Effects Of Inhalation Anesthetics Research Articles

Reducing the carbon footprint of operating rooms through education on the effects of inhalation anesthetics on global warming: A retrospective study.

Environmental concerns, especially global warming, have prompted efforts to reduce greenhouse gas emissions. Healthcare systems, including anesthesia practices, contribute to these emissions. Inhalation anesthetics have a significant environmental impact, with desflurane being the most concerning because of its high global warming potential. This study aimed to educate anesthesiologists on the environmental impact of inhalation anesthetics and assess changes in awareness and practice patterns, specifically reducing desflurane use. This study included data from patients who underwent surgery under general anesthesia 1 month before and after education on the effects of inhalation anesthetics on global warming. The primary endpoint was a change in inhalational anesthetic use. Secondary endpoints included changes in carbon dioxide equivalent (CO2e) emissions, driving equivalent, and medical costs. After the education, desflurane use decreased by 50%, whereas sevoflurane use increased by 50%. This shift resulted in a reduction in the overall amount of inhalational anesthetics used. The total CO2e and driving-equivalent values decreased significantly. The cost per anesthesia case decreased, albeit to a lesser extent than expected. Education on the environmental impact of inhalation anesthetics has successfully altered anesthesiologists' practice patterns, leading to reduced desflurane usage. This change has resulted in decreased CO2e emissions and has had a positive effect on mitigating global warming. However, further research is required to assess the long-term impact of such education and the variability in practice patterns across different institutions.

Inhalation Anesthetics for Postoperative Nausea and Vomiting in General Anesthesia Patients

Background: Postoperative nausea and vomiting is an anesthetic complication which is related to various factors. Patients who experience postoperative nausea and vomiting have worse quality of recovery which causes delay in patient discharge from the hospital which will increase the cost of care. Objective: To knowing the effect of inhalation anesthetics on postoperative nausea and vomiting in general anesthesia patients at Dr Soedirman Hospital Kebumen. Method: The study is a quasi-experimental quantitative study with a pre-test-post-test design with a control group design. The population of the study were all patients undergoing general anesthesia at Dr Soedirman Hospital Kebumen. The study was conducted in September - October 2022 with a sample of 56 respondents for each group which was determined using a purposive sampling technique. Data analysis using the Wilcoxon test. Result: Results of analysis of the effect of inhalational anesthesia on postoperative nausea and vomiting in general anesthesia patients at Dr Soedirman Hospital Kebumenp (sig) 0.000. Conclusion: There is an effect of inhalation anesthetics on postoperative nausea and vomiting in general anesthesia patients

Сравнительный анализ применения наркозно-дыхательных контуров для ингаляционной анестезии у лабораторных животных

The article presents a study on the effect of inhalation anesthetics on the body of laboratory animals, depending on the choice of the respiratory circuit. As a result of the research, it was found that the most suitable circuit for inhalation anesthesia in laboratory animals is a semi-open breathing circuit.

Effects of Inhalation Anesthesia and Intravenous Anesthesia on Postoperative Cardiac Function in Elderly Patients with Coronary Artery Disease

Effects of Inhalation Anesthesia and Intravenous Anesthesia on Postoperative Cardiac Function in Elderly Patients with Coronary Artery Disease

Effects of inhalation and propofol anaesthesia on postoperative cognitive dysfunction in elderly noncardiac surgical patients: A systematic review and meta-analysis.

Background:Postoperative cognitive dysfunction (POCD) is a very common event in elderly noncardiac surgical patients. The effects of inhalational anaesthetics and propofol on the incidence of POCD and postoperative cognitive status at different time points after surgery are currently unclear.Methods:We searched the Embase, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs), in which inhalation anaesthesia and propofol anaesthesia were compared. The incidence of POCD or postoperative cognitive status was assessed in elderly patients undergoing noncardiac surgery.Results:Fifteen RCTs with 1854 patients were included in this meta-analysis. The incidence of POCD on postoperative Days 2–6 after propofol anaesthesia was markedly lower than that after inhalation anaesthesia (risk ratio (RR): 0.37, 95% confidence interval (CI): 0.15–0.88, P = .025), and Mini-Mental State Examination (MMSE) scores after propofol anaesthesia were substantially higher than those after inhalation anaesthesia (standard mean difference (SMD): 0.59, 95% CI: 0.07–1.11, P = .026). The levels of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were much lower after propofol anaesthesia than after inhalation anaesthesia (SMD: -2.027, 95% CI: -3.748– -0.307, P = .021; SMD: -0.68, 95% CI: -0.93– -0.43, P < .001).Conclusions:The moderate evidence from this meta-analysis shows that, in elderly noncardiac surgical patients, propofol anaesthesia is superior to inhalation anaesthesia for attenuating of early POCD incidence, and low-level evidence shows that cognitive status is higher and systemic inflammation is less severe after propofol anaesthesia in the early days after surgery.Limitations:The sample size was not sufficiently large for systemic inflammation, and the tools to identify POCD were not uniform in the included studies.

Effect of Xenon on the Phosphorylation of Glycogen Synthase Kinase 3β and Antioxidant Enzymes in Rat Brain

Relevance. The increase in the number of severe brain injuries due to stroke and traumatic brain injury determines the need to study and develop effective strategies for neuroprotection. The article highlights new mechanisms of the neuroprotective action of the inhalation anesthetic xenon based on the data of our own experimental studies.Aim of study. To assess the effect of anesthesia with xenon at a concentration of 0.5 MAC (minimum alveolar concentration) on the phosphorylation of glycogen synthase kinase 3β (GSK-3β) and the content of antioxidant defense enzymes in the rat brain.Material and methods. The effect of inhalation anesthesia with xenon on the phosphorylation of the GSK-3β enzyme in comparison with lithium chloride, as well as on the content of heme oxygenase, catalase, and Mn-superoxide dismutase in rat brain homogenates was studied by immunoblotting.Results. The use of xenon at a concentration of 0.5 MAA causes an almost twofold increase in the content of the phosphorylated form of the GSK-3β enzyme in comparison with the control (p&lt;0.05) and significantly increases the pool of antioxidant defense enzymes: heme oxygenase by 50% (p &lt;0.05) and Mn-superoxide dismutase by 60% (p&lt;0.05).Conclusion. The conducted experimental study revealed new molecular mechanisms of action of the inhalation anesthetic xenon. The effect of xenon on the pool of enzymes involved in the protection of the brain from oxidative distress was found. The data obtained indicate the prospects for using xenon and require further research in this direction. The use of xenon at a concentration of 50 vol.% (0.5 MAA) for 30 minutes does not affect the content of the glycogen synthase-3β enzyme, at the same time causing an almost twofold increase in its phosphorylated form, the glycogen synthase-3β enzyme, and is accompanied by a significant increase the content of heme oxygenase, Mn-superoxide dismutase and a slight increase in the content of catalase in rat brain homogenates. Thus, the results of the study suggest that one of the possible mechanisms of the neuroprotective effect of xenon is the phosphorylation of glycogen synthase-3β, which prevents the opening of the mitochondrial pore, inhibiting the death of mitochondria-mediated apoptosis of neurons and increasing the level of antioxidant protection in them.

Effect of inhalation anesthesia with isoflurane on circadian rhythm of murine intraocular pressure

PurposeFor research on circadian intraocular pressure (IOP), rebound tonometers are widely used with or without general anesthesia as a non-invasive approach to obtain IOP values. However, whether general anesthesia such as inhalation anesthesia with isoflurane affects the circadian rhythm of IOP and in turn IOP measurements is currently unclear. As such, data reporting IOP values obtained under general anesthesia should be interpreted with caution. The purpose of this study was to evaluate how general anesthesia with isoflurane inhalation affects the circadian rhythm of IOP. MethodsC57Bl/6J strain mice maintained using a 12h:12h light/dark cycle (lights on and off at ZT0 and ZT12, respectively) were used. IOPs were measured using a rebound tonometer (Icare TonoLab) before and 3, 5, 10, 15, and 30 min after initiating anesthesia in both light and dark phases (ZT 2–6 and ZT 14–18, respectively). Awake IOPs and IOPs at 3 and 5 min after anesthesia initiation were also obtained at ZT5, 8, 11, 14, 17, and 20 to assess IOP diurnal curves under gas anesthesia. ResultsIOP values gradually decreased after anesthesia initiation in both light and dark phases (P < 0.001) and there was no interaction between light/dark phase and anesthesia time (P = 0.88). There was a slight, but not significant, reduction in IOP 3 min after initiating anesthesia (P = 0.23), and significant decreases in IOP occurred at subsequent timepoints (P ≤ 0.001). Both awake and anesthetized mice showed a robust IOP rhythm that reached a peak and trough in the dark and light phase, respectively. Awake IOP levels did not significantly differ from those for anesthetized mice at 3 min after anesthesia initiation at all time points (P ≥ 0.07). ConclusionsBoth awake and anesthetized mice demonstrated a robust circadian rhythm for IOP. Murine IOP showed similar gradual decreases under inhalation anesthesia with isoflurane in both the light and dark phases. IOPs measured using a rebound tonometer within 3 min of initiating isoflurane anesthesia were comparable to awake IOPs, and thus may be useful to monitor the circadian rhythm of IOP in mice.

Comparison of the effects of inhalation anesthetics in the intraand postoperative periods during kidney transplantation

Background. Every year the number of patients with chronic renal failure is steadily increasing. Allogeneic kidney transplantation from a post-mortem donor is a radical method to cope with chronic renal failure, improving the quality and life expectancy of patients. Currently available inhalation anesthetics make it easy to control the depth of anesthesia; they are excreted by the lungs unchanged, providing a quick emergence from anesthesia and easy waking up of the patient. An “ideal” inhalation anesthetic used for kidney transplantation should have a minimal amount of adverse effects.The aim was to compare the efficacy of inhaled anesthetics used for allogeneic kidney transplantation from a posthumous donor.Material and methods. A randomized, prospective, single-center study included 62 patients with end-stage chronic renal failure. The subjects were divided into three groups depending on the type of the inhalation anesthetic used. The first group included patients who underwent low-flow inhalation anesthesia with desflurane, the second and third groups were comparator groups where patients received sevoflurane or isoflurane, respectively, as an inhalation anesthetic. When assessing hemodynamic parameters, most episodes of hemodynamic instability were seen in the isoflurane group; the most stable statistically significant values were observed in the sevoflurane group, and desflurane took an intermediate position.Results. The use of desflurane as an inhalation anesthetic in a kidney transplant provided a quicker recovery of consciousness and early extubation of the patient after anesthesia compared to the sevoflurane or isoflurane use. So desflurane proved to be the most efficient of the three studied inhalation anesthetics. Conclusion. Desflurane is the optimal inhalation anesthetic used in kidney transplantation.

Intraoperative Assessment of Coronary Artery Stenosis by 2D Speckle-Tracking Echocardiography: The Correlation Between Peak Strain Rate During Early Diastole and the Severity of Coronary Artery Stenosis in Patients Undergoing Coronary Artery Bypass Grafting

The effects of inhalation anesthetics on cardiac function and the low correlation between transthoracic and transesophageal echocardiographic measurements may alter the ability of transesophageal echocardiography-derived strain rate during early diastole to detect coronary artery stenosis in anesthetized patients. The authors assessed the correlation between coronary artery stenosis and strain-based parameters during early diastole in heart failure patients with preserved ejection fraction undergoing coronary artery bypass grafting. Retrospective clinical study. Single university hospital. Thirty-two adult patients with preserved ejection fraction undergoing coronary artery bypass grafting between December 2016 and December 2018. None. Transesophageal echocardiography images and coronary artery angiographies of the participants were studied. The correlation between the severity of coronary artery stenosis and strain-based indices measured in the corresponding left ventricular segments were assessed. Receiver operating characteristic curve analysis of strain rate during early diastole was used to predict the presence of coronary artery stenosis ≥70%. Regarding the severity of coronary artery stenosis, it demonstrated a strong and inverse correlation with strain rate during early diastole (r = -0.71, p < 0.001), but showed no significant correlation with time to peak strain rate during early diastole (r = 0.19, p = 0.18). Strain rate during early diastole ≤1.5 s-1 had a sensitivity of 77% and a specificity of 87% for predicting coronary artery stenosis ≥70% (area under the curve, 0.88). Strain rate during early diastole significantly correlates with the severity of coronary artery stenosis in anesthetized patients suffering from heart failure with preserved ejection fraction.

Neurotoxicity of Inhalation Anesthetics in the Neonatal Rat Brain: Effects on Behavior and Neurodegeneration in the Piriform Cortex.

There is concern that clinical use of anesthetic drugs may cause neurotoxicity in the developing brain and subsequent abnormal neurobehavior. We therefore evaluated neurotoxic effects of inhalation anesthetics in the neonatal rat brain, using in vivo histological and neurobehavioral outcomes. Wistar rats (n=79, postnatal day 15) were subjected to a clinically relevant single exposure of urethane, isoflurane, sevoflurane, or placebo, without surgery. At 48 h and 96 h, behavioral parameters were recorded and the animals were sacrificed. In cryosectioned brains, total cells and dying cells in layer II of the piriform cortex were counted using unbiased stereology. At 48 h, cell numbers in layer II of the piriform cortex of all drug-treated animals were reduced versus controls (p=0.01). The effect persisted at 96 h in isoflurane- and urethane-exposed animals. Piriform cortical layer II neurons undergoing degeneration, detected histologically by pyknotic nuclei and eosinophilic cytoplasm, were increased in the animals treated with isoflurane (1.9 ± 0.7 at 96 h) and urethane (2.4 ± 0.8 at 96 h) versus sevoflurane (0.8 ± 0.3 at 96 h) and controls (0.9 ± 0.2 at 96 h). Sevoflurane- and isoflurane-treated animals exhibited increased activity and decreased suckling compared with controls, and sevoflurane-exposed animals also displayed increased rearing behavior at both timepoints.

The Effect of Inhalation Anesthesia with Hyperventilation and Total Intravenous Anesthesia on Intracranial Pressure Control in Pediatrics with Craniosynostosis Surgery: A Randomized Clinical Trial

Background: Intracranial pressure (ICP) control is one of the anesthesiologist challenges in craniosynostosis repair surgery, especially in multiple sutures involvement. The aim of this study was comparing the effect of two anesthesia methods including inhalation with hyperventilation and total intravenous anesthesia (TIVA) on ICP control and surgeon satisfaction in pediatrics with craniosynostosis surgery. Materials and Methods: In this randomized clinical trial study, 40 pediatric patients with American society of anesthesiologists (ASA) І-ІІ, 6 months to 2 years old were included. All of the patients were scheduled for craniosynostosis repair at Mofid Children Hospital, Tehran, Iran, in May 2016 to January 2017. The patients were randomly divided into two groups. In hyperventilation group, patients received isoflurane for maintenance of anesthesia and hyperventilation (Paco2=25-30 mmHg) established during surgery. The total intravenous anesthesia (TIVA) group received propofol infusion for anesthesia maintenance and Paco2 was maintained 35 mmHg. Intra cranial pressure (ICP) was assessed by surgeon using a 4-point scale. Hemodynamic (mean arterial pressure and heart rate) changes and blood loss were compared between hyperventilation and TIVA groups. Results: The mean age of patients in hyperventilation group was 10.9±3.25 months and in TIVA group was 8.7 ± 2063 months (p=0.11). Fourteen (70%) patients in hyperventilation group and 6 (30%) patients in TIVA group were male (p=0.74). A significant difference was seen in ICP control and surgical condition between hyperventilation and TIVA groups (p=0.032). ICP was controlled better in hyperventilation group. There was no difference in hemodynamic parameters and blood loss between hyperventilation and TIVA groups (p>0.05). Conclusion: This study showed inhalation anesthesia with hyperventilation was more effective than TIVA on ICP control in craniosynostosis surgery.

Effects of Inhalation Anesthesia vs. Total Intravenous Anesthesia (TIVA) vs. Spinal-Epidural Anesthesia on Deep Vein Thrombosis After Total Knee Arthroplasty.

BackgroundThe objective of the present study was to evaluate the varying efficacy of general anesthesia (GA), combined spinal-epidural anesthesia (CSEA), and total intravenous anesthesia (TIVA) on the occurrence of deep vein thrombosis (DVT) following total knee arthroplasty (TKA).Material/MethodsFrom July 2013 to May 2015, a total of 197 cases of patients who had undergone TKA treatment at either the Drum Tower Hospital or Nanjing General Hospital of Nanjing Military Command were recruited to participate in the study. The patients in the study were separated into 3 groups depending on the anesthesia approach received: the GA group, the CSEA group, and the TIVA group. The baseline characteristics and relative parameters of patients were monitored before and after surgery for analytic purposes. A 3-month follow-up after surgery was conducted to observe the rate of DVT occurrence and any DVT-related complications.ResultsThe TIVA group exhibited significant decreases in relation to the swallowing time reflex, extubation, and consciousness recovery in comparison to other groups in the study. Additionally, platelet count was significantly decreased and there was drastic extension of the activated partial thromboplastin time (APTT) in the CSEA group and the TIVA group. There were clear differences in the incidence of DVT and its complications among the 3 groups. The TIVA group displayed the lowest incidences of DVT and DVT-related complication during the study. Based on logistic regression analysis, the type of anesthesia was utilized as an independent correlative factor for the occurrence of DVT after surgery.ConclusionsThe results obtained during the study established a clinical basis for comparative analysis of various anesthesia methods. We found that, compared with GA and CSEA, patients undergoing TIVA had a reduced rate of risk in relation to the occurrence of DVT following TKA.

Effects of inhalation anesthesia with desflurane and sevoflurane on cognitive function after off-pump coronary arterybypass grafting

Effects of inhalation anesthesia with desflurane and sevoflurane on cognitive function after off-pump coronary arterybypass grafting

Anesthetic-dependent changes in the chain-melting phase transition of DPPG liposomes studied using near-infrared spectroscopy supported by PCA

The effect of inhalation anesthetics (enflurane, isoflurane, sevoflurane or halothane) on the lipid chain-melting phase transition of negatively charged phospholipid membranes was studied using near-infrared (NIR) spectroscopy supported by Principal Component Analysis (PCA). NIR spectra of anesthetics-mixed dipalmitoylphosphatidylglycerol (DPPG) membranes were recorded in a range of the first overtone of the symmetric and antisymmetric stretching vibrations of CH2 groups of lipid aliphatic chains as a function of increasing temperature. Anesthetic-dependent changes in the trans to gauche conformers ratio of CH2 groups in the hydrocarbon lipid chains were characterized in detail and compared with the zwitterionic lipid membranes, which were built of dipalmitoylphosphatidylcholine (DPPC) molecules.

Effects of inhalational anesthesia on blood gases and pH in California sea lions

AbstractDespite the widespread use of inhalational anesthesia with spontaneous ventilation in many studies of otariid pinnipeds, the effects and risks of anesthetic‐induced respiratory depression on blood gas and pH regulation are unknown in these animals. During such anesthesia in California sea lions (Zalophus californianus), blood gas and pH analyses of opportunistic blood samples revealed routine hypercarbia (highest PCO2 = 128 mm Hg [17.1 kPa]), but adequate arterial oxygenation (PO2 &gt; 100 mm Hg [13.3 kPa] on 100% inspiratory oxygen). Respiratory acidosis (lowest pH = 7.05) was limited by the increased buffering capacity of sea lion blood. A markedly widened alveolar‐to‐arterial PO2 difference was indicative of atelectasis and ventilation‐perfusion mismatch in the lung secondary to hypoventilation during anesthesia. Despite the generally safe track record of this anesthetic regimen in the past, these findings demonstrate the value of high inspiratory O2 concentrations and the necessity of constant vigilance and caution. In order to avoid hypoxemia, we emphasize the importance of late extubation or at least maintenance of mask ventilation on O2 until anesthetic‐induced respiratory depression is resolved. In this regard, whether for planned or emergency application, we also describe a simple, easily employed intubation technique with the Casper “zalophoscope” for sea lions.

Effect of Inhalational Anesthetics and Positive-pressure Ventilation on Ultrasound Assessment of the Great Vessels: A Prospective Study at a Children's Hospital.

Bedside ultrasound has emerged as a rapid, noninvasive tool for assessment and monitoring of fluid status in children. The inferior vena cava (IVC) varies in size with changes in blood volume and intrathoracic pressure, but the magnitude of change to the IVC with inhalational anesthetic and positive-pressure ventilation (PPV) is unknown. Prospective observational study of 24 healthy children aged 1 to 12 yr scheduled for elective surgery. Ultrasound images of the IVC and aorta were recorded at five time points: awake; spontaneous ventilation with sevoflurane by mask; intubated with peak inspiratory pressure/positive end-expiratory pressure of 15/0, 20/5, and 25/10 cm H2O. A blinded investigator measured IVC/aorta ratios (IVC/Ao) and changes in IVC diameter due to respiratory variation (IVC-RV) from the recorded videos. Inhalational anesthetic decreased IVC/Ao (1.1 ± 0.3 vs. 0.6 ± 0.2; P < 0.001) but did not change IVC-RV (median, 43%; interquartile range [IQR], 36 to 58% vs. 46%; IQR, 36 to 66%; P > 0.99). The initiation of PPV increased IVC/Ao (0.64 ± 0.21 vs. 1.16 ± 0.27; P < 0.001) and decreased IVC-RV (median, 46%; IQR, 36 to 66% vs. 9%; IQR, 4 to 14%; P < 0.001). There was no change in either IVC/Ao or IVC-RV with subsequent incremental increases in peak inspiratory pressure/positive end-expiratory pressure (P > 0.99 for both). Addition of inhalational anesthetic affects IVC/Ao but not IVC-RV, and significant changes in IVC/Ao and IVC-RV occur with initiation of PPV in healthy children. Clinicians should be aware of these expected vascular changes when managing patients. Establishing these IVC parameters will enable future studies to better evaluate these measurements as tools for diagnosing hypovolemia or predicting fluid responsiveness.

Erratum: Comparison of the effects of inhalational anesthesia with desflurane and total intravenous anesthesia on cardiac biomarkers after aortic valve replacement

Erratum: Comparison of the effects of inhalational anesthesia with desflurane and total intravenous anesthesia on cardiac biomarkers after aortic valve replacement

Inhalational Anesthetic Agents and Their Effects on Cancer Cell Biology

An improved understanding of the cellular mechanisms that account for the protective effect of inhalational anesthetics on tissues subjected to ischemia–reperfusion injury has led some to question whether a similar survival advantage may be afforded to cancer cells in patients undergoing surgery. Such an effect would be potentially detrimental to long-term cancer outcomes. Anesthetic-induced activation of hypoxia-inducible factors and upstream cell signaling pathways such as PI3K/Akt/mTOR appear to underpin the adaptive and pro-survival responses of cells to potentially lethal injuries. These same pathways are heavily implicated in malignancy and metastasis and their activity is associated with poor prognosis in most human solid cancers. This review gives an account of the manner in which inhalational anesthetics amplify cell signaling and induce transcriptional modifications to a variety of cell types, with a particular focus on how this relates to cancer cell biology and the various hallmarks of malignancy such as angiogenesis, cell proliferation, metabolic adaptation, invasion, and metastasis.

Effects of inhalational anaesthetics in experimental allergic asthma

We evaluated whether isoflurane, halothane and sevoflurane attenuate the inflammatory response and improve lung morphofunction in experimental asthma. Fifty-six BALB/c mice were sensitised and challenged with ovalbumin and anaesthetised with isoflurane, halothane, sevoflurane or pentobarbital sodium for one hour. Lung mechanics and histology were evaluated. Gene expression of pro-inflammatory (tumour necrosis factor-α), pro-fibrogenic (transforming growth factor-β) and pro-angiogenic (vascular endothelial growth factor) mediators, as well as oxidative process modulators, were analysed. These modulators included nuclear factor erythroid-2 related factor 2, sirtuin, catalase and glutathione peroxidase. Isoflurane, halothane and sevoflurane reduced airway resistance, static lung elastance and atelectasis when compared with pentobarbital sodium. Sevoflurane minimised bronchoconstriction and cell infiltration, and decreased tumour necrosis factor-α, transforming growth factor-β, vascular endothelial growth factor, sirtuin, catalase and glutathione peroxidase, while increasing nuclear factor erythroid-2-related factor 2 expression. Sevoflurane down-regulated inflammatory, fibrogenic and angiogenic mediators, and modulated oxidant-antioxidant imbalance, improving lung function in this model of asthma.

Effect of Isoflurane on Myocardial Energetic and Oxidative Stress in Cardiac Muscle from Zucker Diabetic Fatty Rat

The effect of inhalational anesthetics on myocardial contraction and energetics in type 2 diabetes mellitus is unknown. We investigated the effect of isoflurane (ISO) on force and intracellular Ca(2+) transient (iCa), myocardial oxygen consumption (MVo(2)), and energetics/redox behavior in trabecular muscles from Zucker diabetic fatty (ZDF) rats. At baseline, force and corresponding iCa were lower in ZDF trabeculae than in controls. ISO decreased force in both groups in a dose-dependent manner. ISO did not affect iCa amplitude in controls, but ISO > 1.5% significantly reduced iCa amplitude in ZDF trabeculae. ISO-induced force depression fully recovered as a result of increased iCa when external Ca(2+) was raised in controls. However, both force and iCa remained low in ZDF muscle at elevated external Ca(2+). In controls, force, iCa, and MVo(2) increased when stimulation frequency was increased from 0.5 to 1.5 Hz. ZDF muscles, however, exhibited blunted responses in force and iCa and decreased MVo(2). Oxidative stress levels were unchanged in control muscles but increased significantly in ZDF muscles after exposure to ISO. Finally, the depressive effect of ISO was prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) in ZDF muscles. These findings suggest that ISO dose-dependently attenuates force in control and ZDF muscles with differential effect on iCa. The mechanism of force depression by ISO in controls is mainly decreased myofilament Ca(2+) sensitivity, whereas in ZDF muscles the ISO-induced decrease in contraction is due to worsening oxidative stress, which inhibits iCa and force development.