Post-operative endothelial dysfunction assessment using laser Doppler perfusion measurement in cardiac surgery patients.

BACKGROUND: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) is associated with systemic inflammatory response and endothelial dysfunction. Our hypothesis is that CPB-induced post-operative endothelial dysfunction may be detected using laser Doppler perfusion monitoring (LDPM) in the skin microcirculation. METHODS: We used LDPM to investigate the subacute effects of the CPB on systemic microvascular reactivity among patients undergoing CABG surgery with CPB. Thirty patients were submitted to the study of skin microcirculation and blood sample collection at baseline (pre-surgery) and at 7 days post-surgical procedure. The skin microcirculation was evaluated by acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, and thermal hyperemia (TH). Plasma levels of nitrite/nitrate were also analyzed, and cytokine profiles were determined using a multiplex system. RESULTS: On-pump CABG surgery induced a significant reduction of the increased microvascular dermal flux observed after cumulative doses of ACh iontophoresis and after TH. On-pump CABG surgery did not induce any significant changes in the microvascular flux after cumulative doses of SNP. Patients still presented high levels of interleukin (IL)-6, IL-8, and C-reactive protein, and low bioavailability of nitric oxide 7 days after the CABG surgery with CPB. CONCLUSION: We observed a significant impairment of systemic microvascular endothelial function and well-preserved endothelium-independent vasodilatation in the skin microcirculation of patients 1 week after CABG surgery with CPB. Our results suggest that LDPM is a useful tool for the assessment of on-pump CABG-induced subacute post-operative endothelial dysfunctions.

Beneficial effects of high positive end-expiratory pressure in lung respiratory mechanics during laparoscopic surgery.

BACKGROUND: The effect of neuromuscular blockade (NMB) and positive end-expiratory pressure (PEEP) on the elastic properties of the respiratory system during pneumoperitoneum (PnP) remains a controversial subject. The main objective of the present study was to evaluate the effects of NMB and PEEP on respiratory mechanics. METHODS: We performed a dynamic analysis of respiratory mechanics in patients subjected to PnP. Twenty-one patients underwent cholecystectomy videolaparoscopy and total intravenous anesthesia. The respiratory system resistance (R(RS)), pulmonary elastance (E(P)), chest wall elastance (E(CW)), and respiratory system elastance (E(RS)) were computed via the least squares fit technique using an equation describing the motion of the respiratory system, which uses primary signs such as airway pressure, tidal volume, air flow, and esophageal pressures. Measurements were taken after tracheal intubation, PnP, NMB, establishment of PEEP (10 cmH2O), and PEEP withdrawal [zero end-expiratory pressure (ZEEP)]. RESULTS: PnP significantly increased E(RS) by 27%; both E(P) and E(CW) increased 21.3 and 64.1%, respectively (P < 0.001). NMB did not alter the respiratory mechanic properties. Setting PEEP reduced E(RS) by 8.6% (P < 0.05), with a reduction of 10.9% in E(P) (P < 0.01) and a significant decline of 15.7% in R(RS) (P < 0.05). These transitory changes in elastance disappeared after ZEEP. CONCLUSIONS: We concluded that the 10 cmH2O of PEEP attenuates the effects of PnP in respiratory mechanics, lowering R(RS), E(P), and E(RS). These effects may be useful in the ventilatory approach for patients experiencing a non-physiological increase in IAP owing to PnP in laparoscopic procedures.

Cardioprotective action of fentanyl in a model of central sympathetic overactivity in rabbits: antiarrhythmic and anti-ischemic effects.

BACKGROUND: Sympathetic overactivity resulting from perioperative noxious stimuli elicits hyperdynamic cardiovascular responses that may lead to myocardial ischemia and/or ventricular arrhythmia, especially in patients presenting with coronary artery disease. In the present study we investigated the cardioprotective effects of clinically relevant doses of fentanyl in an experimental model of sympathetic overactivity associated with myocardial ischemia in anesthetized rabbits. METHODS: Central sympathetic stimulation was achieved through intracerebroventricular (i.c.v.) injection of L-glutamate (10 micro mol), with simultaneous inhibition of nitric oxide (NO) synthesis through i.v. administration of N(omega)-nitro-l-arginine methyl ester (L-NAME; 40 mg kg(-1)). RESULTS: L-glutamate triggered ventricular arrhythmia and electrocardiographic alterations indicative of myocardial ischemia. The intravenous administration of fentanyl (5, 10 or 50 micro g kg(-1)) reduced the incidence of ST-segment shift (70, 20 and 10%, respectively, vs. 66.7% in controls) as well as of T-wave inversion from 58.3% to 30, 20 and 10%, respectively. The total number of ventricular premature complexes per minute fell from 65.2 +/- 16 in the control group to 6.8 +/- 3, 3.5 +/- 2 and 2.6 +/- 1.5, respectively. The occurrence of ventricular tachycardia and bigeminy was completely abolished by fentanyl. Finally, the i.v. administration of fentanyl did not induce significant hemodynamic effects (except for dP/dt(max) in the 50 micro g kg(-1)-dose). CONCLUSION: Fentanyl elicits significant cardioprotective effects in a model of arrhythmia resulting from the association of central sympathetic overactivity with myocardial ischemia in rabbits, independently from its systemic hemodynamic actions.

Inhibition of the centrally induced increases in myocardial oxygen demand in rabbits by chronic treatment with baclofen, a selective GABAB agonist.

1. A previous study from our group demonstrated that neurones of the paraventricular nucleus of the hypothalamus (PVN) are selectively involved in the central control of the cardiac function. Moreover, in that study, it was shown that baclofen, a selective GABAB receptor agonist, is capable of modulating the increases in myocardial contractility and oxygen demand evoked by electrical or pharmacological stimulation of the PVN. Nevertheless, the acute administration of this compound was frequently accompanied by a cardiodepressant effect. 2. In the present study, the effects of a long term treatment (14 days) with baclofen (3 or 10 mg kg-1, i.p.) have been examined on the excitatory haemodynamic responses evoked by central pharmacological stimulation in anaesthetized rabbits. 3. The i.c.v. injection of L-glutamate (3 mg kg-1) induced marked increases in dP/dtmax (32%), mean arterial pressure (39%) and on two indices of myocardial oxygen consumption: the rate-pressure product (34%) and the triple product (78%). 4. Baclofen blunted the positive inotropic response and the increases in myocardial oxygen consumption induced by L-glutamate in a dose-related manner. The higher dose of baclofen (10 mg kg-1, i.p.), reduced by more than 50% these excitatory effects of L-glutamate without eliciting any significant negative effect on basal haemodynamics. The same doses of baclofen were not able to blunt the hypertensive response induced by central stimulation. 5. These results confirm and extend our previous findings suggesting that it is possible to discriminate the central control of vasomotor tone from that of cardiac function and also that baclofen can modulate the latter. It is concluded that when given chronically, baclofen modulates the increases in myocardial oxygen demand induced by activation of the central nervous system in doses which do not depress the resting cardiac function.