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Biomedical subjects

A F Roberts

Publications and source records attributed to A F Roberts.

10 recordsLinked to original sources
PubMed1993

Impairment of cardiac function and energetics in experimental renal failure.

Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements.

Adenosine Diphosphate↗
PubMed1990

Effect of endothelin on the function of the isolated perfused working rat heart.

1. The effect of endothelin on the performance of the isolated perfused working rat heart has been examined. 2. A low concentration of endothelin (60 pmol/l) produced a gradual but sustained increase in cardiac output; coronary vascular resistance was unaffected. 3. A high concentration of endothelin (600 pmol/l) produced a rapid increase in cardiac output, followed by a marked fall in cardiac output as progressive, severe coronary vasoconstriction developed. 4. The coronary vasoconstriction induced by endothelin (600 pmol/l) was partially blocked by nicardipine (0.5 mumol/l). 5. In the presence of either nicardipine (0.5 mumol/l) or verapamil (0.2 mumol/l), the increment in cardiac output induced by endothelin (600 pmol/l) was greater than that induced by the addition of the same concentration of endothelin to hearts which had not been exposed to calcium-entry blockers. 6. The effect of endothelin on myocardial contractility has a different time course, concentration dependence and response to calcium-entry blockade than the effect on the coronary vasculature. This suggests that different mechanisms are involved in the generation of the myocardial and vascular responses to endothelin.

Animals↗
PubMed1985

Energy metabolism in reperfused heart muscle: metabolic correlates to return of function.

An important question in energy metabolism of the reperfused, previously ischemic myocardium is whether the return of a normal tissue adenosine triphosphate (ATP) content is a prerequisite for normal rates of oxygen consumption (that is, ATP turnover) and cardiac function. To study this problem, isolated working rat hearts were perfused with bicarbonate saline solution containing glucose (10 mM) at near physiologic work load. After 20 minutes, hearts were made totally ischemic by clamping the aortic and atrial lines for 5, 10 or 20 minutes and then were reperfused for another 10 minutes. Heart rate, aortic pressure, cardiac output and myocardial oxygen consumption were measured continuously. Adenine nucleotides, phosphocreatine, glycogen and the products of glycolysis were determined in freeze-clamped tissue extracts. Functional recovery was assessed by return of aortic pressure and oxygen consumption to preischemic values. Time required for return of function after reperfusion was 90 seconds after 5 minutes and 124 seconds after 10 minutes of ischemia. No recovery was observed after 20 minutes of ischemia. Tissue ATP content decreased significantly at the end of 5 (-38%) and 10 (-56%) minutes of ischemia and did not increase significantly at return of aortic pressure and oxygen consumption to preischemic values. Glycogen stores decreased by more than 50% at the end of 10 minutes of ischemia and did not normalize on recovery. In contrast to ATP or glycogen, the phosphocreatine content decreased to even lower levels at the end of ischemia, but returned to levels higher than the control level after recovery from 5 to 10 minutes of ischemia in association with return of function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

Resetting of pressure-natriuresis and frusemide sensitivity in spontaneously hypertensive rats.

We compared pressure-natriuresis in isolated perfused kidneys of spontaneously hypertensive rats (SHR), and age-matched controls, and studied the effect of frusemide on sodium excretion. Okamoto SHR and age-matched Wistar-Kyoto controls (WKY) were used. Conscious BP was measured in a tail artery cannulated before the experiment. Isolated kidneys were perfused at 37 degrees C and glomerular filtration rate, urinary sodium excretion (UNaV) and percentage sodium reabsorption (%TNa) were measured as mean perfusion pressure was increased in steps from 100 to 180 mmHg and repeated after addition of frusemide. At all perfusion pressures GFR and UNaV were lower in SHR and %TNa higher, consistent with a 50 mmHg rightward shift of the pressure-natriuresis relationship in SHR. However, at intrarenal perfusion pressure equal to MBP, sodium excretion was the same (2.9 microEq/min/g WKY; 2.7 microEq/min/g SHR). Subsequent response to frusemide was markedly reduced in SHR. We conclude that resetting of pressure-natriuresis in SHR compensates exactly for increased renal perfusion pressure. The mechanism by which these are so precisely linked is not known, nor is the reason for the blunted sensitivity to frusemide in SHR, but it is possible that Na-K-Cl cotransport in Henle's loop may be altered in this genetic model of hypertension.

Absorption↗
PubMed1983

The effect of cysteine oxidation on isolated hepatocytes.

Isolated hepatocytes incubated with 4mM-cysteine lose reduced glutathione, adenine nucleotides and intracellular enzymes, thus showing extensive membrane damage. The toxic effects of cysteine are enhanced by NH4Cl. Lactate, ethanol and unsaturated fatty acids afford significant protection against cysteine-induced cytoxicity. Addition of catalase to the incubation medium also protected against cysteine toxicity, indicating that H2O2 formed during the oxidation of cysteine is involved in the toxic effects observed. Under anaerobic conditions cysteine did not cause leakage of lactate dehydrogenase from cells, confirming that rapid autoxidation is an essential condition for development of the toxic effects of cysteine.

Adenosine Triphosphate↗
PubMed1983

Short-term dietary regulation of lipogenesis in the lactating mammary gland of the rat.

Short-term (6 hr) withdrawal of chow diet from lactating rats decreases the rate of lipogenesis in mammary gland by 87%. This inhibition is in part explained by a 60% decrease in the extraction of glucose (the major lipogenic precursor) by the mammary tissue. These changes are not accompanied by any significant alteration in the arterial concentrations of glucose, lactate or insulin; the concentration of acetoacetate did increase by about 30%. Removal of food for 6 hr did not alter the activation state of acetyl-CoA carboxylase or the total activity of the enzyme. Glucose utilization by mammary gland acini from short-term starved rats was not depressed although a higher proportion of the glucose appeared as lactate in the medium and consequently less glucose was converted to lipid. Insulin was able to reverse these changes. Glucagon, adrenaline or cAMP did not inhibit glucose utilization or lipogenesis in isolated acini. It is concluded that the inhibition of lipogenesis in mammary gland after short-term withdrawal of food is mainly due to decreased extraction of glucose. The signal for this change does not appear to be an alteration in plasma insulin and it is postulated that there may be an intestinal factor(s) which acts synergistically with insulin.

Acetyl-CoA Carboxylase↗
PubMed1983

Calcium sensitivity and cardiac performance in genetic and renal models of hypertension.

We have compared cardiac performance, hypertrophy and sensitivity to calcium and verapamil of hearts of six to nine-month-old spontaneously hypertensive rats (SHR), two-kidney, one clip renal hypertensive rats (RHR) and age-matched controls. Cardiac output and heart rate were measured using an isolated perfused heart preparation. Mean blood pressure (BP) and heart weight were equally increased in SHR and RHR as was optimal left atrial filling pressure. Cardiac output was increased in both SHR and RHR at any given work load; this improvement was seen especially in SHR and at high aortic pressure (160 cm H2O) was significant in SHR but not RHR. In low [Ca2+], 0.6 mM, cardiac output of RHR and controls fell markedly, but changed little in SHR, whereas in high [Ca2+], 5.1 mM, cardiac performance deteriorated in SHR but was improved in RHR and controls. Verapamil 2 X 10(-7) M reduced Ca2+ responsiveness of RHR and controls threefold but had no effect in SHR. The results suggest there may be an abnormality of cardiac calcium utilization in inherited but not in acquired hypertension.

Animals↗
PubMed1982

Effects of inhibition of protein synthesis by cycloheximide on lipogenesis in mammary gland and liver of lactating rats.

1. Administration of cycloheximide (an inhibitor of protein synthesis) to lactating rats raised the concentrations of amino acids, and in particular, the branched-chain amino acids (valine, leucine and isoleucine) in blood, liver and mammary gland. 2. Inhibition of protein synthesis increased the incorporation in vivo of L-[U-14C]leucine into lipids of mammary gland and liver. 3. Cycloheximide treatment caused no immediate change in the overall rate of lipogenesis in vivo (measured with 3H2O) in mammary gland but increased the rate in liver 3-fold; this latter effect also occurred in livers of virgin rats. 4. The increased rate of hepatic lipogenesis was not accompanied by significant changes in the plasma insulin concentration or the activity of acetyl-CoA carboxylase. 5. Although cycloheximide decreased the entry of total triacylglycerol into the circulation it did not alter the rate of secretion of newly synthesized saponifiable lipid. 6. Cycloheximide slightly stimulated lipogenesis from endogenous substrates in isolated hepatocytes, but this effect was abolished when lactate was the exogenous substrate. 7. Administration of cycloheximide to virgin rats decreased liver glycogen and increased the hepatic content of glucose 6-phosphate, pyruvate and lactate. 8. It is concluded that (a) there is no short-term link between the rate of protein synthesis and lipogenesis in the lactating mammary gland and (b) the increased rate of hepatic lipogenesis in cycloheximide-treated rats is mainly due to stimulation of glycogenolysis, glycolytic flux and consequent increased availability of pyruvate.

Animals↗