Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

BACKGROUND: Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS: We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

Expandable prosthesis for sutureless anastomosis in thoracic aorta prosthetic substitution.

OBJECTIVE: Most complications of descending aorta prosthetic substitution seem mainly to be related directly (ischemia to distal organs, i.e. liver, kidney, spinal cord) or indirectly (extracorporeal circulation or shunts and systemic heparinization complications) to the duration of blood flow interruption. the purpose of this study is to report the results of animal experimentation of a new device for sutureless prosthetic substitution of the descending thoracic aorta, with a very short cross-clamping phase. METHODS: The device consists of expandable loops of stainless steel wires, sewn to the proximal end of a Dacron prosthesis. The stainless steel wire loops can be expanded and tightened by activating a removable guide in such a way that the prosthesis varies its diameter, while maintaining a regular cylindrical shape. The device was prepared in two different configurations, one for long segments (expandable prosthesis end) and the other to be used for very short segments or as an anastomotic ring between prosthetic or vascular stumps (quick anastomotic ring). The expandable prosthesis end was tested in swine experiments by performing the prosthetic substitution of the first 10 cm of descending cross-clamped aorta, the prosthesis being fixed with the device both at the proximal and the distal ends (six experiments). All animals survived the procedure, that was accomplished with a very short cross-clamping time. The quick anastomotic ring was used to anastomose two prosthesis ends, at the middle of the prosthetic segment used for descending aorta substitution (two swine), to perform the distal anastomosis in the same model of descending aorta substitution (one swine) and simply to re-anastomose a subtotally transected descending aorta (one swine). RESULTS: The present experience proved the reliability of the device to carry out a sutureless, accurate, simple and quick anastomosis. Its advantage over an intraluminal ringed prosthesis is much easier insertion of the retracted wired end into the vascular stumps, thus allowing for a prosthetic diameter appropriate to the substituted vessel. CONCLUSIONS: The reduced cross-clamping feature of the device would suggest its use mainly in thoracic aorta prosthetic substitution for the prevention of ischemic damage to distal organs; it can also be used to advantage wherever an end-to-end vascular or prosthetic anastomosis is indicated, providing an accurate, stented anastomosis.

Aortic wall structural strengthening by intraluminal net prosthesis to arrest aneurysm progression and to prevent dissection and rupture.

The major limitation implicit in the endovascular procedures for aortic prosthetic substitution is that they cannot be used in those tracts of the aorta where important collateral branches originate (aortic arch, thoraco-abdominal tract, upper abdominal), that would be occluded by the prosthesis. In order to overcome this limitation we hypothesized the endovascular positioning of a prosthesis in the form of a wide mesh network that would be gradually and spontaneously covered by new intima and included in the aortic wall. The fabric framework linked to the aortic wall would then condition its significant, regular and uniform mechanical strengthening that fractionates and partially absorbs the centrifuge pulsatile stress of the bloodstream. The purpose of this paper is to report the results of the insertion of a braided Prolene net prosthesis in the first 7 cm of the descending aorta of ten swine. The animals were killed after 6 weeks, the substituted segment removed and aortic wall compliance measured under standardized conditions. The prosthesis was found entirely covered by new intima, well embodied in the aortic wall. The intercostal collateral included in the substituted segment was patent, as proved by bubble formation during underwater insufflation. Compliance of the prosthesis segment was significantly lower than that of the adjacent descending aorta. Histology showed a regular net prosthesis inclusion deep in the neo-intima layer. Present results indicate the technical feasibility of the procedure, achieving significant aortic wall strengthening without affecting the collateral (intercostal) circulation.

[Quality of life of geriatric patients after surgery. VII. Lung tumors]. / Qualità di vita del paziente geriatrico dopo intervento chirurgico. Nota VII: Tumori del polmone.

After reviewing the literature on this subject, the authors examine the results of a five-year follow-up in all patients undergoing lung cancer surgery. The results obtained showed that old-age patients (third age) are more numerous than geriatric (fourth age) patients, and males are more frequently affected than females. The most frequent localisation in the series examined was the upper right lobe and the majority of these patients underwent lobectomy, the form of surgery that produced the best results (30.3% alive and well with a Karnofski index as high as 90 in some cases). The authors conclude that when the patient's conditions allow, surgery is advisable in lung cancer in an attempt to improve the patient's quality of life.

[Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like growth factor-I]. / Trattamento della nefrotossicità da farmaci immunosoppressori con insulin-like growth factor-I.

BACKGROUND: Delayed graft function is a common and severe complication after cadaveric kidney transplantation. Besides a more complicated postoperative course, DGF can worsen the overall graft survival. In particular, DGF enhances the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This study evaluates a new therapeutical approach to the treatment of DGF related nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis rats underwent a bilateral clamping of the renal pedicles (20') as standard damage. The animals were stratified in six groups, according to the postoperative treatment. Group 1 served as control and received only the standard ischemic injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6 had the same treatment of groups 1, 3, 5 respectively, plus the administration of IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days. RESULTS: The rats treated with IGF-I had significantly better values compared to the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF-I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its use is potentially beneficial for transplantation.

[Whole pancreatic transplantation and islet transplantation. Experiment notes]. / Trapianto di pancreas intero e trapianto di isole. Note sperimentali.

BACKGROUND: The results of pancreas transplantation have greatly improved in recent years. The path to further improvements goes through extensive experimental researches. METHODS: This study describes the effects of different procedures as hemodynamic asset and postoperative outcome. Twenty-nine swine underwent a total pancreatectomy, and were stratified into five groups. Group one (n = 5) served as control. Group two (n = 7) was autotransplanted. Group three (n = 6) and group four (n = 6) underwent allotransplantation; the first without immunosuppression and the second treated with cyclosporine and steroids. In group five (n = 5) Langerhans Islets transplantation was performed. RESULTS: Survival was different depending on which methodology was applied. The postoperative survival was 7 +/- 2 days in group one, 24 +/- 16 days in group two, 17 +/- 7 days in group three, 27 +/- 8 days in group four and 12 +/- 6 days in group five. CONCLUSIONS: The postoperative glucose control was normal in group two and group four while a severe diabetes appeared in group one (group 1 vs group 2: p < 0.05) and in group three during acute graft rejection after the 12th postoperative day (group 3 vs group 4: p < 0.05). Glycemia was slightly controlled in group five. The intraoperative hemodynamic status was evaluated at the time of pancreatectomy, harvesting, revascularization, and when surgery was over. Among the different parameters studied (mean arterial and pulmonary pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), a statistically significant difference between group one and group five (p < 0.05) was observed.

[The hemodynamic effects of the in-vivo administration of insulin-like growth-factor I]. / Effetti emodinamici della somministrazione in vivo dell'Insulin-like Growth Factor-I.

BACKGROUND: Recent studies have demonstrated that IGF-I has several biological activities that correlate with the GH axis, by acting as a cell protecting factor and a promoting compound in different tissues and organs. Our latest findings have demonstrated a potential application of IGF-I in the treatment of postischemic renal injury, which frequently appears after a kidney transplant. The beneficial effect of the renal postoperative recovery probably correlates with the regulation of the vascular tone, in which IGF-I plays a role with other cytokines. However, this rises the question whether IGF-I has any effect on the general hemodynamic status. This study was designed to underline the intraoperative hemodynamic effect of exogenous IGF-I in an experimental setting of renal transplantation in swine. METHODS: Twelve female swine underwent a left renal autotransplantation. At the reperfusion the animals were separated in two groups. Group one served as control. Group two received 400 micrograms of IGF-I (added to the flushing solution). The animals were kept under complete hemodynamic monitoring over the operation. RESULTS: Among the different parameters studied (mean arterial pressure, mean pulmonary arterial pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), any statistically significant difference between group one and two were observed. CONCLUSIONS: While the clinical administration of IGF-I requires further studies, the in vivo administration of this peptide is apparently well tolerated, and does not cause any hemodynamic instability to the operation.