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Biomedical subjects

R S Walsh

Publications and source records attributed to R S Walsh.

11 recordsLinked to original sources

Developing shared learning in multiprofessional health care education: for whose benefit?

A selection of examples from programmes of shared learning indicates that the movement towards collaboration among health care professionals is thought of as a good thing and ways and means of achieving it need to be fostered. But just who are the supposed beneficiaries of such collaboration and should more work be done in analysing the assumptions that underpin much of this work? A literature review indicates a number of threats as well as opportunities for health care professionals emanating from this work, each of which needs careful consideration by educationalists. A brief analysis of the intentions of the teachers on a BA(Hons) Health Care Studies programme indicates that their approach may be useful in respecting the professional autonomy of participants by not pressing too hard for collaboration, but allowing them as individuals to select relevant learning from and about each other for themselves. History indicates that collaboration is not new and the specific, specialized contributions of professionals have a long history in holding the organization of health care services together. The organizational skills of nurses and others should not be lost but should be fostered carefully so that they are not damaged but included in an atmosphere of non-exclusion of all interested stakeholders in the National Health Service. The authors recommend that the best practices of shared learning in multiprofessional programmes be extended to benefit consumers, administrators and politicians in joint initiative programmes which could be of benefit to all.

Cooperative Behavior↗

Hypoxia preconditions rabbit myocardium via adenosine and catecholamine release.

It has been proposed that brief hypoxia can substitute for ischemia in the preconditioning of cardiac tissue and salvage of ischemic myocardium. To elucidate a possible mechanism isolated rabbit hearts were subjected to a 30-min period of regional ischemia by occluding a previously snared coronary artery. Following 2 h of reperfusion infarct size was measured by staining left ventricular slices with triphenyltetrazolium chloride. In control hearts infarction averaged 28.7 +/- 1.9% of the risk zone. If the hearts were preconditioned with 5 min global ischemia/10 min reperfusion prior to the regional ischemia, then infarction was significantly reduced to 7.2 +/- 2.0% (P < 0.01). When global hypoxia (pO2 of perfusate 42.0 +/- 2.1 mmHg) for ten min substituted for the five min period of global ischemia, protection was comparable to that observed after ischemic preconditioning (10.2 +/- 1.5% infarction, P< 0.01 v control). During hypoxic perfusion adenosine release increased 16-fold over baseline levels. This protection could not be blocked by adding levels either the adenosine antagonist 8-(p-sulfophenyl)theophylline or the alpha 1-adrenergic blocker phenoxybenzamine to the hypoxic perfusate. However, co-administration of both agents to the hypoxic perfusate successfully aborted protection (22.6 +/- 2.9% infarction, P N.S. v control). Therefore, 10 min of hypoxia releases both norepinephrine and adenosine in sufficient quantities such that either can completely precondition the heart.

Adenosine↗

Hypoxia preconditions rabbit myocardium by an adenosine receptor-mediated mechanism.

OBJECTIVES: To test the ability of hypoxia without reoxygenation to precondition myocardium and to test a possible involvement of adenosine receptors in that response. DESIGN: Isolated rabbit hearts were perfused with oxygenated Krebs-Henseleit buffer. Control hearts underwent 30 min regional ischemia followed by 2 h reperfusion. A second group received 10 min global perfusion with hypoxic buffer (PO2 = 33 +/- 3 mmHg) immediately before coronary occlusion. A third group was subjected to a similar protocol as group 2, with the adenosine receptor blocker 8-(p-sulfophenyl) theophylline (SPT) (100 microM) added to the buffer immediately before and throughout hypoxia. At the end of reperfusion the area at risk for infarction was determined by fluorescent particles while infarction size was measured by triphenyltetrazolium staining. RESULTS: Hearts without hypoxic perfusion preceding ischemia experienced 38.2 +/- 2.4% infarction. The hypoxic group, despite a longer total period of oxygen deprivation, had only 21.0 +/- 4.2% infarction (P < or = 0.05). SPT blocked the protection (42.1 +/- 6.9% infarction). CONCLUSIONS: Hypoxia without subsequent reoxygenation before ischemia protected the heart from infarction, indicating that reoxygenation may not be the critical feature of reperfusion typically employed in an ischemic preconditioning protocol. Because adenosine receptor blockade abolishes the protection from hypoxic perfusion, the mechanism of this protection may be similar to that seen with ischemic preconditioning.

Animals↗

Hydrogen peroxide as a protective agent during reperfusion. A study in the isolated perfused rabbit heart subjected to regional ischemia.

In spite of extensive research during the last decade it has not been possible to prove that endogenously generated hydrogen peroxide or any reduced oxygen species reaches sufficient concentration during reperfusion after myocardial ischemia to contribute significantly to irreversible cell injury. In an attempt to further test this hypothesis we subjected isolated perfused rabbit hearts to 30 min regional ischemia followed by reperfusion and supplied hydrogen peroxide in low levels with or without catalase during the first 30 min of reperfusion and thereafter continued the reperfusion for a total of 120 min. Five different groups were studied: controls, and hearts supplied with 2 microM H2O2, 1 microM H2O2, 1 microM H2O2 + catalase (IU/l) or catalase alone in the initial part of the reperfusion. At the end of 120 min reperfusion, area at risk was measured with fluorescent particles and infarct zone size with tetrazolium staining. The results were: in the control group 32 +/- 5.0% of the risk zone infarcted, in the 2 microM H2O2 group 16.3 +/- 5.6% and in the 1 microM H2O2 group 6.9 +/- 0.8% (P < 0.05 compared to control). The reduction in infarct size was not present when catalase was added to the hydrogen peroxide-containing solution (26.4 +/- 4.5) or if catalase was present alone (22.9 +/- 1.8% infarction). In conclusion, hydrogen peroxide, 1 microM, protected the heart during reperfusion and reduced the amount of cell death after 120 min of reperfusion. The study demonstrated reduction or delay in infarction based only on treatment in the reperfusion period. The mechanism behind this protection remains to be determined.

Analysis of Variance↗

Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.

OBJECTIVE: Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. METHODS: Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. RESULTS: In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 microM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 microM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. CONCLUSIONS: Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor.

Adenosine↗

Ketamine-xylazine anaesthesia permits a KATP channel antagonist to attenuate preconditioning in rabbit myocardium.

OBJECTIVE: ATP sensitive potassium (KATP) channels have been implicated in the mechanism of ischaemic preconditioning, though apparently not in the pentobarbitone anaesthetised rabbit model. The aim of this study was to test whether potassium channel activation and blockade would alter protection in ketamine-xylazine anaesthetised rabbits. METHODS: In situ rabbit hearts (n = 50) received 30 min regional ischaemia and 3 h reperfusion. Some hearts were preconditioned by 5 min regional ischaemia and 10 min reperfusion prior to the long ischaemia. Infarct size was determined by tetrazolium staining. RESULTS: In rabbits anaesthetised with ketamine-xylazine, brief preconditioning ischaemia continued to produce much smaller infarcts than in non-preconditioned animals [19(SEM 2)% v 47(3)%, p < or = 0.05]. blocking KATP channels by pretreating with glibenclamide resulted in 35(3)% infarction in non-preconditioned hearts and aborted protection in preconditioned hearts [35(4)% infarction]. Substituting the potassium channel activator pinacidil for the short ischaemia caused comparable reductions in infarct size [28(4)%, p < or = 0.05 v non-preconditioned hearts]. This protection, however, could be blocked by concomitant administration of the adenosine receptor blocker 8-(p-sulphophenyl)theophylline (SPT) [44(3)% infarction]. CONCLUSIONS: When ketamine-xylazine anaesthesia was employed, the protective effects of ischaemic preconditioning in the rabbit heart could be blocked by glibenclamide, and pinacidil could mimic the protection of ischaemic preconditioning. Because the protection afforded by pinacidil could be blocked by SPT, however, there is still some question whether the KATP channel is the end effector of preconditioning.

Animals↗

Response of lamb ductus arteriosus to nitroglycerin and nitroprusside.

In certain forms of congenital heart disease, patency of the ductus arteriosus is critical for survival. Since the administration of prostaglandin is associated with adverse side effects, this study was undertaken to evaluate the effects of nitroglycerin and nitroprusside on ductal blood flow during oxygen-induced ductal closure. Fifteen near-term fetal lambs were instrumented acutely. Ductal blood flow and pre- and post-ductal pressures were monitored continuously. After obtaining control data, intravenous bolus injections of nitroglycerin (250 micrograms), nitroprusside (250 micrograms), or prostaglandin E1 (5 micrograms) were administered during ventilation with either 100% nitrogen or 100% oxygen. All three agents significantly increased ductal blood flow during nitrogen ventilation (PO2 = 15 +/- 1 mm Hg). When the lambs were ventilated with 100% oxygen, the arterial PO2 increased to 107 +/- 14 mm Hg, and this was associated with a marked decrease in ductal blood flow from 275 +/- 44 to 83 +/- 11 ml/min (P less than 0.05). When nitroglycerin was administered during oxygen-stimulated ductal closure, ductal blood flow increased 184%, from 79 +/- 18 to 225 +/- 18 ml/min (P less than 0.05); nitroprusside increased ductal blood flow 126%, from 86 +/- 20 to 195 +/- 25 ml/min (P less than 0.05); prostaglandin E1 increased ductal blood flow 110%, from 84 +/- 18 to 178 +/- 17 ml/min (P less than 0.05). These data demonstrate that both nitroglycerin and nitroprusside are potent vasodilators of the ductus arteriosus and, like prostaglandin E1, can markedly attenuate the oxygen-induced ductal vasoconstriction. These results imply that nitroglycerin and nitroprusside may be useful clinically in maintaining ductal patency.

Alprostadil↗

Role of cyclic nucleotides in relaxation of fetal lamb ductus arteriosus.

Although prostaglandin E1 is used to dilate the constricted ductus arteriosus in infants with cyanotic heart disease, the mechanism is unknown. To test the hypothesis that the cyclic nucleotides adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) play a role in relaxation, isolated rings of the ductus arteriosus of fetal lambs were studied. Tension of isometric contraction was measured by force displacement transducers. After contraction with oxygen, a control group was compared with rings in which the stimulus for relaxation was either nitrogen gas, prostaglandin E1 (PGE1), nitroglycerin (NTG), or nitroprusside (NPS). During relaxation, tissue was frozen at 30 seconds and at 1, 2, and 5 minutes and analyzed for cAMP and cGMP. PGE1 (10(-6) mol/L) decreased tension by 33% compared with 70% for nitrogen gas, 81% for NTG (10(-5) mol/L), and 92% for NPS (10(-5) mol/L). The maximal relaxation induced by PGE1 was associated with an 11-fold increase in cAMP; PGE1 had no significant effect on cGMP tissue levels. Nitrogen gas, NTG, and NPS produced similar increases in cAMP, and eight-, 25-, and nine-fold increases in cGMP, respectively. These results suggest that the patency of the ductus arteriosus is dependent on activation of both guanylate cyclase and adenylate cyclase and that the nitrovasodilators may be clinically useful in maintaining patency of the ductus arteriosus.

Alprostadil↗

Hypoxia-induced release of atrial natriuretic factor (ANF) from the isolated rat and rabbit heart.

The effect of hypoxia on the release of atrial natriuretic factor (ANF) was studied in isolated, constant-flow perfused hearts of rats and rabbits. Effluent samples were frozen pending extraction and radioimmunoassay of ANF. Hypoxia (10 min) caused a 3.9-fold (rats) and 4.6-fold (rabbits) increase of ANF release over control values. ANF release returned to control levels within 8-11 min of reoxygenation. Prolonged (20 min) hypoxia evoked further ANF release. The increase in ANF release and decrease in ventricular pressure, heart rate and coronary perfusion pressure were fully reversible, suggesting that tissues were not damaged. These results demonstrate that hypoxia induces a massive release of ANF by an as yet unexplained mechanism.

Animals↗

Heterogenomic recombinants from compatible nocardiae.

Recombinants obtained from matings of Nocardia erythropolis x N. canicruria were tested for their genetic stability by comparing phenotypes from direct selection with the same population after unselected growth. Contraselective loci were employed in various combinations in order that all of the mapped characters might be subjected to unselected analysis. Some recombinant class types appeared as stable haploids, whereas others behaved as heterozygous diploids, segregating out new phenotypes. All regions of the parental genomes were found to be involved in segregation, implying that the entire mapped region can become merozygotic under standard mating conditions. On the basis of segregating phenotypes, the genetic potentials of these compatible nocardiae were ascertained as follows: the formation of a diploid with subsequent segregation of parental or haploid recombinant genomes or both; persistence of the diploid through many generations; continuing reassortment of genetic information by multiple matings between parental or recombinant organisms; and, very probably, second-round recombinations within the diploid. A considerable difference in the nuclear division time between the parental organisms was postulated to have significant effects on the nature of the unselected segregants.

Crosses, Genetic↗

Clinical experience with the Nimbus pump.

The Nimbus pump is an indwelling, electromagnetic powered left ventricular (LV) assist device inserted transfemorally. The inflow cannula (7 mm) is positioned across the aortic valve and the pump in the descending aorta. Indications for insertion include cardiogenic shock despite maximal medical support and PCWP greater than 18 mmHg, MAP less than 90 mmHg, and Cl less than 2 L/min/m2. Twelve patients underwent the attempt at surgical insertion of the Nimbus pump. Diagnoses included eight acute myocardial infarctions (AMI), two ischemic cardiomyopathy, one postpartum cardiomyopathy, and one transplanted heart rejection. Eight (67%) of twelve patients had successful insertion. One patient had peripheral vascular disease preventing passage, and three had femoral vessels too small for insertion (less than 7.5 Hagar dilator). Five patients with the diagnosis of AMI had successful insertion and three (60%) underwent sufficient LV recovery for removal of the device; the other two patients died of stroke and ventricular arrhythmias, respectively. Three patients with the diagnosis of cardiomyopathy had progression of the disease process, and their needs exceeded the capabilities of the pump and they died of multiorgan failure. The Nimbus pump is an attractive LV assist device because of its pumping capacity (3.5 L/min) and minor surgical procedure for insertion. However, its application is limited because of access route and size. The device appears to work well for patients in cardiogenic shock after AMI (60% recovery) but does not appear indicated for patients with cadiomyopathy.

Adult↗