Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels

In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia and their angiotensinergic innervation with mesenteric resistance blood vessels. Angiotensinogen - and angiotensin converting enzyme-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia, while renin mRNA was untraceable. Cathepsin D, a protease responsible for cleavage beneath other substrates also angiotensinogen to angiotensin I, was successfully detected in rat coeliac ganglia indicating the possibility of existence of alternative pathways. Angiotensinogen mRNA was also detected by in situ hybridization in the cytoplasm of neurons of rat coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia as well as with mesenteric resistance blood vessels. By using confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally with the mesenteric resistance blood vessels.

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

AIMS/HYPOTHESIS: Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. METHODS: Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. RESULTS: RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA(1c) in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. CONCLUSIONS/INTERPRETATION: RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.

Endovascular treatment for chronic atherosclerotic occlusive mesenteric disease: is stenting superior to balloon angioplasty?

Endovascular treatment is an increasingly used therapeutic option in patients with chronic atherosclerotic occlusive mesenteric disease. Purpose of this study was evaluation of patency and mortality in patients treated with visceral artery percutaneous transluminal angioplasty (PTA) or stenting including follow-up.

Aortic flow patterns resulting from right axillary artery cannulation

Right axillary artery (RAA) cannulation is increasingly used in cardiac surgery. Little is known about resulting flow patterns in the aorta. Therefore, flow was visualized and analyzed. A mock circulatory circuit was assembled based on a compliant transparent anatomical silicon aortic model. A RAA cannula was connected to a continuous flow rotary blood pump (RBP), pulsatile heart action was provided by a pneumatic ventricular assist device (PVAD). Peripheral vascular resistance, regional flow and vascular compliance were adjusted to obtain physiological flow and pressure waveforms. Colorants were injected automatically for flow visualization. Five flow distributions with a total flow of 4 l/min were tested (%PVAD:%RBP): 100:0, 75:25, 50:50, 25:75, 0:100. Colorant distribution was assessed using quantitative 2D image processing. Continuous flow from the RAA divided in a retrograde and an antegrade portion. Retro- to antegrade flow ratio increased with increasing RAA-flow. At full RBP support flow was stagnant in the ascending aorta. There were distinct flow patterns between the right- and left-sided supra-aortic branches. At full RBP support retrograde flow was demonstrated in the right carotid and right vertebral arteries. Further studies are needed to confirm and evaluate the described flow patterns.

Myocardial blood volume and coronary resistance during and after coronary angioplasty

Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml · min(-1) · g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml · min(-1) · g(-1) during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml · min(-1) · g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.

Coronary artery disease, nitric oxide and oxidative stress: the "Yin-Yang" effect--a Chinese concept for a worldwide pandemic

Prevention of coronary artery disease (CAD) and reduction of its mortality and morbidity remains a major public health challenge throughout the "Western world". Recent evidence supports the concept that the impairment of endothelial function, a hallmark of insulin resistance states, is an upstream event in the pathophysiology of insulin resistance and its main corollaries: atherosclerosis and myocardial infarction. Atherosclerosis is currently thought to be the consequence of a subtle imbalance between pro- and anti-oxidants that produces favourable conditions for lesion progression towards acute thrombotic complications and clinical events. Over the last decade, a remarkable burst of evidence has accumulated, offering the new perspective that bioavailable nitric oxide (NO) plays a pivotal role throughout the CAD-spectrum, from its genesis to the outcome after acute events. Vascular NO is a critical modulator of coronary blood flow by inhibiting smooth muscle contraction and platelet aggregation. It also acts in angiogenesis and cytoprotection. Defective endothelial nitric oxide synthase (eNOS) driven NO synthesis causes development of major cardiovascular risk factors (insulin resistance, arterial hypertension and dyslipidaemia) in mice, and characterises CAD-prone insulin-resistant humans. On the other hand, stimulation of inducible nitric oxide synthase (iNOS) and NO overproduction causes metabolic insulin resistance and characterises atherosclerosis, heart failure and cardiogenic shock in humans, suggesting a "Yin-Yang" effect of NO in the cardiovascular homeostasis. Here, we will present a concise overview of the evidence for this novel concept, providing the conceptual framework for developing a potential therapeutic strategy to prevent and treat CAD.

Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants

BACKGROUND: A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries. OBJECTIVE: To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants. DESIGN: Sixteen preterm neonates of <34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography. RESULTS: The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO2, and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively). CONCLUSION: A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.

Combined endurance/resistance training early on, after a first myocardial infarction, does not induce negative left ventricular remodelling

BACKGROUND: Resistance training (RT) is safe and practicable in low-risk populations with coronary artery disease. In patients with left ventricular (LV) dysfunction after an acute ischaemic event, few data exist about the impact of RT on LV remodelling. METHODS: In this prospective, randomized, controlled study, 38 patients, after a first myocardial infarction and a maximum ejection fraction (EF) of 45%, were assigned either to combined endurance training (ET)/RT (n=17; 15 men; 54.7+/-9.4 years and EF: 40.3+/-4.5%) or to ET alone (n=21; 17 men; 57.0+/-9.6 years and EF: 41.9+/-4.9%) for 12 weeks. ET was effectuated at an intensity of 70-85% of peak heart rate; RT, between 40 and 60% of the one-repetition maximum. LV remodelling was assessed by MRI. RESULTS: No statistically significant differences between the groups in the changes of end-diastolic volume (P=0.914), LV mass (P=0.885) and EF (P=0.763) were observed. Over 1 year, the end-diastolic volume increased from 206+/-41 to 210+/-48 ml (P=0.379) vs. 183+/-44 to 186+/-52 ml (P=0.586); LV mass from 149+/-28 to 155+/-31 g (P=0.408) vs. 144+/-36 to 149+/-42 g (P=0.227) and EF from 49.1+/-12.3 to 49.3+/-12.0% (P=0.959) vs. 51.5+/-13.1 to 54.1% (P=0.463), in the ET/RT and ET groups, respectively. Peak VO2 and muscle strength increased significantly in both groups, but no difference between the groups was noticed. CONCLUSION: RT with an intensity of up to 60% of the one-repetition maximum, after an acute myocardial infarction, does not lead to a more pronounced LV dilatation than ET alone. A combined ET/RT, or ET alone, for 3 months can both increase the peak VO2 and muscle strength significantly.

[Arterial-adaptive dilatation and Doppler velocimetry in normal fetuses with a single umbilical artery]

PURPOSE: In this study we examined the arterial-adaptive dilatation and Doppler velocimetry, especially RI values, in normal fetuses with a single umbilical artery (SUA). MATERIALS AND METHODS: We studied 195 fetuses from 18 to 39 weeks of gestational age with a prenatally identified SUA retrospectively. They were enrolled in this study if the following information applied: > 18 weeks of gestational age, no structural or chromosomal abnormalities, and histopathological confirmation of SUA. Sonographic examination included evaluation of the umbilical artery resistance and the cross-sectional area of the umbilical cord, and its vessels were measured in all cases. Small for gestational age (SGA) was diagnosed when the birth weight was below the 10th percentile for gestational age. Fetuses with intrauterine growth restriction were defined as those with biometric data below the 5th percentile. RESULTS: There were 119 cases of prenatally identified SUA which met the inclusion criteria. RI values were below the 10th percentile in 33/119 (27.33) and below the 50th percentile in 73/119 (61.33). RI values below the 10th percentile were significantly more likely to be in the normal collective than in the growth restricted collective [31/87 (35.63%) vs. 2/32 (6.25%); p = 0.001]. Even more significant differences became apparent when comparing the RI values below the 50th percentile of both groups. An umbilical artery diameter over the 90th percentile was found in 49 (41.9%) of cases and was significantly more likely to be present in normal growing fetuses than in the growth restricted group. CONCLUSION: Normal fetuses with SUA are at higher risk to be born as SGA. With our study results we can confirm the hypothesis that Doppler flow measurements and arterial diameter in SUA are different from those found in normal fetal umbilical arteries. RI values over the 50th percentile or a cross-sectional area of the artery below 95th percentile after 26th week of gestation significantly increases the risk of SGA.

Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol

BACKGROUND The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.

Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension

BACKGROUND & AIMS Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY-effects in portal hypertension, we investigated its role for non-receptor-mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham-operated rats. METHODS Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non-receptor-mediated vasoconstriction. Dose-response curves to KCl (30-300 mM) were used to bypass G protein-coupled receptor mechanisms. Potential involvement of the cyclooxygenase-pathway was tested by non-selective cyclooxygenase-inhibition using indomethacin. RESULTS KCl-induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl-evoked vascular sensitivity being not different between study groups. However, KCl-induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY-induced enhancement of vasoconstriction. CONCLUSIONS Receptor-independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non-receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension.