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Biomedical subjects

R H Cox

Publications and source records attributed to R H Cox.

At least 91 records · Page 5Linked to original sources

Baroreceptor reflex cardiovascular control in mongrel dogs and racing greyhounds.

The open-loop carotid sinus baroreflex control of arterial pressure-flow relations were compared in mongrel dogs and racing greyhounds (GH) anesthetized with alpha-chloralose. The carotid sinuses were bilaterally isolated and perfused under controlled pressure. Pulsatile pressure and flow were simultaneously measured in the ascending aorta, the celiac, superior mesenteric, left renal, and right iliac arteries. Open-loop set point values of mean arterial pressure were higher in GH before and after vagotomy. Reflex gains were similar before vagotomy but lower in GH after vagotomy. The overall range of control of arterial pressure was the same before vagotomy but smaller in GH after vagotomy. The variation of mean arterial pressure with mean carotid sinus pressure in GH was shifted toward higher pressure levels similar to resetting. The overall effects of vagotomy on carotid sinus baroreceptor reflex responses were smaller in GH. Operating point values of regional resistance were generally smaller in GH. Operating point sensitivities of regional resistance were the same except for the iliac bed, which was more sensitive in GH. These results document significant regional differences in the baroreceptor control of regional hemodynamics between mongrels and greyhounds that could contribute to altered responses especially to "hypertensive" perturbations.

Animals↗

Cardiovascular and sympathoadrenal responses to stress in swim-trained rats.

Chronic exposure to swim stress (i.e., training) is associated with functional adaptations of the cardiovascular system. On the other hand, repeated exposure to tail shock, an emotional stress, often results in deleterious changes in resting blood pressure and myocardial pathology. We hypothesized that the pathological adaptation following chronic exposure to tail shock was associated with a larger acute physiological response compared with swim stress. Therefore, acute responses to swim and shock stress were compared. A second concern of this study examined the extent to which adaptation to swim training influences responses to predictable tail shock stress. The cardiovascular and sympathoadrenal responses to swim stress, using 1% body wt attached to the tail, were compared with predictable tail shock (0.2-0.4 mA intensity, 1-s duration, 1/min) in two groups of Long-Evans male rats. In the first, 11 rats were studied following 5-7 wk of swim training, consisting of daily 1-h sessions of swimming with 2% body wt attached to their tails. They were compared with an age-matched nontrained (NT) group (n = 8). During swimming, the trained animals showed significantly lower heart rate (387 +/- 10 vs. 449 +/- 18 beats/min) and significantly lower lactate (0.9 +/- 0.09 vs. 2.0 +/- 0.24 mmol/l), epinephrine (332 +/- 57 vs. 739 pg/ml), and corticosterone (32 +/- 10 vs. 62 +/- 9 micrograms/dl) responses. Systolic and diastolic blood pressures were elevated in swim stress by the same degree in trained (167/110 mmHg) and NT (177/116 mmHg) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Cardiac output and peripheral vascular resistance during intravenous infusion of 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine in conscious normotensive and spontaneously hypertensive rats.

Cardiovascular responses to intravenous 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (56 and 112 pmoles/kg/min) were examined in conscious Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHR) instrumented with arterial and venous catheters, and an electromagnetic flow probe around the ascending aorta. The results suggest that this compound reduces mean blood pressure via a dose related fall in peripheral vascular resistance and cardiac index in conscious SHR and WKY rats.

Animals↗

Blood pressure and plasma renin activity responses to chronic stress in the borderline hypertensive rat.

The purpose of this study was to examine the systolic blood pressure and plasma renin activity (PRA) responses to chronic stress in normotensive rats and in rats with one hypertensive parent. Twenty-four male Wistar-Kyoto (WKY) and 24 male F1 offspring of spontaneously hypertensive and WKY rats (BHR) were randomly assigned to 3 groups of 8 each. Experimental (E) animals were subjected to 2 hr daily of shock-shock conflict. Each response produced a 0.2 sec, 0.2-0.4 mA cutaneous electric shock. Failure to respond in 10 sec resulted in a train of 5 shocks (0.2 sec each sec). Yoked animals (Y) received the same shocks as E but had no control over their presentation. Finally, a control group (C) for maturation received no shocks. The E and Y animals were subjected to 14 weeks of conflict and were then monitored an additional 14 weeks in the absence of shock. All animals had their tail cuff blood pressures taken weekly except for 3 times when bloods were obtained for PRA assays. Analysis of blood pressure data revealed that:(1) BHR animals showed more of a blood pressure response to shock than WKY animals; (2) Y animals showed more of a response to conflict than E, especially for the BHR group; and (3) BHR shocked animals remained permanently elevated compared to BHR control animals even in the 14 week post-conflict period during which no shocks were given. Although PRAs for BHR animals were significantly higher than for WKY at the beginning of study, the stress-induced hypertension was associated with either normal or suppressed PRA values, suggesting that the hypertension in these animals is not a high renin hypertension.

Animals↗

Viscoelastic properties of canine pulmonary arteries.

Ring segments of extralobar and intralobar canine pulmonary arteries were used in vitro to study their frequency-dependent viscoelastic properties. Measurements of force in response to sinusoidal perturbations of length were made over the frequency range of 0.002-10 Hz. These measurements were made under three conditions: 1) passive smooth muscle at a physiological value of wall circumference (passive), 2) active smooth muscle at the same circumference (active), and 3) passive smooth muscle at a higher force (circumference) approximating the active value (high strain). Most of the frequency dependence of the dynamic modulus occurred over the range of 0.002-0.1 Hz. Variations in dynamic modulus for frequencies between 0.1 and 10 Hz were smaller in comparison. Larger variations in dynamic modulus were found 1) under conditions of active smooth muscle than under passive or high strain conditions, 2) at high strain compared with low strain (passive) conditions, and 3) for the intralobar compared with extralobar arteries under equivalent conditions. Values of modulus ratio were computed by dividing dynamic modulus by a low-frequency value (f = 0.002 Hz). Values of modulus ratio were similar at high and low wall strain under passive conditions and were higher for intralobar than for extralobar arteries. Values of modulus ratio with active muscle were larger than for passive conditions, but no differences were found between extralobar and intralobar arteries. The "amount" of viscoelasticity correlated with the amount of muscle at the two sites but not with the force-generating capacity of the muscle, so that viscoelasticity and force development may represent different manifestations of muscle properties.

Animals↗

Effects of chronic cigarette smoking on canine arteries.

Segments of carotid and femoral arteries were obtained from beagles subjected to cigarette smoking (12/day for 2 yr) and from unexposed controls. The segments were used for in vitro studies of active and passive mechanics, dose responses to norepinephrine (NE) and K+, connective tissue content, and water and electrolyte content and distribution. No significant differences in passive arterial wall mechanics or geometry at 100 mmHg were found, but a small (significant) increase in passive stiffness was found at wall loads corresponding to higher values of pressure for arteries from smokers. No significant changes in connective tissue composition were found at either site. No significant differences in maximum active force development were found at either site between the two groups. However, values of active force near the middle of the active force-length curve were lower (P less than 0.05) for smoker's arteries when expressed as a fraction of the maximum developed force. No differences in cell volume were found in arteries from the two groups. Mg2+ and K+ content of the femoral and Ca2+ content of both arteries were greater in the smokers. No difference in NE dose-response relations were found for either site. A statistically significant decrease in responsiveness to K+ was found for femoral arteries from smokers, but not for the carotids. The results of these studies demonstrate that some significant changes in arterial wall properties occur in beagle dogs exposed to chronic cigarette smoke.

Animals↗

Antihypertensive effects of I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine on plasma renin activity and catecholamine responses in spontaneously hypertensive rats.

Fourteen 23 week old male spontaneously hypertensive rats (SHR) were randomly divided into saline control or phospholipid (I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) treatment groups. Four weeks of baseline systolic blood pressure (SBP) and heart rate (HR) measurements were determined via tail plethysmography. On week 25 of the baseline period a 1.5 ml blood sample was taken by tail clip for analysis of norepinephrine (NE), epinephrine (E), and plasma renin activity (PRA). On the following week, a single injection of phospholipid (11 ug/kg, s.c.) was given to the experimental animals following baseline SBP and HR determinations. A similar procedure was employed for control subjects, except they received an injection of normal saline (0.5 ml, s.c.). Systolic BP and HR responses were monitored for 24 minutes following the injection. A 1.5 ml blood sample was taken at the end of the 4th minute for NE, E, and PRA assays. A significant drop in SBP (202 +/- 5 mmHg to 124 +/- 6 mmHg) and an increase in HR (431 +/- 17 bpm to 519 +/- 21 bpm) were observed for experimental animals, but not for control subjects. Plasma NE increased significantly (446 +/- 42 pg/ml to 1099 +/- 77 pg/ml), but E remained unchanged following treatment with the phospholipid. Plasma renin activity increased for both groups, but this change was only significant for the experimental group (18.1 +/- 5.7 ng Al/ml/hr to 34.3 +/- 3.6 ng Al/ml/hr). Thus, it appears that I-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine is a potent antihypertensive vasodilating agent which stimulates baroreceptor mediated sympathetic discharge to the heart and kidneys of the SHR.

Animals↗

Age-related changes in arterial wall mechanics and composition of NIA Fischer rats.

Segments of carotid and tail arteries and descending thoracic aorta were obtained from the NIA colony of Fischer rats at ages 3, 12, 24 and 30 months. Measurements of pressure and diameter were made on intact cylindrical segments under conditions of active (147 mM K+) and passive (Ca2+-free and 2 mM EGTA) smooth muscle. These data were used to compute active and passive mechanics. Contiguous segments were used for the analysis of connective tissue, water and electrolyte contents. Passive stiffness of the carotid and tail arteries increased monotonically with increasing age. Collagen content in the aorta and tail artery generally increased with age, while elastin content decreased in the aorta and carotid artery. The ratio of collagen to elastin increased at all sites with age. Maximum values of active stress response (force development) increased from 3 to 12 months for the carotid artery, but decreased with age (at 24 and 30 months compared to 3 and 12-months) for the tail artery. Changes in relative cell content were such that active cellular force development was the same at all ages for the carotid artery but was smaller at 24 and 30 months compared to the younger animals for the tail artery. Decreased cellular force development by arterial smooth muscle is not an anatomically uniform finding in this animal model.

Aging↗

Pulmonary vascular response to carotid sinus hypotension in the awake and anaesthetized dog.

The pulmonary haemodynamic response to brachiocephalic artery occlusion (BCO) was studied in nine dogs. The animals were chronically instrumented for the measurement of pulmonary artery pressure and flow together with left atrial pressure. Measurements were performed in the awake state and also at end-tidal halothane levels averaging 0.74 +/- 0.02 (H1), 0.92 +/- 0.02 (H2) and 1.13 +/- 0.03 (H3) %, with and without nitrous oxide. Halothane at any of the above concentrations, with or without nitrous oxide, had no effect on pulmonary vascular resistance compared to awake values. Most importantly, we found no evidence for active pulmonary vasomotion in response to BCO in the awake animal, or at any anaesthetic concentration.

Anesthesia, Inhalation↗

Comparison of arterial wall mechanics using ring and cylindrical segments.

Thin rings and intact cylindrical segments of canine carotid and iliac arteries were used to determine wall mechanics. Measurements of force and length were obtained from the ring segments, whereas measurements of pressure and diameter were obtained from the cylindrical segments under conditions of active (147 mM K+) and passive smooth muscle (Ca2+ free and 2 mM ethyleneglycolbis (beta-aminoethylether)-N,N'-tetraacetic acid). These measurements were normalized to values of segment stress and strain. Under passive conditions stress-strain relations for the rings appeared to be stiffer than those obtained using cylindrical segments. Pressure-diameter curves computed using force-length data from the rings were shifted to higher values of diameter compared with values from the intact segments at all pressure levels. Passive mechanics derived from measurements on ring segments yielded poor estimates of mechanics derived from intact segments. Despite this finding, values of active force development from the two sample geometries were similar. No statistically significant differences were found in values of maximum force development expressed in terms of sample cross-sectional area. Some differences in values of active force development at low values of muscle length were found. The latter were probably related to the differences in passive mechanics and the procedure used to normalize muscle length. Reasonable values of active force development can be obtained from ring segments.

Animals↗

Effect of hyperoxia on metabolic and catecholamine responses to prolonged exercise.

The use of inspired gas mixtures with an oxygen fraction in excess of 0.3 has been associated with a decrease in the gas exchange ratio (R) during prolonged work in humans. It had been hypothesized that the lower R was due to a lower plasma catecholamine concentration caused by the hyperoxia (Med. Sci. Sports 10: 167-170, 1978). We tested this hypothesis by measuring changes in plasma epinephrine and norepinephrine when the subjects were switched from breathing air to 60% O2 (and vice versa) during 40 min of cycle ergometer exercise at 67% maximal oxygen uptake (VO2max). The subject breathed one gas mixture for the first 30 min and was switched to the other in the last 10 min. The order was reversed in the second test. The switch in gas mixtures from air to 60% O2 resulted in a significant reduction in R, heart rate, minute ventilation, blood lactate concentration, and plasma epinephrine concentration (P less than 0.05). The plasma norepinephrine concentration (0.1 greater than P greater than 0.05) and the plasma free fatty acid concentration were not significantly changed. Although the direction of the epinephrine change was consistent with the change in R, the epinephrine change was quantitatively small (20 pg/ml) and of questionable physiological significance. This suggests a direct effect of PO2 on cellular metabolism as one cause of the change in R when the subjects were switched from air to 60% O2.

Epinephrine↗

Lactate accumulation during incremental exercise with varied inspired oxygen fractions.

Six subjects pedaled a stationary cycle ergometer to exhaustion on three separate occasions while breathing gas mixtures of 17, 21, or 60% O2 in N2. Each subject rode for 3 min at work rates of 60, 90, 105 W, followed by 15-W increases every 3 min until exhaustion. Inspired and expired gas fractions, ventilation (V), heart rate, and blood lactate were measured. O2 uptake (VO2) and CO2 output (VCO2) were calculated for the last minute of each work rate; blood samples were drawn during the last 5 s. "Break points" for lactate, V, VCO2, V/VO2, and expired oxygen fraction (FEO2) were mathematically determined. VO2 was not significantly different at any work rate among the three different conditions. Nor did maximal VO2 differ significantly among the three treatments (P greater than 0.05). Lactate concentrations were significantly lower during hyperoxia and significantly higher during hypoxia compared with normoxia. Lactate values at exhaustion were not significantly different among the three treatments. Four subjects were able to work for a longer period of time during hyperoxic breathing. The variations in lactate accumulation as reported in this study cannot be explained on the basis of differences in VO2. The results of this research lend support to the hypothesis that differences in the performance of subjects breathing altered fractions of inspired oxygen may be caused by differences in lactate (or H+) accumulation.

Adult↗

Effects of various levels of hypoxia on plasma catecholamines at rest and during exercise.

The purpose of this study was to investigate the relationship between hypoxia and heart rate (HR), pulmonary ventilation, plasma epinephrine (E) and norepinephrine (NE) at rest and during exercise at 40% of maximal oxygen uptake. Six subjects were exposed to inspired gas mixtures containing 21%, 19%, 17%, 15%, and 13% O2. The duration of exposure to each mixture was 10 continuous min at rest, followed by 10 continuous min during exercise. The order of the inspired gas mixtures was randomized. During the exercise test, HR was elevated with exposure to 15% and 13% O2 (p less than 0.001). Pulmonary ventilation was higher at 13% O2 than at the higher O2 percents (p less than 0.001). There were no significant changes in plasma E or NE at rest or during exercise in response to the gas treatments. These results indicate that acute exposure to hypoxic gas mixtures at rest and during light work does not result in significant increases in sympathetic nervous system activity, as judged by the plasma E and NE response.

Adult↗

Nitrous oxide and the baroreceptor reflexes in the dog.

The effects were studied of 67% nitrous oxide on the baroreceptor control of systemic haemodynamics in the dog. Nitrous oxide was added to end-tidal halothane concentrations of about 0.9% (H2) together with halothane levels approximately 25% above (H3) and below (H1) the H2 concentration. Baroreceptor function was assessed by brachiocephalic artery occlusion (BCO) or perfusion of the isolated carotid sinuses. In the intact animal, nitrous oxide significantly increased mean arterial pressure only at the H2 level (P less than 0.001). At the closed loop operating point of the carotid sinus reflex (CSR), for all halothane levels, nitrous oxide decreased cardiac output and stroke volume, increased systemic vascular resistance and central venous pressure with no effect upon mean arterial pressure. The operating point gain of the CSR was significantly depressed by nitrous oxide at the H1 and H3 levels (P less than 0.05). The CRS operating characteristics were significantly modified by N2O in a manner which depended upon the underlying concentration of halothane.

Anesthesia, General↗

Comparison of mechanical and chemical properties of extra- and intralobar canine pulmonary arteries.

Segments of pulmonary arteries from five extralobar and intralobar sites in the form of circumferential rings were used for the determination of active and passive mechanics, analysis of connective tissue, and determination of water and electrolyte content. Measurements of ring length and tension were made under conditions of active (145 mM K+) and passive (Ca2+ free and 2 mM EGTA) smooth muscle and were used to compute values of segment stress and strain. Passive stress-strain relations among the various sites studied were not significantly different. Collagen and total connective tissue content increased from the largest extralobar to the smallest intralobar sites studied. This suggests differences in the organization of the connective tissue proteins at the secondary and tertiary levels in the various sites studied. The maximum active stress (force/area) developed in response to high K+ was largest in the intralobar arteries and lower in the larger extralobar arteries. The K+ content of these arteries decreased significantly with distance from the heart. The extracellular water content decreased with distance from the heart, whereas total water content was unchanged. These results suggest that relative cell volume decreased with distance from the heart in pulmonary arteries. Thus differences in the relative cell content per se were not responsible for the differences in maximum active stress development among the various arteries.

Animals↗

Changes in arterial wall properties during development and maintenance of renal hypertension.

Segments of carotid and tail arteries were used to determine the effects of two-kidney Goldblatt hypertension on mechanical properties and chemical contents. Arteries were obtained after 4 and 12 wk of hypertension. Systolic pressures averaged 129 mmHg in control animals and 150 mmHg in hypertensive ones. Pressure-diameter data were recorded under conditions of active (145 mM K+) and passive (0 Ca2+ and 2 mM EGTA) smooth muscle. Small increases in passive stiffness were found after 4 and 12 wk in the carotid arteries of hypertensive animals, but no significant change occurred in the tail arteries. Small but significant decreases in total connective tissue content of these arteries were found after 12 wk of hypertension. Maximum values of active stress response were significantly larger in carotid arteries from hypertensive animals at both 4 and 12 wk of hypertension. No significant differences were found for the tail arteries. The K+ content of the carotid but not the tail artery was larger for the hypertensive animals. When corrected for differences in relative cell content most of the differences in active force development were eliminated. The differences in passive mechanics can not be explained on the basis of the changes in connective tissue content. The active smooth muscle responses and content changes suggest that they are directly related to the moderate elevation of arterial pressure.

Animals↗