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

The influence of an intake of garlic powder (1%--corresponding to Kwai/Sapec--added to a standard chow for a 10-week period) on the susceptibility to ventricular arrhythmias under ischemia and reperfusion was investigated in the isolated rat heart (Langendorff preparation) perfused with a modified Krebs-Henseleit solution. The incidence of ventricular tachycardia (VT) and fibrillation (VF) after ligation of the descending branch of the left coronary artery (LAD) (20 min) was significantly reduced in the garlic group as compared to untreated controls (VT: 0% vs. 35.5%; VF: 50% vs. 88%). The size of the ischemic zone was significantly smaller (31.7% vs. 40.9% of total heart tissue). The reperfusion experiments (5 min after 10 min ischemia) revealed similar results (VT: 50% vs. 100%; VF: 30% vs. 90%). The time until occurrence of extrasystoles and VT or VF was prolonged in most cases, and the duration of arrhythmias was abbreviated. No significant alterations in cardiac membrane fatty acid composition could be found. Inhibition of cyclooxygenase by acetylsalicylic acid (ASA) caused a moderate increase in arrhythmias and ischemic zone in the garlic group as well as in untreated controls under the conditions of the present experiments. Thus, it seems that the prostaglandin system does not play a predominant role in the cardioprotective action of garlic. The significance of free radical scavenging activity of garlic for its antiarrhythmic effects has to be established.
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PMID:Cardioprotective actions of garlic (Allium sativum). 845 43

The effects of TAK-044 on the extension of ischemia/reperfusion-induced myocardial infarction were studied in rats. Acute myocardial infarction was induced by occlusion of the left coronary artery for 1 h followed by reperfusion for 24 h. Infarct size and the area at risk were determined histochemically. Infarct size as a percentage of the area at risk (IS) was significantly reduced in a dose-dependent manner by TAK-044 administered 30 min before reperfusion (0.3-3.0 mg/kg, i.v.). Size-limiting effects similar to those in rats were also obtained in rabbits and dogs. In addition, TAK-044 administered 3 h after reperfusion also reduced the IS significantly. Preconditioning (5 min of LAD occlusion preceding 1 h of coronary occlusion) inhibited the extension of the IS. These effects of preconditioning and TAK-044 were inhibited by glibenclamide (0.1 mg/kg, i.v.; an inhibitor of the ATP-sensitive K channel) but not by DPCPX (1 mg/kg, i.v.; an adenosine A1 receptor antagonist). These results indicate that endogenous endothelin plays an important role in the extension of myocardial infarction and that the cardioprotective effects of TAK-044 can be partially explained by a mechanism similar to that of preconditioning in rats.
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PMID:Role of endogenous endothelin in the extension of myocardial infarct size studied with the endothelin receptor antagonist, TAK-044. 858 16

The beneficial effect of beta-blockade has been reported in acute myocardial ischemia as well as in the postinfarction period. Recent interest focused on the special effect of beta-blocking agents regarding the changes of lipid metabolism, free radical mediated reactions and arachidonic acid cascade. In previous experiments on dogs we have shown that ultrashort-acting beta-blocker (Brevibloc) could modify production of prostacyclin and thromboxane in ischemic heart tissue. The purpose of this study was to investigate the effect of Brevibloc on the function of isolated neutrophils and platelets during myocardial ischemia and reperfusion. In mongrel dogs the left descending coronary artery (LAD) was ligated for 1 or 2 hours followed by one hour reperfusion. Animals were divided into two groups: Group I control dogs (n = 21) no drugs were given; in Group II. (n = 20) short half-life beta-blocker esmolol HCl (Brevibloc) was administered intravenously. Polymorphonuclear leukocytes (PMN) were isolated from venous blood before and after LAD ligature and following reperfusion. Spontaneous and phorbol myrystate acetate (PMA) stimulated superoxide radical generation of isolated PMN was measured. Platelets were separated at the same periods and maximal aggregation was determined in platelet rich plasma (PRP) after stimulation with collagen, adrenaline and ADP. There was no spontaneous radical production of PMN neither in the control, nor in the Brevibloc treated animals. Neutrophil superoxide production after activation in Group I was 9.54 +/- 0.3 O2-/min/1.5 x 10(6) before LAD ligature, and significant elevation was present following one hour reperfusion (14.8 +/- 0.8 O2-/min/1.5 x 10(6)). Increased production of neutrophils was inhibited by beta-blocker therapy (9.32 +/- 1.05, 8.25 +/- 0.82 respectively). Collagen and ADP stimulated platelet aggregation increased more than 20% during ischemia in Group I, which elevated further after reperfusion. Administration of Brevibloc diminished maximal aggregation in both cases, after 1-2 hours of LAD ligature and after reperfusion, compared to the initial value. Our findings suggested that ultrashort-acting beta-blocker has in vivo inhibitory action on neutrophil superoxide generation and platelet aggregation influencing the pathological cellular interactions.
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PMID:Influence of the beta-blocker therapy on neutrophil superoxide generation and platelet aggregation in experimental myocardial ischemia and reflow. 858 3

The purpose of this investigation was to assess the effects of hyperglycemia, in the absence of changes in plasma insulin and arterial free fatty acid (FFA) levels, on interstitial glucose levels and glucose uptake across the left ventricular wall during ischemia in domestic swine. Insulin secretion was suppressed with a continuous infusion of somatostatin. Arterial FFA levels remained stable due to the suppression of insulin. Microdialysis probes were used to estimate changes in interstitial glucose and lactate, and were placed in the subepicardium and the subendocardium of the left anterior descending ([LAD] ischemic) coronary artery perfusion bed and in the midmyocardium of the circumflex ([CFX] nonischemic) perfusion bed. The LAD coronary artery was cannulated and perfused with blood from the femoral artery through an extracorporal perfusion circuit. Ischemia was induced in the LAD perfusion bed by reducing the flow of the LAD perfusion pump by 60% for 50 minutes, and was followed by 30 minutes of reperfusion. Twenty minutes into the ischemic period, seven animals were given a bolus injection of 50% glucose (200 mg/kg) followed by a glucose infusion (10 mg/kg/min), resulting in an increase in arterial glucose levels from 5 to 13 mmol/L in the hyperglycemic group. Hyperglycemia resulted in a marked increase in dialysate glucose during ischemia and a greater than twofold increase in glucose extraction and uptake. Dialysate glucose correlated with plasma glucose in all three perfusion beds. In conclusion, hyperglycemia, in the absence of an increase in insulin and a decrease in arterial FFA, resulted in a doubling of glucose extraction, delivery, and uptake, which corresponded to the twofold elevation in interstitial glucose during ischemia.
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PMID:Hyperglycemia results in an increase in myocardial interstitial glucose and glucose uptake during ischemia. 862 95

The purpose of this experiment is to study the possibility of intra-QRS high-frequency electrocardiographic (HFECG) changes for the evaluation of and recovery from myocardial ischemia in both the time-domain and spectral-turbulence analyses on the signal-averaged ECG using the Holter ECG monitoring (Holter SAECG) system. A balloon catheter was inserted into the left anterior descending coronary artery (LAD of 8 mongrel dogs and was maintained inflated for 2 hours to occlude the LAD and then was deflated to allow for reperfusion. The cardiac signal from the three orthogonal leads of the surface ECG (X, Y, and Z) was recorded and analyzed with a Del Mar Avionics (model 459, Irvine, CA) recorder and analyzer (model 563). The Holter SAECG was assessed before the LAD occlusion phase (control), during the coronary occlusion phase (ischemia), after the reperfusion phase (recovery). To evaluate intra-QRS ECG changes in the time-domain analysis, root-mean-square (RMS) voltage of the entire QRS in 40-250 HZ (40 RMS), 100-250 Hz (100 RMS), and 150-250 Hz (150 RMS) were studied and the vector magnitude of the QRS was depicted. In the spectral-turbulence analysis and spectrocardiogram to study the discordance of the ECG wave front velocity by fast Fourier transformation analysis, the interslice correlation mean (IC mean) and interslice correlation standard deviation (IC SD), which were calculated as the mean and standard deviation of the Pearson correlation coefficient of each time slice with its neighbor, were investigated. In the time-domain analysis, the LAD occlusion by balloon catheter at ischemia produced a reduction in 40 RMS, 100 RMS, and 150 RMS, while a restoration was seen at recovery in 40 RMS and 100 RMS. In the spectral-turbulence analysis, LAD occlusion at ischemia caused a decrease in IC mean and an increase in IC SD. The waveform of the vector magnitude and the spectrocardiogram seen at control showed changes with ischemia and was restored at recovery with the coronary reperfusion. It was thought possible to capture the intra-QRS HFECG changes that occur during myocardial ischemia and recovery from it in the time-domain analysis and spectral-turbulence analysis on the Holter SAECG system in spite of the limitation of this methodology. To evaluate myocardial ischemia and recovery, this method should be useful clinically.
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PMID:Intra-QRS high-frequency ECG changes with ischemia. Is it possible to evaluate these changes using the signal-averaged Holter ECG in dogs? 865 20

Recent data suggest that reduced Ca2+ sensitivity of tension is a mechanism of the post-ischemic myocardial dysfunction, termed stunning. The purpose of the present study was to determine whether the decrease in myofilament Ca2+ sensitivity occurs during ischemia or during the subsequent period of reperfusion. Serial biopsies from an in vivo open-chest porcine model of regional LAD myocardial stunning (n = 6) were used to obtain in vitro measurements of Ca2+ sensitivity of tension in myocardium from the LAD bed. Regional ventricular myocardial function was assessed from percentage systolic myocardial wall thickening (%Th) and the load-independent end-systolic pressure wall thickness relation (ESPTR). Stunning was induced by 45 min of low flow LAD ischemia (43 +/- 4 ml/min/100 gm) followed by 30 min of reperfusion with control aerobic flow (117 +/- 7 ml/min/100 g). Endocardial biopsies were obtained from the LAD bed during pre-ischemia, ischemia (immediately prior to reperfusion), and post-ischemia (after 30 min of reperfusion). Biopsies were mechanically disrupted and single cell-sized preparations of permeabilized myocardium were attached to a force transducer to measure directly steady-state tension-pCa relationships. The % decreased to 7 +/- 11% of control during ischemia (P < 0.001) and returned to 30 +/- 11% of control in the post-ischemic stunned state (P < 0.001). Stunning resulted in a significant leftward shift of the ESPTR as compared to control, indicating depressed regional myocardial function. The pCa (-log[Ca2+]) for half maximal activation of tension, i.e. pCa50, was 5.96 +/- 0.04 in control myocardium and was unchanged during ischemia (5.95 +/- 0.03), but significantly decreased to 5.82 +/- 0.04 upon reperfusion (P < 0.05). These data show that the decrease in Ca2+ sensitivity of tension associated with stunning occurs during reperfusion, and supports the idea that reperfusion injury is a mechanism of myocardial stunning.
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PMID:Onset of reduced Ca2+ sensitivity of tension during stunning in porcine myocardium. 873 97

Both the severity and duration of postischemic myocardial dysfunction ("stunned" myocardium) are unpredictable and may vary considerably between subjects that underwent apparently similar ischemic insults. To explain this heterogeneous response of the heart to ischemia and reperfusion, we investigated the determinants of stunning in conscious dogs. Twenty-five dogs were chronically instrumented for measurement of global and regional myocardial performance (wall thickening) and myocardial perfusion (coloured microspheres). A hydraulic occluder was positioned around the LAD coronary artery. Conscious dogs were subjected to acute coronary artery occlusions of predetermined duration (2, 5 and 10 min), followed by complete reperfusion. Multiple regression analysis identified the following variables as determinants of postischemic contractile recovery: 1) the duration of ischemia (p < 0.01),2) the amount of collateral perfusion (p = 0.01) and 3) left ventricular end-diastolic pressure during ischemia (p < 0.01). Neither the severity of regional dyskinesia during ischemia nor indices of global systolic hemodynamic performance correlated with the rate of recovery. Our data confirm that myocardial stunning relates primarily to the intensity of preceding ischemia. Variations in the preexisting level of collateral perfusion may result in markedly different recovery profiles. Except for LV end-diastolic pressure during ischemia, indices of global and regional cardiac performance fail to predict the severity of postischemic contractile failure.
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PMID:Ischemic event characteristics determine the extent of myocardial stunning in conscious dogs. 874 May 30

We studied the effect of the Na+/H+ exchanger inhibitor methylisobutyl amiloride (MIA, 1 microM) on action potential characteristics and arrhythmias induced by: (a) reperfusion following regional ischemia in rat hearts and (b) realkalization after lactate acidosis in rabbit hearts. We also determined the effect of MIA on the incidence of transient inward currents (ITIs) induced by acidosis-realkalization in rabbit cardiocytes. Ligation of the LAD coronary artery for 10 min depolarized the resting potential from -78 +/- 1.9 mV to -66.9 +/- 1.0 mV and depressed the action potential but did not induce overt arrhythmias. Delayed afterdepolarizations were observed during ischemia in 50% of untreated hearts whereas reperfusion produced severe ventricular tachyarrhythmias in all of them. MIA reduced the incidence of arrhythmias to 27% and their duration to less than 1 min. MIA increased action potential duration by 38 +/- 4.1%. BaCl2 produced a similar APD lengthening and had an antifibrillatory effect. Acidic reperfusion induced bradycardia and reduced severity of arrhythmias. In rabbit hearts, MIA increased the action potential duration by 61 +/- 4.3% and abolished arrhythmias on realkalization. Eleven out of 18 cells developed transient inward currents during acidosis-realkalization and seven of them underwent irreversible injury. MIA prevented the appearance of ITIs, had no effect on ICa,L but decreased the outward component of IK1 by 50%. Our results suggest that the protective effect of MIA is in part due to changes in cellular electrical activity that modulate Na+ and Ca2+ entry via different pathways.
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PMID:Modulation of the electrophysiological effects of ischemia reperfusion by methylisobutyl amiloride. 876 49

Studies were performed to test the influence of propionate as a competing myocardial substrate on acetate and palmitate metabolism in reperfused pig hearts after an exposure of mild-to-moderate regional ischemia. Experiments were conducted in intact, working pig hearts (n = 10) using an extracorporeal coronary perfusion technique. Half the animals received 2 mM propionate selectively into the anterior descending (LAD) perfusate. Perfusion conditions in the LAD circulation were divided into three intervals: an aerobic, preischemic period (0-20 min); an ischemic period affected by a 60% reduction in LAD flow (20-60 min); and an aerobic, postischemic period (60-100 min). Steady-state infusions of (1(-14)C) acetate and [9, 10(-3)H] palmitate were begun at 60 min perfusion to monitor metabolism during reperfusion. Propionate had no effect on oxidation of acetate except for a slight delay in CO2 appearance. Propionate significantly suppressed oxidation of long-chain fatty acids (-38 delta %, P < 0.018), which was not explained by a selective scavenging of CoA units or carnitine by propionate, which might otherwise enhance fatty acid activation, transfer, or oxidation. Propionate by indirect estimates had no apparent effect on glucose metabolism. Propionate-treated hearts, despite shifts in substrate preference, were not further compromised in energy metabolism as levels of creatine phosphate and adenine nucleotides were comparable to control hearts. Recovery of regional mechanical function was also comparable between groups but incompletely, with respect to preischemic performance, compatible with myocardial stunning. The data show in reperfused myocardium that propionate is capable of altering the preferred use of fatty acids, but that anaplerotic entry of carbon units during this reperfusion interval was sufficient to prevent a selective imbalance of energy metabolism or deficit in mechanical recovery.
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PMID:Anaplerotic effects of propionate on oxidations of acetate and long-chain fatty acids. 876 74

S-T segment changes have been cited as evidence for preconditioning in the human heart during repeated angioplasty inflations. Opening of preformed collaterals, however, could explain these observations. We have measured the profile of S-T segment and monophasic action potential (MAP) changes in a species with low collateralization. Open-chested pigs were subjected to two cycles of 8-min LAD occlusion and 8-min reperfusion prior to 60-min ischemia and 2-h reperfusion. Two epicardial ECGs and MAP were continuously recorded from the ischemic zone and one ECG from the normal zone. Flow was measured using Xenon washout. Infarct (IS) and risk zone (RZ) sizes were assessed after reperfusion in a subset of six pigs and confirmed profound protection with preconditioning (IS/RZ = 14 +/- 9% v 42 +/- 3% in controls, P < 0.05). S-T segment elevation was smaller early in the 2nd or 3rd (0-3 min) ischemic cycles than in the 1st. In contrast, in the 1st ischemic cycle, MAP duration after 3 min was reduced to 90 +/- 2% control and this was further reduced in the 2nd and 3rd ischemic episodes to 74 +/- 4% and 77 +/- 3% respectively. Thus, preconditioning increased APD shortening while simultaneously decreasing S-T segment elevation during the early minutes of ischemia. It therefore seems unlikely that the ability of preconditioning to limit S-T segment changes is related to limitations in APD shortening. All electrophysiological differences were lost later during ischemia. Collateral flow during the three ischemic cycles was 4.8 +/- 3.7, 5.8 +/- 2.3 and 5.6 +/- 2.9% (n = 5/grp, ns) respectively. Thus, in the absence of a significant increase in collateral flow. S-T segment and MAP changes provide an index of preconditioning but only during the first few minutes of occlusion. S-T segment changes observed during PTCA may therefore reflect genuine preconditioning in man although the contribution of ischemia-induced increases in collateral flow cannot be ignored.
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PMID:Electrophysiological characteristics of repetitive ischemic preconditioning in the pig heart. 878 75


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