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Biomedical subjects

J L Cleek

Publications and source records attributed to J L Cleek.

18 recordsLinked to original sources
PubMed1986

Methylprednisolone and gentamicin effects on hepatosplanchnic blood flow and carbohydrate metabolism in endotoxemic Yucatan miniature pigs.

Conjoint therapy of a glucocorticoid and aminoglycoside antibiotic have been recommended for septic shock. These studies examined the hemodynamic and metabolic effects of methylprednisolone sodium succinate (MPSS) with and without gentamicin sulfate in a nonanesthetized model of nonseptic endotoxemia in Yucatan miniature pigs. Methylprednisolone sodium succinate alone had no effect on endotoxin-induced systemic hypotension. Endotoxemic pigs treated with MPSS in combination with gentamicin sulfate had lower mean arterial pressures than did MPSS-treated and nontreated endotoxemic pigs. Methylprednisolone sodium succinate alone and with gentamicin sulfate improved portal and hepatic venous blood flows moderately. Net hepatic lactate extraction, glucose production, and whole body [6-3H]glucose-derived rates of glucose appearance were also improved, but [6-3H]glucose-derived rates of glucose disappearance and blood lactate concentrations were increased, leading to no improvement in plasma glucose concentration. Pancreatic insulin secretion was higher in treated groups, which may have contributed to greater glucose utilization rates. Hepatic oxygen extraction efficiency was not affected by treatment, but increased in all groups to maintain hepatic oxygenation at base-line values. Although a calcium-antagonistic activity of gentamicin has been reported to synergize with endotoxin, thereby adversely affecting cardiovascular function, such effects did not complicate the metabolic response to steroid in the present studies.

Animals↗
PubMed1984

Hyperosmotic oral replacement fluid for diarrheic calves.

Twenty-five diarrheic neonatal calves, none of which was recumbent, were used to determine oral efficacy of a commercial product for fluid replacement, either by suckle or intubation. Changes in plasma protein, glucose, sodium, potassium, and osmolality as well as blood lactate and PCV were measured. Core body temperature and surface temperature at the hock and fetlock were monitored. Data were analyzed for interaction with time and response according to clinical condition. Significant differences (P less than 0.05) following therapy were restricted to glucose and potassium changes. Beneficial posttreatment trends were observed in cutaneous temperature, blood lactate, plasma protein, and PCV values.

Animals↗
PubMed1984

Naloxone therapy in awake endotoxemic Yucatan minipigs.

Twelve Yucatan miniature pigs were fitted with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate portosystemic and transhepatic kinetics. Seventy-two hours later they were placed in slings, and following a 3-hr control period were infused with Escherichia coli endotoxin at 15 micrograms/kg/hr for 6 hr. Eight were controls and 4 received a primed (2 mg/kg) continuous infusion (2 mg/kg/hr) of naloxone 1 hr after initiation of endotoxin. In the naloxone group, arterial hypotension developed by 60 min. Arterial pressure increased to 125 mm Hg by 80 min (20 min post naloxone) and maintained this level for 3 hr. [6-3H]Glucose-derived rate of disappearance (Rd) values were increased above their own control period at 60 and 80 min, but were approximately 55% lower than untreated controls. Rate of appearance (Ra) values remained unchanged in the naloxone group resulting in a net glucose deficit. After 1 hr of endotoxin, blood pyruvate increased from 1.0 to 1.8 mg%, reached 3.3 mg% at 80 min, and remained elevated. Blood lactate similarly increased from 11 to 35 mg% by 60 min, increasing further to 82 mg% 20 min after naloxone infusion, in concert with signs of severe distress. Portal and hepatic total O2 decreased by 60 min and 100 min, respectively, reflecting depressed hepatic O2, input. Lethality was 75% in naloxone-treated pigs by the end of the experiment, vs 0% in untreated animals. Naloxone improves some hemodynamic parameters. However, in these conscious postsurgical patients, naloxone blocked some beneficial effects of endogenous opiates resulting in severe metabolic derangements and increased mortality.

Animals↗
PubMed1984

Effects of captopril on hemodynamic and metabolic parameters in awake endotoxemic Yucatan minipigs.

Angiotensin II (AII), a potent vasoconstrictor, contributes to ischemic and decompensatory phases of shock. Captopril may benefit vital organ and tissue perfusion by inhibiting AII formation. We fitted 13 approximately 50-kg pigs with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate portosystemic and transhepatic kinetics. We placed them in slings 72 hr later and following a 3-hr control period, they were infused with E. coli endotoxin at 15 micrograms/kg/hr for 6 hr. We kept eight as controls and five received a primed (2 mg/kg) continuous infusion (2 mg/kg/hr) of captopril 1 hr after initiation of endotoxin. Arterial hypotension developed by 60 min and hypoglycemia by 100 min in both groups; captopril had no effect on these parameters. Blood lactate increased from 7.8-32.1 mg/dl 80 min postendotoxin, and for the third to fifth hours of endotoxin infusion was significantly higher than those of the control group. 6-3H-glucose-derived appearance (Ra) values remained at 1.88-2.35 mg/kg/min throughout the experiment. Glucose disappearance (Rd) values were elevated from 60-120 min of endotoxin, increasing to 2.68-3.13 mg/kg/min versus 1.86 mg/kg/min preendotoxin. These changes corresponded to those in lactate, and incurred only a brief significant net glucose deficit (%Rd-%Ra) that peaked at 61.1% at 100 min. For 140-360 min postendotoxin, glucose balance was at most 8.3% in deficit (200 min) and 13.6% in positive balance (280 min) versus a net deficit of up to 25.4% (220 min) for the untreated group for much of the experiment. Portal and hepatic venous blood flow in captopril-treated pigs was lower than that in untreated pigs before endotoxin (8.2 and 10.0 ml/kg/min versus 12.9 and 17.9 ml/kg/min, respectively), but was not depressed following endotoxin infusion, versus 50% reductions in the untreated pigs, postendotoxin. Captopril maintained hepatosplanchnic blood flow and effected modest improvements in glucose kinetics.

Animals↗
PubMed1984

Lidocaine therapy in awake endotoxemic Yucatan minipigs. I. Metabolic parameters and glucose biokinetics.

Cellular membrane destabilization induced by endotoxin and endogenous inflammatory mediators contributes significantly to the progression of metabolic and hemodynamic dysfunction in endotoxemia. Owing to its membrane-stabilizing properties, lidocaine may prove beneficial in the treatment of endotoxic shock. Twelve 50-kg pigs were surgically fitted with jugular venous and carotid arterial catheters. Seventy-two hours later they were placed in restraint slings, and following a 3-h control period, were infused with Escherichia coli endotoxin (Difco 055:B5) at 15 micrograms/kg for 6 h. Eight were controls and four received a primed (2 mg/kg) continuous infusion (2 mg/kg/h) of lidocaine 1 h following the initiation of endotoxin infusion. In the lidocaine-treated group, arterial hypotension (113 mmHg) developed by 60 min, continued to fall to 104 mmHg by 200 min and rose terminally to 118 mmHg. These values were higher than the control group, but were below those of the control period of the lidocaine group. Six -3H-glucose-derived Rd values were increased above their own control period at 60 min, but were approximately 55% lower than in the untreated group. Ra values were not significantly changed in the lidocaine-treated group resulting in a net glucose deficit which was more profound than in untreated pigs, whose Ra values did increase. The degree of hypoglycemia was more profound in lidocaine-treated pigs from 100-260 min, stabilizing at 29-37 mg/dl. Blood lactate (70 mg/dl) was above those of the control pigs (44 mg/dl) from 160 to 220 min. U-14C-glucose-derived glucose recycling was increased above the lidocaine group's preendotoxin control period and reached values twice those of the untreated pigs' endotoxin infusion period. Compared to their own control period and the untreated group's endotoxin infusion period, percentage lactate/glucose was decreased from 40 min on. Lidocaine treatment elicited modest improvements in systemic arterial blood pressure and reduced relative glucose utilization and gluconeogenesis, but in itself, was not a sufficient therapy for endotoxic shock in this model.

Acid-Base Equilibrium↗
PubMed1984

Lidocaine therapy in awake endotoxemic Yucatan minipigs. II. Hepatosplanchnic metabolism.

Reductions in hepatosplanchnic blood flow and oxygen delivery contribute to the hepatic metabolic dysfunction observed in endotoxemia. Through its membrane-stabilizing activity, systemic lidocaine therapy may modify visceral hemodynamics and preserve hepatocellular metabolic function in endotoxic shock. Twelve 50-kg pigs were surgically fitted with jugular, portal, hepatic venous and carotid arterial catheters, and hepatic arterial and portal venous flow cuffs to quantitate portosystemic and transhepatic kinetics. Seventy-two hours later they were placed in slings, and following a 3-h control period were infused with Escherichia coli endotoxin (Difco 055:B5) at 15 micrograms/kg/h for 6 h. Eight were controls and four received a primed (2 mg/kg) continuous infusion (2 mg/kg/h) of lidocaine 1 h following the initiation of endotoxin infusion. Hepatosplanchnic blood flow was relatively unaffected by lidocaine infusion. In both untreated and treated pigs, hepatic arterial flow decreased by 25-30%, portal venous flow fell by approximately 60%, and hepatic venous flow was reduced by 50%. Following 2 h of endotoxin infusion, net splanchnic glucose uptake was increased significantly in lidocaine-treated pigs, but not in untreated endotoxemic animals. Transhepatic lactate kinetics were unaffected by treatment, but net hepatic pyruvate uptake in the lidocaine-treated group increased as compared to the untreated group by 140 min postendotoxin, being significantly greater at 220, 280, and 320 min. Hepatic oxygen input was significantly reduced by 25-30% in both groups within 1 h of the onset of endotoxemia, but hepatic oxygen extraction efficiency increased two-to-three-fold, thereby maintaining net hepatic oxygen uptake. Despite the maintenance of hepatic oxygen uptake and improved hepatic pyruvate extraction in lidocaine treated endotoxemic pigs, no significant improvements in glucose homeostasis were incurred, leading to the conclusion that lidocaine therapy offered few significant advantages in the treatment of overall metabolic derangements during acute endotoxemia.

Animals↗
PubMed1984

Persistent hyperinsulinemia due to induced euglycemia in awake endotoxic minipigs.

Transient hyperinsulinemia has been incriminated as a contributing factor to endotoxin-induced hypoglycemia. However, a recent study using endotoxic minipigs noted an increase in the rate of glucose utilization prior to when hyperinsulinemia was seen. Based on this, the "misinformed beta-cell" hypothesis was proposed. If endotoxic pancreatic beta-cells experience an early increase in glucose uptake, they could over-estimate the true glycemic state and release insulin, further contributing to the hypoglycemia. Hypoglycemia would offset increased glucose uptake by the beta-cell and insulin secretion would return to basal rates, explaining the transient nature of the insulin response. According to this hypothesis, maintenance of euglycemia should elicit a sustained rather than transient insulin release. The hypothesis was tested with a euglycemic clamp technique in a group of five endotoxic (Difco 055:B5; 15 micrograms/kg/hr) minipigs (EC) compared to three nonclamped endotoxic minipigs (E). Persistent, profound hyperinsulinemia (15 ng/ml) occurred in the EC group, further supporting the hypothesis. The clamp appeared to be beneficial, since arterial pressure and pH were significantly (P less than or equal to 0.05) higher and arterial lactate levels were lower in EC pigs compared to E pigs. A significant discrepancy was noted between the radioisotope ( [6-3H] glucose)-derived rate of glucose appearance and the rate of exogenous glucose infusion (clamp), which may have been due to unaccounted for changes in glucose pool size and/or futile cycling of glucogenic substrates or glucose through glycogen and lipid.

Acid-Base Equilibrium↗
PubMed1984

Hepatosplanchnic insulin kinetics in awake endotoxemic Yucatan minipigs: the "misinformed B-cell" hypothesis revisited.

Increased pancreatic insulin secretion may be one of the factors associated with the insulinlike activity (ILA) of endotoxemia. While there is little doubt that the prominent hypoglycemia of endotoxicosis is often preceded by systemic hyperinsulinemia, the cause of this increased secretion and its cause-and-effect relationship to the glucose deficit is less obvious. Recently, a "misinformed B-cell" hypothesis was proposed in which it was suggested that increased glucose flux across the pancreatic B-cell early in endotoxemia might lead to a misinterpretation of the existing glycemic state, resulting in increased insulin release. This possibility was based in part on the observation that increased 6-3H-glucose-derived rates of glucose disappearance (Rd) in endotoxic Yucatan minipigs preceded the onset of systemic hyperinsulinemia. Examination herein of the chronological order of events in this group of pigs and three other groups treated with lidocaine, naloxone, or captopril reveals an increase in pancreatic insulin secretory rate most often before increases in systemic Rd. Each of the three therapies were administered as a primed continuous intravenous infusion, 1 hour after the initiation of a continuous intravenous infusion of Difco 055:B5 E. coli lipopolysaccharide at an LD67 dose of 15 micrograms/kg/hr. In those pigs receiving no therapy, lidocaine, or naloxone, significant increases in pancreatic insulin secretion recurred at 40, 40, and 60 min following the onset of endotoxemia respectively. This was followed in 20 min by the first significant increase in relative glucose disappearance rates (%Rd). Captopril-treated pigs experienced a significant increase in %Rd at 60 min, which was followed in 20 min by a significant increase in pancreatic insulin secretion. In all groups, a significant hyperinsulinemia occurred transiently at 80 min postendotoxin, followed in 20 min by the onset of significant hypoglycemia. These observations suggest that increases in %Rd and transient increases in insulin secretion may be simultaneous events at best, and that along with significant increases in absolute levels of hepatic insulin extraction (observed in all groups at 60 or 80 min postendotoxin) may indicate some local effect of insulin release on hepatic glucose.

Animals↗
PubMed1983

Endotoxin dose. I. Hemodynamic, metabolic, and lethal consequences in Yucatan minipigs.

This study was performed in part to establish an endotoxin dosage in miniature swine that would yield reproducible cardiovascular and metabolic aberrations over a specific 6-h sampling period, minimizing lethality during that time. Five groups of three 6-mo-old Yucatan miniature pigs were surgically fitted with jugular vein and carotid artery catheters. One week later they were placed in slings and infused for 6 h with Difco 055:B5 endotoxin at dosages of 0, 2.5, 7.5, 15, and 25 micrograms X kg-1 X h-1. Significant (P less than or equal to 0.05) time-dose interactions were observed in mean arterial pressure, plasma glucose, serum potassium, blood lactate, pyruvate, bicarbonate, pH, PO2, PCO2, and urea nitrogen. Significant (P less than or equal to 0.05) differences were seen in lethality by 5 days postendotoxin: 0 = 0%, 2.5 = 0%, 7.5 = 33%, 15 = 67%, and 25 = 100% lethal. These animals exhibited a sensitive dose response to endotoxin, often at two- or threefold dose differences. The 15 and 25 micrograms X kg-1 X h-1 groups consistently demonstrated the most profound changes in the parameters measured.

Animals↗
PubMed1983

Increased glucose uptake precedes hyperinsulinemia in awake endotoxemic minipigs.

The role of hyperinsulinemia in the development of hypoglycemia was evaluated in awake Yucatan minipigs. Eight adult minipigs were fitted with jugular, portal, and hepatic vein and carotid artery catheters, and hepatic artery and portal vein flow cuffs for determination of transhepatic kinetics and insulin secretion. Three days later they were infused with E. coli endotoxin at 15 micrograms/kg/hr. Transient hyperinsulinemia was preceded by an elevation of the rate of glucose uptake (Rd) determined from [6-3H] glucose-specific activity. This finding suggested that hyperinsulinemia might be caused by, and then be contributory to, increased Rd. If an increase in glucose uptake was also experienced by pancreatic beta-cells, the existing glycemic state could be overestimated and an inappropriate insulin release elicited.

Animals↗
PubMed1983

Reduced hepatic blood flow does not limit gluconeogenesis in awake endotoxic minipigs.

Hypoglycemia associated with endotoxic shock is due to increased glucose utilization coupled with inadequate hepatic glucogenesis. Decreased hepatic blood flow is common in shock and could conceivably reduce hepatic gluconeogenic substrate and oxygen delivery, thereby limiting gluconeogenesis. A study was conducted to assess endotoxin-induced alteration of hepatic hemodynamics and its effect on glucose metabolism. Eight adult minipigs were fitted with jugular, portal, and hepatic vein and carotid artery catheters, and hepatic artery and portal vein flow cuffs for determination of transhepatic kinetics. Three days later they were infused with endotoxin at 15 micrograms/kg/hr. Hepatic blood flow and portal vein oxygen (O2) content became significantly (P less than or equal to 0.05) reduced thereby decreasing hepatic O2 input. Hepatic O2 extraction increased from 24 to 73% but never achieved the reported maximum of 97%. Therefore, reduction of O2 input did not seem to rate limit gluconeogenesis. Reductions in gluconeogenic substrate delivery were not involved since hepatic lactate and pyruvate input actually increased due to elevated blood lactate and pyruvate concentrations.

Animals↗
PubMed1982

Influence of genetics and diet on the development of diabetes in Yucatan miniature swine.

The intent of this study was to examine the effect of a diet nutritionally similar to that consumed by most Americans on Yucatan miniature swine that have been bred for enhanced and impaired glucose tolerance. Seventeen Yucatan miniature pigs from the glucose-intolerant line (low K) and 17 from the glucose-tolerant line (high K) were selected. The oral glucose tolerance (OGT) of both groups of pigs was determined. After the OGT test (OGTT), 13 low K pigs and 12 high K pigs were placed on the American Swine Diet (ASD). The remaining animals were left on the regular swine diet. After 5 months, the pigs were again tested with an OGTT. Mean plasma glucose levels observed during the OGTT showed significant differences between the low K and high K groups on ASD at all time intervals from 60 to 150 minutes postdosing. Serum insulin levels in the high K group were significantLy elevated over those in the low K group during the OGTT at 10, 20, and 30 minutes prediet, and at 10 minutes after 5 months on diet. Both low and high K groups showed a dietary effect with aN elevated plasma glucose response to an OGTT, although the mean increase was not significant in the high K group. In the low K group, plasma glucose levels were significantly elevated (P less than 0.05) over prediet values at 20, 30, 60, 90 and 120 minutes. In addition, 7 out of the 10 low K pigs tested at 5 months developed insulin resistance, and noninsulin-dependent diabetes.

Animals↗
PubMed1981

Effects of osmolality of liquid nutrient diets on meal passage and nutrient absorption in Yucatan miniature swine.

The effects of varying the osmolality of liquid nutrient diets on the absorption of water, electrolytes, and carbohydrate from the small intestine were studied in Yucatan miniature swine. Pigs were killed and their gastrointestinal contents recovered at either 30 or 60 min after consuming liquid diets adjusted to 340, 450, 540, or 700 mOsm/kg and labeled with 3H2O, 22NaCl, U--14C-sucrose, and 51Cr-EDTA as a passage marker. Intragastric dilution and gastric emptying were not effected by diet osmolality. Gastric contents of all pigs converged toward 450 mOsm/kg, and osmolality of small intestine contents did not differ between diets. The absorption of carbohydrate, water, sodium, and potassium from jejunal contents increased with increasing osmolality of the diets. The rates of appearance of 3H, 22Na, and 14C in plasma also increased with increasing diet osmolality. These findings suggest that moderately hyperosmotic liquid diets may be beneficial, as compared with isoosmotic diets.

Absorption↗
PubMed1981

Metabolic alterations related to reverse portal vein flow in an endotoxic pig.

Chronic hepatic artery and portal vein flowcuffs, in concert with hepatic vein and portal vein catheters, were placed in a Yucatan miniature pig. One week following surgery an endotoxin infusion was initiated. During endotoxemia there was a period of reverse portal vein flow while hepatic artery flow continued. This aberration resulted in unusual portal vein substrate and hormone concentrations. As endotoxemia progressed, the pig became hypoglycemic and hyperlactemic. Specific activity of [6-3H] - glucose was constant during developmental hypoglycemia, while insulin secretion rate was minimal indicating a significant endotoxin-induced, insulin-like activity. Hepatocytes isolated from the pig's liver at termination had inhibited gluconeogenic capacity.

Animals↗
PubMed1980

Lactic acid and glucose metabolism in healthy, lactic acid-infused, and diarrheic calves.

Kinetics of glucose and lactate metabolism were measured in healthy (normal) calves, healthy calves infused with lactate, and in calves which had received an enteropathogenic coronavirus inoculum and had become diarrheic. Lactate utilization was positively correlated with blood lactate concentration in the healthy calves, but its turnover was markedly reduced in diarrheic animals. The decreased turnover was not due to inhibition of lactate oxidation, but appeared to relate to decreased gluconeogenesis. Glucose entry rate was not affected by diarrhea, but was a function of glucose concentration.

Animals↗
PubMed1979

Availability of oral carbohydrates to neonatal calves.

Four experiments were conducted to determine the availability of 3 carbohydrate sources given orally to 1- to 3-week-old clinically normal calves. In terms of effect on plasma glucose concentration, commercial fruit pectin was equivalent to glucose, corn syrup was less effective (P less than 0.05) than glucose, and sucrose was totally unavailable. The addition of 80 mM NaCl to a 10% glucose solution enhanced glucose absorption (P less than 0.01). Increasing the glucose concentration of a commercial product from 1% to 3% resulted in a significant (P less than 0.01) increase in plasma glucose concentration. Lactose availability from suckled fluids was greater (P less than 0.01) than that from fluids given by stomach tube.

Administration, Oral↗