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Biomedical subjects

I J Fox

Publications and source records attributed to I J Fox.

At least 73 records · Page 4Linked to original sources
PubMed1986

Myoglobin facilitated oxygen diffusion maintains mechanical function of mammalian cardiac muscle.

Myoglobin, an intracellular iron containing protein that binds oxygen reversibly, has been shown in model systems to facilitate the diffusion of oxygen and thereby maintain the mechanical function of exercising canine skeletal muscle and of hypoxic benthic fish hearts. Since no such role has yet been established for mammalian cardiac muscle small diameter (less than or equal to 0.70 mm) isolated kitten papillary muscles were stimulated at 24 X min-1 under isometric conditions in a physiological bath maintained at 30 degrees C with an oxygen tension of approximately equal to 450 mm Hg (59.8 kPa) to obtain a level of oxygenation just adequate to meet the metabolic needs of the muscles, as confirmed experimentally. Myoglobin was inactivated by adding 2 X 10(-3) mol X litre-1 sodium nitrite to the bath to abolish the facilitated diffusion of oxygen in the presence or absence of glycolytic blockade by 10(-4) mol X litre-1 sodium iodoacetate. This resulted in a 22(8)% (with blockade) or 10(3)% (without blockade) decrease (p less than 0.05) in the maximal rate of relaxation (-dT/dtmax) of the papillary muscles. Since the depression in mechanical function was reversible by increasing the bath oxygen tension to approximately equal to 600 mm Hg (79.8 kPa) it is concluded that the myoglobin facilitated diffusion of oxygen plays a role in maintaining the mechanical function of mammalian cardiac muscle under normal conditions. Furthermore, the maximal rate of relaxation of cardiac muscle is a sensitive indicator of the presence of hypoxia.

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PubMed1984

Use of intracoronary KCl in the beating and asystolic heart to determine the mechanism of initiation of the left ventricular mechanoreceptor reflex.

To provide further evidence that the veratrum alkaloids' mechanical, positive inotropic effect and not their chemical depolarising action predominates in initiating the left ventricular mechanoreceptor (including the Bezold) reflex the effect of intracoronary KCl, a chemical depolarising agent like the veratrum alkaloids, but with a negative inotropic effect, was studied in beating and verapamil-asystolic hearts. Five dogs were placed on a total cardiac bypass, pneumonectomised and their coronary and systemic circulations isolated and perfused separately, at a constant rate, so that changes in systemic pressure reflected changes in systemic resistance. Injection of 5 mmol X litre-1 KCl into the isolated coronary circulation caused cardiac asystole and a resultant reflex rise in systemic pressure (resistance) of 26 +/- 9% (p less than 0.05) above the control of 10.5 +/- 0.7 kPa (79 +/- 5 mmHg). This pressure rise, which indicates predominance of KCl's mechanical, negative inotropic over its chemical depolarising effect, was abolished by vagotomy, indicating its reflex nature. Contrariwise, in five other pneumonectomised dogs, similarly perfused on total cardiac bypass but with cardiac asystole from intracoronary verapamil, a subsequent, similar intracoronary dose of KCl now produced a fall in systemic pressure (resistance) of 8 +/- 2% (p less than 0.005) below the control of 12.8 +/- 0.5 kPa (96 +/- 4 mmHg). This pressure fall, presumably due to chemical depolarisation of the left ventricular mechanoreceptors, was also abolished by vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1984

A Ca2+-dependent mechanism for the positive inotropic response to an increase in afterload in cat papillary muscle.

In cat papillary muscles, under control conditions (1.25 mmol/L Ca2+ bathing solution, 25 degrees C), increasing the afterload by switching from isotonic to isometric contraction elicited a positive inotropic response. Halving the bath [Ca2+] resulted in a percentagewise similar or greater positive inotropic response to increased afterload, while doubling the bath [Ca2+] reduced and caffeine abolished or reversed this response, indicating [Ca2+]i predictably influences it. Since it was markedly reduced by verapamil and unaffected by propranolol, the positive inotropic response to increased afterload was concluded to be largely due to increased Ca2+ influx, unrelated to catecholamine release, caused by increased mean muscle length over time owing to the changing from isotonic to isometric contraction. While at 25 degrees C, increasing the afterload caused a positive inotropic response at 12 to 48 stimulations/min, at 37 degrees C and at similar frequencies, a negative inotropic response occurred. This reversed to a positive inotropic response at 86 stimulations/min, well below the normal cat heart rate, suggesting an increased afterload would cause a positive inotropic response via this mechanism in vivo, as observed for years in intact mammalian hearts. Similarities between positive inotropic responses to increased afterload in isolated cardiac muscle, isolated hearts, and intact animals indicate all may be examples of the same phenomenon (Anrep effect).

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PubMed1981

Changes in regional myocardial blood flow and variable development of hypertrophy after aortic banding in puppies.

Supravalvar aortic banding was performed in 6 to 12 week puppies. Sixteen animals were studied 7.3 (3.5 to 10) months later, closed-chested under morphine-chloralose, catheters being positioned in the great vessels and heart, including the left atrium for microsphere injection. Compared with 11 controls, eight dogs developed biventricular hypertrophy, four isolated left ventricular hypertrophy and four had no hypertrophy. The left ventricular systolic pressure was similar (P greater than 0.05) in these 3 banded groups (mean, 30 +/- 2 [SEM] kPa, [222 +/- 16 mmHg], n = 16). The left ventricle was divided into three coronal slices with approximately 59 samples being taken from subendocardial, midwall, and subepicardial layers and additional samples from the atria and right ventricle for regional myocardial flow measurement. As left ventricular hypertrophy increased, the subendocardial/subepicardial flow ratio decreased (r = -0.8). Heterogeneity of left ventricular regional myocardial flow, including a base-to-apex decrease in flow, present in controls, was markedly reduced in the banded dogs. Analysis of variance was found to be the most sensitive test for detecting left ventricular perfusion abnormalities since in banded dogs without hypertrophy, total and regional subendocardial/subepicardial flow ratios were not significantly different from control values, whereas the subendocardial circumferential flow pattern determined by analysis of variance was significantly different from control in these dogs (P less than 0.05).

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PubMed1981

Impairment of antigen-presenting cell function by ultraviolet radiation. II. Effect of in vitro ultraviolet irradiation on antigen-presenting cells.

The s.c. injection of 10 mM 2,4,6-trinitrobenzene sulfonic acid (TNBS) derivatized splenic adherent cells (SACs) into syngeneic mice primes for contact sensitivity or delayed-type hypersensitivity (DTH) when these animals are challenged with picryl chloride on the ear or trinitrophenol (TNP)-coupled cells in the footpad, respectively. If recipient mice are exposed to ultraviolet light (UV) irradiation and are immunized with normal TNP-treated SACs, they develop marked DTH reaction upon challenge but develop limited DTH reactions if immunized with hapten-derivatized SACs that had been obtained from UV-treated recipients. Moreover, if the SACs are obtained from normal mice but are treated in vitro with UV light (1.2 to 1.4 mJ/cm2/sec over the wavelength range 280 to 340 nm at a tube to target distance of 20 cm) these cells can neither prime nor elicit hapten-specific T cell immunity in UV-treated recipients. If UV-treated TNP SACs are used to prime UV-irradiated recipients, TNP-specific suppressor T cells are generated rather than T effector cells.

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PubMed1979

The Bezold reflex: a special case of the left ventricular mechanoreceptor reflex.

Our previous finding that increasing myocardial contractility caused reflex systemic hypotension, the left ventricular (LV) mechanoreceptor reflex, suggested that the classical Bezold reflex (systemic hypotension and bradycardia after intracoronary administration of veratrum alkaloids) may be initiated by these same LV mechanoreceptors. In our working LV preparation with the coronary and systemic circulations isolated and perfused separately, intracoronary injection of veratrum alkaloids, like that of catecholamines or ouabain, had a positive inotropic effect which produced the hypotensive response typical of the LV mechanoreceptor reflex. To test directly if veratridine's positive inotropic effect initiates the Bezold reflex, verapamil, which blocks the slow Ca(2+) channels of myocardial cells but leaves intracardiac nerves unaffected, was injected by the intracoronary route to prevent the increased contractility from intracoronary injection of veratridine which also abolished the reflex hypotension, demonstrating conclusively that increasing myocardial contractility and thereby activating LV mechanoreceptors but not chemoreceptors initiates the Bezold reflex. Contrariwise, decreasing contractility or cardiac asystole by administration of tetrodotoxin, verapamil, or EDTA resulted in an increase in the systemic resistance, indicating that changes in the magnitude of the stimulus initiating the LV mechanoreceptor reflex (i.e., changes in myocardial contractility) lead to directionally opposite changes in peripheral resistance, as in the sino-aortic mechanoreflexes. Thus, it is concluded that the Bezold reflex is a special case of the LV mechanoreceptor reflex. The latter, by means of feedback mechanisms, functions normally by continuously matching the peripheral resistance to the LV contractile state so as to maintain the arterial pressure constant, thereby playing an important role in blood pressure regulation.

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PubMed1977

Left ventricular mechanoreceptors: a haemodynamic study.

1. To study the function of the left ventricular mechanoreceptors, a working left ventricle preparation was devised in dogs which permitted control of pressure and flow of the isolated perfused coronary circulation and of the flow of the isolated, separately perfused systemic circulation. The systemic circulation was perfused at a constant rate so that changes in systemic pressure reflected changes in systemic resistance.2. Increases in myocardial contractility produced by injection of catecholamines into the isolated, perfused coronary circulation produced a fall in the pressure (resistance) of the isolated, separately perfused (at a constant rate) systemic circulation.3. Completeness of isolation of the coronary and systemic circulations was shown by the marked difference in appearance times between the reflex hypotensive responses from catecholamine injections into the isolated coronary circulation and the direct hypertensive response from a similar injection when the circulations were connected as well as by the marked difference between the pressure pulses recorded simultaneously on both sides of the aortic balloon separating the two circulations.4. Myocardial beta receptor blockade produced by injection of propranolol into the isolated coronary circulation abolished or attenuated the changes in left ventricular myocardial contractility as well as the subsequent hypotensive responses following the similar injection of catecholamines.5. Electrical stimulation of a sympathetic nerve innervating the heart resulted in increases in left ventricular myocardial contractility and subsequent systemic hypotensive responses indistinguishable from those following injection of catecholamines.6. That distortion of the mechano- or stretch receptors in the left ventricular myocardium was the cause of the hypotensive responses was demonstrated by increasing left ventricular myocardial contractility by mechanically obstructing the left ventricular outflow which produced hypotensive responses similar to those following the injection of catecholamines or nerve stimulation.7. Bilateral high cervical vagotomy abolished the hypotensive responses following injection of catecholamines into the isolated coronary circulation or following left ventricular outflow obstruction in all but one instance, indicating the importance of vagal fibres to the afferent arm of the reflex.8. It is suggested that the left ventricular mechanoreceptors function normally to reduce the peripheral resistance in order to prepare the systemic circulation to receive the left ventricular output and, especially during exercise, to prepare the systemic circulation to receive the augmented cardiac output with a minimum alteration in the systemic blood pressure and to distribute this augmented output preferentially to the skeletal muscles.

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PubMed1977

Simultaneous regional myocardial blood flows by tritiated water and microspheres.

Regional myocardial blood flow (RMF) was measured simultaneously by use of labeled 8-mum microspheres and the constant-rate infusion of 3H2O in 22 open-chest dogs (Na pentobarbital anesthesia) under markedly different hemodynamic conditions. Following cardiac excision, three adjacent 80-mg tissue samples were taken from the subendocardial, mid-wall, and subepicardial layers of quadrantal left ventricular (LV) segments of the basal and midventricular cardiac slices, and from one segment of the apical slice, totaling 81 samples per LV. RMF was calculated by the microsphere reference-flow technique and by two 3H2O tissue-uptake models. Good agreement between techniques (r=0.9-0.96) was found in comparing flows to the myocardial layers. Using Kety's "single-mixer" model of 3H2O tissue uptake, fairly good agreement was found between techniques in the 80-mg tissue samples; the cofficient of variation from regression was 18.5% which improved markedly to 12.3% when the flow values for each technique were averaged in the three adjacent samples. Analysis of variance showed that flow to the various LV subdivisions (layer, segment, slice) of control animals was heterogeneous.

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PubMed1976

Effect of nitroglycerin with and without systemic hypotension on canine regional myocardial tritiated water deposition.

A marked alteration in the transmural distribution of left ventricular blood flow, with a relative increase in subendocardial and mid-wall flows, but with no change in the distribution of the relative blood flow to the two ventricles occurred when nitroglycerin was administered and the systemic arterial blood pressure in the upper body maintained near control levels in anaesthetized, open-chested dogs. The relative increase in subendocardial and mid-wall flows may have resulted from a direct action of nitroglycerin on the coronary vasculature. On the other hand, the intravenous administration of nitroglycerin, when followed by the hypotension which it produces, did not alter the transmural distribution of blood flow in the left ventricle of the dog. Blood flow to the right ventricle relative to flow to the left ventricle increased in this situation.

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