Respiratory Homeostasis Research Articles

Respiratory protease/antiprotease balance determines susceptibility to viral infection and can be modified by nutritional antioxidants.

The respiratory epithelium functions as a central orchestrator to initiate and organize responses to inhaled stimuli. Proteases and antiproteases are secreted from the respiratory epithelium and are involved in respiratory homeostasis. Modifications to the protease/antiprotease balance can lead to the development of lung diseases such as emphysema or chronic obstructive pulmonary disease. Furthermore, altered protease/antiprotease balance, in favor for increased protease activity, is associated with increased susceptibility to respiratory viral infections such as influenza virus. However, nutritional antioxidants induce antiprotease expression/secretion and decrease protease expression/activity, to protect against viral infection. As such, this review will elucidate the impact of this balance in the context of respiratory viral infection and lung disease, to further highlight the role epithelial cell-derived proteases and antiproteases contribute to respiratory immune function. Furthermore, this review will offer the use of nutritional antioxidants as possible therapeutics to boost respiratory mucosal responses and/or protect against infection.

The Effects of Hyper- and Hypocapnia on Phonatory Laryngeal Airway Resistance in Women.

The larynx has a dual role in the regulation of gas flow into and out of the lungs while also establishing resistance required for vocal fold vibration. This study assessed reciprocal relations between phonatory functions-specifically, phonatory laryngeal airway resistance (Rlaw)-and respiratory homeostasis during states of ventilatory gas perturbations. Twenty-four healthy women performed phonatory tasks while exposed to induced hypercapnia (high CO2), hypocapnia (low CO2), and normal breathing (eupnea). Effects of gas perturbations on Rlaw were investigated as were the reciprocal effects of Rlaw modulations on respiratory homeostasis. Rlaw remained stable despite manipulations of inspired gas concentrations. In contrast, end-tidal CO2 levels increased significantly during all phonatory tasks. Thus, for the conditions tested, Rlaw did not adjust to accommodate ventilatory needs as predicted. Rather, stable Rlaw was spontaneously accomplished at the cost of those needs. Findings provide support for a theory of regulation wherein Rlaw may be a control parameter in phonation. Results also provide insight into the influence of phonation on respiration. The work sets the foundation for future studies on laryngeal function during phonation in individuals with lower airway disease and other patient populations.

Anesthetic management in atrial fibrillation ablation procedure: Adding non-invasive ventilation to deep sedation

Anesthetic management of patients undergoing pulmonary vein isolation for atrial fibrillation has specific requirements. The feasibility of non-invasive ventilation (NIV) added to deep sedation procedure was evaluated.Seventy-two patients who underwent ablation procedure were retrospectively revised, performed with (57%) or without (43%) application of NIV (Respironic® latex-free total face mask connected to Garbin ventilator-Linde Inc.) during deep sedation (Midazolam 0.01–0.02 mg/kg, fentanyl 2.5–5 μg/kg and propofol: bolus dose 1–1.5 mg/kg, maintenance 2–4 mg/kg/h).In the two groups (NIV vs deep sedation), differences were detected in intraprocedural (pH 7.37 ± 0.05 vs 7.32 ± 0.05, p = 0.001; PaO2 117.10 ± 27.25 vs 148.17 ± 45.29, p = 0.004; PaCO2 43.37 ± 6.91 vs 49.33 ± 7.34, p = 0.002) and in percentage variation with respect to basal values (pH −0.52 ± 0.83 vs −1.44 ± 0.87, p = 0.002; PaCO2 7.21 ± 15.55 vs 34.91 ± 25.76, p = 0.001) of arterial blood gas parameters. Two episodes of respiratory complications, treated with application of NIV, were reported in deep sedation procedure. Endotracheal intubation was not necessary in any case. Adverse events related to electrophysiological procedures and recurrence of atrial fibrillation were recorded, respectively, in 36% and 29% of cases.NIV proved to be feasible in this context and maintained better respiratory homeostasis and better arterial blood gas balance when added to deep sedation.

Histological and antioxidant responses inRhamdia quelensedated with propofol

Morphometry of gills and antioxidant/oxidant status in gills, brain, liver and blood of Rhamdia quelen sedated with propofol were studied. The purpose was to investigate structural and functional responses upon administration of the drug in order to validate its use for the species. The fish were exposed to 0, 0.4 or 0.8 mg L−1 propofol for 1, 6 or 12 h, which are times normally used in live fish transport. Propofol induced an increase in chloride cell in the non-respiratory epithelium of the gill. Standard biochemical assays (thiobarbituric acid reactive substances and lipid hydroperoxides) indicated that the lowest concentration of propofol did not induce lipoperoxidation in gills, brain, liver or blood. The oxidative status of enzymatic (catalase, superoxide dismutase and glutathione-S-transferase) and non-enzymatic (non-protein thiols) antioxidants differed among the tested sites. Apart from the blood, superoxide dismutase was the enzyme to show the highest activity in the presence of propofol, which is known to possess antioxidant properties that resemble those of vitamin E. The absence of chloride cells in the respiratory epithelium (lamella) in association with the stability of the lamellar structure (i.e. lamellar area, total height of lamella and width of lamella) indicate that ion and oxygen uptake were preserved under propofol sedation. Thus, 0.4 mg L−1 propofol should be considered to sedate R. quelen during lengthy procedures, such as transport, for it was able to maintain ionic and respiratory homeostasis as well as prevent peroxidative damage in vital organs.

Chronic Intermittent Hypoxia Blunts the Expression of Ventilatory Long Term Facilitation in Sleeping Rats.

We have previously reported that chronic intermittent hypoxia (CIH), a central feature of human sleep-disordered breathing, causes respiratory instability in sleeping rats (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012). Long term facilitation (LTF) of respiratory motor outputs following exposure to episodic, but not sustained, hypoxia has been described. We hypothesized that CIH would enhance ventilatory LTF during sleep. We examined the effects of 3 and 7 days of CIH exposure on the expression of ventilatory LTF in sleeping rats. Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5 % O(2) at nadir; SaO(2) ~ 80 %) per hour, 8 h per day for 3 or 7 consecutive days (CIH, N = 7 per group). Corresponding sham groups (N = 7 per group) were subjected to alternating cycles of air under identical experimental conditions in parallel. Following gas exposures, breathing during sleep was assessed in unrestrained, unanaesthetized animals using the technique of whole-body plethysmography. Rats were exposed to room air (baseline) and then to an acute IH (AIH) protocol consisting of alternating periods of normoxia (7 min) and hypoxia (FiO(2) 0.1, 5 min) for 10 cycles. Breathing was monitored during the AIH exposure and for 1 h in normoxia following AIH exposure. Baseline ventilation was elevated after 3 but not 7 days of CIH exposure. The hypoxic ventilatory response was equivalent in sham and CIH animals after 3 days but ventilatory responses to repeated hypoxic challenges were significantly blunted following 7 days of CIH. Minute ventilation was significantly elevated following AIH exposure compared to baseline in sham but not in CIH exposed animals. LTF, determined as the % increase in minute ventilation from baseline following AIH exposure, was significantly blunted in CIH exposed rats. In summary, CIH leads to impaired ventilatory responsiveness to AIH. Moreover, CIH blunts ventilatory LTF. The physiological significance of ventilatory LTF is context-dependent but it is reasonable to consider that it can potentially destabilize respiratory control, in view of the potential for LTF to give rise to hypocapnia. CIH-induced blunting of LTF may represent a compensatory mechanism subserving respiratory homeostasis. Our results suggest that CIH-induced increase in apnoea index (Edge D, Bradford A, O'halloran KD. Adv Exp Med Biol 758:359-363, 2012) is not related to enhanced ventilatory LTF. We conclude that the mature adult respiratory system exhibits plasticity and metaplasticity with potential consequences for the control of respiratory homeostasis. Our results may have implications for human sleep apnoea.

Electrical aspects of the osmorespiratory compromise: TEP responses to hypoxia in the euryhaline killifish (Fundulus heteroclitus) in freshwater and seawater.

The osmorespiratory compromise, the trade-off between the requirements for respiratory and ionoregulatory homeostasis at the gills, becomes more intense during environmental hypoxia. One aspect that has been previously overlooked is possible change in transepithelial potential (TEP) caused by hypoxia, which will influence branchial ionic fluxes. Using the euryhaline killifish, we show that acute hypoxia reduces the TEP across the gills by approximately 10 mV in animals acclimated to both freshwater (FW) and seawater (SW), with a higher PO2 threshold in the former. TEP becomes negative in FW, and less positive in SW. The effects are immediate, stable for at least 3 h, and reverse immediately upon return to normoxia. Hypoxia also blocks the normal increase in TEP that occurs upon transfer from FW to SW, but does not reduce the fall in TEP that occurs with transfer in the opposite direction. These effects may be beneficial in FW but not in SW.

Selective Expression of Galanin in Neuronal-Like Cells of the Human Carotid Body.

The carotid body is a neural-crest-derived organ devoted to respiratory homeostasis through sensing changes in blood oxygen levels. The sensory units are the glomeruli composed of clusters of neuronal-like (type I) cells surrounded by glial-like (type II) cells. During chronic hypoxia, the carotid body shows growth, with increasing neuronal-like cell numbers. We are interested in the signals involved in the mechanisms that underlie such response, because they are not well understood and described. Considering that, in literature, galanin is involved in neurotrophic or neuroprotective role in cell proliferation and is expressed in animal carotid body, we investigated its expression in human. Here, we have shown the expression and localisation of galanin in the human carotid body.

Chair's summary: Innate and adaptive immune responses in airway disease.

The lungs are constantly exposed to the external environment, which contains myriad particles and molecules that are potentially antigenic. The respiratory immune system must maintain a state of tolerance, discriminating between potentially harmful pathogens that could promote infectious disease while ignoring innocuous particles such as dust or pollen. These immunological control systems develop during early life and are greatly influenced by genetics, infection history, age, and environmental conditions such as smoking, diet, and pollution. Asthma, emphysema, chronic obstructive pulmonary disease (COPD) and pneumonia are thought to occur as a consequence of disruption of these control systems and disturbance of respiratory tolerance. Conversely, excessive immunological tolerance may lead to ineffective clearance of infectious agents such as influenza, tuberculosis, respiratory syncytial virus, or Streptococcus pneumoniae, which in turn may lead to inflammatory lung disease, bronchitis, pneumonia, and sepsis. Respiratory diseases represent an important cause of morbidity and mortality globally, and deaths due to these diseases are increasing worldwide. Moreover, the very young and the elderly are disproportionately represented at the more severe end of the disease spectrum, with asthma being more common in children and COPD and emphysema occurring later in life. It is clear that a better understanding of the basic mechanisms underlying respiratory immune homeostasis is vital to developing novel therapeutic agents and vaccines for disease prevention and control. Traditionally, diseases have been associated specifically with either innate or adaptive immune pathways—for example, innate immunity for infections and COPD or adaptive immune systems for asthma. However, the distinction between the different arms of the immune system is becoming less apparent, and it is clear that most diseases involve contributions from both sides of the immune system. Understanding these interactions is critical in the search for more effective therapies for diseases, which are common and ever-increasing. The focus of the 29th Transatlantic Airway Conference was how innate and adaptive immune system pathways contribute to the development of a variety of lung diseases, such as asthma, COPD, and respiratory infections. The papers that the speakers presented at the meeting covered the broad areas of epithelium–immune system interactions, early effector mechanisms, the influence of the microbiome and host defense mechanisms, and immunomodulatory and regulatory pathways. The talks highlighted novel aspects of the immune system and revealed the complexity of interactions that operate within the lung.

Predicting performance and plasticity in the development of respiratory structures and metabolic systems.

The scaling laws governing metabolism suggest that we can predict metabolic rates across taxonomic scales that span large differences in mass. Yet, scaling relationships can vary with development, body region, and environment. Within species, there is variation in metabolic rate that is independent of mass and which may be explained by genetic variation, the environment or their interaction (i.e., metabolic plasticity). Additionally, some structures, such as the insect tracheal respiratory system, change throughout development and in response to the environment to match the changing functional requirements of the organism. We discuss how study of the development of respiratory function meets multiple challenges set forth by the NSF Grand Challenges Workshop. Development of the structure and function of respiratory and metabolic systems (1) is inherently stable and yet can respond dynamically to change, (2) is plastic and exhibits sensitivity to environments, and (3) can be examined across multiple scales in time and space. Predicting respiratory performance and plasticity requires quantitative models that integrate information across scales of function from the expression of metabolic genes and mitochondrial biogenesis to the building of respiratory structures. We present insect models where data are available on the development of the tracheal respiratory system and of metabolic physiology and suggest what is needed to develop predictive models. Incorporating quantitative genetic data will enable mapping of genetic and genetic-by-environment variation onto phenotypes, which is necessary to understand the evolution of respiratory and metabolic systems and their ability to enable respiratory homeostasis as organisms walk the tightrope between stability and change.

Role of orexin in respiratory and sleep homeostasis during upper airway obstruction in rats.

Chronic upper airway obstruction (UAO) elicits a cascade of complex endocrine derangements that affect growth, sleep, and energy metabolism. We hypothesized that elevated hypothalamic orexin has a role in maintaining ventilation during UAO, while at the same time altering sleep-wake activity and energy metabolism. Here, we sought to explore the UAO-induced changes in hypothalamic orexin and their role in sleep-wake balance, respiratory activity, and energy metabolism. The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed; UAO and sham-operated control animals were monitored for 7 weeks. We measured food intake, body weight, temperature, locomotion, and sleep-wake activity. Magnetic resonance imaging was used to quantify subcutaneous and visceral fat tissue volumes. In week 7, the rats were sacrificed and levels of hypothalamic orexin, serum leptin, and corticosterone were determined. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and respiration was also explored. UAO increased hypothalamic orexin mRNA and protein content by 64% and 65%, respectively. UAO led to 30% chronic sleep loss, excessive active phase sleepiness, decreased body temperature, increased food intake, reduction of abdominal and subcutaneous fat tissue volume, and growth retardation. Administration of almorexant normalized sleep but induced severe breathing difficulties in UAO rats, while it had no effect on sleep or on breathing of control animals. In upper airway obstruction animals, enhanced orexin secretion, while crucially important for respiratory homeostasis maintenance, is also responsible for chronic partial sleep loss, as well as considerable impairment of energy metabolism and growth.

Loss aversion and hypoxia: less loss aversion in oxygen-depleted environment

Hypoxia, the deprivation of adequate oxygen supply, constitutes a direct threat to survival by disrupting cardiovascular or respiratory homeostasis and eliciting a respiratory distress. Although hypoxia has been shown to increase brain vulnerability and impair basic cognitive functions, only one study has examined its effect on decision-making. The present study examined the effect of mild hypoxia on individual’s loss aversion, that is, the tendency to be more affected by losses than equal sized gains. A sample of 26 participants were asked to either accept or reject a series of mixed gambles once in an oxygen-depleted environment (14.1% oxygen concentration) and once in a normoxic environment (20.9% oxygen concentration). Each gamble involved a 50–50 chance of winning or losing specified amounts of money. Mild hypoxia decreased loss aversion: on average in the normoxic condition participants accepted gambles if the gain was at least 2.4 times as large as the loss, whereas in the oxygen-depleted condition participants accepted gambles if the gain was at least 1.7 times as large as the loss. Mild hypoxia may push individuals to be less cautious in daily decisions that involve a trade-off between a gain and a loss.

P258 A case-control study of associations between hereditary haemorrhagic telangiectasia and common respiratory conditions

BackgroundHereditary haemorrhagic telangiectasia (HHT) is an inherited disease of the vasculature presenting with nosebleeds, telangiectasia and arteriovenous malformations (AVMs). HHT is caused by gene mutations affecting the transforming growth factor...

Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4

We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. Invitro and invivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia.

Sternohyoid and diaphragm muscle form and function during postnatal development in the rat

What is the central question of this study? Co-ordinated activity of the thoracic pump and pharyngeal dilator muscles is critical for maintaining airway calibre and respiratory homeostasis. Whilst postnatal maturation of the diaphragm has been well characterized, surprisingly little is known about the developmental programme in the airway dilator muscles. What is the main finding and its importance? Developmental increases in force-generating capacity and fatigue in the sternohyoid and diaphragm muscles are attributed to a maturational shift in muscle myosin heavy chain phenotype. This maturation is accelerated in the sternohyoid muscle relative to the diaphragm and may have implications for the control of airway calibre in vivo. The striated muscles of breathing, including the thoracic pump and pharyngeal dilator muscles, play a critical role in maintaining respiratory homeostasis. Whilst postnatal maturation of the diaphragm has been well characterized, surprisingly little is known about the developmental programme in airway dilator muscles given that co-ordinated activity of both sets of muscles is needed for the maintenance of airway calibre and effective pulmonary ventilation. The form and function of sternohyoid and diaphragm muscles from Wistar rat pups [postnatal day (PD) 10, 20 and 30] was determined. Isometric contractile and endurance properties were examined in tissue baths containing Krebs solution at 35°C. Myosin heavy chain (MHC) isoform composition was determined using immunofluorescence. Muscle oxidative and glycolytic capacity was assessed by measuring the activities of succinate dehydrogenase and glycerol-3-phosphate dehydrogenase using semi-quantitative histochemistry. Sternohyoid and diaphragm peak isometric force and fatigue increased significantly with postnatal maturation. Developmental myosin disappeared by PD20, whereas MHC2B areal density increased significantly from PD10 to PD30, emerging earlier and to a much greater extent in the sternohyoid muscle. The numerical density of fibres expressing MHC2X and MHC2B increased significantly during development in the sternohyoid. Diaphragm succinate dehydrogenase activity and sternohyoid glycerol-3-phosphate dehydrogenase activity increased significantly with age. Developmental increases in force-generating capacity and fatigue in the sternohyoid and diaphragm muscles are attributed to a postnatal shift in muscle MHC phenotype. The accelerated maturation of the sternohyoid muscle relative to the diaphragm may have implications for the control of airway calibre in vivo.

RETRACTED: Mutual antagonism between hypoxia-inducible factors 1α and 2α regulates oxygen sensing and cardio-respiratory homeostasis

Breathing and blood pressure are under constant homeostatic regulation to maintain optimal oxygen delivery to the tissues. Chemosensory reflexes initiated by the carotid body and catecholamine secretion from the adrenal medulla are the principal mechanisms for maintaining respiratory and cardiovascular homeostasis; however, the underlying molecular mechanisms are not known. Here, we report that balanced activity of hypoxia-inducible factor-1 (HIF-1) and HIF-2 is critical for oxygen sensing by the carotid body and adrenal medulla, and for their control of cardio-respiratory function. In Hif2α(+/-) mice, partial HIF-2α deficiency increased levels of HIF-1α and NADPH oxidase 2, leading to an oxidized intracellular redox state, exaggerated hypoxic sensitivity, and cardio-respiratory abnormalities, which were reversed by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. Conversely, in Hif1α(+/-) mice, partial HIF-1α deficiency increased levels of HIF-2α and superoxide dismutase 2, leading to a reduced intracellular redox state, blunted oxygen sensing, and impaired carotid body and ventilatory responses to chronic hypoxia, which were corrected by treatment with a HIF-2α inhibitor. None of the abnormalities observed in Hif1α(+/-) mice or Hif2α(+/-) mice were observed in Hif1α(+/-);Hif2α(+/-) mice. These observations demonstrate that redox balance, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardio-respiratory homeostasis.

Synthesis of frataxin genes by direct assembly of serial deoxyoligonucleotide primers and its expression in Escherichia coli

Frataxin, a small nuclear-encoded protein targeted to mitochondria, is known to play an important role in both the mitochondrial respiratory chain and iron homeostasis. The protein is highly conserved in most eukaryotic organisms with no major structural changes, suggesting that it serves a crucial function in all organisms. Recently, purified frataxin was used as a therapeutic treatment of Friedreich’s ataxia, a common degenerative disorder that results from a frataxin protein deficiency, by directly applying the protein to the diseased cells. In this report, we describe a novel and rapid method of synthesizing genes encoding frataxin proteins for the purpose of efficient protein production. The artificial yeast and human frataxin genes were synthesized by direct assembly of serial deoxyoligonucleotide primers designed based on the optimal nucleotide sequences. When we tested the expression of these synthetic genes in two E. coli host strains, the yeast frataxin gene was expressed 20 folds higher in Rosetta (DE3) cells than in BL21 (DE3) cells, whereas the expression levels of human frataxin were similar in both E. coli strains. Attenuation of the Fenton reactions by the purified yeast and human frataxin proteins was observed under the defined conditions, which suggests that the recombinant frataxin proteins are active and functional. The procedure described here could be applied to many known genes or to generate novel synthetic genes that can be redesigned by arranging functional domains from previously identified genes and to study the structure and function of synthetic recombinant proteins and potential usage.

Time‐dependent muscle‐specific protein oxidation in a mouse model of chronic hypoxia

Respiratory muscle redox homeostasis is altered by chronic hypoxia (CH). Protein oxidation potentially contributes to respiratory muscle dysfunction in respiratory‐related diseases where hypoxia features. The objective of this study was to determine the type and extent of respiratory and limb muscle protein oxidation temporally in a mouse model of CH.C57/Bl6J mice were exposed to hypoxia (1, 3 and 6 weeks; 10% FiO2) or normoxia. Following treatment, excised respiratory and limb muscles were homogenised and incubated with carbonyl‐ or thiol‐reactive fluorophores before gel electrophoresis and fluorescence scanning. Optical density (OD) of fluorescence was normalised to total protein, determined by colloidal coomassie staining.Diaphragm free‐thiol content increased ~9‐fold after 1 week of CH. By 6 weeks, both diaphragm and sternohyoid free‐thiol content were significantly decreased (40% and 80% decrease from control respectively; n=6–8 per group; P=0.0046 and P<0.0001, Student's unpaired t‐test) whereas there was a significant increase in the extensor digitorum longus (232%; P=0.0007) and in soleus (143%; P<0.0001). Diaphragm carbonyl content was unchanged after 1 week of CH, but was increased significantly by 3 weeks and was increased further again after 6 weeks. The extent of carbonylation was different between muscle groups.We conclude that CH exposure causes differential time‐dependent protein oxidation in respiratory and limb muscles.

The influence of steep Trendelenburg position and CO 2 pneumoperitoneum on cardiovascular, cerebrovascular and respiratory homeostasis during robotic prostatectomy

The influence of steep Trendelenburg position and CO 2 pneumoperitoneum on cardiovascular, cerebrovascular and respiratory homeostasis during robotic prostatectomy

Cardiovascular and respiratory effects of the degree of head‐down angle during robot‐assisted laparoscopic radical prostatectomy

Robot-assisted laparoscopic radical prostatectomy (RALP) requires a steep Trendelenburg position and CO2 pneumoperitoneum for several hours to secure the surgical visual field. The present study was performed to investigate the influence of each angle of Trendelenburg position during RALP on cardiovascular and respiratory homeostasis. Forty-seven ASA physical status 1 and 2 patients underwent open retropubic radical prostatectomy (RRP) or RALP. Patients receiving RALP were randomized to undergo the operation in the 20°, 25° or 30° Trendelenburg position. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), end-tidal CO2 pressure (PetCO2 ), tidal volume (Vt), peak inspiratory pressure (PIP) and dynamic compliance (Cdyn) were recorded during the operation. Angle of head-down tilt was significantly correlated with MAP, PIP and Cdyn, but not with HR, RR or PetCO2 . MAP decreased gradually over time in each group in the Trendelenburg position with pneumoperitoneum. As the angle of head-down tilt became stronger, MAP, RR, PetCO2 and PIP tended to increase and Cdyn tended to decrease. This study demonstrated that the degree of the head-down angle at RALP affected the cardiovascular and respiratory parameters. Pneumoperitoneum with head-down position in RALP influenced the cardiovascular and respiratory system to a greater extent than RRP, and these effects were stronger with deeper head-down angle.

Anaesthesia for laparoscopic kidney transplantation: Influence of Trendelenburg position and CO 2 pneumoperitoneum on cardiovascular, respiratory and renal function

Background:Laparoscopic donor nephrectomy is a routine practice since 1995. Until now, the recipient has always undergone open surgery for transplantation. In our institute, laparoscopic kidney transplantation (LKT) started in 2010. To facilitate this surgery, the patient must be in steep Trendelenburg position for a long duration. Hence, we decided to study the effect of CO2 pnuemoperitoneum and Trendelenburg position in chronic renal failure (CRF) patients undergoing LKT.Methods:A total of 20 adult CRF patients having mean age of 31.7±10.36 years and body mass index 19.65±3.41 kg/m2 without significant coronary artery disease were selected for the procedure. Cardiovascular parameters heart rate (HR), mean arterial pressure (MAP), Central venous pressure (CVP) and respiratory parameters (ETCO2, peak airway pressure) were noted at the time of induction, after induction, 15 min after creation of pnuemoperitoneum, 30 min after Trendelenburg position, 15 min after decompression of pnuemoperitonuem and after extubation. Arterial blood gas analysis was carried out after induction, 15 min after creation of pnuemoperitoneum, 30 min after Trendelenburg position and 15 min after clamp release. Total duration of surgery, anastomosis time, time for the establishment of urine output and total urine output were noted. Serum creatinine on the 1st and 7th post-operative day were recorded.Results:Significant increase in HR was observed after creation of CO2 pneumoperitoneum and just before extubation. Significant increase in the MAP and CVP was noted after creation of pneumoperitoneum and after giving Trendelenburg position. No significant rise in the ETCO2 and PaCO2 was observed. Significant increase in the base deficit was observed after the clamp release, but none of the patients required correction.Conclusion:LKT performed in steep Trendelenburg position with CO2 pneumoperitoneum significantly influenced cardiovascular and respiratory homeostasis; however, measured parameters remained within clinically acceptable range without affecting early function of the transplanted kidney.