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Biomedical subjects

R A Olsson

Publications and source records attributed to R A Olsson.

At least 73 records · Page 4Linked to original sources
PubMed1983

Pericardial superfusion to measure cardiac interstitial adenosine concentration.

The steady-state concentration of adenosine in pericardial superfusates, [Ado]SS, may estimate the concentration in the cardiac interstitium. As reaching a steady state may sometimes require many minutes, the concentration at an earlier time is often used as an index of [Ado]SS. The latter assumes that the rate of approach to [Ado]SS is uniform and insensitive to perturbations of cardiac oxygen usage (MVO2). In 11 open-chest dogs superfusate adenosine rose at a rate (+/- SD) of 0.53 +/- 0.99/min to an [Ado]SS of 68 +/- 32. The mean rate of equilibration has a very large coefficient of variation, indicating substantial dog-to-dog variation. In five dogs the rate of equilibration during the second of successive superfusions was significantly lower than the first. Raising MVO2 by cardiac pacing or isoproterenol infusion changed neither the rate of equilibration nor [Ado]SS. Aortic constriction or propranolol slowed equilibration but had no effect on [Ado]SS. Thus superfusate adenosine concentration early in the course of equilibration seems an unreliable index of [Ado]SS. That interventions that change MVO2 do not change [Ado]SS from control means either that [Ado]SS fails to reflect the concentration in the vicinity of the coronary resistance vessels or, alternatively, that adenosine does not regulate coronary blood flow.

Adenosine↗
PubMed1983

Role of adenosine in the maintenance of coronary vasodilation distal to a severe coronary artery stenosis. Observations in conscious domestic swine.

The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with 125I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. 125I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior descending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 +/- 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 +/- 0.38, P less than 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 +/- 0.36 vs. circumflex zone = 1.45 +/- 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distal: circumflex epicardial flow ratio declined vs. control 1 (0.98 +/- 0.14) during adenosine deaminase infusion (0.87 +/- 0.17, P less than 0.05). The distal:circumflex endocardial flow ratio during adenosine deaminase (0.72 +/- 0.20) was unchanged vs. control 1 (0.76 +/- 0.22) but was less than control 2 (0.80 +/- 0.18, P less than 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s).

Adenosine↗
PubMed1983

Ligand selectivity of dog coronary adenosine receptor resembles that of adenylate cyclase stimulatory (Ra) receptors.

Adenosine receptors on the surface of coronary myocytes initiate coronary relaxation, but events subsequent to receptor occupancy are uncertain. We assayed the coronary vasoactivity of receptor-selective adenosine analogs in open chest dogs to test the hypothesis that the coronary adenosine receptor is an adenylate cyclase stimulatory (Ra) receptor. The potency order was: ethyl adenosine-5'-uronamide greater than cyclopropyl adenosine-5'-uronamide greater than 2-chloroadenosine greater than N6-[R(-)-1-phenyl-2-propyl] adenosine (R-PIA) greater than N6-cyclohexyladenosine greater than adenosine greater than S-PIA. Such a hierarchy of activity resembles that of the Ra receptors of thyroid and aortic myocyte adenylate cyclases and of tracheal smooth muscle relaxation. The potency order R-PIA greater than adenosine and the stereoselective coronary vasoactivity of R-PIA suggest that the coronary receptor may be a hybrid receptor which contains the "N6 site" typical of inhibitory (Ri) receptors in addition to the "5'-uronamide site' which expresses Ra activity.

Adenosine↗
PubMed1983

Natural history of potassium-deficiency myopathy in the dog: role of adrenocorticosteroid in rhabdomyolysis.

Potassium deficiency occurs in several conditions and is reported to cause muscle weakness and rhabdomyolysis. The mechanisms by which potassium deficiency cause muscle disease remain unknown, but the primary purpose of the present study was to determine whether abnormal muscle glycogen metabolism causes muscle weakness, as suggested by previous work. We monitored the natural history of potassium deficiency in two groups of dogs, one of which also received deoxycorticosterone acetate (DOCA), an agent commonly used in other studies to accelerate potassium loss. Group I dogs on potassium-free diet alone showed a 41% decrease in muscle potassium, no change in serum CO2, creatine kinase (CK), or muscle phosphorylase activity and only mild histopathologic abnormalities before death, after 198 +/- 42 days on the diet (mean +/- S.D.). In contrast, group II dogs on the same diet plus DOCA developed clinically similar severe weakness and died more rapidly than group I, 37 +/- 7 days (p less than 0.03). DOCA dogs showed a more rapid decrease in muscle potassium to the same level as group I, a 37% increase in serum CO2, an increase in serum CK to 1060 to 2775 IU/ml, a 23% decrease in muscle phosphorylase activity, and severe muscle histopathology, including rhabdomyolysis. Neither group showed any change in body weight, electromyogram (EMG), muscle glycogen concentration, glycogen synthetase activity, serum or muscle magnesium or phosphorus, or serum T3 or T4. In conclusion, dietary potassium deficiency in dogs causes severe weakness and death without causing rhabdomyolysis or abnormal muscle glycogen metabolism. Adding DOCA to the potassium-free diet creates a different model characterized by rapid clinical deterioration and rhabdomyolysis.

Animals↗
PubMed1982

Decrease in myocardial oxygen extraction with aortic constriction in the dog.

In the open-chest dog constriction of the descending thoracic aorta, which raises central aortic pressure by 30-80 mmHg, increases cardiac oxygen usage (MVO2) and coronary blood flow (CBF) but reduces heart rate and myocardial oxygen extraction [(A-V)O2]. Pacing tachycardia superimposed on aortic constriction further increases MVO2 and CBF but does not alter (A-V)O2. Atropine or vagotomy abolishes the effect of aortic constriction on (A-V)O2, whereas vagal stimulation in the presence of alpha- and beta-adrenergic blockade reduces (A-V)O2. L-propranolol and phenoxybenzamine fail to modify the effect of aortic constriction on (A-V)O2. These results indicate that aortic constriction reduces (A-V)O2 by eliciting parasympathetically-mediated coronary vasodilation.

Animals↗
PubMed1981

Intracoronary adenosine deaminase reduces canine myocardial reactive hyperemia.

We employed intracoronary infusions of calf intestine adenosine deaminase (ADA) to test the hypothesis that adenosine regulates coronary blood flow during myocardial reactive hyperemia (RH). Infusions of 4.5 U ADA/min per kg body weight into the left circumflex coronary artery of 10 open-chest dogs reversibly reduced repayment of flow debt by 30-39% (P less than 0.05) following 5-, 10-, 15-, 20-, and 30-second coronary occlusions, the percentage reduction being independent of occlusion length. ADA reduced peak RH flow rate (17%, P less than 0.05) only after 5-second occlusions. Intracoronary infusions of [131]ADA in seven dogs produced interstitial ADA concentrations between 1.2 and 13.1 U/ml in perfused myocardium and, in five of these dogs, 131I activity in the cardiac node was 1.8-35 times that of contiguous mediastinal tissue. Theophylline, a specific adenosine antagonist, reduced repayment of flow debt by 27-36% (P less than 0.02) in eight dogs, an effect similar to that of ADA. In six other dogs, ADA plus theophylline did not reduce RH flow debt repayment below that produced by ADA alone. This experiment confirms the contribution of adenosine to myocardial RH but shows that this nucleoside accounts for but a third of volume flow. Other, as yet unidentified, factors are collectively more important.

Adenosine Deaminase↗
PubMed1980

Limitations in predicting oxyhemoglobin saturation of dog blood from PO2.

This study compared oxyhemoglobin saturation (SO2) and O2 content (CO2) estimated from O2 tension (PO2) by the Rossing-Cain nomogram (J. Appl. Physiol. 21: 195-201, 1966) with SO2 and CO2 estimated by a galvanometric O2 analyzer in blood samples from eight dogs. The nomogram consistently and significantly overestimated SO2 over the range of 20-60%. The greatest absolute difference, which averaged 10% saturation, was between 40 and 59% saturation. Between 30 and 39% saturation, the difference averaged 30% of SO2 estimated galvanometrically. CO2, calculated as the product of SO2, hemoglobin concentration (cyanmethemoglobin method), and hemoglobin O2 capacity, was significantly overestimated by the nomogram by as much as 1.2 ml/dl between 2 and 9.9 ml/dl. Between 14 and 21.9 ml/dl, the nomogram underestimated CO2 by as much as 1.2 ml/dl. We conclude that because coronary venous SO2 and CO2 values normally lie in the range of greatest error, estimates of these values based on PO2 are particularly unsuited for studies of myocardial O2 usage.

Animals↗
PubMed1980

Relationship of cardiac oxygen usage, adenosine content, and coronary resistance in dogs.

Analysis of the relationships between cardiac oxygen usage (MVO2), cardiac muscle adenosine levels([Ado]), and coronary vascular resistance (R) in open-chest, anesthetized dogs tested the hypothesis that adenosine is a physiological regulator of coronary flow. Experiments using each dog as its own control showed that [Ado] varied directly with MVO2 as the latter changed spontaneously or in response to atrial pacing, paired pacing, aortic constriction, of beta-adrenergic blockade. In turn, R varied inversely with changes in [Ado]. Stimulating MVO2 with isoproterenol significantly increased the slope of the regression of [Ado] on MVO2 as well as of R-1 on [Ado]. The effect of beta-adrenergic stimulation on [Ado] is unexplained, but its effect on R-1 seems to reflect the combined effects of adenosine and direct beta-adrenergic coronary relaxation. These results support the hypothesis that adenosine mediates the coronary flow responses to changes in MVO2.

Adenosine↗
PubMed1979

Factors determining delayed peak flow in canine myocardial reactive hyperaemia.

It has been suggested that delayed restoration of flow to the deeper layers of the myocardium is responsible for the gradual rise to peak flow rate characteristic of myocardial hyperaemia (RH). The distribution of coronary flow during RH was studied by injecting radiomicrospheres into the left atrium open chest dog preparations just prior to the end of a 15 s occlusion of the left circumflex branch. The artery was then reoccluded after 1, 2, or 4 s of RH. Myocardium perfused by the left anterior decending branch served as a control; the ratio of endocardial to epicardial (end/epi) perfusion in this bed averaged 1.14. During coronary occlusion and during the first second of RH the end/epi ratio in the hyperaemic zone averaged 50% of control, but rose progressively to equal control at the time of peak flow. Although evanescent subendocardial ischaemia may contribute to the gradual rise to peak flow rate it cannot by itself account for the time course of this response.

Animals↗
PubMed1979

Coronary vasoactivity of adenosine in the conscious dog.

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.

Adenine Nucleotides↗
PubMed1978

Ligand binding to the adenine analogue binding protein of the rabbit erythrocyte.

Adenine analogue binding protein of rabbit erythrocytes reversibly binds [3H] adenosine with a KD of 5.3 X 10(-9) M, an association rate constant of 1.4 X 10(-12) M-1 min-1 and a dissociation rate constant of 7.5 X 10(-3) min-1, as estimated by a nonlinear curve-fitting program applied to data on the time course of the binding reaction. Independent estimates of KD by Scatchard plots and of the dissociation rate constant by dilution or adsorption of free [3H] adenosine on charcoal or by the addition of excess adenosine agreed closely with the estimates from the curve-fitting program. Inhibition of [3H] adenosine binding by a series of 77 adenosine analogues was used to define the factors determining the binding affinity of this nucleoside. These are: (1) the size and aromaticity of the purine base; (2) a glycosylic torsion angle of approximately -120 degrees; (3) the ribo configuration of the 2'-and 3'-hydroxyls and also the 5'-hydroxyl. Bulky substituents in the region of C-2' and to a lesser extent in the region of C-3' reduce binding affinity.

Adenosine↗
PubMed1978

Exercise performance and hemodynamics during dietary potassium depletion in dogs.

Dietary potassium depletion plus high sodium intake has been reported to elevate resting heart rate and cardiac output and to cause heart failure during exercise. We implanted aortic root electromagnetic flowmeters and aortic and pulmonary artery catheters in five splenectomized dogs condition-trained to run at 9 km/h on an 11% grade for 20 min. Postoperatively, the dogs ate a potassium-enriched diet until completion of control studies; then potassium was withdrawn. During 4 wk of depletion, skeletal muscle potassium fell from 380 +/- 22 to 311 +/- 8 meq/kg, and muscle sodium rose from 142 +/- 14 to 207 +/- 27 meq/kg (mean +/- SE). Cardiac output, aortic blood pressure, heart rate, acceleration of aortic blood flow at rest or during exercise, and the oxygen cost of exercise remained at control levels. Serum creatine phosphokinase at rest, an indicator of rhabdomyolysis, was never elevated. A 24% dietary depletion of muscle potassium in the dog did not change resting and exercise hemodynamics and exercise performance from control.

Animals↗