The prevalence of cardiac allograft arteriosclerosis.
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Adolescent↗
Biomedical subjects
M L Hess
Publications and source records attributed to M L Hess.
Percutaneous transfemoral placement of the Kimray-Greenfield vena cava filter.
In 109 patients in whom inferior vena caval interruption was indicated to prevent pulmonary embolism, Kimray-Greenfield (K-G) filters were inserted from a percutaneous transfemoral approach, 94 from the right common femoral vein and 15 from the left common femoral vein. All attempts at transfemoral filter insertion were successful except in two patients in whom a left common femoral approach was used. No complications occurred during insertion. In four patients, clinical evidence of femoral vein thrombosis ensued within 48 hours of filter insertion. There were no complications related to filter migration, and in 97% of patients the alignment was satisfactory. The percutaneous transfemoral route is a rapid and effective method for inserting K-G filters. The most frequent postinsertion complication was femoral vein thrombosis (ten patients), but only two patients suffered permanent sequelae.
Adolescent↗
Attenuation of dysfunction in the postischemic 'stunned' myocardium by dimethylthiourea.
The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 +/- 9% (mean +/- SEM) vs 9 +/- 14% (p less than .03) at 1 hr, 55 +/- 9% vs 23 +/- 13% (p less than .05) at 2 hr, 60 +/- 9% vs 28 +/- 14% (p less than .05) at 3 hr, and 67 +/- 5% vs 36 +/- 13% (p less than .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occurring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical.
Animals↗
Advances in the diagnosis and management of congestive heart failure.
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Amrinone↗
Lipid mediators in organ transplantation: does cyclosporine accelerate coronary atherosclerosis?
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Adolescent↗
Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C.
Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH.
Purified PGH synthase when acting on arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate generated superoxide in burst-like fashion. In eight experiments using different batches of enzyme, the mean +/- SE rate of superoxide generation from 100 U of enzyme measured as the superoxide dismutase-inhibitable reduction of cytochrome c was 5.06 +/- 0.19 nmol/min in the first minute and 0.35 +/- 0.03 nmol/min subsequently. Optimum rates of superoxide were seen at concentrations of reduced nicotinamide-adenine dinucleotide in excess of 80 microM and reduced nicotinamide-adenine dinucleotide 3'-phosphate in excess of 100 microM. Using prostaglandin G2 or linoleic acid as substrate rather than arachidonate also resulted in superoxide generation. When prostaglandin H2 was used as substrate, no superoxide was generated. The rate of superoxide generation was markedly inhibited by cyclooxygenase inhibitors. Superoxide generation was also observed during the action of lipoxygenase on either linoleic or arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate but not in their absence. Indomethacin had no effect on superoxide generation from lipoxygenase. We conclude that PGH synthase and lipoxygenase produce superoxide via a side-chain reaction dependent on the presence of suitable reducing cosubstrate. This mechanism is analogous to that described for peroxidases in general.
Arachidonic Acid↗
Cardiac transplants in Virginia: progress report.
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Forecasting↗
Role of 5-HT2 receptor inhibition in pulmonary embolization.
We examined the role of serotonin at the 5-HT2 receptor site after pulmonary embolization for changes in hemodynamics, gas exchange, and lung water. Pulmonary embolization was induced using 0.75 gm/kg autologous clot in anesthetized artificially ventilated dogs. Pulmonary vascular resistance rose by 5 min from 3.4 +/- 1.5 to 14.2 +/- 2.1 mm Hg/liter/min (p less than 0.001), arterial oxygenation decreased from 91 +/- 5 to 68 +/- 5 mm Hg (p less than 0.01), platelet count decreased from 201 +/- 64 to 141 +/- 32 ml X 10(3), and the wet to dry weight lung ratio increased from 2.59 +/- 0.34 to 4.21 +/- 0.21 (p less than 0.001). Inhibition by ketanserin, a selective serotonergic inhibitor at the 5-HT2 receptor site substantially attenuated the increase in pulmonary vascular resistance from 3.6 +/- 1.4 to 8.0 +/- 2.5 mm Hg/liter/min, ablated the hypoxemia and platelet reduction and inhibited the formation of pulmonary edema. Infusion of serotonin simulated only some of the above changes as the pulmonary vascular resistance increased from 3.16 +/- 1.6 to 13.5 +/- 4.1 mm Hg/liter/min (P less than 0.01) and the oxygenation decreased from 96 +/- 5 to 57 +/- 4 mm Hg (P less than 0.01). Serotonin infusion, however, did not cause pulmonary edema. The administration of ketanserin ablated the increase in pulmonary vascular resistance and the hypoxemia following serotonin infusion. We conclude that following pulmonary embolization, serotonin at the 5-HT2 receptor is responsible for the fall in PaO2 and partially responsible for the increased pulmonary vascular resistance. Although ketanserin inhibits the formation of pulmonary edema following pulmonary embolization, serotonin does not seem to be directly responsible.
Animals↗
Effect of reduced oxygen intermediates on sarcolemmal muscarinic receptors from canine heart.
The effect of oxygen free radicals generated by xanthine-xanthine oxidase system and hydrogen peroxide were investigated on cardiac muscarinic cholinergic receptors. We have used highly enriched sarcolemmal preparations isolated from canine myocardium. Exposure of the sarcolemma to oxygen free radicals by xanthine-xanthine oxidase system resulted in a significant (P less than 0.05) decrease of Bmax of (3H)-QNB (4.66 +/- 0.51 to 2.68 +/- 0.22 pmoles/mg protein). Addition of superoxide dismutase (SOD) and catalase (10 micrograms/ml) resulted in a significant reversal of Bmax value to 3.72 +/- 0.39 pmoles per mg protein (p less than 0.05). However, the affinity constants of dissociation (KD) were not altered appreciably with the exposure to oxygen free radicals with or without scavengers. Hydrogen peroxide significantly depressed 3H-QNB binding to the receptors in a dose-dependent manner in a concentration range between 4.41 mM -441 mM. This depression was completely inhibited by 10 micrograms/ml catalase. The study demonstrates that the oxygen free radical species are capable of disrupting (3H)-QNB binding to the cardiac muscarinic receptors.
Animals↗
Inhibition by free radical scavengers and by cyclooxygenase inhibitors of the effect of acidosis on calcium transport by masseter muscle sarcoplasmic reticulum.
In vitro, arachidonic acid depressed calcium transport by sarcoplasmic reticulum (SR) in the homogenate of canine masseter muscle. This effect was inhibited by superoxide dismutase (SOD), a scavenger of the superoxide anion radial ( . O-2), at pH 7.0, and by SOD plus d-mannitol, a scavenger of hydroxyl free radical ( . OH), at pH 5.5. Indomethacin and 2-aminomethyl-4-tert-butyl-6-propionyl phenol (ONO-3144), a compound known to accelerate the conversion of prostaglandin G2 (PGG2) to PGH2 and scavenge free radicals, inhibited the effect of arachidonic acid at both pH 7.0 and pH 5.5. PGG2, but not PGH2, duplicated the effect of arachidonic acid. The effect of PGG2 on SR function was similar to that of exogenous free radicals generated from the xanthine-xanthine oxidase system. Incubation at pH 5.5, in the absence of an exogenous free-radical generating system, depressed SR calcium transport in the homogenate and in isolated SR. This effect in the homogenate was inhibited by indomethacin or by ONO-3144. At 10-min incubation at pH 5.5, SOD partially and temporarily reversed the depressant effect of acidosis. The addition of SOD plus d-mannitol completely reversed the system. d-Mannitol alone was ineffective. Arachidonic acid was able to mimic these effects of acidosis, except that arachidonic acid further depressed isolated SR calcium transport. These results demonstrate that acidosis can depress SR calcium transport in the homogenate of masseter muscle by an oxygen-free radical mechanism by the generation of . O-2 and . OH. Our results also demonstrate that significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism at an acidotic pH in the cellular environment outside of the SR of the muscle cell, and seems to be responsible for the generation of the . OH derived from . O-2.
Acidosis↗
The oxygen free radical system and myocardial dysfunction.
The pathways for the metabolism of molecular oxygen involve one electron-transfer reaction with the subsequent production of reduced-oxygen intermediates. These reduced-oxygen intermediates include the superoxide anion (.O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (.OH), which are highly reactive, short-lived species. Normally intracellular enzyme systems that include superoxide dismutase, catalase, and glutathione peroxidase are responsible for "scavenging" these products of oxygen metabolism. However, in many pathological states such as inflammation, ischemia, and reperfusion, there is an increased production of these reduced-oxygen intermediates, which are capable of extensive tissue damage. It is the purpose of this symposium to examine, in depth, the role of oxygen free radical systems as mediators of myocardial dysfunction and expand our knowledge of myocardial ischemia, ischemia-reperfusion injury, and the inflammatory response of the myocardium.
Coronary Disease↗
The effect of short term normothermic global ischemia and acidosis on cardiac myofibrillar Ca2+-Mg2+ ATPase activity.
There is now good evidence to indicate the onset of myocardial ischemia is accompanied by a decline in intracellular pH which parallels the decrease in tension development. The component of the excitation--contraction coupling system which is responsible for the loss in tension development has not been determined although the contractile proteins are a likely candidate since the calcium sensitivity of tension development and of myofibrillar ATPase are both inhibited by a decrease in pH. However, these studies have utilized normal tissues and the effects of pH compounded with ischemia have not been determined. It is plausible to suggest that there may occur ischemic damage to the excitation--contraction coupling system which would depress function in a manner distinct from that incurred by acidosis. Toya-Oka and Ross have demonstrated a loss in regulatory proteins during regional ischemia, suggesting an effect of ischemia independent of pH. We recently demonstrated, in sarcoplasmic reticulum isolated from ischemic myocardium, a defect in function which could not be accounted for solely on the decrease in pH. It was, therefore, the purpose of this study to determine the effects of decreasing pH on cardiac myofibrillar ATPase activity isolated from hearts which had been subjected to short-term, global normothermic ischemia. This design permits us to answer the following questions: Is there a decrease in myofibrillar ATPase activity in the canine heart following 30 min of normothermic global ischemia? Does acidosis play a contributory role in any observed depression of myofibrillar ATPase activity during ischemia? and Does the ischemic process, independent of acidosis, produce a further depression of myofibrillar ATPase activity?
Acidosis↗
The oxygen free radical system: potential mediator of myocardial injury.
The sequential univalent reduction of oxygen gives rise to very reactive intermediate products including superoxide anion radical, hydrogen peroxide and free hydroxyl radicals. Normally, the tissue concentration of these intermediate products of oxygen is severely limited; however, if oxygen free radicals are produced in excess of the capacity of the tissues to eliminate them, they may cause serious damage. The biochemistry and possible sources of free radical generation in animal models of ischemic/reperfusion injury are reviewed. The ability of scavengers of oxygen free radicals to improve mechanical, mitochondrial and sarcoplasmic reticulum function in animal models of ischemic/reperfusion injury suggests that oxygen free radicals are partly responsible for myocardial injury in these models. Future research should be directed at establishing the relevance of oxygen radical-mediated myocardial injury in the experimental setting to analogous clinical situations.
Acute Disease↗
Cardiac transplantation.
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Cardiomyopathy, Dilated↗
Oxygen radicals in the adult respiratory distress syndrome, in myocardial ischemia and reperfusion injury, and in cerebral vascular damage.
Recent work suggests that oxygen radicals may be important mediators of damage in a wide variety of pathologic conditions. In this review we consider the evidence supporting the participation of oxygen radicals in the adult respiratory distress syndrome, in ischemia reperfusion injury in the myocardium, and in cerebral vascular injury in acute hypertension and traumatic brain injury. In the adult respiratory distress syndrome there is active sequestration of polymorphonuclear neutrophils in the pulmonary vascular system. There is evidence that activation of these neutrophils results in the production of oxygen radicals which injure the capillary membrane and increase permeability, leading to progressive hypoxia and decreased lung compliance which are hallmarks of the syndrome. In acute arterial hypertension or experimental brain injury oxygen radicals are important mediators of vascular damage. The metabolism of arachidonic acid is the source of oxygen free radical production in these conditions. In myocardial ischemia and reperfusion injury, the ischemic myocyte is "primed" for free radical production. With reperfusion and reintroduction of molecular oxygen there is a burst of oxygen radical production resulting in extensive tissue destruction. Myocardial ischemia--reperfusion injury shares in common with the other two syndromes activation of the arachidonic acid cascade and acute inflammation. Thus it would appear that the generation of toxic oxygen species may represent a final common pathway of tissue destruction in several pathophysiologic states.
Animals↗
Direct sagittal CT of the temporomandibular joint.
An apparatus for direct sagittal computed tomography (CT) of the temporomandibular joint is described. Direct sagittal CT allows visualization of the meniscus and of osseous changes of the mandibular condyle without the technical problems and limitations associated with sagittal reformations from axial scans. The device can be constructed easily and economically and adapted to most CT installations.
Humans↗
Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats.
When increased prostaglandin synthesis was induced in anesthetized cats equipped with cranial windows by topical application of arachidonate (200 micrograms/ml) or bradykinin (20 micrograms/ml), there was reduction of nitroblue tetrazolium, resulting in deposition of the reduced insoluble form of this dye on the brain surface. The amount of reduced nitroblue tetrazolium deposited on the brain surface was measured spectrophotometrically after fixation of the brain by perfusion with aldehydes to eliminate interference from hemoglobin. Topical application of 56 U/ml superoxide dismutase or 20 micrograms/ml indomethacin inhibited nitroblue tetrazolium reduction by 76.5%-82.5% and by 78%-85.5%, respectively. These results show that most of the nitroblue tetrazolium reduction was accounted for by superoxide anion radical generated in the course of arachidonate metabolism via the cyclooxygenase pathway. No superoxide production could be detected in the absence of arachidonate or bradykinin. Histological examination showed no evidence of parenchymal cellular damage or vascular damage and no accumulation of leukocytes. Pronounced leukocyte accumulation occurred 24 hours after topical arachidonate in rabbits with chronically implanted cranial windows. Superoxide appearance was reduced severely by 4,4'-diisothiocyano-2,2'-stilbene disulfonate and phenylglyoxal, two specific inhibitors of the anion channel. The most likely explanation for these findings is that increased metabolism of exogenous or endogenous arachidonate via cyclooxygenase results in the appearance of superoxide anion radical in cerebral extracellular space. Superoxide crosses the membrane of undamaged cells via the anion channel.
Animals↗