Regulation Of Microvascular Perfusion Research Articles

Changes in microvascular perfusion of heart and skeletal muscle in sheep around the time of birth.

What is the central question of this study? How does the microvascular perfusion of striated muscle change during the dynamic developmental period between the late gestation fetus and early neonate? What is the main finding and its importance? In both myocardium and skeletal muscle, perfusion of striated muscle is significantly reduced in the neonate compared to the late term fetus, but flow reserve is unchanged. The results suggest striated muscle capillary networks grow more slowly relative to the myofibres they nourish during the perinatal period. Microvascular perfusion of striated muscle is an important determinant of health throughout life. Birth is a transition with profound effects on the growth and function of striated muscle, but the regulation of microvascular perfusion around this transition is poorly understood. We used contrast-enhanced ultrasound perfusion imaging (CEUS) to study the perfusion of left ventricular myocardium and hindlimb biceps femoris, which are populations of muscle with different degrees of change in pre- to postnatal workloads and different capacities for postnatal proliferative growth. We studied separate groups of lambs in late gestation (135days' gestational age; 92% of term) and shortly after birth (5days' postnatal age). We used CEUS to quantify baseline perfusion, perfusion during hyperaemia induced by adenosine infusion (myocardium) or electrically stimulated unloaded exercise (skeletal muscle), flow reserve and oxygen delivery. We found heart-to-body weight ratio was greater in neonates than fetuses. Microvascular volume and overall perfusion were lower in neonates than fetuses in both muscle groups at baseline and with hyperaemia. Flux rate differed with muscle group, with myocardial flux being faster in neonates than fetuses, but skeletal muscle flux being slower. Oxygen delivery to skeletal muscle at baseline was lower in neonates than fetuses, but was not significantly different in myocardium. Flow reserve was not different between ages. Given the significant somatic growth, and the transition from hyperplastic to hypertrophic myocyte growth occurring in the perinatal period, we postulate that the primary driver of lower neonatal striated muscle perfusion is faster growth of myofibres than their associated capillary networks.

Microcirculation and Hemorheology: points of interaction

Transport of respiratory gases and the entire spectrum of substances for the metabolism of cells is carried out by coordinated work of circulation and blood. The review considers the main theoretical and experimental studies on microcirculation and hemorheology with an emphasis on the mechanisms of their interrelation and on the influence of individual hemorheological characteristics on the regulation of microvascular tissue perfusion. The analysis of the leading microrheological characteristics of erythrocytes - deformability is performed, the signal molecular mechanisms associated with the change of this cell parameter are shown. Data on the role of erythrocytes in the regulation of arteriolar tonus and functional density of capillaries are given. The mechanism of this regulation by exocytosis with erythrocytes adenosine triphosphate (ATP) and its stimulation of nitric oxide synthesis by endothelial cells is discussed. The review performed a comprehensive analysis of the participation of major hemorheological characteristics in the regulation of microvascular perfusion, including the role of the optimal viscosity of whole blood and the viscosity of plasma for effective tissue perfusion and oxygenation.

Investigation of hemorheological parameters at the diagnosis and the follow-up of nutritional vitamin B12 deficient children

We aimed to investigate the effects of vitamin B12 deficiency on hemorheological parameters, and the changes in these parameters following vitamin B12 treatment. 33 patients (mean-age:7 ± 5.7 years) diagnosed as nutritional vitamin B12 deficiency, and 31 age and sex matched controls (mean-age:7.1 ± 5.2 years) were enrolled. Erythrocyte deformability and aggregation were determined by an ectacytometer, plasma and whole blood viscosities by a cone-plate rotational viscometer. The differences between patients and controls were compared. Hemorheological parameters were repeated in the patient group following vitamin B12 treatment, and the results were compared with the initial results. In vitamin B12 deficiency, erythrocyte deformability and whole blood viscosity were found to be significantly decreased, eythrocyte aggregation was found to be significantly increased compared with the controls. Plasma viscosity was found to be decreased in deficiency but this decrease was not statistically significant. In patient group, erythrocyte deformability, whole blood and plasma viscosities were found to be significantly increased and erythrocyte aggregation was significantly decreased, after treatment. This study indicates that vitamin B12 deficiency has important effects on hemorheological parameters and adequate treatment of deficiency not only corrects the hematological parameters, but also by helping to normalize the hemorheological parameters, may contribute to the regulation of microvascular perfusion.

Preclinical evaluation of the mitochondria‐targeted antioxidant MitoTEMPO on the renal microcirculation in a pediatric model of sepsis‐induced renal injury

Microcirculatory failure, mitochondrial dysfunction and oxidant generation are thought to be key events during sepsis that lead to multi-organ failure. Acute kidney injury is a leading cause of mortality in septic children. We developed a clinically relevant cecal ligation and puncture (CLP) sepsis model in rat pups 17-19 days old to identify and evaluate new therapeutic approaches. Analysis of the renal microcirculation using intravital video microscopy at 18 h post CLP or sham surgery showed a significant decrease in the percentage of continuously flowing capillaries (from 75% to 40%) and an increase in capillaries with no flow (from 5% to 30%). Microcirculatory failure was associated with a 2-fold increase in mitochondrial superoxide generation in renal tubules. We then performed dose-response studies to evaluate the effectiveness of the mitochondria-targeted antioxidant MitoTEMPO to reduce mitochondria superoxide and to improve renal microcirculation. MitoTEMPO was administered at doses of 1, 3, or 10 mg/kg (ip) at the time of CLP or sham surgery. Superoxide and perfusion were measured at 18 h. MitoTEMPO produced dose-dependent decreases in mitochondrial superoxide and increases in microcirculatory perfusion with 3 mg/kg being the lowest most efficacious dose to preserve the renal microcirculation. These findings suggest a previously unrecognized link between mitochondrial oxidants in the renal tubule epithelium and the regulation of microvascular perfusion. The protective effect of MitoTEMPO in the kidney suggests that agents like it should be evaluated further for their effectiveness at reducing sepsis-induced multi-organ failure. Supported by T32 GM106999 and AHA PRE20450050.

Acute Hyperglycemia Does Not Impair Microvascular Reactivity and Endothelial Function during Hyperinsulinemic Isoglycemic and Hyperglycemic Clamp in Type 1 Diabetic Patients

Aims. The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp. Patients and Methods. Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L−1). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry. Results. Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s−1, P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s−1, P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = −0.70, P = 0.007). Conclusion. Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.

Impact of Diabetes on Postinfarction Heart Failure and Left Ventricular Remodeling

Diabetes mellitus, the metabolic syndrome, and the underlying insulin resistance are increasingly associated with diastolic dysfunction and reduced stress tolerance. The poor prognosis associated with heart failure in patients with diabetes after myocardial infarction is likely attributable to many factors, important among which is the metabolic impact from insulin resistance and hyperglycemia on the regulation of microvascular perfusion and energy generation in the cardiac myocyte. This review summarizes epidemiologic, pathophysiologic, diagnostic, and therapeutic data related to diabetes and heart failure in acute myocardial infarction and discusses novel perceptions and strategies that hold promise for the future and deserve further investigation.

Last Word on Point:Counterpoint: There is/is not capillary recruitment in active skeletal muscle during exercise

TO THE EDITOR: The vigorous commentary on this debate underscores the importance of understanding muscle microvascular perfusion and its control.

Blockade of Kupffer cells by gadolinium chloride or dichloromethylene diphosphonate influences hepatic microcirculation after sepsis and haemorrhagic shock

Abstract Background The liver plays a key role in the host defence response after haemorrhagic shock–resuscitation (H/R) and sepsis. Kupffer cells (KCs) have been shown to be a trigger and motor of the subsequent inflammatory response syndrome. This may lead to hepatocellular dysfunction, microcirculatory alterations and liver injury involving, for example, tumour necrosis factor α, interleukin (IL) 1 and IL-6. In a double-blind study the effect of KC blockade with either gadolinium chloride or liposome-entrapped dichloromethylene diphosphonate (DMD) on hepatic microvascular flow after H/R and sepsis was investigated. Methods After pretreatment with intravenous gadolinium chloride 10 mg kg−1, DMD 1 mg kg−1 or saline 24 h before induction of shock, male Sprague-Dawley rats (n = 6–10 per group and time) were subjected to either haemorrhagic shock (mean arterial pressure 40 mmHg) for 60 min followed by resuscitation or lipopolysaccharide (LPS) 1 mg kg−1 intravenously. Microvascular flow was assessed by intravital microscopy of fluorescence-marked leucocytes in liver sinusoids at baseline, and 1, 6 and 12 h after shock induction. Results In saline groups, the mean(s.d.) leucocyte flow was significantly (P &amp;lt; 0·05) higher at 1 h (20 759(2901) μm3 s−1) and 6 h (16 278(2916) μm3 s−1) after H/R as well as at 6 h after LPS (17 661(3949) μm3 s−1) compared with the baseline value (13 509(1580) μm3 s−1). Animals pretreated with gadolinium chloride showed a significant flow increase compared with baseline (11 797(1124) μm3 s−1) at l h following H/R (26 269(5909) μm3 s−1). In DMD-pretreated animals leucocyte flow showed no significant change over time, following either H/R or LPS treatment. However, flow was significantly higher at baseline (18 054(998) μm3 s−1) versus gadolinium chloride and saline groups. In addition, DMD-treated animals showed higher flow values 1 h after LPS challenge (20 665(2337) μm3 s−1) compared with gadolinium chloride (13 110(1224) μm3 s−1) and saline (15 311(800) μm3 s−1) groups. Similarly, at 12 h after H/R the DMD group (21 782(1887) μm3 s−1) had higher flow values than the gadolinium chloride (14 026(1616) μm3 s−1) and saline (15 999(3175) μm3 s−1) groups. Conclusion These results imply a significant influence of KCs on regulation of microvascular perfusion in liver sinusoids under normal conditions as well as after H/R and sepsis. The data indicate differential pathways and effects of blocking KCs by gadolinium chloride and DMD.