Propofol Attenuates the Myocardial Protection Properties of Desflurane by Modulating Mitochondrial Permeability Transition.

BACKGROUND: Desflurane and propofol are cardioprotective, but relative efficacy is unclear. The aim was to compare myocardial protection of single, simultaneous, and serial administration of desflurane and propofol. METHODS: Sixty New Zealand White rabbits and 65 isolated Sprague Dawley rat hearts randomly received desflurane, propofol, simultaneous desflurane and propofol, or sequential desflurane then propofol. Rabbits were subdivided to receive either ischemia-reperfusion with temporary occlusion of the left anterior descending artery or a time-matched, nonischemic perfusion protocol, whereas rat hearts were perfused in a Langendorff model with global ischemia-reperfusion. End points were hemodynamic, functional recovery, and mitochondrial uptake of H-2-deoxy-D-glucose as an indicator of mitochondrial permeability transition. RESULTS: In rabbits, there were minimal increases in preload-recruitable stroke-work with propofol (P < .001), desflurane (P < .001), and desflurane-and-propofol (P < .001) groups, but no evidence of increases with pentobarbitone (P = .576) and desflurane-then-propofol (P = .374). In terms of end-diastolic pressure-volume relationship, there was no evidence of increase compared to nonischemic controls with desflurane-then-propofol (P = .364), a small but significant increase with desflurane (P < .001), and larger increases with pentobarbitone (P < .001), propofol (P < .001), and desflurane-and-propofol (P < .001).In rat hearts, there was no statistically significant difference in mitochondrial H-activity between propofol and desflurane-and-propofol (165 ± 51 × 10 vs 154 ± 51 × 10 g·mL·min/µmol; P = .998). Desflurane had lower uptake than propofol (65 ± 21 × 10 vs 165 ± 51 × 10 g·mL·min/µmol; P = .039), but there was no statistically significant difference between desflurane and desflurane-then-propofol (65 ± 21 × 10 vs 59 ± 11 × 10 g·mL·min/µmol; P = .999). CONCLUSIONS: Propofol and desflurane are cardioprotective, but desflurane is more effective than propofol. The added benefit of desflurane is lost when used simultaneously with propofol.

A systematic review and meta-analysis evaluating ischemic conditioning during percutaneous coronary intervention.

AIM: A systematic review and meta-analysis, evaluating ischemic conditioning during percutaneous coronary intervention (PCI). METHODS & RESULTS: A database search of randomized trials of ischemic conditioning in PCI created three subgroups for meta-analysis: mortality in elective PCI with remote ischemic preconditioning (RIPreC; subgroup 1a, n = 3) - no outcome difference between RIPreC and control (odds ratio: 0.34; 95% CI: 0.08-1.56), myocardial salvage index in ST-elevation myocardial infarction (STEMI) with RIPreC (subgroup 1b, n = 2) - favored RIPreC (mean difference: 0.13; 95% CI: 0.07-0.19), and infarct size in STEMI with local ischemic postconditioning (LIPostC) (subgroup 4b, n = 12) - favored LIPostC (mean difference: -4.13 g.m-2; 95% CI: -7.36 to -0.90 g.m-2). CONCLUSION: RIPreC and LIPostC improve myocardial salvage index and myocardial infarct size respectively in PCI for STEMI. No mortality benefit detected with RIPreC in elective PCI.

Molecular mechanisms of ischemic conditioning: translation into patient outcomes.

Following the initiation of an ischemic insult, reperfusion injury (RI) can result in numerous deleterious cardiac effects, including cardiomyocyte death. Experimental data have suggested that ischemic conditioning, when delivered either before or after the ischemic event, can provide considerable cardioprotection against RI. Ischemic conditioning involves delivering brief repetitive cycles of ischemia to the myocardium (local) or to another distal organ or structure (remote). This review will discuss recent advances in the molecular mechanisms involved in RI, the signaling pathways recruited by ischemic conditioning and conclude with an appraisal of the evidence for the use of ischemic conditioning in current clinical practice.

Randomised Comparison of the AMBU AuraOnce Laryngeal Mask and the LMA Unique Laryngeal Mask Airway in Spontaneously Breathing Adults.

We conducted a randomised single-blind controlled trial comparing the LMA-Unique (LMAU) and the AMBU AuraOnce (AMBU) disposable laryngeal mask in spontaneously breathing adult patients undergoing general anaesthesia. Eighty-two adult patients (ASA status I-IV) were randomly allocated to receive the LMAU or AMBU and were blinded to device selection. Patients received a standardized anesthetic and all airway devices were inserted by trained anaesthetists. Size selection was guided by manufacturer recommendations. All data were collected by a single, unblinded observer. When compared with the LMAU, the AMBU produced significantly higher airway sealing pressures (AMBU 20 ± 6; LMAU 15 ± 7 cm H(2)O; P = 0.001). There was no statistical difference between the two devices for overall success rate, insertion time, number of adjustments, laryngeal alignment, blood-staining, and sore throat (P ≥ 0.05). The AMBU AuraOnce disposable laryngeal mask provided a higher oropharyngeal leak pressure compared to the LMA Unique in spontaneously breathing adult patients.

The mitochondrial permeability transition pore and its role in anaesthesia-triggered cellular protection during ischaemia-reperfusion injury.

This review summarises the most recent data in support of the role of the mitochondrial permeability transition pore (mPTP) in ischaemia-reperfusion injury, how anaesthetic agents interact with this molecular channel, and the relevance this holds for current anaesthetic practice. Ischaemia results in damage to the electron transport chain of enzymes and sets into play the assembly of a non-specific mega-channel (the mPTP) that transgresses the inner mitochondrial membrane. During reperfusion, uncontrolled opening of the mPTP causes widespread depolarisation of the inner mitochondrial membrane, hydrolysis of ATP, mitochondrial rupture and eventual necrotic cell death. Similarly, transient opening of the mPTP during less substantial ischaemia leads to differential swelling of the intermembrane space compared to the mitochondrial matrix, rupture of the outer mitochondrial membrane and release of pro-apoptotic factors into the cytosol. Recent data suggests that cellular protection from volatile anaesthetic agents follows specific downstream interactions with this molecular channel that are initiated early during anaesthesia. Intravenous anaesthetic agents also prevent the opening of the mPTP during reperfusion. Although by dissimilar mechanisms, both volatiles and propofol promote cell survival by preventing uncontrolled opening of the mPTP after ischaemia. It is now considered that anaesthetic-induced closure of the mPTP is the underlying effector mechanism that is responsible for the cytoprotection previously demonstrated in clinical studies investigating anaesthetic-mediated cardiac and neuroprotection. Manipulation of mPTP function offers a novel means of preventing ischaemic cell injury. Anaesthetic agents occupy a unique niche in the pharmacological armamentarium available for use in preventing cell death following ischaemia-reperfusion injury.

L-arginine cardioplegia reduces oxidative stress and preserves diastolic function in patients with low ejection fraction undergoing coronary artery surgery.

PL-arginine cardioplegia decreases biochemical markers of myocardial damage and oxidative stress in patients with normal left ventricular function. We investigated the effects of L-arginine supplemented cardioplegic arrest in patients with reduced ejection fraction. Fifty-three adult patients with left ventricular ejection fraction <35% undergoing elective coronary artery bypass surgery were randomised to receive blood cardioplegia with or without L-arginine. Following cardiopulmonary bypass, measured endpoints were cardiac troponin-I concentration at 12 and 24 hours, coronary sinus concentrations of malondialdehyde and superoxide dismutase activity at five and 15 minutes, lactic acid flux at one, five and 15 minutes and left ventricular systolic and diastolic function after protamine administration. There were no differences in cardiac troponin-I between groups. Malondialdehyde was lower in the L-arginine group, 0.28 ± 0.12 vs 0.48 ± 0.32 (5 minutes) and 0.31 ± 0.14 vs 0.38 ± 0.15 nmol.ml(-1) (15 minutes) (P=0.0004). Superoxide dismutase activity was higher in L-arginine group, 229 ± 87 vs 191.3 ± 68 (5 minutes), 229 ± 54 vs 198 ± 15 nmol.minute(-1).m(l) (15 minutes) (P=0.005). Lactic acid flux was lower in L-arginine group, 0.15 ± 0.23 vs 0.48 ± 0.32 (1 minute), 0.08 ± 0.19 vs 0.38 ± 0.31 (5 minutes) and -0.15 ± 0.13 vs 0.26 ± 0.30 mmol.l(-1) (15 minutes), (P=0.0003). There was no difference in left ventricular systolic function. The mitral annular tissue Doppler inflow (e') velocity during early diastole improved in the L-arginine group following cardiopulmonary bypass (control 4.2 ± 1.9 cm.s(-1) to 3.6 ± 1.2 cm.s(-1) vs L-arginine 3.8 ±1.2 cm.s(-1) to 4.6 ± 1.4 cm.s(-1)) (P=0.018). In patients with reduced ejection fraction, L-arginine supplemented cardioplegic arrest did not affect postoperative cardiac troponin-I levels, but attenuated cardiac cellular peroxidation and improved early left ventricular diastolic function.