Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.     

Effects of l-arginine administration before cardioplegic arrest on ischemia-reperfusion injury

Background. Administration of l-arginine during reperfusion or its addition to cardioplegic solution has been shown to protect myocardium against ischemia-reperfusion injury. This study aimed at evaluating the role of l-arginine in ischemia-reperfusion injury when administered intraperitoneally 24 hours before cardioplegic arrest.Methods. Two groups of Sprague-Dawley rats (control, n = 10; and l-arginine, n = 10) were studied in an isolated buffer-perfused heart model. Both groups were injected intraperitoneally 24 hours before ischemia. Before experimentation blood samples were collected for cardiac troponin I and cGMP analysis. In the coronary effluents, cardiac troponin I, adenosine, cyclic guanosine monophosphate, and nitric oxide metabolites were assayed.Results. Before heart excision, serum cardiac troponin I concentrations were higher in the l-arginine than in the control group (0.037 ± 0.01 versus 0.02 ± 0.05 μg · L⁻¹; p < 0.05). During reperfusion, cardiac troponin I release was lower in the l-arginine than in the control group (0.04 ± 0.01 versus 0.19 ± 0.03 ng · min⁻¹; p < 0.05). The coronary flow as well as the left ventricular developed pressure were higher in the l-arginine than in the control group before ischemia and remained so throughout the experimentation.Conclusions. These results indicate that l-arginine administered intraperitoneally 24 hours before cardioplegic arrest reduced myocardial cell injury and seems to protect myocardium against ischemia-reperfusion injury.     

Effects of retroviral-mediated tissue plasminogen activator gene transfer and expression on adherence and proliferation of canine endothelial cells seeded onto expanded polytetrafluoroethylene

Purpose: Seeding prosthetic arterial grafts with genetically modified endothelial cells (ECs) has the potential to substantially improve graft function. However, preliminary applications suggest that grafts seeded with retrovirally transduced ECs yield a significantly lower percent surface coverage than those seeded with nontransduced ECs. The objective of this study was to test the hypothesis that canine ECs transduced with the human tissue plasminogen activator (tPA) gene would have a lower rate of adherence to pretreated expanded polytetrafluoroethylene (ePTFE) both in vitro and in vivo and that they would proliferate at a slower rate on pretreated ePTFE in vitro.Methods: Early passage ECs derived from canine external jugular vein were transduced with the retroviral MFG vector containing the gene for human tPA. ECs exposed to media alone served as controls. Iodine 125 – labeled ECs were seeded in vitro onto ePTFE graft segments pretreated with canine whole blood, fibronectin (50 μg/ml), or media alone, and the percent of ECs adherent at 1 hour were determined (n = 3). Additional tPA-transduced and –nontransduced ECs were grown for 10 days on either fibronectin (50 μg/ml) – pretreated ePTFE wafers or tissue culture plastic pretreated with gelatin (1%) or fibronectin (50 μg/ml), and the EC proliferation rates were determined (n = 3). Furthermore, ¹²⁵I-labeled ECs were seeded onto fibronectin (50 μg/ml) – pretreated ePTFE graft segments implanted as carotid and femoral artery interposition grafts (n = 3). The grafts were harvested after 1 hour, and the percent of ECs adherent was determined.Results: Human tPA was detected by immunohistochemical staining in 61% ± 5% of the transduced ECs and was expressed at 35.4 ± 12.9 ng/hr/10⁶ cells. Fibronectin and whole blood pretreatment of the ePTFE grafts led to greater EC adherence in vitro than did media alone (90.9% ± 5.3% vs 77.8% ± 5.8% vs 4.7% ± 1.1%, p ≤ 0.05). No significant difference in the rates of adherence or proliferation was seen in vitro between the transduced and nontransduced ECs. No significant difference in proliferation was found for the transduced ECs on the three matrices tested in vitro. In contrast, adherence of the transduced ECs in vivo was significantly lower than that of nontransduced ECs (64.7% ± 2.1% vs 73.7% ± 4.1%, p ≤0.05) 1 hour after implantation.Conclusions: Lower rates of surface endothelialization by genetically modified ECs in vivo do not appear to be due to an impaired capacity to initially adhere or proliferate on the synthetic graft but may result from decreased adherence after exposure to in vivo hemodynamic forces. (J VASC SURG 1995;22:795-803.)     

Acceptable warm ischemia time of tracheal grafts from non-heart-beating donors in rats

Objectives

Warm ischemia (WI)-induced airway complications are common in clinical lung transplantation. However, the acceptable WI time of tracheal grafts from non–heart-beating donors (NHBDs) is unknown. The purpose of this study was to determine the acceptable WI time by observing tracheal epithelial regeneration among NHBD.

Method

Forty-eight rats were randomly divided into four groups (each with 12 rats): WI-0 minutes (group A), WI-30 minutes (group B), WI-45 minutes (group C), and WI-60 minutes (group D). In each group, the tracheas from 6 rats were imbedded in the greater omentum of 6 other rats. Fourteen days later, the transplanted trachea was obtained from the recipient to evaluate epithelial thickness and regeneration. Six tracheas were obtained from living donors as a control group.

Results

There were no significant differences in tracheal transplantation time (mean, 17.66 ± 1.21 minutes). There were no significant differences in epithelial thickness and regeneration between the controls and groups A, B, and C (P < .05). Group D showed no normal epithelial structure of the trachea only with monolayer cells.

Conclusions

The time limits of tolerance to WI of tracheal grafts from NHBDs may be 45 minutes.     

Evaluation of a novel hirudin-coated polyester graft to physiologic flow conditions: Hirudin bioavailability and thrombin uptake

Purpose: Our laboratory has developed methods required to covalently bind recombinant hirudin (rHir) to the surface of polyester vascular grafts. Using alkaline hydrolysis of the polyester surface, carboxyl-binding sites are created on the outer periphery of each fiber. A series of static, in vitro experiments have demonstrated that surface-bound rHir rapidly removes and inhibits activated human α-thrombin from the reaction system; however, the performance of this modified graft material under physiologic flow conditions was undefined. Methods: An in vitro flow loop was used to evaluate structural stability of the ¹²⁵I-rHir and ¹³¹I-albumin covalently bound to the surface of 6 mm interior diameter crimped polyester grafts exposed to either constant flow (n = 4; shear rate, 300 sec^–1) or pulsatile flow (n = 4; maximum shear rate, 780 sec^–1) conditions for a 7-day period. In a separate series of experiments, the kinetics of thrombin-rHir interaction were evaluated through perfusion of ¹²⁵I-rHir-coated grafts (n = 6) with ¹³¹I-thrombin for a 27-hour period under constant flow conditions. Identically prepared ¹²⁵I-albumin-coated grafts (n = 3) were used as controls. Results: Results of the stability experiments were independent of flow conditions, demonstrating moderate loss of both proteins, with rHir and albumin losses of 52.1% and 19.9% under constant flow and 49.1% and 21.6% under pulsatile flow, respectively. With results comparable with those of previous static experiments, rHir-coated grafts were significantly more effective at removing thrombin from the perfusion stream with ¹³¹I-thrombin binding densities of 3.08 ± 0.61 and 0.64 ± 0.04 NIHU/cm² (p < 0.01) for rHir-coated and albumin-coated grafts, respectively. Estimates of the total amount of thrombin inactivated during the perfusion period similarly demonstrated a marked difference between the rHir-coated and control graft segments (125 ± 8 vs. 3 ± 14 NIHU; p < 0.005). Conclusions: These in vitro flow results illustrate that polyester grafts with covalently bound rHir can provide significant reductions in local thrombin concentration under physiologic flow conditions, and can serve as a foundation with which to understand the performance of these grafts when implanted in vivo under physiologic flow and shear rates. (J Vasc Surg 1998;27:1117-27.)     

Lung transplantation from ventilated non-heart-beating donors: experimental study in a neonatal swine model

BACKGROUND/PURPOSE: A shortage of transplantable lungs is a constant and frustrating reality. The use of organs retrieved from ventilated non-heart-beating donors (VNHBD) may alleviate this problem. The purpose of this work was to assess lung function of donor grafts subjected to different time lengths of in situ warm ischemia (WIT). METHODS: Twenty piglets weighing between 6 and 8 kg were allocated randomly to the following study groups: Sham (n = 5), heart-beating donors, non warm ischemia; I-30 (n = 5), I-60 (n = 5) and I-90 (n = 5), VNHBD-WIT of 30, 60, and 90 minutes, respectively. Recipients were rendered dependent on the single left transplanted lung by clamping right pulmonary artery and bronchus 1 hour after transplantation. Assessment of pulmonary function was monitored hourly by hemodynamic, oxygenation, and pulmonary mechanic measurements during a period of 6 hours after reperfusion. Lung grafts were weighed pre- and posttransplantation. RESULTS: Final mean lung weight was significantly greater in VNHBD (92.5+/-3.1 v Sham values 75.6 g+/-2.4; P < .01). Cold ischemic time averaged 80.1+/-2.7 minutes. After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated with a gradual rise in airway resistance and a fall in compliance. CONCLUSIONS: These data suggest that posttransplantation lung graft function from VNHBD with up to 90 minutes of WIT, is preserved and equivalent to those achieved by grafts harvested after heart-beating donation.     

The haemodynamic effects of phenylephrine after cardiac surgery

Background

Phenylephrine increases systemic- and pulmonary resistances and therefore may increase blood pressures at the expense of blood flow. Cardio-pulmonary bypass alters vasoreactivity and many patients exhibit chronotropic insufficiency after cardiac surgery. We aimed to describe the haemodynamic effects of phenylephrine infusion after cardiac surgery.

Methods

Patients in steady state after low-risk cardiac surgery received incremental infusion rates of phenylephrine up to 1.0 μg/kg/min with the aim of increasing systemic mean arterial blood pressure 20 mmHg. Invasive haemodynamic parameters, including pulmonary wedge pressures, were captured along with echocardiographic measures of biventricular function before, during phenylephrine infusion at target systemic blood pressure, and 20 min after phenylephrine discontinuation.

Results

Thirty patients were included. Phenylephrine increased mean arterial pressure increased from 78 (±9) mmHg to 98 (±10) mmHg with phenylephrine infusion. Also, pulmonary blood pressure as well as systemic- and pulmonary resistances increased. The ratio between systemic- and pulmonary artery resistances did not change statistically significantly (p = .59). Median cardiac output was 4.35 (interquartile range [IQR] 3.6–5.4) L/min at baseline and increased significantly with phenylephrine infusion (median Δcardiac output was 0.25 [IQR 0.1–0.6] L/min) (p = .012). Pulmonary artery wedge pressure increased from 10.2 (±3.0) mmHg to 11.9 (±3.4) mmHg (p < .001). This was accompanied by significant increases in central venous pressure. Phenylephrine infusion increased left ventricular end-diastolic volume from 105 (±46) mL to 119 (±44) mL (p < .001). All results of phenylephrine infusion were reversed with discontinuation.

Conclusion

In haemodynamically stable patients after cardiac surgery, phenylephrine increased PVR and SVR, but did not change the PVR/SVR ratio. Phenylephrine increased biventricular filling pressures and left ventricular end-diastolic area. Consequently, CO increased as ejection fraction was maintained. These findings do not discourage the use of phenylephrine after low-risk cardiac surgery. Registration: clinicaltrial.gov (identifier NCT04419662).     

Effect of Preconditioning With Triiodothyronine on Renal Ischemia/Reperfusion Injury and Poly(ADP-Ribose) Polymerase Expression in Rats

The ischemia/reperfusion (I/R) model in rats allows pharmacological investigation of protective renal effects of certain agents to thereby diminish the incidence of delayed graft function (DGF). The aim of this study was to determine the effects of preconditioning with triiodothyronine (T₃) on renal function and oxidative status in renal I/R injury. Forty male Wistar rats were preconditioned with T₃ (100 μg/kg) or control (normal saline) at 24 hours prior to 45 minutes of renal ischemia, followed by a 4-hour (groups C-4h and T₃-4h) or 24-hour (groups C-24h and T₃-24h) reperfusion period. We determined renal function parameters (urea, creatinine, and proteinuria), oxidative stress biomarkers in plasma (malondialdehyde [MDA], glutathione [GSH], and superoxide dismutase [SOD]), urine (hydrogen peroxide [H₂O₂]), and renal tissue (GSH and MDA), and poly(ADP-ribose) polymerase (PARP-1) expression. Proteinuria was significantly lower in the T₃-treated group (4.63 ± 1.9 vs 9.27 ± 0.72 mg/mL/100 g body weight). Pretreated rats showed lower levels of plasma and tissue MDA and urine H₂O₂ (50.57 ± 1.17 vs 71.16 ± 1.14 μmol/100 g body weight). The T₃ treatment was associated with lower postischemia GSH concentrations (3.82 ± 1.16 vs 4.89 ± 0.68 nmol/mg protein) and higher SOD levels at 24 hours (11.27 ± 0.86 vs 9.92 ± 1.77 nmol/mg protein). Preconditioning with the hormone also reduced PARP-1 tissue expression by 18% (P ≤ .05). These findings suggested that preconditioning with T₃ reduced proteinuria, improved lipid peroxidation biomarkers, and increased antioxidant enzyme levels in renal I/R injury.     

Obstacles of Non–heart-beating Donor Kidney Transplantation in Japan to Date and Future Perspectives

In Japan, multiple organ retrieval from brain-dead heart-beating donors has been gradually increasing since the law was adopted in 1997 and amended in 2009. However, almost more than 90% of total deceased donor kidney transplantation (DDKT) in Japan are still obtained from non–heart-beating donors (NHBD). The majority of NHBD are Maastricht categories IV and III. In category IV, we usually place a double balloon arterial and a venous drainage catheter via the femoral vessels after the diagnosis of clinical brain death and acquisition of informed consent from the family. After controlled cardiac arrest, the double balloons are inflated and in situ cold perfusion started as soon as possible to minimize warm ischemic time (WIT), seeking to achieve a zero to within a few minutes WIT in most cases. In category III, it is impossible to place the device prior to cardiac arrest. In these cases, after declaration of cardiac death, cardiopulmonary compression is accompanied by systemic heparinization, immediate laparotomy, and insertion of a cold perfusion catheter at the aortic and caval bifurcations to minimize WIT. NHBD kidney retrieval is critical; extirpation must be performed as rapidly as possible. The results of NHBD kidney transplantation in Japan are excellent, according to the advancement and utilization of in situ cannulation, organ perfusion, and sophisticated retrieval techniques. The patient and graft survival rates of DDKT at 1, 3, and 5 years in most recent 2001 to 2007 era were 95.4%, 92.2%, 89.1% (n = 945) and 89.2%, 83.7%, 77.8% (n = 919), respectively.     

l-Arginine Administration During Reperfusion Improves Pulmonary Function

Background. Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of l-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury.Methods. Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing l-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6).Results. The partial pressure of oxygen in the whole blood group (113.8 ± 33.1 mm Hg) was significantly less than in controls (417.3 ± 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 ± 0.2 mL/cm H₂O) than in controls (2.9 ± 0.4 mL/cm H₂O; p < 0.01). The l-arginine and leukocyte-depleted blood groups showed no significant difference from controls.Conclusions. l-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.     

Influence of internal mammary artery grafting and completeness of revascularization on long-term outcome in octogenarians

Background. It has been well established that complete revascularization with internal mammary artery (IMA) grafting is important in young patients undergoing coronary artery bypass grafting (CABG). Applying these principles to octogenarians remains controversial.Methods. From 1986 to 1999, 358 consecutive patients aged 80 to 94 years underwent CABG. Revascularization was complete in 291 (81%) and incomplete in 67 (19%). The IMA was used in 231 (65%) cases.Results. Operative mortality was 7% ± 1%, but was not statistically different with or without IMA grafting (IMA 5% ± 2% versus no IMA 10% ± 3%, p = 0.11) or complete revascularization (p > 0.41). Midterm survival improved with IMA grafting (70% ± 3% versus 56% ± 5% at 4 years, p < 0.03; 36% ± 4% versus 29% ± 5% at 8 years, p < 0.08), but was not significant beyond 8 years. Among 138 survivors, those with IMA grafts were more likely to be angina free (82% versus 53%, p < 0.001) and in New York Heart Association class I (60% versus 36%, p < 0.03). Survival, recurrent angina, and functional class were independent of completeness of revascularization (p > 0.21).Conclusions. IMA grafting improved survival, angina, and functional class of octogenarians, but complete revascularization did not have a similar impact.     

The choice of recipient does not have a bearing on early outcome in liver transplant patients receiving grafts from non-heart-beating donors: a reappraisal?

INTRODUCTION: Donation after cardiac death has reemerged as a potential way of increasing the supply of organs for transplantation. We retrospectively reviewed the outcomes of non-heart-beating donor (NHBD) liver transplantation (OLT) experience and compared with standard heart-beating donation (HBD) at a single center. METHODS: From October 2003 to November 2006, 13/111 liver transplantations were performed in our institution with NHBD. Living donor liver transplantation, splitting procedures, combined, and pediatric liver transplantations were excluded from this analysis. RESULTS: Donor population was similar in both groups. The median warm ischemia time was 10 minutes (range 6 to 38). The median cold ischemia times 6 hours and 16 minutes (2.4 to 6.30 hours and 9 hours and 14 minutes (2.15 to 15.35 hours) for NHBD and HBD groups, respectively (P = .0002). In the NHBD groups, 4/13 (31%) grafts were retransplanted within 3 months, due to ischemic biliary lesions with severe cholestasis (n = 3) or due to the occurrence of primary nonfunction (n = 1). The retransplantation rate was significantly lower in the HBD group (11/98, 11%; P = .03). One-year patient and graft survivals were 62% and 54% versus 86% and 79%, respectively, for the NHBD and HBD groups (P = .107 and P = .003). CONCLUSION: Liver grafts procured from donors after cardiac death accounted for a significantly greater retransplantation rates, mainly due to nonanastomotic biliary strictures. This risk must be taken into account when transplanting such grafts. Based upon this experience, NHBD cannot rival HBD to be a comparable source of quality organs for liver transplantation.     

Insuffisance surrénalienne aiguë postopératoire

Acute adrenal insufficiency is an uncommon complication of lung cancer and adrenal metastasis resection. Diagnosis is difficult to establish but an early recognition and treatment may be life-saving. A 55-year-old man underwent right upper lobectomy and adrenalectomy for lung carcinoma with right adrenal metastasis. Anaesthesia was obtained with propofol, alfentanil, atracurium and isoflurane. Blood pressure remained stable throughout surgical procedure and blood loss was about 3 000 ml. Several hours after the end of the procedure which was uneventful the circulator status worsened. The blood pressure was initially controlled with 500 ml of gelatin. External blood loss was about 200 ml. Clinical examination, chest X-ray and ECG were normal. Postoperative laboratory data showed a serum sodium at 134 mmol⁻¹ · l⁻¹ and a serum potassium 5.1 mmol · l⁻¹ ; haemoglobin concentration was 93 g · l⁻¹. Arterial blood gas analysis, with a 5 l · min⁻¹ nasal o₂ flow showed a Pao₂ at 108 mmHg, a Paco₂ at 30 mmHg and a pH at 7.44. Twelve hours later, a transient cardiac arrest occurred which responded to fluid load, dopamine and dobutamine. Six hours later, the patient went in ventricular fibrillation respanding to an external electric countershock. No change in clinical status was noticed, except hyperthermia at 39.5°C. Serum potassium concentration before cardiac arrest was 4.7 mmol · l⁻¹. Main considered diagnoses were septic shock and acute adrenal insufficiency. Antibiotics (imipenem, amikacin and vancomycin) and hormonal treatment (hydrocortisone 200 mg · day⁻¹), after blood samples had been obtained for bacteriological and hormonal examinations. The patient's condition improved dramatically within 48 hours. Shock was under control, dopamine and dobutamine were rapidly discontinued. Stimulation of the adrenals with synthetic corticotrophin tetracosactide (Synacthene® 250 μg) demonstrated failure of the serum cortisol to rise. The cortisol concentrations were very low before and after stimulation (1.4 μg · 100 ml⁻¹ before stimulation and 0.1 μg · 100 ml⁻¹ thereafter). These data as well as negative bacteriological data substantiate the diagnosis of acute adrenal insufficiency. A computer tomography showed an enlargement and inhomogeneous mixed-density of the remaining adrenal which was normal preoperatively. A CT-guided needle biopsy obtained necrotical and haemorrhagic tissue but no tumoral cells. It was concluded that adrenal insufficiency was due to necrosis of the remaining gland. Adrenal necrosis and haemorrhage has been described after sepsis, major trauma, chronic illness, severe surgical stress and systemic anticoagulant therapy. It is a well known but uncommon complication of metastatic carcinoma. In this case, neither heparin was administered nor sepsis occurred and it is speculated that this adrenal gland could have been metastatic with a special susceptibility to necrosis. Initialtime course was satisfying and the patient was discharged to medical unit ten days after surgery. However three days later, a vascular cerebral haemorrhage resulted in death.     

Leucocyte filtration of salvaged blood during cardiac surgery: effect on red blood cell function in concentrated blood compared with diluted blood

Objective: Leucocyte filtration of salvaged blood has been suggested to prevent patients from receiving activated leucocytes during auto-transfusion in cardiac surgery. This study examines whether leucocyte filtration of salvaged blood affects the red blood cell (RBC) function and whether there is a difference between filtration of the concentrated and diluted blood on RBC function. Methods: Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly divided into a group receiving leucocyte filtration of concentrated blood (High-Hct, n = 20) and another group receiving leucocyte filtration of the diluted blood (Low-Hct, n = 20). During operation, all the salvaged blood, as well as the residual blood, from the heart–lung machine was filtered. In the High-Hct group, blood was concentrated with a cell saver prior to filtration, whereas in the Low-Hct group, blood was filtered without concentration. RBC function was represented by RBC aggregation and deformability measured by a laser-assisted optical rotational cell analyser and by the RBC 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) contents with conventional biochemical tests. Results: Leucocyte filtration of diluted blood with a low haematocrit (14 ± 4%) did not affect RBC function. However, when the concentrated blood with a high haematocrit (69 ± 12%) was filtered, there was a reduction of ATP content in RBCs after passing through the filter (from 1.45 ± 0.57 μmol g⁻¹ Hb to 0.92 ± 0.75 μmol g⁻¹ Hb, p < 0.05). For patients who received the concentrated blood, their in vivo RBC function did not differ from those who received diluted blood. Conclusions: Leucocyte filtration of the diluted salvaged blood during cardiac surgery does not affect RBC function, but it tends to deplete the ATP content of RBCs as the salvaged blood has been concentrated prior to filtration.     

Propofol en perfusion ou isoflurane en circuit fermé. Etude du coût

The choice of an anaesthetic agent is influenced by its cost. The use of a circle absorber system decreases the cost of the maintenance of anaesthesia with halogenated agents. Fast recovery and low incidence of postoperative nausea and vomiting are the main advantages of propofol. The cost of propofol can limit its use for the maintenance of anaesthesia except for short procedures. This prospective study compared in 50 ASA 1 and 2 patients the cost of anaesthesia with either propofol (group P, n = 25) or the association thiopentone-isoflurane administered with a rebreathing circuit (group I, n = 25). Patients were premedicated the evening before surgery with 2.5 mg lorazepam. Anaesthesia was induced with either propofol (2–3 mg · kg⁻¹) or thiopentone (4–6 mg · kg⁻¹) and maintained with either propofol (6–10 mg · kg⁻¹ · h⁻¹) in group P or isoflurane continuously injected as liquid in the expiratory limb of the circuit in group I. The side effects of anaesthesia and the delay of recovery and discharge from the recovery room were assessed. Peroperative cost of anaesthesia included nitrous oxide, isoflurane and i.v. agents, fluids volumes and disposable devices. The total cost of anaesthesia included also the recovery room stay. The mean duration of anaesthesia was not significantly different between the two groups (109.4 ± 7.1 min vs 107.3 ± 7.3 min group P vs group I). The delay of recovery (eyes opening) was shorter in the propofol group (14.4 ± 1.3 min vs 19.4 ± 1.4 min) as well as the delay of discharge from the recovery room (70 ± 4 min, vs 82.4 ± 4.6 min). Nausea or vomiting occurred in 2 group P patients and 6 group I patients. The cost of propofol anaesthesia was 1.7 times that of thiopentone-isoflurane (305.7 ± 13.3 FF vs 179.6 ± 8.9 FF, p < 0.001). This additionnal cost of propofol is not excessive in comparison with the cost of surgery and is out-weighted by the advantages of this drug. When the use of propofol for maintenance of anaesthesia is considered, the cost should not be a contraindication to this technique.     

Experimental Small Bowel Transplantation From Non-Heart-Beating Donors: A Large-Animal Study

Introduction

The shortage of organs in the last 20 years is stimulating the development of new strategies to expand the pool of donors. The harvesting of a graft from non-heart-beating donors (NHBDs) has been successfully proposed for kidney and liver transplantation. To our knowledge, no studies are available for small bowel transplantation using NHBDs. In an experimental setting of small bowel transplantation, we studied the feasibility of using intestinal grafts retrieved from NHBDs.

Materials and Methods

Twenty five Large White piglets underwent total orthotopic small bowel transplantation and were randomly divided as follow: NHBD group (n = 15) received grafts from NHBDs; heart-beating donor (HBD) group (n = 10) received grafts from HBDs. The NHBD pigs were sacrificed inducing the cardiac arrest by a lethal potassium injection. After 20 minutes (no touch period = warm ischemia), they underwent cardiac massage, laparotomy, and aorta cannulation for flushing and cooling the abdominal organs. In HBDs, the cardiac arrest was induced at the time of organ cold perfusion. In both groups, immunosuppression was based on tacrolimus oral monotherapy. The animals were observed for 30 days. The graft absorptive function was studied at day 30 using the D-xylose absorption test. Histological investigation included HE (Hematoxilin and Eosin) microscopical analysis and immunohistological staining.

Results

Animals in the NHBD group died due to infection (n = 3), acute cellular rejection (n = 2), technical complications (n = 2), and intestinal failure (n = 8). In the HBD group, all animals but two were alive at the end of the study. The D-xylose absorption was significantly lower among the NHBD compared with the HBD group (P < .05).

Conclusions

This study confirmed that intestinal mucosa is sensitive to ischemic injury. When the intestinal graft is harvested from NHBDs, the infectious-related mortality was higher and the absorptive function lower. Histological examination confirmed a higher grade of ischemic injury in the NHBD grafts that correlated with the clinical data. Therefore, this experimental study suggested that non-heart-beating donation may not be indicated for small bowel transplantation.     

Effects of halothane on mucociliary activity in vivo

The effect of halothane on mucociliary activity in the rabbit maxillary sinus in vivo was recorded photoelectrically. Administration of halothane (1%, 2% or 4%) into the maxillary sinus induced a temporary acceleration of mucociliary activity. The peak increase (39.1% ± 9.1%, p < 0.05, n = 5) was seen after the 4% concentration. Long-term exposure (60 minutes) of the maxillary sinus to halothane (2%) first induced an increase of 28.4% ± 4.6% (p < 0.05, n = 6), lasting approximately four minutes, and followed after about 15 minutes by a decrease of mucociliary activity. The maximum decrease during the 60-minute period was 19.6% ± 2.8% (p < 0.05, n = 6). Mucociliary activity returned to its baseline level approximately 25 minutes after withdrawal of halothane. Halothane delivered to the rabbit through a tracheal cannula at 1.1% for 60 minutes did not impair mucociliary activity in the maxillary sinus. On the contrary, it initially stimulated mucociliary activity, 19.9% ± 2.7% (p <0.05, n = 5). There was also an initial increase in respiratory rate from 62 ± 7.3 to 89 ± 12.9 breaths per minute (p < 0.05), which was noticeable after approximately 10 seconds and lasted 4 to 5 minutes. The dose-dependent increase in mucociliary activity seen after short-term exposure to halothane is probalby due to stimulation of afferent C fibers, because halothane may be considered an airway irritant. The reversible depressant effect seen after 15 minutes of exposure is in accordance with findings in previous studies in vitro. The mechanism by which halothane impairs mucociliary activity is at present not known. However, halothane administered to the lower airways does not impair mucociliary activity in the maxillary sinus, indicating that halothane affects the ciliated epithelium directly and that the state of anesthesia itself has no effect on mucociliary activity. (OTOLARYNGOL HEAD NECK SURG 1995;112:714-22.)     

alpha1-Adrenoceptors during simulated ischemia and reoxygenation of the human myocardium: effect of the dose and time of administration.

OBJECTIVE: We sought to investigate the effect of alpha1-adrenoceptor activity on the ischemic and reoxygenated human myocardium. METHODS: Right atrial appendages (n = 6 per group) obtained during elective cardiac operations were sliced and stabilized in normoxic normothermic buffer solution for 30 minutes and then subjected to 90 minutes of simulated ischemia, followed by 120 minutes of reoxygenation. In study 1 the dose responses to the alpha1-adrenoceptor agonist phenylephrine (0.01, 0.1, 1, 10, and 100 micromol/L) and to the alpha1-adrenoceptor antagonist prazosin (0.1, 1, 10, and 100 micromol/L) when administered for 10 minutes before ischemia, during ischemia, and during reoxygenation were examined. The influence of the time of administration (ie, before ischemia, during ischemia, or during reoxygenation) of phenylephrine (0.1 micromol/L) and prazosin (10 micromol/L) was then investigated in study 2. In study 3 the effect of the combined administration of phenylephrine given before ischemia and prazosin given during ischemia was investigated. In study 4 the protective effect of phenylephrine given before ischemia (for 10 minutes or for 5 minutes with a 5-minute washout period) was compared with that of ischemic preconditioning (5 minutes of ischemia and 5 minutes of reoxygenation). At the end of each protocol, the leakage of creatine kinase (in units per gram of wet weight) and the reduction of 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide to insoluble formazan dye (in millimoles per gram of wet weight) were measured. RESULTS: Phenylephrine is maximally beneficial at 0.1 and 1 micromol/L (creatinine kinase, 0.97 +/- 0.06 and 0.95 +/- 0.03 U/g, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 153.0 +/- 7.8 and 156.2 +/- 6.7 mmol/g, respectively) compared with ischemic control (creatine kinase, 1.87 +/- 0.03 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 108.5 +/- 6.8 mmol/g; P <.05) but prazosin is detrimental at concentrations above 10 micromol/L (creatine kinase, 5.22 +/- 0.29 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 69.8 +/- 2.9 mmol/g; P <.05 vs ischemic control). In addition, phenylephrine (0.1 micromol/L) is protective when given before ischemia (creatine kinase, 2.06 +/- 0.21 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 148.5 +/- 4.5 mmol/g; P <.05 vs ischemic control) but is detrimental when given during ischemia alone (creatine kinase, 4.49 +/- 0.98 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 70.5 +/- 6.1 mmol/g; P <.05 vs ischemic control) and has no significant effect during reoxygenation. In contrast, prazosin (10 micromol/L) is beneficial when given during ischemia alone (creatine kinase, 1.34 +/- 0.10 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 148.5 +/- 4.5 mmol/g; P <.05 vs ischemic control), is detrimental when given during reoxygenation alone (creatine kinase, 1.5 +/- 0.16 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 85.0 +/- 4.7 mmol/g; P <.05 vs ischemic control), and has no effect when given before ischemia. The use of phenylephrine before ischemia alone is as protective as prazosin given during ischemia alone, but the combination of the two drugs does not cause additional benefit. Interestingly, the protection afforded by phenylephrine when given before ischemia is similar to that obtained with ischemic preconditioning. CONCLUSIONS: In the human myocardium activation of alpha1-adrenoceptors before ischemia is protective but is detrimental during ischemia, whereas blockade of alpha1-adrenoceptors is beneficial during ischemia but detrimental during reoxygenation. The degree of protection achieved by activation of the alpha1-adrenoceptors before ischemia is similar to that obtained with blockade of alpha1-adrenoceptors during ischemia and that of ischemic preconditioning.     

Continuous infusion of nitroglycerin improves pulmonary graft function of non-heart-beating donor lungs

BACKGROUND: The warm ischemic period of lungs harvested from a non-heart-beating donor (NHBD) results in an increased ischemia-reperfusion injury after transplantation. The intravenous application of nitroglycerin (NTG), a nitric oxide (NO) donor, proved to be beneficial during reperfusion of lung grafts from heart-beating donors. The objective of the present study was to investigate the effect of nitroglycerin on ischemia-reperfusion injury after transplantation of long-term preserved NHBD-lungs. METHODS: Sixteen pigs (body weight, 20-30 kg) underwent left lung transplantation. In the control group (n=5), lungs were flushed (Perfadex, 60 mL/kg) and harvested immediately after cardiac arrest. In the NHBD group (n=5) and the NHBD-NTG group (n=6), lungs were flushed 90 min (warm ischemia) after cardiac arrest. After a total ischemia time of 19 hr, lungs were reperfused and graft function was observed for 5 hr. Recipient animals in the NHBD-NTG group received 2 microg/kg/min of NTG administered intravenously during the observation period starting 5 min before reperfusion. Tissue specimens and bronchoalveolar lavage fluid (BALF) were obtained at the end of the observation period. RESULTS: Compared with the control group, pulmonary gas exchange was significantly impaired in the NHBD group, whereas graft function in the NHBD-NTG group did not change. Leukocyte fraction and protein concentration in the BALF and histologic alteration of the NHBD-NTG group were not different from controls. CONCLUSIONS: Continuous infusion of NTG in the early reperfusion period improves pulmonary graft function of NHBD lungs after long-term preservation. The administration of an NO donor during reperfusion may favor the use of NHBD lungs to alleviate the critical organ shortage in lung transplantation.