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Biomedical subjects

H G McDaniel

Publications and source records attributed to H G McDaniel.

At least 19 recordsLinked to original sources
PubMed1991

Changes in AMP deaminase activities in the hearts of diabetic rats.

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).

AMP Deaminase↗
PubMed1991

Experimental hyperthermia: protective effect of oxygen carrying fluorocarbon and crystalloids intraperitoneally.

The treatment of hyperthermia produced by passive warming was studied in anesthetized rats weighing 250-300 grams. In the first set of seven experiments, the authors found that venous blood oxygen fell as core temperature rose. Intraperitoneal injection of 20 ml of the oxygen carrying fluorocarbon (perfluorotributylamine, FC-43) emulsion in three of the animals shifted the curve to the right improving venous oxygen content (p less than 0.1). In the second series of experiments, a catheter was placed in the carotid artery. This catheter was attached to a pressure transducer for continuous recording of blood pressure and heart rate. Periodic blood samples were removed for measurement of blood gases, pH, and lactate. Four of the animals received 20 ml of isotonic saline, three received 20 ml of FC-43 emulsion both given intraperitoneally, and four served as controls. In the control group, there was an increase in systolic blood pressure and heart rate which peaked at a colon temperature of 42 degrees C, followed by cardiovascular collapse and death around 43 degrees C. Arterial PO2 (corrected for temperature) remained relatively constant up to 42 degrees C, and then fell. The arterial PCO2 rose sharply when the core temperature exceeded 43 degrees C. Arterial lactate content began to increase at 42 degrees C and above 43 degrees C was 2.5 fold elevated. Isotonic saline provided circulatory support but did not change the hypoxia or mixed acidosis from CO2 and lactate above 43 degrees C. FC-43 emulsion decreased hypoxia and improved circulatory performance but was associated with a mild respiratory alkalosis as arterial PCO2 fell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Control of serum potassium during fasting in patients with end-stage renal disease.

In order to evaluate internal potassium balance in patients with end-stage renal disease (ESRD), epinephrine (0.015 micrograms/kg/min) was infused intravenously into normal control (N = 9) and ESRD subjects (N = 7) after a 26 hour fast. Hyperkalemia developed in ESRD patients after 16 hours of fasting, as compared with control subjects (P = 0.02). The hemodynamic response to epinephrine was similar in the two groups. During epinephrine infusion for one hour, the serum potassium decreased in normal subjects, from 4.3 +/- 0.2 mEq/liter to 3.9 +/- 0.1 mEq/liter, but did not change in ESRD patients (P = 0.005). Serum CO2 declined in ESRD, but not in control subjects, while glucose levels were not different in the two groups. Plasma aldosterone was significantly higher in fasting ESRD patients and failed to decrease during epinephrine infusion as compared to controls. Plasma insulin levels remained low in both groups even though serum glucose levels increased. These results demonstrate that hyperkalemia occurs during fasting in ESRD probably as the result of insulinopenia, and suggest that a diminished response to epinephrine may contribute to hyperkalemia.

Adult↗
PubMed1988

Demonstration of the adenosine reservoirs with nitrobenzylthioinosine in liver and diaphragm by high-performance liquid chromatography.

Purine nucleotides, nucleosides, nucleobases, dinucleotides and nucleosides derivatives from acid-extracted rat liver and diaphragm were separated and quantitated by reversed-phase ion-pair high-performance liquid chromatography with a mobile phase composed of 90 mM potassium phosphate, 15 mM tetrabutylammonium hydroxide and a 1-30% methanol gradient. During 5 min of ischemia, adenine and guanine nucleotides decreased along with significant declines in NAD and increases in adenosine, inosine, hypoxanthine, xanthine, NADP and adenylosuccinate. Nitrobenzylthioinosine by gavage (5 mg/kg per day for five days) increased adenosine levels but without any alteration in nucleobase levels. Adenosine was shuttled to every available intracellular reservoir which included in declining order of magnitude GDP greater than adenosylhomocysteine greater than adenosine greater than ADP greater than AMP greater than IMP = XMP = GMP.

Adenine Nucleotides↗
PubMed1988

Association-dissociation studies of bovine and rat liver glutamic dehydrogenase by high-performance liquid chromatography gel filtration.

The concentration-dependent association-dissociation tendency of purified bovine liver and rat liver glutamic dehydrogenase (GDH) has been demonstrated by high-performance liquid chromatographic gel filtration. In the concentration range of 100 to 1.0 micrograms bovine GDH/ml molecular species ranged from dimer and unimer to subunimeric forms. The dissociation process of the unimeric hexapeptide, consisting of six polypeptide chains, to the subunimeric tripeptide, consisting of three polypeptide chains, was irreversible without added ionic support, but reversible with added ionic support. In dilute Tris-HCl bovine liver GDH was dispersed to subunimeric sizes. Increasing the ionic strength in 20 mM phosphate as the mobile phase increased dissociation to a subunimeric tripeptide while sustaining as much as 80% of its activity. Activity of a eluting subunimer was verified by the inclusion of reaction substrates (NAD and glutamute) in the mobile phase and quantification of reaction products (NADH) in chromatograms. Gel filtration of GDH in the presence of GTP with NADH rendered a subunimeric tripeptide, largely independent of ionic strength or GDH concentration. Rat liver GDH, differing from bovine liver GDH, was dissociated by gel filtration to an active tripeptide independent of ionic or buffer conditions.

Adenosine Diphosphate↗
PubMed1988

Myocardial fuel and energy balance, acute ischemia and diabetes.

When glucose-insulin-potassium (GIK) is infused, glucose supplies most of the energy demands of the heart. Fatty acid becomes the major substrate during fasting, pathologically increased work loads or insulin deficiency. Myocardial purine breakdown reflects myocardial energy status and influences coronary tone. Ischemia accelerates breakdown of ATP to AMP, which is further metabolized to adenosine, which causes vasodilatation and a blunted response to catecholamines. If normal circulation is restored, ADP and AMP are rapidly converted to ATP and purine metabolism is changed from degradation to salvage and de novo synthesis of purines. Ischemia impairs mitochondrial function, causing decreased capacity to oxidize fatty acids once aerobic conditions return. Thus, reperfusion with elevated plasma free fatty acids results in acyl-CoA accumulation in the heart. In diabetic animals, phosphorylation of AMP to ATP is defective in the heart, and AMP degradation is increased. Therefore, careful regulation of the blood sugar with concomitant lowering of plasma free fatty acids in diabetics with ischemic heart disease should improve myocardial salvage by preserving and repleting myocardial ATP. Thus, along with reestablishment of coronary flow and reduction in myocardial oxygen demands, may significantly reduce the morbidity of acute ischemia in diabetics.

Acute Disease↗
PubMed1988

Adenine nucleotide metabolism in hearts of diabetic rats. Comparison to diaphragm, liver, and kidney.

High-performance liquid chromatography analysis of acid-extracted tissues revealed decreases of high-energy nucleotides and increases in low-energy nucleotides and metabolites in heart, diaphragm, and liver but not in kidneys of diabetic rats. In comparison with nondiabetic rats, the total adenine nucleotide content of diabetic rat heart and diaphragm but not liver decreased, indicating an increase in catabolism of AMP. Maximal initial rates of the AMP catabolic enzymes 5'-nucleotidase, adenosine deaminase, and AMP deaminase were elevated in the hearts of BB/Wistar and streptozocin-induced diabetic rats. Nucleotide salvage enzymes adenylosuccinate synthetase and adenylosuccinate lyase were elevated above normal in the diabetic heart, whereas hypoxanthine-guanine phosphoribosyl transferase was not altered. Cytosolic-to-mitochondrial ratios from maximal initial rates after correction for mitochondrial breakage were increased above controls in diabetic hearts for nucleoside diphosphokinase and aspartate aminotransferase. Nucleotide levels, degradation rates, and substrate compartmentation between cytosol and mitochondria are discussed in relation to concurrent diabetes.

Adenine Nucleotides↗
PubMed1985

Improved myocardial contractility with glucose-insulin-potassium infusion during pacing in coronary artery disease.

The metabolic and mechanical effects of a solution of glucose-insulin-potassium (G-I-K) were investigated in 18 patients who underwent diagnostic cardiac catheterization for coronary artery disease. All patients were paced at a rate of approximately 140 beats/min before and after infusion of G-I-K. Basal and paced left ventricular (LV) end-diastolic pressure, dP/dt, arterial substrate levels and osmolarity were measured in all 18 patients. In 13 patients cardiac index was also measured. In 5 patients arterial-coronary sinus measurements of oxygen, carbon dioxide, glucose, free fatty acids, lactate, alanine, glutamate, glutamine, ammonia and urea were made, in addition to coronary sinus blood flow. G-I-K increased the blood sugar level to approximately 200 mg/dl and raised the serum osmolarity 9 mosmol. Pacing alone raised the cardiac index 4% and pacing with G-I-K increased the cardiac index 6% (p less than 0.05). Pacing before G-I-K augmented dP/dt (21%) and pacing with G-I-K increased it (30%) (p less than 0.01). The metabolic changes noted included a shift in the respiratory quotient from 0.77 to 0.96 with G-I-K infusion (p less than 0.05). During G-I-K infusion the myocardial oxygen consumption at rest increased from 17.1 to 21.8 ml/min (23%, p less than 0.05). Myocardial oxygen consumption during pacing was similar before and after G-I-K infusion. Before G-I-K infusion nitrogen balance was slightly positive; after G-I-K infusion it was negative with regard to the nitrogen-containing compounds measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Elevated catecholamines during cardiac surgery: consequences of reperfusion of the postarrested heart.

This study determines whether reperfusion of the heart with elevated blood levels of epinephrine (E) and norepinephrine (NE) during cardiac surgery produces deleterious effects. The study was conducted in 60 patients undergoing coronary artery bypass surgery. Arterial catecholamine values increased significantly (p less than 0.05), from prebypass control levels of 152 +/- 29 and 327 +/- 30 pg/ml of E and NE, respectively, to 415 +/- 78 and 554 +/- 49 pg/ml, at initiation of perfusion of the heart after the aortic cross-clamp was removed. Serial measurement of arterial (A) and coronary sinus (CS) E, NE, potassium, lactate, PO2 and CK-MB revealed that during 10 minutes of reperfusion the heart extracted E (positive A-CS difference, p less than 0.05), but that the NE A-CS difference was 0. The CS effluent contained significantly (p less than 0.05) higher concentrations of potassium, lactate and CK-MB during reperfusion than before aortic occlusion. There was no significant correlation of arterial E and NE, CS E and NE or A-CS differences in E and NE with myocardial release of lactate, potassium or CK-MB. There was a weak association (r = 0.4, p less than 0.01) between coronary sinus CK-MB and aortic occlusion time. Maximal arterial E and NE values did not correlate with 10-hour postoperative (maximal) CK-MB values. These results indicate that reperfusion of the postarrested ischemic heart with high levels of endogenously released catecholamines does not worsen ischemia or contribute significantly to myocardial damage.

Cardiopulmonary Bypass↗
PubMed1984

Glutamic dehydrogenase from rat heart mitochondria. I. Purification and physical properties including molecular weight determination.

Glutamic dehydrogenase extracted with tris buffer from fresh freeze-thawed rat heart mitochondria was purified by ammonium sulphate fractionation, affinity chromatography on GTP agarose, hydroxyapatite chromatography and concentration using a molecular sieve. The final specific activity is 80 units/mg protein. Thin gel SDS electrophoresis of the purified enzyme preparation after reduction with dithiothreitol shows a major band with a molecular weight of 38 000 Daltons. Two minor bands are also present. Sucrose density gradient centrifugation reveals a molecular weight of 230 000 Daltons for unreduced mitochondrial GDH activity. By gel filtration rat heart mitochondrial glutamic dehydrogenase has a major peak at 230 000 Daltons, a minor peak at 300 000 Daltons and some larger molecular weight species. Rat liver mitochondrial glutamic dehydrogenase has a minor peak at 230 000, a major peak at 300 000 and some larger molecular weight species. The rat liver mitochondrial glutamic dehydrogenase predominance at 300 000 is unchanged by incubation, extraction and purification with rat heart mitochondria. The purified GDH is stable frozen at -10 degrees C in tris-HCl buffer with EDTA. It loses activity at 4 degrees C especially when stored in 0.2 M phosphate buffer. It also loses activity when dialyzed for 24 h. This loss of activity is not completely prevented by adding nucleotides to the buffer (AMP or ADP) but is decreased by their presence.

Animals↗
PubMed1984

Glutamic dehydrogenase from rat heart mitochondria. II. Kinetic characteristics.

Glutamic dehydrogenase purified from rat heart mitochondria has been characterized with regard to its substrate kinetics and the influence of nucleotides and potassium phosphate on its kinetic properties. The enzyme had characteristics similar to liver mitochondrial glutamic dehydrogenase. These included several double reciprocal plots which were biphasic, indicating homotropic interaction; inhibition by GTP, which was overcome by ADP and phosphate; and activity with both NAD(H) and NADP(H). There were a number of significant differences however, in the specific kinetic properties of heart mitochondrial glutamic dehydrogenase. The Vmax of reductive amination was four-fold greater with NADH than with NADPH. The maximum rate of oxidative deamination was ten-fold greater with NAD compared to NADP. The differences also included: saturating levels of NADH and NADPH were stimulatory rather than inhibitory; ammonia was stimulatory at millimolar levels; NADP and alpha-ketoglutarate were both inhibitory at saturating levels; and ADP increased reductive amination 30% at lower levels of NADH but inhibited at higher (stimulatory) levels of NADH.

Adenosine Diphosphate↗
PubMed1984

Glutamic dehydrogenase activity in rat heart: demonstration of two forms of enzyme activity.

Glutamic dehydrogenase (GDH) activity in rat heart was found to be 2.1 U/g of heart (wet wt). The mitochondrial glutamic dehydrogenase activity accounted for only 18% of the total. This percentage of the total activity in heart mitochondria was not altered by nagarse treatment, acetone extraction, sonication in Triton X-100, and extraction with buffer containing a protease inhibitor. The remainder of the activity was present in the cytosol. Cytosolic GDH activity differed from mitochondrial GDH activity by its pH curve, stability to heat, Arrhenius plot, and the effect of different nucleotides. Acetone extraction of the mitochondria resulted in GDH that was stable to heat and had a shallow temperature activation curve resembling cytosolic GDH. Acetone extraction of cytosolic GDH inactivated it. The cytosolic activity was purified 288-fold and the mitochondrial activity 100-fold. Purified cytosolic and mitochondrial GDH enzymes had different monomeric molecular weights on sucrose density gradient centrifugation. Gel filtration of cytosolic and mitochondrial GDH also showed different monomeric molecular weights. We conclude that rat heart GDH exists in two forms with different physical and kinetic characteristics. The majority of GDH activity in rat heart is cytosolic. The mitochondrial enzyme has a lipid-soluble component that can be removed with acetone without destroying its activity.

Animals↗
PubMed1984

A randomized comparison of crystalloid and blood-containing cardioplegic solutions in 60 patients.

To determine whether adding blood to a cardioplegic solution affects myocardial preservation, a randomized prospective study was carried out in 60 patients undergoing coronary revascularization to compare the effects of crystalloid potassium cardioplegics (group C) and potassium cardioplegic solutions to which blood has been added (group B) on markers of myocardial metabolism (lactate, inorganic phosphate, base deficit release, glucose and lactate uptake, oxygen extraction), myocardial damage (creatine kinase [CK]-MB levels), and cardiac performance (cardiac index and left atrial pressure). The solution with added blood had a significantly (p less than .05) greater oxygen content, a lower pH, and higher concentrations of potassium, calcium, sodium, and glucose. In group B patients there was a suggestion (p less than .06) of greater uptake of oxygen during the beginning of the initial cardioplegic infusion. During reperfusion there was no evidence of differential release of the metabolites of anaerobiosis and myocardial oxygen extraction and glucose and lactate uptake were similarly depressed in both groups. Likewise, CK-MB release after bypass was the same in both groups. Prompt, adequate functional recovery of cardiac index and left atrial pressure was observed in both groups. It was concluded that although there may be more oxygen available from the blood-containing solution during early infusion, there is no evidence that under the conditions of this investigation adding blood to cardioplegic solution improves myocardial preservation.

Blood↗
PubMed1983

Platelet function abnormalities in response to arachidonic acid in the acute phase of myocardial infarction.

The aggregation of platelets to arachidonic acid was studied serially in patients admitted to the hospital with suspected acute myocardial infarction (MI) and no history of platelet-altering drug ingestion. Of 17 patients studied within the first 48 hours after MI, 16 had a marked decrease in aggregation, to 0.5 mM arachidonic acid (15 +/- 12% compared with 64 +/- 15% for control subjects, p less than 0.01). The exception was a patient with documented coronary artery spasm who was receiving nifedipine at the time of MI. He had a delayed but normal final percent aggregation. The aggregation response returned to normal at 2 to 4 days and was slightly above normal at 6 to 10 days (change not statistically significant). Thromboxane B2 formation correlated with the response of patients' platelets to arachidonic acid (38 +/- 15 ng in the low responders versus 161 +/- 30 ng/3 X 10(8) platelets/4 min in the normal responders, p less than 0.05). Low responding platelets after washing had normal adenosine diphosphate and adenosine triphosphate contents and aggregated and formed thromboxane B2 normally with arachidonic acid. The plasma of patients with MI was found to inhibit platelet aggregation and thromboxane B2 formation to arachidonic acid.

Adenosine Diphosphate↗
PubMed1983

Carbohydrate metabolism during fasting in chronic hemodialysis patients.

Carbohydrate metabolism was studied during a 72-hr fast in 11 nondiabetic endstage renal disease (ESRD) patients on chronic hemodialysis and six normal subjects. Blood was obtained every 12 hr for metabolic substrate, insulin, and potassium concentrations. Serum potassium concentrations were significantly higher in the ESRD patients at the end of each fasting day, and two patients were removed before completion of the fast when severe hyperkalemia developed. Mean blood glucose, alanine, pyruvate, beta-hydroxybutyrate, and serum insulin concentrations were similar in the two groups. Mean blood lactate concentration tended to be higher in the ESRD group. Mean blood acetoacetate and plasma free fatty acid (FFA) concentrations were lower in the ESRD group. When compared to serum insulin levels, the FFA concentration was lower in the ESRD group.

3-Hydroxybutyric Acid↗
PubMed1982

Detection of myocardial injury after coronary artery bypass grafting using a hypothermic, cardioplegic technique.

Fifty patients undergoing isolated coronary artery bypass grafting procedures using a clear, cold cardioplegic solution, topical hypothermia, and reduced systemic flow for intraoperative myocardial protection were evaluated for myocardial injury by serial plasma creatine kinase-MB isoenzyme (CK-MB) measurements and electrocardiograms. Forty-one (82%) of the patients had three-vessel disease. Preoperative left ventricular contractility determined angiographically was normal in 13 patients (26%), mildly abnormal in 26 (52%), and moderately or severely abnormal in 11 (22%). The number of arteries grafted ranged from 2 to 6 (mean, 3.5). The mean duration of aortic clamping was 38.6 +/- 1.6 minutes. There were no hospital deaths. Enzymatic and electrocardiographic (ECG) evidence of myocardial infarction occurred in 1 patient. Nonspecific ECG changes occurred in 16 patients (32%), and th electrocardiograms were unchanged in the remaining 33 patients (66%). In the 49 patients without ECG evidence of infarction, the mean peak plasma CK-MB value, which occurred 6 hours after the onset of cardiopulmonary bypass, was 7.9 +/- 0.8 IU/L (standard error of the mean) and the mean integrated area 158 +/- 19.5 IU/L X hours. There was no correlation between these CK-MB values and the extent of disease, number of arteries grafted, or the duration of myocardial ischemia. These data document a low incidence of perioperative myocardial injury with this technique, and can serve as a baseline for comparison with other techniques for intraoperative myocardial protection in this setting.

Adult↗