Pulmonary Vasodilation by Intravenous Infusion of Organic Mononitrites Of 1,2-Propanediol in Acute Pulmonary Hypertension Induced by Aortic Cross Clamping and Reperfusion: A Comparison With Nitroglycerin in Anesthetized Pigs.

INTRODUCTION: Suprarenal aortic cross clamping (SRACC) and reperfusion may cause acute pulmonary hypertension and multiple organ failure. HYPOTHESIS: The organic mononitrites of 1,2-propanediol (PDNO), an nitric oxide donor with a very short half-life, are a more efficient pulmonary vasodilator and attenuator of end-organ damage and inflammation without significant side effects compared with nitroglycerin and inorganic nitrite in a porcine SRACC model. METHODS: Anesthetized and instrumented domestic pigs were randomized to either of four IV infusions until the end of the experiment (n = 10 per group): saline (control), PDNO (45 nmol kg min), nitroglycerin (44 nmol kg min), or inorganic nitrite (a dose corresponding to PDNO). Thereafter, all animals were subjected to 90 min of SRACC and 10 h of reperfusion and protocolized resuscitation. Hemodynamic and respiratory variables as well as blood samples were collected and analysed. RESULTS: During reperfusion, mean pulmonary arterial pressure and pulmonary vascular resistance were significantly lower, and stroke volume was significantly higher in the PDNO group compared with the control, nitroglycerin, and inorganic nitrite groups. In parallel, mean arterial pressure, arterial oxygenation, and fraction of methaemoglobin were similar in all groups. The serum concentration of creatinine and tumor necrosis factor alpha were lower in the PDNO group compared with the control group during reperfusion. CONCLUSIONS: PDNO was an effective pulmonary vasodilator and appeared superior to nitroglycerin and inorganic nitrite, without causing significant systemic hypotension, impaired arterial oxygenation, or methaemoglobin formation in an animal model of SRACC and reperfusion. Also, PDNO may have kidney-protective effects and anti-inflammatory properties.

Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia-reperfusion model involving aortic clamping.

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia-reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)-sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.

Comparison of anaesthetic gas consumption and stability of anaesthesia using automatic and manual control over the course of anaesthesia.

BACKGROUND: The automatic control module of end-tidal volatile agents (EtC) was designed to reduce the consumption of anaesthetic gases, increase the stability of general anaesthesia and reduce the need for adjustments in the settings of the anaesthesia machine. The aim of this study was to verify these hypotheses. METHODS: The course of general anaesthesia with the use of the EtC module was analysed for haemodynamic stability, depth of anaesthesia, end-expiratory concentration of anaesthetic, number of ventilator key presses, fentanyl supply, consumption of volatile agents and anaesthesia and operation times. These data were compared with the data obtained during general anaesthesia controlled manually and were processed with statistical tests. RESULTS: Seventy-four patients underwent general anaesthesia for scheduled operations. Group AUTO-ET (n = 35) was anaesthetized with EtC, and group MANUAL-ET (n = 39) was controlled manually. Both populations presented similar anaesthesia stability. No differences were noted in the time of anaesthesia, saturation up to MAC 1.0 or awakening. Data revealed no differences in mean EtAA or the fentanyl dose. The AUTO-ET group exhibited fewer key presses per minute, 0.0603 min⁻¹, whereas the MANUAL-ET exhibited a value of 0.0842 min⁻¹; P = 0.001. The automatic group consumed more anaesthetic and oxygen per minute (sevoflurane 0.1171 mL min⁻¹; IQR: 0.0503; oxygen 1.8286 mL min⁻¹, IQR: 1,3751) than MANUAL-ET (sevoflurane 0.0824 mL min⁻¹, IQR: 0.0305; oxygen 1,288 mL min⁻¹, IQR: 0,6517) (P = 0.0028 and P = 0.0171, respectively). CONCLUSION: Both methods are equally stable and safe for patients. The consumption of volatile agents was significantly increased in the AUTO-ET group. EtC considerably reduces the number of key presses.