Effects of short-term hyperoxia on sytemic hemodynamics, oxygen transport, and microcirculation: An observational study in patients with septic shock and healthy volunteers.

PURPOSE: To characterize the microvascular effects of a brief period of hyperoxia, in patients with septic shock and in healthy volunteers. MATERIALS AND METHODS: In 20 patients with septic shock, we assessed systemic hemodynamics, sublingual microcirculation by SDF-videomicroscopy, and skin perfusion by capillary refill time (CRT), central-peripheral temperature (ΔT°), and perfusion index. Measurements were performed at baseline and after 5 min of inspired oxygen fraction of 1.00. Additionally, we studied 8 healthy volunteers, in whom hyperoxia was prolonged to 30 min. RESULTS: In septic patients, hyperoxia increased mean arterial pressure and systemic vascular resistance, but cardiac output remained unchanged. The only significant change in sublingual microcirculation was a decreased heterogeneity flow index (1.03 [1.01-1.07] vs 1.01 [0.34-1.05], P = .002). Perfused vascular density (13.1 [12.0-15.0] vs 14.0 [12.2-14.8] mm/mm2, P = .21) and the other sublingual microvascular variables were unmodified. CRT and ΔT° did not change but perfusion index slightly decreased. In healthy volunteers, sublingual microcirculation and skin perfusion were stable. CONCLUSIONS: Short-term hyperoxia induced systemic cardiovascular changes but was not associated with noticeable derangement in sublingual microcirculation and skin perfusion. Nevertheless, longer exposures to hyperoxia might have produced different results.

Differences in control of parasympathetic vasodilation between submandibular and sublingual glands in the rat.

We examined blood flow in the submandibular gland (SMGBF) and sublingual gland (SLGBF) during electrical stimulation of the central cut end of the lingual nerve (LN) in the urethane-anesthetized rats using a laser speckle imaging flow meter. LN stimulation elicited intensity- and frequency-dependent SMGBF and SLGBF increases, and the magnitude of the SMGBF increase was higher than that of the SLGBF increase. The increase in both glands was significantly inhibited by intravenous administration of the autonomic cholinergic ganglion blocker hexamethonium. The antimuscarinic agent atropine markedly inhibited the SMGBF increase and partly inhibited the SLGBF increase. The atropine-resistant SLGBF increase was significantly inhibited by infusion of vasoactive intestinal peptide (VIP) receptor antagonist, although administration of VIP receptor antagonist alone had no effect. The recovery time to the basal blood flow level was shorter after LN stimulation than after administration of VIP. However, the recovery time after LN stimulation was significantly delayed by administration of atropine in a dose-dependent manner to the same level as after administration of VIP. Our results indicate that 1) LN stimulation elicits both a parasympathetic SMGBF increase mainly evoked by cholinergic fibers and a parasympathetic SLGBF increase evoked by cholinergic and noncholinergic fibers, and 2) VIP-ergic mechanisms are involved in the noncholinergic SLGBF increase and are activated when muscarinic mechanisms are deactivated.

Gut and sublingual microvascular effect of esmolol during septic shock in a porcine model.

INTRODUCTION: Esmolol may efficiently reduce heart rate (HR) and decrease mortality during septic shock. An improvement of microcirculation dissociated from its macrocirculatory effect may a role. The present study investigated the effect of esmolol on gut and sublingual microcirculation in a resuscitated piglet model of septic shock. METHODS: Fourteen piglets, anesthetized and mechanically ventilated, received a suspension of live Pseudomonas aeruginosa. They were randomly assigned to two groups: the esmolol (E) group received an infusion of esmolol, started at 7.5 µg⋅kg(-1)⋅min(-1), and progressively increased to achieve a HR below 90 beats⋅min(-1). The control (C) group received an infusion of Ringer's lactate solution. HR, mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), systemic vascular resistance (SVR), arterio-venous blood gas and lactate were recorded. Oxygen consumption (VO2), delivery (DO2) and peripheral extraction (O2ER) were computed. Following an ileostomy, a laser Doppler probe was applied on ileal mucosa to monitor gut microcirculatory laser Doppler flow (GMLDF). Videomicroscopy was also used on ileal mucosa and sublingual areas to evaluate mean flow index (MFI), heterogeneity, ratio of perfused villi and proportion of perfused vessels. Resuscitation maneuvers were performed following a defined algorithm. RESULTS: Bacterial infusion induced a significant alteration of the gut microcirculation with an increase in HR. Esmolol produced a significant time/group effect with a decrease in HR (P <0.004) and an increase in SVR (P <0.004). Time/group effect was not significant for CI and MAP, but there was a clear trend toward a decrease in CI and MAP in the E group. Time/group effect was not significant for SI, O2ER, DO2, VO2, GMLDF and lactate. A significant time/group effect of ileal microcirculation was found with a lower ileal villi perfusion (P <0.025) in the C group, and a trend toward a better MFI in the E group. No difference between both groups was found regarding microcirculatory parameters in the sublingual area. CONCLUSIONS: Esmolol provided a maintenance of microcirculation during sepsis despite its negative effects on macrocirculation. Some parameters even showed a trend toward an improvement of the microcirculation in the gut area in the esmolol group.

Impaired microcirculation predicts poor outcome of patients with acute myocardial infarction complicated by cardiogenic shock.

AIMS: we investigated the relationship between sublingual perfused capillary density (PCD) as a measure of tissue perfusion and outcome (i.e. occurrence of organ failure and mortality) in patients with cardiogenic shock from acute myocardial infarction. METHODS AND RESULTS: we performed a prospective study in 68 patients. Using Sidestream Dark Field imaging, PCD was measured after hospital admission (T0, baseline) and 24 h later (T1). We compared patients with baseline PCD ≤ median to patients with baseline PCD > median. Sequential organ failure assessment (SOFA) scores were calculated at both time points. The Kaplan-Meier 30-day survival analyses were performed and predictors of 30-day mortality were identified. The baseline PCD was a predictor of the change in the SOFA score between T0 and T1 (ΔSOFA; ρ = -0.25, P = 0.04). Organ failure recovered more frequently in patients with PCD > median (>10.3 mm mm(-2); n = 33) than in patients with PCD ≤ median (n = 35; 52 vs. 29%, P < 0.05). Twenty-two patients (32%) died: 17 patients (49%) with PCD ≤ median vs. 5 patients (15%) with PCD > median (P = 0.004). After adjustment, the cardiac power index [odds ratio (OR): 0.48, 95% CI: 0.24-0.94) and PCD (OR: 0.65, 95% CI: 0.45-0.92) remained significant predictors of 30-day outcome. Patients with baseline sublingual PCD ≤ median that improved at T1 had a considerable better prognosis relative to patients who had a persistently low PCD. CONCLUSION: diminished sublingual PCD, at baseline or following treatment, is associated with development of multi-organ failure and is a predictor of poor outcome in patients with acute myocardial infarction complicated by cardiogenic shock.

Acute microflow changes after stop and restart of intra-aortic balloon pump in cardiogenic shock.

BACKGROUND: The intra-aortic balloon counter pulsation (IABP) is the most frequently used method of mechanical cardiac support in cardiogenic shock (CS). Microcirculatory impairment correlates with outcome in critically ill patients. We therefore investigated the acute influence of IABP therapy on sublingual microflow in patients with CS. METHODS: Sidestream darkfield intravitalmicroscopy was used in 13 patients with severe CS. The sublingual microvascular bed (10-100 microm) was examined according to current guidelines. We measured microflow in means of microvascular flow index at baseline and after intentional stop of IABP support. A computerized model was used for blinded off-line analysis. RESULTS: Microflow in vessels 10-50 microm in diameter was improved during IABP support (P < 0.001). Norepinephrine had a negative effect on the response to IABP related microflow improvement. Cardiac Perfusion Index (product of Cardiac Power index and microflow) correlated best with blood lactate levels. CONCLUSIONS: It was the aim of this study to evaluate the acute influence of IABP therapy on microflow in vivo. In this setting we found that IABP therapy improves sublingual microflow. Future studies should investigate Cardiac Perfusion Index under such conditions with respect to clinical decision making.

[Evaluation of sublingual microcirculation in septic shock. Report of one patient treated with high volume hemofiltration]. / Evaluación de la microcirculación sublingual en un paciente en shock séptico refractario tratado con hemofiltración de alto volumen.

Microcirculation is severely compromised in sepsis, with a reduction of capillary density and flow impairment. These alterations have important prognostic implications, being more severe in non-survivors to septic shock. Today microcirculation may be assessed bedside, non-invasively using polarized light videomicroscopy a technique known as SDF (side dark field). We report a 54 year-old man with an extramembranous nephropathy that developed a necrotizing fasciitis associated to septic shock, in whom microcirculation was periodically assessed during his management. The patient was treated with fluids, vasoactive drugs, antibiotics and was operated for exploration and debridement. As the patient persisted in refractory shock despite treatment, high-volume hemofiltration was started. Before hemofiltration the patient had severe microcirculatory alterations that improved during and after the procedure. Physiologic endpoints of high-volume hemofiltration in septic shock remain unknown, but it has the capacity to clear inflammatory mediators. Since microcirculatory alterations are in part secondary to these mediators, their removal is beneficial. Like other authors, we found no relation between microcirculation and other haemodynamic and perfusion variables.

Evaluación de la microcirculación sublingual en un paciente en shock séptico refractario tratado con hemofiltración de alto volumen / Evaluation of sublingual microcirculation in septic shock: report of one patient treated with high volume hemofiltration

Microcirculation is severely compromised in sepsis, with a reduction of capillary density and flow impairment. These alterations have important prognostic implications, being more severe in non-survivors to septic shock. Today microcirculation may be assessed bedside, non-invasively usingpolarized light videomicroscopy a technique known as SDF (side dark field). We report a 54 year-old man with an extramembranous nephropathy that developed a necrotizing fascitis associated to septic shock, in whom microcirculation was periodically assessed during his management. The patient was treated with Buids, vasoactive drugs, antibiotics and was operated for exploration and debridement. As the patient persisted in refractory shock despite treatment, high-volume hemofiltration was started. Before hemofiltration the patient had severe microcirculatory alterations that improved during and after the procedure. Physiologic endpoints of high-volume hemofiltration in septic shock remain unknown, but it has the capacity to clear inflammatory mediators. Since microcirculatory alterations are in part secondary to these mediators, their removal is beneficial. Like other authors, we found no relation between microcirculation and other haemodynamic and perfusion variables.

Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia.

OBJECTIVE: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. DESIGN: Controlled experimental study. SETTING: University-based research laboratory. SUBJECTS: A total of 14 anesthetized, mechanically ventilated sheep. INTERVENTIONS: Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 microg/kg endotoxin, followed by 4 microg x kg(-1) x hr(-1) for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. MEASUREMENTS AND MAIN RESULTS: Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 +/- 10 vs. 51 +/- 20 mm Hg, 145 +/- 30 vs. 90 +/- 30 mL x min(-1) x kg(-1), and 643 +/- 203 vs. 317 +/- 93 mL x min(-1) x kg(-1), respectively; p < .05 vs. basal), whereas it increased intramucosal-arterial PCO2 (deltaPCO2) and arterial lactate (3 +/- 3 vs. 14 +/- 8 mm Hg, and 1.5 +/- 0.5 vs. 3.7 +/- 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 98% +/- 3% vs. 76% +/- 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 +/- 13 mm Hg), cardiac output (165 +/- 32 mL x min(-1) x kg(-1)), superior mesenteric artery blood flow (683 +/- 192 mL x min(-1) x kg(-1)), and sublingual and serosal intestinal microvascular flow indexes (2.8 +/- 0.5 and 3.5 +/- 0.7). Nevertheless, deltaPCO2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 +/- 6 mm Hg, 3.7 +/- 0.9 mmol/L, 2.3 +/- 0.4, and 78% +/- 11%; p < .05). CONCLUSIONS: In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion.

Objective assessment of blood stasis using computerized inspection of sublingual veins.

In traditional Chinese tongue diagnosis, inspection of the sublingual veins has been developed as a new diagnostic examination method especially for determining blood stasis. The main purpose of this research is to develop a computerized inspection system, used to quantitatively extract the chromatic and geometrical properties of sublingual veins. A method based on color equalization is presented to assist the image segmentation of sublingual veins. Color image analysis techniques are applied to extract the length, width, area and color information from sublingual veins. Experimental results are compared with the visual inspection of physicians. The severity of blood stasis was classified into three groups: normal, moderate and pronounced. Each group consisted of eight subjects. The overall recognition rate is 87.5% in the leaving-one-out classification using the developed system.

Disorder of salivary secretion in inbred polydipsic mouse.

To find mechanisms of an extreme polydipsia in an inbred strain of mice, STR/N, this study was undertaken using Institute of Cancer Research (ICR) mice as a control. During food deprivation, daily water intake of both strains decreased. The decrement in the STR/N mice was larger than that in the ICR mice. During dehydration, daily food intake of the STR/N mice was smaller than that of the ICR mice. These data indicate that prandial drinking was more severely affected for the STR/N mice. Under anesthesia, the stimulated salivary secretion by pilocarpine of the STR/N mice was significantly smaller than that of the ICR mice. The submandibular gland of the STR/N mice was lighter and harder than that of the ICR mice. After desalivation from the major three salivary glands, the ICR mice drank as much as the STR/N mice. Young STR/N mice with undeveloped polydipsia did not show different salivary secretion stimulated by pilocarpine from the young ICR mice. These findings indicate a dysfunction with age in the salivary glands of the STR/N mice, and they suggest that the decreased saliva induces thirst and triggers extraordinary drinking in the polydipsic mice.

Vascular changes in major and lingual minor salivary glands in primary Sjögren's syndrome.

A histological investigation of the vascular changes of three major and lingual minor salivary glands in primary Sjögren's syndrome was carried out on eight autopsied Japanese patients. This study compares vascular lesions in salivary glands between one group of four short-term corticosteroid-treated patients (Cases 1, 3, 4 and 7) and the other group of four long-term corticosteroid-treated patients (Cases 2, 5, 6 and 8). We proposed the following five stages for morphogenesis of arteritis; (1) endothelial swelling, (2) thrombosis, (3) fibrinoid degeneration, (4) necrotizing panarteritis and (5) endarteritis obliterans. Endothelial swelling was seen in small-to-large arteries of major salivary glands and the tongue, and this finding was considered as the initial change of vascular lesion. Thrombosis was observed in the small arteries of both organs. Fibrinoid degeneration and necrotizing panarteritis were predominantly localized in small and middle-sized arteries. Endarteritis obliterans was observed in small and large arteries of major and lingual minor salivary glands in primary Sjögren's syndrome. Vascular lesion of this type was common in the four patients who received corticosteroid for more than 12 months. Corticosteroid therapy appears to accelerate the fibrotic change of the vascular wall. Therefore, we suggest that essential vascular lesions of major and lingual minor salivary glands in primary Sjögren's syndrome may include four types (endothelial swelling, thrombosis, fibrinoid degeneration and necrotizing panarteritis), excluding endarteritis obliterans.

Effect of substance P administration on vascular permeability in the rat oral mucosa and sublingual gland.

Neuropeptides, including substance P (SP) may play a role in neurogenic inflammation. Although SP-immunoreactive (SP-IR) axons are known to be present within the oral mucosa (OM) and salivary glands, the functional significance of SP in oral mucosa and sublingual salivary gland (SLG) is not fully understood. The present experiments were carried out to study the effects of SP infused into the left common carotid artery on vascular permeability in the OM and in the SLG of male rats. Vascular permeability was assessed on the basis of Evans Blue extravasation. Separate groups of animals received histamine (H1) receptor antagonist (chloropyramine, 10 mg kg-1 i.v.) or prostaglandin synthesis inhibitor (indomethacin, 4 mg kg-1 i.v.) prior to SP infusions. Infusion of SP in doses of 30 and 74 pmol min-1 increased the vascular permeability of OM by 162.3 +/- 16.3% (n = 8, p < 0.05) and 482.7 +/- 46.7% (n = 8, p < 0.001), respectively. SP in a dose of 15 pmol min-1 did not increase Evans Blue extravasation in OM (38.3 +/- 4.0 micrograms g-1, n = 8, compared to the control: 44.0 +/- 7.9 micrograms g-1, n = 8, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic analysis of rat exocrine gland muscarinic receptors in vivo.

Recently we employed two enantiomers of the muscarinic antagonist quinuclidinyl iodobenzilate (IQNB), and pharmacokinetic analyses, to define and quantitate nonspecific and specific binding to rat parotid gland muscarinic acetylcholine receptors (mAChRs) in vivo (Hiramatsu et al., 1993). The present studies were designed to utilize this same approach for evaluating mAChRs in three other morphologically different rat exocrine glands: the submandibular, sublingual and lacrimal glands. The metabolism and tissue distribution of the intravenously injected IQNB enantiomers were determined, and the resulting data were assessed in terms of their goodness of fit to several multicompartmental models. All three exocrine glands showed substantial nonspecific ligand distribution as measured with the receptor-inert enantiomer (SS)-IQNB. Nonspecific distribution represented 45, 21 and 36% of total ligand distribution in submandibular, sublingual and lacrimal glands, respectively, as measured with the receptor-active enantiomer (RR)-IQNB. The rank order of the binding potential, kinetically equivalent to Bmax/Kd, for (RR)-IQNB and these mAChRs was lacrimal > sublingual > submandibular glands (674 +/- 235 > 575 +/- 109 > 345 +/- 29). These results demonstrate that specific mAChRs in the exocrine glands can be measured in vivo with the (RR)-IQNB enantiomer and that despite some small quantitative differences, the distribution of (RR)- and (SS)-IQNB is similar in the three exocrine glands but is substantially different from that in brain and heart.

The microvasculature of rat salivary glands. A scanning electron microscopic study.

The blood vessels together with the parenchymal components of rat salivary glands were studied by scanning electron microscopy (SEM) after removal of stromal connective tissue by acid hydrolysis plus enzymatic digestion. The three-dimensional vascular architecture was also studied by SEM of vascular corrosion cats. Each cluster of 4-5 polymorphous acini is connected with the convoluted duct via an intercalated duct. The convoluted duct usually has a sigmoid course and drains to the intralobular striated duct (about 20 microns in diameter); this has a rather straight course before connecting with the interlobular excretory duct. Myoepithelial cells with radiating processes were observed on the stromal surface of the secretory acini. Pericytes with longitudinal and circular processes were also observed surrounding the stromal surface of capillaries. The acini and convoluted ducts are surrounded by plexuses of capillaries derived from terminal arterioles which run along the intralobular duct system. The sinusoidal capillary plexus enveloping the striated duct receives blood from capillaries surrounding the acini and convoluted ducts through portal venules. The interlobular excretory ducts are richly supplied by a subepithelial network of capillaries which receive blood directly from the interlobular artery and drain into the interlobular vein. Thus, the excretory duct circulation is separated from the intralobular circulation. No arterio-venous anastomoses were observed in the gland. However, veno-venous and arterio-arterial anastomoses were often seen along the excretory duct; such anastomoses may participate in controlling the direction of blood flow through the vascular plexus around the excretory duct. The well-developed subepithelial plexus of capillaries observed around this duct is appropriate for its known absorptive/secretory functions. The capillary network around the acini is densest in the parotid gland and sparsest in the sublingual gland. The subepithelial capillary network of the excretory ducts of the submaxillary gland is denser than those of the other two glands which had similar densities.