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Biomedical subjects

T A Brandon

Publications and source records attributed to T A Brandon.

At least 19 recordsLinked to original sources

The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes.

UNLABELLED: A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues. IMPLICATIONS: We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.

Animals↗

Care of collegiate athletes.

Caring for collegiate athletes requires the coordinated efforts of a sports medicine team that includes primary care physicians, specialists, trainers, and other allied health personnel. In addition to screening requirements, team physicians must be knowledgeable of a wide array of conditions, including cardiovascular, infectious, and eating disorders, as well as traumatic injuries. In today's managed care environment, obtaining appropriate care for an injured college athlete may be challenging.

Adolescent↗

Neuromuscular stimulation selectivity of multiple-contact nerve cuff electrode arrays.

The feasibility of an electrical stimulation method selectively for activating skeletal muscles innervated by a common peripheral nerve trunk has been investigated. The method utilises 'snugly' fitting nerve cuffs that incorporate an array of 12 electrodes. These electrodes have been tested as four longitudinally aligned tripoles (located 90 degrees apart on the cuff inner surface). In acute experiments on rabbit sciatic nerves, we have found that tripolar stimulation with this implant system is in general highly selective. 'Field steering,' wherein a subthreshold transverse current is used in combination with a longitudinal tripolar current, tends to increase the selectivity of stimulation. On a rabbit sciatic nerve, a combination of adjacent longitudinal tripoles of the 12 electrode array generally yields a stimulation performance similar to that which would be expected if a 24 electrode array is used. This system may find a use in functional neuromuscular stimulation applications which require highly selective control over multiple muscles.

Animals↗

Hemodynamic responses to 6 degree head-down rest in dogs: effect of aerobic conditioning.

The -6 degree head-down position is used in humans to produce fluid shifts that resemble those occurring in microgravity. Alternative animal models of microgravity may be helpful for extensive exploration of this unique condition. The dog may be a viable candidate. Sixteen dogs were assigned to one of three conditions: anesthetized open chest, anesthetized closed chest, and awake. Dogs in groups 1 (N = 6) and 2 (N = 6) were divided into an exercise or a sedentary treatment, and dogs in group 3 (N = 4) served as their own controls. Following instrumentation the dogs were put in the head-down position for 1 h. Measurements included right atrial pressure, heart rate, and mean arterial pressure for all groups, left ventricular pressure and LV dp/dt for group 1, and cardiac output and iliac flow for group 2. Right atrial pressure increased for all groups. Heart rate demonstrated non-significant changes over time or group. Significant differences were noted for mean arterial pressure, left ventricular pressure and LV dp/dt for exercise condition in response to HDR. It appears that -6 degrees of head-down rest produces similar cardiovascular responses in dogs as those observed in humans and that exercise has a minor effect on those responses.

Animals↗

Thermoelectric enzyme sensor for measuring blood glucose.

A new calorimetric sensor has been developed which employs a thin-film thermopile in association with an immobilized enzyme. The thermopile detects the minute temperature rise that occurs when a specific chemical substrate is catalyzed by the enzyme. A prototype sensor is described which generates an equivalent proportional voltage response to glucose concentrations present in either buffer solution or blood. These sensors have remained useful for up to 18 days when operated intermittently for measuring glucose in buffer solutions, or for up to 4 days when operated continuously. When implanted inside cardiovascular shunts on anesthetized dogs, the sensors responded appropriately to changes in the blood glucose concentration.

Animals↗

Hemodynamic basis of renal arteriosclerosis in young greyhounds.

Renal arteriosclerosis occurs with unusually high frequency in young race-trained greyhounds. Light and electron microscopic studies were used to examine the arterial walls of renal vessels in six greyhounds. Lesions characteristic of mechanical forces, namely pressure and shear stresses, were found consistently on the endothelial surfaces of damaged vessels. Such damage was found in both the main renal vessel and its branches. Although the patterns of endothelial damage showed quantitative differences among individuals, the qualitative features were remarkably similar in the group. Quantitatively, fibrous plaques were greatest in narrow and curved portions of renal vessels. The plaques were found on the outer luminal surface of the bend and the bifurcation segments, but were absent on the flow dividers. Hemodynamic forces appear to play an important role in the pathogenesis of renal fibrous plaques. Renal arteriosclerosis in greyhounds provides an excellent model for the study of pressure pulse velocity and shear stress damage under various physiological conditions.

Animals↗

Effect of 60-minute head-down tilt on arterial baroreflex function in anesthetized dogs.

Arterial baroreflex control of heart rate was assessed in 6 anesthetized dogs with a bolus infusion of phenylephrine before and during cardiopulmonary receptor stimulation by 6 degrees head-down tilt (HDT) for 60 min. No difference in arterial baroreflex function was observed between the control and HDT conditions. It appears that the attenuation of baroreflex function that occurs during acute stimulation of cardiopulmonary baroreceptors disappears when cardiopulmonary baroreceptors reset after prolonged stimulation.

Anesthesia↗

Influence of alpha-adrenergic blockade on platelet-mediated thrombosis in stenosed canine coronary arteries.

The functional significance of platelet alpha-adrenergic receptors in vivo is uncertain. The aim of this study was to elucidate their role in experimental coronary thrombosis. In 46 open-chest dogs with a critical coronary stenosis produced by plicating the coronary artery wall with a suture, blood flow showed cyclical reductions followed by an abrupt return to control levels. The flow reduction were previously shown to be caused by platelet aggregation. In the present study they were unaffected by heparin (1,000 U . kg-1 . h-1) at the start of the experiment but consistently abolished by aspirin (30 mg . kg-1) at the end of the protocol, further supporting platelet aggregation as the primary mechanism. After 1 h of observation, dogs were assigned to one of the following groups: control (no intervention, n = 9), phentolamine (a nonselective alpha-blocker) "low dose" (0.07 mg . kg-1 bolus followed by 0.1 mg . kg-1 . min-1, n = 4), phentolamine "high-dose" (3 mg . kg-1 bolus followed by 0.07 mg . kg-1 . min-1, n = 6), prazosin (an alpha 1-blocker, 2 mg . kg-1, n = 8), yohimbine (an alpha 2-blocker, 3 mg . kg-1, n = 11) or prazosin + yohimbine (same doses, n = 8). In controls, cyclical reductions in flow continued unchanged for another hour. Phentolamine effected a partial dose-related inhibition of flow reductions; however, prazosin and yohimbine, given separately or in combination, failed to produce any significant effect despite an alpha-blocking action equivalent to or greater than that of phentolamine (alpha-agonist dose-response studies).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Acute right ventricular failure is caused by inadequate right ventricular hypothermia.

The hypothesis of this study was that inadequate right ventricular hypothermia contributes to the right ventricular dysfunction occasionally observed after cardiac operations. Dogs were placed on cardiopulmonary bypass, and 60 minute periods of hypothermic myocardial ischemia were imposed. Left ventricular temperature was always maintained at 15 degrees C and right ventricular temperatures were maintained at 15 degrees C (Group I, n = 8), 25 degrees C (Group II, n = 8), and 35 degrees C (Group III, n = 8). These temperatures were produced by infusion of hypothermic crystalloid cardioplegic solution and appropriate topical cooling and heating of the left and right ventricles, respectively. Multiple indices of ventricular function were obtained 15, 30, 45, and 60 minutes after bypass and compared to prebypass control values. In all Group I animals (left ventricular temperature = 15 degrees C, right ventricular temperature = 15 degrees C), postischemic indices of right ventricular function were not different from control values (p = NS). In Group II (left ventricular temperature = 15 degrees C, right ventricular temperature = 25 degrees C), two animals died 30 and 45 minutes after bypass, respectively, of right ventricular failure. In the other six animals in Group II, all indices of right ventricular function were significantly reduced (p less than 0.05) except for right ventricular systolic pressure. In Group III (left ventricular temperature = 15 degrees C, right ventricular temperature = 35 degrees C), two animals could not be weaned from cardiopulmonary bypass because of right ventricular akinesia. Six animals were weaned from bypass, but two died 15 minutes, one died 30 minutes, and one 45 minutes after bypass. Two animals lived 60 minutes, but all indices of right ventricular function were decreased. Failure to maintain right ventricular temperatures below 25 degrees C during 1 hour of cardiac ischemia in the dog can result in fatal right ventricular failure.

Animals↗

Hemodynamic effects of oral smokeless tobacco in dogs and young adults.

Oral smokeless tobacco (snuff) is increasingly used among the young male population. To determine cardiovascular effects of an oral smokeless tobacco product, 10 anesthetized dogs were instrumented to measure blood pressure, heart rate, left ventricular end diastolic pressure, and circumflex coronary, renal, and femoral flows. After a 5-min baseline, a 2.5-g, approximately 1.2% nicotine bolus dose was placed in the buccal space, and measurements were made for 20 min. Significant increases were seen in heart rate, blood pressure, left ventricular pressure, left ventricular end diastolic pressure, and left ventricular dP/dt. Significant decreases in flow were noted in the coronary circumflex, renal, and femoral arteries. The flow reduction was thought to have been mediated by an alpha-adrenergic mechanism. Additionally, 20 human males, mean age 20 years, without nicotine exposure for 72 hr, were given a 2.5-g dose of the same oral smokeless product. From baseline to 20 min, heart rate increased from 69 to 88 beats/min (P less than 0.05), blood pressure from 118/72 to 126/78 mm Hg (P less than 0.05). Thus, oral smokeless tobacco use can produce significant hemodynamic changes in both dogs and normal humans.

Administration, Oral↗

Platelet-mediated thrombosis in stenosed canine coronary arteries: inhibition by nicergoline, a platelet-active alpha-adrenergic antagonist.

The effects of nicergoline, a new agent that blocks alpha-adrenergic receptors and inhibits platelet phospholipase, were evaluated in a canine model of platelet-mediated coronary thrombosis. In 48 open chest dogs, the circumflex coronary artery was stenosed by plicating the artery wall with a suture. Thirty-four of the 48 dogs exhibited cyclic reductions in flow in the stenotic vessel, followed by a sudden return to control levels. The reductions in flow were unabated in all but two dogs after heparin administration (1,000 U/kg per h), unaffected by large doses of nitroglycerin and nifedipine and associated with platelet aggregates in the stenotic segment (demonstrated by histologic and electron microscopic examination). These observations support the conclusion that the flow reductions were caused by platelet aggregation rather than by fibrin deposition or vasospasm. Twenty dogs were monitored for 1 hour after heparin administration and then assigned to a control (n = 7) or nicergoline-treated (n = 13; 1 mg/kg intravenously) group. In control dogs, cyclic reductions in flow continued unchanged for another hour, whereas in the treated group they were markedly decreased in 1 dog and completely abolished in the other 12 dogs. Aspirin (30 mg/kg intravenously) suppressed flow reductions in all control dogs, confirming the primary role of platelet aggregation in the phenomenon. This study provides a modified model of platelet-mediated thrombosis in stenosed coronary arteries. Furthermore, the results indicate that nicergoline can effectively interfere with platelet function in vivo. The potent antithrombotic activity exhibited by nicergoline might enhance the therapeutic usefulness of this vasodilator.

Animals↗

Effect of intermittent infusions of glucose-containing crystalloid cardioplegic solution on myocardial tissue lactic acid and recovery of contractility.

The objective of this study was to determine the effects of single or intermittent infusions of cardioplegic solution with glucose (5 gm/L) or without glucose on myocardial tissue lactic acid and recovery of myocardial contractility following 80 minutes of total ischemia at 28 degrees C in the isolated, blood-perfused, beating rabbit heart. Ischemia without cardioplegia increased tissue lactic acid (6.79 mg/gm tissue) above the control value (0.9 mg/gm tissue), p less than 0.0025). Lactic acid following single infusions with (4.19 mg/gm tissue) or without glucose (3.67 mg/gm tissue) was significantly greater (p less than 0.0025) than tissue lactic acid following intermittent infusions with (1.06 mg/gm tissue) or without glucose (1.05 mg/gm tissue). Cardioplegic arrest in all cases significantly decreased tissue lactate accumulation when compared to arrest without cardioplegia (p less than 0.01). The decrease in myocardial contractility demonstrated when no cardioplegic protection was employed (86% recovery) was completely eliminated (100% recovery) with a single-bolus infusion of cardioplegic solution containing glucose (p less 0.025). Intermittent infusions of cardioplegic solution containing glucose (92% recovery) and single infusions without glucose (93% recovery) also improved recovery of contractility following ischemia, but the results were not statistically significant.

Animals↗

Beneficial effects of the alpha-adrenergic antagonist nicergoline during acute myocardial ischemia and reperfusion in the dog.

Recent experimental and clinical data have stimulated interest in the use of alpha-adrenergic antagonists in acute myocardial infarction. We evaluated nicergoline, a new relatively selective alpha 1-antagonist which uniquely lowers heart rate. Open-chest dogs, randomized to control (n = 25) or intravenously treated group (n = 20; 0.5 mg/kg bolus, then 0.10 to 0.15 mg/kg/min), underwent coronary artery occlusion (CAO) followed after 25 minutes by coronary artery reperfusion (CAR). Nicergoline decreased heart rate by 47 +/- 5 bpm and mean aortic pressure by 39 +/- 4 mm Hg. Following CAO, nicergoline reduced total coronary collateral resistance (radiolabeled microspheres; 698 +/- 75 vs 2167 +/- 530 mm Hg/ml/min/gm, p less than 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 +/- 0.04 vs 0.06 +/- 0.02, p less than 0.05), and reduced the rise in intramyocardial CO2 tension in the ischemic zone (mass spectrometry, p less than 0.001). Furthermore, the drug decreased the rate of ventricular tachycardia (VT; 191 +/- 13 vs 243 +/- 3 bpm, p less than 0.001) and the incidence of ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p less than 0.05). Following CAR, nicergoline did not significantly reduce the incidence of VF but did lower rate (154 +/- 8 vs 212 +/- 10 bpm, p less than 0.001) and incidence (p less than 0.05) of VT. Thus nicergoline reduced severity of ischemia and afforded protection against arrhythmias induced by myocardial ischemia and reperfusion. The observed reduction in heart rate may have contributed importantly to these beneficial effects. Clinical investigation of this potentially useful vasodilator seems warranted.

Animals↗

Combined vasodilator and inotropic therapy of heart failure: experimental and clinical concepts.

Vasodilators facilitate ventricular emptying by affording earlier onset of left ventricular (LV) ejection and increased stroke volume with achievement of a reduced end-systolic pressure and volume. Agents with positive inotropic properties increase stroke volume by shifting the end-systolic pressure-volume curve to the left through augmented force and velocity of contraction. With impedence reduction, improvement in pump performance occurs concomitant with reduced cardiac energy requirements (MVO2); positive inotropic agents most circumstances increase MVO2. The combination of a vasodilator and positive inotropic agent, as opposed to either alone, in the conscious animal shifts to the left and increases the slope of the LV end-systolic pressure-volume relation. Cardiac efficiency, defined by the slope of the relation between stroke volume and systolic tension, is increased by the combination of the drugs. In clinical heart failure, nitroprusside alone lowers LV preload with a modest increase in cardiac output (CO); dopamine markedly increases CO with little fall in LV preload. In combination the two agents achieve the individual beneficial effects of each drug, and cardiac efficiency indices are improved. Thus combined vasodilator and inotropic therapy appears to have a sound physiologic rationale and clinically documented beneficial effect superior to either modality alone.

Animals↗