Defining a new standard for IVUS optimized drug eluting stent implantation: the PRAVIO study.

OBJECTIVES: Preliminary Investigation to the Angiographic Versus IVUS Optimization Trial is a single center prospective observational intravascular ultrasound (IVUS) guided stent implantation study assessing new criteria for optimal drug eluting stent (DES) deployment. BACKGROUND: IVUS assessment of DES often reveals underexpansion and malapposition. Optimal stent deployment is currently poorly defined and previous criteria may not be suitable in long and complex lesions. METHODS: Optimization was defined as achieving >/or 70% of the cross-sectional area (CSA) of the postdilation balloon. This criterion was applied in 113 complex lesions. The size of this balloon was calculated according to vessel media-to-media diameters at various sites inside the stented segment. The IVUS guided treated lesions were matched according to diabetes, vessel type, reference vessel diameter, minimum lumen diameter (MLD), and lesion length with a group of angiographic treated lesions to compare final MLD achieved. RESULTS: Mean minimum stent CSA according to the postdilation balloon utilized was 4.62 mm(2), 6.26 mm(2), 7.87 mm(2), and 9.87 mm(2) for 2.5 mm, 3.0 mm, 3.5 mm, and 4 mm balloons, respectively. Final MLD (mm) was significantly larger in the IVUS compared to the angiographic-guided group (3.09 +/- 0.50 vs. 2.67 +/- 0.54; P < 0.0001). There were no procedural complications related to IVUS use. CONCLUSIONS: We propose new IVUS criteria based on vessel remodeling that results in an increment in the final MLD, compared to angiographic guidance, which is much larger than any previously published study. This criterion seems to be safely achievable. A proposed randomized study (angiographic vs. IVUS optimization trial) has been launched to test these concepts.

Increase of the isoprostane 8-isoprostaglandin f2alpha in maternal and fetal blood of rats with streptozotocin-induced diabetes: evidence of lipid peroxidation.

OBJECTIVE: Pregnancy complicated by diabetes is associated with maternal complications and fetal abnormalities. Animal models of diabetes suggest that heightened free radical production may be implicated in the pathogenesis of this condition. The purpose of this investigation was to evaluate oxidative stress in plasma from diabetic rats and their fetuses through measurement of concentrations of 8-isoprostaglandin F(2alpha), a stable marker of lipid peroxidation. STUDY DESIGN: Diabetes was induced in virgin and pregnant rats with streptozotocin. Blood samples were collected after 20 days of diabetes. Adult and fetal plasma 8-isoprostaglandin F(2alpha) concentrations were determined by gas chromatography-mass spectroscopy. RESULTS: Significantly higher plasma 8-isoprostaglandin F(2alpha) concentrations were observed in the virgin rats with diabetes and in both the pregnant dams with diabetes and their fetuses when compared with their respective control groups without diabetes (P <.001). CONCLUSION: Oxidative stress was induced in both mother and fetus in rodent pregnancy complicated by diabetes. This finding may have implications for fetal dysmorphogenesis and in fetal programming for adulthood disease.

Cholesterol-independent endothelial dysfunction in virgin and pregnant rats fed a diet high in saturated fat.

1. Western diets high in saturated fat are associated with an increased incidence of cardiovascular diseases. In this study we have evaluated vascular endothelial function and oxidative stress in virgin rats fed a normal (VC) or high in saturated fat diet (VHF) (20 % lard and corn oil w/w) from weaning until adulthood, and throughout subsequent pregnancy (PC and PHF, respectively). 2. The saturated fat diet was associated with enhanced noradrenaline sensitivity in small mesenteric arteries from VHF rats (VHF vs. VC, P < 0.05) and blunted endothelium-dependent relaxation in VHF and PHF rats (VHF vs. VC, P < 0.001; PHF vs. PC, P < 0.05). Endothelial dysfunction was attributable to a reduced nitric oxide component of relaxation in VHF rats, and blunted prostacyclin and endothelium-derived hyperpolarizing factor components in PHF rats. 3. Other than plasma cholesterol, which was reduced in VHF and PHF rats, plasma lipids were normal. Fasting plasma insulin and glucose concentrations were raised in VHF rats (P < 0.05) and the plasma marker of oxidative stress, 8-iso PGF2alpha, was increased in PHF animals (P < 0.01). 4. These findings suggest that endothelial dysfunction induced by a saturated fat diet is cholesterol independent and likely to be of different mechanistic origin in virgin and pregnant rats.

Streptozotocin diabetes in the pregnant rat induces cardiovascular dysfunction in adult offspring.

Severe diabetes in pregnant rats produces persistent metabolic consequences in adult offspring. This study investigated whether diabetes in pregnant rats could also lead to cardiovascular abnormalities in the adult offspring. Blood pressure, heart rate and in vitro vascular reactivity of small arteries were evaluated in female adult offspring of control rats and of rats rendered diabetic with streptozotocin. Rise in blood pressures were similar in both groups of offspring but heart rate was lower in the diabetic offspring (p < 0.05). The rise in blood pressure associated with infusion of a nitric oxide synthase inhibitor was similar in both groups, but the associated decrease in heart rate was more pronounced in diabetic offspring (p < 0.01). Small mesenteric arteries from this group showed enhanced sensitivity to noradrenaline (p < 0.05) and abnormal endothelium-dependent relaxation to acetylcholine (p < 0.01) and bradykinin (p < 0.05). Reduction in acetylcholine induced relaxation, reflected reduced synthesis of nitric oxide or a cyclooxygenase product and was not attributable to an endothelium-derived hyperpolarizing factor. Sensitivity to exogenous nitric oxide was normal. A subgroup of pups born to diabetic dams were suckled by control maternal dams and a subgroup of those born to controls by diabetic dams. Suckling was an important determinant of impaired growth; offspring of diabetic rats suckled by their own mother and those of control rats by diabetic dams showed impaired growth rates whereas growth of offspring of diabetic rats suckled by control dams paralleled those of control rats suckled by their own mother.

Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium-derived hyperpolarizing factor (EDHF).

1. Small mesenteric arteries from pregnant rats demonstrated greater sensitivity (pEC50 : P<0.001) and maximum relaxation (P<0.01) to acetylcholine (ACh) than those of control non-pregnant animals. 2. Maximum relaxation, but not sensitivity, to ACh remained greater (P<0.01) in pregnant animals when evaluated in 25 mM KCl, which prevents relaxation dependent upon hyperpolarization. ACh induced relaxation in the presence of 25 mM KCl was completely inhibited in pregnant and non-pregnant groups by N(omega)-nitro L-arginine methyl ester (L-NAME, 100 microM), indomethacin (INDO, 10 microM) and oxadiazole quinoxalin (ODQ, 1 microM), suggesting pregnancy associated enhancement of dilator prostanoid and/or nitric oxide (NO) synthesis. 3. ACh induced relaxation in 5 mM KCI was only partially inhibited by a combination of N(omega)-nitro L-arginine methyl ester (L-NAME, 100 microM), indomethacin (INDO, 10 microM) and oxadiazole quinoxalin (ODQ, 1 microM). The residual relaxation, which was greater in arteries from pregnant rats (maximum relaxation: P<0.01), was prevented by 25 mM KCl, indicating pregnancy associated enhanced synthesis/ reduced degradation of a hyperpolarizing factor. Residual relaxation to ACh in 5 mM KCl was inhibited by the cytochrome P450 inhibitor, proadifen (1 microM) in the pregnant group (P<0.001). 4. Relaxation to spermine NONOate was similar in pregnant and non-pregnant groups and totally inhibited by ODQ (in the presence of L-NAME). 5. This study suggests that, in addition to enhanced endothelium dependent NO/dilator prostanoid synthesis, a hyperpolarizing factor may contribute to the vascular adaptation to pregnancy.