Biomedical subjects

T H Adair

Publications and source records attributed to T H Adair.

14 recordsLinked to original sources

PubMed1991

Morphometric measurements of chorioallantoic membrane vascularity: effects of hypoxia and hyperoxia.

We studied the effects of hypoxia and hyperoxia on the angiogenesis process in the chick embryo chorioallantoic membrane (CAM) using four different morphometric measurements of vascularity. Chick eggs were incubated in various oxygen atmospheres (12, 16, 21, 45, or 70% oxygen) beginning on the 7th day of development, and vascularity was measured on the 14th day. Measurements of vascularity included vessel endpoint density (VED), length density, fractional image area, and a vascular density index. All measurements were made on blood vessels in randomly selected areas of CAM using a computerized image analysis system. An opaque colloidal carbon-albumin perfusate was used as a vascular marker. All four measurements showed that vascularity of CAM was inversely related to the oxygen tension to which the embryos were subjected. The VED, an estimate of total number of pre- and postcapillary vessels, exhibited the greatest degree of change, but overall changes in vascularity were modest. Prolonged exposure to a 12% oxygen atmosphere increased VED by approximately 16%, whereas 70% oxygen decreased VED by approximately 19% compared with room air control groups. We also studied the normal growth of CAM vasculature from days 8 to 18 of development. In these studies, the values of VED increased progressively throughout the entire period of development, whereas the other measurements of vascularity reached maximum values by the 14th day. We conclude that hypoxia stimulates angiogenesis in the CAM in a dose-related manner, hyperoxia inhibits CAM angiogenesis in a dose-related manner, and VED provides a sensitive estimate of vascularity in chick CAM throughout its development.

Allantois↗

PubMed1991

Effect of skin concavity on subcutaneous tissue fluid pressure.

We tested the hypothesis that mechanical factors associated, with a skin concavity can cause the local tissue fluid pressure to become more negative. Perforated Teflon collars, 26 mm in diameter and having various heights (5, 10, 13, and 16 mm), were implanted into the fascial plane of the inguinal and abdominal areas of six sheep. After several weeks, visible signs of edema were no longer apparent, and the skin formed a concavity within the center of each collar. The depth of each concavity was measured using an electronic micrometer, and the tissue fluid pressure beneath the concavity was measured using a needle method. Over the entire range of collar heights, the average depth of the concavities ranged from 1.1 to 4.7 mm in the abdominal tissues and from 1.8 to 5.5 mm in the inguinal tissues. The respective values of tissue fluid pressure averaged -4.6 to -13.0 and -5.7 to -12.8 mmHg. The results therefore indicate that implanting deeper collars leads to the formation of deeper concavities in the skin and also to greater negativity in the free tissue fluid pressure beneath the skin. Linear regression extrapolation to a collar height of 0 mm corresponded to a tissue fluid pressure of -1.0 mmHg in the abdominal tissue and -2.4 mmHg in the inguinal tissues. A model based on excessive pumping of the lymphatic system in the vicinity of a concavity is provided to explain this newly described phenomenon. We conclude that mechanical factors associated with the formation of a skin concavity cause or permit the tissue fluid pressure to reach levels of negativity far greater than those that exist in the absence of a concavity.

Abdomen↗

PubMed1990

Growth regulation of the vascular system: evidence for a metabolic hypothesis.

Prolonged imbalances between the perfusion capabilities of the blood vessels and the metabolic requirements of the tissue cells often lead to modification of the vasculature to satisfy the tissue needs. This homeostatic response appears to be bidirectional, since the vascularity of a tissue can increase or decrease in parallel with primary changes in metabolic rate. The factors that mediate the responses are not well understood, but oxygen has been implicated as a major control element, since vessel growth increases during hypoxic conditions and decreases during hyperoxic conditions. The following feedback control hypothesis may apply to many different physiological situations. Decreased oxygenation causes the tissues to become hypoxic, and this initiates a variety of signals that lead to the growth of blood vessels. The increase in vascularity promotes oxygen delivery to the tissue cells by decreasing diffusion distances, increasing capillary surface area, and increasing the maximum rate of blood flow. When the tissues receive adequate amounts of oxygen even during periods of peak activity, the intermediate effectors return to normal levels, and this negative signal, in turn, stops the further development of the vasculature. Although the effector mechanisms of the hypoxic stimulus are still being investigated, adenosine, which is produced in hypoxic tissues, appears to mediate hypoxia-induced increases in vascularity in some instances. Roles for fibroblast growth factor as well as mechanical factors associated with vasodilation and increased blood flow are postulated. Although blood vessel growth is a multifactorial process, a major influence in its regulation appears to be metabolic need. If this view is correct, it may be found that many of the quantitatively significant factors that control growth in a given vasculature are themselves modulated or controlled by metabolic signals reflecting the nutritional status of the tissues which that vasculature supplies.

Animals↗

PubMed1989

A simulation support system for solving large physiological models on microcomputers.

Although physiological modeling and computer simulation have become useful research tools to test new scientific theories and to design and analyze laboratory experiments, developing a new model can be a tedious process because the investigator must often write very complex and specific routines for data input and output. To facilitate the design of new models (as well as the use of existing models), we have developed MODSIM, a FORTRAN-based simulation support system for the IBM PC computer than can accommodate very large dynamic models having up to several thousand equations. It provides the investigator with utilities for continuous on-line graphical and/or tabular output, as well as facilities for dynamic interaction with the model. The user must only supply a model as a list of mathematical equations written in FORTRAN, along with the initial values of the model variables and parameters. The model is precompiled, compiled, and then linked to the MODSIM utilities. Without further programming, the user can then solve the model, select variables for graphical output, and stop the model at any time to analyze the data or to change a parameter before resuming the simulation. This simulation system makes it very easy to develop new models that actively interact with the experimental research of the investigator.

Computer Simulation↗

PubMed1989

Regulation of cardiac output during aldosterone-induced hypertension.

The classical haemodynamic transients of volume-loading hypertension have been difficult to demonstrate in aldosterone-induced hypertension. Because recent studies have shown that continuous whole-day measurements of cardiac output are superior to short-term recordings, we studied the transient haemodynamic effects of aldosterone-induced hypertension while monitoring arterial pressure and cardiac output (electromagnetic flow probe) continuously for 20 h a day. In six dogs maintained on a fixed sodium intake of 150 mmol/day, we infused aldosterone (12 micrograms/kg per day, intravenously) for 10 days. The aldosterone induced a progressive increase in mean arterial pressure, from a control value of 88 +/- 1 to 107 +/- 2 mmHg. Cardiac output increased progressively, reaching a peak average value on the 4th day of infusion of +14 +/- 5% above control, and remained slightly elevated throughout the infusion period. Total peripheral resistance increased slowly to a value averaging +13 +/- 4% above control. Therefore, our experiments show that aldosterone induces a primary increase in cardiac output followed by a secondary vasoconstriction, which is consistent with the classical transient haemodynamic effects of volume-loading hypertension.

Aldosterone↗

PubMed1989

Vascular development in chick embryos: a possible role for adenosine.

We studied the possible role of adenosine in the development of the vasculature using 217 chick embryos. Adenosine (2-32 mumol/day), inosine (16 mumol/day), dipyridamole (0.04-0.4 mumol/day), or aminophylline (400 and 800 micrograms/day) were administered twice each day into the air space on days 11-14. Control embryos received Ringer solution. Whole body vascularity was estimated on day 15 as the whole body structural vascular resistance (SVR), i.e., the hydraulic resistance of the maximally dilated vasculature. Adenosine decreased the SVR in a dose-related manner at the lower dosage amounts but caused a maximum decrease in SVR at the higher dosage amounts averaging 30% below the Ringer control values. Equimolar amounts of adenosine and inosine decreased the SVR by the same extent. Dipyridamole, which potentiates the biological effects of endogenous adenosine, also decreased the SVR in a dose-related manner to values averaging approximately 30% below control. When the effects of endogenous adenosine were blocked by aminophylline, the SVR increased in a dose-related manner to approximately 100% above control at the highest dosage amount. These results suggest that adenosine could have a physiological role in growth regulation of the vascular system in the chick embryo.

Adenosine↗

PubMed1989

Reflex modulation of lymphatic pumping in sheep.

Lymphatic pumping activity was examined in halothane-anesthetized sheep. A doubly cannulated preparation of the mesenteric lymph duct was "isolated" from lymph input, other than that from a constant pressure reservoir of artificial lymph attached to its inflow cannula, but had its blood supply and innervation intact. A cerebral ischemic response, evoked by injection of 2 ml air into the common carotid artery, increased both mean arterial pressure and fluid propulsion by the lymphatic. The latter rose from a control value of 45 microliters/min to a peak of 74 microliters/min. When 10(-4) M phentolamine was introduced into the lymphatic lumen, there was a transient increase followed by a sustained fall in lymph pumping. Repetition of the air injection while phentolamine was present in the duct lumen produced no increase in lymph pumping. In adrenalectomized animals, resting lymph propulsion by the mesenteric duct was depressed, and the response to air injection was attenuated but remained significantly greater than control. These results suggest that reflex activation of the sympathetic nervous system can increase lymph propulsion and that this may be augmented by the release of circulating catecholamines.

Adrenalectomy↗

PubMed1988

Hypotensive effect of chronic intrarenal infusion of acetylcholine during angiotensin hypertension.

We examined the role of the pressure natriuresis phenomenon in long-term arterial pressure control. Uninephrectomized dogs were housed in metabolic cages and made hypertensive with a continuous background intravenous infusion of angiotensin II (AngII, 12 ng/kg/min). To increase the ability of the kidney to excrete salt and water, we infused acetylcholine (ACH, 2.0 micrograms/kg/min), a potent natriuretic agen, directly into the renal artery. In four dogs, ACH decreased mean arterial pressure (MAP) from 144 +/- 5 mm Hg to 113 +/- 3 mm Hg. Sodium excretion increased by about 60% on the first day of infusion and then returned rapidly toward the control value. On cessation of the ACH infusion, there was a transient but marked sodium retention, and the hypertension returned. A control infusion of ACH intravenously rather than into the renal artery in the same four dogs did not affect MAP or sodium excretion during AngII hypertension.

Acetylcholine↗

PubMed1988

Effects of intermittent hypoxia on structural vascular adaptation in chick embryos.

We explored whether the blood vascular system of the chick embryo adapts its structure to meet the maximum or average oxygen needs of the tissue cells. Chick embryos were grown in continuous 12% oxygen, continuous 16% oxygen, and intermittent 12% oxygen in which the embryos were exposed to 12% oxygen for 4 h each day. Control groups were grown in room air. Measurements of structural vascular resistance (SVR), i.e., the resistance of the maximally dilated vasculature, were used to estimate the whole body vascularity of the 14- or 15-day-old embryos. Continuous exposure to 12% oxygen decreased SVR by 63.1 +/- 1.2 (SE) %, and intermittent exposure to 12% oxygen decreased SVR by 55.6 +/- 0.5% when compared with a 15-day-old normoxic control group. Based on studies with continuous exposure to different levels of low oxygen, it was predicted that exposure to 19.5% oxygen, the average concentration for the intermittent hypoxia group, would decrease SVR by 15.0 +/- 0.3%. These results indicate that intermittent hypoxia at 12% oxygen was approximately 90% as effective as continuous hypoxia at the same level in decreasing SVR and about four times more effective than 19.5% continuous oxygen. Therefore, the results support the hypothesis that the blood vascular system adapts its structure to meet almost entirely the maximum oxygen needs of the tissue cells.

Aerobiosis↗

PubMed1987

Whole body structural vascular adaptation to prolonged hypoxia in chick embryos.

We studied the role of hypoxia in the development of the blood vascular system using functional measurements of whole body and hindlimb structural vascular resistance in the chick embryo. The method is based on a newly developed whole body perfusion technique in which the maximally dilated blood vasculature of 14- to 15-day chick embryos is perfused through the extraembryonic blood vessels. Embryos were grown in 12% oxygen (Po2 65 mmHg, n = 18) or 16% oxygen (Po2 96 mmHg, n = 19) for the last 7 days of incubation and were compared with weight-matched (n = 17) and age-matched (n = 18) normoxic control groups (Po2 134 mmHg). Pressure-flow curves were generated for all embryos by increasing and decreasing the aortic pressure along 1-mmHg steps over a pressure range of 0-6 mmHg. Venous pressure was held at 0 mmHg by allowing the perfusate to flow freely from severed extraembryonic veins. The hydraulic resistance of the maximally dilated vascular bed, called the "structural vascular resistance," was decreased in a dose-related manner in the hypoxic groups to greater than 50% of control in the whole body and hindlimbs of the 12% oxygen group. The vessels of the 12% oxygen group were able to carry two and three times as much flow to the whole body and hindlimb tissues, respectively, as compared with the weight-matched normoxic control group. Therefore, the results support the hypothesis that prolonged exposure to hypoxia causes the blood vascular system to adapt its structure to allow greater amounts of blood to flow to the tissues at any given perfusion pressure gradient.

Adaptation, Physiological↗

PubMed1985

Modification of lymph by lymph nodes. III. Effect of increased lymph hydrostatic pressure.

Previous studies have shown that lymph nodes function as fluid exchange chambers in which the protein concentration of lymph is changed in the direction required to establish equilibrium of the Starling forces acting across the nodal blood-lymph barrier. We examined the effect of increased lymph hydrostatic pressure on efferent lymph by use of an isolated dog popliteal node preparation in which lymph having a protein concentration averaging 27.6 +/- 1.2% (SD) of that of plasma was infused into the node at a flow rate averaging 45.6 +/- 0.2 (SD) microliter/min. We compared steady-state values of prenodal and postnodal lymph flow and protein concentration following step increases in efferent lymph pressure from 0 to over 15 mmHg. Increasing efferent lymph pressure to values less than about 8 mmHg caused the efferent lymph protein concentration to increase; however, further increases in lymph pressure caused the lymph protein concentration to decrease to values approaching those attained at very low lymph pressures. We suggest that the failure of high lymph pressure to increase lymph protein concentration might be caused by blood vessel collapse within the node, a condition believed to increase nodal blood capillary pressure and to decrease blood-lymph barrier filtration coefficient. An important finding was that increasing efferent lymph pressure caused significant amounts of lymph proteins to be lost during nodal transit. Therefore, it appears that increasing efferent lymph pressure to very high values has little effect on lymph protein concentration but has great effect on postnodal lymph protein flux.

Animals↗

PubMed1985

Measurement of subcutaneous tissue fluid pressure using a skin-cup method.

We developed a new method for measuring tissue fluid pressure in subcutaneous tissue. Porous Teflon cylinders were permanently implanted subcutaneously into the inguinal area of 10 dogs, and after several weeks a skin concavity formed in the center of each of the cylinders. A small needle attached to a recording system was inserted into the free tissue fluid lining the concavity, and the tissue fluid pressure averaged -8.8 +/- 2.7 (SD) mmHg. Next, a hollow Plexiglas cup was placed over the concavity and glued to the skin. The air pressure in the skin cup was continually adjusted (using an electromechanical servo-control system) to pull the skin upward and to hold it perfectly flat across the upper ridge of the Teflon cylinder. The simultaneously recorded needle and cup pressures averaged -9.1 +/- 2.4 and -8.6 +/- 2.6 mmHg, respectively, during steady-state conditions with the skin in a flat position. Both pressures also responded appropriately to dynamic changes in tissue fluid pressure caused by increasing and decreasing the volume of the free tissue fluid. Because the skin was flat, the equivalences of pressures above and below the skin is consistent with the hypothesis that the skin was not tethered significantly to the underlying tissues and that cup pressure accurately estimates the tissue free fluid pressure.

Animals↗

PubMed1985

Studies of lymph modification by lymph nodes.

This paper will focus on physiological evidence for a lymph node concentrating-diluting mechanism. The mechanism is based on the finding that the protein concentration of efferent lymph leaving the node will change in the direction required to establish equilibrium of the Starling forces acting across the blood-lymph barrier of the lymph node. Therefore, the lymph proteins may become concentrated or diluted during nodal transit, depending on the direction of net fluid transfer between the lymph and blood vascular compartments; if the Starling forces are balanced perfectly, the lymph will not be altered.

Animals↗

PubMed1979

Gram-negative sepsis in thermally injured sheep.

Burn wound sepsis was studied for four days in awake, unanesthetized sheep. Each of the animals was given a 40% third-degree burn, and the wound was infected with Pseudomonas aeruginosa. According to their cardiopulmonary response, the animals were divided into three groups: hyperdynamic, normodynamic, and hypodynamic. The hyperdynamic group had an increased cardiac index and a decreased total peripheral resistance index. The hypodynamic group was characterized by the following: decreased cardiac index, increased total peripheral resistance index, increased hematocrit, decreased PaO2, increased pulmonary vascular resistance index, and decreased neutrophils (P less than or equal to 0.05). The hypodynamic group was inoculated with more P aeruginosa, had more positive cultures for P aeruginosa, and had a greater mortality rate than the other two groups. It is suggested that the hypodynamic group was hypovolemic as a result of a fluid shift from the vascular compartment, that this fluid shift may be important in preventing the animals from responding to sepsis with an elevated cardiac index, and that the derivation of the cardiovascular response to sepsis is related to the severity of the initial septic insult.

Animals↗