Global and Regional Respiratory Mechanics During Robotic-Assisted Laparoscopic Surgery: A Randomized Study.

BACKGROUND: Pneumoperitoneum and nonphysiological positioning required for robotic surgery increase cardiopulmonary risk because of the use of larger airway pressures (Paws) to maintain tidal volume (VT). However, the quantitative partitioning of respiratory mechanics and transpulmonary pressure (PL) during robotic surgery is not well described. We tested the following hypothesis: (1) the components of driving pressure (transpulmonary and chest wall components) increase in a parallel fashion at robotic surgical stages (Trendelenburg and robot docking); and (2) deep, when compared to routine (moderate), neuromuscular blockade modifies those changes in PLs as well as in regional respiratory mechanics. METHODS: We studied 35 American Society of Anesthesiologists (ASA) I-II patients undergoing elective robotic surgery. Airway and esophageal balloon pressures and respiratory flows were measured to calculate respiratory mechanics. Regional lung aeration and ventilation was assessed with electrical impedance tomography and level of neuromuscular blockade with acceleromyography. During robotic surgical stages, 2 crossover randomized groups (conditions) of neuromuscular relaxation were studied: Moderate (1 twitch in the train-of-four stimulation) and Deep (1-2 twitches in the posttetanic count). RESULTS: Pneumoperitoneum was associated with increases in driving pressure, tidal changes in PL, and esophageal pressure (Pes). Steep Trendelenburg position during robot docking was associated with further worsening of the respiratory mechanics. The fraction of driving pressures that partitioned to the lungs decreased from baseline (63% ± 15%) to Trendelenburg position (49% ± 14%, P < .001), due to a larger increase in chest wall elastance (Ecw; 12.7 ± 7.6 cm H2O·L) than in lung elastance (EL; 4.3 ± 5.0 cm H2O·L, P < .001). Consequently, from baseline to Trendelenburg, the component of Paw affecting the chest wall increased by 6.6 ± 3.1 cm H2O, while PLs increased by only 3.4 ± 3.1 cm H2O (P < .001). PL and driving pressures were larger at surgery end than at baseline and were accompanied by dorsal aeration loss. Deep neuromuscular blockade did not change respiratory mechanics, regional aeration and ventilation, and hemodynamics. CONCLUSIONS: In robotic surgery with pneumoperitoneum, changes in ventilatory driving pressures during Trendelenburg and robot docking are distributed less to the lungs than to the chest wall as compared to routine mechanical ventilation for supine patients. This effect of robotic surgery derives from substantially larger increases in Ecw than ELs and reduces the risk of excessive PLs. Deep neuromuscular blockade does not meaningfully change global or regional lung mechanics.

Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin II-induced microcirculatory changes in a model of primary hypertension.

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.

Central Sympathetic Modulation Reverses Microvascular Alterations in a Rat Model of High-Fat Diet-Induced Metabolic Syndrome.

OBJECTIVES: The objective of this study was to investigate the role of the SNS on hemodynamic, metabolic, and microvascular alterations in a rat model of HFD-induced MS with salt supplementation. METHODS: In total, 40 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. FCD was evaluated using intravital video microscopy, and the SCD was evaluated using histochemical analysis. RESULTS: 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. CONCLUSIONS: 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 MS in rats.

Cardiac microvascular rarefaction in hyperthyroid rats is reversed by losartan, diltiazem, and propranolol.

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 ß-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 < 0.001) presented higher systolic blood pressure (SBP) compared with EUT + VEH (132 ± 3 mmHg). HYPER + LOS (144 ± 2 mmHg), HYPER + DILT (147 ± 3 mmHg) and HYPER + PROP (153 ± 4 mmHg) presented lower SBP compared with HYPER + VEH (P < 0.001). Chronic treatment with losartan, diltiazem, and propranolol reversed cardiac structural microvascular rarefaction (HYPER + VEH 0.16 ± 0.01; EUT + VEH 0.35 ± 0.02; HYPER + LOS 0.46 ± 0.03; HYPER + DILT 0.49 ± 0.02; HYPER + PROP 0.58 ± 0.04 (Vv[cap]/Vv[fib]); P < 0.001) and enhanced the LV ejection fraction of hyperthyroid rats (HYPER + VEH 71 ± 3; EUT + VEH 85 ± 2; HYPER + LOS 90 ± 3; HYPER + DILT 85 ± 3; HYPER + PROP 86 ± 2%; P < 0.05). In conclusion, chronic treatment with losartan, diltiazem, and propranolol improved the cardiac microcirculation and function in an experimental model of hyperthyroidism in rats.

Effectiveness of laser Doppler perfusion monitoring in the assessment of microvascular function in patients undergoing on-pump coronary artery bypass grafting.

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.

Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice.

Dexmedetomidine (DEX) is a α2 -adrenoceptor (α2 -AR) agonist used as an anesthetic adjuvant and as sedative in critical care settings. Typically, α2 -AR agonists release nitric oxide (NO) and subsequently activate NO-GMPc pathway and have been implicated with antinociception. In this study, we investigate the pharmacological mechanisms involved in the antinociceptive effects of DEX, using an acetic acid-induced writhing assay in mice. Saline or DEX (1, 2, 5, or 10 µg/kg) was intravenously injected 5 min before ip administration of acetic acid and the resulting abdominal constrictions were then counted for 10 min. To investigate the possible mechanisms related to antinociceptive effect of DEX (10 µg/kg), the animals were also pretreated with one of the following drugs: 7-nitroindazole (7-NI; 30 mg/kg ip); 1H-[1,2,4] oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 2.5 mg/kg, ip); yohimbine (YOH; 1 mg/kg, ip); atropine (ATRO; 2 mg/kg, ip); glibenclamide (GLIB; 1 mg/kg, i.p.) and naloxone (NAL; 0.2 mg/kg, ip). A rotarod and open-field performance test were performed with DEX at 10 µg/kg dose. DEX demonstrated its potent antinociceptive effect in a dose-dependent manner. The pretreatment with 7-NI, ODQ, GLIB, ATRO, and YOH significantly reduced the antinociceptive affects of DEX. However, NAL showed no effecting DEX-induced antinociception. The rotarod and open-field tests confirmed there is no detectable sedation or even significant motor impairment with DEX at 10 µg/kg dose. Our results suggest that the α2 -AR and NO-GMPc pathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain. Furthermore, the antinociceptive effect exerted by DEX appears to be dependent on KATP channels, independent of opioid receptor activity.

Structural and functional microvascular alterations in a rat model of metabolic syndrome induced by a high-fat diet.

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) but not in the skin (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.

Opioid receptor blockade prevents propofol-induced hypotension in rats.

BACKGROUND: Propofol is an intravenous anesthetic that is widely used to anesthetize patients during neurosurgical procedures. Although propofol is considered to be an essential component of contemporary management of acute brain injury in the operating room and in critical care settings, propofol-induced hypotension (PIH) remains a frequent and undesirable side effect. After 3 decades of clinical use, multiple proposed causes of PIH, and conflicting experimental results, the mechanism of PIH is still a puzzle for neuroscience and anesthesiology. This study evaluated the role of opioid receptors in PIH. METHODS: Pentobarbital-anesthetized rats were subjected to systemic or central pretreatment with naloxone followed by intravenous or central administration of propofol. RESULTS: In the absence of pretreatment with naloxone, intravenous (7.5 mg/kg) and intracistenal propofol (10 µg) injection induced 45% and 35% reductions in the mean arterial pressure, respectively (P<0.05). Both systemic (5 mg/kg) and central (100 µg) pretreatment with naloxone prevented PIH without independently affecting mean arterial pressure. CONCLUSIONS: This experiment in anesthetized rats indicates that central and peripheral opioid receptor blockade prevents PIH, suggesting that these receptors are involved in the cardiovascular alterations elicited by propofol administration.

The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis.

BACKGROUND: The use of vasoactive drugs to restore arterial blood pressure in patients with septic shock remains a cornerstone of intensive care medicine. However, vasopressors can accentuate the hypoperfusion of the gut during septic shock, allowing bacterial translocation and endotoxemia. In this study, we compared the effects of different vasoactive drugs on intestinal microcirculation and tissue oxygenation, independent of the effects of fluid therapy, in a rat model of endotoxemic shock. METHODS: Pentobarbital-anesthetized Wistar Kyoto rats were submitted to endotoxemic shock induced by Escherichia coli lipopolysaccharide (2 mg/kg IV). Arterial blood pressure was normalized by a continuous infusion of different vasoactive drugs, including epinephrine, norepinephrine, phenylephrine, dopamine, dobutamine, or a combination of dobutamine and norepinephrine. The functional capillary density (FCD) of the muscular layer of the small intestine was evaluated by intravital video-microscopy. Mesenteric venous blood gases and lactate concentrations were also analyzed. RESULTS: FCD decreased by approximately 25% to 60% after the IV infusion of epinephrine, norepinephrine, and phenylephrine. Administration of dopamine, dobutamine, and the combination of dobutamine and norepinephrine did not induce significant alterations in gut FCD. In addition, the mesenteric venous lactate concentration increased in the presence of phenylephrine and showed a tendency to increase after the administration of epinephrine and norepinephrine, whereas there was no observable increase after the administration of dopamine, dobutamine, and the combination of dobutamine with norepinephrine. CONCLUSION: This study confirms dissociation of the systemic hemodynamic and microvascular alterations in an experimental model of septic shock. Moreover, the results indicate that the use of dopamine, dobutamine, and dobutamine in combination with norepinephrine yields a protective effect on the microcirculation of the intestinal muscular layer in endotoxemic rats.

Effects of antihypertensive drugs on capillary rarefaction in spontaneously hypertensive rats: intravital microscopy and histologic analysis.

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, P < 0.01) and ear skin (WKY 391 +/- 18 and SHR 210 +/- 15 capillaries/mm, P < 0.01). A linear relationship was seen between skeletal muscle and skin capillary densities (r = 0.654, P < 0.0001). 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, P < 0.01). 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, P < 0.01). 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, P > 0.05). 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.

Pharmacologic evidence for the involvement of central and peripheral opioid receptors in the cardioprotective effects of fentanyl.

BACKGROUND: We investigated the involvement of central and peripheral opioid receptors (OR) in the cardioprotective effects of fentanyl (FENT) in a model of myocardial ischemia/reperfusion injury associated with pharmacologically induced sympathetic overactivity in anesthetized rabbits. METHODS: Central sympathetic stimulation was achieved through intracerebroventricular injection of l-glutamate in animals submitted to 35 min of coronary occlusion followed by 120 min of reperfusion. Rabbits received naloxone HCl intracerebroventricularly or naloxone methiodide IV, a quaternary compound that does not cross the blood-brain barrier, 5 min before FENT treatment (5 or 50 microg/kg, IV). RESULTS: Infarct area was reduced only by FENT 50 (from 51% +/- 2% to 24% +/- 2%). This protective effect was abolished by peripheral (42% +/- 4%), but not central, OR blockade (32% +/- 3%). The number of premature ventricular complexes during the ischemic period (54 +/- 3) was reduced by FENT 50 (19 +/- 7), an effect blunted by central (40 +/- 3) but not peripheral (18 +/- 7) blockade of OR. During reperfusion, the number of premature ventricular complexes (134 +/- 50) was reduced to 9 +/- 5 by FENT 50 and was prevented by central (42 +/- 4) as well as peripheral (20 +/- 11) OR blockade. The mortality rate (50%) and incidence of ventricular tachycardia (55%) were completely abolished by FENT 50. CONCLUSIONS: We conclude that fentanyl's effects for limiting myocardial ischemic injury are mediated via peripheral ORs while opioid's antiarrhythmic actions are mediated via central OR agonism.