Improvement In Regional Blood Flow Research Articles

Evaluation of gastric blood supply in diabetic patients with gastroparesis by contrast-enhanced ultrasound.

Improvement in regional blood flow has been shown to ameliorate diabetic gastroparesis. We compared the gastric blood supply in patients with diabetes with gastroparesis with that in healthy subjects, by using contrast-enhanced ultrasound (CEUS). 30 healthy subjects and 40 patients with diabetic gastroparesis were enrolled. The CEUS parameters of greater curvatures of the antrum (GCOA) and lesser curvatures of the antrum (LCOA), including peak intensity (PI) and the area under the curve (AUC), were compared between the two groups. Intraclass correlation coefficient (ICC) for PI in healthy subjects measured on CEUS were 0.831-0.857 and 0.803-0.823, respectively. Intra-ICC and inter-ICC values for AUC were 0.805-0.823 and 0.813-0.815, respectively. In both groups, no significant difference was observed in PI and AUC values of GCOA and LCOA (p > 0.05). The PI and AUC of GCOA and LCOA in the diabetes group were less than those in the normal group (p < 0.05). CEUS can assess stomach wall vascularity with a high reproducibility. Microcirculation in the antrum of patients with diabetic gastroparesis is poorer than that of normal group, which is consistent with the mechanisms of diabetic neuropathy. CEUS can be used for evaluation of microvascular perfusion in patients with stomach wall disease. Advances in knowledge: This was the first study to use CEUS for assessment of blood supply of the gastric wall and to compare microvascular perfusion between healthy individuals and patients with diabetes with gastroparesis.

The Hydrogen Sulfide Donor NaHS Promotes Angiogenesis in a Rat Model of Hind Limb Ischemia

It is not known whether H(2)S can promote angiogenesis with improvement of regional blood flow in ischemic organs. Sodium hydrosulfide (NaHS, a H(2)S donor) was administered once a day for 4 w following femoral artery ligation. Collateral vessel growth, capillary density, regional tissue blood flow, the expression of endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and Akt were examined during or at the end of the treatment period. NaHS treatment significantly increased collateral vessel growth, capillary density, and regional tissue blood flow in ischemic hind limb muscles compared with the controls. These effects were associated with an increase in VEGF expression in the skeletal muscles and VEGFR2 phosphorylation in the neighboring vascular endothelial cells, suggesting a role of VEGF in mediating the NaHS effects in a cell-cell interaction pattern. Moreover, NaHS treatment also resulted in an increase in Akt phosphorylation in ischemic hind limb muscles. In conclusion, our observations with NaHS strongly suggest that H(2)S is a proangiogenic factor in chronic ischemia. The proangiogenic effect of NaHS may be mediated by interaction between the upregulated VEGF in the skeletal muscle cells and the VEGFR2 as well as its downstream signaling element Akt in the vascular endothelial cells.

Invited commentary

Invited commentary

Therapeutic Angiogenesis Induced by Injecting Hepatocyte Growth Factor in Ischemic Canine Hearts

Therapeutic angiogenesis, induced by the direct injection of angiogenic growth factors or by transmyocardial laser revascularization (TMLR), has shown great potential as a new therapeutic strategy for end-stage coronary artery disease. However, no significant differences in angiogenic effects of TMLR and vascular endothelial growth factor (VEGF) have been reported. We compared the effects of the intramyocardial injection of hepatocyte growth factor (HGF), a novel angiogenic factor, with those of TMLR, by evaluating the improvement in regional blood flow and regional function in a canine heart model of chronic ischemia. To create a model of chronic ischemia, we ligated the left anterior descending artery (LAD) in 15 beagles. We divided the dogs into three groups according to the treatment given 1 month after ligation. Four dogs were given an intracardial injection of human recombinant HGF (H group), six dogs were given TMLR (T group), and five dogs were used as a control (C group). We compared the degree of improvement in regional blood flow and regional function 1 month after the treatment. The regional myocardial blood flow and function were significantly better in the H group than in the T or C groups (P < 0.05). Histologically, there were significantly more von Willebrand factor-positive cells in the LAD region in the H group than in the T or C groups. The intramural injection of recombinant human HGF resulted in therapeutic angiogenesis with an intrinsic contractile state, and it may have greater advantages than TMLR for the treatment of chronic ischemic heart disease.

Tissue engineering of angiogenesis with autologous endothelial progenitor cells.

Adult bone marrow and peripheral blood contain small subsets of mononuclear cells that can be differentiated into endothelial-like cells in vitro. Experimental and clinical transplantation of such cell isolates--often referred to as endothelial stem/progenitor cells--into ischaemic or infarcted areas shows their incorporation into sites of new vessel growth along with improvement of regional blood flow. Emerging evidence suggests that these beneficial effects on vascular growth can be attributed to the paracrine activation of resident endothelial cells, rather than their integration into new endothelium. Autologous endothelial progenitor cells can also substitute for native vessel-derived endothelial cells in tissue-engineered vascular autografts.

Comparison of developmental endothelial locus-1 angiogenic factor with vascular endothelial growth factor in a porcine model of cardiac ischemia

Background This study compared the angiogenic effects of developmental endothelial locus-1 (DEL-1), vascular endothelial growth factor (VEGF), as well as the negative control, β-galactosidase (β-gal), in a porcine model of cardiac ischemia. Methods Twenty pigs underwent left circumflex artery occlusions. After 3 weeks, the animals received myocardial injections of adenovirus expressing β-gal (n=6), DEL-1 (n=7), or VEGF (n=7). At 7 weeks, animals were assessed for both function and coronary flow and compared with baseline measurements. Results Regional wall motion index and global ejection fraction showed deterioration in function in the β-gal group and no change in the VEGF and DEL-1 groups between the treatment and harvest time points. Preload recruitable stroke work suggested functional improvement in the VEGF group (35.8 ± 8.6 vs 56.4 ± 17.8, p = 0.033). The increase in the DEL-1 group was not statistically significant (27.3 ± 9.8 vs, 40.2 ± 19.4, p = 0.067). The β-gal group exhibited minimal change (30.7 ± 14.8 vs 35.9 ± 12.1, p = 0.96). Regional blood flow as assessed by fluorescent microspheres was improved under stress conditions in the VEGF group (1.00 ± 0.15 vs 1.15 ±0.22, p = 0.03). Conclusions Treatment with VEGF led to a modest improvement in regional blood flow and cardiac function in previously ischemic myocardial tissue.

Protective and Ameliorative Effects of Benidipine Hydrochloride Against Renal Damage in the Stroke-prone Spontaneously Hypertensive Rat(SHR-SP).

The potential of benidipine hydrochloride (BH), a 1,4-dihydropyridine calcium antagonist and a possible vasodilator, to protect against renal damage in the stroke-prone spontaneously hypertensive rat (SHR-SP) was examined using fifty-five males (10 weeks old). The animals were allotted into experiments 1 and 2, in each case subdivided into three groups (control and BH at doses of 3 and 10 mg/kg). Administration of BH was initiated before identification of clinical stroke in Experiment 1 and after its onset in Experiment 2. Measurement of body weight (BW) and systolic blood pressure (SBP) indicated that treatment of BH was associated with increased BW gain and reduced blood pressure in both experiments. Histopathological assessment revealed significant and dose-dependent decrease in the degree of fibrinoid necrosis in renal blood vessels, sclerosis, hyalinization, edematous thickening and Bowman's space dilatation in glomeruli, as well as protein casts, dilated or regenerative tubules, and interstitial inflammatory infiltration with fibrosis in tubulointerstitium in the BH treated groups as compared with the control group. These results indicated that BH exerts vasodilative effects on the kidney with improvement of regional blood flow, then preventing and ameliorating renal damage.

Pediatric Regional Anesthesia: Beyond the Caudal

Pediatric Regional Anesthesia: Beyond the Caudal

Expression of angiogenic factors in rabbit spinal cord after transient ischaemia.

It is known that angiogenic factors are induced in brain by ischaemia, and new vessel formation is correlated with better prognosis in patients of stroke. However, the role of angiogenesis and expression of angiogenic factors in spinal cord ischaemia is uncertain. We here investigated expression of three highly potent angiogenic peptides, i.e. basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the rabbit spinal cord after transient ischaemia, by Western blot and immunohistochemical analysis. Western blot analysis revealed that bFGF was induced at 8 h after transient ischaemia and decreased thereafter. Immunoreactive VEGF was also induced at 8 h, and it disappeared thereafter. HGF was not detected in the spinal cord with sham-operation or ischaemic injury. By immunohistochemical analysis, bFGF was weakly expressed in only a few small interneurons in sham-operated spinal cords. However, it was induced to a marked degree in motor neurons and interneurons of the anterior horn at 8 h after reperfusion. It was also induced in small neurons of the posterior horn. The expression in the anterior horn decayed thereafter though it lasted until 7 d in the posterior horn. VEGF was not expressed in sham-operated spinal cords, but the expression was induced in large motor neurons and interneurons at 8 h with marked reduction at 1 d. In contrast, HGF was not expressed in the spinal cord with sham-operation or ischaemic injury. These factors are known to play pivotal roles in angiogenesis, regulation of blood flow, and protection of endothelial cells. Through induction of these angiogenic peptides, protection of vascular endothelial cells and improvement of regional blood flow might be occurring in the spinal cord after ischaemia.

Stable prostacyclin improves postischaemic microcirculatory changes in hypertensive rats.

The prostacyclin analogue TTC-909 is incorporated in lipid microspheres and is chemically very stable. We examined the efficacy of TTC-909 on cerebral microcirculation following focal cerebral ischaemia. Focal cerebral ischaemia was produced by the occlusion of the distal middle cerebral artery in stroke-prone spontaneously hypertensive rats. Intravenous administration of TTC-909 (100 ng/kg/day) or vehicle was started 30 minutes after the occlusion and repeated for 7 days. On day 7, cerebral blood flow and blood-brain barrier permeability were measured autoradiographically. Brain oedema was estimated by the gravimetric method. The size of the infarction was calculated from area measurements on serial histologic sections. Treatment with TTC-909 resulted in significant improvement in regional blood flow in the ischaemic rim (p < 0.01) and the surrounding area (p < 0.05). With TTC-909 treatment, the increased permeability was significantly reduced in the ischaemic centre (p < 0.01) and rim (p < 0.05). A decrease in specific gravity in the ischaemic region and the remote non-ischaemic regions was prevented by the treatment (p < 0.01). We assumed that the efficacy of TTC-909 maintains the blood supply in the ischaemic area, improves disruption of the blood-brain barrier and prevents development of ischaemic oedema.

Effects of N-Acetyl-L-Cysteine on Regional Blood Flow during Endotoxic Shock

We previously reported that N-acetyl-L-cysteine (NAC), an oxygen free-radical scavenger, can increase the oxygen extraction capabilities during endotoxic shock when blood flow is progressively reduced. In the present study, we investigated whether the protective effects of NAC are related to an improvement in regional blood flow following endotoxemia. Fourteen anesthetized, saline-infused and ventilated dogs were divided into two groups: 7 dogs received NAC (150 mg/kg, followed by a 20 mg/kg.h infusion), and the other 7 dogs served as a control time-matching group. Thirty minutes later all the dogs received Escherichia coli endotoxin (2 mg/kg) i.v. A saline infusion was started 30 min after endotoxin challenge to restore pulmonary artery occlusion pressure to baseline and maintain it constant. Regional blood flow was measured by ultrasonic volume flowmeter. In the control group, arterial pressure, left ventricular stroke work index and systemic vascular resistance remained lower than baseline. Mesenteric, renal and femoral arterial blood flow increased but only femoral blood flow returned to baseline levels. In the NAC group, cardiac index and left ventricular stroke work index remained higher and systemic and pulmonary vascular resistance were lower than in the control group. Blood flow in mesenteric, renal and especially femoral arteries was higher than in the control group. Fractional blood flow increased only in the femoral artery. PaO2 and PvO2 had similar courses in the two groups. A higher venous admixture was associated with a higher cardiac index and a lower pulmonary vascular resistance in the NAC group. Oxygen delivery and oxygen-uptake were higher in the NAC-treated than in the control animals throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Advances in Cerebral Ischemia: Experimental Approaches

Drugs that dissolve clots, such as streptokinase and rTPA, and drugs that promote vasodilation are undergoing clinical testing for the treatment of hyperacute stroke, but an adjuvant therapy that either prolongs temporal thresholds before irreversible injury occurs or actually protects the brain from ischemia would transform these trials. Mild hypothermia, either intraischemically or at the onset of reperfusion, provides us with a gold standard for cytoprotection against which new pharmacologic strategies can be measured. The cytoprotective effects of the voltage-sensitive calcium channel blockers and the NMDA antagonists have been relatively less compelling than more recent findings with non-NMDA or AMPA antagonists. Their ability to inhibit SINN or reduce neocortical infarction is remarkable. Future randomized clinical trials for both resuscitated cardiac arrest victims and patients sustaining embolic stroke are predicted by this major advance in the field of stroke medicine.