David W. Mercer

Open-chest cardiac massage without major thoracotomy: metabolic indicators of coronary and cerebral perfusion.

OBJECTIVEnTo compare the coronary and cerebral perfusion achieved using a novel method of minimally-invasive, direct cardiac massage to that obtained using bimanual, open-chest cardiac massage.nnnDESIGNnProspective, controlled animal study with repeated measures.nnnSETTINGnUniversity research laboratory.nnnSUBJECTSnLarge domestic swine.nnnINTERVENTIONSnAortic, coronary sinus, jugular venous and pulmonary artery catheters were placed. Following an equilibration period, ventricular fibrillation was induced. After 4 min of untreated ventricular fibrillation, animals underwent bimanual, open-chest cardiac massage (N = 6) or minimally-invasive, direct cardiac massage using a novel device for direct cardiac compression (N = 6). Adrenaline was administered at a dose of 1 mg intravenously every 5 min.nnnMEASUREMENTSnSystemic metabolic parameters, (arterial PO2, PCO2 and lactate concentration) and coronary sinus and jugular venous metabolic parameters (pH, PVO2, SVO2, PVCO2 and lactate concentration) were measured and calculated (coronary sinus/jugular-arterial SVO2, coronary sinus/jugular-arterial PCO2 and lactate differences) at baseline and at 10, 20 and 30 min following induction of ventricular fibrillation. Animals were euthanised after 30 min with no attempt at defibrillation.nnnMAIN RESULTSnOxygen tension and oxygen saturation of coronary sinus blood declined significantly during the experimental period, but no differences were noted between treatment groups. The coronary sinus-arterial oxygen saturation difference increased during the study with no significant differences between groups. Coronary sinus PCO2 and the coronary sinus-arterial PCO2 difference increased significantly in both experimental groups during cardiac massage. No inter-group differences were noted. A similar relationship was noted in coronary sinus lactate values. The coronary sinus-arterial lactate difference displayed a positive balance at all intervals with no differences noted between group values. The oxygen tension and oxygen saturation of jugular venous blood, were reduced from baseline levels with both treatments. The jugular-arterial oxygen saturation difference increased in both groups compared to baseline values. Between group values were significantly different only at the 20 min interval. Both the jugular venous PCO2 and the jugular-arterial PCO2 gradient were elevated at all intervals, but no inter-group differences were noted. Jugular venous lactate concentration rose steadily with time in both groups. No significant increase in the jugular-arterial lactate gradient was noted at any time point.nnnCONCLUSIONSnMinimally-invasive, direct cardiac massage provides coronary and cerebral perfusion similar to that achieved using standard open-chest cardiac massage. This method may provide a more effective substitute for standard, closed-chest cardiac massage in cases of refractory cardiac arrest.

Leukotriene receptor blockade reduces bile acid-induced superficial gastric mucosal injury

Leukotriene C4 and D4 are putative mediators of the severe gastric mucosal injury caused by a variety of topical irritants. The purpose of this present study was (1) to investigate the effect of pretreatment with topical leukotriene C4 and D4 on the more superficial injury caused by low concentrations of bile acid and (2) to determine the effect of leukotriene receptor blockade, alone and during leukotriene pretreatment, on this injury. Prior to injury with topical 5 mM acidified taurocholate (pH 1.2) rat stomachs were pretreated with either normal saline, leukotriene C4 or D4, SKF-104353 (a leukotriene receptor antagonist), SKF-104353/LTC4, or SKF-104353/LTD4. Injury was assessed by measuring hydrogen ion flux and DNA efflux, a marker of gastric mucosal cell exfoliation. Both LTC4 and LTD4 significantly increased bile acid-induced luminal hydrogen ion loss and DNA efflux. Leukotriene receptor blockade not only blocked this effect, but also significantly decreased the injury from bile acid alone. Thus, both LTC4 and LTD4 exacerbate the superficial gastric mucosal injury caused by physiologic concentrations of bile acids. Leukotriene receptor blockade with SKF-104353 completely blocks these effects and reduces injury from bile acid alone.

Isoproterenol-induced gastric mucosal protection from bile acid: Role of endogenous prostaglandins

Topical isoproterenol is a potent protective agent against bile acid-induced gastric mucosal injury in hypotensive and normotensive rats. This study was undertaken to ascertain what role endogenous prostaglandins and gastric mucosal blood flow play in isoproterenol-induced protection. Accordingly, anesthetized, fasted rats were given the cyclooxygenase inhibitor, indomethacin (5 mg/kg subcutaneously), 30 min prior to topical pretreatment with 3 ml of intragastric saline, isoproterenol (3 μM), or 16,16-dimethyl prostaglandin E2 (3 μM) for 15 min. Gastric injury was induced with topical 5 mM acidified taurocholate and damage assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology of the gastric epithelium. In a separate set of experiments, the effects of topical isoproterenol on gastric mucosal blood flow (laser Doppler flowmetry) and luminal PGE2 concentrations (125I radioimmunoassay) were examined. Pretreatment with topical isoproterenol or 16,16-dimethyl prostaglandin E2 significantly decreased bile acid-induced net luminal ion fluxes and DNA accumulation, suggesting mucosal protection. The protective effect of isoproterenol, but not 16,16-dimethyl prostaglandin E2, was negated by indomethacin (corroborated by histology). Further, isoproterenol did not significantly alter gastric mucosal blood flow, but did augment luminal PGE2 concentrations, an effect also abolished by indomethacin. Thus, isoproterenol appears to protect the gastric mucosa from the damaging effects of bile acid through a mechanism that requires the synthesis and release of cytoprotective endogenous prostaglandins.

Model for evaluation of infectibility of CO2 laser fusion anastomoses

In every surgical endeavor, the process of tissue repair should ideally result in the reapproximation of diided structures ith the restoration of anatomical tissue plane ind minimal scarring. Over the past to centuries, fine needle nd suture techniques have been used to accompliBh this; they have, however, fallen quite short of ideal repair. Ihe use of even fine suture for the reapproxirnation of arteries results in chronic inflammatory response that eventually lead to a neointimal hyperplasia, atherosclerosis, stenosis, and occIuion These problems the needle and suture led us to explore the use of thermal lasers for tissue repair.

Selective lipoxygenase inhibitor reduces bile acid-induced gastric mucosal injury☆

Leukotriene receptor blockade attenuates topical bile acid-induced gastric mucosal injury, suggesting that peptidyl-leukotrienes may be mediators of this injury. The purpose of this study was to test the hypothesis that a selective 5-lipoxygenase inhibitor protects against bile acid-induced gastric epithelial injury in the rat. Prior to injury with 10 and 20 mM acidified taurocholate (pH 1.2), rat stomachs were pretreated with either vehicle or WY50295K (selective 5-lipoxygenase inhibitor, 20 mg/kg). Injury was assessed by measuring net transmucosal hydrogen ion flux, luminal appearance of DNA, and gross mucosal injury. Topical 5-lipoxygenase inhibitor significantly reduced luminal H+ ion loss, surface epithelial cell loss (as measured by luminal accumulation of DNA), and gross mucosal injury in bile acid-injured stomachs compared to controls. This study lends further support to the hypothesis that leukotrienes may be mediators of bile acid-induced gastric mucosal injury.