Biomedical subjects
J C Alexander
Publications and source records attributed to J C Alexander.
Terminal magnesium cardioplegia: protective effect in the isolated rat heart model using calcium accentuated ischemic damage.
We have developed a modified isolated working rat heart model to study the effect of potassium and magnesium cardioplegia given just prior to reperfusion, "terminal cardioplegia," on preservation of aortic flow following a standard ischemic insult. The model incorporates a short-term calcium challenge at the beginning of reperfusion to accentuate ischemic injury. All hearts were given initial potassium cardioplegia and subjected to 30 min of normothermic ischemia. Terminal cardioplegia was given for the 2 min prior to reperfusion. Calcium-challenged hearts were reperfused initially with calcium-enriched reperfusate and then switched to standard reperfusate. Aortic flow prior to and 60 min after ischemia was used to determine functional protection. Hearts recovered 82 +/- 3% of preischemic aortic flow when reperfused with normocalcemic reperfusate. When the initial reperfusate was enriched with calcium, aortic flow was only 43 +/- 4% of control. Hearts given terminal magnesium cardioplegia and then challenged with calcium-enriched reperfusate recovered 79 +/- 4% of control aortic flow. Hearts given terminal potassium cardioplegia recovered only 53 +/- 5% of control aortic flow when challenged with calcium-enriched initial reperfusate. Our results indicate that the recovery of aortic flow is significantly reduced by short-term postischemic calcium challenge. This damage is blocked by terminal magnesium cardioplegia, but not by terminal potassium cardioplegia.
Chylothorax review.
Chylous leakage from the thoracic duct into the pleural space may occur after any type of thoracic surgery; however, there are few reports of this condition after coronary artery bypass grafting. A case of chylothorax after combined coronary bypass and mitral valve replacement is reported to illustrate a discussion of its pathologic basis, diagnosis and management.
Long-term experience with nadolol in treatment of hypertension and angina pectoris.
Two-hundred ninety-one patients with hypertension and 313 patients with angina pectoris were enrolled and treated with nadolol for up to 2 years. The efficacy of nadolol in hypertension and angina was maintained over the 2-year period. Discontinuation because of an adverse reaction occurred with 8.3% of the hypertensive patients and 8.6% of the angina patients. The observed reactions were typical of those which occur with beta-blocking drugs. Serum creatinine levels fell significantly (p less than 0.05) after 12 months of treatment for both the angina and hypertensive patients. After 24 months of treatment the serum creatinine levels had decreased 20% from baseline (p less than 0.001). Blood urea nitrogen levels fell in the angina patients after 12 months of treatment but not in the hypertensive patients. Nadolol is safe and effective for the long-term treatment of both hypertension and angina. Renal function, as measured by serum creatinine levels, improved with long-term treatment.
Stapled esophagogastric anastomosis.
In a consecutive, nonrandomized series of 92 patients, esophagogastric anastomosis was performed with a suture technique in 32 patients and with a stapler in 60 patients. Only one anastomotic leak occurred in each group. Stricture later formed in three sutured anastomoses and in eight of the stapled anastomoses. A review of published reports shows anastomotic leak in 3.5 percent of the patients with stapled anastomoses. In patients with sutured anastomoses, leak occurred in approximately 10 percent. The improved results with the stapler do not alter the necessity for meticulous attention to technical detail.
Inhibition of chemiluminescence in human neutrophils by dapsone.
Dapsone at doses of 0.5 to 5.0 micrograms/ml was found to produce a dose-dependent inhibition of opsonized zymosan-induced human polymorphonuclear leukocyte (PMN) chemiluminescence (CL) in vitro. Simultaneous exposure of PMN to dapsone and zymosan was as effective in reducing CL as preincubation of PMN with dapsone. Preincubation of PMN with dapsone followed by washing, resulted in the loss of dapsone-mediated CL inhibition, indicating that dapsone did not permanently alter the CL-generating mechanism and that the drug had to be present to inhibit CL. Dapsone did not absorb light at the wavelength of CL and was not toxic to PMN at concentrations tested. Sodium azide, an inhibitor of myeloperoxidase-mediated CL inhibited PMN CL to the same degree as dapsone. When incubated together with PMN, dapsone and azide did not produce an additive inhibition of CL. These data suggest that inhibition of myeloperoxidase may be the mechanism by which dapsone inhibits PMN CL.
Captopril in the treatment of scleroderma renal crisis.
Scleroderma is a disease of unknown cause characterized by interstitial fibrosis and vascular lesions in many organ systems. Renal failure, often associated with malignant hypertension, may ensue as a life-threatening component of this disorder. Activation of the renin-angiotensin-aldosterone system has been hypothesized as a cause of this complication. Captopril has been used in 23 patients with this condition. Of this group, 20 (87%) responded favorably with a decrease of the supine diastolic BP to less than 90 mm Hg and a reduction in the serum creatinine level in 14 patients. During long-term therapy (median, 29 months), 11 of the 23 patients continued to have a good clinical response while receiving captopril. Six patients died and six patients were alive after captopril therapy was discontinued. These data suggest that captopril is beneficial in the treatment of scleroderma renal crisis.
Drug delivery system.
Explore the source record for details and available documents.
Enzymatic hydrolysis in vitro of thermally oxidized sunflower oil.
The hydrolysis of thermally oxidized sunflower oil by pancreatic lipase was studied in relation to chemical changes in the acylglycerols. Four classes of compounds (monomers, dimers, trimers and polymers) formed from the acylglycerols were separated from the heated oils by column chromatography on silica gel, and further verified by thin layer chromatography. Each fraction, after analyses for generaly properties, was subjected to a time course study of hydrolysis by pancreatic lipase over a 30-min period. After 70 hr of heating, the amount of hydrolysis for the acylglycerol dimers was only about half that of the monomers, and that for the trimers was, in turn, about one-third that of the monomers. The polymers were the least hydrolyzed and showed no further reaction after 5 min. The reduction in enzymatic hydrolysis of isolated fractions from the thermally oxidized oils indicates structural differences, related to formation of polar compounds and polymerization products. Adverse effects on animals from feeding these materials can be attributed partly to inhibition of hydrolysis resulting in less available energy.
Enzymatic hydrolysis of fractionated products from oils thermally oxidized in the laboratory.
Enzymatic hydrolysis of the acylglycerol products obtained from thermally oxidized vegetable oils was studied. Corn, sunflower and soybean oils were heated in the laboratory at 180 C for 50, 70 and 100 hr with aeration and directly fractionated by silicic acid column chromatography. By successive elution with 20%, then 60% isopropyl ether in n-hexane, and diethyl ether, the thermally oxidized oils were separated into three fractions: the nonpolar fraction (monomeric compounds), slightly polar fraction (dimeric compounds), and polar fraction comprising oligomeric compounds. Enzymatic hydrolysis with pancreatic lipase showed that the monomers were hydrolyzed as rapidly as the corresponding unheated oils, the dimers much more slowly, and the oligomeric compounds barely at all. Overall, the hydrolysis of the dimers was less than 23% of that for the monomers, with small differences among the oils. Longer heating periods resulted in greater reductions in hydrolysis of the dimeric compounds. These results suggest that the degree of enzymatic hydrolysis of the fractionated acylglycerol compounds is related to differences in the thermal oxidative deterioration, and amounts of polar compounds in the products.
Dysrhythmias caused by histamine release in guinea pig and human hearts.
Histamine is released into the systemic circulation during anaphylaxis, by drugs and by surgical procedures. Studies in animal models have conclusively demonstrated that released cardiac histamine is a major mediator of arrhythmias that occur during anaphylaxis and following the administration of histamine-releasing drugs. Several lines of evidence suggest a similar arrhythmogenic role for cardiac histamine in humans: (1) The human heart is rich in histamine; (2) cardiac histamine can be readily released from human heart in vitro by therapeutic concentrations of drugs; (3) histamine has potent arrhythmogenic effects on the human heart in vitro. Arrhythmogenic effects of histamine include enhancement of normal automaticity, induction of abnormal automaticity, induction of triggered tachyarrhythmias, depression of atrioventricular conduction, and increase in the vulnerability of the ventricles to fibrillation. A combination of H1 and H2 antihistamines is needed to block the arrhythmogenic effects of histamine. Certain arrhythmogenic effects of histamine (e.g. induction of slow responses and delayed afterdepolarizations) can also be blocked by drugs which inhibit the influx of cations through slow channels. In contrast, the commonly-used drug digitalis potentiates the arrhythmogenic effects of histamine. We propose that histamine release produced by drugs and surgical procedures may be an overlooked factor in fatal cardiac arrhythmias. Experimental studies suggest that selective pharmacological methods can be developed to block the arrhythmogenic effects of histamine.
Asepsis: the Hampshire dressing aid.
Explore the source record for details and available documents.
Cytotoxicity of thermally oxidized fats.
The effects of oxidized fat components (free fatty acids from the distillable nonurea adductable fraction) isolated from heated corn oil or heated olive oil on the morphology and growth of heart cells in primary culture were investigated. The free fatty acid fractions isolated from the fresh fats served as controls. Different concentrations of the fat fractions (20, 60, and 100 micrograms/ml) were added to the medium in the form of an emulsion with bovine serum albumin (Fraction V, poor in unesterified fatty acids). In the cell cultures treated with heated fats, intracellular lipid accumulation, increased cytoplasmic vacuolization, mitotic aberrations, pyknotic cells, and decreased mitosis were observed and were more pronounced in the case of the heated olive oil. These cytotoxic effects increased with higher concentrations of heated fats in the medium. The fresh fats also produced intracellular lipid accumulation, reductions in mitosis, and changes in the nucleus and cytoplasm, at the higher levels. These effects were greater in fresh olive oil-treated cultures. These observations indicate that oxidized fat components interfere physically or biochemically with normal cell functions resulting in pathological changes.
Maintenance of distal aortic perfusion by a heparin-bonded shunt during repair of coarctation of the aorta with minimal collateral circulation.
Explore the source record for details and available documents.
Effects of vitamin E and ascorbyl palmitate on cultured myocardial cells exposed to oxidized fats.
Primary cultures of rat heart cells were used as a model system to study the influence of two antioxidants, vitamin E and ascorbyl palmitate, on biological effects of thermally oxidized fat. The free fatty acid fraction of the distillable non-urea-adductable fraction of heated corn oil (HCO) was used as the test lipid; the free fatty acid fraction of fresh corn oil was the control. HCO (100 microgram/ml medium) depressed the mitotic index, induced excessive lipid accumulation, and increased the number of pyknotic nuclei in the cells. Addition of extra vitamin E (10 microgram/ml medium) reduced the toxicity of HCO by counteracting these changes. In comparison, ascorbyl palmitate (10 microgram/ml medium) in the presence of HCO was beneficial in that it produced only a slight increase in the mitotic index. HCO treatment also resulted in reduced levels of linoleic and arachidonic acids in the phospholipid fractions of the cells, and addition of vitamin E or ascorbyl palmitate increased the level of arachidonic acid. The triacylglycerol fraction of HCO-treated cells showed markedly reduced linoleic acid and increased arachidonic acid. These changes were unaffected by the antioxidant treatments. Vitamin E counteracted the adverse effects of HCO treatment on the rat heart cells. Ascorbyl palmitate only was as efficient as vitamin E in elevating the concentration of arachidonic acid at the membrane level in the presence of HCO.
Chemical and biological properties related to toxicity of heated fats.
Heating of fats brings about measurable changes in their chemical and physical characteristics. Heat is applied in processing for food manufacture, such as during hydrogenation of oils with a catalyst, and in frying for meal preparation. Partially hydrogenated products generally contain substantial quantities of geometric and positional isomers of the original unsaturated fatty acids. During deep-fat frying, when the fat is used repeatedly, oxidative and thermal effects result in the formation of many volatile and nonvolatile products, some of which are potentially toxic, depending on the level of intake. Because of concern about the types of changes that take place in fats during oxidative and thermal deterioration and the effects the derivatives could have on the consumer, many chemical and biological studies have been carried out. Experimental findings indicate that any potential danger to the consumer is relative to the severity of the overall treatment of the fat. In some studies we evaluated biological effects on rats of trans fatty acid in the diet and of concentrates of fatty acid derivatives produced in thermally oxidized fats. trans-Octadecenoic acid changed the concentrations of the phospholipid classes in the liver lipids, and interfered with conversion of the essential n - 6 series of fatty acids to higher members. Compared to oleic acid, elaidic acid was preferentially incorporated into the phospholipids instead of the triacylglycerols and was also concentrated in the lipoprotein fractions. Administration of non-urea-adductable concentrates from thermally oxidized fats produced cellular damage in hearts, livers, and kidneys of the animals. Since even practical processing and frying conditions can produce some nutritionally undesirable products, a concerted effort should be made to minimize substantial accumulation of these in our dietary fats.
Captopril in severe treatment-resistant hypertension.
Explore the source record for details and available documents.