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

On anaesthetized open-chest mongrel dogs (n = 7) short-time (3 min), repeated ischemia of relatively large parts of the myocardium was produced by proximal, intermittent occlusion of the LAD artery in intervals of 45 min. Usually, 2-3 control occlusions and 2-3 occlusions under therapy were performed. From hemodynamic data, coronary blood flow and AVD-O2 myocardial oxygen consumption (MVO2) and energy demand (Et) were continuously recorded by use of a micro-computer. The occurring difference between MVO2 and Et (dO2) allowed to calculate during the occlusion period the O2-debt (DO2) and during the reperfusion period the O2-repayment (RO2). Furthermore, the releases of the metabolic ischemia parameters lactate, inorganic phosphate and potassium were determined in the first minute of postischemic reperfusion. Compared to control occlusions, premedication with verapamil (Isoptin) 0.12--0.2 mg/kg b.w.) led intra- and interindividually to a significantly reduced O2-debt (p less than 0.001) during the occlusion period combined with a significantly reduced amount of oxygen, additionally taken up in the early reperfusion period (p less than 0.001). Under verapamil the amounts of metabolic parameters released in the first minute of reperfusion decreased significantly: lactate: -36% (p less than 0.001), inorganic phosphate: -32% (p less than 0.001), potassium: -30% (p less than 0.001). The improvement of the metabolic and energetic situation of ischemic myocardium indicates that verapamil may be of importance in reducing the extent and severity of acute myocardial ischemic injury.
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PMID:Improvement of the metabolic and energetic situation of ischemically stressed myocardium by verapamil after experimental coronary artery occlusion. 668 50

Using the ultrastructural criteria established by Schaper et al. 1979 [27] for distinguishing between different degrees of ischemic change in dog myocardium, slight ischemic changes are observed in the pig suboendocardium as early as 1 min after occlusion of the LAD artery. Moderate change throughout the thickness of the myocardium is seen after 6 to 12 min of ischemia and continues to be found up until 20 min after commencement of the ischemic period. 20 to 30 min ischemia produces severe ischemic damage and more than 30 min leads to irreversible damage. The changes are uniform at all stages of ischemia and there is no evidence of a transmural gradient of ultrastructural damage. Of particular interest in the early part of the ischemic period is the observation of ultrastructural changes in the subendocardial specialized conducting tissue. In these specialized cells, although morphological features consistent with slight and moderate ischemia are found as early as 1 to 2 min after occlusion, spontaneous recovery occurs and is complete by 15 min. This biphasic time course parallels the electro-physiological changes known to occur in ischemic Purkinje fibres.
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PMID:Ultrastructural changes of ischemic injury due to coronary artery occlusion in the porcine heart. 669 20

As criterion for the degree of ischemic stress on myocardium during repeated coronary artery occlusion, the reproducibility of the release of potassium, lactate and inorganic phosphate in the early reperfusion period was examined. On 20 anaesthetized open-chest mongrel-dogs, local ischemia was induced by intermittent occlusion of the LAD artery. In each experiment the artery was occluded for 3 min 4 to 6 times with intervals of 45 min. Just before beginning, at the end of occlusion and after 5 min of reperfusion, arterial and coronary venous blood was collected simultaneously. Additionally, 3 ml of blood were withdrawn by syringe-pumps during the first minute of reperfusion. Intra-individually, the following standard-deviations were found in a representative experiment with 5 occlusions: potassium +/- 7% (22.62 +/- 1.6 mumol/min); inorganic phosphate +/- 9% (19.82 +/- 2.06 mumol/min); lactate +/- 11% (55.38 +/- 5.93 mumol/min). Interindividually, the correlation between the release of these markers and the perfusion bed of the ligated artery led to coefficients of about r approximately 0.88. On an average, per gram ischemic tissue/wet weight 0.74 mumol potassium, 0.6 mumol inorganic phosphate and 1.98 mumol lactate were released. The ratios between the releases remained constant independent of the size of ischemic area. An even closer correlation with coefficients of about r approximately 0.97 was found between the O2-debt in the occlusion period. Based on a synoptic assessment of metabolic and energetic parameters, this experimental model may render more detailed information on pharmacological interventions during ischemic stress.
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PMID:Quantification of ischemic stress during repeated coronary artery occlusion in the dog. A method for validation of therapeutic effects. II. Reproducibility of the release and uptake of electrolytes and substrates. 673 19

To assess the results of transluminal coronary angioplasty (TCA), 42 patients (mean age 50 years) with for coronary artery disease were investigated at rest and during exercise with the ECG (n = 40), thallium-201 myocardial scintigraphy (n = 23) and equilibrium-radionuclide ventriculography (n = 32). Each method of stress testing was quantified: the exercise ECG by means of an ischemia score, incremented with increasing ST-segment depression and decremented as a function of duration of exercise and workload in watts; thallium-201 scintigraphy by means of an index for minimal to maximal perfusion region (vitality index) and redistribution factors; equilibrium-radionuclide ventriculography by means of global ejection fraction and maximum systolic volume change with respect to the end-diastolic volume. The patients were divided into three groups: 30 had successful TCA defined as demonstrating at least a 20% reduction in the stenosis; six underwent aortocoronary bypass operation (nine grafts; complete revascularization in four patients); and in six patients TCA was unsuccessful. TCA was successful in 24 LAD stenoses, 5 RCA stenoses, and in one proximal anastomosis of an aortocoronary bypass graft. Dilatation could not be achieved in three LAD stenoses and three stenoses of the RCA. In those in whom it was successful, TCA yielded an average reduction of coronary artery stenosis from 84 to 43%. Both TCA and bypass operation (OP) led to comparable degrees of functional improvement. The ischemia score decreased from 2.8 to 0.9 after TCA and from 1.6 to 0 after OP. The vitality index increased from 67 to 77% and from 74 to 81% after TCA and OP respectively while the corresponding redistribution factors decreased (TCA: at 1 hour from 5 to 1% and at 3.5 hours from 11 to 4%; OP: at 1 hour from 2.2 to 1.4% and at 3.5 hours from 7.6 to 4.1%. The global ejection fractions at rest improved from 46 to 52% and from 38 to 45% and during exercise from 42 to 50% and from 36 to 43% after TCA and OP respectively. The maximum--dV/dt/EDV increased at rest (TCA: from 2.7 to 3.5 per second; OP: from 2.1 to 3.8 per second) and during exercise (TCA: from 3.1 to 4.0 per second; OP: from 2.6 to 3.3 per second). In the group with unsuccessful TCA, no significant differences in the latter parameters were observed. Ten of the 30 patients who had undergone successful dilatation were reinvestigated after three months. Maintenance of good functional results could be documented in eight while deterioration was seen in two patients, one with a significant restenosis and one who developed a new narrowing distal to the successfully dilated stenosis. Thus, the results show that in selected cases, TCA can render improved ventricular function and perfusion comparable to that of aortocoronary artery bypass surgery.
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PMID:[Improved myocardial function after transluminal coronary angioplasty (author's transl)]. 697 30

This study examines the relative importance of the duration of ischemia versus the adequacy of cardioplegic distribution and protection in hearts with coronary stenoses. Of 18 dogs on cardiopulmonary bypass, 12 underwent critical narrowing (greater than 90%) of the left circumflex artery (LCA) and total occlusion of the anterior descending coronary artery (LAD). In six dogs (control) the coronary arteries were patent. A 16 degrees C blood cardioplegic solution was given at 20 minute intervals of aortic clamping. In control dogs and in six dogs with stenoses, the aorta was clamped for 60 minutes. In the latter group, the stenoses were removed after 20 and 40 minutes to simulate sequential completion of grafts and better cardioplegic distribution. In the remaining dogs with stenoses, the aorta was clamped for only 30 minutes, with stenoses removed after the heart had been returned to the beating empty state for 30 minutes to simulate doing distal grafts with cardioplegic protection and proximal grafts during reperfusion (traditional technique). With sequential grafting, myocardial temperature was lower (16 degrees C versus 22 degrees C) and incidence of reperfusion fibrillation less than with the traditional technique. Despite a greater ischemic interval, sequential grafting with adequate cardioplegic distribution resulted in less lactate washout (5 +/- 15 versus 35 +/- 6 cc/100 gm/min), greater recovery of compliance, and higher stroke work indices (1.32 +/- 0.12 versus 0.75 +/- 0.15 kg-m/min). We conclude that the success of myocardial protection with potassium cardioplegia in hearts with coronary stenoses is related more to ensuring its distribution than to limiting the duration of ischemic arrest with the false assumption that the heart is reperfused adequately while proximal grafts are completed in the beating empty state.
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PMID:Critical importance of ensuring cardioplegic delivery with coronary stenoses. 720 57

This study was performed to determine the early and delayed metabolic effects of myocardial ischemia on the major membrane phospholipids and to reassess the potential role of lysophospholipids in the genesis of malignant dysrhythmias induced by ischemia. Samples taken from in situ hearts before ant at various intervals up to 40 minutes after abrupt ligation of LAD were extracted by the classical Folch technique with modifications to avoid artifactual lysophospholipid production and losses. Following thin layer chromatography of lipid extracts, phospholipid fractions were quantified by phosphorus estimation and lysophospholipids by a more sensitive method employing gas liquid chromatography. The total phospholipid content with the exception of lysophospholipids remained essentially constant throughout the early phases of acute ischemia, but fell by 6 and 14% after 8 and 24 ours, respectively. At 8 minutes, lysophospholipid levels n ischemic myocardium were significantly increased by 60% compared to pre-occlusion controls in the ischemic zone and by 25% in post-occlusion controls. They changed little thereafter. The molecular species of lysophospholipids remained unchanged throughout the period of ischemia studied. The mole fraction of other phospholipids as well as their fatty acyl and aldehyde profiles also were unchanged. Despite significant elevations in lysophospholipids levels, their absolute quantities were very small (0.6% of total phospholipid P) and 15-fold smaller than that reported in vitro to simulate electrophysiological manifestation of ischemia. However, such small amounts in vivo, if produced in the microenvironment of certain membrane-bound enzymes along with acidosis, hypoxia, and fatty acids, could be potentially deleterious to cell functions.
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PMID:Time course of changes in porcine myocardial phospholipid levels during ischemia. A reassessment of the lysolipid hypothesis. 724 69

This study was designed to compare a new investigational coronary perfusion balloon (Wave, Scimed Life Systems Inc.) with that of an approved, widely used, current generation device (Flowtrack 40, Advanced Cardiovascular Systems). Domestic swine were anesthetized with pentobarbital and instrumented using standard percutaneous technique. Left ventricular contractile function (dP/dt) was monitored using a micromanometer while intracoronary and surface ECGs were also recorded. Eight target vessels were studied (4 LAD and 4 Cx) in random order. The perfusion balloons were kept inflated for 10 min. Complete coronary occlusion with a standard angioplasty balloon produced marked decreases in mean aortic pressure, left ventricular developed pressure, peak +dP/dt, peak -dP/dt, and significant ST segment elevation in both intracoronary and surface ECG at 30 seconds. Neither the Wave or Flowtract 40 produced any change in heart rate or mean aortic pressure. Both catheters caused a drop in left ventricular developed pressure immediately after balloon inflation. At 10 min, however, there was a small but significant decrease only with the Flowtrack 40. Similarly, peak +dP/dt was slightly depressed during Flowtrack 40 inflation at 10 min but not with the Wave catheter. Both catheters produced ST segment elevation on the surface and intracoronary electrocardiographic records. These changes were significantly greater with the Flowtrack 40 system. Thus, both the Flowtrack 40 and Wave perfusion balloons are effective in preventing ischemia during coronary occlusion in swine; however, the latter system may be more effective in this model.
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PMID:Functional characteristics of a new coronary perfusion balloon: comparison with the Flowtrack 40 in closed chest swine. 871 99

We studied the electrophysiologic and antifibrillatory properties of MS-551 (1,3-dimethyl-6-((2-[N-hydroxy-ethyl)-3-(4-nitrophenyl) propylamino] ethylamino) 2,4(1H,3H) pyrimidinedione hydrochloride) in a conscious canine model of sudden cardiac death. Three to 5 days after surgically induced myocardial infarction (MI: 2-h occlusion of the left anterior descending coronary artery, LAD), animals were subjected to programmed electrical stimulation (PES) to identify those at risk for sudden cardiac death. MS-551 was administered (2.0, 3.0, or 4 x 2.0 mg/kg intravenously, i.v.). Vehicle-treated animals received 0.9% sodium chloride solution for injection. MS-551 (multiple-dose regimen) increased ventricular effective refractory period (VERP) from 112 +/- 4 to 137 +/- 4 ms (p < 0.05) as compared with vehicle treatment, which did not alter VERP (125 +/- 6 to 121 +/- 5 ms). MS-551 prolonged QTc interval from a predrug value of 293 +/- 8 to 333 +/- 18 ms postdrug. The size of surgically induced MI did not differ among groups: 2.0 mg/kg, 23 +/- 4%; 3.0 mg/kg, 28 +/- 2%; 4 x 2.0 mg/kg, 25 +/- 3%; and vehicle, 28 +/- 3% of the left ventricle. Single bolus administration of MS-551 (2.0 or 3.0 mg/kg i.v.) did not confer significant protection against sudden cardiac death. However, repeated administration of MS-551 protected against sudden cardiac death in 8 of 10 dogs as compared with 2 of 12 in the vehicle-treated group (p < 0.05). The data indicate that a multiple-dose regimen of MS-551 provides protection against ischemia-induced ventricular fibrillation (VF) in the postinfarcted heart. The mechanism by which MS-551 achieves its antifibrillatory effect most likely depends on its ability to prolong VERP of myocardium without altering ventricular conduction velocity.
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PMID:MS-551 protects against ventricular fibrillation in a chronic canine model of sudden cardiac death. 775 58

We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if mitigates electrophysiologic changes produced by regional myocardial ischemia in vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, i.v.) or glibenclamide (0.15 or 0.3 mg/kg, i.v.) was administered before the third occlusion, and the data were compared to the second occlusion data. 5-HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 +/- 2% during the second occlusion vs. 5 +/- 3% during the third occlusion, n = 8, p < 0.01) and APD50 (16 +/- 3% vs. 10 +/- 3%, n = 8, p < 0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias.
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PMID:Blockade of ATP-sensitive potassium channels by 5-hydroxydecanoate suppresses monophasic action potential shortening during regional myocardial ischemia. 787 72

Calcium antagonists are generally considered to have no substantial effect on repolarization of the myocardium, so they have no direct effect on T wave, either. But in a pig model of myocardial ischemia, intracoronary nifedipine was found to reverse the inverted T wave induced by ischemia to upright promptly. Ten pigs were anesthetized with the chest opened, anterior interrentricular branch of left coronary artery (LAD) was narrowed to 4.67 kPa of LAD pressure, and then adenosine or nifedipine was infused into the coronary respectively. During the 9-minute ischemia, intracoronary adenosine or intracoronary nifedipine got the similar HR, LVEDP, LVDP, CAP, CAQ, and the intracoronary adenosine even got higher CAQ than the intracoronary nifedipine did. However, the T wave was retained inverted during the adenosine infused, but during the intracoronary nifedipine, the inverted T wave was promptly turned upright. The relevant factors and mechanisms are discussed.
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PMID:[Effect of nifedipine on T wave in ischemic myocardium]. 789 45


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