Skin perfusion patterns (fluorescein perfusography) during reactive hyperaemia in peripheral arterial occlusive disease.

From the pathophysiological point of view the regional distribution of blood flow is of special importance in ischaemic tissues. Within this study foot sole skin perfusion was investigated by means of fluorescein perfusography at rest and during reactive hyperaemia in patients with peripheral arterial occlusive disease confined to one limb (Fontaine stage II). Ambient temperatures were maintained around 21 degrees C. Mean fluorescein appearance times on the one side and their standard deviations (SD) and coefficients of variation (CV) on the other side were taken as measures of overall blood supply and homogeneity of flow, respectively. At rest no differences in these parameters could be detected between diseased legs and controls. After a 3-min supra-systolic circulatory arrest at the thigh, a significant reduction of fluorescein appearance times was observed for both groups but was statistically more pronounced in the controls. Furthermore, during reactive hyperaemia standard deviations as well as coefficients of variation decreased significantly only in normal limbs whereas they either remained constant (SD) or even increased (CV) in those with arterial obstructions. All effects associated with reactive hyperaemia showed statistically significant correlations with systolic ankle pressure indices. From these results it is concluded that haemodynamically effective arterial obstructions are followed by not only a restriction of overall hyperaemic blood supply but also a failure to homogenize microcirculatory perfusion in the case of increased flow requirements.     

Cerebral reactive hyperaemia and arterial pressure in anaesthetized goats

The effects of arterial pressure on cerebral reactive hyperaemia were studied in anaesthetized goats measuring electromagnetically middle cerebral artery flow and performing arterial occlusions of 5–30 s. Under normotension (mean arterial pressure, MAP = 11± 0.3 kPa), reactive hyperaemia (peak hyperaemic flow to control flow and repayment to debt ratios) increased, and cerebrovascular resistance during peak hyperaemic flow decreased, as ischaemia duration lengthened; the virtual maximal changes were obtained after 20 s ischaemia. During hypertension by aorta constriction (MAP = 18 ± 0.7 kPa) or by i. v. infusion of noradrenaline (MAP = 19 ± 0.8 kPa) middle cerebral artery flow did not change significantly and cerebrovascular resistance increased 25 and 46%, respectively (P < 0.05). During both types of hypertension reactive hyperaemia was over 50% higher, and the decrement in cerebrovascular resistance during peak hyperaemic flow was also higher, than under normotension. During hypotension by constriction of the inferior vena cava (MAP = 5 ±.5 kPa) or by i. v. infusion of isoproterenol (MAP = 6±.5 kPa), middle cerebral artery flow decreased 35% or did not change, and cerebrovascular resistance decreased 41 and 45 %, respectively (P < 0.05). In these conditions, reactive hyperaemia and the decrement in cerebrovascular resistance during peak hyperaemic flow were reduced SOY, and it was similar in both types of hypotension. The absolute levels of cerebrovascular resistance obtained during peak hyperaemia were similar during normotension, hypertension and hypotension. Thus, arterial pressure is a main determinant of postocclusive cerebral reactive hyperaemia, and myogenic mechanisms may be of significance in determining the early stage of cerebral reactive hyperaemia after brief ischaemias. Adrenergic mechanisms might be of minor significance in this type of cerebral reactive hyperaemia.     

Coronary reactive hyperaemia and arterial pressure in anaesthetized goats

To study the effects of arterial pressure on coronary reactive hyperaemia, left circumflex coronary artery flow was measured, and reactive hyperaemia was determined after 5, 10 or 20 s of occlusion of this artery in anaesthetized goats during normotension, hypertension and hypotension. During hypertension induced by aortic constriction (mean arterial pressure, MAP = 140 +/- 6 mmHg) coronary vascular resistance (CVR), reactive hyperaemia (ratio of peak in hyperaemic flow to control flow and ratio of repayment to debt) and the decrease in CVR during the peak in hyperaemic flow were comparable to those during normotension. During hypertension induced by noradrenaline (MAP = 144 +/- 6 mmHg) CVR was 16% lower (P < 0.05), reactive hyperaemia was reduced by 14-25% (P < 0.05) and the decrease in CVR during the peak in hyperaemic flow was lower than the values of these parameters during normotension. During hypotension induced by constriction of the caudal vena cava (MAP = 40 +/- 4 mmHg) CVR was 22% lower (P < 0.05), reactive hyperaemia was reduced by 25-65% (P < 0.05) and the decrease in CVR during the peak in hyperaemic flow was less compared to the values of these parameters during normotension. During hypotension induced by isoprenaline (MAP = 45 +/- 4 mmHg) CVR was 59% lower, reactive hyperaemia was reduced by 55-100% (P < 0.01) and the decrease in CVR during the peak in hyperaemic flow was less compared to the values of these parameters during normotension. Arterial pressure is a main determinant of coronary reactive hyperaemia after brief periods of ischaemia, and the relationship between arterial pressure and reactive hyperaemia may depend in part on changes in CVR after variations in arterial pressure. These changes in CVR may be related to the action on coronary vessels of myocardial factors and vascular myogenic mechanisms.     

Nailfold capillaroscopy in non-insulin dependent diabetes mellitus: blood flow velocity during rest and post-occlusive reactive hyperaemia

Direct intravital microscopic examinations of nailfold capillaries were made in two groups of subjects: 15 healthy volunteers (C) and 16 non-insulin dependent (D II) diabetic patients. In the diabetic group, the disease duration was less than 1 year (n = 4), between 1 and 10 years (n = 8) and between 10 and 18 years (n = 4). Capillary morphology was evaluated and the distribution of morphological patterns was significantly different between the two groups (P less than 0.001). The number of enlarged capillaries was increased in the D II group compared to the C group and capillaries with nodular apical elongations were only found in diabetics. Capillary blood flow velocity (CBFV) was measured during rest and after release of 60 s arterial occlusion. To assess autoregulatory capacity we determined peak CBFV post occlusion and time to reach it in single capillaries. Mean resting CBFV was not statistically different in the two groups but mean peak CBFV post occlusion was significantly lower (C: 1.49 +/- 0.14 mm s-1; mean +/- SE; D II: 0.93 +/- 0.13 mm s-1, P less than 0.05) and mean time to reach it significantly prolonged (C: 8.9 +/- 0.6 s; D II: 18.0 +/- 1.9 s; P less than 0.05) in diabetics compared to controls. Thus skin microvascular autoregulatory responses are disturbed in these patients. The impairments of the reactive hyperaemia response could not be correlated to either metabolic control or duration of the disease.     

Antiplatelet effects of intravenous iloprost in patients with peripheral arterial obliterative disease

Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.Abbreviations ADP Adenosinediphosphate - PGI₂ Prostacyclin - PRP platelet rich plasma - TXA₂ Thromboxane A₂ - 12-HPETE 12-hydroperoxy-eicosatetraenoic acid Presented in part as a preliminary report at the II. International Prostaglandin Symposium, Nürnberg-Fürth, 1984     

干细胞移植治疗糖尿病下肢血管病变的Meta分析

目的:干细胞移植己用于糖尿病下肢血管病变的临床治疗,因各研究样本量小,研究结论不一致.文章系统评价干细胞移植治疗糖尿病下肢血管病变的有效性和安全性.方法:计算机检索PubMed、The Cochrane Library(2019年第11期)、EMbase、中国知网、CBM、维普、万方数据库中干细胞移植治疗糖尿病下肢血管...     

Skin capillary abnormalities in patients with Raynaud's phenomenon

The digital skin microcirculation was studied by vital capillaroscopy in 32 consecutive patients with Raynaud's phenomenon. A detailed classification (stages 0-6) of the capillary abnormalities based upon observations of the capillaries in many different sites of the fingers was used. Associated diseases were searched for by an extensive clinical and immunological investigation. Seventeen (53%) of the patients had distinct structural changes in the capillaries but only 6 of them showed a restricted total digital circulation. Fifteen (88%) of these 17 patients displayed an underlying disease and/or immunological abnormalities. The corresponding figure for patients with mild or no capillary changes was 40% (p less than 0.01). Thus, the presence of marked (greater than or equal to stage 3) skin capillary abnormalities seems to be a good indicator of an associated systemic disease. The majority of patients in this category improved their capillary status during successful treatment of the underlying disease. We conclude that the form of capillaroscopy used in this study is a sensitive method for evaluating disturbances of the skin microcirculation in patients with Raynaud's phenomenon. The method may also contribute to the clinical evaluation of patients with this syndrome by identifying those with an underlying systemic disease.     

Determinants of post-ischaemic reactive hyperaemia in patients with diabetes mellitus type II.

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5.0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40.5 +/- 15.3; males 51.8 +/- 17.7 ml min-1 100 ml-1, P < 0.01). In diabetic patients, in addition to gender, actual blood glucose (r = 0.377, P < 0.05) and meal intake (non-fasting 42.8 +/- 19.2; fasting 51.2 +/- 19.5 ml min-1 100 ml-1, P < 0.05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P < 0.001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.     

Local regulation of subcutaneous blood flow and capillary filtration in limbs with occlusive arterial disease. Studies before and after arterial reconstruction

The aim of the study was to examine the local blood flow regulation and the capillary filtration rate in patients with occlusive arterial disease before and after arterial reconstructive surgery. Fourty-seven normal subjects and 99 patients were studied. Subcutaneous blood flow was measured on the forefoot by the local 133Xenon method. Forefoot arterial blood pressure was measured indirectly by cuff and strain-gauge technique. Capillary filtration rate was measured by strain-gauge plethysmography on the forefoot. The arterial and venous pressures of the forefoot were changed by elevating or lowering the foot in relation to heart level. In normal limbs autoregulation was demonstrated during elevation of the limb when blood flow remained almost constant despite the reduction in arterial and perfusion pressures. The local vasoconstrictor response to increased venous transmural pressure was demonstrated when the limb was lowered and blood flow decreased about 30% despite a constant perfusion pressure. In limbs with occlusive arterial disease both local blood flow regulation mechanisms became progressively more abnormal the severe the symptoms and the lower the distal blood pressure. Estimations of the changes in local vascular resistance suggested that the abnormalities in blood flow regulation in all but the severest cases are the result of changes in local perfusion pressure rather than the result of inability of the arteriolar smooth muscle to dilate and constrict in response to changes in arterial and venous pressures. After arterial reconstruction the two mechanisms generally normalized within about a week. However, disturbances occurred in some cases in the early postoperative period, possibly as the result of postoperative pain and stress. Postreconstructive hyperaemia developed in most limbs despite the early normalization of local blood flow regulation. Compared with normal limbs, the forefoot capillary filtration rate was reduced in limbs with occlusive arterial disease. In the early postoperative period the filtration rate remained reduced, but it increased to normal values within three months. Postreconstructive oedema developed independently of the normalization of blood flow regulation, and almost exclusively after femoro-distal by-pass surgery. The study supports the hypothesis that the postreconstructive oedema is a lymphoedema due to surgical trauma, rather than the result of microvascular derangement.     

Peripheral blood lymphocyte subpopulations in patients with primary proliferative and secondary polycythaemia.

Peripheral blood lymphocyte subpopulations were measured in 18 patients with primary proliferative polycythaemia and 13 patients with secondary polycythaemia. A decrease in numbers of suppressor T lymphocytes and an increase in the helper:suppressor T lymphocyte ratio was found in those with primary polycythaemia compared with normal subjects and patients with secondary polycythaemia. If other causes of an increased helper:suppressor ratio are excluded this variable may be useful in confirming the myeloproliferative nature of patients with erythrocytosis.     

Forefoot capillary filtration rate measured during lowering in normal subjects and in patients with occlusive arterial disease before and after arterial reconstruction

Capillary filtration rate (CFR) was measured by a mercury-in-silastic strain-gauge around the forefoot when the forefoot was lowered 40 cm below heart level. In seven normal limbs, CFR was 0.061 (0.049-0.086) ml (100 g min)-1 against 0.049 (0.016-0.071) ml (100 g min)-1 in 24 limbs with occlusive arterial disease (P = 0.01). About 8 days after arterial reconstruction CFR decreased to 0.039 (0.018-0.071) ml (100 g min)-1, but before 3 months after reconstruction CFR increased to normal values 0.061 (0.037-0.071) ml (100 g min)-1. The explanation offered for the reduced CFR before and immediately after arterial reconstruction is temporary thrombosis in the smallest distributing arteries and in the arterioles resulting in heterogeneous flow distribution and decreased fluid filtration in poorly perfused segments of the capillary bed. The results speak against increased capillary filtration as the aetiology of the post-reconstructive oedema.     

Hodgkin's disease: a tumor with disturbed immunological pathways

Hodgkin's disease is a lympltoid neoplasia characterized by low frequeny of malignant Hodgkin and Reed-Sternberg (H-RS) cells in an abundant background of non-neoplastic cells. H-RS cells and their neighbors interact via a complex network of cellular activation/adhesion molecules and cytokines. Here, Hans-Jürgen Gruss and colleagues suggest that H-RS cells can be regarded as antigen-presenting cells able to interact with surrounding T cells, resulting in an intense, bid ineffective, immune response.     

Doppler ultrasound measurement of phasic renal arterial blood flow velocity in patients with chronic glomerulonephritis]

The phasic renal arterial blood flow velocity was measured using a Doppler-Based Toshiba SSH-160A scanner in 25 healthy subjects and 78 patients with chronic glomerulonephritis. Renal arterial blood flow at the renal hilum was visualized with color Doppler ultrasound, and the velocity waveform was obtained by pulsed Doppler ultrasound. The velocity waveform was then analyzed to give the peak systolic velocity (S), end-diastolic velocity (D), resistive index (RI), and pulsatility index (PI). Creatinine clearance correlated with S (r = 0.76), D (r = 0.80), RI (r = -0.74), and PI (r = -0.85). The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of Tc-99m DTPA, also correlated well with these parameters. These findings suggest that renal arterial blood flow as detected by Doppler ultrasound may be useful for the noninvasive, direct, rapid, and simple evaluation of renal hemodynamics and renal function, although various modifying factors also need to be considered.     

Simultaneous occurrence of multiple aetiologies of polycythaemia: renal cell carcinoma, sleep apnoea syndrome, and relative polycythaemia in a smoker with masked polycythaemia rubra vera

A 58 year old male heavy smoker presented with intracranial haemorrhage and erythrocytosis. Four aetiologies of polycythaemia--polycythaemia rubra vera (PRV), renal cell carcinoma, sleep apnoea syndrome, and relative polycythaemia--were found to be associated with the underlying causes of erythrocytosis. He did not fulfill the diagnostic criteria for PRV at initial presentation, but an erythropoietin independent erythroid progenitor assay identified the masked PRV, and the low post-phlebotomy erythropoietin concentration also suggested the likelihood of PRV evolution. This case demonstrates that a search for all the possible causes of erythrocytosis is warranted in patients who already have one aetiology of polycythaemia.     

Detection and quantitation of circulating immune complexes in arterial blood of patients with rheumatic disease

We developed antigen-nonspecific enzyme-linked immunoassays (ELISA) to quantitate IgG-C3- and IgM-C3-containing circulating immune complexes (CIC) in venous and arterial blood from rheumatic disease patients. Standards were diethylaminoethyl (DEAE)-purified, heat-aggregated IgG incubated with fresh human serum (for IgG-C3 CIC) and IgM rheumatoid factor-rich serum incubated with reduced, alkylated IgG and then with fresh human serum (for IgM-IgG-C3 CIC). Venous serum and plasma IgG-C3 and IgM-C3 CIC correlated closely (P less than 0.01). Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) patients had elevated levels of venous IgM-C3 CIC (P less than 0.0001) but not IgG-C3 CIC; patients with vasculitis, inflammatory rheumatic diseases, or noninflammatory rheumatic diseases had mean values similar to normal individuals. Venous IgG-C3 and IgM-C3 CIC did not correlate. Paired venous and arterial samples from 16 rheumatic disease patients averaged comparable amounts of IgG-C3 and IgM-C3 CIC, respectively; venous and arterial IgM-C3 CIC levels in patients significantly exceeded normals (P less than 0.05). Venous and arterial IgG-C3 CIC levels correlated closely (P less than 0.01) as did venous and arterial IgM-C3 levels (P less than 0.05). Thus, arterial CIC offered no advantage over venous determinations for rheumatic disease patients. IgM-C3 CIC were elevated in patients with RA and SLE when IgG-C3 CIC were not. Ig isotype-specific CIC quantitation may be useful for certain rheumatic diseases.     

Resistance responses in proximal arterial vessels, arterioles and veins during reactive hyperaemia in skeletal muscle and their underlying regulatory mechanisms

The reactive hyperaemia response cat skeletal muscle to 2-120 s arterial occlusions was analysed with regard to amplitude, duration, 'excess blood flow' and site of dilator action along the vascular bed. The last-mentioned was assessed with a new whole-organ technique permitting continuous segmental resistance recordings in arterial vessels greater than 25 microns, arterioles less than 25 microns and veins. Peak amplitude, duration and excess flow all increased with increasing occlusion length, of which excess flow was linearly related to occlusion length. The site of active dilatation was preferentially confined to arterioles less than 25 microns in which complete relaxation was observed after only 20 s occlusion, although the duration of the response continued to increase with more prolonged occlusions. A graded, but less pronounced, dilatation occurred in the arterial vessels greater than 25 microns and in the veins, the former exhibiting a 63% inhibition of tone as a maximum response at 120 s occlusion. The recovery phase was characterized by a vivid active constrictor component apparently protecting the capillaries from excessive pressure load upon arterial occlusion release, but this constriction became attenuated at long occlusions, thereby prolonging the hyperaemia response. The role of myogenic regulatory mechanisms in the responses was assessed from observed segmental resistance reactions to selectively applied transmural pressure stimuli similar to those elicited by arterial occlusion/release. It was concluded that myogenic mechanisms alone could explain the amplitude of the reactive hyperaemia response at short (up to 30 s) occlusions. Metabolic mechanisms seemed to be responsible for further relaxation of the proximal arterial vessels at longer occlusions, and also for the increased duration of the hyperaemia response at occlusions exceeding 10 s. Blockade of nitric oxide formation (endothelium-derived relaxing factor) did not seem to affect the reactive hyperaemia response.