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Introduction: This systematic review aims to summarize the existing evidence relating to preoperative anemia and clinical outcomes in peripheral vascular surgery patients. Methods: The following databases were searched—PubMed, COCHRANE, LILACS, and Science Research—from 1 January 2010 up to 8 May 2020, with the last search performed on 1 January 2021. An additional manual search for potential primary studies was conducted on major journals (e.g., Anesthesiology, the British Journal of Anesthesia and the European Journal of Anaesthesiology) and reference lists of included studies. Google Scholar was also checked for additional eligible studies. Reviewers independently screened potentially eligible articles and extracted data from included studies on populations, interventions, comparisons, and outcomes. This review was registered at PROSPERO as CRD 180954. Results: In total, 6 observational studies with a combined total of 87,327 participants were analyzed. Data collected in this review suggest that preoperative anemia, especially when hemoglobin is p < 0.0001), limb amputation (OR: 5.2; 95% CI 3.1–8.6, p < 0.0001), and death (p < 0.0031). Conclusions: These data suggest an association between preoperative anemia, blood transfusion requirements, and other adverse clinical outcomes among patients subjected to peripheral vascular interventions. However, further investigations, particularly randomized controlled trials, are warranted to better understand the association between preoperative anemia and patients’ prognosis.

The objective of this study was to investigate the role of the sympathetic nervous system (SNS) on hemodynamic, metabolic and microvascular alterations in a rat model of high-fat diet (HFD)-induced metabolic syndrome with salt supplementation. In total, forty adult male Wistar rats were fed normal chow (n=10) or a HFD (n=30) for 20 weeks. Thereafter, the HFD group received the centrally acting sympatho-modulatory drugs clonidine (0.1 mg/kg) or rilmenidine (1 mg/kg) or vehicle (n=10/group) orally by gavage. Functional capillary density (FCD) was evaluated using intravital video microscopy, and the structural capillary density (SCD) was evaluated using histochemical analysis. The pharmacological modulation of the SNS induced concomitant reductions in SBP, HR and plasma catecholamine levels. These effects were accompanied by a reversal of functional and structural capillary rarefaction in the skeletal muscle in both treated groups and an increase in SCD in the left ventricle only in the rilmenidine group. Improvement of the lipid profile and of glucose intolerance was also obtained only with rilmenidine treatment. Modulation of sympathetic overactivity results in the reversal of microvascular rarefaction in the skeletal muscle and left ventricle and improves metabolic parameters in an experimental model of metabolic syndrome in rats. This article is protected by copyright. All rights reserved.

Objective: We investigated the acute effects of SIM on cerebral microvascular rarefaction and dysfunction in SHRs. Methods: Male WKY and SHRs were divided into 4 groups of 8 animals each: WKY-CTL and SHR-CTL, treated with 0.9% saline; and WKY+SIM and SHR+SIM, treated with SIM (30 mg/kg/d) for 3 days by gavage. Cerebral FCD was assessed by intravital fluorescence videomicroscopy. mCBF before and after administration within the cranial window of angiotensin II (1 μmol L−1) was investigated using laser speckle contrast imaging. Results: Cerebral FCD was reduced in SHR-CTL compared to WKY-CTL (P < .05). SIM increased cerebral FCD in SHRs compared to SHR-CTL (P < .05). The mCBF was reduced in SHR-CTL compared to WKY-CTL (P < .05), and SIM increased mCBF compared with SHR-CTL (P < .05). Angiotensin II elicited a reduction of mCBF in SHR-CTL and increased mCBF in WKY-CTL (SHR-CTL -13.53 ± 2% vs WKY-CTL +13.74 ± 4%; P < .001), which was attenuated in SHRs treated with SIM (SHR+SIM -6.7 ± 1% vs SHR-CTL -13.53 ± 2%; P < .01). Conclusions: The antihypertensive effect of SIM is associated with an improvement in cerebral microvascular perfusion and capillary density that may help to prevent hypertension-induced cerebrovascular damage independent of cholesterol-lowering.

Cardiac microvascular rarefaction appears to be involved in hyperthyroidism-induced left ventricular hypertrophy and dysfunction. We investigated the effects of losartan, an AT1 receptor antagonist; diltiazem, a calcium channel blocker; and propranolol, a β-adrenergic receptor antagonist, on cardiac function and structural microcirculatory cardiac alterations in an experimental model of l-thyroxin-induced hyperthyroidism in rats. Hyperthyroidism (HYPER) was induced by intraperitoneal injections of l-thyroxin for 35 days (600 μg/kg/day; n = 32). The euthyroid group was treated with distilled water (EUT + VEH; n = 8). On the 14th day, the HYPER group was divided into four groups that received an oral treatment for 21 days with saline (HYPER + VEH; n = 8), losartan (10 mg/kg/day; HYPER + LOS, n = 8), diltiazem (10 mg/kg/day; HYPER + DILT, n = 8), or propranolol (10 mg/kg/day; HYPER + PROP, n = 8). An echocardiographic study was performed at baseline, at the beginning and at the end of the pharmacological treatment protocol (35th day). The structural capillary density in the left ventricle (LV) was analyzed using histochemical analysis with fluorescein isothiocyanate-conjugated Griffonia simplicifolia lectin. HYPER + VEH (182 ± 5 mmHg; P

Objective The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model. Methods Male Wistar rats (170–250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively. Results Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats. Conclusions Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations.

Objective To investigate microvascular alterations in an experimental model of metabolic syndrome induced by a high-fat diet (HFD) associated with salt supplementation (0.5% NaCl). Design and Methods Wistar Kyoto rats were fed standard chow (control group, CONT) or HFD for 20 weeks. The functional capillary density (FCD) was assessed using intravital fluorescence videomicroscopy. Results The HFD group presented a higher systolic blood pressure, plasma glucose and insulin levels, total and LDL-cholesterol levels, triglycerides, and visceral and epididymal fat when compared with the CONT group. When compared with the CONT group, the HFD group showed a lower FCD in the skeletal muscle (P 0.05). The HFD group also had a lower capillary-to-fiber ratio in the skeletal muscle (P < 0.01). The capillary volume density-to-fiber volume density ratio in the left ventricle of the HFD was also reduced (P < 0.01). Finally, rats fed with HFD showed ventricular hypertrophy and increased cardiomyocyte diameter (P < 0.01). Conclusions The long-term administration of a HFD associated with salt supplementation to rats generates an experimental model of metabolic syndrome characterized by central body fat deposition, insulin resistance, glucose intolerance, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, cardiac remodeling, and rarefaction of the microcirculation in the heart and skeletal muscle.

We examined the functional and structural microcirculatory alterations in the brain, skeletal muscle and myocardium of non-diabetic spontaneously hypertensive rats (SHR) and diabetic SHR (D-SHR), as well as the effects of long-term treatment with the angiotensin AT1-receptor antagonist olmesartan and the angiotensin-converting enzyme inhibitor enalapril. Diabetes was experimentally induced by a combination of a high-fat diet with a single low dose of streptozotocin (35 mg/kg, intraperitoneal injection). D-SHR were orally administered with olmesartan (5 mg/kg/day), enalapril (10 mg/kg/day) or vehicle for 28 days, and compared with vehicle-treated non-diabetic SHR or normotensive non-diabetic Wistar-Kyoto rats. The cerebral and skeletal muscle functional capillary density of pentobarbital-anesthetized rats was assessed using intravital fluorescence videomicroscopy. Chronic treatment with olmesartan or enalapril significantly lowered blood pressure and reversed brain functional capillary rarefaction. Brain oxidative stress was reduced to non-diabetic control levels in animals treated with olmesartan or enalapril. Histochemical analysis of the structural capillary density showed that both olmesartan and enalapril increased the capillary-to-fiber ratio in skeletal muscle and the capillary-to-fiber volume density in the left ventricle. Olmesartan and enalapril also prevented collagen deposition and the increase in cardiomyocyte diameter in the left ventricle. Our results suggest that the association between hypertension and diabetes results in microvascular alterations in the brain, skeletal muscle and myocardium that can be prevented by chronic blockade of the renin-angiotensin system.

— Aim: To compare the amount of cardioprotection induced by a single exercise session with those achieved after an 8-week aerobic exercise training following ischemia reperfusion injury in rats. Methods: Twenty-five male Wistar rats (250-300g) were assigned into a group submitted to physical training (TR; n=12) or a single maximal exercise session (EXE; n=13). Following sedentarism or physical training (8 weeks, 5 sessions/wk, 1h/session at 70% of maximal speed) both groups performed a maximal exercise test. Then, groups were submitted to ischemia reperfusion injury (30 min/1h) through an isolated heart protocol, in which left ventricle developed pressure was measured. Results: The TR group presented greater maximal oxygen consumption compared to the EXE group (77.25±20.41 vs 41.32±25.86 ml/Kg/min; P=0.003). Regarding left ventricle developed pressure, no differences were detected between groups at baseline (TR: 89.78±24.40 vs EXE: 81.37±31.84 mmHg; P=0.48). However, after reperfusion, the TR group presented superior intraventricular pressure than EXE group (37.94±18.34 vs 21.59±13.67 mmHg; P=0.03). Conclusion: Eight-week aerobic training induced greater cardioprotection against ischemia reperfusion injury in rats compared to a single exercise session, due to an increased cardiac function. This suggests that exercise-induced cardioprotection is a multifactorial process that may involve different mediators according to the exercise duration.

The ability of continuous aerobic exercise training (AET) to increase baroreflex control and cardiac function in heart failure (HF) has been well described, but the comparison between continuous and interval AET on these functions is inconclusive.To compare the effects of continuous and interval AET on cardiac function and baroreflex sensitivity (BrS) in an experimental model of HF.Rats were divided into the following groups: continuous training (HF-CT), intense interval training (HF-IIT), moderate interval training (HF-MIT), sedentary group (HF-SED), and sham sedentary (SHAM-SED). Animals underwent surgery to induce HF by ligation of the interventricular coronary artery. Six weeks after surgery, AET was started (8weeks, 3sessions/week). Echocardiography studies to assess cardiac function were performed before and after AET. At the end of the training protocols, the BrS index was assessed by stepwise intravenous infusions of sodium nitroprusside and phenylephrine.All methods of exercise prevented the HF-induced increase in left ventricular diameter in diastole observed in the HF-SED rats (0.88±0.09 vs. 1.03±0.09cm; P0.05), but only the HF-CT (28.5±6.3 vs. 39.2±12.7%; P0.05) and HF-MIT (31.0±8.5 vs. 42.0±10.3%; P0.05) groups exhibited an increase in ejection fraction. Nevertheless, the HF-CT group was the only group that showed a tachycardia reflex higher than that of the HF-SED group (0.87±0.34 vs. 0.20±0.05bpm/mmHg; P0.05) and similar to that of the SHAM-SED group (1.04±0.11bpm/mmHg).These results suggest that continuous and moderate interval training induced similar improvements in cardiac function but that only continuous training induced higher BrS in HF rats.

Obesity and metabolic syndrome are related to systemic functional microvascular alterations, including a significant reduction in microvessel density. The aim of this study was to investigate the effects of exercise training on functional capillary density in the skeletal muscle and skin of obese rats with metabolic syndrome.We used male Wistar-Kyoto rats that had been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks. Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and anthropometric parameters; and functional capillary density were assessed. In addition, a maximal exercise test was performed.Exercise training increased the VO2max (69 ± 3 mL/kg per min) and exercise tolerance (30 ± 1 min) compared with the HFD+SED (41 ± 6 mL/kg per min, P0.05 and 16 ± 1 min, P0.001) and with the CON (52 ± 7 mL/kg per min and 18 ± 1 min, P0.05) groups. The HFD+TR group also showed reduced retroperitoneal fat (0.03 ± 0.00 vs. 0.05 ± 0.00 gram/gram, P0.001), epididymal fat (0.01 ± 0.00 vs. 0.02 ± 0.00 gram/gram, P0.001), and systolic blood pressure (127 ± 2 vs. 150 ± 2 mmHg, P0.001). The HFD+TR group also demonstrated improved glucose tolerance, as evaluated by an intraperitoneal glucose tolerance test, fasting plasma glucose levels (5.0 ± 0.1 vs. 6.4 ± 0.2 mmol/L, P0.001) and fasting plasma insulin levels (26.5 ± 2.3 vs. 38.9 ± 3.7 μIU/mL, P0.05). Glucose tolerance did not differ between HFD+TR and CON groups. Exercise training also increased the number of spontaneously perfused capillaries in the skeletal muscle (252 ± 9 vs. 207 ± 9 capillaries/mm(2)) of the training group compared with that in the sedentary animals (260 ± 15 capillaries/mm(2)).These results demonstrate that exercise training reverses capillary rarefaction in our experimental model of metabolic syndrome and obesity.

Objectives To evaluate the effectiveness of single-point laser Doppler perfusion monitoring (LDPM) in the assessment of microvascular reactivity in the skin during cardiopulmonary bypass (CPB). Design Cross-sectional observational study. Setting Government-affiliated teaching hospital. Participants Twenty male patients aged 60±2 years who underwent coronary artery bypass grafting under CPB. Interventions The authors assessed the endothelium-dependent vasodilation of the skin microcirculation at the forehead and forearm using LDPM coupled with thermal hyperemia. This measurement was performed before and after the induction of anesthesia, during and after CPB, and 24 h after the end of the surgical procedure. Results The basal values of microvascular flow before the induction of anesthesia were significantly higher in the skin of the forehead compared with that of the forearm. There were no significant alterations in microvascular reactivity throughout the recording periods for both recording sites, as assessed by the vasodilation range expressed as cutaneous vascular conductance (arbitrary perfusion units/mean arterial pressure). Conclusions Using LDPM, the authors showed that the microcirculatory bed of the skin of the forehead, which is readily accessible during cardiac surgery, is a suitable model for the study of microvascular reactivity and tissue perfusion in cardiovascular surgical procedures using CPB. This technique could, thus, be suitable for evaluating the effects of drugs or technical procedures on tissue perfusion during cardiac surgery under cardiopulmonary bypass.

Background: Aerobic interval exercise training has greater benefits on cardiovascular function as compared with aerobic continuous exercise training. Objective: The present study aimed at analyzing the effects of both exercise modalities on acute and subacute hemodynamic responses of healthy rats. Methods: Thirty male rats were randomly assigned into three groups as follows: continuous exercise (CE, n = 10); interval exercise (IE, n = 10); and control (C, n = 10). Both IE and CE groups performed a 30-minute exercise session. The IE group session consisted of three successive 4-minute periods at 60% of maximal velocity (Max Vel), with 4-minute recovery intervals at 40% of Max Vel. The CE group ran continuously at 50% of Max Vel. Heart rate (HR), blood pressure(BP), and rate pressure product (RPP) were measured before, during and after the exercise session. Results: The CE and IE groups showed an increase in systolic BP and RPP during exercise as compared with the baseline values. After the end of exercise, the CE group showed a lower response of systolic BP and RPP as compared with the baseline values, while the IE group showed lower systolic BP and mean BP values. However, only the IE group had a lower response of HR and RPP during recovery. Conclusion: In healthy rats, one interval exercise session, as compared with continuous exercise, induced similar hemodynamic responses during exercise. However, during recovery, the interval exercise caused greater reductions in cardiac workload than the continuous exercise.

1. A previous study from our group demonstrated that neurones of the paraventricular nucleus of the hypothalamus (PVN) are selectively involved in the central control of the cardiac function. Moreover, in that study, it was shown that baclofen, a selective GABAB receptor agonist, is capable of modulating the increases in myocardial contractility and oxygen demand evoked by electrical or pharmacological stimulation of the PVN. Nevertheless, the acute administration of this compound was frequently accompanied by a cardiodepressant effect. 2. In the present study, the effects of a long term treatment (14 days) with baclofen (3 or 10 mg kg-1, i.p.) have been examined on the excitatory haemodynamic responses evoked by central pharmacological stimulation in anaesthetized rabbits. 3. The i.c.v. injection of L-glutamate (3 mg kg-1) induced marked increases in dP/dtmax (32%), mean arterial pressure (39%) and on two indices of myocardial oxygen consumption: the rate-pressure product (34%) and the triple product (78%). 4. Baclofen blunted the positive inotropic response and the increases in myocardial oxygen consumption induced by L-glutamate in a dose-related manner. The higher dose of baclofen (10 mg kg-1, i.p.), reduced by more than 50% these excitatory effects of L-glutamate without eliciting any significant negative effect on basal haemodynamics. The same doses of baclofen were not able to blunt the hypertensive response induced by central stimulation. 5. These results confirm and extend our previous findings suggesting that it is possible to discriminate the central control of vasomotor tone from that of cardiac function and also that baclofen can modulate the latter. It is concluded that when given chronically, baclofen modulates the increases in myocardial oxygen demand induced by activation of the central nervous system in doses which do not depress the resting cardiac function.

We investigated the effects of oral long-term antihypertensive treatment using centrally acting sympathoinhibitory drugs on capillary density in the skin, skeletal muscle, and heart in the spontaneously hypertensive rat (SHR). Wistar Kyoto rats (WKY) were used as normotensive control groups. Functional capillary density was assessed using intravital fluorescence videomicroscopy and structural capillary density with histochemical analysis. Groups of 10 SHRs were orally treated over 28 days with clonidine (0.1 mg x kg x d), rilmenidine (1 mg x kg x d), or moxonidine (10 mg x kg x d). A group of WKY was also treated with clonidine (0.1 mg x kg x d). Treatment with all antihypertensive drugs induced a normalization of arterial pressure accompanied by a reversion of functional capillary rarefaction in the skeletal muscle and skin of SHR. Clonidine treatment also reduced arterial pressure and increased functional capillary density in the skin and skeletal muscle of WKY. Histochemical analysis showed that SHR had a lower capillary to fiber ratio in the skeletal muscle (P < 0.0001), which was normalized by all treatments. The capillary volume density to fiber volume density ratio in the left ventricle of SHR was also significantly reduced (P < 0.0001). However, myocardial capillary rarefaction was not altered by the different treatments. In conclusion, the results showed that long-term antihypertensive treatment with centrally acting drugs enhanced tissue perfusion and reversed capillary rarefaction in the skeletal muscle of SHRs.

We investigated the effects of chronic oral antihypertensive treatment on functional and structural capillary rarefaction in spontaneously hypertensive rats (SHR). Wistar Kyoto rats (WKY) were used as a normotensive control group. In untreated rats, intravital videomicroscopy showed that functional capillary density was lower in SHR skeletal muscle (WKY 395 +/- 17 and SHR 258 +/- 13 capillaries/mm, P0.01) and ear skin (WKY 391 +/- 18 and SHR 210 +/- 15 capillaries/mm, P0.01). A linear relationship was seen between skeletal muscle and skin capillary densities (r = 0.654, P0.0001). Histologic analysis showed that SHR had a lower capillary-to-fiber ratio in the skeletal muscle (WKY 1.74 +/- 0.08 and SHR 1.40 +/- 0.06, P0.01). Capillary volume density-to-fiber volume density ratio in the left ventricle of SHR was also reduced (WKY 0.55 +/- 0.09 and SHR 0.42 +/- 0.09, P0.01). The animals were treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril, the angiotensin II type I receptor (AT1) receptor antagonist losartan, the beta-blocker atenolol, or the calcium channel blocker nifedipine, resulting in similar reductions in systolic blood pressure (19.8%, 19.1%, 17.4%, and 18.2%, respectively, P0.05). Atenolol did not induce any change in functional capillary density of SHR. Losartan and nifedipine completely reversed functional capillary rarefaction in both muscle and cutaneous tissues, whereas enalapril significantly increased functional capillary density only in the skin. The skeletal muscle capillary-to-fiber ratio was normalized by enalapril, losartan, and nifedipine. Treatments with enalapril or losartan normalized the cardiac structural capillary rarefaction of SHRs, whereas atenolol and nifedipine had no effect. Our results suggest that different pharmacologic classes of antihypertensive drugs with similar effect on blood pressure differ in terms of their effect on the microcirculation.

We investigated the vascular effects of a crude aqueous extract (AEEG) of Echinodorus grandiflorus (Alismataceae) using the in vitro experimental models of the rabbit isolated aorta and perfused kidney. Echinodorus grandiflorus, a native semi-aquatic plant widely distributed in Brazil, has been extensively used in Brazilian folk medicine for the treatment of high blood pressure and inflammatory diseases. The bolus injection of AEEG (0.1-10 mg) into the rabbit renal circulation pre-contracted with norepinephrine induced marked and dose-dependent vasodilator responses (maximum of 37+/-4%; n=6; P