UMLS:C0151744 - FACTA Search

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Query: UMLS:C0151744 (myocardial ischemia)
31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine whether basic fibroblast growth factor (bFGF) administered to the heart by perfusion can improve cardiac resistance to injury we employed an isolated rat heart model of ischemia-reperfusion injury and determined the extent of functional recovery in bFGF-treated and control hearts. Global ischemia was simulated by interruption of flow for 60 min. Recovery of developed force of contraction (DF), recorded after reestablishment of flow for 30 min, reached 63.8 +/- 1.5% and 96.5 +/- 3.5% of preischemic levels in control and bFGF-treated hearts (10 micrograms/heart), respectively, indicating that bFGF induced significantly improved recovery of mechanical function. Recoveries of the rates of contraction or relaxation were also significantly improved in bFGF-treated hearts. Extent of myocardial injury, assessed by determination of phosphocreatine kinase in the effluent, was reduced as a result of bFGF treatment. As a first step towards understanding the mechanism and direct cellular target(s) of bFGF-induced cardioprotection, we investigated its fate after perfusion. Perfusion of 10 micrograms bFGF/heart resulted in a 4-fold increase in bFGF associated with the heart compared to control levels, as estimated by biochemical fractionation and immunoblotting. Immunofluorescent staining of the bFGF-perfused hearts revealed intense anti-bFGF staining in association with blood vessels as well as the periphery of cardiomyocytes, suggesting that the latter may be a target for direct bFGF action. In conclusion, our findings of bFGF-induced increases in cardiac resistance to, and improved functional recovery from, ischemia-reperfusion injury indicate that bFGF may have clinical applications in the treatment of ischemic heart disease.
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PMID:Basic fibroblast growth factor is cardioprotective in ischemia-reperfusion injury. 759 47

Cardiac ischemia can be provoked by different methods in animal models and in isolated organs. Accordingly, three different procedures were followed to find the most sensitive model for the analysis of the anti-ischemic activity of calcium antagonists. The experiments were performed in the isolated working heart preparation of the rat, paced at the frequency of 5 Hz and perfused with Tyrode solution at 37 degrees C. Global ischemia was achieved by closing off the supply of the perfusion medium and surrounding the heart with Tyrode solution of 37 degrees C gassed with N2; low-flow ischemia was achieved by reducing the cardiac afterload from 51.5 to 11.0 mm Hg; ligation of the left descending coronary artery was performed in order to provoke regional ischemia. Nifedipine was applied in a concentration (EC50) known to reduce the contractile force by one-half of its basal value. The following parameters were determined after 15 min of nifedipine pretreatment and at the end of the experiment: LVP (left ventricular pressure),+dP/dtmax (LVP's first derivative), AO (aortic output), CF (coronary flow), and CO (cardiac output). From the data obtained, the percentages of recovery were calculated. Nifedipine caused a significant improvement in the functional recovery of most of the parameters studied. This improvement, however, was much more pronounced in the model of the low-flow ischemia, which is obviously more sensitive to the anti-ischemic activity of calcium antagonists than the other experimental procedures studied. Low-flow ischemia appears to be preferable to other procedures for the screening of the potential anti-ischemic activity of calcium antagonists and other drugs.
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PMID:Cardioprotection by nifedipine in isolated working hearts: a comparative study on three different types of experimental ischemia. 767 82

A potential detrimental role of endothelin-1 in myocardial ischemia/reperfusion injury was studied by use of the endothelin-1 antagonists BQ123 and BQ610. Isolated isovolumetric rat hearts were perfused at constant pressure. BQ123 (7 micrograms/min) and BQ610 (1.75 micrograms/min) did not alter mechanical function or coronary flow and shifted dose-response curves for endothelin-1 significantly to the right. In rats subjected to 30 min of no-flow ischemia, the increase of left ventricular resting pressure was significantly delayed by BQ123 and BQ610 compared to control (BQ123: 20 +/- 2* mmHg, BQ610: 19 +/- 2* mmHg, control: 44 +/- 4 mmHg at 15 min of ischemia, respectively, *P < 0.05 v control). With reperfusion after 30 min of ischemia, recovery of left ventricular developed pressure was not significantly affected but tended to be better with endothelin-1 antagonist pretreatment (BQ123: 20 +/- 3 mmHg; BQ610: 19 +/- 3 mmHg, control 12 +/- 3 mmHg). However, in hearts subjected to 15 min of ischemia followed by reperfusion, recovery of left ventricular developed pressure was improved by BQ610 pretreatment (BQ610: 52 +/- 8* mmHg, control: 24 +/- 6 mmHg). We conclude: BQ123 and BQ610 effectively antagonize the coronary constrictive effect of endothelin-1. BQ123 and BQ610 delay the development of contracture during ischemia and may improve functional recovery during reperfusion. Our findings suggest that endogenous endothelin-1 may contribute to ischemia/reperfusion injury.
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PMID:Endothelin-1 contributes to ischemia/reperfusion injury in isolated rat heart-attenuation of ischemic injury by the endothelin-1 antagonists BQ123 and BQ610. 777 81

This experiment was designed to determine the relative degree of cardiac functional recovery provided by various forms of resuscitative retrograde blood cardioplegia after global ischemic injury. Twenty-four dogs were subjected to 20 minutes of normothermic global myocardial ischemia followed by 60 minutes of cardioplegic arrest by one of three methods: group 1, standard cold blood cardioplegia with a cold terminal dose (n = 8); group 2, aspartate-glutamate-enhanced blood cardioplegia with warm induction and terminal enhancement (n = 8); and group 3, continuous warm blood cardioplegia (n = 8). Sonomicrometry was used to analyze left ventricular function for maximal elastance and preload recruitable stroke work area. Data were recorded at baseline and after 30 and 60 minutes of unloaded reperfusion. The results showed improved early recovery of preload recruitable stroke work area, but not of maximal elastance, after reperfusion of ischemic hearts with warm resuscitative blood cardioplegic solution enhanced with amino acids. The functional improvement provided by this technique was transient, however, and no significant differences were detectable among the groups after 60 minutes of unloaded reperfusion. Neither amino acid enhancement nor continuous warm cardioplegia offered a significant advantage in functional recovery over the standard method of cold blood cardioplegia reperfusion.
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PMID:Resuscitative retrograde blood cardioplegia. Are amino acids or continuous warm techniques necessary? 785 77

Stunning (reversible myocardial ischemia without necrosis) occurs with induced global ischemia during cardiac operations and depresses the ability of the heart to utilize oxygen efficiently because less contractile work is developed per unit of oxygen utilized. Interestingly, regional studies have demonstrated dramatic infarct size reduction with stunning episodes before prolonged ischemia, a phenomenon known as myocardial preconditioning. It is postulated that the postischemic contractile dysfunction noted after stunning causes reduced energy demands, which "preconditions" myocardium to withstand a subsequent longer ischemic episode. Some evidence from regional studies suggests that preconditioning may improve functional recovery after ischemia. This study examined the complex relationship between stunning and preconditioning to functional recovery in a surgical setting of global ischemia. To study the effect of stunning, myocardial oxygen consumption, oxygen extraction, and functional indices of contractility were measured before and after isolated rabbit hearts were subjected to 10, 20, or 45 minutes of normothermic 37 degrees C global ischemic stun intervals. This demonstrated that while oxygen consumption and extraction quickly recover to prestun levels, contractility remains depressed well beyond the stun interval. To study the effect of preconditioning using stunning, isolated hearts were then subjected to 120 minutes of 34 degrees C cardioplegic-induced ischemia after preconditioning. Hearts received either modified St. Thomas cardioplegic solution as a control or cardioplegia administered after preconditioning with 37 degrees C ischemic stunning for 5, 10, 15, 20, or 45 minutes or multiple 5- or 10-minute stuns, with reperfusion before cardioplegic-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stunning, preconditioning, and functional recovery after global myocardial ischemia. 794 10

This study was designed to determine whether the novel perfluoroperhydrophenanthrene-egg yolk phospholipid emulsion, APE-LM, was an effective oxygen carrier for long-term hypothermic heart preservation. We postulated that hearts preserved with APE-LM would be well oxygenated during 24-hour preservation and that reperfusion of such hearts with blood would not produce functional or metabolic evidence of myocardial ischemia. Four groups of rabbit hearts were studied (n = 7 per group): fresh controls: nonpreserved, nontransplanted hearts; surgical controls: fresh hearts transplanted heterotopically for 75 minutes before explant and study for 4 hours as isolated working hearts perfused at 37 degrees C; crystalloid-preserved: hearts preserved with crystalloid medium, followed by transplantation and isolated heart perfusion; APE-LM-preserved: hearts treated as those in the crystalloid-preserved group, but preservation was with medium containing APE-LM emulsion (10 ml/dl). Preservation was with continuous coronary perfusion at 18 mm Hg pressure, 12 degrees C, and oxygen tension 838 +/- 11 mm Hg. During preservation, APE-LM hearts had significantly higher pyruvate consumption, and correspondingly higher oxygen consumption, than that of crystalloid hearts. No significant differences were found among fresh controls, surgical controls, and APE-LM-preserved hearts with respect to contractile or output function, oxygen consumption and efficiency indexes, or lactate production during in vitro perfusion. Left ventricular peak systolic pressure and peak rate of pressure development were significantly lower for crystalloid-preserved hearts than for fresh and surgical controls. Left ventricular end-diastolic pressure of crystalloid-preserved hearts was higher than that of the other three groups. The data indicate that rabbit hearts in this model were well preserved with APE-LM and that this emulsion produced better recovery of function than did crystalloid preservation, possibly as a consequence of the high oxygen delivery by the fluorocarbon during preservation.
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PMID:Posttransplantation function of hearts preserved with fluorochemical emulsion. 794 84

Recent evidence suggests a cardioprotective effect of adenosine in myocardial ischemia and reperfusion. The present study was undertaken to determine (1) whether adenosine attenuates myocardial stunning, (2) if so, whether the beneficial effect of adenosine takes place during ischemia or after reperfusion, and (3) whether adenosine preconditions against myocardial stunning. A total of 93 dogs were used. In phase A of the study, open-chest dogs undergoing a 15-minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion received an intracoronary infusion of either saline (group I [control], n = 14), 2 mg/min adenosine from 30 minutes before occlusion until 1 hour after reperfusion (group II, n = 10), or 2 mg/min adenosine from 2 minutes before reperfusion until 1 hour after reperfusion (group III, n = 11). Regional myocardial function (assessed as systolic wall thickening) was similar in the three groups at baseline and during ischemia. After reperfusion, dogs treated with adenosine before, during, and after ischemia (group II) demonstrated a significant improvement in the recovery of function that persisted throughout the 4 hours of reperfusion. In contrast, in dogs treated only during the reperfusion period (group III), the recovery of function was not statistically different from that in control dogs. The enhanced recovery effected by adenosine in group II could not be ascribed to differences in ischemic zone size, collateral flow during occlusion, coronary flow after reperfusion, arterial pressure, heart rate, or other hemodynamic variables. In phase B of the study, dogs received an intracoronary infusion of either saline (group IV [control], n = 6) or adenosine (4 mg/min from 40 to 10 minutes before occlusion [group V, n = 6]). Despite pretreatment with adenosine, the recovery of function in group V was indistinguishable from that in the control group. This study demonstrates that (1) continuous administration of adenosine before, during, and after ischemia results in a significant and sustained attenuation of myocardial stunning; (2) this improved recovery of function cannot be attributed to nonspecific variables, such as collateral flow during coronary occlusion, coronary flow after reperfusion, or other hemodynamic factors, and therefore reflects a direct cardioprotective action of adenosine; (3) the protection against stunning is lost or markedly diminished if adenosine is given only at reperfusion; and (4) administration of adenosine before ischemia does not precondition the myocardium against the stunning induced by a 15-minute occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of adenosine on myocardial 'stunning' in the dog. 800 Dec 81

The aim of the study was to compare the ability of dobutamine and dipyridamole echocardiography to detect stunned but viable myocardium early after acute myocardial infarction, to predict spontaneous functional recovery of the reperfused myocardium at 2 months and to detect myocardial ischemia in the infarcted area. Within 10 days from acute myocardial infarction, 47 patients, 29 anterior and 18 inferior, 41 Q-wave and 6 non Q-wave infarctions, underwent dobutamine echocardiography test at low-dose (5-10 mcg/kg/min over 5 min) and high-dose (20-40 mgc/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) in different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at 2 months in 38/47 patients. Regional wall motion analysis was performed in a qualitative manner on a 14-segment model; viability was defined as improvement of 1 grade or more of at least 2 basally asynergic segments in the infarcted area. Ischemia was defined as an improvement followed by significant deterioration of contractility of the infarcted segments or deterioration of the infarcted area. All patients underwent coronary arteriography within 1 month from admission. Viability was detected by low-dose dobutamine in 34/47 patients (72%) and in 131/297 (44%) of basally asynergic segments compared to only 21/47 patients (45%) and in 66/297 segments (22%) detected by dipyridamole; myocardial ischemia was induced by dobutamine in 64% of patients compared to 36% by dipyridamole. Late spontaneous functional recovery was detected in 21/38 patients (57%) and in 70/244 (29%) of asynergic segments. Sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 70% and 46% specificity 69% and 83%, positive predictive value 48% and 52%, negative predictive value 85% and 79% respectively. Dobutamine correctly identified the presence of a significant stenosis of the infarct-related artery in 74% of cases compared with 43% of dipyridamole; specificity for detecting stenosis was 67% for dobutamine and 83% for dipyridamole. In conclusion, in patients with thrombolyzed myocardial infarction dobutamine echocardiography detects viable myocardium with late spontaneous recovery in a greater proportion of patients and segments than dipyridamole; dobutamine has a higher sensitivity but a lower specificity compared to dipyridamole for identifying a residual stenosis of the infarct-related artery that may jeopardize myocardium in the area at risk.
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PMID:[The echo-dobutamine and echo-dipyridamole tests in assessing vital myocardium and residual ischemia in myocardial infarct after thrombolysis]. 801 19

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 +/- 2.8 mmHg in group II and 31.3 +/- 8.1 mmHg in group III vs 45.0 +/- 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 +/- 5.4%, 98.9 +/- 6.1%, 85.3 +/- 4.8% of baseline values, respectively, in group II, to 64.5 +/- 3.0% (P > 0.05), 76.8 +/- 3.0%, 70.2 +/- 4.0% in group III, vs 52.0 +/- 6.5%, 58.9 +/- 6.9% and 53.6 +/- 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 +/- 2.2 ml/min and 19.8 +/- 1.8 ml/min in groups II and III vs 14.8 +/- 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before or after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca(2+)-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.
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PMID:R56865, a Na(+)- and Ca(2+)-overload inhibitor, reduces myocardial ischemia-reperfusion injury in blood-perfused rabbit hearts. 815 64

Myocardial ischemia and infarction are known to cause changes in both ventricular shape and function. Little is known about the recovery of ventricular geometry after transient myocardial ischemia and its relationship to recovery of function. To examine the pattern of recovery of ventricular geometry following transient coronary artery occlusion and to assess the relationship of this to the return of systolic function, we used echocardiography to study 13 dogs following 15-minute occlusion of the left anterior descending coronary artery. During ischemia, total endocardial surface area (ESA) increased from 32.55 +/- 1.77 to 45.36 +/- 3.18 cm2 (p = 0.001). The most striking increase was at the apex, where circumference increased from 5.04 +/- 0.24 at baseline to 7.86 +/- 0.43 cm at the end of occlusion (p = 0.0001), an increase of 58%. During reperfusion, ventricular geometry rapidly returned toward normal (baseline), with recovery of 80% of the increase in ESA evident by 15 minutes of reperfusion. Recovery of systolic function was substantially slower (p < 0.005 for all periods of observation during the 2 hours of reperfusion). During reperfusion, recovery of ventricular geometry and function was not uniform throughout the ischemic bed. The apex recovered most slowly, with the centroid of the area of abnormal contraction progressively moving along the long axis of the left ventricle toward the apex. There was also a progressive decrease in the radius of the area of dysfunction, from 2.0 +/- 0.15 at end occlusion to 0.13 +/- 0.07 cm at 120 minutes of reperfusion (p = 0.0001). There was no difference in blood flow between the apical and anterior segments during ischemia or reperfusion. Reperfusion favorably reduced the ischemic zone dilation before recovery of active systolic function and geometric recovery thus may be important in determining ultimate functional recovery. In addition, recovery of function proceeded inward towards the center of the ischemic territory and in a wavefront from the base to apex. This heterogeneous and asymmetric recovery suggests that sampling at one point within the ischemic zone may not reflect the true temporal pattern of recovery.
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PMID:Spatial and temporal variability in the pattern of recovery of ventricular geometry and function after acute occlusion and reperfusion. 817 51

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