Geoffrey M. Collins

Life expectancy and late stroke following carotid endarterectomy.

A review of the UCSD experience with 456 consecutive carotid endarterectomy procedures confirms the acceptably low operative mortality and morbidity associated with this operation. Immediate complications were not different when routine or selective shunting was performed, but the patients with a low internal carotid artery back pressure had higher operative complication rates. The coexistence of atherosclerosis in other parts of the body severe-enough to warrant surgery for them was not associated with either higher early or late carotid surgery complication rates. Following both coronary bypass and carotid procedures, the late mortality was decreased, and the late incidence of stroke was particularly low in comparison to the remainder of the patient group. Late follow-up emphasized the high continuing attrition rate from all causes in these patients. Late strokes continued to occur, particularly in patients with prior strokes and severe preoperative bilateral carotid disease. The late course of patients with posterior circulation transient ischemic attacks treated by carotid endarterectomy was quite similar to that of patients treated for anterior circulation transient ischemia attacks (TIAs). Newer postoperative screening procedures may decrease the incidence of late postoperative stroke by identifying recurrent carotid stenosis while it is still in the asymptomatic stage.

Modification of rejection by polyethylene glycol in small bowel transplantation.

The use of polyethylene glycol (PEG) in preservation solutions has been associated with a decreased incidence of rejection in clinical and experimental organ transplantation. In this study, we examined the effect of PEG with different molecular configurations on rejection of small bowel allografts in the rat. Male ACI and LEW rats were used as donors and recipients, respectively. Orthotopic small bowel transplantation was performed using the following preservation solutions: lactated Ringers solution (n = 7), University of Wisconsin solution (n = 7), University of Wisconsin solution without hydroxyethyl starch (sUW; n = 7), sUW with PEG20M (n = 9), sUW with PEG8000 (n = 6), and sUW with PEG20L (n = 7). No immunosuppression was given. In orthotopic small bowel transplantation, only groups with a high molecular weight PEG, PEG20M and PEG20L, demonstrated longer survival (P < 0.01 and P < 0.001, respectively) and delayed onset of unkempt appearance (P < 0.05 and P < 0.001, respectively). In heterotopic small bowel transplantation, sUW was compared with sUW with PEG20L. Rejection occurred later and its progression was slower in the sUW with PEG20L than in the sUW alone. Our observations suggest that the onset and progression of rejection after small bowel transplantation were influenced by the molecular weight and configuration of the PEG molecule. The mechanism is unclear, but high molecular weight PEG appears to reduce or change the immunogenicity of the small bowel allograft.

The effects of oxygen free radicals on the preserved kidney

This study evaluated the effect of specific scavengers of oxygen derived free radicals on the results of kidney preservation. The immediate function of rabbit kidneys preserved for 24 hr by hypothermic perfusion was studied on an ex vivo shunt. A significant improvement in creatinine clearance was seen when the perfusate was treated with superoxide dismutase (SOD) and catalase (CAT), with values of 261 +/- 82 ml/hr vs control values of 203 +/- 72 ml/hr, P less than 0.05. This effect was enhanced if a long-persistent polyethylene glycol-linked form of SOD, namely PEG-SOD, was used (330 +/- 58 ml/hr, P less than 0.01). Recipient treatment and other modifications designed to protect against free radicals resulted in similar improvement in function. In contrast, no effect of free radical scavengers could be demonstrated in kidneys which were preserved by flush cooling, whether the agents were added to the flushing solution, given to the recipient, or both.

Should aortography be used routinely in the elective management of abdominal aortic aneurysm

Until recently aortography was performed routinely for elective abdominal aortic aneurysm at our institution. A death resulting from this procedure prompted us to evaluate this policy by a retrospective study of 105 elective aneurysm patients. These studies identified 21 renal artery stenoses, 2 renal artery aneurysms, 2 cases of multiple renal arteries, 8 celiac stenoses, 6 superior mesenteric artery stenoses or occlusions, and a number of peripheral occlusive processes and associated iliac aneurysms. However, the impact of these findings on surgical management was limited to six renal artery reconstructions: one for reimplantation of a renal artery arising from the aneurysm, one for serious hypertension, and four in normotensive patients with severe arterial stenosis. No celiac or mesenteric reconstructions were undertaken, and no visceral complications ensured. In only one patient, the one with renal artery reimplantation, was the angiographic information unsuspected and significant for operative management. This did not appear to justify the risk and expense involved in routine preoperative aortography.

Acute pancreatitis following renal allotransplantation. A lethal complication.

Since first described by Starzl in 1964 (1), acute pancreatitis following renal homotransplantation has been the subject of sporadic reports and reviews (2–5). The generally reported incidence has been around 2%, with a mortality rate of 50–60%. A recent experience with such a patient caused us to retrospectively analyze our own series of renal transplant recipients. In an eight-year period, there were six patients who had documented pancreatitis out of a total 120 renal homograft recipients, an incidence of 5%. The mortality was distressingly high; five out of the six succumbed directly to this complication, a rate of 83%. The purpose of this paper is to review these six patients in detail, with special attention to the protean etiologies and manifestations of this lethal complication.

Importance of anion content and osmolarity in flush solutions for 48 to 72 hr hypothermic kidney storage

Abstract Some new formulations of the “intracellular” flush solution for hypothermic kidney storage have been characterized by increased osmolarity and the use of anions other than phosphate. The influence of these factors has been investigated in a 48- and 72-hr canine kidney preservation model. Neither substitution of citrate or sulphate for phosphate nor increase of the osmolarity of the C 2 solution improved the results.

Pharmacological protection of rabbit kidneys from normothermic ischemia.

This study investigated the influence of the administration of pharmacological agents on the recovery of rabbit kidneys from the effects of 1 hr of in situ normothermic ischemia, utilizing acute and chronic models. The agents tested included the diuretics mannitol and furosemide, the vasoactive agents phenoxybenzamine, propranolol, and dopamine, and the membrane stabilizers chlorpromazine and methylprednisolone. A beneficial effect was detected only with the diuretic agents and propranolol when given prior to the ischemic insult. In cadaveric kidney transplantation, normothermic ischemia is known to have a particularly adverse effect on renal function (1–4). In order to protect the kidney from both this and subsequent preservational injury, it is common practice to administer pharmacological agents singly or in combination to both donors and recipients (5–7). Many reports exist advocating the use of individual substances, but the lack of comparative experimental data makes it difficult for the clinician to determine which of these is the most effective. Accordingly, this study was undertaken to compare several of the most widely used agents in a small animal experimental model in which 1 hr of normothermic ischemia served as the test injury.

Calcium antagonists in sodium lactobionate sucrose solution for rat liver preservation

The effects of the calcium antagonists, chlorpromazine (CPZ), nisoldipine (NIS), trifluoperazine (TFP), and nicardipine (NIC) were compared in rat livers following either 20- or 30-hr ice storage in sodium lactobionate sucrose solution (SLS). Survivals beyond 7 days after orthotopic liver transplantation following 20-hr cold storage were 1/14 in the University of Wisconsin solution, 4/14 in SLS, 4/8 in UW+CPZ, 7/8 in SLS+CPZ. Survivals beyond 7 days after OLT following 30-hr cold storage were 3/8 in SLS+CPZ, 3/8 in SLS+NIS, 2/8 in SLS+TFP, 0/8 in SLS+NIC, and 0/8 in SLS alone. Survival rates were significantly (P less than 0.05) better in both SLS+CPZ and SLS+NIS than in UW and SLS alone. The effluent lactate dehydrogenase (LDH) levels and pH changes were measured at the time of OLT. After 20 hr, LDH levels were 525 +/- 78 IU/L (mean +/- SEM) in UW, 492 +/- 44 in SLS, 322 +/- 35 in UW+CPZ, and 290 +/- 39 in SLS+CPZ. After 30 hr, LDH values were 416 +/- 40 in SLS+CPZ, 450 +/- 25 in SLS+NIS, 448 +/- 21 in SLS+TFP, 573 +/- 18 in SLS+NIC, and 614 +/- 68 in SLS. The LDH levels for SLS+CPZ and SLS+NIS were significantly lower than those of SLS and UW (P less than 0.01). The pH changes in the effluent were significantly less in both the CPZ and NIS groups (P less than 0.01). This study demonstrated improved liver preservation by the use of a simplified colloid-free lactobionate solution containing sodium as the principal cation. The addition of CPZ or NIS to the solution demonstrated the same potency for significant improvement in efficacy of this solution, while NIC was ineffective.

Improved function of perfused rabbit kidneys by prevention of oxidative injury.

This study explored the effect of adding small amounts of the reducing agents ascorbic acid and glutathione to a Ringers-albumin perfusate used for 24-hr hypothermic perfusion of rabbit kidneys. Maintenance of function during preservation was evaluated with a shunt perfusion model and by measuring the ability of cortical slices to restore normal K/Na ratios after incubation in a electrolyte medium. When placed in contact with the unmodified perfusate, an electrode of pyrolytic carbon registered a potential of +190 mV relative to the silversilver chloride couple. This reading fell rapidly by 100–125 mv when kidneys were placed on the circuit. The mean creatinine clearance after 24-hr perfusion was significantly improved from 162 ± 56 ml/hr in controls to 284 ± 92 ml/hr when the potential indicated by this electrode was preadjusted to 43–54 mv with reducing agents, and to 237 ± 62 ml/hr when this adjustment was made after 2 hr. These creatinine clearances were similar to those of kidneys stored on ice for only 1 hr. These findings indicate minimal injury occurred in the chemically reduced groups and emphasize the importance of preventing oxidative damage to kidneys during hypothermic organ perfusion. The time course of the changes in potential registered by this electrode was consistent with our previous finding that much of the damage to perfused kidneys occurs very early in the course of perfusion. The tissue slice studies showed no detectable damage to the renal parenchyma of the kidneys in the control group despite diminished creatinine clearance. This suggests that the site of oxidation injury is the vascular compartment.

Studies of the ideal [H+] for perfusional preservation.

The neutral point of water, being a function of its dissociation constant, is temperature dependent. This is also true of protein-buffered solutions such as perfusates. In organ preservation these facts have been long ignored and, as a result, perfusions have been carried out in a relatively acidotic environment. These studies evaluated the effects of correcting the pH partially or completely for the level of hypothermia involved in perfusional presevation. The findings both in rabbits and dogs were that a pH of 7.4 (measured at 7 C) is dangerously close to the pH below which there is rapid deterioration of function. On the other hand, perfusate pHs up to 7.75 in dogs and 8.25 in rabbits were tolerated at no detriment. As a result, the recommendation is made to carry out hypothermic organ perfusion at a pH well above 7.4; 7.60 or 7.65 seems reasonable.