Signaling pathways involved in postconditioning-induced cardioprotection of human myocardium, in vitro

We examined the respective role and relationship between protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channel and p38 mitogen-activated protein kinase (MAPK) in postconditioning of human myocardium, in vitro. Isometrically contracting, isolated human right atrial trabeculae were exposed to 30 min hypoxia and 60 min reoxygenation. Phorbol 12-myristate 13-acetate (a PKC activator), diazoxide (a mitoK(ATP) opener) and anisomycin (a p38 MAPK activator) were superfused in early reoxygenation alone and with calphostin C (a PKC inhibitor), 5-hydroxy-decanoate (5-HD, a mitoK(ATP) channel inhibitor) and SB 202190 (a p38 MAPK inhibitor). Developed force at the end of the 60 min reoxygenation (FoC(60)) period was compared between groups (mean +/- SD). Phorbol 12-myristate 13-acetate (91 +/- 4% of baseline), diazoxide (85 +/- 5% of baseline) and anisomycin (90 +/- 4% of baseline) enhanced the FoC(60) as compared with the control group (53 +/- 7% of baseline, P < 0.0001). The enhanced FoC(60) induced by phorbol 12-myristate 13-acetate was abolished by calphostin C (52 +/- 5% of baseline) and 5-HD (56 +/- 3% of baseline), but not by SB 202190 (90 +/- 8%). The diazoxide-induced recovery of FoC(60) was attenuated by 5-HD (55 +/- 6% of baseline), but was not modified by calphostin C (87 +/- 5% of baseline) and SB 202190 (90 +/- 8% of baseline). The anisomycin-induced recovery of FoC(60) was abolished by calphostin C (61 +/- 9% of baseline) and SB 202190 (52 +/- 8% of baseline), but not by 5-HD (88 +/- 6% of baseline). In conclusion, PKC activation, opening of mitoK(ATP) channels and p38 MAPK activation in early reoxygenation induced the postconditioning of human myocardium, in vitro. Furthermore, PKC activation was upstream of the opening of mitoK(ATP) channels; p38 MAPK acted on PKC. Therefore, mitoK(ATP) and p38 MAPK seemed to be involved in two independent pathways

The prognostic value of B-type natriuretic peptide after cardiac surgery: a comparative study between coronary artery bypass graft surgery and aortic valve replacement

OBJECTIVES: The influence of the cardiac surgical procedure on B-type natriuretic peptide (BNP) for the identification of high-risk patients has not been evaluated. This study aimed to compare the prognostic utility of pre- and postoperative BNP in predicting adverse long-term outcome after coronary artery bypass graft (CABG) surgery and aortic valve replacement (AVR). DESIGN: A retrospective study. SETTING: A university teaching hospital. PARTICIPANTS: One hundred eighty-nine patients. MEASUREMENTS AND MAIN RESULTS: Preoperative, early postoperative (24 hours), and late postoperative (day 5) BNP levels were measured. Major adverse cardiac events (MACEs) within 12 months after surgery were chosen as study endpoints. The predictive abilities of BNP measurements were compared using receiver operating characteristic (ROC) curves. Patients were stratified by CABG surgery (n = 100) and AVR (n = 89). Thirty-four (18%) patients experienced 44 MACEs over the study period. Preoperative BNP values were significantly different between groups. Postoperative BNP gradually increased by 431% on day 5 after CABG surgery and by 100% after AVR (both p < 0.001 v preoperative values). Pre- and early postoperative BNP values were accurate in predicting MACEs after AVR (areas under the ROC curves: 0.78 [95% confidence interval, 0.66-0.90] and 0.76 [95% confidence interval, 0.62-0.89], respectively) and inaccurate after CABG surgery (0.54 [95% confidence interval, 0.38-0.70] and 0.54 [95% confidence interval, 0.36-0.73], respectively). The late postoperative BNP value was of limited value. CONCLUSIONS: BNP measurements should take into account the type of cardiac surgery. Whatever the time of measurement, BNP accurately predicts long-term adverse outcome in valve surgery patients. A late postoperative BNP measurement is useless after cardiac surgery

The inotropic and lusitropic effects of ketamine in isolated human atrial myocardium: The effect of adrenoceptor blockade

We studied the direct myocardial effects of racemic ketamine, in the presence of \u3b1- and \u3b2-adrenoceptor blockade, on isolated human right atrial myocardium. Isometric force of contraction (FoC), its first derivative with time (+dF/dt), the contraction relaxation coupling parameter R2 = (+dF/dt) / (-dF/dt), and time to half relaxation (T1/2) were recorded before and after addition of 10-6, 10-5 and 10-4 M racemic ketamine alone and in the presence of \u3b1-adrenoceptor blockade (phentolamine 10-6 M) and \u3b2-adrenoceptor blockade (propranolol at 10-6 M). Ketamine had a moderate positive inotropic effect at 10-5 M (FoC, 104% \ub1 5% of baseline value; P = 0.03) and 10-4 M (FoC, 107% \ub1 11% of baseline value; P = 0.09). Racemic ketamine had a negative inotropic effect in the presence of propranolol (FoC, ketamine 10-6 M, 77% \ub1 11%; ketamine 10-5 M, 63% \ub1 16%; ketamine 10-4 M, 62% \ub1 17% of baseline; P < 0.001) but not phentolamine (FoC, ketamine at 10-6 M, 94% \ub1 6%; ketamine 10-5 M, 96% \ub1 5%; and ketamine 10-4 M, 98% \ub1 15% of baseline). Ketamine decreased T1/2 (ketamine 10-5 M, 94% \ub1 3% of baseline value; P < 0.001 and ketamine 10-4 M, 90% \ub1 9% of baseline value; P = 0.007) but did not modify R2. In human right atrial myocardium, racemic ketamine induced a moderate positive inotropic effect and hastened isometric relaxation. In the presence of \u3b2-adrenoceptor blockade it induced a direct negative inotropic effect

A comparison of endotracheal bioimpedance cardiography and transpulmonary thermodilution in cardiac surgery patients

OBJECTIVES: The authors hypothesized that bioimpedance cardiography measured by the Endotracheal Cardiac Output Monitor (ECOM; ConMed, Utica, NY) is a convenient and reliable method for both cardiac index (CI) assessment and prediction in fluid responsiveness. DESIGN: A prospective observational study. SETTING: A teaching university hospital. PARTICIPANTS: Twenty-five adult patients. INTERVENTIONS: Admission to the intensive care unit after conventional cardiac surgery and investigation before and after a fluid challenge. MEASUREMENTS AND MAIN RESULTS: Simultaneous comparative CI data points were collected from transpulmonary thermodilution (TD) and ECOM. Correlations were determined by linear regression. Bland-Altman analysis was used to compare the bias, precision, and limits of agreement. The percentage error was calculated. Pulse-pressure variations (PPVs) and stroke-volume variations (SVVs) before fluid challenge were collected to assess their discrimination in predicting fluid responsiveness. A weak but statistically significant relationship was found between CI(TD) and CI(ECOM) (r = 0.31, p = 0.03). Bias, precision, and limits of agreement between CI(TD) and CI(ECOM) were 0.08 L/min/m(2) (95% confidence interval, -0.11 to 0.27), 0.68 L/min/m(2), and -1.26 to 1.42 L/min/m(2), respectively. The percentage error was 51%. A nonsignificant positive relationship was found between percent changes in CI(TD) and CI(ECOM) after fluid challenge (r = 0.37, p = 0.06). Areas under the ROC curves for both PPV and SVV to predict fluid responsiveness were 0.86 (95% confidence interval, 0.67-1.06) and 0.89 (95% confidence interval, 0.74-1.04, respectively; p = 0.623). CONCLUSIONS: Continuous measurements of CI under dynamic conditions are consistent and easy to obtain with ECOM although not interchangeable with transpulmonary thermodilution. SVV given by ECOM is a dynamic parameter that predicts fluid responsiveness with good accuracy and discrimination

Etomidate has no effect on hypoxia reoxygenation and hypoxic preconditioning in isolated human right atrial myocardium

BACKGROUND: We examined the effects of etomidate on recovery of contractile function after hypoxia reoxygenation and hypoxic preconditioning in vitro using isolated human myocardium. METHODS: Human right atrial myocardium were obtained at the time of cardiac surgery from 38 adults patients. We recorded isometric force of contraction (FoC) of atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation (HR). In separate groups, muscles were exposed to etomidate (10(-7), 10(-6), 10(-5) M) 10 min before and throughout the HR periods. Hypoxic preconditioning was induced by 4-min hypoxia followed by 7-min reoxygenation applied before HR periods. Etomidate 10(-5) M was administered before, throughout, and after the hypoxic preconditioning stimulus. Recovery of FoC (expressed as % of baseline value) at the end of HR was compared among groups. RESULTS: Compared with the control group (FoC: 52%+/-10%), etomidate 10(-7) M (FoC: 57%+/-9%; P=0.24), 10(-6) M (FoC: 61%+/-11%; P=0.10), and 10(-5) M (FoC: 54%+/-9%; P=0.29) did not modify the recovery of FoC after HR. Hypoxic preconditioning-induced increase in the recovery of FoC (87%+/-5%; P<0.001 vs control group) was not modified in the presence of etomidate 10(-5) M (FoC: 86%+/-7%; P=0.74 vs hypoxic preconditioning group). CONCLUSIONS: Etomidate did not modify the in vitro FoC of human myocardium exposed to HR. Furthermore, etomidate did not modify the protective effect of hypoxic preconditioning

Reactive oxygen species mediate sevoflurane- and desflurane-induced preconditioning in isolated human right atria in vitro

BACKGROUND: We examined the role of reactive oxygen species (ROS) in sevoflurane- and desflurane-induced preconditioning on isolated human right atrial myocardium. METHODS: We recorded isometric contraction of human right atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation. Ten minutes before hypoxia reoxygenation, muscles were exposed to 5 min of sevoflurane 2% or desflurane 6%. In separate groups, the sevoflurane 2% (Sevo + N-(2-mercaptopropionyl)-glycine [MPG]) or desflurane 6% (Des + MPG) was administered in the presence of 0.1 mM MPG, a ROS scavenger. The effect of 0.1 mM MPG alone was tested. Recovery of force after a 60-min reoxygenation period was compared between groups (mean +/- sd). RESULTS: Preconditioning with sevoflurane 2% (85% +/- 4% of baseline) or desflurane 6% (86% +/- 7% of baseline) enhanced the recovery of the force of myocardial contraction after 60 min reoxygenation compared with the control group (53% +/- 11% of baseline, P < 0.001). This effect was abolished in the presence of MPG (56% +/- 12% of baseline for Sevo + MPG, 48% +/- 13% of baseline for Des + MPG). The effect of MPG alone on the recovery of force was not different from the control group (57% +/- 7% of baseline versus 53% +/- 11%; P = NS). CONCLUSIONS: In vitro, sevoflurane and desflurane preconditioned human myocardium against hypoxia through a ROS-dependent mechanism