Suppression of Graft Spasm by the Particulate Guanylyl Cyclase Activator in Coronary Bypass Surgery.

BACKGROUND: Spasm of arterial grafts is still a clinical problem in coronary artery bypass surgery. The present study was designed to examine the effect of particulate guanylyl cyclase activator (carperitide) as an antispastic agent in internal thoracic artery and gastroepiploic artery grafts. METHODS: Isolated arterial grafts taken during surgery were studied in organ bath in three ways: the relaxing effect of carperitide on vasoconstrictor-induced precontraction; the inhibitory effect of pretreatment with carperitide on subsequent vasoconstrictor-induced contraction; and the effect of carperitide and nitroglycerin on increase of intracellular cyclic guanosine monophosphate levels. RESULTS: Carperitide produced a concentration-related, endothelium-independent relaxation contracted with potassium chloride, phenylephrine, prostaglandin F2α, or endothelin-1. Carperitide showed significantly higher potency and efficacy than nitroglycerin and nifedipine. Pretreatment with carperitide significantly attenuated the subsequent vasoconstrictor-induced contraction. Carperitide produced more cyclic guanosine monophosphate than nitroglycerin. CONCLUSIONS: Carperitide has a potent inhibitory effect on the vasoconstriction mediated by different vasoconstrictors in human internal thoracic artery and gastroepiploic artery grafts. The use of carperitide in patients during and after coronary artery bypass surgery is favored for the prevention and reversal of graft spasm.

Endothelial dysfunction of internal thoracic artery graft in patients with chronic kidney disease.

OBJECTIVES: The present study was designed to evaluate the association between chronic kidney disease and the endothelial function of internal thoracic artery (ITA) grafts in patients undergoing coronary bypass surgery. An isometric tension study was performed in ITA strips obtained during surgery. Concentration-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed in ITA strips partially precontracted with phenylephrine under the inhibition of cyclooxygenase. The integrity of the endothelium was verified histologically by en-face staining of the luminal surface with the use of silver nitrate solution. RESULTS: In endothelium-intact ITA strips, ACh produced a concentration-dependent relaxation in patients with glomerular filtration rate (GFR, mL/min/1.73 m2) > 60. A concentration-dependent relaxation response also was observed in patients with GFR 30 to 60, but it was reduced significantly compared with those with GFR > 60. In both groups, removal of endothelium or treatment with nitric oxide (NO) synthase inhibitors almost abolished the ACh-induced relaxation. On the other hand, in patients with GFR < 30, mild contraction rather than relaxation was induced at a high concentration of ACh, which was modified neither by treatment with NO synthase inhibitors nor by removal of the endothelium. Vasodilator responses to sodium nitroprusside were comparable among the 3 groups. The relaxation of endothelium-intact strips to a peak ACh concentration correlated positively with GFR. This relationship held true in a multiple linear regression model, and interaction terms between GFR and other risk factors were not statistically significant. CONCLUSIONS: Endothelial function of ITA grafts to release NO is impaired at the time of surgery in patients with chronic kidney disease.

Intact neural system of the portal vein is important for maintaining normal glucose metabolism by regulating glucagon-like peptide-1 and insulin sensitivity.

The portal neural system may have an important role on the regulation of glucose homeostasis since activation of the gut-brain-liver neurocircuit by nutrient sensing in the proximal intestine reduces hepatic glucose production through enhanced liver insulin sensitivity. Although there have been many studies investigating the role of portal neural system, surgical denervation of the sole portal vein has not been reported to date. The aim of this study was to clarify the role of the portal neural system on the regulation of glucose homeostasis and food intake in the physiological condition. Surgical denervation of portal vein (DV) was performed in 10 male 12 week-old Wistar rats. The control was a sham operation (SO). One week after surgery, food intake and body weight were monitored; an oral glucose tolerance test (OGTT) was performed; and glucagon-like peptide-1 (GLP-1) and insulin levels during OGTT were assayed. In addition, insulinogenic index, homeostatic model assessment, and Matsuda index were calculated. All rats regained the preoperative body weight at one week after surgery. There was no significant difference in food intake between DV and SO rats. DV rats exhibited increased blood glucose levels associated with decreased insulin sensitivity but increased GLP-1 and insulin secretion during OGTT. In summary, in the physiological state, loss of the portal neural system leads to decreased insulin sensitivity and increased blood glucose levels but does not affect food intake. These data indicate that an intact portal neural system is important for maintaining normal glucose metabolism.

Transfer of bone marrow progenitors prevents coronary insufficiency and systolic dysfunction in the mechanical unloaded heart in mice.

BACKGROUND: Left ventricular-assist device (LVAD) can lead to improvement of cardiac performance in a subset of patients, but chronic mechanical unloading in this fashion may result in left ventricular (LV)-atrophy and impaired functional recovery. Here, we evaluate the efficacy of transferring bone-marrow KSL cells (Lin-/c-kit+/Sca1+), a fraction containing endothelial progenitor cells, for preventing LV-atrophy and malfunction in a mouse model of mechanical unloading of the heart. MATERIALS AND METHODS: Recipients of an isogenic heart transplant received intramyocardial isogenic KSL cells or PBS in three different locations of the left ventricle (LV). Coronary blood flow and LV systolic function were evaluated by echocardiography, and morphologic changes were analyzed on d 7 and 56. RESULTS: PBS-treated mice showed severe systolic dysfunction and large thrombi in LV at both time points. In contrast, KSL cell transfer markedly reduced systolic dysfunction and thrombus size. Furthermore, in comparison with PBS control, KSL recipients had increased coronary blood flow (3-fold, P < 0.01) accompanied by increased LV capillary density and muscle mass. CONCLUSIONS: These results indicate that intramyocardial transfer of bone marrow KSL cells significantly protects against coronary insufficiency and systolic dysfunction in the chronic LV-unloading heart, suggesting that this approach may have clinical potential as a combination therapy with LVAD.

Developmental expression of glial cell-line derived neurotrophic factor, neurturin, and their receptor mRNA in the rat urinary bladder.

AIMS: Glial cell-line derived neurotrophic factor (GDNF) and related factors neurturin (NRTN), artemin, and persephin are members of the GDNF family of neurotrophic factors. GDNF and NRTN bind to the tyrosine kinase receptor Ret and the receptors GFRalpha1 and GFRalpha2. The objective was to examine the developmental expression of GDNF, NRTN, and their receptors within the rat urinary bladder. METHODS: Rat bladders dissected from embryonic day (E) 15, postnatal day (P) 0, P14, P28, and adult rats (P60) were investigated by semiquantitative reverse transcriptase polymerase chain reaction. Embryos (E15, E16, and E17) were immunohistochemically stained for neurofilament. RESULTS: GDNF and Ret mRNA levels at E15 were the highest of all the stages we examined and then immediately decreased. In contrast, NRTN mRNA levels did not change between E15 and postnatal day 14; thereafter, they gradually but insignificantly increased. GFRalpha1 and GFRalpha2 mRNA levels were high at E15, after which their signal intensities decreased. In whole-mounted specimens, neurofilament-positive axons were first detected in the bladder at E16. CONCLUSIONS: Our results suggest that GDNF and NRTN may act as trophic factors for neural in-growth to the bladder and/or for the maintenance of mature neurons innervating the bladder. These factors might also be involved in bladder morphogenesis.