Impaired endothelial function in isolated human uremic resistance arteries

BACKGROUND: Patients with chronic renal failure (CRF) face a markedly increased risk of cardiovascular death. CRF is frequently complicated by hypertension and changes in both the heart (left ventricular hypertrophy) and the vasculature (endothelial dysfunction and accelerated atherosclerosis). The mechanisms underlying changes in vascular function and specifically endothelial dysfunction are unclear. This present study therefore examined subcutaneous resistance artery function in vitro, comparing adult uremic patients and controls using wire myography. METHODS: Subcutaneous fat biopsies were obtained from 12 patients with CRF (median serum creatinine 735 micromol/L) at the time of renal transplantation or peritoneal dialysis catheter insertion, and from eight controls without renal disease at the time of abdominal surgery. Resistance arteries were mounted on a wire myograph. Their contractile ability was tested with high potassium depolarization, and endothelial integrity was tested by relaxation to acetylcholine. Cumulative concentration-response curves were then constructed for norepinephrine, endothelin-1, acetylcholine, and sodium nitroprusside (SNP). RESULTS: Following preconstriction with norepinephrine, vessels from uremic patients vasodilated less well to acetylcholine compared with vessels from controls [maximum % relaxation 77% (range 41, 97) vs. 98% (78, 100), P < 0.001]. The vasodilation to SNP was similar [95% (63, 100) vs. 94% (71, 100), P = 0.751]. There was a trend toward increased maximum pressure (kPa) achieved with both norepinephrine and endothelin-1 in vessels from uremic patients, and the contractions to both of these agents were more prolonged in the uremic vessels. CONCLUSIONS: The pattern of normal vasodilation to SNP but reduced vasodilation to acetylcholine is consistent with endothelial dysfunction due to impaired nitric oxide (NO) production in uremic vessels. Similar results have been demonstrated in vivo in uremia, one suggested mechanism being accumulation of endogenous inhibitors of NO synthase such as asymmetric dimethylarginine (ADMA). This in vitro study suggests that a short-lived circulating factor is not entirely responsible and that there may be an inherent abnormality in endothelial function in uremia, although the exact pathophysiology remains unclear. Endothelial dysfunction may predispose the patient to accelerated atherosclerosis and may be involved in the pathogenesis of hypertension in end-stage renal failure.     

Electrophysiologic and mechanical evidence of superiority of hyperpolarizing versus depolarizing cardioplegia in protection of endothelium-derived hyperpolarizing factor-mediated endothelial function: a study in coronary resistance arteries

OBJECTIVE: The advantages of hyperpolarizing cardioplegia with potassium-channel openers versus depolarizing cardioplegia have been suggested but not demonstrated in coronary microarteries. This study examined the simultaneous electric and tonic alteration of coronary microarteries at the cellular level during and after exposure to depolarizing cardioplegia or hyperpolarizing cardioplegia, with emphasis on endothelium-derived hyperpolarizing factor-mediated relaxation and hyperpolarization. METHODS: Porcine coronary microarteries (diameter, approximately 200-400 microm) were incubated with depolarizing cardioplegia (20 mmol/L KCl) or hyperpolarizing cardioplegia (10 micromol/L aprikalim) for 1 hour. Cellular membrane potential with a glass microelectrode in a coronary smooth muscle cell and isometric force of the muscle were simultaneously measured in a myograph. RESULTS: Depolarizing cardioplegia incubation produced a stable contraction (from 4.9 +/- 0.3 mN to 7.3 +/- 0.4 mN) and depolarization (from -51 +/- 1 mV to -41 +/- 2 mV). In contrast, hyperpolarizing cardioplegia relaxed (from 4.8 +/- 0.3 mN to 3.5 +/- 0.3 mN) and hyperpolarized (from -51 +/- 2 mV to -56 +/- 1 mV) the smooth muscle. After exposure to depolarizing cardioplegia, the bradykinin-induced, endothelium-derived hyperpolarizing factor-mediated relaxation reduced from 66.2% +/- 5.0% to 18.4% +/- 3.7% (P <.001), and the membrane hyperpolarization reduced from 18 +/- 1 mV to 7 +/- 1 mV (P <.001) in the presence of indomethacin and N(G)-nitro-L-arginine. In contrast, hyperpolarizing cardioplegia did not affect the bradykinin-induced responses. CONCLUSIONS: In the coronary microarteries, exposure to hyperpolarizing cardioplegia preserves whereas depolarizing cardioplegia reduces the endothelium-derived hyperpolarizing factor-mediated electric (hyperpolarization) and mechanical (relaxation) responses. Thus hyperpolarizing cardioplegia is superior to depolarizing cardioplegia in protecting the endothelial function in the coronary microcirculation.     

Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients

This study attempted to establish whether a calcineurin inhibitor (CNI)‐free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty‐nine kidney recipients were randomized to receive since transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow‐mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7 months (M7) after transplantation. Endothelium‐independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 ± 3 vs. CsA: 138 ± 4 mmHg, P < 0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1 ± 0.9 vs. CsA: 9.9 ± 0.9%, P < 0.05) without any difference for hyperaemia, endothelium‐independent dilatation and GFR (SRL: 66.7 ± 1.05 vs. CsA: 67.5 ± 1.22 ml/min). Our results demonstrate that a CNI‐free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure.     

Effects of progesterone and estrogen on endothelial dysfunction in porcine coronary arteries

BACKGROUND: The effects of hormone replacement therapy (HRT) on the vascular endothelium have been controversial. In this study, we determined the effects of HRT on endothelium-dependent relaxation in a porcine coronary artery model. METHODS: Coronary artery rings harvested from female swine were incubated as controls or with estrogen (10(-9), 10(-8), 10(-7) g/L), progesterone (1 x 10(-6), 1 x 10(-5), 5 x 10(-5) g/L), or a combination of the two (10(-8)g/L estrogen, 1 x 10(-5)g/L progesterone). After 24 h in tissue culture, the rings were tested on a myograph system to measure contraction and endothelium-dependent relaxation. Myograph analysis was performed with the thromboxane A2 analogue U46619 for contraction and bradykinin or sodium nitroprusside for relaxation. Nitric oxide synthase (eNOS) levels were determined by immunohistochemistry. Levels of superoxide anion in the progesterone or estrogen treated tissues were assessed by lucigenin-enhanced chemiluminescence analysis. RESULTS: In response to 10(-7)M bradykinin, porcine coronary artery rings treated with 1 x 10(-6), 1 x 10(-5) and 5 x 10(-5) g/L of progesterone showed a significant reduction in endothelium-dependent vasorelaxation by 36%, 45%, and 68%, respectively, as compared to controls (P <0.05). However, rings treated with estrogen showed no significant difference as compared to controls. Furthermore, estrogen treatment with progesterone reversed the effect of progesterone, showing no difference in vessel relaxation as compared to controls. There were no differences in endothelium-independent vasorelaxation (sodium nitroprusside) or in smooth muscle contractility (U46619) between the control and the hormone-treated groups. The eNOS immunoreactivity was reduced in progesterone-treated coronary artery rings. Furthermore, coronary endothelium exposed to progesterone showed a 59% increase in superoxide anion production, while estrogen produced a 67% decrease when compared to controls (P <0.05 for both). CONCLUSION: This data suggests that the progesterone component of HRT has a detrimental influence on endothelium-dependent relaxation. This effect appears to be related to decreased eNOS levels, as well as increased consumption of NO by superoxide anion in the endothelium of tissues exposed to progesterone. Estrogen can block progesterone-induced endothelial dysfunction and superoxide anion production in the pig coronary artery model.     

Curcumin inhibits Homocysteine-induced endothelial dysfunction in porcine coronary arteries

Background. Curcumin, a yellow polyphenolic compound from the plant Curcuma ionga, has anti-tumor, anti-inflammatory, and anti-oxidant activities. The aim of this study was to determine the effect of curcumin on homocysteine (HCY)-induced endothelial dysfunction and superoxide anion production in a porcine coronary artery model. Methods. Five-millimeter porcine coronary artery rings from 8 hearts were incubated for 24 h as either controls, with HCY (50 μM), curcumin (5 μM), or a combination of curcumin (5 μM) and HCY (50 μM). Following this, vasomotor function was analyzed with a myograph device in response to thromboxane A₂ analogue U466419, bradykinin, and sodium nitroprusside (SNP), respectively. Additionally, superoxide anion production was determined by lucigenin-enhanced chemiluminescence assay. Results. All groups of porcine coronary artery rings showed no difference in maximal contraction in response to U46619. However, endothelium-dependent relaxation (bradykin) was 40% in the HCY-treated group as compared to 73% in controls (P = 0.03, n = 8). The curcumin plus HCY group showed a significant improvement of endothelium-dependent relaxation as compared to the HCY-treated group (P = 0.04), but no difference over controls. Curcumin alone showed no difference with controls. All groups showed no difference in endothelium-independent relaxation. Superoxide levels was 13.3 ± 2.1 RLU/s/mm² in control vessels, 40.5 ± 8.7 RLU/s/mm² in HCY-treated vessels, 20.0 ± 2.2 RLU/s/mm² in curcumin treated vessels, and 10.0 ± 1.9 RLU/s/mm² in HCY plus curcumin-treated vessels. Conclusion. These results show that curcumin effectively reverses the endothelial dysfunction induced by HCY. Additionally, curcumin also significantly decreases HCY-induced superoxide production. This study may suggest a therapeutic role of dietary curcumin for patients with hyperhomocysteinemia, thereby reducing cardiovascular morbidity and mortality.     

Curcumin blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries

PURPOSE: Curcumin, a yellow polyphenolic compound from the plant Curcuma ionga , is a commonly used spice and coloring agent with beneficial effects of anti-tumor, anti-inflammatory, and antioxidant activities. The objective of this study was to determine the effect of curcumin on homocysteine-induced endothelial dysfunction in a porcine coronary artery model. METHODS: Porcine coronary arteries were cut into 5-mm rings, which were incubated for 24 hours either as control rings, with homocysteine (50 micromol/L), curcumin (5 micromol/L), or a combination of curcumin (5 micromol/L) and homocysteine (50 micromol/L). Myograph tension analysis was performed in response to vessel active drugs including thromboxane A2 analog U466419 (contraction), endothelium-dependent vasorelaxation (bradykinin), and endothelium-independent vasorelaxation (sodium nitroprusside). Immunohistochemical staining was performed for endothelial nitric oxide synthase (eNOS). In addition, superoxide anion production was determined by lucigenin-enhanced chemiluminescence. RESULTS: All groups of porcine coronary artery rings showed no difference in maximal contraction after U46619 challenge. However, endothelium-dependent vasorelaxation in response to 10(-5) mol/L bradykinin was 40% in the homocysteine-treated group, as compared to 73% in the control group (P = .03). Of importance, curcumin could effectively block homocysteine-induced impairment of endothelium-dependent vasorelaxation. All groups showed no difference in endothelium-independent vasorelaxation. In addition, eNOS immunoreactivity was reduced in the homocysteine group, but the combined homocysteine and curcumin group showed eNOS levels comparable to those in the control group. Furthermore, superoxide anion levels of the endothelial layer were significantly increased by 2-fold in homocysteine-treated vessels as compared to control vessels (P = .02), whereas curcumin could block the effect of homocysteine on superoxide anion production. CONCLUSION: These data demonstrate that curcumin effectively reverses the endothelial dysfunction induced by homocysteine. In addition, curcumin significantly blocked homocysteine-induced superoxide anion production and eNOS down-regulation. This study suggests a therapeutic role for dietary curcumin in patients with homocysteinemia, thereby reducing cardiovascular morbidity and mortality. CLINICAL RELEVANCE: Hyperhomocysteinemia is a significant clinical problem. It is an independent risk factor for cardiovascular diseases. This study provides new information for better understanding the molecular mechanisms of homocysteine-induced vascular injury. More importantly, curcumin, a natural substance, can effectively block the detrimental effect of homocysteine on the vascular system. Thus curcumin could be used in patients with hyperhomocysteinemia, and to prevent cardiovascular diseases.     

Physical and mechanical effects of cardioplegic injection on flow distribution and myocardial damage in hearts with normal coronary arteries

The physical and mechanical effects of injecting crystalloid cardioplegic solution under various pressures and flows was studied (in canine hearts) to establish a safe method for administering it in the presence of normal coronary arteries. A constant pressure system (300 mm Hg = 15 psi) was maintained in the solution reservoir, and flows and pressures were varied with the use of cannulas of different inner diameters: 0.8, 1.35, 1.6, 2.3, 2.58, and 2.80 mm. Cardioplegia distribution was measured by 15 microns radioactive microspheres. Peak flow rate, total flow, and mean flow rate per infusion were measured by an inline electromagnetic flowmeter probe. Direct aortic root pressure, time to standstill, and myocardial temperatures were recorded by continuous monitoring. Cardiac isoenzymes were measured in the coronary sinus, peripheral blood, and directly in the myocardial tissue. Histologic changes in the left ventricle were examined by light microscopy. The results showed that the higher the flow and pressure, the shorter the prearrest period, the better the flow distribution, and the faster the myocardial temperature drop. Mean aortic root pressures higher than 110 mm Hg and peak flow rates greater than 1500 ml/min caused a higher incidence of mechanical-physical trauma to the vascular endothelium and the endocardium, but cellular protection was good. Low pressure (less than 30 mm Hg) and peak flows (less than 125 ml/min) showed a higher incidence of cellular (myocardial) ischemia, focal necrosis, and uneven flow distribution. An aortic root pressure of 61 +/- 5 mm Hg, a mean peak flow rate of 622 +/- 52 ml/min, and a total flow of 600 ml for the first injection seem to offer the best cellular protection with minimal physical injury to the endothelium and endocardium for a mean canine heart weight of 236 gm.     

Surgical radiofrequency ablation induces coronary endothelial dysfunction in porcine coronary arteries.

OBJECTIVES: Surgical radiofrequency ablation is increasingly used during open heart surgery for the treatment of chronic atrial fibrillation. The purpose of this study was to determine the effects of application of radiofrequency on coronary endothelial function and structure and establish the relationship between coronary lesions and distance of radiofrequency application. METHODS: Six Landrace swine (25.9+/-2.0 kg) were included in the study. With the heart kept beating, three epicardial radiofrequency lesions (20 W, 20 s duration, 60 degrees C) 2 cm in length each, were created 1, 5 and 10 mm away from the left anterior descending and the right coronary arteries. The circumflex artery served as control. Coronary rings were placed in organ chambers. After contraction to KCl and prostaglandin F2alpha, endothelium-dependent relaxations to bradykinin were studied. Gomori trichrome and hematoxylin-eosin safran staining were used for histological evaluation. RESULTS: Exposure to radiofrequency 1 mm from the coronary arteries caused a significant decrease in endothelium-independent contractions to KCl and endothelium-dependent relaxations to bradykinin compared to controls (P<0.05). No significant decrease of endothelium-dependent relaxations occurred for rings exposed to radiofrequency at a distance of 5 and 10 mm, compared to controls. Histological examination showed endothelial disruption and medial smooth muscle cells at different stages of necrosis up to 5 mm from the radiofrequency application site. CONCLUSIONS: Radiofrequency may induce coronary endothelial functional and morphological damages when applied less than 5 mm from the artery. Caution must be exerted during left atrial radiofrequency application due to the proximity of the circumflex artery.     

Celsior液和UW液保存供肝的前瞻性随机对照研究

目的比较Celsior液和UW液保存供肝的效果。方法随机选取拟行肝移植的患者60例，平均分为两组，一组接受以Celsior液灌洗和冷保存的供肝（Celsior液组）移植，另一组接受以UW液灌洗和冷保存的供肝（UW液组）移植，两组在患者年龄、性别构成、肝功能分级以及原发病、肝移植术式等方面的差异无统计学意义。比较两组供肝组织学变化、术后早期肝功能恢复情况及术后3个月内缺血性胆道狭窄的发生率。结果Celsior液组供肝冷缺血时间为（8．83±1．53）h，UW液组为（9．08±1．85）h，差异无统计学意义（P〉0．05）。两组术后早期血清丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、胆红素总量、出血时间及胆汁量的差异无统计学意义（P〉0．05），术后3个月内，Celsior液组缺血性胆道狭窄发生率为6．7％（2／30），UW液组为13．3％（4／30），差异无统计学意义（P〉0．05）。两组移植肝的组织学改变相似。结论在冷缺血时间一致的情况下，Celsior液保存供肝的效果与UW液相同。     

Ginkgolide A attenuates homocysteine-induced endothelial dysfunction in porcine coronary arteries

BACKGROUND: Homocysteine is an independent risk factor for atherosclerosis. The objective of this study was to investigate whether ginkgolide A (GA), a major constituent of Ginkgo biloba, could block homocysteine-induced endothelial dysfunction in porcine coronary arteries. METHODS: Porcine coronary artery rings were assigned to six treatment groups: control; homocysteine (50 micromol/L); low-dose (50 micromol/L) or high-dose (100 micromol/L) GA; and homocysteine plus low-dose or high-dose GA. After 24 hours' incubation, the rings were analyzed for vasomotor function in response to a thromboxane A2 analogue (U46619), bradykinin, and sodium nitroprusside. Endothelial nitric oxide synthase (eNOS) was studied by using real-time polymerase chain reaction and immunohistochemistry analysis. Superoxide anion production was assessed by chemoluminescence analysis. RESULTS: Endothelium-dependent relaxation (bradykinin) was significantly reduced in ring segments treated with homocysteine as compared with the control (P < .05). When homocysteine was combined with either low-dose or high-dose GA, endothelium-dependent relaxation was markedly recovered. There was no significant difference in maximal contraction (U46619) or endothelium-independent relaxation (sodium nitroprusside) among all groups. In addition, superoxide anion production was increased by 113% in the homocysteine-treated group, whereas there was no statistically significant difference between the control and GA/homocysteine groups. Furthermore, eNOS messenger RNA and protein levels were substantially reduced in the homocysteine-treated group (P < .05), but not in the GA/homocysteine combined groups. CONCLUSIONS: Homocysteine significantly impairs endothelium-dependent vasorelaxation through oxidative stress and downregulation of eNOS in porcine coronary arteries. GA effectively prevents homocysteine-induced endothelial dysfunction and molecular changes in porcine coronary arteries. This study underscores the potential clinical benefits and applications of GA in controlling homocysteine-associated vascular injury and cardiovascular disease. CLINICAL RELEVANCE: Homocysteine is an independent risk factor for atherosclerosis. This study showed that ginkgolide A, a major constituent of Ginkgo biloba, effectively prevents homocysteine-induced endothelial dysfunction and molecular changes in porcine coronary arteries. This study underscores potential clinical benefits and applications of ginkgolide A in controlling homocysteine-associated vascular injury and cardiovascular disease.     

The effect of vardenafil on endothelial function of brachial and cavernous arteries

The aim of the present study was to examine the effect of new phosphodiesterase type 5 inhibitor vardenafil on endothelial function of cavernous and brachial arteries in healthy men and in patients with different forms of erectile dysfunction (ED). This prospective, double-blind, placebo-controlled study was performed on 135 men with ED and 30 healthy controls. Complex evaluation was performed in all patients with ED. All participants also underwent our modification of ultrasound (US) assessment of postocclusive changes in the diameter of cavernosal arteries and endothelium-dependent flow-mediated dilation (FMD) of the brachial artery before and 1 h after administration of 20 mg of vardenafil or placebo. After study drug administration, PICAD and FMD significantly increased in patients receiving vardenafil (P < 0.001) but not in patients receiving placebo. Increase in PICAD values was significantly greater in patients with arteriogenic ED compared with patients with organic nonarterial ED (P = 0.007), psychogenic ED (P < 0.001) and controls (P = 0.001). The most prominent increase in brachial artery FMD values were found in patients with arteriogenic ED, although statistically significant differences were present only between patients with arteriogenic ED and control group (P = 0.035). We have found a moderate negative correlation between initial PICAD and its increase after vardenafil and between pretreatment flow-mediated vasodilation of brachial arteries and its increase after vardenafil administration (r = -0.57 and -0.55, respectively). These findings suggest that the use of vardenafil restores impaired endothelial function of cavernous and brachial arteries.     

Red wine prevents homocysteine-induced endothelial dysfunction in porcine coronary arteries

BACKGROUND: Hyperhomocysteinemia is an independent risk factor of coronary artery disease. Clinical studies have indicated that moderate red wine consumption is associated with a reduction of incidence of coronary artery disease. In this study, we determined the effect of red wine on homocysteine- induced endothelial dysfunction in porcine coronary arteries. MATERIALS AND METHODS: Porcine coronary arteries were dissected from 6 pig hearts and cut into 5-mm ring segments, which were assigned into 4 groups (9 rings/group): blank control, homocysteine treated (50 muM), red wine treated (0.08% alcohol), and homocysteine plus red wine treated. The rings were cultured in cell culture medium with or without treatment for 24 h. Myograph analysis was performed with U46619 (10(-7) M) for contraction and cumulative bradykinin (10(-9) to 10(-5) M) for endothelium-dependent relaxation. The endothelial nitric oxide synthase (eNOS) levels were analyzed by RT-PCR, Western blot, and immunohistochemistry. RESULTS: In response to 10(-5) M bradykinin, porcine coronary artery rings treated with homocysteine (50 muM) showed a significant reduction of endothelium-dependent vasorelaxation by 43% as compared to controls (P < 0.05). However, rings treated with red wine (0.08% alcohol) plus homocysteine showed no significant difference as compared to controls. Endothelium-dependent vasorelaxation was not different between control and red wine treated groups. Furthermore, eNOS mRNA density levels were significantly reduced by 36% in homocysteine treated group as compared to controls (P < 0.05). eNOS protein levels were also substantially reduced in the homocysteine-treated group. However, red wine treatment reversed the effect of homocysteine-induced eNOS downregulation. CONCLUSIONS: Homocysteine significantly impaired endothelial functions including endothelium-dependent vasorelaxation and eNOS mRNA and protein levels in porcine coronary arteries; and red wine effectively prevented homocysteine-induced endothelial dysfunction. This study suggests that protecting coronary endothelial cells from homocysteine damage may be an important mechanism of red wine for preventing coronary artery disease.     

Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution.

OBJECTIVES: We examined the effect of St Thomas' Hospital solution on endothelium-derived hyperpolarizing factor-mediated function in the porcine coronary microarteries with emphasis on the effect of temperature and washout time. METHODS: Microartery rings (diameter, 200-450 micrometers) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4 degrees C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22 degrees C for 1 hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U 46619. The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied when endothelium-derived nitric oxide and prostaglandin I2 were inhibited with the presence of 7 micromol/L indomethacin and 300 micromol/L NG-nitro-L -arginine. RESULTS: After exposure to St Thomas' Hospital solution, the maximal endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of the precontraction) was significantly reduced at either temperature after washout for 45 minutes (group Ia, 42.7% +/- 3.5% vs 69.0% +/- 5.3%; n = 9; P =.000; and group IIa, 12.3% +/- 1.6% vs 56.1% +/- 4. 4%; n = 8; P =.000) but fully recovered after washout for 90 minutes. The U46619-induced contraction force was also significantly reduced after washout for 45 minutes (P <.001) but fully recovered at 90 minutes. CONCLUSIONS: Under profound and moderate hypothermia, St Thomas' Hospital solution impairs endothelium-derived hyperpolarizing factor-mediated relaxation and smooth muscle contraction in the coronary microarteries. These effects exist during the reperfusion period for at least 45 minutes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.     

Improvement of rat lung structure and function after preservation with celsior

Ischemia/reperfusion-induced increase in pulmonary microvascular permeability was shown to be reduced after preservation with Celsior. We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia. Arterial and veneous oxygen tensions were recorded during 50 min of in vitro reperfusion after which the lungs (10 right lungs per experimental group) were fixed by vascular perfusion. The tissue was further processed for microscopy, and histological changes were quantified stereologically. Lung preservation with Celsior resulted in a significantly higher volume of air-filled alveolar space with a large proportion of widely distended alveoli compared with the other groups. In the Euro-Collins group the fraction of atelectatic alveoli exceeded that observed in Celsior-preserved lungs. In accordance, the difference between arterial and venous oxygen tensions was significant among Euro-Collins- and Celsior-protected lungs, with improved oxygenation values in the Celsior group. In contrast, addition of prostacyclin to Celsior treatment resulted in rather variable structural as well as functional data. There were no differences in the volumes of intraalveolar edema among the groups tested. However, the volume of alveolar tissue was increased in the Euro-Collins group. In conclusion, compared with Euro-Collins and Celsior + prostacyclin solutions, preservation with Celsior resulted in improved structural characteristics which in combination with improved oxygenation parameters supports the prospective advantage of Celsior in clinical organ preservation.     

Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine coronary arteries

OBJECTIVE: Resistin, a novel adipocyte-derived cytokine, is involved in the development of insulin resistance and diabetes mellitus. In this study, we determined whether resistin could affect vasomotor function, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in porcine coronary arteries. METHODS: Porcine coronary arteries were treated with resistin or antioxidant seleno-L-methionine (SeMet). Vasomotor function was studied by using a myograph system. Levels of superoxide anion (O 2 - ) were detected by the lucigenin-enhanced chemiluminescence method. The eNOS mRNA and protein levels were determined by real-time polymerase chain reaction and immunohistochemistry, respectively. Culture of isolated porcine coronary artery endothelial cells (PCAECs) was also included. RESULTS: Endothelium-dependent relaxation in response to bradykinin was reduced by 15% and 30% for the rings treated with 10 and 40 ng/mL of resistin, respectively, as compared with controls ( P < .05). Endothelium-independent relaxation in response to sodium nitroprusside (SNP) was also reduced by 11% after treatment with 40 ng/mL of resistin ( P < .05). The O 2 - level was increased in the 40 ng/mL resistin-treated vessels by 88% as compared with controls ( P < .05). SeMet reversed these effects. The eNOS mRNA levels in PCAEC cultures treated with resistin (10 and 40 ng/mL) were decreased by 27% and 55%, respectively ( P < .05) and by 39% in the endothelial cells purified from porcine coronary artery rings after treatment with 40 ng/mL of resistin ( P < .05). Immunoreactivity of eNOS in the resistin-treated vessel rings was also substantially reduced. CONCLUSIONS: Resistin reduces the endothelium-dependent and endothelium-independent vasorelaxation. This effect is associated with increased superoxide radical production, decreased eNOS expression, and is effectively reversed by the antioxidant SeMet. CLINICAL RELEVANCE: Obesity has been considered to be an independent risk factor for coronary artery disease and other vascular lesions. Resistin is a newly discovered adipocyte-derived cytokine, and its plasma levels are increased in obese individuals. However, it is not clear whether resistin could directly contribute to vascular disease formation. This study showed that resistin can cause endothelial dysfunction in porcine coronary arteries through oxidative stress and down-regulation of eNOS. Thus, this study may suggest a new mechanism of obesity-associated vascular disease and that antioxidants may effectively prevent vascular disease in obese individuals.     

The histological effects of cryocoagulation on the myocardium and coronary arteries

The effects of epicardial and endocardial cryolesions were histologically studied in 29 dogs. To produce epicardial lesions, hypothermic exposure was applied at -60 degrees C for 3 minutes, over or adjacent to the left anterior descending coronary artery. To produce endocardial lesions, exposure was applied at -60 degrees C for 2 minutes, using the inflow occlusion technique over the ventricular septum. The dogs were killed 30 minutes to 6 months later. The cryolesions were sharply demarcated from the surrounding tissues and showed similar healing processes. The lesions showed no tendency to form aneurysms or rupture, although moderate intimal thickening of the coronary artery subjacent to the probe was observed. Our results indicate that cryocoagulation may greatly contribute to the surgical treatment of cardiac arrhythmias.