Search PubMed⌕ Search

Biomedical subjects

M J Daly

Publications and source records attributed to M J Daly.

At least 127 records · Page 7Linked to original sources
PubMed1984

Sarcolemmal enzymes and Na+ -Ca2+ exchange in hypoxic, ischemic, and reperfused rat hearts.

Isolated spontaneously beating rat hearts were perfused in the Langendorff mode and divided into four groups, i.e., control (aerobic), hypoxic (95% N2-5% CO2), ischemic, and ischemic reperfused. After a total of 90 min of perfusion, the sarcolemma was isolated and enzymatically characterized. Ouabain-sensitive Na+-K+-ATPase was inhibited in all three experimental groups, whereas K+-stimulated phosphatase activity was decreased only in the ischemic and reperfused groups compared with control. 5'-Nucleotidase activity was inhibited (P less than 0.05) only in the ischemic group. Mg2+-ATPase activity was not different from control. Passive Ca2+ uptake and Ca2+ efflux were not significantly altered by any of the interventions. Na+-Ca2+ exchange rate, but not capacity, was decreased (by 32-42%) in the ischemic group but this was partially reversed on reperfusion. These results suggest that changes secondary to lack of flow rather than O2 play a major role in the etiology of ischemic damage to the membrane and that a 15-min period of reperfusion after 60 min of ischemia does not exacerbate this damage.

5'-Nucleotidase↗
PubMed1984

Calcium, sodium, and the calcium paradox.

The effect of "sodium loading," of verapamil and of nifedipine on the gain in calcium and sodium, and on the loss of myoglobin, during the calcium paradox in adult rat hearts was examined. Raising cell sodium from 56.5 +/- 2.6 to 129.5 +/- 10.2 mumol sodium/gram dry weight did not alter the degree or rate of calcium gain or myoglobin release during calcium repletion after long periods (greater than 2 minutes) of calcium-free perfusion; under these conditions, and in the presence of 10 micrograms/liter verapamil, calcium gain was enhanced. However, after shorter periods (0.5-1.5 minutes), of calcium-free perfusion, calcium gain was enhanced in "sodium-loaded" hearts, even in the absence of verapamil, and particularly during the early stages of repletion. The presence of 1 and 10 mumol/liter dl-verapamil and 1 mumol/liter nifedipine before, during, and after 10 minutes of calcium-free perfusion significantly (P less than 0.01) slowed the early (up to 1 minute for verapamil and 2 minutes for nifedipine) but not the late gain in calcium. When verapamil was present, the late gain in calcium was actually enhanced. These agents also abolished the early (45 seconds) but not the late (greater than 2 minutes) gain in sodium that occurs during repletion. We propose that the gain in calcium that occurs during calcium repletion after a period of calcium-free perfusion can be divided into at least two phases (early and late), and that the early phase contains a verapamil/nifedipine-sensitive component and a verapamil/nifedipine-insensitive component, the latter probably involving sodium-calcium exchange.

Animals↗
PubMed1984

The classification of adrenoceptors and their effects on gastric acid secretion.

The actions of adrenoceptor agonists and antagonists are by no means agreed even though experiments with adrenal medulla extract date back to the beginning of the century. This review will consider the work of my own group and that of others in an attempt to classify the adrenoceptors which modulate gastric acid secretion. There are a number of factors to consider. Species differences are important and particular attention will be given to results from rat, dog and human. The secretagogue used is also important because the effect of adrenoceptor agonists and antagonists can be modified by the choice of histamine, muscarinic agonist, (penta) gastrin or food. Other factors include the gastric model used and the presence or absence of anaesthesia. The broad conclusions are that both alpha- and beta-adrenoceptors can inhibit gastric acid secretion. Both beta 1- and beta 2-adrenoceptors mediate inhibition of pentagastrin-induced secretion while alpha-adrenoceptors are important in the reduction of histamine-induced gastric acid secretion.

Adrenergic alpha-Antagonists↗
PubMed1983

Calcium antagonists and calmodulin: effect of verapamil, nifedipine and diltiazem.

The effect of three calcium antagonists (verapamil, nifedipine and diltiazem) on the calcium-induced activation of phosphodiesterase (a calmodulin dependent process) was investigated. Therapeutically relevant concentrations of verapamil, nifedipine and diltiazem were used. In the presence of calmodulin, phosphodiesterase activity was stimulated by calcium in the range 4 X 10(-6)-2.5 X 10(-5) M. Diltiazem (10(-6) M), verapamil (10(-6) M) and nifedipine (10(-7) and 10(-6) M) had no influence on phosphodiesterase activity in the presence or absence of calmodulin at any concentration of calcium employed. By contrast trifluoroperazine abolished the Ca2+ activation of the phosphodiesterase enzyme. From this it is concluded that while the interaction of calcium antagonists with calmodulin may be of interest in the study of the mode of action of calmodulin, it probably does not contribute to their vasodilator activity.

Animals↗
PubMed1983

Comparison of antisecretory potency and duration of action of the H2-receptor antagonists AH 22216, cimetidine, ranitidine and SK & F 93479 in the dog.

The antisecretory potency and duration of action of the new histamine H2-receptor antagonist AH 22216 have been compared with those of cimetidine, ranitidine and SK & F 93479 against histamine-induced gastric acid secretion in the conscious Heidenhain pouch dog. Ranitidine was 4-6 times more potent than cimetidine, with a similar duration of action. SK & F 93479 was approximately twice as potent as ranitidine and had a slightly longer duration of action. AH 22216 was most potent of the four H2-antagonists, some 20-30 times more active than cimetidine, and had an extremely prolonged duration of action.

Animals↗
PubMed1983

Cobalt, manganese and the calcium paradox.

The reperfusion of hearts with Ca2+-containing buffers after relatively short periods of Ca2+-free perfusion results in tissue damage, Ca2+ overload, loss of mechanical function and displacement of intracellular components into the extracellular phase. Using isolated, spontaneously beating Langendorff perfused rat hearts we have investigated whether Mn2+ and Co2+ exert a dose dependent inhibitory effect on this gain in Ca2+ and loss of intracellular constituents (assayed as myoglobin). We have also determined if the timing of the addition of Co2+ or Mn2+ is critical, and whether their protective effect is Ca2+-sensitive. When added only at Ca2+ repletion neither Co2+ nor Mn2+ provided protection. When present during the entire period of Ca2+ depletion and repletion, Mn2+ (005 to 4.0 mM) and Co2+ (0.1 to 4.0 mM) exerted a dose-dependent protective effect, indicted by a reduced and delayed onset of myoglobin release, a reduced gain in Ca2+, and an improved recovery of mechanical function. This protection was proportionally diminished if the cations were added late during the 10 min period of Ca2+ depletion and further reduced if after their late addition, Mn2+-free or Co2+-free Ca2+ repletion buffer was used. Mn2+ was more effective than Co2+, and decreasing the Ca2+ content of the perfusion buffer from 2.5 to 1.3 mmol.1-1 shifted the dose-response curve for this protection to the left. These results are discussed in terms of the possible mechanisms involved in the dose and time dependent protective effect of Mn2+ and Co2+.

Animals↗
PubMed1983

The biochemistry of uncontrolled calcium entry.

The Ca2+ paradox is characterized by a rapid and uncontrolled entry of Ca2+. Whilst the consequence of the resultant gain in Ca2+ are relatively well defined, uncertainty exists concerning the route of entry. Possible routes include passive diffusion across damaged sarcolemma and intercalated discs, active transport in exchange for K+, or Na+, and entry through the voltage-activated, Ca2+-selective slow channels. The following experiments were designed to differentiate between these possibilities. Isolated spontaneously beating Sprague-Dawley rat hearts were perfused at 37 degrees C with Ca2+-free perfusion buffer for greater than 1 min before starting Ca2+ repletion. Adding 2-4 mmol l-1 Co2+ or Mn2+ before, during but not coincident with Ca2+ repletion protected against the paradox as indicated by an absence of myoglobin release and Ca2+ overload. Despite this protection marked distortion of the glycocalyx occurred, with splitting of the basement coat and blebbing. The intercalated discs, however, remained intact. It seems unlikely therefore that splitting of the basement coat necessarily results in an uncontrolled entry of Ca2+. Since Mn2+ and Co2+ block Ca2+ entry through the slow channels their failure to prevent the uncontrolled entry of Ca2+ when added at the time of Ca2+ repletion favours the view that Ca2+ entry during the paradox does not depend upon entry of Ca2+ through the slow channels. In other experiments hearts were preloaded with Na+, to alter intracellular Na+ before Ca2+ repletion. This procedure did not markedly affect the gain in Ca2+. These findings will be discussed in terms of the route(s) and consequence(s) of the uncontrolled entry of Ca2+ that occurs when Ca2+ is reintroduced after a period of Ca2+-free perfusion.

Animals↗
PubMed1982

Pharmacological interactions between ranitidine, cimetidine, metiamide and tiotidine at histamine H2-receptor sites in guinea-pig atria.

Cumulative concentration-response curves to histamine or dimaprit were constructed on guinea-pig isolated right atria and agonist dose-ratios were determined following addition of ranitidine, cimetidine, metiamide or tiotidine alone or a combination of any two of these H2-receptor blocking drugs. The observed histamine or dimaprit dose-ratios for combinations of any two of the H2-antagonists tested were consistent with results predicted from the equation, DR1+2 = DR1 + DR2 - 1, for two antagonists competing for the same receptor sites. Therefore we conclude that all four H2-antagonists compete for the same histamine H2-receptor.

Animals↗
PubMed1982

Estrogen effects on NADH oxidase and superoxide dismutase i prepubertal female rats.

Thirty-four day old, ovariectomised rats were treated with increasing doses of estradiol, 2-hydroxyestradiol 2,3-dimethyl ether (23E2), 4-hydroxyestradiol 3,4-dimethyl ether (34E2) and 4-methoxyestradiol (4ME2) for five days by subcutaneous injection. Superoxide dismutase, phenol activated NADH oxidase and uterine dry weights were determined. Only estradiol was found to be uterotrophic and increased NADH oxidase activity in these experiments. Both 23E2 and 34E2 treatment reduced the enzyme activity significantly. Though 4ME2 showed a decrease in NADH oxidase at 0.05 micrograms/100 gm body weight there was no further decrease at higher dose (5 micrograms/100 gm). The superoxide dismutase (SOD) in uterus and liver was unaffected by estradiol, while 23E2, 34E2, and 4ME2 significantly reduced SOD in both liver and uterus. These results indicate that 23E2, 34E2 and 4ME2, in spite of their nonuterotrophic property property, affect uterine metabolism. Furthermore, in view of the reports indicating the importance of SOD levels in various tumors and since catecholestrogens are observed to reduce SOD levels in liver and uterus, it is suggestive that catecholestrogens may play an important role in the pathophysiology of certain tumors.

Animals↗
PubMed1982

Effects of H2-receptor antagonists and anticholinoceptor drugs on gastric and salivary secretion induced by bethanechol in the anaesthetized dog.

1 The H2-receptor antagonists, ranitidine and cimetidine, have been compared with atropine and pirenzepine for their effects on gastric acid output, and on salivary secretion from the left parotid gland in the anaesthetized dog. Gastric and salivary secretions were elicited by intravenous infusion of bethanechol. 2 Atropine (0.3-1 microgram/kg) or pirenzepine (3-10 micrograms/kg) reduced both gastric and salivary secretions, pirenzepine showing little evidence of any selectivity for gastric secretion. 3 The H2-receptor antagonists, ranitidine (30-1000 micrograms/kg) and cimetidine (100-3000 micrograms/kg), selectively inhibited gastric secretion and even at relatively high dose levels did not alter salivary volume.

Anesthesia↗
PubMed1982

A possible mechanism of inotropic action of prolactin on rat heart.

Prolactin possesses positive inotropic actions in isolated heart preparations although the mechanism of this influence is not understood. Our study was designed to investigate the mechanism of this effect on the rat heart. Prolactin (50 ng/ml) produced a time-dependent increase (60%) in contractile force that reached maximum after 30 min and remained steady for a further 30 min. A similar time-dependent phenomenon was seen with 200 ng/ml prolactin although the maximum inotropic effect was reduced. Indomethacin (30 micrograms/ml) significantly reduced the inotropic effect of both prolactin concentrations although the effect of the hormone was not related to the release of 6-keto-PGF1 alpha, the prostacyclin metabolite. Propranolol (1-20 micrograms/ml) significantly reduced the positive inotropic effect of prolactin. Prolactin however had no influence on myocardial adenylate cyclase activity. Hearts that were removed from animals pretreated with 1.25 or 2.50 mg/kg reserpine did not respond to prolactin administration. It is suggested that the inotropic influence of prolactin is mediated by endogenous catecholamine liberation.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Prospective use of xenon Xe 133 clearance for amputation level selection.

Xenon Xe 133 clearance was used to select the most distal amputation level that would allow sufficient blood flow for healing. Capillary blood flow was first measured at the most distal potential amputation level, then at successive proximal levels until an amputation site was found that had a capillary skin blood flow rate greater than or equal to 2.6 mL/min/100 g of tissue. Xenon Xe 133 in saline (100 to 500 mCi) was injected intracutaneously at each level, and flow rates were determined using a gamma camera interfaced with a computer system programmed for the Ketty-Schmidt formula modified for capillary blood flow. There were 45 cases, including one toes, six transmetatarsal, five Syme's, 25 below-knee, four knee disarticulation, three above-knee, and one hip disarticulation amputation. All amputations in patients with flow rates exceeding 2.4 mL/min/100 g of tissue healed, with two exceptions.

Aged↗
PubMed1981

The effect of ranitidine on gastric acid secretory response curves to histamine, pentagastrin or bethanechol in the dog with a Heidenhain pouch.

The H2-receptor antagonists ranitidine and cimetidine were tested against gastric secretory dose-response curves to histamine, pentagastrin and bethanechol in the Heidenhain-pouch dog. Histamine-induced gastric secretion was antagonized in a competitive manner by both ranitidine and cimetidine, but ranitidine was approximately 8 times more potent than cimetidine. Pentagastrin -induced secretion was markedly reduced by ranitidine and cimetidine but this antagonism was not competitive in nature. Bethanechol-induced gastric secretion was slightly reduced by both drugs. These findings are discussed in relation to the physiological control of gastric secretion.

Animals↗
PubMed1981

H2-receptor antagonists protect against aspirin-induced gastric lesions in the rat.

Gastric mucosal lesions were produced in rats by dosing orally with aspirin, 300 mg/kg. Predosing orally with either ranitidine or cimetidine inhibited this lesion formation; the respective ED50 values were 0.8 and 3.9 mg/kg p.o. Oral ranitidine also inhibited lesion formation in the presence of exogenous 160 mM HCl, with an ED50 value of 23.2 mg/kg p.o. Subcutaneous injection of ranitidine inhibited the formation of aspirin-induced lesions both in the presence and in the absence of excess HCl. The ED50 values were respectively 3.4 and 0.9 mg/kg s.c. Mepyramine maleate (5 mg/kg p.o.) alone had no effect on gastric lesion formation, and did not influence the level of inhibition produced by ranitidine either in the absence of presence of exogenous acid.

Animals↗
PubMed1981

Lack of effect of prostaglandins on rat heart myofibrillar ATPase activity.

Although various prostaglandins have been shown to elicit an inotropic response in the rat heart, the subcellular basis responsible for this effect is unknown. The purpose of this study was to examine the influence of three prostaglandins with varying inotropic potencies on myofibrillar ATPase activity in the rat heart. PGF2 alpha, PGI2 and PGE2 were found to have no influence on basal or Ca2+-stimulated myofibrillar ATPase activity. In addition, no influence was observed on the sensitivity of myofibrillar ATPase activity to Ca2+. Alternative mechanisms to explain the inotropic effect are discussed.

Adenosine Triphosphatases↗