Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects

Background

Habitual smoking is a risk factor for a variety of vascular diseases, including ocular pathologies. In the current study, we set out to investigate whether the regulation of retinal vascular tone is impaired in habitual smokers. For this purpose, vascular reactivity was tested during flicker light induced vasodilatation in smokers and in a non-smoking control group.

Methods

In this prospective, balanced, parallel group study 24 chronic smokers (28.1 ± 3.3 years) and 24 age-matched never-smoking volunteers (28.2 ± 4.0 years) were included. Flicker induced vasodilatation was measured in major retinal arteries and veins using a retinal vessel analyzer and flicker induced changes in retinal blood velocities were assessed in retinal veins by laser Doppler velocimetry. Three flicker periods of 60 s were scheduled. Blood cotinine concentration was determined and a Fagerstrom questionnaire was performed to evaluate nicotine dependency.

Results

In non-smoking subjects, stimulation with flicker light increased retinal venous diameter by + 7.7 ± 3.1%, + 6.9 ± 2.9% and + 7.1 ± 2.8% during the three flicker periods, respectively. Flicker induced vasodilatation in veins was significantly diminished in chronic smokers (+ 4.9 ± 2.4%, + 6.3 ± 3.1% and + 5.7 ± 3.4%, ANOVA between groups, p = 0.032) as compared to the non-smoking control group. Calculated retinal blood flow in the measured veins increased by a maximum of + 54 ± 21%, + 43 ± 18% and + 46 ± 19% during the three stimulation periods in the non-smoking subjects, respectively. The flicker induced increase in retinal blood flow as assessed in the veins was significantly reduced in chronic smokers as compared to the non-smoking control group (+ 19 ± 16%, + 26 ± 14%, + 24 ± 13%, ANOVA between groups, p = 0.013). In retinal arteries, flicker stimulation increased retinal arterial diameters by 5.2 ± 3.8%, 5.8 ± 4.8% and 5.5 ± 5.6% during the three flicker periods in the non-smoking group. In smokers, the flicker induced arterial vasodilatation was not significantly different compared to non-smokers (4.6 ± 4.1%, 3.8 ± 3.7% and 4.8 ± 3.4%, ANOVA between groups, p = 0.4).

Conclusion

Our data indicate that the flicker induced hemodynamic response of retinal veins is reduced in chronic smokers as compared to age matched healthy volunteers. This supports the hypothesis that chronic smoking leads to vascular dysfunction in the eye.     

Effects of ethanol and wine on hepatic arterial and portal venous flows in conscious dogs.

The effects of ethanol and wine on hepatic arterial and portal venous flows were examined in conscious dogs. Ethanol was given intravenously or intragastrically, and red wine (ethanol: 14%) was given intragastrically over 30 min. Intravenous ethanol (0.8 g/kg) and intragastric ethanol (14% vol/vol) increased hepatic arterial flow, which remained elevated for 60 min after the cessation of ethanol administration. Ethanol also increased portal venous flow. Portal venous flow returned gradually toward basal levels after the cessation of intravenous ethanol infusion, whereas it remained elevated even after the cessation of intragastric ethanol. Intragastric wine increased hepatic arterial and portal venous flows. In contrast to intragastric ethanol, hepatic arterial flow continued to rise after the cessation of intragastric wine infusion, while portal venous flow returned toward basal levels. We conclude that, though both ethanol and wine increase hepatic blood flow, the responses of hepatic arterial and portal venous flows differ substantially among intravenous ethanol, intragastric ethanol and intragastric wine.     

Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects

BackgroundHabitual smoking is a risk factor for a variety of vascular diseases, including ocular pathologies. In the current study, we set out to investigate whether the regulation of retinal vascular tone is impaired in habitual smokers. For this purpose, vascular reactivity was tested during flicker light induced vasodilatation in smokers and in a non-smoking control group.MethodsIn this prospective, balanced, parallel group study 24 chronic smokers (28.1 ± 3.3 years) and 24 age-matched never-smoking volunteers (28.2 ± 4.0 years) were included. Flicker induced vasodilatation was measured in major retinal arteries and veins using a retinal vessel analyzer and flicker induced changes in retinal blood velocities were assessed in retinal veins by laser Doppler velocimetry. Three flicker periods of 60 s were scheduled. Blood cotinine concentration was determined and a Fagerstrom questionnaire was performed to evaluate nicotine dependency.ResultsIn non-smoking subjects, stimulation with flicker light increased retinal venous diameter by + 7.7 ± 3.1%, + 6.9 ± 2.9% and + 7.1 ± 2.8% during the three flicker periods, respectively. Flicker induced vasodilatation in veins was significantly diminished in chronic smokers (+ 4.9 ± 2.4%, + 6.3 ± 3.1% and + 5.7 ± 3.4%, ANOVA between groups, p = 0.032) as compared to the non-smoking control group. Calculated retinal blood flow in the measured veins increased by a maximum of + 54 ± 21%, + 43 ± 18% and + 46 ± 19% during the three stimulation periods in the non-smoking subjects, respectively. The flicker induced increase in retinal blood flow as assessed in the veins was significantly reduced in chronic smokers as compared to the non-smoking control group (+ 19 ± 16%, + 26 ± 14%, + 24 ± 13%, ANOVA between groups, p = 0.013). In retinal arteries, flicker stimulation increased retinal arterial diameters by 5.2 ± 3.8%, 5.8 ± 4.8% and 5.5 ± 5.6% during the three flicker periods in the non-smoking group. In smokers, the flicker induced arterial vasodilatation was not significantly different compared to non-smokers (4.6 ± 4.1%, 3.8 ± 3.7% and 4.8 ± 3.4%, ANOVA between groups, p = 0.4).ConclusionOur data indicate that the flicker induced hemodynamic response of retinal veins is reduced in chronic smokers as compared to age matched healthy volunteers. This supports the hypothesis that chronic smoking leads to vascular dysfunction in the eye.     

Dynamic retinal vessel response to flicker in obesity: A methodological approach

Obesity and related metabolic disorders affect vascular endothelial function. The use of the Dynamic Vessel Analyzer (DVA) represents a modern methodological approach to analyze vascular function in the retinal microcirculation. Whether the dynamic reaction to flicker stimulation in retinal vessels is altered in obese subjects is investigated. Retinal vessel reactions to flicker stimulation were examined by DVA in 46 obese individuals (49.6 ± 10.0 years) and 46 age- and gender-matched healthy controls. The clinical examination included anthropometry, blood pressure measurements and blood sampling. Mean maximal arteriolar dilation in response to flicker was reduced in the obese group (3.2 ± 1.8%) compared to controls (4.1 ± 2.0%, p < 0.05) and the time to maximal arteriolar dilation was prolonged (18.0 ± 9.4 s vs. 14.6 ± 3.8 s, p = 0.03). In addition, mean maximal venular dilation was reduced in obese subjects (3.9 ± 1.7% vs. 4.7 ± 1.8%, p < 0.05). Among the microvascular parameters, the most significant correlation with waist circumference was found for the “area under the reaction curve 50-80 s after stimulation” in arterioles (r = − 0.40; p < 0.001). Functional retinal arteriolar reactivity to flicker stimulation differs between obese and healthy lean subjects. Time course analysis of retinal vessel response and its quantitative parameters can comprehensively characterize alterations of retinal vessel reactivity in metabolic disease.     

Preserved endothelial-dependent and endothelial-independent skin vasodilator responses in relatives of type 1 diabetes patients

Since increased plasma and cell levels of oxidative products have been found in non diabetic relatives of type 1 diabetic patients, we hypothesized the occurrence of an endothelial dysfunction in these subjects. To verify this hypothesis we investigated the skin blood flow responses to iontophoresis of both the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial-independent vasodilator sodium nitroprusside (SNP) in 31 non diabetic healthy relatives (DR) (14 siblings, 17 parents) of 17 type 1 diabetic patients. Twenty healthy control subjects (CS) without a family history of diabetes, matched for age (± 5 years) and gender, were also investigated. DR and CS did not significantly differ either in basal skin blood flux (6.75 ± 0.72 PU and 5.78 ± 0.37 PU, respectively) or in skin vasodilator response to both ACh (728 ± 53% and 711 ± 44%, respectively) and SNP iontophoresis (758 ± 71% and 731 ± 64%, respectively). This finding is consistent with a preserved skin microvascular endothelial function in the studied subjects. However, since previous data suggest that both nitric oxide (NO) and prostacyclin released form the cutaneous vascular endothelium have an interchanging compensatory role in controlling the skin vasodilator response to ACh iontophoresis, our finding does not allow a defect in NO dependent skin vasodilatation to be excluded in the studied relatives of diabetic patients.     

Ozagrel reverses streptozotocin-induced constriction of arterioles in rat retina

Retinal blood flow decreases early in the progression of diabetic retinopathy; however, the mediators and mechanisms responsible for this decrease have yet to be determined. In this study, diabetes was induced by streptozotocin in rats, and retinal blood flow was measured via intravital microscopy 1 or 3 weeks following the induction of hyperglycemia. Additionally, retinal arteriolar diameters and flow were measured prior to and following acute administration of the thromboxane synthase inhibitor ozagrel to investigate the potential role of thromboxane in the observed constriction. Minimal changes in the retinal diameters and flow were observed at 1 week of diabetes; however, at 3 weeks of diabetes, arteriolar constriction and decreases in blood flow were significant. Notably, the constriction occurred only in the arterioles that were in closer proximity to the venules draining the retina. Acute administration of ozagrel reversed the constriction of the closely venule-paired arterioles. In summary, the results suggest that thromboxane mediates localized, venule-dependent arteriolar constriction induced by streptozotocin-induced diabetes in rats.     

Valsartan and retinal endothelial function in elderly hypertensive patients

BACKGROUND: The aim of this study was to investigate the impact of short-term treatment with the angiotensin II receptor blocker (ARB) valsartan on retinal endothelial function in elderly patients with mild to moderate essential hypertension. METHODS: In an open-labeled study, 20 elderly, male patients with arterial hypertension (WHO I-II) were treated with the ARB valsartan (80-160 mg once daily) over 8 days. Central retinal artery perfusion at rest and during flicker light stimulation was measured before and after treatment using pulsed wave Doppler sonography. Retinal capillary flow was assessed with scanning laser Doppler flowmetry at rest and following systemic infusion of the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA). RESULTS: While valsartan significantly lowered blood pressure, central retinal artery perfusion at rest as well as after flicker light stimulation was similar before and after treatment. Similarly, retinal capillary flow at rest and after infusion of L-NMMA did not change with valsartan after 7 days of treatment. Subgroup analysis revealed that changes in retinal capillary flow in response to L-NMMA might be dependent on serum low-density lipoprotein (LDL) cholesterol levels of study participants. After treatment with valsartan, retinal capillary flow in response to L-NMMA decreased more in patients with low (< 3.54 mmol/l) than with high LDL-cholesterol levels (-12.6 +/- 20.2% vs 12.3 +/- 19.5%, p < 0.05). CONCLUSION: Short-term treatment with valsartan did not improve retinal endothelial function in elderly hypertensive patients.     

The effect of consecutively larger doses of l-arginine on hepatic microcirculation and tissue oxygenation in hepatic steatosis

Background: Impairment of hepatic microcirculation in fatty liver is thought to render it more susceptible to the effects of ischaemia–reperfusion injury as compared to non-fatty liver grafts. The present study aimed to investigate the effect of consecutively larger doses of l-arginine on the hepatic microcirculation and tissue oxygenation of fatty liver.Methods: Sprague–Dawley rats (200–250 g) were fed a liquid ethanol diet to induce hepatic steatosis or a normal diet for 6 weeks. Hepatic blood flow, microcirculation, tissue oxyhaemoglobin (HBO₂) in response to consecutive intravenous bolus administrations of l-arginine (50 mg/kg, 100 mg/kg, 300 mg/kg and 500 mg/kg) or normal saline, were assessed.Results: Baseline hepatic arterial flows and hepatic microcirculation values were significantly lower in steatotic livers vs. control livers. l-arginine significantly improved hepatic arterial, portal venous blood flow, hepatic microcirculation and tissue oxygenation in both fatty and control livers.Conclusions: The administration of NO in cumulatively larger doses is effective at improving hepatic blood flow, microcirculation and hepatic tissue oxygenation in steatotic liver and these results could form the basis of further work into using NO as a therapeutic tool to reclaim moderately steatotic grafts for use in liver transplantation.     

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.     

Acute and chronic effects of marathon running on the retinal microcirculation

Objective

Previous studies indicate an association between marathon running and premature atherosclerosis. Retinal vessel diameter alterations, in particular narrower arterioles and wider venules, reflect early stages of atherosclerosis, but the influence of marathon on the retinal microcirculation is unknown.

Methods

Retinal vessel diameters were measured in 85 male runners (age 31–60 years; previous marathons 0–56) and in 45 age-matched healthy controls using a static vessel analyzer. In runners, diameters were also measured immediately and 24 h after a marathon. Cardiovascular risk profiles, clinical chemistry and, in a subgroup of 46 runners, peripheral arterial wave reflections were also assessed.

Results

Runners had larger arterioles (median 196 μm (IQR 25) vs. 190(25); p = 0.068) and smaller venules (222(25) vs. 224(18); p = 0.063) than controls, resulting in a significantly increased arteriolar-to-venular ratio (AVR; 0.89(0.08) vs. 0.85(0.07); p < 0.001). In runners, retinal vessel diameters were not associated with body mass index, blood pressure, smoking, lipids or training history, and no differences were observed between the lowest (0.71–0.84) and highest (0.95–1.06) AVR quintiles. The marathon run induced a significant increase of AVR (0.91 (0.09); p = 0.007) due to larger arteriolar than venular dilatations, correlating weakly to race duration (r = 0.32; p = 0.003) and to a lower increase in leucocytes (r = −0.35; p = 0.001). Vessel diameters normalized 24 h after the race. Augmentation index and pulse pressure decreased significantly after the race, but no associations with retinal vessel diameters were observed.

Conclusion

Marathon running is not associated with an impairment of the retinal microcirculation. These findings contrast previous reports on atherosclerotic alterations of peripheral vessels.     

Ethanol in pancreatic juice after oral and intravenous administration.

Six patients with a drain in the main pancreatic duct were studied. Ethanol was given orally with individually adjusted doses aiming at a blood value of 0.8/1000 (17.6 mmol/l). Concentrations of ethanol in venous blood and pancreatic juice were recorded for three hours. Similar studies were made when ethanol was administered as an intravenous priming dose followed by a maintenance infusion. After orally administered ethanol, pancreatic juice values were higher than those in blood for a short period of time. The relations between median concentrations and time were incongruous curves consistent with a significant treatment by time interaction. Intravenous administration resulted in a similar pattern, but the interaction was not statistically significant. These findings indicate that the human pancreas may secrete ethanol.     

Effects of Ethanol and Naltrexone in a Model of Traumatic Brain Injury With Hemorrhagic Shock

BACKGROUND: Ethanol predisposes to traumatic injury and causes respiratory depression and cardiovascular compromise in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). Endogenous opioids may play a role in ethanol intoxication and TBI. We studied the effects of ethanol and the opiate antagonist agent naltrexone (NTX) in a TBI/HS model. METHODS: Fifty-six pigs (20 kg) were anesthetized with isoflurane, intubated, instrumented, and subjected to fluid percussion TBI with concurrent 30 ml/kg hemorrhage over 30 min. Seven groups were studied: Control, EtOH, NTX, INJ, INJ/EtOH, INJ/NTX, and INJ/EtOH/NTX. Ethanol (2 g/kg IV) was given preinjury, followed by infusion of 0.4 g/kg/hr. NTX 0.3 mg/kg intravenous was given 5 min postinjury. Parameters monitored for 120 min postinjury included minute ventilation (VE), blood pressure (MAP), cerebral perfusion pressure (CPP), cerebral venous lactate (Lac), arterial and cerebral venous blood gases, and brain tissue PtiO2. RESULTS: Ethanol levels at injury were 220 mg/dL. Ethanol-treated animals had depression of hypercapnic ventilatory response, which was reversed by administration of naltrexone. MAP and CPP were significantly lower in injured animals, but were not significantly improved by NTX. Cerebral venous pH was lower and lactate was higher in ethanol-treated animals. CONCLUSION: In this TBI/HS model, NTX reverses ethanol-induced depression of hypercapnic ventilatory response but does not improve MAP, CPP, or metabolic acidosis. This suggests that the respiratory effects of ethanol in TBI, but not the hemodynamic effects, may be mediated by opiate receptor activation.     

Penetration of Ethanol into the Male Reproductive Tract

We studied the pharmacokinetics of ethanol in the rat rete testis fluid, interstitial fluid, seminiferous tubules, epididymal fluid, and whole testis after 0.75 g/kg and 1.5 g/kg intraperitoneal injections. Ethanol concentration in these tissues was compared to that in capillary and arterial blood. The data was characterized by fitting to a mathematical model. The highest ethanol concentrations in orbital capillary blood were measured 10 min after the injections. Ethanol content in testis homogenate and interstitial fluid did not generally differ from that of orbital blood. However, in rete testis fluid the highest ethanol values were measured at 60 min by the 1.5 g/kg dose and at 30 min by 0.75 g/kg. Ethanol values before this differed from those of capillary blood and interstitial fluid (p less than 0.05-0.001). In seminiferous tubules, the highest ethanol concentration was reached at 20 min, and ethanol content was in general lower than in orbital blood (p less than 0.001-0.01). Ethanol levels in epididymal fluid were comparable to capillary blood. The transportability factor from the model for rete testis was low, which indicates a barrier of penetration of ethanol from blood. In addition, water contents of testicular compartments were calculated. The area under the curve values of rete testis and seminiferous tubules were approximately 10 and 30%, respectively, smaller than that of interstitial fluid, for example. Therefore, the germ cells are somewhat better protected from ethanol than the interstitial cells.     

A laser Doppler velocimetry study of the effect of hypoglycaemia on retinal blood flow in the minipig

Summary The effect of acute hypoglycaemia (plasma glucose <2.2mmol/l) on retinal venous blood flow in the minipig has been determined using bidirectional laser Doppler velocimetry and red free retinal photography. In six pigs the mean flow in a retinal vein increased from 19.3 (±2.8 SEM) l/min to 29.7 (±7.5) l/min during hypoglycaemia (p<0.05) with a return to 18.6 (±3.6) l/min when euglycaemia was restored. Retinal blood flow is affected by hypoglycaemia or its haemodynamic consequences.     

A Reinvestigation of the Usefulness of Breath Analysis in the Determination of Blood Acetaldehyde Concentrations

Human volunteers were given ethanol (0.4 g/kg) either intravenous or per os. They were also given ethanol (0.2 g/kg) intravenous 4 hr after receiving a dose of 50 mg titrated calcium carbimide, an aldehyde dehydrogenase inhibitor. During the first hour after starting the administration of ethanol, ethanol and acetaldehyde concentrations were determined in expired air, blood from the right atrium, arterial blood, and venous blood. In the absence of calcium carbimide treatment, the respective maximal blood acetaldehyde concentrations were (range): 6-30 μM (calculated from breath analysis using a Moodrbreath partition ratio of 190 for acetaldehyde); 0-3.5 μM (right atrium blood); and 0 μM (arterial and venous blood). After calcium carbimide treatment, the maximal blood acetaldehyde concentrations were 10-220 μM (calculated from concentrations in expired air), 38-280 μM (right atrium), 31-250 μM (arterial Wood), and 7-186 μM (venous blood). With aldehyde dehydrogenase inhibition, a clear correlation existed between breath concentrations and blood concentrations. Without this inhibition, no such correlation was found. A clear arterio-venous difference was seen for acetaldehyde concentrations whUe they were artificially elevated by calcium carbimide. Our study suggests that factors other than the equilibration of acetaldehyde between alveolar air and pulmonary blood are of great importance in determining the concentration of acetaldehyde in expired air.     

Effect of lidocaine onin Vivo hepatic function

Lidocaine is administered to assess donor or recipient liver function during hepatic transplantation. This study was performed to determine whether lidocaine administered at a constant concentration affected hepatic function or had demonstrable effects on hepatocellular ultrastructure. Fourteen pigs were randomly allocated to receive either a two-stage infusion of lidocaine hydrochloride or of saline. Transhepatic blood samples were taken and ultrasonic portal venous and hepatic arterial blood flow readings made on animals anesthetized with isoflurane in nitrous oxide. Liver biopsies were taken for histological analysis and determination of adenine nucleotide status prior to and after 2 hr of the two-stage infusion. A mean systemic constant plasma lidocaine concentration of 5.9 g/ml was achieved during the second hour of infusion. There were no differences between the two groups in a large number of indices of hepatic function and plasma composition prior to and during the second hour of the respective infusions. Hepatic blood flow was also similar at these times. On histological examination there were no electron microscopic changes that could be specifically attributed to the administration of lidocaine. However, there were progressive changes with time. This study suggests that in anesthetized pigs a constant lidocaine concentration of about 6 g/ml has no detrimental effect on hepatic function. Progressive hepatic ultrastructural changes occurred that could not be attributed to the administration of lidocaine. These may be the result of anesthetic administered or the surgery performed.Support was gratefully received from the Medical Research Council of South Africa and from the Mauerberger Foundation.     

The diameter of arterial and venous abdominal vessels during acute and chronic administration of nitrates. A sonographic study

Fourteen male patients with coronary heart disease were randomly assigned to treatment periods with isosorbide dinitrate (ISDN) 120 mg/day (6 X 20 mg) and placebo for 4 weeks each, according to a double-blind protocol with intraindividual cross-over. The luminal diameters of the superior mesenteric artery, the hepatic artery, the superior mesenteric vein and the portal vein were determined sonographically in the supine position on days 1, 14 and 28 of both treatment periods 90 min after drug intake. The measurements were repeated after 1.6 mg sublingual nitroglycerin. On day 1 of drug intake the vessel diameters increased significantly after ISDN as compared to placebo: superior mesenteric artery: +11%; hepatic artery: +26%; superior mesenteric vein: +17%; portal vein: +11% (p less than 0.05). No differences in luminal diameters between both drug regimens were found on days 14 and 28. Additional nitroglycerin caused a marked diameter increase during the placebo period (14-21%; p less than 0.001) and on days 14 and 28 of ISDN therapy, while the drug effects were absent after maximal ISDN-induced vasodilatation on day 1. Thus, nitroglycerin and isosorbide dinitrate administered acutely caused a comparable vasodilatation of arterial and venous vessels in the splanchnic region. During sustained therapy with isosorbide dinitrate the vasodilatory effects of the drug were lost. It is supposed that a decrease of blood pooling in the splanchnic region occurs during sustained ISDN therapy. Despite this tolerance development to the circulatory effects of isosorbide dinitrate, nitroglycerin remained effective with regard to arterial and venous vasodilatation.     

Effects of intravenous ethanol on hepatic and pancreatic blood flow in dogs

Changes in hepatic and pancreatic blood flow in response to ethanol infusion were determined simultaneously and continuously in anesthetized dogs, using a transit-time ultrasonic flowmeter and a laser-Doppler flowmeter. In addition, the effect of intravenous ethanol on exocrine pancreatic secretion was investigated. With a background infusion of secretin, ethanol (1.3 g/kg body wt) was infused intravenously over a 40-min period. Ethanol infusion significantly increased blood flow in the common hepatic artery (by 49%, at the time of the cessation of ethanol infusion), and this increased flow was maintained for 60 min after the cessation of ethanol infusion. In contrast, blood flow in the portal vein was not altered significantly by ethanol. Pancreatic blood flow and secretion showed no significant difference from those seen in the controls. Our data suggest that intravenous ethanol induces a redistribution of the splanchnic blood flow. The increased hepatic arterial flow seen in response to ethanol may play an important role in preventing ethanol-induced hypoxic liver damage.     

Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris

Adipocyte cytokines regulate glucose metabolism and insulin resistance and adiponectin is thought to have a protective effect against atherosclerosis. Studies have shown that adiponectin expression is decreased in obese subjects and those with metabolic syndrome or diabetes mellitus. The purpose of this study was to investigate the relationship between circulating adipocyte cytokine concentrations and angiographic coronary artery disease (CAD) progression in patients with chest pain. Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of first catheterization between March 1999 and January 2004 were enrolled. A modified Gensini scoring system was used to define angiographic coronary artery progression between the index and follow-up angiograms. Those who had significant angiographic progression of coronary lesions were classified into the progression group (N = 55). Those who did not have CAD progression were classified into the non-progression group (N = 102). Univariate analysis showed that CAD progression was associated with male gender (93% vs. 78%, p = 0.038), higher baseline total cholesterol (187 ± 43 vs. 173 ± 39 mg/dl, p = 0.037) and higher baseline fasting blood glucose (128 ± 57 vs. 110 ± 40 mg/dl, p = 0.037). Patients in the progression group had a significantly lower serum adiponectin level (14.3 ± 7.9 vs. 18.9 ± 13.2 μg/ml, p = 0.007) than, but resistin (28.9 ± 13.4 vs. 34.4 ± 26.0 ng/ml, p = 0.142) and leptin (7.4 ± 4.6 vs. 7.7 ± 6.5 ng/ml, p = 0.675) levels similar to, those in the non-progression group. In a multivariate binary logistic regression model, male gender (odds ratio 4.283, p = 0.015), higher serum cholesterol (odds ratio 1.010, p = 0.032) and lower serum adiponectin (odds ratio 0.959, p = 0.030) were all significant independent predictors of CAD progression. In conclusion, we found that a decreased circulating level of adiponectin is associated with angiographic CAD progression in patients with angina pectoris.     

Endothelial nitric oxide synthase G894T gene polymorphism and response to skin reactive hyperemia

Post occlusive skin reactive hyperemia (PORH) is a tool used to assess microcirculation. Endothelial nitric oxide synthase (eNOS) mediates nitric oxide (NO) production; polymorphism of the eNOS gene may affect response to the PORH process. This study aims to determine whether eNOS G894T gene polymorphism affects response to skin PORH. 230 normotensive male and females between 18 and 40 years participated in this cross-sectional study. 170 subjects were of the homozygous GG genotype, whereas 60 were of the GT genotype. Skin PORH was performed by occlusion of the upper arm at 200 mm Hg for 3 min. Skin perfusion and temperature were monitored before, during and after occlusion release using the laser Doppler fluximetry. There were no significant differences between genotypes in their baseline blood pressure, serum cholesterol, BMI and age. Maximum change in perfusion after occlusion release (PORHmax) for the GG and GT genotypes were not significantly different at 50.15 ± 1.29 vs. 47.92 ± 2.17 AU; ANCOVA, p = 0.351. Peak perfusion (PORHpeak) were also not significantly different between the two genotypes (61.23 ± 1.36 vs. 57.72 ± 2.32 AU; p = 0.169). Minimum baseline perfusion were however higher in the GG compared to the GT genotype (10.83 ± 0.29 vs. 9.61 ± 0.50, p = 0.029). We conclude that microvascular reactivity, assessed by change in perfusion after temporary ischemia was not significantly different between the GG and GT genotypes of the eNOS G894T gene. eNOS 894T allele carriers however, have lower baseline perfusion compared to the homozygous G894 allele carrier.