Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determin the effect of nitroglycerin upon transmural distribution of myocardial blood flow in the awake dog during normal conditions and in the presence of ischemia-induced coronary vasodilation. Studies were performed in chronically prepared dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was estimated by using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. During control conditions endocardial flow (0.86 plus or minus SEM 0.05 ml/min per g) slightly exceeded epicardial flow (0.72 plus or minus 0.03 ml/min per g, P smaller than 0.05), and this distribution of flow was not significantly altered by nitroglycerin. After a 5-s coronary artery occlusion, reactive hyperemia occurred with excess inflow of arterial blood effecting 360 plus or minus 15% repayment of the blood flow debt incurred during occlusion. When arterial inflow was limited to the preocclusion rate during coronary vasodilation after a 5-s total coronary artery occlusion, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium, and the delayed reactive hyperemia was markedly augmented (mean blood flow debt repayment =775plus or minus 105%, P smaller than 0.01). Tese data suggested that subendocardial underperfusion during the interval of coronary vasodilation in the presence of a flow-limiting proximal coronary artery stenosis caused continuing subendocardial ischemia which resulted in augmentation of the reactive hyperemic response. In this experimental model both the redistribution of myocardial blood flow which occurred during an interval of restricted arterial inflow after a 5-s coronary artery occlusion and augmentation of the subsequent reactive hyperemic response were returned toward normal by nitroglycerin. This effect of nitroglycerin may have resulted, at least in part, from its ability to vasodilate the penetrating arteries which deliver blood from the epicardial surface to the subendocardium.
 ...
PMID:Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog. 80 96

Changes in the ventricular diastolic excitability threshold following occlusion of the left anterior descending coronary artery (LAD) were studied in open-chest anesthetized dogs by using a new automatic threshold-following pacemaker (ATFP). The ATFP measures the diastolic excitability threshold by successively decreasing the duration of regularly occurring pacing stimuli until the ventricle fails to respond. Under control conditions, the threshold stimulus duration was 60 +/- 4 (mean +/- SEM) musec. In the first 1-3 minutes following occlusion of the LAD, the diastolic excitability threshold in the ischemic zone (IZ) decreased to 51 +/- 5 musec and then rapidly increased to 600 musec at 5 minutes. The initial decrease in excitability threshold at IZ could be abolished by elevating the serum K+ concentration prior to the LAD occlusion. These changes in excitability threshold at IZ could be prevented by infusing nonoxygenated solutions into the LAD at a site distal to the occlusion. As the excitability threshold increased in IZ during ischemia, the earliest time at which IZ could be reactivated by a stimulus with a voltage equal to twice the preligation diastolic voltage threshold was increased. In nine of 16 dogs, after 5 minutes of LAD ligation, the IZ to normal zone (NZ( activation time (when stimulating at IZ) exceeded the NZ to IZ activation time (when stimulating at NZ) by an average of 9 msec. We also found that in four dogs the NZ to IZ activation time exceeded the IZ to NZ activation time by an average of 10 msec. We conclude from these findings that a gradient of increasing excitability threshold exists as one moves from normally perfused toward more ischemic tissue, passing through a heterogenous border zone that manifests some areas which have a decreased excitability threshold and other areas which have an increased excitability threshold, and that these changes in excitability importantly influence the determination of refractory period durations and conduction times.
 ...
PMID:Alterations in canine myocardial excitability during ischemia. 83 Apr 42

Renal cortical blood flow of rats with postischemic, myohemoglobinuric, and mercury-induced acute renal failure was measured by the hydrogen washout technique using implanted platinum electrodes. Total renal blood flow was determined by venous cannulation in separate series of rats. The values obtained with the two methods were in excellent qualitative agreement (r=0.99, P less than 0.001), although venous cannulation gave values that were constantly lower than those calculated for whole kidney from the cortical flow rate and assumed cortical mass. Myohemoglobinuria produced by glycerol injection caused cortical blood flow to fall from a control value of 7.37+/-0.23 (SEM) ml/min X g of cortex to approximately one-half that value for four hours after injection (P less than 0.001). Flow rates 12 and 24 hr after glycerol injection were 85% (P less than 0.001) and 90% (P less than 0.05) of control, respectively. Cortical flow was reduced to 5.49+/-0.39 (SEM) ml/min X g of cortex four hours after release of one hour's total bilateral renal arterial occlusion (P less than 0.001), but rose to normal within 24 hr. Poisoning with 4.7 mg/kg of body wt of mercuric chloride produced a cortical blood flow value that was 30% higher than control 24 hr after injection (P less than 0.01), while a 12 mg/kg of body wt dose gave a normal flow value. Inulin clearance was severely depressed in all models at all study times. Thus, in contrast to human acute renal failure, marked renal cortical ischemia is not an essential feature of these different forms of murine acute renal failure.
 ...
PMID:Normal renocortical blood flow in experimental acute renal failure. 85 3

Recent studies have shown that after total coronary artery occlusion, there is impaired "reflow" of blood accompanied by myocardial and capillary endothelial cell swelling. To investigate the effect of prolonged low flow myocardial ischemia on coronary vascular resistance, regional hypoperfusion of the distal left anterior descending coronary artery was studied in 31 autonomically blocked dogs on right heart bypass. Heart rate, aortic pressure, and, during ischemia, left ventricular end-diastolic pressure were held constant. The distal left anterior descending coronary artery was perfused at a substantially reduced perfusion pressure which resulted in an antegrade coronary blood flow that usually was between 3% and 7% (0.5-1 ml/min) of control. When relative hypothermia (33-34 degrees C) was induced in nine dogs, left anterior descending coronary artery vascular resistance did not change during 2.5-3 hours of low flow ischemia. Under euthermic conditions (37-40 degrees C) in 17 dogs there was a consistent progressive increase in distal left anterior descending coronary artery vascular resistance starting at 90 minutes (median) after onset of ischemia. By 110-140 minutes ischemic antegrade flow decreased by 35 +/- 4% (SEM) (P less than 0.01). Directionally similar flow changes were observed in six euthermic experiments using the krypton-85 washout technique. Light microscopy did not reveal hemorrhage as a cause of the increased vascular resistance. The perfusion impairment did not occur in two euthermic, nonischemic hearts. In five dogs elevation of serum osmolality by 23 +/- 11 mOsmol/liter with mannitol attenuated the progressive decrease in flow. Thus, a progressive perfusion defect exists in the ischemic low flow state in the heart which presumably contributes to the extent of eventual necrosis.
 ...
PMID:Progressive perfusion impairment during prolonged low flow myocardial ischemia in dogs. 93 13

Blood flow velocities were measured and, with the help of vessel diameters, volume flow rates were calculated in the ascending and descending vasa recta of the renal papilla of young rats using microkymography. Measurements were done under control conditions, and one or three days after temporary ischemia of the kidney (one hr of renal artery occlusion). To test whether the osmolality of the final urine which surrounds the papilla influences the papillary microcirculation, the papillary surface was rinsed with 300 or 1500 mOsm solutions. However, the rinse fluid osmolality had no effect on blood flow. Flow velocity in descending vasa recta(hypertonic rinse fluid) averaged 0.60 +/- 0.04 SEM mm/sec under control conditions, 0.68 +/- 0.08 mm/sec one day after temporary ischemia, and 0.73 +/- 0.04 mm/sec three days after temporary ischemia. The corresponding blood flow rates are 9.3 +/- 1.0, 8.3 +/- 1.2, and 10.5 +/- 1.5 nl/min; these values are not significantly different from each other. Flow rate in the ascending vasa recta was 6.4 +/- 0.6 nl/min under control conditions and 9.3 +/- 1.2 nl/min one day postischemia. The significance increase in ascending vasa recta blood flow after ischemia was probably due to an increase in the permeability of the papillary epithelium. An exact quantitative comparison between blood inflow and outflow from the papilla is not possible at present, because it is not yet clear to what extent the number of ascending vasa recta outnumber the descending vasa recta.
 ...
PMID:Microcirculation of the renal papilla of rats under control conditions and after temporary ischemia. 106 29

Changes in permeability following ischemia-reperfusion injury were assessed in the intact rabbit hindlimb by measuring the transvascular clearance of 125I-labeled rabbit serum albumin. Ischemia was induced for periods of 1 or 2 hours by use of a pneumatic tourniquet inflated to 300 mmHg. Following ischemia, the limb was reperfused for 1, 2, or 3 hours. The albumin clearance in the gastrocnemius muscle of control rabbits was 5.1 +/- 0.7 (mean +/- SEM) microliters/hr/g dry weight. Following 1 hour of ischemia and reperfusion, muscle albumin clearance rose to 71.4 +/- 26 microliters/hr/g dry weight which was not significantly different from those animals that underwent 2 hours of ischemia. Muscle albumin clearance continued to be elevated following 2 hours of reperfusion; however, it returned toward control levels after 3 hours of reperfusion. These data suggest there is a transient increase in albumin permeability following ischemia-reperfusion injury in skeletal muscle.
 ...
PMID:Permeability changes following ischemia-reperfusion injury in the rabbit hindlimb. 128 6

Endopeptidase 24.11 (EC 3.4.24.11) enzymatic activity was spectrofluorimetrically measured in human urine, using a synthetic peptidic substrate. Urinary endopeptidase 24.11 output (Uendo) was determined in 24-hour urine samples of 10 kidney transplant recipients during the first 2 weeks after surgery. In 9 patients, a large increase in Uendo levels was noted during the 1st and/or the 2nd postoperative days (mean +/- SEM of peak Uendo 624 +/- 122 micrograms/24 h, p = 0.0003 as compared to 239 +/- 20 micrograms/24 h in a healthy control population). This occurred whether patients received OKT3 (n = 6) or cyclosporine A (n = 3) as primary immunosuppression. Uendo returned to normal between the 3rd and the 5th postoperative day. We conclude that renal transplantation is associated with an early and marked release of endopeptidase 24.11 in urine. This could be due to the potentially toxic effects of ischemia and/or immunosuppressive drugs on the proximal tubular epithelium. The clinical usefulness of urinary endopeptidase 24.11 as a marker of tubular injury remains to be assessed.
 ...
PMID:Pathological release of urinary endopeptidase 24.11 early after renal transplantation. 130 55

Superoxide anion (O2-) and polymorphonuclear leukocytes (PMNs) have been implicated in the genesis of skeletal muscle ischemia-reperfusion (I-R) injury, but the source of (O2-) has not been established. We studied PMNs as a potential source of O2- using a ferricytochrome reduction assay in 5 anesthetized dogs. Using a gracilis muscle model of I-R, 6 hours of ischemia was followed by 2 hours of reperfusion. The contralateral muscle served as control. Prior to ischemia and after 0.5 and 2.0 hours of reperfusion, PMNs were separated from the gracilis venous effluent of ischemic (I) and control (C) muscles. Central venous samples were also obtained prior to surgical preparation and after reperfusion. Assays for O2- were performed with and without zymosan (Z) activation. Results are expressed as nmol O2-/2 x 10(6) PMNs +/- SEM. Baseline production of O2- was 0.49 +/- 0.54 in central venous samples; Z increased the values to 6.77 +/- 2.13. After 2 hrs of reperfusion, central O2- was 1.57 +/- 0.75, which increased to 7.1 +/- 1.04 with Z. Gracilis venous samples O2- values with and without Z are reported in Table I. One way measures of analysis of variance showed no significant (p > 0.05) differences between samples. Our results demonstrate that PMNs are not the sole source of O2- in the pathophysiology of skeletal muscle I-R injury. PMN associated injury may be mediated by mechanisms other than O2- production.
 ...
PMID:Superoxide anion production by leukocytes exposed to post-ischemic skeletal muscle. 133 45

Iron is suggested to play an important role in free radical generation during ischemia reperfusion. In the present study, the protective action of 4 iron-chelating agents, with different iron affinities, against reperfusion injury was examined in Langendorff-perfused hearts of neonatal rabbits. The chelators and their iron-binding constants (log Km) were as follows: catechol (43), mimosine (36), deferoxamine (31) and kojic acid (27). Following cardiac arrest, the hearts were subjected to global ischemia for 45 min at 37 degrees C, and then reperfused with modified Krebs-Henseleit solution for 30 min. In control, the left ventricular developed pressures (LVDP) after 30 min reperfusion recovered to 50.5 %/- 3.0% (mean +/- SEM; n = 5) of the preischemic level. In the hearts treated with catechol (30 microM), mimosine (30 microM) or deferoxamine (30 microM), the LVDP recovery was significantly improved up to 84.9 +/- 1.3, 88.2 +/- 2.9 or 87.4 +/- 1.5%, respectively (p < 0.01 vs. control). Creatine phosphokinase (CPK) leakage during the initial 5 min of reperfusion was significantly decreased to about half of control in the hearts treated with catechol, mimosine, or deferoxamine. However, the treatment with kojic acid (30 microM) showed no improvement in the LVDP recovery and CPK leakage. Free radical generation was measured with an electron spin resonance using a spin-trapping agent, 5,5-dimethyl-pyrroline-N-oxide (DMPO). The treatment with catechol, mimosine, or deferoxamine reduced the maximum intensity of DMPO-OH signal to about one third of control. However, the maximum intensity in the hearts treated with kojic acid showed a similar level to control.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Protective action of iron-chelating agents (catechol, mimosine, deferoxamine, and kojic acid) against ischemia-reperfusion injury of isolated neonatal rabbit hearts. 133 45

The rectus femoris muscle of the rabbit is perfused by a single artery and vein and is a valuable new model for study of ischemia-reperfusion injury of skeletal muscle. The consequences of increasing duration of ischemia to the rectus femoris have been examined. Postischemic muscle survival (means +/- SEM), as measured by Nitro blue tetrazolium (NBT) staining 24 hr after ischemia, was 90.5 +/- 1.5% after 2 hr normothermic ischemia, 77.1 +/- 7.7% after 3 hr, 41.8 +/- 7.6% after 3 1/2 hr, and 10.7 +/- 8.7% after 4 hr. Histology confirmed the NBT findings at 24 hr and showed considerable regeneration of muscle fibers 1-2 weeks after injury. The injury caused by 3 1/2 hr normothermic ischemia is the most suitable baseline for study of the effects of pharmacological agents in ischemic muscle injury. Further study of the effects of 3 1/2 hr ischemia by a quantitative Evan's blue method revealed a rapid increase in vascular permeability commencing at the start of reperfusion and lasting for 5-6 hr. Vascular labeling with saccharated ferric oxide showed widespread labeling of venules within the injured muscle and electron microscopic examination showed severe injury to both leaking and nonleaking small blood vessels. However, increased vascular permeability accounted for only a small part of the increase in weight of ischemic muscle.
 ...
PMID:The response of the rabbit rectus femoris muscle to ischemia and reperfusion. 138 14


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