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Biomedical subjects

G J Anderson

Publications and source records attributed to G J Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1985

Monocarboxylate-uptake kinetics in perfused rat heart.

While there is considerable evidence to suggest that lactate and pyruvate transport across the cell membrane is controlled, virtually nothing is known about the mechanisms. To test a prediction that sarcolemmal monocarboxylate transport is mediated by a specific carrier, we have examined the kinetics of pyruvate and lactate uptake into aerobically perfused rat hearts. In preparations depleted of intracellular lactate and pyruvate by a 30-min pre-perfusion in the absence of substrates, various concentrations of [14C]lactate or pyruvate (0.02 Ci/mole), together with [3H]mannitol (50 nCi/ml), were transiently (2 min) infused into the mainstream perfusate immediately above the heart. Uptake was calculated from the difference between the level of 14C-labeled substrate predicted from the extracellular distribution of [3H]mannitol and the actual level (corrected for 14CO2 contamination) measured in successive 20-sec samples of effluent perfusate. Computer optimization analysis of the initially rapid (first 60 sec) uptake rates revealed that monocarboxylate transport is not simply a question of diffusion. On the contrary, the observation of typical saturation kinetics (Vmax 7.7-8.4 mumoles/min per g wet wt.) and cross-inhibition (Ki pyr, 2.3 +/- 0.5 mM; Ki lac, 0.16 +/- 0.02 mM) suggest that transsarcolemmal movement of monocarboxylate may be mediated by a high-affinity lactate (km 3.9 +/- 0.9 mM), low-affinity pyruvate (Km 8.6 +/- 1.1 mM), translocase.

Animals↗
PubMed1983

The effects of ischemia on metabolism and reperfusion arrhythmias.

In attempts to determine the mechanism(s) underlying reflow rhythm disturbances, we have studied the relationship between extent of coronary flow impairment and incidence of reperfusion arrhythmias. In isolated guinea pig hearts perfused with pyruvate (10 mmol/l) and glucose (0.5 mmol/l), coronary flow was reduced to different extents (18, 11, 6, 1, and 0.5%). Following 10 minutes of ischemia, reflow arrhythmias were quantitated with computer-aided statistical determination of rate-independent variations in beat intervals. The results (19 +/- 1, 13 +/- 5, 22 +/- 4, 8 +/- 3 and 6 +/- 1, n = 6, Rhythm Disturbance Units respectively) revealed that rhythm disturbances were more serious after less severe ischemia than after more severe ischemia. To investigate this "paradoxical" observation, we compared the metabolic changes during ischemia and the severity of subsequent reflow arrhythmias. Electrical instability during reperfusion was not related to accumulation of lactate, increase in cyclic AMP or decline in energy status. These were at a maximum in the severely ischemic myocardium. The reduced incidence of arrhythmias following severe (1% and 0.5% flow) as opposed to moderate ischemia, however, may have been associated with a major increase in glycogenolysis (from 1.2 to 7.4 and 7.6 mumol glucose equivalents/min per g dry weight).

Adenosine Triphosphate↗
PubMed1983

Ventricular ectopic beats with exit block: a retrospective Holter monitor study.

A retrospective study was conducted to define the incidence of ventricular ectopic beats with exit block (concealed extrasystoles). Of 904 Holter recordings, 92 were admitted for study on the basis of sufficient ventricular ectopic beats on rhythm strips. Concealed bigeminy conforming to the equation of S = 2n - 1 (where S = the interectopic sinus beat and N = any interger) was the most common and occurred in 42 of 92 (46%) Holters included in this study. Concealed trigeminy was observed in 12 of 92 (13%) studies. These Holters also showed ventricular ectopic beats strongly suggestive of parasystole with entrainment. Of 53 Holters reviewed for parasystole 12 were suggestive of, and five indicated this dysrhythmia. We conclude that: 1. Concealed extrasystoles are more common than previously appreciated. 2. Concealed bigeminy and trigeminy appear together and conversion may not always be associated with a change in heart rate. 3. Recognition of this dysrhythmia is uncommon mostly because of inadequate lengths of rhythm strips. 4. Parasystole with entrainment is suggested as a common dysrhythmia when frequent extrasystoles are present.

Cardiac Complexes, Premature↗
PubMed1983

Electrophysiologic changes induced by external transthoracic countershock.

The purpose of this study was to characterize the electrophysiological effects of suprathreshold transthoracic shocks. Dogs were anesthetized and two consecutive shocks (10 joules/gk) were applied one minute apart. Ventricular extrasystoles were observed in six of the 11 dogs tested, A-V block in three, ventricular tachycardia in three, and asystole in one. Forty eight hours later the hearts were removed. Conventional electrophysiological techniques revealed the following: 1) injured cells had loss of resting potential, triangularization of the action potential and depressed upstrokes; 2) the functional refractory period was shortened, with an increase in time dependence; 3) action potential alternans; 4) discrete areas of marked depression of conduction; 5) re-excitation with premature stimulation and 6) histological evidence of sub-epicardial injury. These studies suggest that the application of suprathreshold shocks may induce electrophysiological changes potentially inducing tachyarrhythmias.

Animals↗
PubMed1983

Intramyocardial current flow in acute coronary occlusion in the canine heart.

Data from numerous experimental infarction studies indicate that rapid myocardial cell depolarization following ischemia causes the flow of injury currents. These currents were measured in the canine myocardium by monitoring voltage gradients across infarct boundaries using silver chloride plunge electrodes, followed by placement of a 100 omega resistor between the electrodes and again measuring the voltage gradients. Current flow was calculated from these measurements with the following results: 1) TQ currents developed within 15 seconds after occlusion and persisted for 120 to 150 minutes, often attaining a magnitude of 1 microA. 2) ST currents also developed within 15 seconds and attained 2 to 3 microA within 15 to 30 minutes, then usually subsided to some degree. 3) T currents were biphasic and attained 2 to 5 microA. Initially, current flowed from normal to ischemic myocardium but usually reversed within 30 minutes after occlusion. 4) The current flow was often disproportionate to the voltage gradient between 120 and 180 minutes after occlusion, possibly indicating electrical uncoupling of the infarcting cells from normal cells. These data indicate that intramyocardial current flow develops early after acute coronary occlusion. These currents may be sufficient to induce reexcitation.

Animals↗
PubMed1983

The effects of insulin and potassium on infarcting canine tissue: an in vitro study.

The electrophysiologic effects of insulin (40 mU/ml) and elevated potassium (4 to 6 mM) on glucose-superfused normal and infarcting tissue from 24 hour coronary artery ligated canine myocardium were studied. With standard intracellular microelectrode techniques, it was observed that insulin infusion for 30 minutes produced an increase in resting membrane potential and a prolongation of action potential duration. In the normal myocardium, the hyperpolarization and the repolarization delay were minimal, but in infarcting tissue with depressed electrophysiologic function, resting membrane potential and action potential duration were significantly improved. This was particularly evident in the presence of an increased potassium concentration (6 mM) when insulin hyperpolarized infarcting cells (n = 8) from 73 +/- 6 to 85 +/- 7 mV (p less than 0.01). In the same studies, action potential amplitudes were increased from 75 +/- 7 to 95 +/- 11 mV (p less than 0.01). In addition, action potential durations at 40 and 80% repolarization were extended from 64 +/- 25 and 141 +/- 46 ms to 132 +/- 34 and 198 +/- 27 ms, respectively (p less than 0.01). Thus, these data are in accord with the reduced ST segment elevation observed in patients treated with glucose-insulin-potassium and support the use of this intervention in the management of acute infarction.

Action Potentials↗
PubMed1981

Acetoacetyl-CoA reductase activity of lactating bovine mammary fatty acid synthase.

Fatty acid synthase, purified from lactating bovine mammary gland, utilizes coenzyme A esters of acetoacetic, 3-hydroxybutyric, and crotonic acids as substrates for its partial reactions at micromolar concentrations. The NADPH:acetoacetyl-CoA reductase had a Km of 5 microM acetoacetyl-CoA and a Vmax of about 4 mumol of NADPH oxidized min-1 mg-1. In contrast, the Km for the model compound, acetoacetyl pantetheine was 820 microM and that of S-acetoacetyl-N-acetylcysteamine was over 40 mM. The reduction of acetoacetyl-CoA was observed with the enzyme from rat tissues also but not with those from avian tissues or yeast. With the bovine mammary enzyme, the reaction was found to oxidize 2 mol of NADPH for every mol of acetoacetyl-CoA consumed. Butyrate was the major product of reduction. The reductase activity was susceptible to inhibition by several sulfhydryl reagents; it was lost when the synthase was dissociated into one-half molecular weight subunits or when the incubation mixture was depleted of CoA. It was competitively inhibited by acetyl-CoA, butyryl-CoA, methylmalonyl-CoA, and 2-methylcrotonyl-CoA. These results as well as its use as a primer in fatty acid synthesis by the enzyme suggest that the acetoacetyl group from acetoacetyl-CoA is transferred to the enzyme, presumably to its 4'-phosphopantheine prosthetic group. The acyl group is then expected to remain attached to the enzyme while it is reduced, dehydrated, and reduced again to form a butyryl group which can either undergo chain elongation, if malonyl-CoA is present, or be released from the enzyme by hydrolysis or transfer to free CoA.

Acetoacetates↗
PubMed1981

Concealed junctional bigeminy inducing pseudo 2:1 AV block.

This case report describes the electrocardiographic features of concealed junctional premature beats. When the junctional premature beats occurred in a bigeminal fashion, pseudo 2:1 AV block occurred. The presence of 2:1 AV block was related to the prematurity (H1-H2) of the junctional extrasystoles, in which coupling intervals less than 425 msec were concealed and those greater than 425 msec were manifest. This report is unusual in that persistent long runs of pseudo 2:1 AV conduction were established. In addition, the extrasystolic beats demonstrated exit block and the interectopic sinus beats (n) followed the formula 2n-1.

Aged↗
PubMed1981

Preferential sensitivity of the left canine purkinje system to cardiac glycosides.

Previous studies have shown that the toxic effects of cardiac glycosides are not manifested uniformly throughout the myocardium. The purpose of our study was to determine whether cardiac glycosides exert different effects on the right vs. left peripheral Purkinje systems and to ascertain mechanisms involved. Control in vitro measurements of paired right and left canine Purkinje fibers showed higher spontaneous rates in left (24.2 +/- 1.75 beats/min) than in right (11.6 +/- 1.55 beats/min, P less than 0.01, n = 81) Purkinje fiber bundles. Following overdrive stimulation, left Purkinje fiber bundles also showed earlier escape beats. After ouabain exposure (2 X 10-7 M), left Purkinje fiber bundles showed earlier signs of toxicity in 20 of 28 experiments, as determined by changes in the maximum diastolic potential, the degree of diastolic depolarization, spontaneous escape intervals, and the magnitude of delayed after-depolarizations. The enhanced sensitivity of left Purkinje fiber bundles was independent of the extracellular potassium concentration and glycoside polarity, and was also observed in situ. We conclude that distal Purkinje fibers are functionally dissimilar and that the left Purkinje system shows greater sensitivity to cardiac glycosides than the right Purkinje system. These data also support the observation that digitalis-induced dysrhythmias arise in the left ventricle.

Action Potentials↗