[Technique and pathophysiology of isolated hypoxic perfusion of the abdomen]. / Technik und Pathophysiologie der isolierten hypoxischen Perfusion des Abdomens.

Isolated hypoxic perfusion (IHP) is a commonly used technique in the treatment of abdominal malignancies. During a phase II-study the pathophysiology of this technique was explored in patients with advanced pancreatic cancer. Twenty perfusions of the abdomen were performed in 17 patients. Under general anesthesia, femoral vessels were dissected and two balloon catheters were inserted into aorta and vena cava cranial the celiac trunk and the hepatic veins. After instillation of 40 mg of Mitomycin C (MMC) into the running perfusion system, the perfusion was maintained for further 20 minutes. Blood samples were taken in 5-minute intervals to determine pH value, blood gases as well as concentrations of electrolytes, lactate and MMC in the arterial blood. Simultaneously, blood samples were taken from the perfusion blood via a side-port of the extracorporeal perfusion system. Additionally, perfusion pressures, arterial and central venous pressure, heart rate, and the pressure in the aorta distal the balloon catheter were registered continuously. All 20 perfusions had been undertaken without perioperative mortality. After inflating the balloon catheters, blood pressure and heart rate increased rapidly. Within 5 minutes of perfusion an increase in pCO2 and the concentrations of K+ and lactate in the perfusate were registered, while pH and pO2 decreased. Fifteen minutes after instillation of MMC, concentrations of MMC in arterial and perfusion blood were equal. Twenty-four hours after the perfusion all parameters had returned to normal values. IHP was well feasible in 20 consecutive perfusions without major technical problems. A distinct but tolerable combined acidosis resulted from IHP. Despite the exact positioning and control of the balloon catheters a complete isolation was not possible.

Isolated hypoxic perfusion with mitomycin C in patients with advanced pancreatic cancer.

AIMS: Chemotherapy as a palliative therapy option for patients with advanced pancreatic cancer remains disappointing. Some authors have recently claimed high response rates and a prolongation of median survival after regional chemotherapy. Isolated perfusion may result in the highest drug concentrations within the target tissue without causing systemic side-effects. An established, commercially available system of isolated hypoxic perfusion (IHP) was therefore evaluated in patients with unresectable or recurrent pancreatic cancer. PATIENTS AND METHODS: IHP was performed in 17 patients with unresectable pancreatic cancer. Five women and 12 men with a median age of 61 years were treated. A 20-min isolated hypoxic perfusion was performed after 40 mg of mitomycin C (MMC) had been instilled into the running perfusion system over 5 min. Tumour response was evaluated by CT-scan 6 weeks after IHP. RESULTS: Twenty perfusions were carried out in 17 patients. Within 10 min of perfusion, the perfusate's PO2 decreased to 13% of the baseline value. Five minutes after the infusion of MMC a local concentration of 15.2 mg/litre was observed. Toxicity-related deaths did not occur. Nausea and vomiting (NCI> or =II: 12 episodes) were the most frequently observed toxicities after IHP. In five patients (29%) a deep vein thrombosis occurred. None of the treated patients responded to the regimen used in this trial. The median survival time after IHP was 4.2 months (range 1.3-21). CONCLUSIONS: The overall rate of side-effects and complications after IHP was high. In spite of some hopeful reports on this treatment in recent years, IHP did not show any benefit in terms of tumour response or median survival. On the basis of these experiences, this procedure should no longer be used as treatment for patients with unresectable or recurrent pancreatic cancer.

[Controlled reperfusion of the extremities for preventing local and systemic damage after prolonged ischemia. An experimental study with the swine model]. / Kontrollierte Extremitäten-Reperfusion zur Verminderung lokaler und systemischer Schäden nach mehrstündiger Ischämie. Eine experimentelle Studie am Schweinemodell.

Our previous studies in isolated rat hindlimbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in-vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of twenty pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 hours and served as controls. Fourteen other pigs underwent 6 hours of complete infrarenal occlusion. Thereafter, embolectomy was stimulated in 8 pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In 6 other pigs, control of the composition of the reperfusate and control of the conditions of reperfusion was done during the first 30 min, followed by normal blood reperfusion. Six hours of infrarenal aortic occlusion lead to a severe decrease in high energy phosphates and muscle temperature and a slight increase in creating kinase (CK) and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive edema developed (80.6% vs. 76.6%, p < 0.0009), the tissue showed a marked decrease in oxygen consumption (7.3 +/- 1.1 vs. 14.3 +/- 2.5 mL )2/100 g/min, p < 0.02), glucose consumption (0.19 +/- 0.06 vs. 0.51 +/- 0.03 mg/100 g/min, p < 0.06), tissue ATP (18.3 +/- 1.9 vs. 36.1 +/- 0.9 mumol/g protein, p < 0.000001), total adenine nucleotides (26.3 +/- 2.6 vs. 45.8 +/- 1.5 mumol/g protein, p < 0.00001), muscle pH (5.9 +/- 0.1 vs. 7.3 +/- 0.1, p < 0.000006) and total calcium in the femoral vein (2. +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, p < 0.002). Furthermore, a massive increase was seen in CK concentration (12,743 +/- 2,562 vs. 513 +/- 80 U/L, p < 0.0003), potassium (7.9 +/- 0.3 vs. 4.4 +/- 0.2 mmol/L, p < 0.000001) and muscle rigidity (60 +/- 11 vs. 122 +/- 1 degree, p < 0.00008). In sharp contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion resulted in normal water content (77.6 +/- 0.4 vs. 76.8 +/- 0.3%), oxygen consumption (13.2 +/- 1.6 vs. 14.9 +/- 3.2 mL O2/100 g/min), glucose consumption (0.58 +/- 0.18 vs. 0.46 +/- 0.11 mg/100 g/min), flow (5.4 +/- 1.1 vs. 4.6 +/- 4.6 +/- 0.5 mL/100 g/min) and muscle rigidity (106 +/- 4 vs. 122 +/- 1 degree). Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content (78% vs. 57% of control), less tissue acidosis (6.6 +/- 0.2 vs. 5.9 +/- 0.1, p < 0.002), severely reduced CK release (2,618 +/- 702 vs. 12,743 +/- 2.562, p < 0.02) and potassium release (5.1 +/- 0.3 vs. 7.9 +/- 0.3 mmol/L, p < 0.0002) as compared to normal blood reperfusion. In conclusion this study shows that 6 hours of acute infrarenal aortic occlusion will result in a severe reperfusion injury (postischemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.

Reperfusion injury in skeletal muscle: controlled limb reperfusion reduces local and systemic complications after prolonged ischaemia.

Previous studies in isolated limbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischaemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of 20 pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 h and served as controls; 14 others underwent 6 h of complete infrarenal occlusion. Thereafter, embolectomy was simulated in eight pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In six other pigs, the composition of the reperfusate and the conditions of reperfusion were controlled during the first 30 min, followed by normal blood reperfusion. Some 6 h of infrarenal aortic occlusion leads to a severe decrease in high-energy phosphates and muscle temperature, together with a slight increase in creatine kinase and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive oedema developed, the tissue showed a marked decrease in oxygen consumption, glucose consumption, tissue ATP, total adenine nucleotides, muscle pH and total calcium in the femoral vein. Furthermore, a massive increase was seen in plasma creatine kinase concentration and potassium, together with the development of muscle rigidity. In sharp contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion resulted in normal water content, oxygen consumption, glucose consumption, flow and muscle rigidity. Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content, less tissue acidosis, markedly reduced creatine kinase release, and potassium release as compared with that of normal blood reperfusion. This study shows that 6 h of acute infrarenal aortic occlusion will result in severe reperfusion injury (postischaemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischaemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.