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F C White

Publications and source records attributed to F C White.

At least 37 records · Page 2Linked to original sources

Effects of drinking and central angiotensin II stimulation on organ blood flow in conscious rats.

While the hemodynamic response pattern accompanying feeding behavior has been well characterized, there is less information about the hemodynamic changes associated with drinking. In the present study, we have measured organ blood flows in conscious, unrestrained rats during schedule-induced drinking behavior, using the tracer microsphere technique (diameter of spheres 15 +/- 3 microns; labels: 141Ce, 113Sn). In addition, we determined the hemodynamic response pattern following intracerebroventricular (i.c.v.) injection of 100 ng angiotensin II (ANG II) (a dose known to be dipsogenic) in rats that were not allowed to drink during the experiment. The hemodynamic responses during drinking behavior included (a) significant increases in blood flow through the kidney, stomach and small intestine, (b) a decrease in blood flow through skeletal muscle, and (c) no significant changes in the rest of the organs. ANG II i.c.v. elicited (a) significant decreases in blood flow through the kidney, stomach, small intestine and skin, (b) a significant increase in blood flow through the liver (hepatic artery), and (c) no significant changes in blood flow through the brain, heart, lung (bronchial arteries), colon, skeletal muscle (biceps) and testis. We conclude that spontaneous drinking behavior in rats is associated with a characteristic hemodynamic drinking response, which resembles a classical feeding reaction. In non-drinking rats the hemodynamic response pattern following ANG II i.c.v. was different from the drinking response, providing further evidence, that the behavioral and cardiovascular effects of the neuropeptide can be dissociated.

Angiotensin II↗

Blood viscosity in phocid seals: possible adaptations to diving.

1. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) of phocid seal red blood cells (RBC) are elevated compared to those of most terrestrial mammalian species. The influence of these characteristics on blood flow was revealed by viscosity (VIS) measurements. 2. RBC morphology and VIS of whole blood from 7 harbor seals and 5 northern elephant seals were compared with blood of the domestic pig. Samples were analysed for RBC count, white blood cell (WBC) count, total plasma proteins, hematocrit (HCT), MCV and MCHC. Viscosity measurements were made at shear rates from 11.5 to 230.4 s-1 on a Wells-Brookfield cone-plate viscometer at 37 degrees C. 3. Mean values for HCT (%), MCV (micron 3) and MCHC (%) were, respectively: elephant seal: 57, 176, 44; harbour seal: 53, 105, 38; domestic pig: 28, 54, 34. Pig blood was reconstituted to match seal blood HCTs. VIS determinations showed that seal and pig blood conform to the general mammalian dependence of VIS upon shear rate and HCT. 4. Seal blood VIS was 28% (harbour seal) and 16% (elephant seal) less than pig blood VIS at low shear (P less than 0.05). Seal blood carried more hemoglobin per unit volume than did pig blood reconstituted to the same HCT. Fewer, larger RBC with higher MCHC, and hence elevated oxygen storage, accompanied by reduced VIS and reduced flow resistance near stasis suggests that this feature of phocid seal blood is an adaptation to circulatory redistribution during long dives.

Adaptation, Physiological↗

Plateau in muscle blood flow during prolonged exercise in miniature swine.

Cardiovascular, metabolic, and thermoregulatory responses were studied in eight male miniature swine during a prolonged treadmill run. Each animal underwent 8-10 wk of exercise training, thoracic surgery, and 3 wk of retraining before the experimental run. This regimen enabled the animals to run at 65% of the heart rate range (210-220 beats/min) for approximately 100 min. Skin wetting and a fan were used to cool the pigs during the run. Regional blood flow was significantly altered with the onset of exercise; however, hindlimb muscle and total gastrointestinal blood flow were unchanged throughout the exercise period. Compared with 5-min values, heart rate and cardiac output were significantly elevated by 17 beats/min and 31 ml.min-1.kg-1 at 60 min and by 20 beats/min and 33 ml.min-1.kg-1 at end exercise, respectively. Core temperatures increased between 5 and 30 min of exercise (39.4 vs. 39.9 degrees C) but then remained unchanged to the end of exercise. Mean arterial pressure, O2 consumption, and blood lactate did not change during the exercise bout. These data indicate that limiting increases in core temperature during prolonged exercise was associated with a plateau in active muscle blood flow.

Animals↗

Altered minimal coronary resistance to antegrade reflow after chronic coronary artery occlusion in swine.

We examined coronary pressure-flow relations after chronic coronary artery occlusion induced by placement of an ameroid occluder on the left circumflex coronary artery in swine. An acute open-chest procedure was performed in nine pigs 27 +/- 2 days (mean +/- SEM) after surgical placement of the ameroid occluder, and in eight nonoperated control pigs. Coronary vascular resistances were measured during maximal coronary vasodilation with adenosine. Minimal coronary resistance was assessed before and after cannulation and extracorporeal perfusion of the left circumflex coronary artery distal to the site of the ameroid occluder in pigs from the ameroid group and in a similar site in control pigs. Minimal coronary resistance to antegrade reflow in the left circumflex region was decreased significantly in ameroid pigs compared with control pigs (0.06 +/- 0.01 vs. 0.26 +/- 0.03 mm Hg.min.100 g/ml, p less than 0.001, respectively). Decreased minimal coronary vascular resistance was present transmurally in the left circumflex region of ameroid pigs. Altered vascular resistance occurred only in myocardium distal to the ameroid occluder since the nonoccluded left anterior descending region in ameroid pigs had minimal coronary resistance similar to that of the same region from control pigs (0.23 +/- 0.03 vs. 0.19 +/- 0.02 mm Hg.min.100 g/ml). Thus altered minimal coronary vascular resistance occurs and probably reflects vascular proliferation and/or vascular alterations which result in an increased total cross-sectional area of the vasculature in the myocardium distal to the occlusion.

Animals↗

Regional capillary and myocyte distribution in normal and exercise trained male and female rat hearts.

Adult Sprague-Dawley male and female rats were exercise trained for five months by either treadmill running or swimming. Significant differences in left ventricular regional capillary density and myocyte cross-sectional area were found. In control rats the epicardial regions had greater capillary density than endocardial regions. Endocardial myocyte cross-sectional areas were greater than those of epicardial myocytes in both sexes. Male rats had larger endocardial myocytes and larger hearts than females. After exercise training, myocyte size increased in the epicardial region but not in the endocardial region, while capillary density increased significantly only in the endocardial region. Similar changes were seen in both male and female rats with comparable degrees of exercise induced hypertrophy. These data suggest that exercise training "normalizes" the distribution of capillaries in the myocardium. Capillary density increased only in the regions where myocyte cross-sectional area did not increase. Further, the effects of exercise on male and female rat hearts is not different when the degree of exercise induced hypertrophy is similar.

Animals↗

Decreased regional contractility in nonischemic myocardium during acute coronary artery occlusion in conscious pigs.

The purpose of this study was to use the relationship between end-systolic left ventricular pressure and segment length to assess the inotropic state of nonischemic myocardium during acute coronary artery occlusion in the conscious pig. Eight pigs were chronically instrumented with sonomicrometers to measure midwall segmental shortening and a micromanometer to measure left ventricular pressure. Occlusion of the inferior vena cava with a pneumatic occlusive cuff caused transient decreases in left ventricular pressure so that the relationship of left ventricular pressure and segment length at end systole could be determined over a range of pressures. In preliminary studies using open-chest pigs, this relation was shown to be highly linear and best quantified using a calculated segment length at a left ventricular pressure of 100 mm Hg (ESL100). During acute, 1-min occlusion of the left anterior descending coronary artery, the ESL100 of the nonischemic lateral and posterior walls was significantly increased from 8.75 +/- .18 mm to 9.64 +/- .21 mm (mean +/- SD, p less than .01), indicating a decreased inotropic state. Similarly, during occlusion of the left circumflex coronary artery, the ESL100 of the nonischemic anterior wall increased from 8.44 +/- 2.53 mm to 9.26 +/- 3.12 mm (p less than .05). This was not associated with a change in the amount of shortening during systole. Pharmacological autonomic blockade using atropine and propranolol failed to alter the response of nonischemic zones to acute coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Organ blood flow haemodynamics and metabolism of the albacore tuna Thunnus alalunga (Bonnaterre).

Metabolic haemodynamic, and organ blood flow measurements were made in tabled, partially anaesthetized albacore Thunnus alalunga. Heart rates were 115 +/- 9 beats/min: blood pressure 98/75 mm Hg (systolic/diastolic): cardiac output 36.1 +/- 5 (ml/min/kg): oxygen consumption 3.4 +/- 0.7 (ml O2/min/kg) and cardiac contractility (dP/dt) 6342 +/- 822 mm Hg/s. Organ blood flows were measured with radiolabelled microspheres. The red muscle, kidney, and spleen received the highest flows and the white-muscle the least. There was a flow gradient in the white-muscle with the inner portion near the red-muscle receiving the highest flows. Arterial and venous blood gas measurements showed a reverse temperature effect on arterial PO2 and a P50 of 15.9 Torr corrected to 37 degrees C. Red-muscle temperature was 7 degrees C higher than ambient water temperature. These measurements record the albacore's markedly high cardiovascular capability.

Animals↗

Increased myocardial beta-receptors and adrenergic responses in hyperthyroid pigs.

Controversy exists presently as to whether thyroid hormone potentiates the action of catecholamines on the heart. Therefore, the relationships between adrenergic sensitivity, myocardial beta-receptor number, and the cardiovascular responses associated with excess thyroid hormone were investigated in pigs (Sus scrofa). A hyperthyroid state was induced by the administration of triiodothyronine (T3; 1 mg/kg iv). After 7 days there was a significant increase in resting heart rate, systolic blood pressure, rate-pressure product, and O2 consumption in the hyperthyroid state. At this time echocardiography showed a substantial increase in myocardial cross-sectional size. Pharmacological tests showed an increased intrinsic heart rate (127 +/- 29 to 205 +/- 25 beats/min; P less than 0.001) and an increased chronotropic sensitivity to isoproterenol. The concentration of isoproterenol required for a 50% of maximal response (ED50) was reduced by 33 +/- 30% (2.1 +/- 1.0 to 1.2 +/- 0.3 micrograms/l; P less than 0.025). The slope of the line relating isoproterenol concentration and change in heart rate was increased by 29 +/- 33% (61 +/- 10 to 78 +/- 10; P less than 0.025). Radioligand studies demonstrated an increase in the number of beta-receptors in right atrial membranes from hyperthyroid animals (41 +/- 7 vs. 75 +/- 18 fmol/mg; P less than 0.02). The apparent dissociation constant (KD) of the receptor for l-isoproterenol was similar in membranes from euthyroid and hyperthyroid animals (157 +/- 57 vs. 219 +/- 59 nM, respectively; P = NS). This study demonstrates that hyperthyroidism is associated with an increased chronotropic sensitivity to isoproterenol, consequent to an up-regulation of beta-adrenergic receptors in the right atrium.

Animals↗

Development of coronary collateral circulation in left circumflex Ameroid-occluded swine myocardium.

Coronary collateral development was examined in 34 pigs after gradual occlusion of the left circumflex coronary artery (LCX) with an Ameroid constrictor. Collateral development was assessed by measurements of myocardial blood flow and regional myocardial function at rest and during exercise over a 16-wk period after placement of the constrictor. Coronary collateral development was adequate to prevent severe infarction and restore blood flow to the collateral-dependent LCX region within 3-7 wk. Infarction averaged 5.0 +/- 1.3% of the LCX region. Blood flows at rest were 1.05 +/- 0.14 and 1.13 +/- 0.15 ml.min-1.g-1 in the subendocardium of the collateral and control regions, respectively, 7 wk postoperatively. Concurrently, collateral vessel development supported normal myocardial function at rest as determined by systolic wall thickening in the LCX region. However, collateral development was limited, since blood flows during moderate and severe exercise were reduced in the LCX region compared with control and left anterior descending and right coronary regions. Blood flow ratios (collateral/control flow) during severe exercise 3 wk postoperatively were 0.23 +/- 0.03 and 0.57 +/- 0.05 in the subendocardium and subepicardium and were constant throughout the 16-wk period throughout the study. Myocardial function of the collateral region also was reduced during exercise and a 30-min recovery period. We suggest that this limited coronary collateral circulation, which develops in response to gradual coronary occlusion in swine, serves as a model for the human collateral circulation for the study of protocols to alter growth and development of coronary collateral vessels.

Animals↗

Effects of left circumflex Ameroid constrictor placement on adrenergic innervation of myocardium.

We evaluated the adrenergic innervation of the swine and canine myocardium after placement of an Ameroid constrictor around the left circumflex coronary artery (LCX). Fluorescent histochemistry was used to identify adrenergic nerve terminals in the myocardium and coronary vasculature. Ameroid occlusion of the proximal LCX in 10 pigs for 3 wk resulted in 6 +/- 1% infarction as well as myocardial ischemia in the left circumflex region of pigs studied during exercise. However, placement of the Ameroid constrictor did not significantly alter the surface density of the nerve terminals in the LCX region of myocardium when compared with innervation of control hearts. Histological examination of the coronary arterial adrenergic innervation in Ameroid-occluded pigs revealed that coronary vessels in the circumflex region of the heart were innervated. Similarly, in seven LCX Ameroid-occluded dogs, no significant decrease in adrenergic innervation of the LCX region of myocardium was observed when compared with control dogs. In contrast LCX Ameroid-occluded pigs demonstrated significant (P less than 0.01) denervation of the left anterior descending (LAD) region of myocardium when compared with control animals. The close proximity of adrenergic nerve bundles in the proximal LAD region indicates that denervation of the myocardium supplied by the LAD may result from the dissection and/or fibrosis associated with placement of the Ameroid constrictor on the proximal LCX. Our results suggest that placement of an Ameroid constrictor on the proximal LCX does not significantly alter the adrenergic innervation of the LCX-perfused myocardium or its associated coronary vasculature. However, denervation of LAD-perfused myocardium and its vasculature may result.

Adrenergic Fibers↗

Adaptation of the left ventricle to exercise-induced hypertrophy.

Cardiac functional and structural adaptations to exercise-induced hypertrophy were studied in 68 pigs. Pigs were exercise trained on a treadmill for 10 wk. Sequential measurements were made of cardiac dimensions, [left ventricular end-diastolic diameter (EDD), changes in diameter (delta D%), wall thickness (WTh), wall thickening (WTh%), left ventricular pressure (LVP), time derivative of pressure (dP/dt), stroke volume, total body O2 consumption (VO2), blood gases, and systemic hemodynamics] at rest and during moderate and severe exercise. Postmortem studies included morphometric measurements of capillary density, arteriolar density, mitochondria, and myofibrils. All of the exercise-trained pigs showed significant increases in aerobic capacity. Maximum O2 consumption (VO2 max) increased by 37.5% in group 1 (moderate exercise training) and 34% in group 3 (heavy exercise training). Cardiac hypertrophy ranged from less than 15% in a group (n = 8) subjected to moderate exercise training to greater than 30% in a group (n = 11) subjected to heavy exercise training. Before training, exercise was characterized by a decreasing EDD during progressive exercise; this was reversed after exercise training. Stroke volume and end-diastolic volumes during exercise showed a highly significant increase after exercise training and hypertrophy. Morphometric measurements showed that mitochondria and cell membranes increased with increasing myocyte growth in all exercise groups, but there was only a partially compensated adaptation of capillary proliferation. Arteriolar number and length increased in all exercise groups. Intrinsic contractility as measured by delta D%, WTh%, or left ventricular dP/dt did not increase with exercise training and in some instances decreased. Therefore, left ventricular adaptation to strenuous exercise in the pig heart is primarily one of changes in left ventricular dimensions and a compensated hypertrophy. Exercise-induced increases in EDD and stroke volume can be accounted for by decreases in peripheral resistance and increased cardiac dimensions.

Acclimatization↗

Association of decreased myocardial beta-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise.

The effects of chronic dynamic exercise on myocardial beta-adrenergic and muscarinic cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan miniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10-19 weeks of treadmill running. Radioligand studies using 125I-iodocyanopindolol (ICYP) and 3H-quinuclidinyl benzilate (QNB) were used to determine the number of beta-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 +/- 5 to 65 +/- 7 ml/kg/min (mean +/- SD; p less than 0.02), maximal workload from 530 +/- 111 to 1,074 +/- 179 KPM/min (p less than 0.01), resting heart rate decreased from 91 +/- 13 to 62 +/- 4 beats/min (p less than 0.01), heart rate at 75% of pretraining maximal workload decreased from 253 +/- 15 to 196 +/- 12 beats/min (p less than 0.01), and maximal exercise heart rate decreased from 273 +/- 6 to 254 +/- 9 beats/min (p less than 0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 +/- 13 to 185 +/- 28 beats/min (p less than 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 +/- 16 to 40 +/- 16 (p less than 0.05). Radioligand studies revealed a decrease in beta-receptor number in the right atrium following chronic exercise (61 +/- 9 vs. 34 +/- 8 fmol/mg; p less than 0.02), but receptor number in membranes from the left ventricle did not change (60 +/- 9 vs. 62 +/- 4 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

The effect of hemodilution with fluorocarbon or dextran on regional myocardial flow and function during acute coronary stenosis in the pig.

The effect of replacement of approximately 50% of the blood volume, in the presence of critical coronary stenosis, was investigated in anesthetized pigs. Two agents were used for replacement: 6% dextran 70 and Fluosol-DA, a fluorocarbon "blood substitute," capable of transporting oxygen by virtue of its high solubility. Critical coronary stenosis of 15-min duration was imposed on the circumflex coronary artery by means of a micrometer snare, before and after an exchange-transfusion with one of the above acellular agents, resulting in comparable reductions of myocardial blood flow (determined by microspheres) to the circumflex zone. In the ischemic zone, systolic wall-thickening (as determined by sonomicrometry) was reduced by 62 +/- 10% in the dextran-diluted pigs, but only by 33 +/- 7% in the Fluosol-diluted pigs (p less than .05). Estimated oxygen delivery-rate in this zone, during coronary constriction, was 6.2 and 7.5 ml min-1 100 g-1, respectively. Electron microscopic examination of the normally perfused zone of the heart showed no morphological change attributable to Fluosol. The findings suggest that, in the presence of critical coronary stenosis, hemodilution by Fluosol-DA can be tolerated, while similar hemodilution with dextran results in aggravation of myocardial hypoxia. In three instances, severe reactions were observed immediately following the administration of Fluosol. These were suggestive of complement-activation and were excluded from the analysis.

Animals↗

Ameroid constriction of the proximal left circumflex coronary artery in swine. A model of limited coronary collateral circulation.

Gradual narrowing and occlusion of a coronary artery in patients with atherosclerotic heart disease frequently causes enlargement of the collateral circulation. Although these vessels may protect from development of myocardial infarction, they frequently do not supply sufficient blood flow to prevent ischemia during periods of augmented myocardial oxygen demand. The purpose of this study was to develop a model of the collateral circulation in pigs, a species that previously has been shown to develop sparse collateral vessels. Eighteen pigs were instrumented with an Ameroid constrictor around the proximal left circumflex artery and left atrial and aortic catheters. In four animals the constrictor was placed just distal to a large proximal obtuse marginal vessel. Seven of the pigs were treated daily with oral aspirin (325 mg) and disopyramide (200 mg) throughout the study; the other 11 served as controls. After an average of 24 days postoperatively, radioactive microspheres were injected at rest, during exercise (mean heart rate = 245 beats/min), and during intravenous infusion of dypridamole (700 micrograms/kg). At autopsy the extent of necrosis was assessed by a point counting technique in the bed at risk. We found that 75-83% of the bed at risk remained viable. Although aspirin and disopyramide did not significantly alter the extent of infarction (37 +/- 36% untreated vs 17 +/- 6% treated), there was less variability of infarction in the treated group, and subendocardial blood flow during exercise was higher in the treated group compared to controls. The majority of infarction occurred in the subendocardial region. Animals with a large obtuse marginal branch developed significantly smaller infarcts (8 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Decreased critical mixed venous oxygen tension and critical oxygen transport during induced hypothermia in pigs.

The effects of hypothermia on oxygen delivery and tolerance to hypoxia were studied in 8 normothermic (36.8 degrees C) and 10 hypothermic (29.3 degrees C) pigs that had been anesthetized and surgically implanted with instruments. Cardiac output (QT), VO2 [oxygen consumption, or QT X C(a-v)O2, where C(a-v)O2 is arteriovenous oxygen content difference], arterial and mixed venous blood gas values, and lactate concentrations were measured as the animals were made progressively hypoxic. Under control, normoxic conditions, mixed venous oxygen tension (PvO2) was 41.4 +/- 2.1 mm Hg (mean +/- SE) in the normothermic animals and 26.1 +/- 1.6 mm Hg in the hypothermic animals; these values are close to those predicted in our previous theoretical analysis. To study tolerance to hypoxia during hypothermia, critical PvO2 and critical total oxygen transport (TOT = QT X CaO2, where CaO2 is oxygen content of arterial blood) were determined by decreasing the inspired oxygen concentration (FIO2) in steps and measuring the point where VO2 and blood lactate levels became PO2 or TOT dependent. Again as predicted, the critical PVO2 was lower in the hypothermic animals (15.5 +/- 1.0 mm Hg at 29.3 degrees C compared with 22.0 +/- 1.4 mm Hg at 36.8 degrees C), but critical venous oxyhemoglobin saturation values were not statistically different at the two temperatures. Critical TOT was also decreased during hypothermia, as was the margin of reserve in both PVO2 and TOT (the difference between the normoxic and the critical values).

Animals↗

Cardiac vasculature and flow during pressure-overload hypertrophy.

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

Animals↗