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Biomedical subjects

S B Jones

Publications and source records attributed to S B Jones.

At least 145 records · Page 8Linked to original sources

Atrial ectopic foci in the canine heart: hierarchy of pacemaker automaticity.

The sinoatrial node (SAN) and adjacent tissue of the sulcus terminalis were surgically excised in sequential multiple sections to study the location and intrinsic rate of emerging pacemakers in the acute open-chest dog. Under chloralose anesthesia total of 17 ectopic atrial pacemakers emerged in 12 dogs ranging in location from the anterior interatrial band, midsulcus terminalis, and junction of the inferior vena cava-inferior right atrium. Four AV junctional and one idioventricular pacemakers also emerged in these experiments. Each successively inferior focus had a slower rate than the SAN. The average heart rate of the atrial ectopic pacemakers was 73 +/- 4% of the SAN but that the AV junctional pacemakers was 56 +/- 4% of the SAN (P less than 0.05). The greatest reductions in rate were achieved with total excision of the SAN and entire sulcus terminalis, but in only 50% of the animals did this result in a junctional rhythm. The location and rate of atrial ectopic foci support the notion that the AV junctional region is not the fastest pacemaker in the absence of the classically defined SAN and suggest that atrial ectopic pacemakers are intermediate in the hierarchy of cardiac pacemakers in the dog.

Action Potentials↗

Isolation of a hibernation inducing trigger(s) from the plasma of hibernating woodchucks.

Plasma from hibernating woodchucks was desalted utilizing a hollow fiber device having a M. W. cut-off of 5,000. This preparation was fractionated by isoelectric focusing (IEF) in a pH gradient extending from 3.5 to 10.0 resulting in protein components having isoelectric points (pIs) of 4.5, 5.2, 5.5, 6.3, and 7.0. Fraction I (comprised of proteins having pIs of 4.5 and 5.2) induced hibernation within 2 to 6 days in 8 out of 10 summer-active ground squirrels. Fraction II (pI 5.5) and Fraction III (pI 6.3 and 7.0) failed to induce any summer hibernation in 10 animal test groups at identical sample concentrations. Polyacrylamide gel electrophoresis of Fraction I indicated that albumin was a major constituent of this still heterogeneous preparation. Thus, in order to more clearly define the plasma locus of this hibernation inducing trigger(s) (HIT) molecule, whole plasma and/or Fraction I was fractionated by 3 distinct resolving techniques. These included sub-fractionation of Fraction I by isoelectric focusing utilizing a narrower pH gradient extending from 3.5 to 6.0, isotachophoresis of whole plasma and affinity chromatography of Fraction I and whole plasma. A total of 40 summer-active ground squirrels were injected and assayed for HIT activity with fractionated preparations derived by the three previously cited separation techniques. A total of 18 of these summer-active ground squirrels hibernated. However, a much more impressive figure is that 16 out of 21 animals hibernated when injected with resolved hibernating plasma fractions in which albumin was the predominant plasma protein. A total of 8 control animals were injected with vehicle and none of these hibernated.

Animals↗

Comparison of SA nodal and subsidiary atrial pacemaker function and location in the dog.

A 3-4 cm length of sulcus terminalis tissue including the sinoatrial node (SAN) was excised from 14 dogs. After an initial junctional rhythm with SAN excision a P wave emerged within days to weeks in 12 animals. Maximum heart rates of the SAN (preoperative) in response to exercise (276 +/- 15 beats/min), isoproterenol infusion in conscious animals (272 +/- 11 beats/min), and stellate stimulation during anesthesia (273 +/- 9 beats/min) were significantly greater than subsidiary pacemakers (postoperatively) for exercise (219 +/- 9 beats/min), isoproterenol (226 +/- 8 beats/min), and stellate stimulation (197 +/- 9 beats/min). During a final experiment, electrophysiological mapping of the area of earliest epicardial activation (pacemaker location) was carried out. By use of a suction electrode in reference to plunge electrodes located in the anterior interatrial band (AIB), eustachian ridge of the coronary sinus, and limbus of the fossa ovalis, the pacemaker was located at the inferior vena cava-inferior right atrial junction in 80% of the animals mapped. During isoproterenol infusion the foci shifted to regions of the AIB in 70% of the animals mapped. The concept of pacemaker hierarchy is discussed.

Animals↗

Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia.

Mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia were investigated through measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output. Hamsters (Mesocricetus auratus) were made hypothermic (rectal temperature (Tre), 7 degrees C) by exposure to helox and cold, or permitted to hibernate with several weeks of cold exposure (Ta approximately 5 degrees C). Mean arterial pressure, 120 Torr in normothermic control animals, demonstrated a 55% and 60% decrease during hibernation and hypothermia, respectively. As the animals rewarmed from hypothermia or aroused from hibernation, blood pressure increased rapidly at 8-12 degrees C, more gradually at 12-17 degrees C, and plateaued thereafter. Blood pressure rapidly returned to near control levels whereas heart rate remained at less than one-half control value at the highest temperature examined. Red blood cell volume, 26.2 +/- 0.6 ml/kg body wt in the control animals appeared unaffected by hypothermia. Plasma volume, by contrast, decreased from control values of 33.0 +/- 0.8 to 21.3 +/- 0.6 ml/kg body wt in hypothermia, a decrease of approximately 35%. Distribution of cardiac output to various organs in hibernation and hypothermia followed a similar pattern. Relative flow to the heart, lung, diaphragm, and brown fat increased while the fraction distributed to the visceral organs appeared to decrease. The normothermic control kidney received approximately 16% of the cardiac output while the hibernating and hypothermic kidneys received approximately 10% and 6%, respectively. The data are discussed in terms of the determinants of glomarular filtration rate and explain, in part, the elimination or marked reduction in renal function observed in depressed metabolic states.

Animals↗

Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 degree C-acclimated hamsters.

Norepinephrine (NE) turnover rates were measured in hamster (Mesocricetus auratus) heart and spleen tissues after 7-10 wk exposure to 7, 22, and 34 degrees C. The competitive inhibitor of NE synthesis, alpha-methyl-p-tyrosine methyl ester, was injected (200 mg/kg, ip) into acclimated animals. At sequential periods after drug treatment, hamsters were sacrificied by cervical transection, and tissues were removed and frozen. Rate constants, turnover time, and turnover rates were determined from regression analysis of NE tissue decay. Heart NE turnover was highest in cold-acclimated and lowest in heat-exposed animals (.111 and .047 mug/g per h, respectively), control values being intermediate (.081 mug/g per h). NE turnover is inversely related to tissue levels in the myocardium of temperature-acclimated hamsters. Spleen NE turnover was lowest with heat exposure, but spleen tissue levels of NE with heat or cold exposure were not different from control (22 degrees C) measurements. Heat-acclimated hamsters are slightly hyperthermic (Tre, 37.24 +/- .18 C; P, .032) compared to 22 degrees C-maintained controls (Tre, 36.85 +/- .07), but body temperature were unchanged with 7 degrees C exposure. The implication of altered NE synthesis is that sympathetic nerve activity is decreased with heat acclimation and increased with cold acclimation.

Acclimatization↗

Mechanisms of temperature regulation in heat-acclimated hamsters.

Mechanisms of temperature regulation were assessed by measurements of oxygen consumption (VO2), body temperature (Rre = rectal, Tsk = skin), evaporative water loss (EWL), regional distribution of blood flow, and blood volume. Hamsters (Mesocricetus auratus) were acclimated to ambient temperatures of 34 or 22 degrees C. VO2 of 34 degrees C-exposed animals was reduced to 50% of that of controls at 22 degrees C, whereas EWL with heat exposure was almost double that of controls. Heat-acclimated animals had a slightly elevated Tre in comparison to 22 degrees C-acclimated animals, whereas there was a marked elevation in Tsk with heat exposure, in contrast to control animals at 22 degrees C. Blood flow distribution measurements indicated that with 34 degrees C exposure there was a decreased flow in liver, kidney, and intestine, whereas there was an increase to the carcass. Red cell and plasma volumes in heat-acclimated hamsters were decreased belwo the values of the 22 degrees C controls. Heat acclimation of the fhamster appears to involve reduced VO2 and increased WEL. Convective and radiative heat loss appear to be maintained by increased Tsk with heat exposure. Nonevaporative heat dissipation mechanisms are of primary importance in thermoregulation of the heat-acclimated hamster, and it is suggested that this is mediated by increased peripheral blood flow with reduced flow to the viscera.

Acclimatization↗

A fragment of vasoactive intestinal peptide, VIP(10-28), is an antagonist of VIP in the colon carcinoma cell line, HT29.

The 19 amino acid carboxyl terminus fragment of vasoactive intestinal peptide (VIP), VIP(10-28), inhibits [125I]VIP binding in intact HT29 colonic adenocarcinoma cells and in membranes from these cells. However, VIP(10-28) alone has no effect on adenylate cyclase activity (membranes) or cyclic AMP synthesis (intact cells) in HT29 cells although VIP receptor agonists are markedly stimulatory. The indicated antagonist character of VIP(10-28) was confirmed by rightward parallel shifts of VIP dose response curves in the presence of VIP(10-28) in adenylate cyclase and cyclic AMP synthesis experiments. The equilibrium dissociation constant values for VIP(10-28) from these experiments agree with values from inhibition binding studies. The lack of effect of VIP(10-28) on forskolin dose response curves in HT29 adenylate cyclase assays indicates the specificity of the VIP(10-28) antagonism, thus suggesting that VIP(10-28) may be a useful tool in studying VIP receptor regulation and other aspects of the mechanisms of VIP action. The potential regulatory role of a proteolytically generated fragment of VIP acting antagonistically at VIP receptors is discussed.

Adenocarcinoma↗

Comparison of adrenergic receptor binding in blood cells from alcoholics and controls.

Ethanol inhibited in vitro alpha-2 adrenergic receptor binding in platelets with an IC50 of 380 mM and beta adrenergic receptor binding in lymphocytes and polymorphonuclear leucocytes with IC50 values of about 1 M. The characteristics of alpha-2 receptor binding were similar in platelets from chronic alcoholics and from non-alcoholics. The densities of beta adrenergic receptors were similar in blood cells from alcoholics and controls, although there were some changes in receptor affinities. Thus, chronic alcohol consumption does not appear to have a substantial effect on adrenergic receptor binding in blood cells.

Adult↗