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Biomedical subjects

M Jellinek

Publications and source records attributed to M Jellinek.

At least 37 records · Page 2Linked to original sources
PubMed1985

Improved myocardial preservation by control of the oxidation-reduction potential.

Simple cold storage remains the current method of preservation of human heart allografts between removal and transplantation, but this technique is not adequate for prolonged periods of preservation. An alternative to cold storage is machine perfusion of the isolated organ. Although this technique has yielded promising results in kidney preservation, there is limited experience with the heart. One factor limiting the effectiveness of perfusion preservation is the toxicity of oxygen free radicals generated during the perfusion. The generation and reduction of these radicals results in an electron transfer, producing an electrochemical potential known as the redox potential. This study examines the role of machine perfusion in heart preservation with and without the use of a new electrochemical cell that is able to control the redox potential during the perfusion. Hearts were preserved for twenty-four hours by either simple cold storage (Group I), or by machine perfusion with redox monitoring (Group II), or redox control (Group III). Control of the oxidation-reduction potential of the perfusate during machine perfusion of isolated hearts resulted in significantly improved systolic and diastolic function after perfusion compared to hearts that underwent machine perfusion without redox control or simple cold storage.

Animals↗
PubMed1984

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 Ringer's-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 silver-silver 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.

Animals↗
PubMed1984

Cold blood potassium diltiazem cardioplegia.

Despite the use of cold blood potassium (CBK) cardioplegia, the severely impaired myocardium and/or long ischemia time continue to be a challenge. Because of the association of Ca++ with cell injury and death, the use of Ca++ entry blockers is logical. Investigation of cold blood diltiazem (CBD) revealed no advantages over CBK cardioplegia. The combination of potassium and diltiazem is appropriate because of their different mechanisms of action. Ten dogs had 1 hour of myocardial ischemia with topical ice (temperature 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing potassium (30 mEq/L) and diltiazem (400 micrograms/kg). Eight dogs had 2 hours of ischemia after perfusion with 200 ml of cold blood containing potassium (30 mEq/L) and diltiazem (200 micrograms/kg) and reperfusion every 30 minutes with 100 ml of cold blood containing KCl (30 mEq/L) and diltiazem (100 micrograms/kg). Six dogs received the same treatment as the previous group except that diltiazem was increased to 1,600 micrograms/kg for all four perfusions. Baseline studies were repeated after 60 minutes of reperfusion without the use of Ca++ or inotropic agents. Heart rate, peak systolic pressure, velocity of the contractile element (Vce), maximum velocity of contractile element (Vmax), peak +dp/dt, peak -dp/dt, dp/dt over common peak isovolumic pressure, left ventricular compliance, stiffness and elasticity, and heart water were unchanged from control. Coronary vascular resistance was unchanged in Groups 1 and 2 but declined in Group 3. Creatine phosphate was preserved during ischemia; adenosine triphosphate (ATP) declined. With reperfusion there was continued fall in ATP, ADP, and the adenosine pool. Ultrastructure was well preserved. In 16 of 24 dogs defibrillation was not required, whereas all 48 dogs with CBK and all 13 with CBD required defibrillation. These data suggest that the addition of diltiazem to CBK provides more effective cardioplegia (preservation of creatine phosphate), although ATP and the adenosine pool continued to decline with reperfusion.

Adenosine Triphosphate↗
PubMed1984

Long-term effects of small intestinal bypass on hepatic lipid content in congenitally obese rats.

This study compares the early (30-d) with the late (14-month) effects of small intestinal bypass on hepatic lipid accumulation in congenitally obese Zucker rats. Heterozygote, lean and homozygote, obese Zucker rats underwent sham operations and homozygote obese rats underwent bypass of 90 percent of their small intestine. Evaluation of hepatic lipid content at 30 d following the operation demonstrated increased hepatic triglyceride content in homozygote obese rats compared to heterozygote lean rats; however, the homozygote rats with small intestinal bypass did not have significantly different hepatic triglyceride content from that present in the homozygote obese sham operated rats. Fourteen months following the operations hepatic lipid content increased from 63 +/- 14 mg/g liver in homozygote, obese sham operated rats to 132 +/- 55 mg/g in homozygote, obese rats with small intestinal bypass. The increased lipid was secondary to increased hepatic triglyceride content. Histologic evaluations of liver specimens demonstrated no increased inflammation, granuloma formation or fibrosis when sham operated rat liver tissue was compared to liver tissue from rats with intestinal bypass. These data indicate that at a late stage following small intestinal bypass, the obese Zucker rat develops hepatic steatosis, as do humans, and can serve as an experimental model for evaluation of methods to decrease the triglyceride accumulation.

Animals↗
PubMed1983

The effects of ATP-MgCl2 and dipyridamole in cold-storage preservation.

The effects of ATP-MgCl2 and dipyridamole were evaluated in a canine model. Twenty-five adult mongrel dogs were divided into five equal groups. All dogs underwent left nephrectomy and 30 min of warm ischemia followed by Collins' C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy were then performed. Group A served as controls; Group B was pretreated with intravenous ATP-MgCl2 (2.5 mM); Group C with intravenous dipyridamole (10 mg), and Group D with both ATP-MgCl2 (2.5 mM) and dipyridamole (10 mg). Group E was treated with ATP-MgCl2 (2.5 mM) at the time of transplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In Groups A and E there were no survivors, whereas Groups B, C, and D had 40, 60, and 40% graft survival. In Groups B and D, ATP and energy charge (EC) were greater than that of controls after 24 hr of preservation, with Group D values being significantly greater (P less than 0.01). AMP and ADP levels were significantly greater (P less than 0.02) in Group C when compared to Group A. One hour posttransplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals, but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with ATP-MgCl2 or dipyridamole maintains intracellular nucleotide levels and has a beneficial effect on graft survival in ischemically injured kidneys undergoing cold-storage preservation.

Adenine Nucleotides↗
PubMed1982

Cold blood-diltiazem cardioplegia.

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.

Adenosine↗
PubMed1981

Renal cortical levels of adenosine triphosphate: restoration after prolonged ischemia by in situ perfusion of ATP-MgCl2.

The metabolic consequences of low-temperature kidney preservation by pulsatile perfusion and cold storage were evaluated in canine kidneys by serial adenosine triphosphate (ATP) determinations. Serial cortical ATP levels were determined (1) after optimal harvest, (2) after 60 minutes of warm ischemia, and (3) after 60 minutes of warm ischemia followed by an intra-aortic infusion of ATP-MgCl2. After 24 hours of preservation, cortical ATP levels were significantly greater when pulsatile perfusion was used-both after optimal harvest and after 60 minutes of warm ischemia. Cortical ATP levels were significantly greater at 24 hours in both perfused and cold-storage kidneys when an intra-aortic infusion of ATP-MgCl2 was used following ischemia. These results may explain the 24-hour limitation of cold storage as well as its inferior results following ischemia injury. Furthermore, since ATP is critical in cellular metabolism, the technique of intra-aortic ATP-MgCl2 infusion warrants further investigation in the field of organ preservation.

Adenosine Triphosphate↗
PubMed1980

Effect of small intestinal bypass on hepatic lipid accumulation in rats.

Bypass of large segments of the small intestine to produce weight loss in morbidly obese human subjects has been associated with increased lipid accumulation in the liver. Congenital and nutritional obese rat models were employed to evaluate hepatic lipid accumulation following bypass of 90% of the small intestine. When small intestinal bypass was performed on nutritionally obese rats ingesting a high-fat diet (17%) supplemented with choline dihydrogen citrate (3,4 g/kg diet), a 59% loss of weight at 1 mo was unassociated with increased hepatic lipid accumulation when compared to sham-operated controls. When small intestinal bypass was performed on a nutritionally obese rat fed a relative choline-methionine-deficient diet following intestinal bypass, marked increases in total hepatic lipid and hepatic triglyceride content were evident when compared to the lipid content in sham-operated controls ingesting a similar choline-deficient diet. Hepatic steatosis following small intestinal bypass could be produced in a rat model only by a deficiency in a required substrate for triglyceride conversion to phospholipid and suggests that similar deficiencies may contribute to the increased hepatic lipid accumulation occurring in human subjects following intestinal bypass.

Acetyl-CoA Carboxylase↗
PubMed1979

Phosphocreatine does not inhibit rabbit muscle phosphofructokinase or pyruvate kinase.

Certain phosphocreatine preparations contain a contaminant that inhibits phosphofructokinase and pyruvate kinase assays. The contaminant can be separated from phosphocreatine by anion exchange chromatography. After appropriate purification, phosphocreatine has no effect on phosphofructokinase or pyruvate kinase; thus, there is no evidence that it serves muscle as a regulator of these enzymes. Although the inhibitory preparations of phosphocreatine contain inorganic phosphate and trace amounts of more negatively charged phosphorylated contaminants, the inhibitor is not inorganic phosphate or pyrophosphate. The nature of the inhibitor remains to be determined.

Animals↗
PubMed1979

Cold blood as the vehicle for potassium cardioplegia.

Cold blood with potassium, 34 mEq/L, was compared with cold blood and with a cardioplegic solution. Three groups of 6 dogs had 2 hours of aortic cross-clamp while on total bypass at 28 degrees C with the left ventricle vented. An initial 5-minute coronary perfusion was followed by 2 minutes of perfusion every 15 minutes for the cardioplegic solution (8 degrees C) and every 30 minutes for 3 minutes with cold blood or cold blood with potassium (8 degrees C). Hearts receiving cold blood or cold blood with potassium had topical cardiac hypothermia with crushed ice. Peak systolic pressure, rate of rise of left ventricular pressure, maximum velocity of the contractile element, pressure volume curves, coronary flow, coronary flow distribution, and myocardial uptake of oxygen, lactate, and pyruvate were measured prior to ischemia and 30 minutes after restoration of coronary flow. Myocardial creatine phosphate (CP), adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were determined at the end of ischemia and after recovery. Changes in coronary flow, coronary flow distribution, and myocardial uptake of oxygen and pyruvate were not significant. Peak systolic pressure and lactate uptake declined significantly for hearts perfused with cold blood but not those with cold blood with potassium. ATP and ADP were lowest in hearts perfused with cardioplegic solution, and CP and ATP did not return to control in any group. Heart water increased with the use of cold blood and cardioplegic solution. Myocardial protection with cold blood with potassium and topical hypothermia has some advantages over cold blood and cardioplegic solution.

Adenosine Diphosphate↗
PubMed1979

Allograft viability determined by enzyme analysis.

Enzymatic analysis of the venous effluent of ischemically injured kidney failed to predict accurately the ability of an isochemically injured kidney to support life. Postoperative serum assay of lactic dehydrogenase (LDH) is of value in the assessment of the functional status of the kidney and correlates with response of the rejection episode to immunosuppression. However, by itself it cannot be a sole guide to withholding of therapy. Successful treatment is associated with a decline in LDH level, and failure to return to base line serves as a guide to irreversibility of the rejection reaction.

Acid Phosphatase↗