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G M Collins

Publications and source records attributed to G M Collins.

At least 37 records · Page 2Linked to original sources
PubMed1991

Successful 20-hour rat liver preservation with chlorpromazine in sodium lactobionate sucrose solution.

We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/- 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment.

Adenosine↗
PubMed1990

Optimal cardioplegia and 24-hour heart storage with simplified UW solution containing polyethylene glycol.

Recent work has shown that UW may be better than standard cardioplegic solutions for short-term heart preservation. In this study we have used a rabbit heart model to evaluate a simplified UW solution in which penicillin, dexamethasone, insulin, allopurinol, and adenosine were omitted and 5% polyethylene glycol (PEG20M) was substituted for hydroxyethyl starch. The test systems consisted of 4-hr cardioplegic storage at 15 degrees C with repeated flushing every 30 min for 2 hr and 24-hr hypoxic low-flow microperfusion (3 ml/g/24 hr) at 0 degrees C. Control groups were arrested with a 15-25 ml flush in iced saline and immediately tested. Cardiac output (CO)* after preservation was measured in a working heart model using an acellular perfusate at 37 degrees C at an aortic pressure of 100 cm H2O. The CO (ml/g heart wt/min) were as follows--Controls: St. Thomas II 20.5 +/- 8.3 (5), UW 34.7 +/- 11.7 (16), PEG20M 41.8 +/- 4.4 (14); 4-hr cardioplegia: St. Thomas II 17.4 +/- 0.9 (4), Bretschneider HTK 14.9 +/- 7.0 (4), UW 25.2 +/- 11.5 (9), PEG20M 41.1 +/- 7.8 (8); 24-hr microperfusion: UW 25.4 +/- 11.1 (18), PEG20M 37.1 +/- 8.2 (18). Following cardioplegic or microperfusion preservation, PEG20M hearts functioned at control levels (P greater than 0.05) and were significantly superior to all other solutions, with approximately double the CO (P less than 0.05, all other groups). We conclude that for heart preservation, 5 components can be eliminated from UW and substitution of PEG20M for HES appears to have improved its performance.

Animals↗
PubMed1989

24-hour rabbit heart storage with UW solution. Effects of low-flow perfusion, colloid, and shelf storage.

A new technique for 24-hr cardiac preservation is described utilizing very low flow perfusion (microperfusion) with a cold flush solution. Rabbit hearts were arrested with UW solution and then perfused with the same solution through the aortic root at 0 degrees C at a rate of 3-6 ml/gm heart weight/24 hr. When tested on an ex vivo working heart model, the cardiac output (CO) was 28.72 +/- 7.69 ml/g/min compared with fresh UW flushed controls of 26.48 +/- 2.25 ml/g/min. Both oxygenated highflow perfusion with a more conventional perfusate and 24-hr ice storage with UW led to inferior results. Omission of the colloid, hydroxyethyl starch (HES), from the UW solution or prolonged shelf storage were also significantly detrimental. When a previously untested colloid, polyethylene glycol 20,000, was substituted for HES for microperfusion, excellent cardiac function was obtained. In fact, the mean CO of this group, 31.91 +/- 5.70, was significantly above that of fresh HES-UW unstored controls. The suggestion that the UW solution might be improved by this substitution warrants further study.

Adenosine↗
PubMed1989

Vascular resistance vs. perfusate osmolarity: the short term microvascular effect of hypotonic and hypertonic perfusion in the isolated kidney.

Vascular resistance changes were measured in response to alteration in perfusate osmolarity in isolated rabbit kidneys perfused at 10 degrees C. The data obtained were found to fit a simple mathematical model of the vascular resistance of the microcirculation in which it was assumed that variation in this parameter depended solely upon osmotic alterations in the size of the cells within and around the blood vessel walls. The model predicts that the volumetric changes due to the different osmolarities are produced in a tissue layer whose thickness is 30% relative to a fixed outer radius. This result is compatible with the hypothesis that the effects are predominantly due to changes of endothelial cell volume and other perivascular capillary cells. The analysis illustrates the significance of perfusate osmolarity as a determinant of vascular resistance, can be used to investigate the hemodynamic effects that occur during the introduction and removal of cryoprotective agents, and is relevant to the interpretation of results obtained with hypertonic solutions in blood volume restoration after hypovolemic shock.

Animals↗
PubMed1987

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.

Animals↗
PubMed1987

Assessment of clinical renal preservation by phosphorus-31 magnetic resonance spectroscopy.

To evaluate the role of magnetic resonance spectroscopy (MRS) and to develop surface coils for assessing cadaveric renal viability during hypothermic storage, we used the monophosphate/inorganic phosphate ratio (MP/Pi) to monitor phosphorous metabolites in intact kidneys during various renal preservation maneuvers. Eighteen canine kidneys and 16 cadaveric kidneys were studied as follows: Group 1 (N = 4) in situ kidneys were monitored by implanted MRS coils; Group 1 (N = 4) ex vivo kidneys were immediately attached to vascular cannulas and monitored by MRS surface coils during normothermic perfusion; Group 3 (N = 4) kidneys were removed, cold-flushed and, after 24 hours of 4C storage, monitored by MRS surface coils before and during four hours of reperfusion via vascular cannulas; Group 4 (N = 6) kidneys were removed, cold-flushed and monitored by surface coils during cold storage up to 72 hours. In addition, 16 cadaveric kidneys were studied while in sterile cold-storage containers. Postoperative renal function was followed in recipient patients. The MP/Pi ratios in Group 1 kidneys correlated with the ability to regenerate adenosine triphosphate (ATP). Groups 2 and 3 showed similar regeneration of ATP and MP/Pi after postischemic reperfusion, and the signal-to-noise ratios of the surface coils were better than those in the implanted coils in Group 1. Surface-coil monitoring in Group 4 kidneys showed predictable decay rates of MP/Pi during one to 72 hours of cold storage; in contrast, simultaneous cortical medullary microcirculation studies with 99mTc-macroaggregated albumin were inconclusive. Human cadaveric kidneys with high MP levels were associated with excellent renal function after transplantation, while those with low MP (less than or equal to 0.50) were associated with nonviability. We conclude that MRS is a practical and safe diagnostic modality for clinical transplantation.

Adenosine Triphosphate↗
PubMed1985

Changing patterns of gastrointestinal bleeding.

This study, a retrospective analysis of 351 patients with acute gastrointestinal (GI) hemorrhage, was undertaken to define patterns of disease and age-related operative and mortality rates and to determine changes over time related to changes in management. One third (116 patients) of the admissions had bleeding esophageal varices. Upper GI hemorrhage accounted for 85% (N = 200) and lower GI hemorrhage for 15% (N = 35). Emergency surgical intervention was required in 90 patients (38%), 40% of the upper and 29% of the lower GI hemorrhage patients. Benign ulcer disease accounted for 86% of the cases requiring emergency surgery and was treated with vagotomy and drainage and/or oversewing. Lower GI bleeding is seen in older patients; it has a lower operative intervention rate and a higher mortality. Stress bleeding as a surgical lesion has disappeared since 1979. A more assertive policy for surgical intervention has decreased operative mortality for all age groups. Bleeding duodenal ulcers are decreasing in incidence while gastric lesions appear to be increasing. These population-specific patterns, different from earlier periods, may have implications for training and patient management decisions.

Acute Disease↗
PubMed1985

Optimal redox electrode potential for 24-hour rabbit kidney perfusion.

This study was conducted to determine whether an optimum redox electrode potential existed for 24-hr hypothermic perfusion of rabbit kidneys. The perfusate consisted of a Ringer's-albumin solution to which was added varying amounts of the reducing agents, glutathione and ascorbate, either individually or in equimolar amounts. Electrode potential was monitored with a vitreous carbon electrode in relation to a silver-silver chloride reference cell, and kidney function was measured after preservation by connection to the circulation of a perfusor animal via a shunt. The best results were obtained using equimolar amounts of the reducing agents. Under these circumstances a definite optimum range for perfusate electrode potential was identified (Es = 40-70 mV) within which renal function was indistinguishable from unpreserved controls. Higher and lower perfusate electrode potentials were associated with significantly lower creatinine clearances. However, the explanation for these results appeared to be more complex than redox control alone, since kidney function was dependent not only on the redox potential of the perfusate but also on the reducing agents with which the adjustment had been made. Ascorbate proved to be significantly better than glutathione within the optimum potential range.

Animals↗
PubMed1984

Studies in cryoprotection. I. A simple method for the controlled introduction and removal of cryoprotective agents during organ perfusion.

A method is presented for the introduction and removal of cyroprotective agents from kidneys, utilizing the principle of gradual addition and elution during continuous perfusion. The method differs from those described previously in that it utilizes a standard perfusion machine (Water MOX 100) and a motorized syringe pump; both of which are widely available in laboratories involved in clinical and experimental organ preservation. In addition, a simple method for measuring vascular resistance is described which relies on a comparison of flow rates through the perfused organs to that through a fixed resistance. The utility of this approach is illustrated by studies of organ function and vascular resistance.

Animals↗
PubMed1984

Damaging effect of subzero temperature (-4 degrees C) on rabbit renal function.

The effect of exposing rabbit kidneys to -4 degrees C for 1 hr in the unfrozen state was evaluated by means of measurement of tissue slice K/Na ratio and whole organ creatinine clearance. Freezing was prevented in one series (groups SC1-SC3) by supercooling with temperature monitoring and in a second series by a 2 M mixture of propylene glycol and glycerol. The latter agent was introduced prior to storage and later removed before the viability testing using a perfusion method (groups CPA1-CPA4). The results indicated a significant loss of slice and whole organ function during this short period of supercooling. The injury did not appear to result from either the rapidity of cooling or the formation of ice. There was some loss of function resulting from perfusion itself. Since this injury was evident in the whole organ but not in the tissue slice it may be ascribed to a vascular affect. When this damage was taken into account the data indicated that cryoprotective agents appeared to protect against any additional damage resulting from 1 hr storage at -4 degrees C.

Animals↗
PubMed1984

Studies in cryoprotection II: Propylene glycol and glycerol.

Propylene glycol (PG), glycerol (G), or a combination of both were introduced into and eluted from 116 rabbit kidneys. The function of the kidneys was then studied on an ex vivo shunt by determining bloodflow and creatinine clearance. The cryoprotective agents ( CPAs ) were introduced and eluted at the rate of about 30 mM/min in an albumin-Ringer's lactate perfusate. In this system, 1.75 to 2.25 M cryoprotectant could be introduced and removed with no demonstrable loss of function. Significant injury was incurred at and above 2.5 M concentrations. When a combination of PG and G (equal proportions) was utilized, both 2.5 and 2.75 M total concentrations were tolerated by the kidney, with no loss of function. These studies demonstrate that in this very rigorous test system, cryoprotectant-induced injury can be significantly diminished by combining two agents of low toxicity. This suggests that osmotic injury may be enhanced by specific toxicities of cryoprotective agents, which can be minimized by using combinations, such as was done in these studies. Also, it has been shown that PG is at least as low in toxicity in the rabbit kidney as is G.

Animals↗
PubMed1984

Beneficial effect of low concentrations of cryoprotective agents on short-term rabbit kidney perfusion.

This report describes observations concerning the influence of the addition of 0.3 M cryoprotective agents (propylene glycol or glycerol) to Ringer's albumin solution used for rabbit kidney perfusion for periods of less than 4 and 24 hr. Endogenous creatinine clearance during short-term parabiotic perfusion on a shunt was used to evaluate function after perfusion. The findings were (A) Perfusion for less than 4 hr resulted in a significant loss of function by comparison with 1 hr ice-stored controls. (B) Continuing the perfusion for 24 hr resulted in a further significant fall in function. Much of the early perfusional injury seen in these two groups could be avoided by including 0.3 M cryoprotective agents in the perfusate.

Animals↗
PubMed1984

Experimental observations on the mode of action of "intracellular" flush solution.

Experiments were conducted using rabbit kidneys stored on ice for 48 hr to elucidate the mode of action of "intracellular" flush solutions. Measurements were made of renal function on a shunt and they were correlated with blood flow and the efficiency of the mechanical expulsion of red cells. By comparison with unflushed, ice-stored kidneys, near complete mechanical expulsion of blood by 30 to 60 min of continuous perfusion with hypertonic Ringer's albumin resulted in significantly higher blood flow with little gain in function. Similarly, increasing the content of nonelectrolyte in Ringer's albumin improved blood flow but not function. A simple flush with a low ionic strength sodium solution (LIE), containing impermeant anions and glucose was superior to that with Ringer's albumin. A high-potassium version of the low ionic strength solution (LIC) was in turn significantly better than LIE for kidney preservation by simple flushing and ice storage. These results were interpreted to mean that whereas mechanical flushing is a relatively minor component of the action of flush solutions, the major benefit results from a reduced sodium and elevated potassium content in the presence of impermeant anions. The primary importance of prevention of cell swelling by the inclusion of nonelectrolytes in "extracellular" flush solutions, is questioned.

Albumins↗