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Biomedical subjects

D Mickle

Publications and source records attributed to D Mickle.

12 recordsLinked to original sources
PubMed1998

Evidence of Trolox and some gallates as synergistic protectors of erythrocytes against peroxyl radicals.

The peroxidation of human erythrocytes induced by peroxyl radical initiator and its inhibition by several gallate esters (e.g., propyl, methyl, ethyl) and Trolox (a more polar analogue of vitamin E) have been studied. The antioxidant activity was determined on erythrocytes against hemolysis generated by a thermal activator, 2,2'-azobis-(2-amidinopropane)dihydrogenchloride. It was found that propyl gallate and its two analogues were more effective than Trolox in preventing cell lysis. However, the combination of gallate esters and Trolox produced a protective effect exceeding the arithmetic sum of their individual contributions. These perceived synergisms occur at more than one level of Trolox at a given level of a gallate ester.

Antioxidants↗
PubMed1997

Comparative protection against oxyradicals by three flavonoids on cultured endothelial cells.

Oxygen-derived free radicals are known to injure the endothelium of aorta in diverse disorders. In this study we compared the cytoprotective effects of three flavonoids against oxyradical damage to porcine aortic endothelial cells in vitro. Cultured porcine aortic endothelial cells were exposed to oxyradicals generated by xanthine oxidase--hypoxanthine (XO-HP). The cytoprotective activities of morin, quercetin, and catechin on these systems were compared using established morphologic criteria. The results in the XO-HP system showed that morin at 0.125, 0.25, and 0.5 mM delayed cell necrosis to 27.4 +/- 1.3, 46.8 +/- 1.8, and longer than 70 min, respectively, compared with 12.0 +/- 1.3 min in the control group. These degrees of protection were significantly stronger than those provided by quercetin and catechin at corresponding concentrations (p < 0.01). Morin and quercetin were moderate inhibitors of xanthine oxidase on the basis of the oxygen consumption rate, whereas catechin at the same concentrations had little inhibitory effect. The data from uric acid formation and cytochrome c reduction were consistent with the oxygen consumption measurement for the three flavonoids.

Animals↗
PubMed1996

Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass grafting: a prospective randomized controlled trial.

INTRODUCTION: We undertook a prospective, randomized, controlled clinical trial to evaluate morbidity outcomes and safety of a modified anesthetic technique to provide shorter sedation and early extubation (1 to 6 hours) than those of the conventional anesthetic protocol used for prolonged sedation and extubation (12 to 22 hours) in patients after coronary artery bypass grafting. METHODS: One hundred twenty patients undergoing elective coronary artery bypass grafting were prospectively assigned randomly to either an early extubation group (n = 60; 15 micrograms.kg-1 fentanyl and 2 to 6 mg.kg-1.hour-1 propofol and isoflurane) or to a conventional extubation group (n = 60; 50 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 midazolam and isoflurane). Cardiac morbidity (postoperative myocardial ischemia, postoperative myocardial infarction, and perioperative sympathoadrenal stress response), respiratory morbidity (postextubation apnea, alveolar-arterial oxygen gradient, pulmonary shunting, oxygen consumption, atelectasis, and reintubation), hemodynamic values and vasoactive medication requirements, intraoperative awareness, postoperative cognitive function, 30 day mortality, and intensive care unit and hospital lengths of stay were compared between the two groups. RESULTS: Fifty-one of the 60 patients in each group (85%) were extubated within the defined time period. Postoperative extubation time and intensive care unit and hospital lengths of stay were significantly shorter in the early group. At 48 hours after operation, there were no significant differences between the two groups in myocardial ischemia incidences, ischemia burdens, or creatine kinase isoenzyme MB levels. Four patients in the conventional group, but not in the early group, had postoperative myocardial infaction. The extubation anesthetics used were effective in suppressing the perioperative plasma catecholamine stress response in both groups. Postextubation apnea characteristics were similar between the groups. Intrapulmonary shunt fraction improved significantly in the early group at 4 hours after extubation. The incidences and degree of atelectasis did not differ significantly between the two groups. The incidences of treated postoperative complications were comparable between the two groups, but three patients in the conventional group died as a result of stroke or postoperative myocardial infarction. CONCLUSION: Early extubation after coronary artery bypass grafting is safe and does not increase perioperative morbidity. There is an improvement in postextubation intrapulmonary shunt fraction and a reduction in intensive care unit and hospital lengths of stay.

Aged↗
PubMed1992

Cultured vascular endothelial cell susceptibility to extracellularly generated oxidant injury.

To understand better the effect of oxidant injury on vascular endothelial cells, human saphenous vein endothelial cells were cultured at atmospheric (pO2 of 150 mmHg) or low (pO2 of 40 mmHg) oxygen tensions. The cellular rates of growth, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), phospholipid fatty acids and cellular susceptibility to extracellularly generated oxidants (hypoxanthine-xanthine oxidase) were measured. The antioxidant enzyme activities were regulated by oxygen tension and significantly differed by day 14. The cells cultured at the low oxygen tension had significantly (P less than 0.01) lower antioxidant activities than the cells cultured at the high oxygen tension. The cells cultured at an oxygen tension of 150 mmHg were more resistant to shrinkage and lipid peroxidation from the oxidants than the cells cultured at a pO2 of 40 mmHg by day 14. Since arterial and venous endothelial cells are perfused with blood at a pO2 of 100 and 40 mmHg, respectively, the postcapillary venous endothelial cells should have lower antioxidant enzyme activities than the precapillary arterial endothelial cells.

Catalase↗
PubMed1988

Quantitation of postischemic skeletal muscle necrosis: histochemical and radioisotope techniques.

Skeletal muscle necrosis will result from prolonged periods of ischemia. The purpose of this study was to develop a method to estimate the extent of necrosis using nitroblue tetrazolium staining and technetium scanning. The bilateral canine gracilis muscle preparation with total vascular isolation was exposed to 4 hr of complete normothermic ischemia followed by reperfusion. After 45 hr of reperfusion 99mTc pyrophosphate (PYP) was injected and 3 hr later the muscles were harvested, cut into six slices, and stained with nitroblue tetrazolium. Biopsies were taken from tetrazolium-positive and -negative areas for electron microscopy to confirm the ability of the stain to distinguish viable from necrotic muscle. Computerized planimetry of the staining pattern was used to estimate the extent of necrosis as a percentage of the total muscle. Electron microscopy confirmed the validity of nitroblue tetrazolium to discriminate between viable and necrotic skeletal muscle in this experimental model. After 4 hr of ischemia the percentage necrosis was 30.2 +/- 6.1% (mean +/- SEM, n = 12), there was no difference in the extent of necrosis in left vs right paired muscles, using tetrazolium staining or technetium PYP uptake. There was a statistically significant correlation between the percentage necrosis and the density of 99mTc PYP uptake per muscle (r = 0.83, P less than 0.001) and per slice (r = 0.94, P less than 0.001). This study demonstrates the ability of tetrazolium staining to accurately differentiate between viable and necrotic skeletal muscle and provides a reproducible method for estimating the extent of necrosis in the gracilis muscle model.

Animals↗
PubMed1982

Comparison of clinical signs and hemodynamic state in the early hours of transmural myocardial infarction.

The initial PCW, Killip-Scheidt classification, presence of third heart sound, and mortality were compared in 90 patients presenting with acute transmural myocardial infarction. Clinical and hemodynamic assessment was performed within 12 hours (time to clinical classification = 4.7 +/- 2.7 hours (mean +/- SD), time to hemodynamic assessment = 5.8 +/- 2.4) of the sentinel event. A poor correlation was observed between early Killip-Scheidt clinical classification and early hemodynamic state when measured as percent correct classification (66%) or as a Kappa statistic (36% for the total population, 9% for nonsurvivors). Increased initial LVFP (greater than 18 mm Hg) was associated with increased mortality (p less than 0.01) and early clinical classification was not. Addition of third heart sound information did not alter this observation.

Aged↗
PubMed1982

A simply constructed treadmill for rodent exercise studies.

A treadmill suitable for studying the exercise physiology of small rodents was constructed. The treadmill itself is a belt sander mounted in an inverted position. Grade elevation is provided by securing the treadmill to a hinged platform. Speed variation is provided by a variable output power supply. Enclosure of the treadmill allows measurement of oxygen consumption by the flow-through technique. We measured oxygen consumption in rats during incremental exercise and found a mean maximum value of 94 +/- 13 ml . kg-1 . min-1. The treadmill is simple and inexpensive to construct and is reliable in performance.

Animals↗
PubMed1981

Prognostic implications of reduction of left ventricular filling pressure in early transmural acute myocardial infarction.

The left ventricular filling pressure (LVFP) was measured within 12 hours of onset of acute myocardial infarction (AMI) in 99 patients, including 21 nonsurvivors. Initial LVFP for survivors was 18 +/- 6 mm Hg (mean +/- SD) and for nonsurvivors was 24 +/- 8 mm Hg (p less than 0.005). Of the total population, 87% had initial LVFP of 12 mm Hg or greater and all nonsurvivors were in this group. Life table analysis was employed to determine LVFP related mortality rates. If initial LVFP was less than or equal to 18 mm Hg, 72-hour mortality rate was 4% and 30-day mortality rate was 10%. For initial LVFP greater than 18 mm Hg, 72-hour mortality rate was 21% and 30-day mortality rate was 33% (p less than 0.005 for both 72 hours and 30 days). When final LVFP was analyzed 30-day mortality rate for final LVFP less than or equal to 18 mm Hg was 5%. Mortality rate of 60% was observed for final LVFP greater than 18 mm Hg. We compared sequential measurements of LVFP in a subset of survivors and nonsurvivors and observed that long-term average trend was for survivors to decrease their LVFP. We conclude that AMI mortality rate is related to LVFP and that LVFP greater than 18 mm Hg is associated with very high mortality rate when compared to LVFP less than or equal to 18 mm Hg. Thus reduction of LVFP either spontaneously or as result of therapy may lower AMI mortality rate.

Actuarial Analysis↗
PubMed1978

Optimal myocardial protection.

The low mortality and perioperative infarction rates for aortocoronary bypass (ACB) make them unsuitable for evaluating the adequacy of myocardial protection. Enzymatic and functional measurements were found to be sensitive and specific indicators of myocardial injury. A prospective concurrent study of 78 patients undergoing triple ACB was conducted to evaluate the effectiveness of three popular methods of myocardial protection. Group I (32 patients) had a single dose of cold (4 degrees C) potassium cardioplegic (CPC) solution infused inducing a mean myocardial temperature (MMT) of 31 +/- 4 degrees C/min. Group II (23 patients) had multiple doses of CPC solution 8nducing a MMT of 22 +/- 2 degrees C/min. Group III (23 patients) had intermittent anoxic arrest at a MMT of 28 +/- 1 degrees C. The groups were not randomized but had comparable clinical symptoms and catheterization findings. Serial measurements of cardiac specific creatine kinase (CK-MB) revealed a peak in enzymatic activity occurring 60 minutes following ACB. The highest CK-MB was significantly (P less than 0.01) lower in group II (25 +/- 8 IU/liter) than group I (50 +/- 8 IU/liter), or group III (68 +/- 14 IU/liter). Myocardial performance was evaluated after ACB by serially measuring left ventricular stroke work index (SW) and left atrial pressure (LAP) in response to volume loading. The rise in SW was significantly (P less than 0.01) greater in group II (3.0 +/- 0.7 gm.m/sq m/mm Hg) than in group I (1.4 +/- 0.7) or group III (1.8 +/- 0.9). The highest SW attained was higher (P less than .01) in group II (43 +/- 7 gm.m/sq m) than group I (19 +/- 6) or group III (34 +/- 8) at comparable LAP values (group I: 20 +/- 5 mm Hg; group II: 18 +/- 3; group III: 18 +/- 4). Post-operative clinical evaluation failed to differentiate among the three groups. The more sensitive indices, however, demonstrated the superiority of cold, multidose cardioplegia in providing optimal myocardial protection.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Albumin-bound bilirubins protect human ventricular myocytes against oxyradical damage.

Synthetic delta-bilirubin (i.e., bilirubin that is covalently bonded to albumin) and, to a lesser extent, bilirubin that is physically adsorbed to albumin substantially prolonged the survival of human ventricular myocytes against in situ generated oxyradicals. This cytoprotection, manifested at micromolar concentrations of either form of bilirubin, surpasses those given by unconjugated bilirubin alone, by equimolar levels of albumin (which has some cytoprotective activity), by known antioxidants ascorbate, mannitol, or Trolox, and by oxyradical scavenging enzymes superoxide dismutase (24,200 IU/L) plus catalase (92,000 IU/L) on the same cells. Our human cell-based data provide the first direct evidence that albumin-bound bilirubins, especially delta bilirubin, are potent circulating cytoprotectors. The latter may be important in defending, among others, the myocardium, which is much less equipped in antioxidant defences than for example the liver or intestines.

Antioxidants↗