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)

Serial assessment of perfusion and viability during myocardial infarction has not been feasible, in part, because of the long half-lives of available tracers. Rubidium-82 (82Rb) is a generator-produced, positron-emitting potassium analog with a short half-life (75 sec) that permits repeated studies. To determine the temporal relation of net myocardial 82Rb accumulation to loss of viability during prolonged ischemia, a 2-3 mCi bolus of 82Rb was given to 46 open-chested dogs while regional myocardial time-activity curves were obtained with beta probes at baseline, and serially after coronary occlusion lasting 1-6 hr. Hearts were then stained with triphenyl tetrazolium chloride (TTC) to assess the viability of the epicardium under the probe to a depth corresponding to the range of positrons. Irreversible injury occurred in two out of 16 experiments at 1 hr and ten out of 15 experiments at 3 hr and also at 6 hr (p less than 0.05 vs. 1 hr). In viable myocardial samples, rubidium extraction increased with low flow as compared with nonischemic controls for all time periods but was unchanged (failed to increase) in nonviable tissue. Net 82Rb accumulation decreased during 1 to 6 hr of occlusion in irreversibly injured samples (0.28 +/- 0.19 to 0.16 +/- 0.07, p less than 0.05) but remained unchanged in myocardial tissue subsequently shown to be viable. For myocardial samples that were nonviable at 3 and 6 hr, changes in net accumulation of tracer became abnormal only after 6 hr of occlusion. The mechanisms primarily responsible for the decrease in net accumulation of 82Rb at 6 hr appeared to be leakage of tracer after first pass. Therefore, failure to increase extraction at low flows may be an early indicator of cell death, whereas membrane leakage occurs several hours after loss of viability.
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PMID:Rubidium-82 kinetics after coronary occlusion: temporal relation of net myocardial accumulation and viability in open-chested dogs. 374 47

The arterial-coronary sinus lactate difference was measured in 17 patients after each step of a programmed ventricular stimulation protocol consisting of single, double, and triple extrastimuli, first at a basic drive cycle length of 600 msec, then at 400 msec, with an inter-train interval of 4 seconds. Four patients had no structural heart disease, four had an idiopathic dilated cardiomyopathy, and nine had coronary artery disease with a significant stenosis in at least one branch of the left coronary artery. Net myocardial lactate production during programmed ventricular stimulation was observed in three patients with coronary artery disease, but not in any patient without coronary artery disease. Among the patients who had coronary artery disease, net myocardial lactate production generally occurred in the patients who had more severe coronary artery disease. Exercise-induced ischemia, as demonstrated by a stress thallium-201 test, did not correlate with myocardial lactate production during programmed ventricular stimulation. Programmed ventricular stimulation, with a stimulation protocol typically used in many electrophysiology laboratories, is capable of inducing myocardial ischemia in at least some patients who have coronary artery disease. This finding suggests that myocardial ischemia may potentially influence the results of programmed ventricular stimulation in some patients with coronary artery disease.
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PMID:Effect of programmed ventricular stimulation on myocardial lactate extraction in patients with and without coronary artery disease. 394 67

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

This study examined the relationships between the left ventricular (LV) regional function, regional myocardial blood flow (RMBF), and myocellular necrosis after sudden proximal occlusion of the left anterior descending coronary artery (LAD) in 36 awake, unsedated dogs. Net wall thickening during systole (NET) was used to assess regional LV function, was expressed as percent control, and was measured with chronically implanted ultrasonic crystals. RMBF was measured with 8- to 10-micrometer radioactive microspheres. In regions with a moderate degree of functional loss, NET fell to 35.3 +/- 2.2% of control at 5 minutes when RMBF fell from 1.9 +/- 0.08 to .086 +/- 0.09 ml/g per min (P less than 0.05). No significant change occurred in midwall or epicardial RMBF. The relationship between endocardial flow and NET was non-linear (r = 0.69, P less than 0.0001). In these segments, subsequent changes in RMBF were unrelated to corresponding functional alterations through 24 hours. In segments with paradoxic systolic wall thinning RMBF fell in endocardial, midwall, and epicardial layers; endocardial ischemia was most severe (0.30 +/- 0.05 ml/g per min). Segmental myocellular necrosis was most severe in the endocardial layer and correlated significantly with both RMBF and segmental function. Myocellular necrosis increased in severity as flow was reduced below 70-75% of normal. Thus, in this model of LV ischemia, (1) regional LV functional loss is most sensitive to reductions in endocardial RMBF; (2) subsequent increases in RMBF are largely unassociated with functional recovery; (3) transmural ischemia results in paradoxical systolic wall thinning.
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PMID:Interrelationships between regional left ventricular function, coronary blood flow, and myocellular necrosis during the initial 24 hours and 1 week after experimental coronary occlusion in awake, unsedated dogs. 723 98

Preparation protocols for human cardiac valves are intended to minimize cytotoxicity because it has been thought that viable leaflet interstitial cells may enhance homograft durability. Preimplantation factors influencing the status of these cells at the time of transplantation include ischemia, disinfection, and cryopreservation freezing programs. In these experiments, adenine nucleotide quantitation was undertaken to assess metabolic consequences of preparation; preharvest ischemia served as an independent variable to examine the relationship between time of procurement (postmortem) and high-energy phosphate status of the cryopreserved leaflets at thaw. Nucleotides were measured using high-performance liquid chromatography performed on extracts of semilunar cusps from 25 cryopreserved human valves with documented ischemic times. Results indicate total adenine nucleotides (TAN; [ATP] + [ADP] + [AMP], in nmol TAN/mg leaflet protein) are higher (P < 0.05) after < 2 h of harvest ischemia (1.16 +/- 0.36) than with ischemic times of 3-6 h (undetected), 7-12 h (0.18 +/- 0.07), and 13-20 h (0.06 +/- 0.06). Depletion of ATP was similar, with many leaflets devoid of detectable levels. Net utilization of leaflet energy stores demonstrates time dependency when assayed after completed processing. However, relatively elevated catabolites, even with brief ischemia, and infrequently identified ATP, ADP, and AMP, suggest a consumption so accelerated that the following cryopreservation it is virtually independent of procurement-associated ischemia. We conclude resumption of a functional cell population obligates significant de novo phosphoanhydride boned reformation or a repopulation of dead/dying interstitial cells from a subset surviving the apparently severe rigors of valve preparation.
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PMID:Adenine nucleotide depletion in cryopreserved human cardiac valves: the "stunned" leaflet interstitial cell population. 778 24

Canine jejunoileal transplantation induces an early profuse watery diarrhea of uncertain etiology. Our aim was to determine the temporal effects of a canine model of jejunoileal autotransplantation (a model devoid of confounding effects of ischemia-reperfusion or immune rejection) on basal jejunal and ileal absorption of water and electrolytes to determine if impaired absorption is responsible for the diarrhea. Our hypothesis was that net absorption of water and electrolytes in an enterically isolated loop would decrease after jejunoileal transplantation. Four groups of dogs (N > or = 6) were prepared with 80-cm modified Thiry-Vella loops: group I, neurally intact jejunum; group II, autotransplanted jejunum; group III, neurally intact ileum; and group IV, autotransplanted ileum. The loops were perfused for 3 hr with 150 mM NaCl at 3 ml/min under fasted conditions; transit time through the loop was determined by bolus of a nonabsorbable marker. Dogs were studied on three separate days at one, two, eight, and nine weeks postoperatively. Net absorptive fluxes of water and electrolytes and transit times were similar (P > 0.05) between neurally intact and autotransplant groups (group I vs II and group III vs IV) at each time point. Ileal loops absorbed more than jejunal loops, and transit was slower in ileal loops (each P < 0.05). Our findings suggest that, despite the obligate disruption of extrinsic innervation, enteric (intrinsic) neural continuity, and lymphatic drainage that accompanies this canine model of jejunoileal autotransplantation, net basal absorptive function of water and electrolytes during the fasted state was not decreased nor was transit altered either in jejunum or ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a model of canine jejunoileal orthotopic autotransplantation on jejunal and ileal transport of water and electrolytes. 814 51

The mechanisms underlying the marked increase in [K+]o in response to ischemia are not fully understood. Accordingly, the present study was performed to assess the contribution of ATP-regulated K+ channels by using simultaneous measurements of cellular K+ efflux, [K+]o, transmembrane action potentials, and tissue ATP, ADP, phosphocreatine, and creatine content in a unique isolated, blood-perfused papillary muscle preparation during hypoxia compared with ischemia. During 15 minutes of hypoxic perfusion (PO2, 6.1 +/- 0.9 mm Hg) with normal [K+]o of 4.1 +/- 0.1 mM, action potential duration (APD) was not altered even though tissue ATP levels decreased markedly from 33.5 +/- 1.8 to 14.7 +/- 2.0 nmol.mg protein-1 (p < 0.01). Net cellular K+ efflux, based on measured differences of [K+] between the venous effluent and the perfusate, was 13.23 +/- 0.79 mumol.g wet wt-1 during hypoxia. In contrast, after 15 minutes of zero-flow ischemia, APD at 80% of repolarization (APD80) decreased by 47% from 171 +/- 5 to 92 +/- 5 msec (p < 0.01), but integrated net cellular K+ efflux over 15 minutes of ischemia was 8.4-fold less (1.57 +/- 0.13 mumol.g wet wt-1) than during hypoxia. Tissue ATP levels, however, decreased by only 35.2% to 21.7 +/- 2.1 nmol.mg protein-1, which was significantly less than that induced by 15 minutes of hypoxia. Perfusion with hypoxic blood containing high [K+]o of 10.3 +/- 0.3 mM resulted in APD shortening similar to that observed during ischemia. Cellular K+ loss, however, was inhibited markedly by high [K+]o perfusion (only 4.51 +/- 0.28 mumol.g wet wt-1). Pretreatment with glibenclamide (5 microM), a drug that has been reported to inhibit ATP-regulated K+ channels and accelerate glycolysis in normoxic tissue, partially inhibited cellular K+ efflux during hypoxic perfusion with normal [K+]o (7.35 +/- 0.71 versus 13.23 +/- 0.79 mumol.g wet wt-1, p < 0.01) but had no significant influence on repolarization time or tissue ATP levels. Although glibenclamide partially prevented action potential shortening induced by hypoxic perfusion in the presence of elevated [K+]o, the proportion of cellular K+ efflux reduced by glibenclamide was less (23%) than that observed with glibenclamide in hypoxic perfusion with normal [K+]o (44%).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dissociation between cellular K+ loss, reduction in repolarization time, and tissue ATP levels during myocardial hypoxia and ischemia. 843 84

The purposes of this study were to: (1) assess myocardial pyruvate dehydrogenase (PDH) activity and substrate exchange under well-perfused and ischemic conditions; (2) determine the metabolic effects of an intra-coronary infusion of the PDH activator, dichloroacetate (DCA); and (3) measure the effects of ischemia and DCA on malonyl CoA levels. Experiments were performed in anesthetised open-chest swine under non-ischemic conditions, followed by 40 min with a 60% reduction in left anterior descending coronary artery (LAD) blood flow. Myocardial needle biopsies for measurement of PDH activity were taken after an intracoronary infusion of either saline or DCA (1 mM in LAD blood) under aerobic conditions, and after 37 min of ischemia. Pyruvate dehydrogenase activity was measured with and without maximal activation by swine PDH phosphatase. Malonyl CoA and acetyl CoA were measured after 40 min of LAD ischemia in myocardium from the ischemic DCA- or saline-treated LAD bed, and the non-ischemic untreated left circumflex coronary artery (CFX) perfusion bed. Net glucose, lactate and free fatty acid (FFA) uptakes were measured across the LAD perfusion bed throughout the study. Dichloroacetate treatment increased the amount of active dephosphorylated PDH to 88% of the total activity under aerobic conditions, compared to 55% with saline (P < 0.01). Ischemia did not significantly change PDH activation state in either group. Acetyl CoA and malonyl CoA contents were significantly elevated in ischemic DCA-treated myocardium compared to saline-treated ischemic myocardium. Dichloroacetate treatment significantly lowered rates of myocardial FFA uptake under both aerobic and ischemic conditions, but did not effect glucose uptake or lactate exchange. Free fatty acid uptake was negatively correlated to malonyl CoA levels (r = -0.68) during ischemia. It is proposed that the inhibition of FFA uptake observed with DCA in ischemic myocardium is due to malonyl CoA inhibition of carnitine palmitoyl transferase I.
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PMID:Pyruvate dehydrogenase activity and malonyl CoA levels in normal and ischemic swine myocardium: effects of dichloroacetate. 876 30

We previously showed that generation of reactive oxygen species during myocardial ischemia and reperfusion stimulates cardiac sympathetic afferent nerve endings. We hypothesized that, in this feline model of brief ischemia and reperfusion, HO. is produced during ischemia and the rate and concentration of production of HO.during reperfusion is dependent on the duration of myocardial ischemia. Therefore, we evaluated the time dependency of production of HO. during reperfusion after 2, 5, and 10 min of reversible occlusion of the left anterior descending (LAD) coronary artery to induce ischemia in cats (n = 10). Blood samples collected from the coronary vein at 0.25, 1, 2, and 4 min after 2 min of ischemia revealed net cumulative rate of production of p-, m-, and o-tyrosine of 99 +/- 31, 10 +/- 5.1, and 0.8 +/- 0.2 nmol.min-1.g-1, respectively. After 5 min of ischemia, net cumulative rates of production of p-, m-, and o-tyrosine during reperfusion were 177 +/- 63, 74 +/- 26, and 1.6 +/- 0.8 nmol.min-1.g-1, respectively, whereas after 10 min of ischemia production rates were 153 +/- 42, 78 +/- 29, and 2.1 +/- 0.5 nmol.min-1.g-1, respectively. The highest rate of production of tyrosines was observed immediately after ischemia, perhaps indicating a washout of HO.-derived products that had accumulated in the myocardium during ischemia. To evaluate production of HO. during ischemia, deoxygenated saline (PO2 10 +/- 0.9 mmHg) containing phenylalanine was perfused into the ischemic coronary vascular bed through a cannula placed in the LAD (n = 16). Perfusate was collected from the coronary vein during the 10 min of ischemia. Net production of HO. during ischemia, measured by the production of p-, m-, and o-tyrosine, was 82 +/- 11, 6.6 +/- 0.4, and 1.7 +/- 0.3 nmol.min-1.g-1, respectively. Pretreatment with deferoxamine (10 mg/kg, n = 7) or dimethylthiourea (10 mg/kg, n = 6) decreased net production of HO. during ischemia and reperfusion. These results demonstrate that HO. is produced during brief ischemia and reperfusion, with the greatest amount being produced immediately after ischemia. Additionally, we show that the duration of brief ischemia determines the rate of production of HO. during reperfusion.
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PMID:Hydroxyl radical production during myocardial ischemia and reperfusion in cats. 877 Jan 9

Triple therapy with S-adenosylmethionine (SAM) (given to the donor animal, included in University of Wisconsin solution [UW], and added to the reperfusing medium) has been shown to reduce the sequential cold and warm ischemia/reperfusion injuries characteristic of the liver transplantation procedure. To clarify the actions of SAM during different stages of ischemia/ reperfusion, we have compared its benefit in five dosage regimens, using perfused rat livers after sequential periods of 24 hr cold and 20 min rewarming ischemia. When added only to UW, the presence of SAM throughout ischemia improved hepatic blood flow by 26% after 15 min of reperfusion versus no treatment (2.32+/-0.18 vs. 1.84+/-0.11 ml/min/g liver, P<0.05). SAM also improved blood flow by 23% during the 3-hr perfusion overall (P<0.05). Oxygen consumption and the release of purine nucleoside phosphorylase (PNP) were decreased (both P<0.05). When added to both UW and the perfusate, SAM additionally increased bile production at 15 min (7.14+/-1.21 vs. 2.31+/-0.74 mg/h/g liver, P<0.01). By pretreating the liver donor with SAM in vivo, and including it in the preservation and reperfusing media, it was possible to prolong and amplify the benefits on blood flow (P<0.001) and bile production (P<0.05) and to sustain glucose uptake (P<0.01). An acute exposure to SAM, when used in saline to flush UW from the graft before reperfusion, increased blood flow at 15 min (by 68%) and over a 3-hr period (both P<0.001), but no indices of metabolic activity were improved. Oxygen consumption and PNP release were both decreased (P<0.05). When added to the perfusate (present throughout reperfusion), SAM increased blood flow at 15 min (58%) and over a 3-hr period (P<0.01 in both cases). Net glucose uptake was increased (P<0.05), whereas oxygen consumption (P<0.001) and PNP release fell (P<0.05). Actions of SAM achieved acutely and over the intermediate- and long-term all seem to underlie its benefits in reducing ischemia/reperfusion injuries.
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PMID:Treatment of experimental ischemia/reperfusion injury with S-adenyosylmethionine: evidence that donor pretreatment complements other regimens. 904 41


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