Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The preservation of heart and lung for transplantation remains a major concern in extended ischemic intervals. This experiment evaluated the effect of high molecular weight deferoxamine and a platelet-activating factor antagonist (CV-3988) in ischemic reperfused tissue. Heart-lung transplantation was performed in a swine model after 4 hours 45 minutes of ischemia. Animals were divided into three groups. Group A was a control without pharmacological intervention. In group B, high molecular weight deferoxamine, 50 mg/kg, was used, and in group C, platelet-activating factor antagonist CV-3988, 10 mg/kg, was used. The results of functional variables (cardiac index, stroke index, lung water, oxygen and carbon dioxide tensions, alveolar-arterial gradient, and alveolar-arterial ratio) demonstrated superior heart and lung function for groups B and C compared with the control group. These alterations of heart and lung function were significantly less (p less than 0.001) in group C, in which the platelet-activating factor antagonist (CV-3988) was used. The study revealed that formation of hydroxyl radicals and platelet-activating factor play an important role in the pathogenesis of ischemia reperfusion injury. Prevention of hydroxyl radical formation with high molecular weight deferoxamine and inactivation of platelet-activating factor with CV-3988 reduce the ischemia-reperfusion injury significantly.
 ...
PMID:Effects of platelet-activating factor antagonist CV-3988 in preservation of heart and lung for transplantation. 192 20

The role of oxygen (O2) in blood cardioplegia (BCP) remains controversial. On the one hand, O2 reduces ischemic injury between BCP infusions by maintaining energy production through oxidative pathways. On the other hand, O2 carried by blood may not be released to the tissue at 4 degrees C or potentially provides substrate for deleterious O2 radical species. This study tests the hypothesis that O2 is a critical component in myocardial protection afforded by BCP. In 17 anesthetized dogs, left ventricular performance was measured by left ventricular end-systolic pressure-volume relations using the position of the end-systolic pressure-volume relation quantitated by the left ventricular midrange volume intercept at 100 mm Hg (V100) to describe performance. After 30 minutes of global normothermic ischemia, hearts were protected with multidose 4 degrees C BCP for 1 hour of arrest. Oxygen content in BCP was adjusted to 1.1 +/- 0.2 vol% (n = 7; desaturated BCP group), 4.3 +/- 0.5 vol% (n = 5; intermediate oxygenated BCP group), or 10.2 +/- 0.6 vol% (n = 5; saturated BCP group) using a membrane oxygenator interposed in the BCP circuit and aerated with an appropriate mixture of O2, nitrogen, and carbon dioxide. After 1 hour of 37 degrees C reperfusion, 3 of the 7 dogs in the desaturated BCP group failed to generate sufficient cardiac output to discontinue bypass. In the remaining 4 dogs, severe left ventricular depression caused a rightward shift in V100 from 17 +/- 4 to 47 +/- 9 mL (p = 0.02). With intermediate BCP, all hearts were weaned from bypass with marginal left ventricular depression (V100, 20 +/- 5 versus 46 +/- 16 mL; p = 0.10). In contrast, hearts protected with saturated BCP showed no significant increase in V100 (13 +/- 4 versus 24 +/- 13 mL; p = 0.23). We conclude that O2 in BCP is critical to its myocardial protective properties.
 ...
PMID:Efficacy of myocardial protection with hypothermic blood cardioplegia depends on oxygen. 192 59

The cheek pouch was prepared as a single layer and attached to a two-piece Lucite chamber that was filled with bicarbonate buffer (pH 7.35, equilibrated with 95% N2-5% CO2). Two microcirculatory areas were circumscribed in the cheek pouch by equilateral triangular chambers. Each chamber was made of 90-microns thick Mylar sheet (2 mm wide, 18 mm long). A cover slip was used as the chamber top. Ischemia was induced by applying pressure to the cover slip. The experimental area was reperfused after 1 h of ischemia by releasing the pressure. The other area served as control. One hour of reperfusion after 1 h of ischemia caused a significant increase in the number of leukocytes adhering to postcapillary venules (PCVs) per 100 microns vessel length in the ischemic area relative to the values in the control area (7.8 +/- 2.5 vs. 3.7 +/- 1.3, respectively, for PCVs 10-19.9 microns diam; and 10.9 +/- 2.8 vs. 6.2 +/- 1.8 for PCVs 20-29.9 microns diam; P less than 0.01 for both comparisons). The results demonstrate the adequacy of the model to investigate leukocyte adhesion to endothelium in ischemia-reperfusion. Because blood flow is maintained in most of the pouch, our model should also be useful for identifying possible interactions between ischemic and nonischemic areas in the microcirculation.
 ...
PMID:A new model for studying ischemia-reperfusion injury in hamster cheek pouch. 195 48

The authors sought to determine how hypoperfusion influences acid-base balance in arterial and mixed venous blood. In anesthetized, ventilated pigs (n = 12), we determined hemodynamics, O2 uptake, CO2 output, dead-space ventilation, arterial and mixed venous blood acid-base balances, and lactate concentrations during graded reductions in cardiac output by incremental positive end-expiratory pressure (PEEP, 0-20 cm H2O). Cardiac output decreased from 3.2 +/- 0.2 (mean +/- SEM) to 1.2 +/- 0.1 L/min at 20 cm H2O PEEP. Oxygen delivery declined more than O2 uptake did by 60% +/- 2% and 27% +/- 2%, respectively. The decrease in CO2 output (by 21% +/- 2%) was less than that in O2 uptake. Fractional dead-space ventilation increased. At a slight increase in carbon dioxide tension (PCO2) of 4 +/- 1 mm Hg, pH decreased in arterial blood from 7.54 +/- 0.01 to 7.47 +/- 0.02 mmol/L, and standard bicarbonate decreased from 30.3 +/- 0.5 to 27.5 +/- 0.6 mmol/L. The decrease in standard bicarbonate exceeded the increase in blood lactate concentrations. At a similar decrease in standard bicarbonate, the decrease in pH was larger (P less than 0.005) in mixed venous blood than in arterial blood owing to a larger increase in PCO2 (from 40 +/- 2 to 50 +/- 2 mm Hg, P less than 0.005). The changes were reversed after discontinuing PEEP. The authors conclude that ischemia after incremental PEEP results in tissue metabolic acidosis with superimposed respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Arterial and mixed venous blood acid-base balance during hypoperfusion with incremental positive end-expiratory pressure in the pig. 195 38

The vascular endothelium is important in the modulation of vascular tone via production of endothelium-derived relaxing and contracting factors. The abdominal aortas of five groups of rabbits were subjected to varying lengths of ischemia (0, 1, 2, 3, or 4 hours), removed, sectioned into transverse rings, and placed in tissue baths containing Krebs' buffer at 37 degrees C and aerated with 95% O2/5% CO2. After equilibration the rings were tested for endothelium-dependent vasodilation with methacholine and nonendothelium-dependent vasodilation with nitroprusside. Endothelium-dependent relaxation as elicited by methacholine was impaired at 3 and 4 hours of ischemia but was not significantly different at 1 and 2 hours as compared to control, whereas endothelium-independent vasodilation remained normal throughout the different periods of ischemia. The addition of 1 x 10(-6) mol/L rabbit hemoglobin reduced the time needed to demonstrate significant impairment of endothelial function to 2 hours. Endothelium-independent vasodilation was not affected by hemoglobin. We conclude that hemoglobin exacerbates ischemia vascular dysfunction in the rabbit aorta.
 ...
PMID:Effects of ischemia and hemoglobin on vascular function in isolated rabbit aortas. 201 Sep 22

We studied the effect of propranolol administration on risk assessment based on submaximal exercise testing performed early after myocardial infarction. A total of 70 patients with recent infarction underwent modified Bruce treadmill testing with simultaneous measurement of expired gases in the absence of antianginal agents including beta-antagonists. Among these, 31 patients who had at least one of the following abnormalities--ST depression greater than or equal to 1 mm (22 patients), chest pain (four patients), or treadmill time less than 360 seconds (12 patients)--were studied in a randomized double-blind fashion and received either placebo or 240 mg of propranolol/day. A total of 28 patients completed the randomized phase and were able to undergo repeat exercise testing an average of 3.4 +/- 1.8 days later. Randomized groups were equivalent at baseline except for a higher peak oxygen consumption and carbon dioxide production (p less than 0.05) in the propranolol compared with the placebo group; these differences were taken into account in statistical analyses of the study data. Resting heart rate (59 +/- 1.2 versus 82 +/- 4.2 beats/min) and peak heart rate x systolic blood pressure (14,208 +/- 496 versus 20,075 +/- 1,062) were both significantly less (p less than 0.01) after propranolol than after placebo. Eight of nine patients treated with placebo maintained ST depression greater than or equal to 1 mm from the initial to the randomized exercise test, compared with only 4 of 13 receiving propranolol (p less than 0.01). In those with continued ST depression, time to positivity was significantly longer in those receiving propranolol compared with those taking placebo (538 +/- 73 versus 318 +/- 44 seconds, p less than 0.05). In contrast, the peak ratio between carbon dioxide production and oxygen consumption was higher in those receiving propranolol compared with those receiving placebo (0.93 +/- 0.04 versus 0.81 +/- 0.03, p less than 0.05). We conclude that propranolol therapy reduces evidence of ischemia and changes traditional estimates of potential cardiac risk derived from submaximal postinfarction exercise testing.
 ...
PMID:Propranolol therapy alters estimation of potential cardiovascular risk derived from submaximal postinfarction exercise testing. 203 80

The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.
 ...
PMID:Effects of carbon monoxide on myocardial ischemia. 204 Feb 54

We measured O2 uptake (VO2), CO2 output (VCO2), and net lactic acid output (L) during a 30-min period of repetitive 1/s isotonic tetanic contractions of the dog gastrocnemius-plantaris muscle group. The conditions were modest ischemic hypoxia (ischemia), hypoxia hypoxia (hypoxia), and free-flow normoxia (control). The major goal was to assess the effects of these perturbations on L during contractions. Ischemia and hypoxia were initiated just before the start of the contractions and at minute 7 of contractions in separate groups of experiments. Whenever applied, both ischemia and hypoxia reduced VO2 compared with the control values. When ischemia was initiated at the start of contractions, L was reduced transiently compared with the controls. When ischemia began at minute 7, L was increased modestly but transiently compared with the controls. When hypoxia was initiated at the start of contractions, L was increased during the entire period of contractions. The L pattern was the same as in the controls, rising to a maximal value at 3 min and declining steadily to a lower value at 30 min. When hypoxia began at minute 7, L declined initially at a slower rate than it did in the controls and was thereby elevated above the controls from 9 to 30 min. Ischemia was associated with a more rapid reduction in mechanical performance than hypoxia. The data suggest that the mechanisms of the decreased mechanical performance and VO2 are different for ischemia and hypoxia.
 ...
PMID:Effects of ischemic and hypoxic hypoxia on VO2 and lactic acid output during tetanic contractions. 210 21

Extraction and clearance kinetics of [1-11C]acetate were examined in 65 experiments in 30 open-chest dogs. Twenty-nine studies were performed at control, 13 during ischemia, eight after reperfusion, 13 during dipyridamole-induced hyperemia, and two during alteration of cardiac workload. [1-11C]Acetate was injected directly into the left anterior descending coronary artery, and myocardial tissue-time activity curves were recorded with a gamma probe. The single-pass extraction fraction averaged 64.2 +/- 9.7% in control, 65.3 +/- 9.1% in ischemia, 70.0 +/- 4.4% in reperfusion, and 46.5 +/- 7.4% in dipyridamole-induced hyperemia groups. 11C clearance was biexponential in all cases. The rate constant k1 for the first rapid clearance phase correlated closely with myocardial oxygen consumption (r = 0.94) in control, ischemia, reperfusion, and dipyridamole-induced hyperemia groups. Monoexponential fitting of only the first linear part of the clearance curve yielded the rate constant kmono, which also correlated with myocardial oxygen consumption (r = 0.96). Arterial lactate concentrations and the amount of free fatty acid oxygen equivalents consumed by the myocardium were shown to have a small but statistically significant impact on the relation between [1-11C]acetate clearance rate constants and myocardial oxygen consumption. The fraction of 14CO2 activity contributing to overall 14C activity leaving the myocardium after simultaneous injection of [1-14C]acetate (n = 24) was relatively high in all cases (97.4 +/- 2.5% in control, 89 +/- 2.6% in ischemia, 94.1 +/- 3.5% in reperfusion, and greater than 99% in dipyridamole groups), indicating that externally measured 11C clearance corresponds to CO2 production and thus to tricarboxylic acid cycle activity. In conclusion, the results validate the use of [1-11C]acetate as a tracer of oxidative myocardial metabolism for use with positron emission tomography.
 ...
PMID:Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium. 211 37

Experiments were designed to determine whether endothelial injury contributes to augmented coronary vascular tone seen during myocardial reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia followed by reperfusion (60 minutes each). Rings (3-4 mm) of the reperfused artery and of normal left circumflex (control) coronary artery segments were prepared. Rings were suspended for isometric force measurement in organ chambers containing modified Krebs' Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). Endothelium-independent contractions to KCl and prostaglandin F2 alpha were unaltered after reperfusion. Endothelium-dependent relaxations to nitric oxide, sodium nitroprusside, and isoproterenol were comparable in control and reperfused arteries. However, reperfused coronary arteries contracted with prostaglandin F2 alpha lost the ability to express endothelium-dependent relaxations to aggregating platelets. Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to acetylcholine, the calcium ionophore A23187, and the platelet-derived compounds ADP and serotonin. Quiescent (noncontracted) reperfused arterial rings exhibited larger contractions than controls when exposed to aggregating platelets. In such quiescent rings, the endothelium-dependent increase in tension to hemoglobin was unaltered after reperfusion. Thus, coronary reperfusion impairs the normal endothelium-dependent relaxations to aggregating platelets and vasoactive drugs. This impairment of platelet-mediated coronary relaxation could help explain the increased vascular tone and tendency toward vasospasm commonly observed after reperfusion of the coronary arteries.
 ...
PMID:Acute impairment of endothelium-dependent relaxations to aggregating platelets following reperfusion injury in canine coronary arteries. 211 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>