Postocclusive Hyperemia Research Articles

Generalised wavelet analysis of cutaneous flowmotion during post-occlusive reactive hyperaemia in patients with peripheral arterial obstructive disease

The purpose of the present study was to assess whether the generalised wavelet analysis (GWA) of the leg cutaneous laser Doppler (LD) flowmotion waves recorded during baseline (Bsl) and after skin post-occlusive hyperaemia (POH) can provide information on the leg cutaneous microcirculatory adaptation to stage II peripheral arterial obstructive disease (PAOD). With this aim the flowmotion was characterised in 20 healthy subjects (HS) and 20 stage II PAOD patients by GWA of LDF tracings during Bsl and POH test. The vascular endothelial and smooth muscle function was also evaluated exploring the arm skin vasodilatory response to iontophoretically delivered acetylcholine (Ach) and sodium nitroprusside (SNP) using LD. During Bsl there was no significant difference in leg skin perfusion between HS and PAOD patients (7.3 ± 5.6 vs. 5.8 ± 2.9 AU, respectively). PAOD patients revealed higher peak powers in the frequency interval of 0.007–0.02 Hz (120 ± 82 vs. 85 ± 62 AU 2/Hz; P < 0.05), 0.02–0.06 Hz (116 ± 128 vs. 63 ± 48 AU 2/Hz, respectively; P < 0.05) and 0.06–0.2 Hz (39 ± 49 vs. 14 ± 10 AU 2/Hz; P < 0.05). These flowmotion frequencies are related to vascular endothelium activity, sympathetic activity and vessel wall myogenic activity, respectively. During POH the mean peak power of the flowmotion waves increased significantly ( P < 0.05) in HS respect to Bsl with the only exception of the 0.02–0.06 Hz band. In the PAOD patients, compared to Bsl the amplitude of the flowmotion waves did not significantly change during POH. In addition, the PAOD patients presented an increased time from release to peak-flux (18.25 ± 15.5 vs. 2.16 ± 1.28 s, respectively; P < 0.05), an increased time from release to recovery of the basal perfusion (90.26 ± 39.14 vs. 26.55 ± 14.05 s, respectively; P < 0.05) and a lower slope of the POH curve (10 ± 15 vs. 54 ± 17°, respectively; P < 0.05), compared with HS. The cutaneous arm vasodilatory response to Ach and to SNP was reduced in PAOD patients in comparison with HS ( P < 0.001). In conclusion, our findings showed an increased amplitude of the frequency interval 0.007–0.02, 0.02–0.06 and 0.06–0.2 Hz during Bsl in PAOD patients which did not change during the POH test. All data suggest that in stage II PAOD patients the leg skin perfusion is not impaired during Bsl because of a compensatory mechanism related to increased endothelial, myogenic and sympathetic activities. However during reactive hyperaemia these mechanisms appear to be exhausted in accordance with the reduced vasoreactivity to Ach and SNP.

Blood flow in the skin of type 1 diabetic patients before and after combined pancreas/kidney transplantation

To analyze effects of long-term glucose normalization after pancreas transplantation, different parameters of skin microcirculation were assessed by laser Doppler fluxmetry. Forty-two type 1 diabetic patients after successful simultaneous pancreas/kidney transplantation (Group A, median 32.3 months posttransplant), 28 patients with functioning kidney grafts, but insulin therapy (Group B, median 64.9 months posttransplant) and 13 diabetic pretransplant patients (Group C, median 14.2 months on dialysis) were compared with 33 healthy subjects (Group D). Resting blood flow, postocclusive hyperemia, venoarteriolar response on the right foot and decrease in blood flow during cold pressure test on the left finger was assessed. Postocclusive hyperemia, decrease in blood flow during cold pressure test and venoarteriolar response were higher in Group D than in all patient groups. Resting blood flow in Group A was significantly lower than in Groups B and C (following values as median): 3.6 perfusion units (PU) versus 7.4 PU in Group B, p < 0.01 and 12.1 PU in Group C, p < 0.001, respectively, and was not significantly different to controls (Group D, 5.2 PU). Postocclusive hyperemia was higher in Group A than in Groups B and C (266.7% vs 160.0%, p < 0.05 and 79.4% n.s., respectively), but significantly less than in Group D (563.5%). The microangiopathy index-high values reflecting less or no microangiopathy-was significantly higher in Group A than in Groups B and C (11.0 vs 4.3, p < 0.001 and 4.7, p < 0.05, respectively), and was very much comparable to the values in healthy controls (Group D, 10,3). The decrease in blood flow during cold pressure test was higher in Group A compared to Groups B and C (25.2% vs 21.1% and 13.8%, n.s., respectively), but much less than in Group D (65,7%). These data suggest an improvement without complete normalization of skin microcirculation by long-term blood glucose normalization achieved by pancreas transplantation.

Effects of aging and type 2 diabetes on resting and post occlusive hyperemia of the forearm; the impact of rosiglitazone

BackgroundBoth Diabetes and ageing are associated with reduced vascular endothelial function. The exact relationship between the 2 and any improvements from the insulin sensitizer rosiglitazone have not been explored.MethodsThirty controls and sixteen subjects with type 2 diabetes participated in a series of experiments to examine the interrelationships between age, diabetes and endothelial cell function. In subjects with diabetes, the insulin sensitizer rosiglitazone (RSG), a drug also known to improve vascular function, was administered for 3 months to see how it altered these relationships. Resting forearm flows (RF) and blood flows after 4 min of vascular occlusion (PF) were measured as an index of endothelial cell function.ResultsRF, measured by venous occlusion plethysmography, was negatively correlated to both age and diabetes. Administration of RSG for 3 months was associated with an increase in the blood flow response to venous occlusion so that it was not significantly different than that of age matched controls. Total PF in control subjects, compared to subjects with diabetes, averaged 56.58 +/- 12.57 and 13.6 +/- 8.01 cc/100 cc tissue per min respectively, and were significantly different (p < 0.01). After 3 months on RSG, differences between PF in the two groups were no longer evident.ConclusionThese studies suggest a different mechanism causing a reduction in vascular reactivity with aging and diabetes.

Impaired microvascular function related to poor metabolic control in young patients with diabetes

The purpose of the present study was to identify whether young patients with type 1 diabetes using modern multiple insulin injection therapy (MIT) have signs of microvascular dysfunction and to elucidate possible correlations with various disease parameters. Skin blood flow on the dorsum of the foot was measured with laser Doppler perfusion imaging in 37 patients (age 10-21 years, disease duration 6.0-16 years) and 10 healthy controls. Measurements were performed at rest, after change in posture (the leg was lowered below heart level) and during postocclusive hyperaemia. Following a change in posture blood flow increased instead of decreased in a majority of the study subjects. Patients with acute HbA1c >7.5% (n = 22) had an increase in skin blood flow at rest and a significantly reduced blood flow when the leg was lowered below heart level as compared with patients with HbA1c <7.5% (0.26 V versus 0.17 V, P<0.01 and 0.12 V versus 0.23 V, P<0.05, respectively) and healthy controls. Following occlusion of the macrocirculation for 3 min a small non-significant decrease in the hyperaemic response was seen in the patients. The postocclusive hyperaemic response and the venoarteriolar reflex were not correlated to duration of disease, long-term metabolic control or electrophysiological signs of peripheral nerve dysfunction. It is concluded that signs of microvascular dysfunction related to poor metabolic control are present in young patients with MIT treatment and rather well-controlled diabetes. Low resting blood flow levels are suggested to contribute to the absence of postural vasoconstrictor response.

Local hyperhemia to heating is impaired in secondary Raynaud's phenomenon

Accurate and sensitive measurement techniques are a key issue in the quantification of the microvascular and endothelial dysfunction in systemic sclerosis (SSc). Thermal hyperhemia comprises two separate mechanisms: an initial peak that is axon reflex mediated; and a sustained plateau phase that is nitric oxide dependent. The main objective of our study was to test whether thermal hyperhemia in patients with SSc differed from that in patients with primary Raynaud's phenomenon (RP) and healthy controls. In a first study, we enrolled 20 patients suffering from SSc, 20 patients with primary RP and 20 healthy volunteers. All subjects were in a fasting state. Post-occlusive hyperhemia, 0.4 mg sublingual nitroglycerin challenge and thermal hyperhemia were performed using laser Doppler flowmetry on the distal pad of the third left finger. In a second study, thermal hyperhemia was performed in 10 patients with rheumatoid arthritis and 10 patients with primary RP. The thermal hyperhemia was dramatically altered in terms of amplitude and kinetics in patients with SSc. Whereas 19 healthy volunteers and 18 patients with primary RP exhibited the classic response, including an initial peak within the first 10 minutes followed by a nadir and a second peak, this occurred only in four of the SSc patients (p < 0.0001). The 10 minutes thermal peak was 43.4 (23.2 to 63), 42.6 (31 to 80.7) and 27 (14.7 to 51.4) mV/mm Hg in the healthy volunteers, primary RP and SSc groups, respectively (p = 0.01), while the 44°C thermal peak was 43.1 (21.3 to 62.1), 42.6 (31.6 to 74.3) and 25.4 (15 to 52.4) mV/mm Hg, respectively (p = 0.01). Thermal hyperhemia was more sensitive and specific than post-occlusive hyperhemia for differentiating SSc from primary RP. In patients with rheumatoid arthritis, thermal hyperhemia was also altered in terms of amplitude. Thermal hyperhemia is dramatically altered in patients with secondary RP in comparison with subjects with primary RP. Further studies are required to determine the mechanisms of this altered response, and whether it may provide additional information in a clinical setting.

Post-occlusive reactive hyperemia in single nutritive capillaries of the nail fold: methodological considerations

Endothelial function at the arterial level has been extensively assessed by a noninvasive method using flow-mediated dilatation (FMD) of the brachial artery. Early disturbances have been found in patient groups prone to later development of manifest macrovascular atherosclerosis. A possible non-invasive means of studying blood-flow regulation and function at the microcirculatory level is through videophotometric capillaroscopy. The most stable variable in such an investigation is the time-to-peak (TtP) flow after a brief arterial occlusion. The short-term reproducibility of such assessments is excellent but the coefficient of variation (CV) in long-term studies is reported to be in the order of slightly less than 20%. The aim of the present methodological study was to evaluate different sources of variations in such microcirculatory assessments in order to be able to propose design recommendations that minimize the number of patients and recordings needed to achieve sufficient statistical power in longitudinal studies. We used a symmetric design with 144 recordings of TtP after a one-minute arterial occlusion in healthy volunteers. We did six occlusions each time in the capillaries of two fingers on each occasion, and repeated the procedure three times with an interval of at least one week between each investigation. All recordings were analyzed off-line using a cross-correlation technique with the Capiflow ® system. Each analysis was performed at least three times, giving a total of slightly less than 500 assessments. In our material (n= 10) TtP had a mean of 6.3 s (95% confidence interval 5.2 - 7.4). The correlation between repeated measurements in a single capillary during a single session was r>0.91 (CV 6%). The between-finger CV was 8% (r= 0.84). The CV of measurements between different days was about 20% when single measurements were compared. However, the CV decreased to less than 13% when the mean of at least two time-to-peak assessments on each occasion was used. In conclusion, the methodological error including day-to-day variation could be minimized using the mean of at least two repeated assessments of post-occlusive hyperemia at each time point in a longitudinal study. This finding should be taken into consideration in the design of future longitudinal studies.

Peripheral and Myocardial Microcirculation

HomeCirculationVol. 104, No. 18Peripheral and Myocardial Microcirculation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPeripheral and Myocardial Microcirculation Johann Auer, MD, Berent Robert, MD and Bernd Eber, MD Johann AuerJohann Auer Department of Cardiology and Intensive Care, General Hospital Wels, Wels, Austria Search for more papers by this author , Berent RobertBerent Robert Department of Cardiology and Intensive Care, General Hospital Wels, Wels, Austria Search for more papers by this author and Bernd EberBernd Eber Department of Cardiology and Intensive Care, General Hospital Wels, Wels, Austria Search for more papers by this author Originally published30 Oct 2001https://doi.org/10.1161/circ.104.18.e100Circulation. 2001;104:e100To The Editor:We do not agree with Bøttcher and colleagues1 when they conclude that the results of their study indicate “…different mechanisms of microvascular activation or regulation…” in coronary and brachial circulation.The assessment of endothelium-dependent and endothelium-independent vasomotor responses in systemic and coronary arteries has confirmed the association between vascular risk factors and endothelial dysfunction.2,3In their study, Bøttcher and colleagues1 used two completely different stimuli to induce hyperemia in coronary and brachial circulation. Coronary microvascular dysfunction was measured by the response to the vasoactive substance dipyridamole using positron emission tomography, and brachial artery vasoreactivity was assessed ultrasonographically by postocclusion hyperemia. The effects of these two stimuli on microvascular function are completely different.In the myocardium, the hyperemic response is mediated by the accumulation of adenosine and the stimulation of adenosine A2 receptors.4 Ischemia-induced accumulation of vasodilating metabolites is assumed to be responsible for the postocclusion hyperemia of the brachial artery.5No evidence is provided to conclude that the results of the study indicate different mechanisms controlling microvascular activation or regulation in peripheral and coronary circulation. In contrast, it would be appropriate to state that there is no correlation of vasomotor responses in the two vascular beds if assessed by these two methods. References 1 Bøttcher M, Madsen MM, Refsgaard J, et al. Peripheral flow response to transient arterial forearm occlusion does not reflect myocardial perfusion reserve. Circulation. 2001; 103: 1109–1114.CrossrefMedlineGoogle Scholar2 Pitkanen OP, Raitakari OT, Ronnemaa T, et al. Influence of cardiovascular risk status on coronary flow reserve in healthy young men. Am J Cardiol. 1997; 79: 1690–1692.CrossrefMedlineGoogle Scholar3 Pedrinelli R, Dell’Omo G, Gimelli A, et al. Myocardial and forearm blood flow reserve in mild-moderate essential hypertensive patients. J Hypertens. 1997; 15: 667–673.CrossrefMedlineGoogle Scholar4 Rump LC, Jabbari-T J, von Kugelgen I, et al. Adenosine mediates nitric-oxide-independent renal vasodilation by activation of A2A receptors. J Hypertens. 1999; 17: 1987–1993.CrossrefMedlineGoogle Scholar5 Leeson P, Thorne S, Donald A, et al. Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart. 1997; 78: 22–27.CrossrefMedlineGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponseBottcher Morten, , MD, PhD, Nielsen Torsten Toftegård, , MD, Madsen Mette M., , MD, Dørup Inge, , MD, Sørensen Keld, , MD, Refsgaard Jens, , MD, PhD, and Buus Niels Henrik, , MD, PhD30102001We thank Drs Auer, Robert, and Eber for their interest in our article. They raise important issues regarding the interpretation of our findings and particularly regarding our statement about different mechanisms controlling vasodilatation in the peripheral vessels and in the coronary circulation.We fully agree that our conclusions regarding the lack of correlation between the regulation of the coronary and peripheral circulation confine themselves to the two methods used. This was specifically the purpose of the study and is stated several times throughout the article. It is also stressed in the article that different mechanisms are in play during the two different stimulations, and the mechanisms are as correctly reiterated in the letter. We also agree with their comments regarding endothelial function, which seems to be related in the brachial and coronary circulation. This, however, was not the objective of our study.We certainly found that both the ultrasound-based evaluation of brachial artery flow and positron-emission tomography-based perfusion measurements in the myocardium are valuable tools in the investigation of cardiovascular disease. However, the ability to extrapolate between the two techniques needs to be kept in mind. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Huang H, Chu C, Tsai C, Wu C, Lai L, Yeh H and Bueno V (2014) Perfusion Index Derived from a Pulse Oximeter Can Detect Changes in Peripheral Microcirculation during Uretero-Renal-Scopy Stone Manipulation (URS-SM), PLoS ONE, 10.1371/journal.pone.0115743, 9:12, (e115743) October 30, 2001Vol 104, Issue 18 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.104.18.e100PMID: 11684647 Originally publishedOctober 30, 2001 PDF download Advertisement

Comparison of laser-Doppler flowmetry with biochemical indicators of endothelial dysfunction related to early microangiopathy in Type 1 diabetic patients

The aim of this study was to compare biochemical markers of endothelial activation with microcirculation measured by laser-Doppler flowmetry in Type 1 diabetic patients with or without microangiopathy. A total of 44 Type 1 diabetic patients were subdivided into those with ( n=24) and without ( n=20) microangiopathy according to ophthalmological findings and the presence or absence of microalbuminuria. The control group consisted of 25 healthy people of comparable age, sex, and body mass index. Postocclusive reactive hyperemia (PORH) and thermal hyperemia (TH, at 44°C) were measured at the forearm. Serum N-acetyl-β-glucosaminidase (NAG) activity, serum E-selectin, and ICAM-1 concentrations were used as biochemical markers of endothelial dysfunction. A significantly lower velocity of perfusion increase during postocclusive hyperemia (PORH max· t 1 −1) and during thermal hyperemia (TH max· t 2 −1) ( P<.01) were accompanied by higher serum NAG activity (20.9±4.6 vs. 16.3±2.5 U l −1, P<.01) in diabetic patients with microangiopathy as compared to healthy persons. An inverse relationship was found between PORH max· t 1 −1 and NAG ( r=−.33) results in diabetic patients. In addition, higher mean values of serum NAG activity, E-selectin, and ICAM-1 concentrations were associated with significantly lower values of microcirculation parameters (PORH max· t 2 −1 and TH max· t 2 −1) in six patients without microangiopathy who had at least one of the above biochemical markers higher than mean+2 S.D. range. We suggest that serum NAG activity, E-selectin, and ICAM-1 concentrations may be used together with laser-Doppler flowmetry in Type 1 diabetic patients as early indicators of vascular changes in very early stage of diabetic microangiopathy.

Acute effects of oats and vitamin E on endothelial responses to ingested fat

Objective: To assess the effects of oats and vitamin E on endothelial function following a high-fat meal in healthy adults as measured by brachial artery reactivity studies (BARS). Methods: A total of 25 men and 25 women (N=50) were recruited from a community population to participate in this randomized, crossover study. All subjects were free of known vascular disease, and female subjects were postmenopausal. Subjects underwent BARS before and after a high-fat meal (50 gm fat) on three occasions 1 week apart, one each with vitamin E 800 IU, oatmeal containing 3 gm β-glucan, or a comparable bowl of wheat cereal serving as a placebo, in random sequence. The ultrasonographer was blinded to treatment status. Results: Endothelial function, as measured by brachial artery peak flow during one minute of post-occlusive hyperemia, declined significantly from baseline when the high-fat meal was consumed with the wheat cereal (−13.4%; p=0.02). There was no difference in brachial artery flow change before and after a high-fat meal with oats (+0.37%; p=0.77) or a high-fat meal with vitamin E (+1.87%; p=0.42). No significant differences in flow-mediated vasodilation before and after the high-fat meal were detected among the three supplements. Conclusions: Endothelial dysfunction induced by acute fat ingestion in healthy adults is apparently prevented by concomitant ingestion of oats or vitamin E, but not wheat. Nutrient distribution and meal composition may have important implications for cardiovascular health.

Quantification of area at risk during coronary occlusion and reperfusion by means of MR perfusion imaging.

Considerable clinical interest has focused on the size of ischemic myocardium. Fast MR imaging in conjunction with MR contrast media has the potential to identify hypoperfused and infarcted myocardium. This study used MR perfusion imaging to detect and quantify reperfused ischemic myocardium during a brief coronary occlusion and reperfusion, and to characterize the spatial extent of ischemic and reperfused ischemic myocardium relative to the "true" size of the area at risk as defined in histochemical morphometry at post mortem. The left circumflex (LCX) coronary artery in 8 dogs was occluded for 15 min followed by reperfusion in order to produce regional reversible myocardial ischemia. Perivascular Doppler probes were used to measure blood flow in the left anterior descending (LAD) and LCX coronary arteries. Fast inversion recovery-prepared gradient-recalled-echo images were acquired to delineate the ischemic area during occlusion, and the area of reversible ischemic injury at 1 and 30 min of reperfusion. The size of ischemic and reperfused ischemic myocardium were compared with the area at risk as determined by histochemical morphometry at post mortem. During LCX occlusion, LCX flow decreased from 16+/-1 to 0.2+/-0.1 ml/min. On contrast-enhanced images, ischemic myocardium was evident as a zone of relatively low signal intensity (SI) compared to normal myocardium. The size of the ischemic region was significantly smaller (30+/-2%) than at post mortem (36+/-3%; p<0.05). Immediately after reperfusion, LCX flow increased to 83+/-11 ml/min and the contrast medium caused greater enhancement in the reperfused ischemic region than in the normal myocardium (69+/-3 vs 42+/-3 arbitrary units; p<0.05). The increase in regional SI correlated closely with the increase in regional blood flow (r=0.73). At 1 min of reperfusion, the size of the reperfused ischemic myocardium was larger (48+/-3%, p<0.05) than the area at risk measured at post mortem. At 30 min of reperfusion, when the flow returned to baseline values (16+/-2 ml/min), contrast bolus produced no differential enhancement between the 2 myocardial territories. MR perfusion imaging has the potential to detect and quantify the size of ischemic myocardium and the region of post-occlusive hyperemia in the early reperfusion period. There is a significant direct linear relationship between the regional contrast enhancement of reperfused ischemic myocardium and the blood flow during post-occlusive hyperemia. The difference in the size of the area at risk at MR perfusion imaging and at histochemical morphometry may reflect an influence of coronary collateral circulation.

Dilatation of saphenous vein grafts by nitric oxide

To investigate firstly whether flow-dependent vasodilation is maintained in vein grafts, and secondly whether nitric oxide donors dilate vein grafts to improve the flow through graft stenoses. The vasodilatation of mature patent vein grafts, in response to reactive hyperaemia and glyceryl trinitrate (GTN), was assessed by the change in external diameter using duplex ultrasonography. The severity (ratio of proximal systolic velocity, V1, to peak systolic velocity at the stenosis, V2, of vein graft stenoses was determined by duplex ultrasonography before and after 24 h of local application of GTN patches. In post-occlusion hyperaemia the diameter of patent distal vein grafts (n = 7) increased to a maximum of 112 +/- 1.9% of resting diameter after 2 min, p = 0.026. The diameter increased further to 117 +/- 2.5% of the resting value 5 min after oral GTN (n = 5), p = 0.007. The velocity ratio, V2/V1, through graft stenoses (n = 6) decreased by 20 +/- 5% after application of GTN patches, principally as a result of reduction in V2, mean difference 0.8, p = 0.15. The changes in response to GTN were more evident for proximal than distal vein graft stenoses. Flow-induced vasodilatation responses, which have been attributed to the endothelial release of nitric oxide, are maintained in patent vein grafts: the grafts dilate even further in response to GTN. The application of GTN patches close to a vein graft stenoses appears to reduce the velocity ratio through vein graft stenoses. GTN patches might be used to reduce the risk of graft occlusion when there is a delay between the detection and the treatment of haemodynamically significant graft stenoses.

Experimental off-pump grafting of a circumflex branch via sternotomy using a suction device

We have shown previously in the pig that coronary artery bypass grafting on the beating heart may be facilitated by local cardiac wall immobilization by a suction device ("Octopus") applied to the anterolateral side of the heart. The purpose of this study was to investigate the feasibility of the method on the posterolateral side. In a consecutive series of 8 pigs, after median sternotomy, the posterior wall was taken hold of by the Octopus and subsequently brought up anteriorly and immobilized while hemodynamics were monitored. A posterolateral branch of the circumflex artery was grafted with the left internal mammary artery. After the coronary artery was ligated proximally, the heart was repositioned. At 6 weeks, bypass graft angiography and functional testing (postocclusion hyperemia testing) were performed. After sacrifice, histologic examination of the anastomosis was performed. Dislocation of the heart to expose the distal anastomosis site caused a minor drop in mean arterial blood pressure from 71 +/- 14 (baseline) to 63 +/- 6 mm Hg (dislocated) (not significant) and recovery to 70 +/- 12 mm Hg, 15 minutes after repositioning. Cardiac output decreased from 4.0 +/- 1.0 to 3.2 +/- 0.7 L/min (p = 0.02) and recovered to 4.3 +/- 0.3 L/min. No inotropic drugs were necessary. Anastomosing required 21.5 +/- 6.5 minutes. Baseline graft flow was 8 +/- 3 mL/min and increased threefold to 24 +/- 10 mL/min (p < 0.05) at postocclusive hyperemia testing. At sacrifice after 6 weeks (n = 8), graft flow increased fourfold from 5 +/- 2 to 20 +/- 8 mL/min (p = 0.002) (n = 7). At histologic examination all eight anastomoses were patent without stenosis or mural thrombus. Off-pump coronary artery bypass grafting of the posterolateral circumflex branches using the Octopus method on the beating pig heart is feasible, with full patency maintained for at least 6 weeks.

Endotoxin-induced inhibition of mesenteric vasodilator responses to acetylcholine, bradykinin, and post-occlusion hyperemia in anesthetized rats.

The effects of endotoxin (20 mg kg-1 i.p.) on the mesenteric vascular responses to acetylcholine, bradykinin, sodium nitroprusside, and to transient occlusion of the superior mesenteric artery were examined in rats anesthetized with pentobarbitone. Mesenteric vasodilator responses to close arterial injections of acetylcholine and bradykinin were reduced at 1.5 h after endotoxin and almost abolished by 4 h; responses to sodium nitroprusside were unaffected. Occlusion of the superior mesenteric artery for 30, 60, or 120 s produced, on release of the occlusion, a time-dependent vasodilator response in the mesenteric circulation (post-occlusion hyperemia). This hyperemia was markedly reduced by nitro-L-arginine methyl ester (L-NAME); L-NAME did not modify acetylcholine-induced vasodilation. Endotoxin-pretreatment did not modify mesenteric post-occlusion hyperemia 1.5 h after administration but markedly reduced the response by 2.5 h. The administration of L-NAME to endotoxin-treated rats did not further attenuate the hyperemic responses. Mesenteric vasoconstrictor responses to phenylephrine were not modified by endotoxin, although systemic pressor responses to this agent were impaired. We concluded that endotoxin impairs endothelium and nitric oxide-dependent vasodilator responses in the mesenteric circulation.

Contribution of Cerebrovascular Parasympathetic and Sensory Innervation to the Short-Term Control of Blood Flow in Rat Cerebral Cortex

In two groups of normotensive rats anaesthetised with halothane, either the nasociliary nerve (NCN) or the NCN and parasympathetic (PS) fibres together (NCN-PS) were functionally blocked at the right ethmoidal foramen. Blocking was achieved reversibly and repeatedly using a cooling probe. Cortical regional CBF (rCBF) was measured bilaterally using laser-Doppler probes. In Group 1, bilateral common carotid occlusion (CCO) was applied for 1 min both with and without block. In Group 2, CCO was applied permanently followed by stages of controlled haemorrhagic hypotension to deepen the ischaemia and the block applied at each stage. In Group 1, during CCO, rCBF was unaffected by blocking NCN-PS. However, during the transient postocclusive hyperaemia, blocking NCN-PS, but not NCN alone, significantly increased right side rCBF. In Group 2 and in Group 1 in the absence of CCO (normotension), rCBF was unaffected by blocking either set of fibres. We conclude that neither NCN nor PS fibres contribute to the tonic level of rCBF or to its autoregulatory control, but PS fibres conduct impulses tending to resolve postischaemic hyperaemia. We suggest that a subpopulation of PS fibres containing neuropeptide Y is activated under conditions of supernormal rCBF.

Neurogenic flare responses are heterogeneous in superficial and deep layers of human skin

Infrared thermography and video image analysis were used to compare the development of the neurogenic flare response in deep and superficial skin layers. Neurogenic vasodilatation was induced by injection or iontophoretic application of histamine. Thermograms were recorded every 10 s to evaluate the local warming reaction. Color-video image analysis was used for computerized delineation of the visible flare. Images derived from video analysis were superimposed to the thermograms after linear transformation. The thermal reaction started within 10 s simultaneously at 2–5 distinct spots after histamine application at distances of 4–25 mm from the application site while the flare reaction seemed to spread from the application site when it became visible after a delay often exceeding 20 s. The visible flare but not the warming reaction was suppressed by topically applied local anesthetic (EMLA®). Warming at focal spots was also observed during post-occlusive hyperemia. About 70% of these spots were identical to those activated by histamine. The results indicate that the vascular axon reflex is differently organized in different layers of the skin.

Reactive hyperemia of skin microcirculation in septic neonates.

Reactive hyperemia after 1 min of arterial occlusion was studied in back, thigh and heel skin of 40 preterm and full-term neonates using laser Doppler flowmetry. Twelve infants had clinical signs of septicemia, but normal laboratory tests at the time of fluxmetry. However, CRP, leukocyte count and the ratio of immature to total neutrophils increased during the following days and septicemia was confirmed by positive blood cultures (septic group). Seven neonates with clinical signs of septicemia had developed neither positive blood cultures nor laboratory signs (non-septic group). Fifteen were healthy neonates. In the septic neonates, time to reach maximal hyperemia, maximum post-occlusive hyperemia and recovery time of skin perfusion were increased significantly in back and thigh skin and the heal skin temperature was decreased when compared to healthy neonates. Healthy and non-septic neonates showed no significant difference in any of the parameters. We conclude that altered reactive hyperemia in the skin may be an earlier sign of neonatal septicemia than laboratory tests.

Correlation between peripheral vascular resistance and time to peak flow during reactive hyperaemia

Earlier studies have proposed that the time to reach peak hyperaemic flux recorded with laser Doppler (tp) is a simple and accurate method of evaluating ischaemic limbs and possibly a method of estimating the peripheral vascular resistance (PR). The aim of this study was to investigate the relationship between the tp and changes in limb vascular resistance caused by arterial stenosis. Forty postocclusive hyperaemia tests with arterial stenoses of different pressure gradients were performed in four pigs. A laser Doppler fluxmeter was used to record postocclusive hyperaemia in the skin of one hind limb. A specially designed tourniquet was used for the arterial occlusion. Proximal and distal to the occlusion level a snare was used to form different grades of stenosis. The PR (mmHg.ml-1.min-1) was either estimated by infusion of a known blood volume into the tested limb over a given time period with simultaneous measurement of pressure or calculated on the basis of measurements of limb blood flow and blood pressure gradients. The tp was closely related to total limb vascular resistance assessed by the blood infusion method (r = 0.83, p < 0.0003) and to the resistance calculated from volume blood flow and intraarterial pressures (r = 0.86, p < 0.0001). This study suggests that the tp accurately reflects limb vascular resistance in an experimental model. Thus tp may be used as a quantitative indicator of overall blood flow impairment, and should be evaluated in patients with lower-limb atherosclerosis.

A corticosteroid, a non-steroidal anti-inflammatory drug and an antihistamine modulate in vivo vascular reactions before and during post-occlusive hyperaemia

Post-occlusive reactive hyperaemia is the temporary increase of blood flow in a tissue following transient vascular obstruction, and has recently been proposed as an in vivo method for ranking topical corticosteroid potency. We investigated in vivo vascular reactions before and during post-occlusive hyperaemia using laser-Doppler flowmetry and reflectance spectroscopy (RS). RS enables resolution of in vivo erythema into deoxygenated (venous) [DOH] and oxygenated (arterial) haemoglobin (OH) components (expressed in arbitrary units, AU). Using a randomized 24-h occlusive exposure in 10 healthy volunteers the effects of a corticosteroid (betamethasone-17-valerate), a non-steroidal anti-inflammatory drug (NSAID) [indomethacin], an antihistamine (diphenhydramine), or vehicle, were studied before and during post-occlusive hyperaemia. The 24-h vehicle exposure decreased total haemoglobin (composed of a small increase in OH [P < 0.001] and a greater decrease in DOH [P < 0.005], [OH, 0.23 +/- 0.18 AU; DOH, 0.28 +/- 0.12 AU]). The blood flow increased 7.1% to 28 +/- 8 AU (P > 0.05). Betamethasone-17-valerate exposure decreased total haemoglobin further (OH, 0.10 +/- 0.09 AU [P < 0.005]; DOH, 0.18 +/- 0.08 AU [P < 0.05]), which corresponded to a 15% blood flow decrease (P < 0.05). Indomethacin reduced OH to 0.18 +/- 0.12 AU (P < 0.02) and increased DOH slightly, with a trend towards decreased blood flow (P > 0.05). Diphenhydramine caused no significant changes in RS or laser-Doppler flowmetry readings before post-occlusive hyperaemia. Post-occlusive hyperaemia increased total haemoglobin maximally at the first observation time (OH, 0.63 +/- 0.13 AU; DOH, 0.31 +/- 0.11 AU [P < 0.001]).(ABSTRACT TRUNCATED AT 250 WORDS)

Pial vessel caliber and cerebral blood flow become dissociated during ischemia-reperfusion in cats

The relationship between pial arteriolar caliber and cerebral blood flow (CBF) was examined in 11 cats subjected to reperfusion for up to 120 min after 10 min of global cerebral ischemia induced by four-vessel occlusion and systemic hypotension. Thirty minutes after reperfusion CBF, as assessed by radiolabeled microsphere injection, had increased to 588% of control in middle cerebral artery (MSEC) cortical gray matter territory. The caliber of MSEC pial arterioles measured using the closed cranial window technique (greater than 33 to less than 213 microns) increased to 172% of baseline. By 60 min of reperfusion, CBF was 76% of basal levels, but pial arterioles remained 133% of baseline. After 120 min, CBF approximated baseline values, but pial dilatation persisted (115% of control). Intracranial pressure measurements did not differ significantly from resting values. At 45 min and beyond, total cerebrovascular resistance did not differ from resting values. The coexistence of vasodilatation within pial arterioles and normal blood flow in cortical gray matter indicates that pial vessels (greater than 33 microns) cannot be responsible for normal blood flow restoration following postocclusive hyperemia. Resistance during the posthyperemic phase must be increased selectively within parenchymal vessels to account for normal total cerebrovascular resistance, pial vessel dilatation, and normal-low parenchymal blood flow. Whether obstruction rather than vasoconstriction explains the resistance changes within intraparenchymal vessels remains for further study.

Capsaicin-sensitive nerves modulate reactive hyperemia in rat gut.

Reactive hyperemia (RH) is a local, vascular response that occurs following release from mechanical occlusion of an artery, with restoration of intra-arterial pressure. The mechanism of this postocclusion hyperemia in the gut has not been identified, although metabolic, myogenic, and neurogenic mediators of this response have been proposed. The present study was conducted to evaluate a possible modulatory role for sensory innervation of the intestinal vasculature in RH, using acute and chronic treatment with capsaicin applied in different ways. In anesthetized rats, the velocity of flowing blood in the gut was determined continuously with a pulsed Doppler velocimeter, and arterial pressure was determined with a transducer. The increase in calculated intestinal vascular conductance at the height of RH (Ch), the excess volume of blood accumulating during RH, and the duration of the hyperemia were also used to quantify RH after occluding the anterior mesenteric artery for 30, 60, and 120 sec. In the initial control group of rats, the maximal increases in the velocity of flowing blood during RH were 61 +/- 4%, 90 +/- 7%, and 129 +/- 10% of control, conductances were increased to 192 +/- 5%, 222 +/- 12%, and 267 +/- 15% of control, volumes were 3.5 +/- 0.6 ml, 7.2 +/- 0.4 ml, and 16.2 +/- 1.8 ml, and durations of hyperemia were 78 +/- 5 sec, 93 +/- 6 sec, and 178 +/- 7 sec, respectively, after each elapsed period of occlusion. Acute treatment with periarterial capsaicin significantly decreased peak conductances in RH by 15-35% for all occlusions tested and reduced both volume and duration values. Rats treated with capsaicin in neonatal life exhibited reduced Ch values, as did adult rats treated chronically with capsaicin. Both periarterial and intrajejunal treatment with capsaicin decreased the duration of RH. Hexamethonium increased both Ch and the duration of RH and tended to reverse reductions in these parameters caused by capsaicin. These results suggest that sensory innervation of the intestinal vasculature exerts a modulatory influence in the regulation of intestinal RH.