Spondyloarthritis: a strong predictor of early coronary artery bypass grafting.

OBJECTIVES: The main aim of the study was to examine whether patients with spondyloarthritides underwent their first coronary artery bypass grafting (CABG) at a younger age than those without spondyloarthritides. METHODS: Patients who underwent their first CABG at the Feiring Heart Clinic during 2001-2005 were preoperatively screened for spondyloarthritides, and the cardiological assessment was registered. We compared the characteristics of patients with and without spondyloarthritides. RESULTS: Of the 3852 patients undergoing their first CABG, 30 (0.78%) had spondyloarthritides. No statistically significant differences in traditional cardiovascular risk factors were found. The mean ages of patients with and without spondyloarthritides were 60.1 (SD = 8.7) and 66.9 (SD = 10.1) years, respectively. Spondyloarthritis was found by multivariate analysis to be a stronger independent predictor of early CABG than traditional cardiovascular risk factors [adjusted beta -6.2, p<0.001, 95% confidence interval (CI) -9.5 to -2.8]. Sixty per cent of spondyloarthritis patients and 52% of control patients had already suffered a myocardial infarction (p = 0.4). CONCLUSION: Spondyloarthritis was a stronger predictor of early CABG than most of the registered traditional cardiovascular risk factors. The prevalence of spondyloarthritis seemed to be higher in the CABG population than in the general population. These findings may indicate accelerated coronary artery disease (CAD) in spondyloarthritides.

Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue Doppler echocardiography.

BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. METHODS: Fifteen patients referred for elective aorto-coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. RESULTS: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.2 cm s-1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.3 cm s-1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 +/- 1 and 12 +/- 1 mmHg before surgery and 13 +/- 1 and 12 +/- 1 mmHg after surgery (P < 0.001 for all), respectively. CONCLUSION: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.

Allopurinol inhibits hypoxic pulmonary vasoconstriction. Role of toxic oxygen metabolites.

The exact mechanism whereby hypoxic pulmonary vasoconstriction (HPV) is elicited is still unsettled. We have evaluated a possible role for toxic oxygen metabolites (TOM), employing a set-up of blood-perfused isolated rat lungs. HPV reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/- 0.2 kPa to 3.2 +/- 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase (XO), allopurinol (AP) reduced the subsequent response to 2.5 +/- 0.2 kPa (P less than 0.001). By contrast, AP did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of XO). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on HPV; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that AP inhibition of XO depresses HPV. This could be due either to reduced production of TOM or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of TOM refutes a role for these metabolites in the elicitation of HPV. More likely, AP inhibits HPV by interfering with the purine metabolism.

Malignant hyperthermia during isoflurane anaesthesia. A case report.

A case of malignant hyperthermia during isoflurane anaesthesia without the use of muscle relaxants in a healthy 7-year-old girl is presented. In this case only premedication and nitrous oxide were used together with isoflurane. Thus isoflurane by itself can trigger malignant hyperthermia, even in the absence of muscle relaxants.

Secretin causes H+ secretion from intrahepatic bile ductules by vacuolar-type H(+)-ATPase.

Intrahepatic bile duct epithelial cells contribute to bile formation by hormone-dependently secreting HCO3- to bile and H+ to periductular fluid. The present study was undertaken to determine whether the secretin-induced H+ secretion is due to activation of a H(+)-ATPase or Na(+)-H+ exchange. H+ secretion was estimated from the rate of intracellular pH (pHi) recovery after acid loading (24 mM NH4Cl) of microdissected bile ductules from pig liver mounted in a flow-through chamber on the stage of a microscope. pHi was measured from an estimated average of 10-15 epithelial cells using the fluorescent pHi indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein and dual-wavelength excitation of fluorescence. The ducts were superfused with HCO3(-)-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffers. We found that secretin induced net H+ secretion of 4.53 +/- 0.7 mumol.ml cell volume-1 x min-1. This H+ secretion was blocked by 10(-6) M bafilomycin A1 but was unaffected by Na+ substitution with choline in the superfusion buffer. The experiments also showed that bafilomycin A1 did not block Na(+)-H+ exchange. The secretin-induced H+ secretion is probably caused by a vacuolar-type H(+)-ATPase and may constitute an important element of the cellular mechanisms causing secretin-dependent ductular HCO3- secretion into bile.

Colchicine inhibits the effects of secretin on pancreatic duct cell tubulovesicles and HCO3- secretion in the pig.

Secretin stimulation clears the cytoplasm of intralobular pancreatic duct cells in pigs of tubulovesicles and causes these cells to secrete HCO3- into the pancreatic juice. To determine whether the clearance of cytoplasmic tubulovesicles involves the microtubule system and is important for initiation of HCO3- secretion, the effect of the microtubule poison colchicine on duct cell morphology and pancreatic HCO3- secretion was measured in anaesthetized pigs. Before colchicine, secretin reduced the density of tubulovesicles in the cytoplasm of pancreatic duct cells from 92 +/- 8 U to 8 +/- 2 U and initiated pancreatic secretion of 176 +/- 21 mumols min-1 HCO3-. After colchicine, secretin failed to lower duct cell tubulovesicle density and caused the secretion of only 77 +/- 14 mumols min-1 HCO3-. By contrast, lumicolchicine, an isomer of colchicine that does not affect microtubules, did not inhibit pancreatic HCO3- secretion. Colchicine did not reduce carbonic anhydrase or Na,K-ATPase activities in in-vitro assays. The clearance of tubulovesicles from the cytoplasm of pancreatic duct cells therefore seems to be microtubule-dependent and important for the pancreatic HCO3- secretion.

Secretin-dependent HCO3- secretion from pancreas and liver.

Ultrastructural studies performed on pigs revealed that numerous cytoplasmic tubulovesicles were present in resting pancreatic duct cells. Elevation of systemic arterial PCO2 from 5.5 to 11 kPa increased the number of vesicles more than twofold. Following secretin administration, concurrent with the onset of HCO3- secretion (JHCO3), the cytoplasm became devoid of vesicles, and the basolateral plasma membrane surface area more than doubled. Similar phenomena were observed in bile duct cells. After pretreatment with the microtubules-inhibiting drug colchicine, secretin failed to reduce duct cell vesicle density, and JHCO3 was reduced by c. 50% compared to the control. These ultrastructural changes resemble those described in other H+/HCO3(-)-transporting organs such as the distal nephron and the urinary bladder. Our findings are compatible with the notion that cytoplasmic vesicles containing H(+)-ATPases are incorporated into the basolateral plasma membrane of secretory cells during secretin stimulation. Active transport of H+ into interstitial fluid might therefore be the driving force underlying JHCO3.

Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase.

BACKGROUND/AIMS: Secretin stimulates pancreatic ductules to secrete HCO3- into pancreatic juice and H+ into interstitial fluid. The aim of the present study was first to examine whether ductular H+ secretion is inhibited by micromolar concentrations of bafilomycin A1, which blocks vacuolar H(+)-adenosine triphosphatase by specific action, and secondly to test for evidence of ductular Na+/HCO3- cotransport. METHODS: Ductular H+ secretion was estimated from the rate of intracellular pH recovery after acid-loading (24 mmol/L NH4Cl) microdissected pancreatic ductules from pig, mounted in a flow-through perfusion chamber on the stage of a fluorescent microscope. Intracellular pH was measured using the fluorescent pH indicator 2'7'-bis (carboxyethyl)-5,6-carboxyfluorescein and dual-wave-length excitation of fluorescence. The ducts were superfused perfused with either HCO3(-)-free HEPES-containing buffers or HCO3(-)-containing buffers. RESULTS: Secretin (10(-8) mol/L) induced a net H+ secretion of 1.87 +/- 0.23 mumol.mL cell vol-1.min-1 that was blocked by 10(-6) mol/L bafilomycin A1 and was unaffected by Na+ substitution with choline using HEPES superfusion buffers. Secretin-stimulated ductules superfused with bicarbonate-containing, Cl(-)-free buffers showed Na(+)-dependent and 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid-inhibitable alkalinization of intracellular pH. CONCLUSIONS: Secretin causes H+/HCO3- secretion from pancreatic ductules by a mechanism involving vacuolar-type H(+)-adenosine phosphatase. Pancreatic ductules also show Na+/HCO3- cotransport, which may account for a small fraction of secreted bicarbonate.

Importance of carbonic anhydrase for canalicular and ductular choleresis in the pig.

To assess the importance of carbonic anhydrase (CA) for canalicular and ductular choleresis, the effect of acetazolamide on bile secretion was measured in three experimental groups of anaesthetized pigs. CA activity in liver homogenate was 46 (43-54) U g-1 wet weight, 150 mg kg-1 b.w. acetazolamide completely abolished the CA activity. Acetazolamide reduced bile HCO3- secretion in six secretin infused, bile-acid depleted pigs by 67 (58-71)% at arterial pH 7.41 (7.38-7.46). By contrast, acetazolamide did not affect HCO3- secretion in six Na-taurocholate (TCA) infused pigs in the absence of secretin stimulation. Acetazolamide reduced ursodeoxycholic-acid- (UDCA) dependent HCO3- secretion by 24 (11-38)% in six other pigs in the absence of secretin stimulation. Histochemical examination using modifications of Hansson's method showed strong reaction in bile ductules and weaker reaction in peripheral zones of liver lobules. Because acetazolamide impairs HCO3- secretion from cells sustaining high rates of H+/HCO3- transport, it is suggested that high rates of H+/HCO3- transport are confined to bile ductules under conditions of secretin- and UDCA-induced choleresis.

Determination of active 5-(N,N-hexamethylene)amiloride in pig plasma.

A simple, cheap and specific quantitative method for the determination of the selective Na+/H+ exchange inhibitor, 5-(N,N-hexamethylene)amiloride, in plasma and aqueous solutions has been developed. The method involves extraction with ethyl acetate, thin-layer chromatography and spectrofluorodensitometry. The compound was separated from several unidentified metabolites in plasma. The detection limit was 6 x 10(-7) M. The calculated metabolic extraction by the liver was 29%, and the plasma half-life was 12.8 min. The free, active concentration of 5-(N,N-hexamethylene)amiloride was 19.4% of the total concentration, as determined by equilibrium dialysis.

Secretin stimulates bile ductules to secrete both H+ and HCO3(-)-ions.

Secretin-dependent ductular HCO3- secretion into bile may involve secretion of H+ to interstitial fluid and HCO3- to bile by the ductular epithelium. To determine whether secretin causes bile ductules to secrete H+, we have examined the effect of secretin on the elimination of an intracellular acid load from bile ductular epithelium during pharmacological blockade of Na(+)-H+ exchange and in the absence of HCO3-. Microdissected bile ductules from pigs were suspended in HCO3- free HEPES buffer and loaded with acid using an NH4Cl prepulse technique. Intracellular pH was measured using dual-wavelength excitation of BCECF fluorescence. Na(+)-H+ exchange was defined as a Na(+)-dependent and amiloride- and 5-(N,N-hexamethylene)-amiloride-sensitive efflux of H(+)-ions following acid loading. We found that secretin stimulated ductular H+ secretion independent of Na(+)-H+ exchange. Blockade of Na(+)-H+ exchange by hexamethylene-amiloride did not affect secretin-dependent ductular HCO3- choleresis in vivo. We conclude that secretin stimulates bile ductules to secrete H(+)-ions to interstitial fluid as well as HCO3- ions to bile by a mechanism independent of Na(+)-H+ exchange.

Intravenous bilirubin infusion causes vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis.

To examine whether intravenous bilirubin infusion causes cholestasis and impairs liver metabolism, bile secretion and ethanol clearance were measured in 34 anaesthetized pigs before and after intravenous infusion of 0.5 mumol kg-1 min-1 bilirubin for 4.5 hours. Bilirubin infusion increased plasma bilirubin to 556 +/- 76 mumol l-1 and hepatic tissue bilirubin to 3.5 +/- 1.3 mmol kg tissue weight-1. Bilirubin infusion depressed bilirubin secretion and net hepatic uptake of cholate and taurocholate, and caused a 86 +/- 6% reduction of cholate-induced bile secretion. Bilirubin caused formation of large cytoplasmic vacuoles in hepatocytes and dilatation of bile canaliculi. Ethanol clearance and secretin-dependent ductular bile secretion were unaffected by bilirubin. We conclude that intravenous infusion of unconjugated bilirubin causes accumulation of bilirubin in the liver, vacuolization of the hepatocyte cytoplasm and canalicular but not ductular cholestasis. The canalicular cholestasis is not due to impaired hepatic mitochondrial energy metabolism, but may be due to inhibition of a common pathway for lipid, bilirubin and bile salt secretion from hepatocytes.

Colchicine blocks the effects of secretin on bile duct cell tubulovesicles and plasma membrane geometry and impairs ductular HCO3- secretion in the pig.

Secretin causes the bile duct cells to secrete HCO3-. To examine whether the transformation of duct cell ultrastructure that follows secretin stimulation depends on microtubules and is important for ductular HCO3- secretion, we examined the effect of colchicine on ductular HCO3- secretion and on the morphology of cells lining bile ductules of anaesthetized pigs. Colchicine blocked secretin-dependent cytoplasmic clearance of tubulovesicles and prevented expansion of the basolateral plasma membrane in duct cells and reduced the ductular HCO3- secretory response from 132 +/- 25 mumol min-1 to 97 +/- 14 mumol min-1. In contrast, lumicolchicine did not affect secretin-dependent tubulovesicle clearance or plasma membrane geometry or ductular HCO3- secretion. Accordingly, secretin-dependent cytoplasmic clearance of tubulovesicles in bile duct cells appears to depend on microtubules and to be important for ductular HCO3- secretion.

Secretin dissipates red acridine orange fluorescence from pancreatic duct epithelium.

This study was undertaken to elucidate whether duct cells in the pancreas contain acidic cytoplasmic compartments regulated by secretin. Microdissected pancreatic ducts from pigs were examined by acridine orange (AO) and 2',7'-biscarboxyethyl-5(6)-carboxyfluorescein/tetraacetoxymethy l ester (BCECF/AM) epifluorescence microscopy. Estimated cytoplasmic pH using BCECF fluorescence was 7.43 +/- 0.04 and was not changed by altering CO2 tension in the incubation medium. The epithelium of acridine orange incubated peripheral interlobular pancreatic ducts exhibited green and red fluorescence; the colour depending on the experimental conditions. Red epithelial fluorescence was seen in resting pancreatic ducts and was greatly accentuated by raising CO2 in the incubation medium from 5.5 to 10 kPa. The red fluorescence was abolished by secretin, or following incubation with chloroquine or NH4Cl or the protonophores carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or carbonyl cyanide m-chlorophenylhydrazone (CCCP), leaving uniform green fluorescence. These findings suggest that pancreatic duct cells contain CO2-dependent acidic compartments which vanish during secretin stimulation and which may be cytoplasmic tubulovesicles.

Na(+)-H+ exchange is not important for pancreatic HCO3- secretion in the pig.

UNLABELLED: Pancreatic inter- and intralobular duct cells extrude H(+)-ions to interstitial fluid when they secrete HCO3- to pancreatic juice. This study assesses the potential importance of Na(+)-H(+)-ion exchange for H(+)-ion extrusion and secretion of HCO3-, using the Na(+)-H+ exchange blockers amiloride and hexamethylene-amiloride. Intracellular pH (pHi) in inter- and intralobular pancreatic duct epithelium was measured using BCECF fluorescence. H(+)-ion efflux was measured using a NH4Cl prepulse, acid-loading technique. In HCO3(-)-free media, pHi recovery following acid loading was blocked by amiloride (10(-4) M) and hexamethylene-amiloride (10(-6) M), demonstrating amiloride- and hexamethylene-amiloride-sensitive Na(+)-H+ exchange. However, 5 x 10(-6) M hexamethylene-amiloride did not reduce secretin-dependent pancreatic HCO3- secretion in vivo. Maximal H(+)-efflux through Na(+)-H+ exchange was 1.5 +/- 0.2 mumol min-1 ml cell volume-1, i.e. less than 1% of estimated net H(+)-ion efflux during HCO3- secretion. CONCLUSION: amiloride- and hexamethylene amiloride sensitive Na(+)-H+ exchange is not important for secretin-dependent pancreatic HCO3- secretion in the pig. Other mechanisms for H+ extrusion dominate.

The effects of chewing gum on gastric content prior to induction of general anesthesia.

To study the effects on gastric content and subjective well being of chewing gum in the immediate preoperative period, 60 female nonsmokers were randomized to use regular, sugar-free chewing gum preoperatively or to continue the overnight fast. In a similar fashion 44 habitual smokers were randomized to use nicotine gum 2 mg or not. Nonsmokers using chewing gum had significantly larger gastric fluid volumes than controls (mean 30 +/- 19 mL vs 20 +/- 15 mL; 95% confidence interval (CI) for difference 1-19 mL; P = 0.03), with no difference in gastric fluid acidity. In smokers, neither gastric fluid volume nor acidity differed significantly between those who were or were not chewing gum. Although the use of nicotine gum in smokers was associated with a reduction in dryness of the mouth, thirst, and irritability, nonsmokers chewing regular gum did not report significant improvements in patient well being. In habitual smokers unable to abstain from nicotine, the use of nicotine gum on the morning of surgery may be beneficial. Although it is difficult to prove a direct influence on the incidence of pulmonary aspiration of increased gastric contents, the fact that regular, sugar-free chewing gum increased gastric fluid volumes probably means that it should not be used on the morning of surgery.