UMLS:C0432222 - FACTA Search

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Query: UMLS:C0432222 (SEM)
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In a first series, we tested whether the relative ischemia distal to a severe stenosis on the left circumflex coronary (CX) artery increases the activity of cardiac sympathetic (CS) nerves which, in turn, may result in a poststenotic vasoconstriction and an aggravation of ischemia. In 23 anesthetized, vagotomized dogs, an acute stenosis that reduced CX blood flow to 50% of control was produced and maintained for 20 min. The activity of postganglionic CS nerves increased by 23 +/- 4% within 20 min. In parallel, poststenotic coronary resistance increased from 0.48 +/- 0.03 (SEM) to 0.61 +/- 0.03 mm Hg.min.100 g/ml, resulting in a net lactate production after 15 min. The selective alpha 2-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.v.; n = 6) and the calcium antagonist nifedipine (10 micrograms/kg i.v.; n = 6) prevented the progressive increase in poststenotic resistance and the net lactate production, but still permitted an increase in CS activity. Segmental anesthesia of CS nerves with epidural infiltration of procaine at segments C7-T6 (n = 6) prevented the sympathetic activation, the progressive increase in poststenotic resistance and the net lactate production. In six additional dogs with intact vagus nerves, CS activation and a concomitant increase in poststenotic resistance resulting in myocardial ischemia were also found. These data suggest a vicious cycle between poststenotic coronary vasoconstriction and CS activation, resulting in severe myocardial ischemia. In a second series, stimulation of high-threshold somatic afferents (= nociceptive stimulation: NCS) was used to cause reflex CS activation. The superficial peroneal nerve was electrically stimulated in 14 anesthetized, vagotomized dogs. With intact CX arteries, a 1 min stimulation resulted in a pronounced increase in CX blood flow and perfusion pressure. In contrast, NCS in the presence of a severe stenosis on the CX artery increased end-diastolic poststenotic coronary resistance by 96 +/- 15% due to a reflex activation of CS nerve fibers. This activation was markedly reduced after injection of fentanyl (27 micrograms/kg i.v.; n = 6). Injection of naloxone (60 micrograms/kg) restored the original effect. Systolic wall thickening (WT; sonomicrometry) in the CX artery-perfused myocardium was increased during NCS (10.9 +/- 3.9 (SD) vs. 13.6 +/- 5.0%) in additional five dogs with intact coronary arteries. In the presence of a stenosis on the CX artery, systolic WT was reduced to 7.0 +/- 2.5% and was further decreased to 4.6 +/- 2.3% during NCS. The additional deterioration of systolic regional function during NCS was prevented after i.v. injection of fentanyl, as was the increase in poststenotic coronary resistance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pain and myocardial ischemia: the role of sympathetic activation. 209 7

Isolated hearts from rabbits, hamsters, ferrets, gerbils, rats, mice and guinea pigs were used to investigate species differences in (i) stability during aerobic perfusion, (ii) susceptibility to ischemic injury and (iii) responsiveness to cardioplegic protection. During 120 minutes of continuous aerobic perfusion, the rate of functional deterioration differed between species. The rabbit was the most stable and the guinea pig the least: the mean +/- SEM of the left ventricular developed pressure falling, after 120 minutes of perfusion, to 82 +/- 4% and 60 +/- 6%, respectively. In studies with 30 minutes of ischemia and 60 minutes of reperfusion, the developed pressure recovered to 72 +/- 2, 71 +/- 2, 65 +/- 3, 64 +/- 2, 58 +/- 3, 50 +/- 8 and 50 +/- 2% of its pre-ischemic value in the rabbit, hamster, ferret, gerbil, rat, mouse and guinea pig, respectively. With 60 minutes of ischemia, the recovery of developed pressure in the guinea pig, rabbit, rat, mouse, hamster, ferret and gerbil was 5 +/- 1, 19 +/- 2, 22 +/- 3, 30 +/- 5, 55 +/- 4, 60 +/- 2 and 45 +/- 5%, respectively. Creatine kinase leakage and changes in tissue metabolite content generally reflected the degree of functional injury. In further studies, groups of 6 hearts were infused for 2 minutes with St. Thomas' Hospital Cardioplegic Solution, then subjected to 30 minutes of ischemia. Cardioplegia improved the recovery of developed pressure in the rabbit, hamster, gerbil, rat and mouse (from 72 +/- 2, 71 +/- 2, 64 +/- 2, 58 +/- 3 and 50 +/- 8% to 82 +/- 3, 103 +/- 3, 84 +/- 4, 77 +/- 2 and 78 +/- 5%, respectively; p less than 0.05 for each species). However, no protection was observed in the ferret and guinea pig (65 +/- 3 and 50 +/- 2% versus 66 +/- 3 and 47 +/- 6%, respectively; p = NS). With cardioplegia, tissue high-energy phosphates increased significantly in all species except the gerbil. Rat and guinea pig hearts were taken for time-response studies (ischemia for 15, 20, 30, 45, 50 and 60 minutes in the rat and 15, 30, 45 and 60 minutes in the guinea pig) with or without cardioplegia. In the rat, cardioplegia improved recovery over an ischemic time-window of 20-45 minutes, but in the guinea pig no improvement was detected. Creatine kinase leakage reflected the patterns of functional recovery. In contrast, high-energy phosphates were preserved better in both species after 30 minutes of ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Species differences in susceptibility to ischemic injury and responsiveness to myocardial protection. 210 1

Using an immunoblotting technique, we investigated changes in the concentrations of microtubule-associated protein 2, 200-kDa neurofilament, tubulin, myelin-associated glycoprotein, and 2':3'-cyclic nucleotide 3'-phosphodiesterase in the brains of 40 rats following occlusion of the left middle cerebral artery or sham operation. Compared with those 4 hours after surgery, concentrations of all proteins decreased significantly in the left hemisphere 3 days after surgery (p less than 0.01). Microtubule-associated protein 2 was the most susceptible to ischemia, and its mean +/- SEM concentration decreased to 23 +/- 9.4% of that in concurrent sham-operated controls. Degradation products of microtubule-associated protein 2 and myelin-associated glycoprotein were detected on the blots. Furthermore, in the contralateral hemisphere (where calpain might be activated), concentrations of these two proteins decreased to 57 +/- 12.0% and 83 +/- 4.3% of those in concurrent sham-operated controls, respectively, 3 days after surgery. Changes in the concentrations of cerebral proteins in the contralateral hemisphere are important for understanding clinical symptoms not attributable solely to the ipsilateral lesion following a focal cerebral stroke.
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PMID:Changes in the concentrations of cerebral proteins following occlusion of the middle cerebral artery in rats. 211 75

The purpose of this study was to compare the degree of ischemic and hypoxic injury in normal versus hypertrophied rat hearts to investigate basic mechanisms responsible for irreversible myocardial ischemic injury. Hearts from rats with bands placed on the aortic arch at 23 days of age (BAND) and sham-operated rats (SHAM, 8 weeks postoperative) were isolated, perfused with Krebs buffer, and had a left ventricular balloon to measure developed pressure. Hearts were made globally ischemic until they developed peak ischemic contracture and were reperfused for 30 minutes. Additional hearts were perfused for 15 minutes with glucose-free hypoxic buffer followed by 20 minutes of oxygenated perfusion. There was an 87% increase in heart weight of BAND compared with SHAM (p less than 0.01). During ischemia, lactate levels increased faster in BAND compared with SHAM, ischemic contracture occurred earlier in BAND than in SHAM despite no difference in ATP levels, and postischemic recovery of left ventricular pressure was less in BAND (26.8 +/- 5.6% of control left ventricular pressure, mean +/- SEM) compared with SHAM (40 +/- 4.6%, p less than 0.05). During hypoxic perfusion, lactate release was greater in BAND than in SHAM (48.8 +/- 1.2 versus 26.6 +/- 0.97 mumols/g, p less than 0.01), and with reoxygenation, lactate dehydrogenase release was less in BAND than in SHAM (13.2 +/- 0.7 versus 19.5 +/- 0.2 IU/g, p less than 0.01). After hypoxia and reoxygenation, left ventricular pressure recovery was greater in BAND than in SHAM (93 +/- 8.4% versus 66 +/- 5.3%, p less than 0.01). Thus, this study suggests that hypertrophied hearts have a greater potential for glycolytic metabolism, resulting in an increased rate of by-product accumulation during ischemia, which may be responsible for the increased susceptibility of hypertrophied hearts to ischemic injury.
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PMID:Increased ischemic injury but decreased hypoxic injury in hypertrophied rat hearts. 214 92

Ischemia in the dog produces denervation of myocardium apical to the ischemic area. To investigate the mechanism(s) of the denervation, we tested the effects of hypoxia and some components of ischemia including high K+, low pH, and adenosine on efferent cardiac autonomic responses. In anesthetized, open-chest dogs, we occluded a diagonal branch of the left anterior descending coronary artery and perfused it with hypoxic Tyrode's solutions (PO2 less than 50 mm Hg). We found that effective refractory period (ERP) shortening induced by bilateral ansae subclaviae stimulation at myocardium basal and apical to the perfusing area did not change during a 20-25 minute period of perfusion with hypoxic normal Tyrode's solution. During perfusion with hypoxic combined Tyrode's solution containing 12 mM K+, pH 6.8, and 10 microM adenosine, ERP shortening at basal sites induced by bilateral ansae subclaviae stimulation remained unchanged but was attenuated at apical sites (16 +/- 1 to 8 +/- 1 msec, mean +/- SEM, n = 35, p less than 0.001), and seven apical sites exhibited denervation (less than or equal to 2-msec shortening). The maximum extracellular K+ concentration of the perfusing area, measured with a K(+)-sensitive electrode, was 5.1 +/- 0.9 mM (N = 3 dogs) during perfusion with normal Tyrode's solution and was 11.8 +/- 0.1 mM (N = 3 dogs) during perfusion with hypoxic combined solution (p = 0.017). In a separate group of dogs, the effects of high K+, low pH, and adenosine in the absence of ischemia were examined. Oxygenated Tyrode's solutions were instilled into the pericardial cavity to superfuse epicardial nerves. The Tyrode's solutions containing high K+ (12 mM), low pH (6.4), or adenosine (10 microM), individually or combined, reduced ERP shortening induced by bilateral ansae subclaviae stimulation in the ventricular intramyocardium to 46%, 55%, 56%, and 33% of each control value obtained during superfusion with normal Tyrode's solution and reduced the magnitude of ERP lengthening induced by bilateral cervical vagal stimulation to 57%, 71%, 61%, and 39%, respectively. ERP responses of the test sites to infused norepinephrine and methacholine, however, remained unaffected by superfusion with combined Tyrode's solution. Thus, high K+, low pH, and adenosine each inhibit efferent sympathetic and vagal neurotransmission presynaptically in the canine heart and may contribute to the development of denervation during early ischemia.
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PMID:Presynaptic modulation of efferent sympathetic and vagal neurotransmission in the canine heart by hypoxia, high K+, low pH, and adenosine. Possible relevance to ischemia-induced denervation. 215 68

Limiting the rate of reperfusion blood flow following prolonged ischemia in skeletal muscle has been shown beneficial. However, the persistence of this benefit with reinstitution of normal blood flow remains undefined. We investigated the role of temporary limited reperfusion on ischemia-reperfusion injury in an isolated gracilis muscle model in six anesthetized dogs. Both gracilis muscles were subjected to 6 hr of ischemia followed by 2 hr of reperfusion. Reperfusion blood flow was limited for the first hour in one gracilis muscle to its preischemic rate followed by a second hour of normal reperfusion (LR/NR). The contralateral muscle underwent 2 hr of normal reperfusion (NR/NR). Muscle injury was quantified by technetium-99m pyrophosphate (TcPyp) uptake and by histochemical staining using triphenyltetrazolium chloride (TTC) with planimetry of the infarct size. Capillary permeability was evaluated by muscle weight gain. Results are reported as the mean +/- SEM: [table: see text] These data demonstrate a sustained benefit from temporary limited reperfusion. This methodology should be considered in the surgical management of the acutely ischemic limb.
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PMID:Sustained benefit of temporary limited reperfusion in skeletal muscle following ischemia. 216 4

Na,K-ATPase concentration was measured by vanadate facilitated 3H-ouabain binding to intact samples taken from various parts of porcine and canine myocardium. In porcine and canine heart 3H-ouabain binding site concentration in ventricles was 1.4-2.5 times larger than in atria. Evaluation of 3H-ouabain binding kinetics revealed no major difference between atria and ventricles: Equilibrium was obtained after the same incubation time in right atrium (RA) as in left ventricle (LV), both in porcine and canine heart. Unspecific uptake and retention of 3H-ouabain was for porcine heart RA and LV 1.5 and 1.4, respectively, and for canine heart RA and LV, both 1.2% filling (i.e., volume (ml) of incubation medium 3H-radioactivity taken up per mass unit (g wet wt.) of tissue multiplied by 100). The apparent dissociation constant (KD) was 1.4 x 10(-8) and 1.9 x 10(-8) in porcine RA and LV and 2.6 x 10(-8) and 6.1 x 10(-8) mol/l in canine RA and LV. Loss of specifically bound 3H-ouabain during the washout procedure occurred with a half-life time (T1/2) of 16.7 and 28.6 in RA and LV of porcine heart and 91.2 and 151.6 h in RA and LV of canine heart. Duly corrected for these errors of the method--factor 1.16 and 1.13, respectively, for porcine RA and LV, and factor 1.11 and 1.13 for canine RA and LV, total 3H-ouabain binding site concentration was found to be 553 +/- 74 and 1037 +/- 45 pmol/g wet wt. (means +/- SEM, n = 5) in porcine RA and LV, and 569 +/- 37 and 1410 +/- 40 pmol/g wet wt. (means +/- SEM, n = 5) in the canine RA and LV. These values were confirmed by measurements of 3H-digoxin binding to the porcine heart. The present quantification of myocardial Na,K-ATPase gives values up to 154 times higher than measurements based upon Na,K-ATPase activities in membrane fractions where the recovery of Na,K-ATPase may be less than 1% due to loss during purification. A higher Na,K-ATPase concentration is found in small animals than in large animals. A relationship between higher concentration of Na,K-ATPase and larger pressure work in ventricles compared to atria is suggested. Myocardial 3H-ouabain binding sites were found to be stable for 20 min of ischemia, followed by 1 h of reperfusion, supporting the concept that myocyte injury induced by short term ischemia may be reversible and that reperfusion may result in normalization.
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PMID:Quantification of the total Na,K-ATPase concentration in atria and ventricles from mammalian species by measuring 3H-ouabain binding to intact myocardial samples. Stability to short term ischemia reperfusion. 217 46

Hindbrain ischemia was induced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats (SHRs). Mean arterial blood pressure was lowered to 80 mmHg in SHRs and to 50 mmHg in Wistar-Kyoto rats (WKYs) by a controlled hemorrhage, and then the vertebral artery was bilaterally occluded through alar foramina of the first cervical vertebra. Following vertebral occlusion, blood flow of the cerebellum was significantly decreased to 9.4 +/- 2.0 mL/100g/min (+/- SEM) while flow of the cerebrum remained at 32.1 +/- 5.4 in SHRs. In contrast, cerebellar blood flow in WKYs was preserved at 24.2 +/- 2.9 mL/100g/min. Brain lactate, pyruvate, and adenosine triphosphate (ATP) were determined in SHRs after sixty minutes of hypotension with or without vertebral occlusion. Although infratentorial metabolites were actually unaltered in rats with hypotension alone, infratentorial lactate and lactate/pyruvate ratio significantly increased to 14.38 +/- 3.61 mmol/kg and 67.7 +/- 12.1, respectively, with a concomitant decrease in ATP in SHRs with hypotension and vertebral occlusion. Bilateral vertebral artery occlusion, together with moderate hypotension, was shown to produce a marked reduction of cerebellar blood flow and to induce ischemic metabolic changes in the infratentorial brain in SHRs.
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PMID:Hindbrain ischemia produced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats. 222 62

We examined whether pentobarbital (PB) inhibited the acute extracellular release of dopamine that occurs in the striatum following the onset of ischemic injury in the gerbil model of stroke. The cerebral dialysis technique was employed to monitor striatal extracellular dopamine concentrations before and after carotid artery occlusion while perfusing either a control solution of artificial cerebrospinal fluid (CSF) or a 1 mM solution of pentobarbital in CSF (PB/CSF). During perfusion with CSF, extracellular dopamine increased from a baseline concentration of 0.40 +/- 0.09 (SEM) pmoles/10 minute collection interval to 30.0 +/- 9.0 pmoles/10 minutes after carotid artery occlusion. In contrast, during perfusion with PB/CSF, dopamine levels increased from a baseline of 1.37 +/- 0.3 pmoles/10 minutes to 8.30 +/- 2.6 pmoles/10 minutes; this increase was significantly less than the increase in controls. In animals with established ischemia, repeatedly alternating the perfusion fluid between CSF and PB/CSF demonstrated that dopamine concentrations were significantly increased with CSF alone and decreased with PB/CSF. These findings demonstrate that pentobarbital perfusion either before or following the onset of ischemia inhibits extracellular release of dopamine in the striatum. Inhibition of neurotransmitter release may, in part, be responsible for the protective effect of pentobarbital in ischemic brain injury.
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PMID:Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum. 222 89

The transport time of enzyme from heart to plasma was studied in two experimental models. First, the enzyme alanine aminotransferase was slowly infused into the left ventricular wall in open-chest dogs. The half-life for the washout of alanine aminotransferase activity into plasma was 20 +/- 4 minutes (mean +/- SEM, n = 8) and was not different in ischemic and normally perfused tissue. From measurements of arteriovenous differences in alanine aminotransferase activity and left ventricular blood flow, it was concluded that 77 +/- 14% of total enzyme washout from ischemic tissue occurred by direct entry into the bloodstream. The corresponding value for the vascular permeability-surface area product was 264 +/- 55 ml.kg-1.hr-1. For a second model, we studied myocardial enzyme release into plasma after abrupt heart injury induced by 10 minutes of calcium-free coronary perfusion followed by reintroduction of calcium (calcium-paradox mechanism). The half-life for the release into plasma was 1.9 +/- 0.2 hours (mean +/- SEM, n = 6) and was again not influenced by sustained ischemia. Slower washout, as observed for this second model, is consistent with increased interstitial protein space and corresponds to a permeability--surface area product between 135 and 285 ml.kg-1.hr-1. These results were used to calculate the time course of cellular enzyme leakage from the rate of enzyme release into plasma in various forms of heart injury. Significant shifts between the time curves of evolving cellular injury and enzyme release into plasma are observed after 2 hours of ischemia followed by coronary reperfusion, but not after permanent ischemia.
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PMID:Time course of cellular enzyme release in dog heart injury. 222 57

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