Outcome of patients with ST segment elevation myocardial infarction (STEMI) following percutaneous transluminal coronary angioplasty: a retrospective study.

OBJECTIVES: To study the characteristics and long term outcome of patients who had segment elevation myocardial infarction (STEMI) and treated with PTCA in a fee levying hospital in Sri Lanka. METHODS: A retrospective study was conducted among patients diagnosed with STEMI and treated with PTCA in a fee levying private hospital in Colombo from 1st January 2009 to 1st November 2012. Details of patients were obtained from medical records and the survival status, cause of death and date of death where relevant, were obtained from records, patients or close relatives. RESULTS: 197 patients (153 men; 77.7%) were included. More than 50% had a history of diabetes, dyslipidaemia or hypertension. The three year survival was 82.7% (95% CI: 77.9%-90.5%). Based on the Cox's Proportional Hazards model, site of arterial occlusion (proximal vs distal segment of left anterior descending artery [LAD] was significantly associated with mortality due to all causes [HR 10.98; 95% CI: 1.09-110.20]. Low ejection fraction, not on regular medication and delay of more than 3 hours between onset to door time were associated with death due to cardiovascular causes in patients whose right coronary artery or left circumflex artery was the culprit artery. CONCLUSIONS: The three year survival of patients with STEMI and who had PTCA was 83%. Patients with proximal LAD occlusion were 11 times more likely to die within 3 years of PTCA as compared to those who had a distal LAD occlusion.

A comparative study on fatty acid profile in selected vessels of coronary artery bypass graft (CABG).

Atherosclerosis is one of the leading non-communicable diseases in Sri Lanka. Analysis of fatty acid composition in blood vessels is important in understanding the development of atherosclerosis. Here, analyses of fatty acid profiles in major arteries which are commonly used in Coronary Artery Bypass Graft surgery (CABG) were subjected to investigation. Patients (n = 27) undergoing elective CABG were enrolled in the study. A small biopsy segment of the saphenous vein (SV), radial artery (RA), and left internal mammary artery (LIMA) of patients was obtained during the surgery. The fatty acid (FA) profile of tissue samples was analyzed using Gas Chromatography-Mass Spectroscopy (GCMS). Among the different arteries tested, palmitic acid and stearic acid were the predominant fatty acids. As far as monounsaturated FA (MUFA) are concerned, oleic acid was found to be the most abundant MUFA in vessels. The FA profile of LIMA samples had a higher SFA percentage and lower unsaturated FA percentage compared to other vessels. Furthermore, the vessel samples of RA indicated the highest percentage of pro-inflammatory ω -6 polyunsaturated fatty acids (PUFA) as well as a higher percentage ratio between ω -6: ω -3 PUFA. The fatty acid composition and ω -6: ω -3 PUFA ratio suggests that LIMA graft is preferred for CABG over RA and SV.

Changes in erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and reduced glutathione (GSH) activities in the development of senile and diabetic cataracts.

Oxidative and osmotic stress have been implicated in the pathogenesis of cataracts. Reactive oxygen intermediates (ROI) mediate peroxidation of membrane lipids and cause irreversible damage to lens proteins. The purpose of this study was to assess the changes in erythrocyte glucose- 6-phosphate dehydrogenase enzyme (G6PD) and reduced glutathione (GSH) levels in the development of senile and diabetic cataracts. The activity of erythrocyte G6PD and the concentration of GSH were measured to assess changes in oxidation-reduction status. The oxidation-reduction status of 26 non-diabetic non-cataract (control) subjects were compared with 24 diabetic non-cataract, 30 diabetic cataract and 28 non-diabetic cataract subjects. The results revealed that the GSH and G6PD levels of the subjects with senile cataracts were significantly lower than the subjects without cataracts. The present study reveals the risk of developing senile cataracts is associated with decreased levels of erythrocyte G6PD and GSH. In the formation of diabetic cataracts an adequate supply of NADPH (G6PD activity) is essential to produce osmotically active sorbitol in the lens.

Serum cystatin C as a marker to identify patients with moderately impaired renal function.

The low molecular weight protein cystatin C produced by all nucleated cells and eliminated by glomerular filtration is of special benefit as a marker of renal function. A study was therefore undertaken to investigate whether serum cystatin C could be used as a marker to identify patients with moderately impaired renal function. A cross-sectional descriptive hospital based study was carried out and serum cystatin C was measured in fifty subjects aged 12 to 74 years with a 24 hr creatinine clearance estimation done at the same time. The gold standard creatinine clearance was used to compare the predicted glomerular filtration rate measured using serum cystatin C. Predicted glomerular filtration rate gave a sensitivity of 82% and specificity of 68% with a diagnostic cut-off value of 1.25mg/L cystatin C for identification of patients with moderately impaired renal function with a single random blood sample.

Effect of oral supplementation with vitamin E on the oxido-reductive status of red blood cells in normal mice and mice subject to oxidative stress by chronic administration of adriamycin.

The effect of oral vitamin E supplementation on the oxido-reductive status of red blood cells in normal mice and those subject to oxidative stress by chronic administration of the anti-tumour drug Adriamycin was investigated. Mice were randomly separated into three groups of 20 animals each and maintained on diets identical in all respects except for vitamin E content. Group 1 received a low vitamin E diet that provided 10 mg vitamin E/kg body weight/day, group 2 received a normal mice chow diet (45 mg vitamin E/kg body weight/day) while group 3 received a high vitamin E diet (200 mg vitamin E/kg body weight/day). In comparison with the normal mice in group 1, their counterparts in groups 2 and 3 exhibited significantly higher (P < 0.001) activities of superoxide dismutase (SOD) in red blood cells (79.4% higher in group 2 and 114.2% higher in group 3, respectively) and produced lower concentrations of malondialdehyde (MDA) (22.9% less in group 2 and 51.2% less in group 3, respectively), with little difference in the glutathione peroxidase (GPX) activity. In Adriamycin-treated animals on the low vitamin E diet (group 1) the red blood cell SOD activity and MDA production were 46.2% and 200.7% higher (P < 0.001), respectively, and the GPX activity was 39.1% lower than in the red blood cells of untreated (normal) animals in the same group. The Adriamycin-induced changes were significantly less in animals receiving higher doses of vitamin E (groups 2 and 3). Thus, in the group maintained on the high vitamin E diet (group 3), Adriamycin administration resulted in only a 38.9% increase in the MDA production above that generated by red blood cells of normal mice in the same group, with no significant change in the SOD or GPX activities. Thus, in normal conditions as well as in conditions of oxidative stress, high doses of vitamin E appear to be able to protect the oxido-reductive status of red blood cells by modulating the extent of lipid peroxidation as well as the activities of antioxidant enzymes.

Indices of stress in housed experimental sheep.

Six trained sheep were used in isotope dilution studies to determine the relations between glucose and lactate metabolism. The animals were judged by their behaviour and by their arterialplasma glucose and cortisol concentrations to be unstressed before and during each experiment. In each animal, however, the concentration of lactate in an arterial plasma sample taken immediately before an experiment was greater than the mean arterial plasma lactate concentration found during the course of the experiment. This increase in the concentration of lactate may be a sensitive index of apprehension in sheep which are well accustomed to being handled and which by other criteria appear to be unstressed.

Methylprednisolone and gentamicin effects on hepatosplanchnic blood flow and carbohydrate metabolism in endotoxemic Yucatan miniature pigs.

Conjoint therapy of a glucocorticoid and aminoglycoside antibiotic have been recommended for septic shock. These studies examined the hemodynamic and metabolic effects of methylprednisolone sodium succinate (MPSS) with and without gentamicin sulfate in a nonanesthetized model of nonseptic endotoxemia in Yucatan miniature pigs. Methylprednisolone sodium succinate alone had no effect on endotoxin-induced systemic hypotension. Endotoxemic pigs treated with MPSS in combination with gentamicin sulfate had lower mean arterial pressures than did MPSS-treated and nontreated endotoxemic pigs. Methylprednisolone sodium succinate alone and with gentamicin sulfate improved portal and hepatic venous blood flows moderately. Net hepatic lactate extraction, glucose production, and whole body [6-3H]glucose-derived rates of glucose appearance were also improved, but [6-3H]glucose-derived rates of glucose disappearance and blood lactate concentrations were increased, leading to no improvement in plasma glucose concentration. Pancreatic insulin secretion was higher in treated groups, which may have contributed to greater glucose utilization rates. Hepatic oxygen extraction efficiency was not affected by treatment, but increased in all groups to maintain hepatic oxygenation at base-line values. Although a calcium-antagonistic activity of gentamicin has been reported to synergize with endotoxin, thereby adversely affecting cardiovascular function, such effects did not complicate the metabolic response to steroid in the present studies.

Hepatitis B and C virus markers among new entrant medical students.

AIM: To investigate the presence of hepatitis B and C virus markers in new entrant medical students at the Faculty of Medicine, University of Kelaniya. METHOD: 456 students (mean age 24 years, SD 3.5, 257 men) were investigated before they were exposed to clinical work, using a questionnaire to assess sociodemographic factors and possible risk factors for contracting hepatitis B or C. Blood samples were tested for HBs Ag and anti HBs (n = 456), and anti-HCV (n = 162 randomly selected samples) with a third generation sandwich radioimmunoassay technique. RESULTS: The students were from 20 of the 25 districts in the country, although their distribution was not inform. A past history of hepatitis or jaundice was obtained from 24 (5.3%) and 6 (1.3%) students respectively. None of them had been vaccinated against hepatitis B. At least one risk factor for hepatitis B or C was present in 32 (7%) of them. None of the samples were positive for HBsAg or anti-HCV, and only two (0.44%) were positive for anti-HBs. CONCLUSION: Our results support the view that exposure to hepatitis B and C seems to be uncommon in this country, at least up to young adulthood. As most new entrant medical students are not immune to these infections there is a strong case to vaccinate them against hepatitis B before they are exposed to clinical work.

Glucose lactate interrelations in sheep.

The constant-infusion, isotope-dilution method was used to investigate the interrelationships between the glucose and lactate pools of six trained sheep deprived of food overnight. Arterial plasma lactate concentration was a linear function of the net lactate entry rate as was the net production of glucose from lactate, which suggests that the net rate of formation of glucose from lactate is dependent on the availability of lactate. Similarly the arterial plasma glucose concentration was correlated with the net entry rate of glucose as was the net production rate of lactate from glucose, suggesting that the net rate of lactate production from glucose is a function of arterial plasma glucose concentration. The demonstration of these two interrelations between glucose and lactate in normal sheep suggests that, in the absence of external factors producing hormonal or other changes that could cause perturbations of carbohydrate homeostasis, the net rates of conversion of glucose to lactate and of lactate to glucose may be largely determined by the arterial concentrations of glucose and lactate, respectively.

Sheep lactate entry-rate measurements: error due to sampling jugular blood.

Carotid arterial and jugular venous blood samples were taken simultaneously during primed continuous infusions of L-[U-14C]lactate in four sheep. The mean rate (n = 4) of total net formation of lactate (0.394 +/- 0.047 mg C/min per kg) calculated from the results obtained by analyzing the jugular blood samples for lactate concentration and specific radioactivity was significantly higher (0.01 greater than P greater than 0.005) than the mean rate (n = 4) calculated from the results of analysis of the arterial samples (0.302 +/- 0.036 mg C/min per kg). The error in the estimation of the rate of total net formation of lactate due to jugular sampling resulted from the negative arteriovenous difference found for lactate across the tissues of the head. These results illustrate the general need for examination of the suitability of venous sampling in experiments that make use of the continuous infusion isotope-dilution method.

Protection by garlic against adriamycin induced alterations in the oxido-reductive status of mouse red blood cells.

The effects of oral garlic supplementation on the activities of (a) the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) and (b) lipid peroxidation, as assessed by malondialdehyde (MDA) production in red blood cells of normal mice and those subject to oxidative stress by chronic administration of the anti-tumour drug adriamycin has been investigated. As expected, adria-mycin administration resulted in a significant increase in MDA generation (by 105.4%) and a decrease in GPX activity (by 23.8%) in the red blood cells. Although garlic had no significant effects on the basal levels of the antioxidant enzymes or MDA generation in red blood cells of normal mice (untreated with adriamycin), at doses of 20 mg/kg or 100 mg/kg, garlic was able to decrease significantly the adriamycin induced changes in the oxido-reductive status of the red blood cells. Thus, on administration of adriamycin to mice fed diets containing 20 mg/kg or 100 mg/kg garlic, the drug-induced increase in MDA generation was 38.2% and 22.5% respectively, less than that produced by adriamycin in mice fed normal diets, containing no garlic (105.4%). Similarly, in mice fed diets providing 20 mg/kg and 100 mg/kg garlic, adriamycin was able to decrease GPX activity by only 15.1% and 7.6% respectively, less than that produced by adriamycin in rats fed normal diets, containing no garlic (23.9%).

A comparative study of ketone body metabolism between the camel (Camelus dromedarius) and the sheep (Ovis aries).

1. Plasma levels of beta-hydroxybutyrate (BHB), and acetoacetate (AcAc) have been measured in camels (Camelus dromedarius) and sheep (Ovis aries). The activity of beta-hydroxybutyrate dehydrogenase (BHB-deH2) (E.C. 1.1.1.30) was studied in the rumen epithelium and the liver of these animals. 2. Concentrations of plasma BHB and AcAc in the camel were in respective order 33 and 4 times lower than that of the sheep. The ratios of BHB to AcAc were 0.61 and 4.8 for the camel and sheep, respectively. 3. The activity of BHB-deH2 in the rumen epithelium of the camel and sheep were 7.15 and 66 mumol/hr/g wet wt tissue, respectively. The activity in both species was higher in the rumen epithelium than in the liver.

Metabolic alterations related to reverse portal vein flow in an endotoxic pig.

Chronic hepatic artery and portal vein flowcuffs, in concert with hepatic vein and portal vein catheters, were placed in a Yucatan miniature pig. One week following surgery an endotoxin infusion was initiated. During endotoxemia there was a period of reverse portal vein flow while hepatic artery flow continued. This aberration resulted in unusual portal vein substrate and hormone concentrations. As endotoxemia progressed, the pig became hypoglycemic and hyperlactemic. Specific activity of [6-3H] - glucose was constant during developmental hypoglycemia, while insulin secretion rate was minimal indicating a significant endotoxin-induced, insulin-like activity. Hepatocytes isolated from the pig's liver at termination had inhibited gluconeogenic capacity.

Increased glucose uptake precedes hyperinsulinemia in awake endotoxemic minipigs.

The role of hyperinsulinemia in the development of hypoglycemia was evaluated in awake Yucatan minipigs. Eight adult minipigs were fitted with jugular, portal, and hepatic vein and carotid artery catheters, and hepatic artery and portal vein flow cuffs for determination of transhepatic kinetics and insulin secretion. Three days later they were infused with E. coli endotoxin at 15 micrograms/kg/hr. Transient hyperinsulinemia was preceded by an elevation of the rate of glucose uptake (Rd) determined from [6-3H] glucose-specific activity. This finding suggested that hyperinsulinemia might be caused by, and then be contributory to, increased Rd. If an increase in glucose uptake was also experienced by pancreatic beta-cells, the existing glycemic state could be overestimated and an inappropriate insulin release elicited.

Endotoxin dose. I. Hemodynamic, metabolic, and lethal consequences in Yucatan minipigs.

This study was performed in part to establish an endotoxin dosage in miniature swine that would yield reproducible cardiovascular and metabolic aberrations over a specific 6-h sampling period, minimizing lethality during that time. Five groups of three 6-mo-old Yucatan miniature pigs were surgically fitted with jugular vein and carotid artery catheters. One week later they were placed in slings and infused for 6 h with Difco 055:B5 endotoxin at dosages of 0, 2.5, 7.5, 15, and 25 micrograms X kg-1 X h-1. Significant (P less than or equal to 0.05) time-dose interactions were observed in mean arterial pressure, plasma glucose, serum potassium, blood lactate, pyruvate, bicarbonate, pH, PO2, PCO2, and urea nitrogen. Significant (P less than or equal to 0.05) differences were seen in lethality by 5 days postendotoxin: 0 = 0%, 2.5 = 0%, 7.5 = 33%, 15 = 67%, and 25 = 100% lethal. These animals exhibited a sensitive dose response to endotoxin, often at two- or threefold dose differences. The 15 and 25 micrograms X kg-1 X h-1 groups consistently demonstrated the most profound changes in the parameters measured.

Reduced hepatic blood flow does not limit gluconeogenesis in awake endotoxic minipigs.

Hypoglycemia associated with endotoxic shock is due to increased glucose utilization coupled with inadequate hepatic glucogenesis. Decreased hepatic blood flow is common in shock and could conceivably reduce hepatic gluconeogenic substrate and oxygen delivery, thereby limiting gluconeogenesis. A study was conducted to assess endotoxin-induced alteration of hepatic hemodynamics and its effect on glucose metabolism. Eight adult minipigs were fitted with jugular, portal, and hepatic vein and carotid artery catheters, and hepatic artery and portal vein flow cuffs for determination of transhepatic kinetics. Three days later they were infused with endotoxin at 15 micrograms/kg/hr. Hepatic blood flow and portal vein oxygen (O2) content became significantly (P less than or equal to 0.05) reduced thereby decreasing hepatic O2 input. Hepatic O2 extraction increased from 24 to 73% but never achieved the reported maximum of 97%. Therefore, reduction of O2 input did not seem to rate limit gluconeogenesis. Reductions in gluconeogenic substrate delivery were not involved since hepatic lactate and pyruvate input actually increased due to elevated blood lactate and pyruvate concentrations.

Persistent hyperinsulinemia due to induced euglycemia in awake endotoxic minipigs.

Transient hyperinsulinemia has been incriminated as a contributing factor to endotoxin-induced hypoglycemia. However, a recent study using endotoxic minipigs noted an increase in the rate of glucose utilization prior to when hyperinsulinemia was seen. Based on this, the "misinformed beta-cell" hypothesis was proposed. If endotoxic pancreatic beta-cells experience an early increase in glucose uptake, they could over-estimate the true glycemic state and release insulin, further contributing to the hypoglycemia. Hypoglycemia would offset increased glucose uptake by the beta-cell and insulin secretion would return to basal rates, explaining the transient nature of the insulin response. According to this hypothesis, maintenance of euglycemia should elicit a sustained rather than transient insulin release. The hypothesis was tested with a euglycemic clamp technique in a group of five endotoxic (Difco 055:B5; 15 micrograms/kg/hr) minipigs (EC) compared to three nonclamped endotoxic minipigs (E). Persistent, profound hyperinsulinemia (15 ng/ml) occurred in the EC group, further supporting the hypothesis. The clamp appeared to be beneficial, since arterial pressure and pH were significantly (P less than or equal to 0.05) higher and arterial lactate levels were lower in EC pigs compared to E pigs. A significant discrepancy was noted between the radioisotope ( [6-3H] glucose)-derived rate of glucose appearance and the rate of exogenous glucose infusion (clamp), which may have been due to unaccounted for changes in glucose pool size and/or futile cycling of glucogenic substrates or glucose through glycogen and lipid.

Hepatosplanchnic insulin kinetics in awake endotoxemic Yucatan minipigs: the "misinformed B-cell" hypothesis revisited.

Increased pancreatic insulin secretion may be one of the factors associated with the insulinlike activity (ILA) of endotoxemia. While there is little doubt that the prominent hypoglycemia of endotoxicosis is often preceded by systemic hyperinsulinemia, the cause of this increased secretion and its cause-and-effect relationship to the glucose deficit is less obvious. Recently, a "misinformed B-cell" hypothesis was proposed in which it was suggested that increased glucose flux across the pancreatic B-cell early in endotoxemia might lead to a misinterpretation of the existing glycemic state, resulting in increased insulin release. This possibility was based in part on the observation that increased 6-3H-glucose-derived rates of glucose disappearance (Rd) in endotoxic Yucatan minipigs preceded the onset of systemic hyperinsulinemia. Examination herein of the chronological order of events in this group of pigs and three other groups treated with lidocaine, naloxone, or captopril reveals an increase in pancreatic insulin secretory rate most often before increases in systemic Rd. Each of the three therapies were administered as a primed continuous intravenous infusion, 1 hour after the initiation of a continuous intravenous infusion of Difco 055:B5 E. coli lipopolysaccharide at an LD67 dose of 15 micrograms/kg/hr. In those pigs receiving no therapy, lidocaine, or naloxone, significant increases in pancreatic insulin secretion recurred at 40, 40, and 60 min following the onset of endotoxemia respectively. This was followed in 20 min by the first significant increase in relative glucose disappearance rates (%Rd). Captopril-treated pigs experienced a significant increase in %Rd at 60 min, which was followed in 20 min by a significant increase in pancreatic insulin secretion. In all groups, a significant hyperinsulinemia occurred transiently at 80 min postendotoxin, followed in 20 min by the onset of significant hypoglycemia. These observations suggest that increases in %Rd and transient increases in insulin secretion may be simultaneous events at best, and that along with significant increases in absolute levels of hepatic insulin extraction (observed in all groups at 60 or 80 min postendotoxin) may indicate some local effect of insulin release on hepatic glucose.