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Biomedical subjects

A J Drake

Publications and source records attributed to A J Drake.

33 records · Page 2Linked to original sources
PubMed1980

Preferential uptake of lactate by the normal myocardium in dogs.

This study was undertaken to investigate whether the normal dog heart would switch to lactate as the preferred substrate when the arterial lactate level was raised. Sodium L-Lactate (pH adjusted to 7.0) was infused intravenously in sufficient quantity to raise the arterial lactate levels to those found in moderate to severe exercise (over 4.5 mmol . litre-1). The dogs were studied under chloralose anaesthesia breathing spontaneously. Blood samples were obtained from a branch of the femoral artery and the coronary sinus, and analysed for lactate, glucose, fatty free acids (FFA) and oxygen content. The ratio of lactate consumption to oxygen consumption was used to express the amount of lactate oxidised as a percentage of total substrate. This ratio was found to be a function of arterial lactate and reached a maximum at an arterial lactate concentration of 4.5 mmol . litre-1; this was uninfluenced by raised arterial glucose or FFA--the myocardium preferred lactate to glucose or FFA. A direct measurement of lactate oxidised as a percentage of total fuel was obtained in experiments with L-Lactate-[14C(U)], these showed that when the arterial lactate concentration was above 4.5 mmol . litre-1, even in the presence of high glucose or FFA, 87% of the total substrate oxidised was lactate. These results show that when the normal dog heart is presented with a choice of substrates, lactate is the preferred substrate for energy production.

Animals↗
PubMed1980

Inhibition of glycolysis in the denervated dog heart.

We measured glucose metabolism in five dogs before and 3 weeks after cardiac denervation; after this time myocardial norepinephrine is depleted. The discharge by the myocardium, of 14CO2 from infused 14C-D-glucose (U), decreased following denervation (P = 0.05). The ratio of 14CO2 to total CO2 production, which measured the proportion of glucose to total substrate oxidized, also decreased following denervation (P = 0.05). The inhibition of glucose oxidation by denervation was not due to an increase in arterial lactate concentration. There was an associated increase in myocardial content of fructose-6-phosphate in an additional seven dogs (P < 0.01). We postulate that myocardial tissue norepinephrine is one of the controllers of the activity of phosphofructokinase.

Animals↗
PubMed1979

The effect of carbon dioxide upon myocardial contractile performance, blood flow and oxygen consumption.

1. Mongrel dogs were anaesthetized with chloralose, paralysed, ventilated and vagotomized and given a beta-blocking drug, sotalol, in sufficient doses to block the effects of 5 microgram of adrenaline. 2. Changes in inspired CO2 concentration were produced, causing increases of arterial PCO2 up to 120 mmHg. The effects on myocardial blood flow were measured with radioactive microspheres. Coronary sinus and arterial blood was sampled. 3. In the absence of beta-blockade, an increase in arterial PCO2 produced variable effects. In some dogs coronary blood flow increased, while in others there was no change. There was a mean increase in coronary blood flow at arterial PCO2 values above 85 mmHg which was abolished by beta-blockade. 4. In the presence of beta-blockade, an increase of arterial PCO2 produced depression of left ventricular performance, i.e. a fall of maximum rate of rise of left ventricular pressure and a rise of left ventricular end-diastolic pressure. 5. In the presence of beta-blockade, there were no consistent changes in myocardial blood flow, left ventricular pressure or cardiac output. 6. In the absence of beta-blockade, coronary arterial minus venous ocygen content was reduced by hypercapnia. In the presence of beta-blockade, the changes were small and not statistically significant. The direct coronary vasodilator effect was therfore negligible. 7. It is concluded that the previously reported hypercapnic vasodilatation was mainly an effect of sympatho-adrenergic stimulation by hypercapnia. 8. In the presence of beta-blockade, coronary sinus PO2 increased markedly, with little change in coronary sinus oxygen content; this was consistent with a shift to the right of the oxy-haemoglobin dissociation curve. Under circumstances of hypercapnia, a rise in coronary sinus (and presumably tissue) PO2 failed to produce vasoconstriction. 9. It is argued that the vasodilator effect of hydrogen ions and the vasoconstrictor effect of oxygen probably cancel one another when the arterial PCO2 is raised.

Animals↗
PubMedDate not supplied

Substrate utilization in the myocardium.

Substrate extraction is the disappearance of a substance from arterial blood into the myocardium, substrate utilization being the combustion of that substrate. The terms used for extraction and utilization are defined. There are many problems of accurately measuring glucose and free fatty acid oxidation. Lactate is the preferred substrate of the normal, blood-perfused heart. If the substrate oxidized affects the myocardial oxygen consumption, this could be of considerable importance under conditions of limited oxygen supply. At present there is conflicting evidence. It may be beneficial to switch the heart from one substrate to another, e.g., from fat to carbohydrate fuels. The conditions of ischaemia and hypoxaemia are not the same, and future investigations should be made under carefully controlled conditions.

Coronary Disease↗
PubMedDate not supplied

Metabolic and haemodynamic responses to adrenaline in normal dogs.

The metabolic and haemodynamic effects of adrenaline were investigated in 6 intact anaesthetized dogs, which were subjected to an infusion of adrenaline. The dose given was similar to the endogenous production rate of adrenaline in experimental myocardial infarction. Adrenaline infusion (0.8, 1.17 ot 1.05 micrograms . kg-1 . min-1) over two hours led to a variable rise in blood level of this amine, regardless of the rate of infusion. Dogs with high blood adrenaline (over 3.5 ng . ml-1) exhibited haemodynamic deterioration, i.e. a rise in peripheral vascular resistance together with a fall in cardiac output and external cardiac work. Dogs with low blood adrenaline showed little change in peripheral vascular resistance, a rise in cardiac output and external cardiac work. The myocardial consumption of each of the substrates lactate, pyruvate, glucose and FFA was measured, and its equivalent oxygen consumption expressed as a percentage of the total myocardial oxygen consumption. No relationship was found between myocardial utilisation of individual substrates and the type of haemodynamic response. Thus in intact dogs exposed to adrenaline excess, similar to that found in acute myocardial infarction, the different types of haemodynamic response cannot be attributed to the type of substrate utilization by the myocardium, but to different rates of clearance of adrenaline. Low clearance rates lead to high blood adrenaline levels and an unfavourable response of the cardiovascular system.

Animals↗
PubMedDate not supplied

Ward's triangle bone mineral density determined by dual-energy x-ray absorptiometry is a sensitive indicator of osteoporosis.

OBJECTIVE: To assess the clinical utility of bone mineral density (BMD) of Ward's triangle by dual-energy absorptiometry (DEXA) as an indicator of osteoporosis in comparison with quantitative computed tomography (QCT) of the lumbar spine and DEXA of the lumbar spine and hip sites (trochanter and femoral neck). METHODS: We conducted a retrospective study of all patients (28 men and 17 women) with decreased BMD by QCT (T-score less than -1.0) who had DEXA BMD performed at the lumbar spine and hip between October 1993 and January 1995 in our Endocrine Clinic. RESULTS: Osteoporosis based on the World Health Organization criteria (T-score less than -2.5) was defined by QCT lumbar spine BMD in 78% of the study subjects and by DEXA of Ward's triangle in 53%, of the femoral neck in 22%, of the trochanter in 7%, and of the lumbar spine in 2%. In the men, the only DEXA BMD measurement that was sensitive for detecting osteoporosis was Ward's triangle. Of the 24 men with osteoporosis by QCT BMD, 14 were defined as having osteoporosis by DEXA exclusively at Ward's triangle. The DEXA lumbar spine BMD measurement was actually above the mean for young normal control subjects in 8 of the 24 men with osteoporosis by QCT BMD. In the 11 women with osteoporosis by QCT BMD, the DEXA BMD at Ward's triangle and the femoral neck were equally sensitive in detecting osteoporosis, whereas the DEXA lumbar spine and trochanter BMD measurements were insensitive. CONCLUSION: DEXA BMD of Ward's triangle is a sensitive indicator of osteoporosis, particularly in men, and should be used to identify patients at increased risk for osteoporosis-related fractures.

Journal Article↗
PubMedDate not supplied

Effect of alendronate treatment on bone mineral density in male patients with osteoporosis.

OBJECTIVE: To assess the efficacy of alendronate therapy on bone mineral density (BMD) at the lumbar spine and hip in men with osteoporosis. METHODS: Medical records of male patients with osteoporosis, who had undergone follow-up in the Endocrinology Clinic at the National Naval Medical Center, were reviewed, and nine patients treated with alendronate for at least 1 year were identified. Patients were excluded from analysis if they had evidence of osteomalacia or if baseline and follow-up BMD results on the same dual-energy x-ray absorptiometry (DEXA) densitometer, at least 10 months apart, were not available. DEXA BMD results at the lumbar spine and hip, before and after at least 10 months of alendronate treatment, were analyzed for significant differences. Patients were also receiving calcium supplementation (1,000 to 1,500 mg/day), and all but one patient received vitamin D (400 to 800 U/day). RESULTS: Lumbar spine BMD increased by 6.4 +/- 1.8% per year with alendronate treatment (P = 0.008). A mean absolute gain of 0.052 +/- 0.010 g/cm 2 (P = 0.005) in lumbar spine BMD was noted for the entire study group (N = 9), after a mean duration of treatment of 14 +/- 1 months. The mean lumbar spine BMD Z score improved by 0.40 +/- 0.09 (P = 0.002) with alendronate therapy. The femoral neck BMD also increased by 4.5 +/- 1.4% per year with alendronate treatment (P = 0.013). The mean absolute gain in femoral neck BMD was 0.028 +/- 0.009 g/cm 2 (P = 0.013) for the study group (N = 9) after 14 +/- 1 months of therapy. The mean femoral neck BMD Z score improved 0.30 +/- 0.08 (P = 0.005) with treatment. BMD gains at the greater trochanter of 3.2 +/- 1.5% per year (P = 0.067) and at Ward's triangle of 9.1 +/- 4.2% per year (P = 0.061) were not statistically significant. Two patients discontinued alendronate treatment after 1 year because of epigastric or retrosternal pain. CONCLUSION: Oral alendronate treatment, given in combination with calcium supplementation and physiologic doses of vitamin D, resulted in significant improvements in lumbar spine and femoral neck BMD after a 14-month period in this small group of men with osteoporosis. Although controlled, prospective trials involving larger numbers of male patients with fracture incidence data are needed before definitive conclusions can be made, alendronate treatment seems to be effective in improving BMD in men with osteoporosis, similar to its efficacy in women.

Journal Article↗