/- 13.29, p less than 0.05 and p less than 0.01, respectively), and Cu2+ contents (Group I 3.22 +/- 0.37; Group II 2.94 +/- 0.22; Group III 2.56 +/- 0.32, p less than 0.02 and p less than 0.001, respectively), and a rise in myocardial Ca2+ content (Group I 36.06 +/- 10.72; Group II 43.22 +/- 7.01; Group III 46.30 +/- 4.85, p = not significant, and p less than 0.01, respectively). The myocardial Zn2+ content did not change significantly (Group I 26.53 +/- 3.99; Group II 26.00 +/- 4.15; Group III 26.40 +/- 3.53). The myocardial Mg2+/Ca2+ ratio was reduced markedly in both groups (Group I 5.328 +/- 1.879; Group II 3.685 +/- 0.735; Group III 3.135 +/- 0.291, p less than 0.001 for both Groups II and III vs Group I). The latter results correlated closely with the myocardial Mg2+/Ca2+ ratios reported in experimental models in peri-infarction zones. Thus, the myocardium of patients who had expired from cyanotic congenital heart disease and acute rheumatic carditis is jeopardized by ischemia, with metal contents similar to the border areas in myocardial infarction.
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PMID:Myocardial metal content in patients who expired from cyanotic congenital heart disease and acute rheumatic heart disease. 717 80

Cold K+ cardioplegia is commonly used to preserve the myocardium during surgical ischemia. Since the K+-induced membrane depolarization could cause a Ca2+-mediated breakdown of adenosine triphosphate, this study compared the influence of different electrolytes on high-energy phosphate metabolism during cardioplegic arrest phosphate metabolism during cardioplegic arrest and subsequent recovery of mechanical function. An isolated working heart was subjected to hypothermic ischemia for one hour. Metabolic studies were assessed on phosphorus 31 nuclear magnetic resonance (NMR). Results show that (1) K+ cardioplegia is harmful when the Ca2+ content is equal to 2 mEq/I; (2) deleterious effects of K+ are markedly reduced by lowering the Ca2+ content; (3) the most adequate preservation is provided by a Mg2+-rich-Ca2+-poor perfusate; (4) this protection is not enhanced by addition of K+. Finally, 31P NMR appears particularly appropriate for evaluating myocardial protection techniques since it allows noninvasive serial monitoring of high-energy phosphate content and subsequent correlation with functional recovery after ischemia.
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PMID:Limitations of potassium cardioplegia during cardiac ischemic arrest: a phosphorus 31 nuclear magnetic resonance study. 731 88


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