Seminars in Cardiothoracic and Vascular Anesthesia, Mar 1, 2011
Background. Anesthetic Agents protect the heart from ischemic injury during perioperative period.... more Background. Anesthetic Agents protect the heart from ischemic injury during perioperative period. We evaluated the protective effects of 2 anesagents on myocardial ischemia -reperfusion injury in rabbit models. Methods. 58 anesthetized and mechaniventilated rabbits randomly received isoflurane (ISO) 2%, propofol (PRP), or were observed as the control group for 15 minutes. We applied vascular tourniquet around the left anterior descending artery (LAD). Myocardium was reperfused for 4 hours. Derivative of pressure over time (dP/dTmax), left ventricular pressure (dLVP), isovolumetric relaxation time (Tau), and segment shortening (SS) were measured over the ischemic and non-ischemic regions of left ventricle (LV). Cardiac troponin I (cTnI), tissue concentrations of tumor necrosis factor á (TNFá), myeloperoxidase activity assay (MPO), and tissue malonyl dialdehyde (MDA) concentrations were measured as indices of cellular injury and inflammatory response. Results. dP/dTmax values significantly decreased during ischemia. Following reperfusion, dP/dTmax, dLVP, and Tau remained depressed in the control animals. Both PRP and ISO restored the function of the myocardium globally. Conclusion. Only ISO improved the recovery of the ischemic myocardium during reperfusion. The effects of PRP were global in nature and involved compensatory hypercontractile state in nonischemic regions of the myocardium. Implication. PRP and ISO protect the heart against an ischemic injury, but only ISO preserves the function of the myocardium at the ischemic region. The survival rate of the PRP-treated group versus the ISO-treated group supports the claim that PRP has smaller contribution to recovery from myocardial ischemia.
BACKGROUND: Experimental data indicate that clinical concentrations of volatile general anestheti... more BACKGROUND: Experimental data indicate that clinical concentrations of volatile general anesthetics like sevofluorane protect the myocardium from ischemia and reperfusion injury, as shown by decreased infarct size and a more rapid recovery of contractile function on reperfusion.1 The exact mechanism of this protective effect is not fully elucidated yet although there are some evidence for involvement of potassium channels, neurotransmitter receptors, protein kinase C activation, and production of reactive oxygen species. OBJECTIVES: We aim to demonstrate the cardio-protective effects of sevoflurane during reperfusion injury when administered concurrently with hydrogen peroxide. We also aim to demonstrate its specificity on mitochondrial ATP sensitive potassium channels (mitoKATP) opening as its mechanism of action during reperfusion. METHODS: Using a Langendorff perfusion system, the hearts were harvested from 48 male, healthy, LE rats that were randomly allocated to 8 groups: contr...
Introduction: Transient periods of hypoxia and ischemia result in myocardial systolic and diastol... more Introduction: Transient periods of hypoxia and ischemia result in myocardial systolic and diastolic dysfunction without causing myocardial cell death. This condition is known as "stunning" and manifest by decreases in contractility and inability of ventricular muscle to relax during diastole.
ABSTRACT Background: Volatile anesthetics have been demonstrated to modulate the release of react... more ABSTRACT Background: Volatile anesthetics have been demonstrated to modulate the release of reactive oxygen species and activation of complement. Both of these immune functions are activated during cardiopulmonary bypass (CPB). Myocardial ischemia reperfusion plays a major role in activation of oxidative metabolism during aortic cross clamping. Methods: The research protocol was approved by the Institutional Review Board subcommittee on human subject at VAMC. Twenty-one patients undergoing CABG were randomized to receive either sevoflurane vapor 2% with cardioplegia (n=11) in a double blinded fashion. Controls received only oxygen (n=10). Anesthesia was maintained by total intravenous anesthesia (TIVA) in both treatment and control groups. Blood samples were obtained at the beginning of CPB, 2 hour and 6 hour after initiation of CPB from an arterial line into CPD-containing test tubes for flow cytometry and heparin-containing tubes for Interleukin 8 (IL-8). They were stained with antiCD13-cy5, antiCD11b-PE and antiCD18-FTIC. Three-color flow cytometry was performed and the ratio of CD11b/CD18 was obtained in CD13+ cell population (neutrophils). Serum IL-8 concentrations were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN).Results: In the control group, IL-8 levels increased from(6.53±6.3 pg/ml) post CPB to (30.23±12.9 pg/ml) and remained elevated for 6 hours (29.4±17.8 pg/ml). In contrast, the plasma concentration of IL-8 was below the detectable range at the 6th post-CPB hour in sevoflurane-treated group, p<0.05. In addition, the plasma concentration of IL-8 was paralleled by the expression of CD-11b/CD-18 on the surface of CD-13+ cells in blood samples obtained from the coronary sinus as assessed by flow cytometry. Neutrophils harvested from coronary sinus blood expressed β2 integrins in higher intensity upon weaning from CPB and 6-hour post-CPB (Figure), when compared to baseline.Conclusion: These results suggest that inclusion of a potent volatile anesthetic in cardioplegia solution decrease the expression of β2 integrins on leukocytes partially by inhibiting IL-8. Complement mediated neutrophil activation may still contribute to the activation of neutrophils during CPB.
... Nader Nader-Djalal, MD a , Wiam Z. Khadra, PhD, CCP a , Wendy Spaulding, CCP a , Anthony L. P... more ... Nader Nader-Djalal, MD a , Wiam Z. Khadra, PhD, CCP a , Wendy Spaulding, CCP a , Anthony L. Panos, MD a ... Group I (n = 10) received a 250-mg/h infusion of propofol after an arterial and mixed venous blood samples were obtained from the CPB machine. ...
Seminars in Cardiothoracic and Vascular Anesthesia, Mar 1, 2011
Background. Anesthetic Agents protect the heart from ischemic injury during perioperative period.... more Background. Anesthetic Agents protect the heart from ischemic injury during perioperative period. We evaluated the protective effects of 2 anesagents on myocardial ischemia -reperfusion injury in rabbit models. Methods. 58 anesthetized and mechaniventilated rabbits randomly received isoflurane (ISO) 2%, propofol (PRP), or were observed as the control group for 15 minutes. We applied vascular tourniquet around the left anterior descending artery (LAD). Myocardium was reperfused for 4 hours. Derivative of pressure over time (dP/dTmax), left ventricular pressure (dLVP), isovolumetric relaxation time (Tau), and segment shortening (SS) were measured over the ischemic and non-ischemic regions of left ventricle (LV). Cardiac troponin I (cTnI), tissue concentrations of tumor necrosis factor á (TNFá), myeloperoxidase activity assay (MPO), and tissue malonyl dialdehyde (MDA) concentrations were measured as indices of cellular injury and inflammatory response. Results. dP/dTmax values significantly decreased during ischemia. Following reperfusion, dP/dTmax, dLVP, and Tau remained depressed in the control animals. Both PRP and ISO restored the function of the myocardium globally. Conclusion. Only ISO improved the recovery of the ischemic myocardium during reperfusion. The effects of PRP were global in nature and involved compensatory hypercontractile state in nonischemic regions of the myocardium. Implication. PRP and ISO protect the heart against an ischemic injury, but only ISO preserves the function of the myocardium at the ischemic region. The survival rate of the PRP-treated group versus the ISO-treated group supports the claim that PRP has smaller contribution to recovery from myocardial ischemia.
BACKGROUND: Experimental data indicate that clinical concentrations of volatile general anestheti... more BACKGROUND: Experimental data indicate that clinical concentrations of volatile general anesthetics like sevofluorane protect the myocardium from ischemia and reperfusion injury, as shown by decreased infarct size and a more rapid recovery of contractile function on reperfusion.1 The exact mechanism of this protective effect is not fully elucidated yet although there are some evidence for involvement of potassium channels, neurotransmitter receptors, protein kinase C activation, and production of reactive oxygen species. OBJECTIVES: We aim to demonstrate the cardio-protective effects of sevoflurane during reperfusion injury when administered concurrently with hydrogen peroxide. We also aim to demonstrate its specificity on mitochondrial ATP sensitive potassium channels (mitoKATP) opening as its mechanism of action during reperfusion. METHODS: Using a Langendorff perfusion system, the hearts were harvested from 48 male, healthy, LE rats that were randomly allocated to 8 groups: contr...
Introduction: Transient periods of hypoxia and ischemia result in myocardial systolic and diastol... more Introduction: Transient periods of hypoxia and ischemia result in myocardial systolic and diastolic dysfunction without causing myocardial cell death. This condition is known as "stunning" and manifest by decreases in contractility and inability of ventricular muscle to relax during diastole.
ABSTRACT Background: Volatile anesthetics have been demonstrated to modulate the release of react... more ABSTRACT Background: Volatile anesthetics have been demonstrated to modulate the release of reactive oxygen species and activation of complement. Both of these immune functions are activated during cardiopulmonary bypass (CPB). Myocardial ischemia reperfusion plays a major role in activation of oxidative metabolism during aortic cross clamping. Methods: The research protocol was approved by the Institutional Review Board subcommittee on human subject at VAMC. Twenty-one patients undergoing CABG were randomized to receive either sevoflurane vapor 2% with cardioplegia (n=11) in a double blinded fashion. Controls received only oxygen (n=10). Anesthesia was maintained by total intravenous anesthesia (TIVA) in both treatment and control groups. Blood samples were obtained at the beginning of CPB, 2 hour and 6 hour after initiation of CPB from an arterial line into CPD-containing test tubes for flow cytometry and heparin-containing tubes for Interleukin 8 (IL-8). They were stained with antiCD13-cy5, antiCD11b-PE and antiCD18-FTIC. Three-color flow cytometry was performed and the ratio of CD11b/CD18 was obtained in CD13+ cell population (neutrophils). Serum IL-8 concentrations were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN).Results: In the control group, IL-8 levels increased from(6.53±6.3 pg/ml) post CPB to (30.23±12.9 pg/ml) and remained elevated for 6 hours (29.4±17.8 pg/ml). In contrast, the plasma concentration of IL-8 was below the detectable range at the 6th post-CPB hour in sevoflurane-treated group, p<0.05. In addition, the plasma concentration of IL-8 was paralleled by the expression of CD-11b/CD-18 on the surface of CD-13+ cells in blood samples obtained from the coronary sinus as assessed by flow cytometry. Neutrophils harvested from coronary sinus blood expressed β2 integrins in higher intensity upon weaning from CPB and 6-hour post-CPB (Figure), when compared to baseline.Conclusion: These results suggest that inclusion of a potent volatile anesthetic in cardioplegia solution decrease the expression of β2 integrins on leukocytes partially by inhibiting IL-8. Complement mediated neutrophil activation may still contribute to the activation of neutrophils during CPB.
... Nader Nader-Djalal, MD a , Wiam Z. Khadra, PhD, CCP a , Wendy Spaulding, CCP a , Anthony L. P... more ... Nader Nader-Djalal, MD a , Wiam Z. Khadra, PhD, CCP a , Wendy Spaulding, CCP a , Anthony L. Panos, MD a ... Group I (n = 10) received a 250-mg/h infusion of propofol after an arterial and mixed venous blood samples were obtained from the CPB machine. ...
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