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Biomedical subjects

F C White

Publications and source records attributed to F C White.

At least 55 records · Page 3Linked to original sources
PubMed1986

Exercise-induced cardiac hypertrophy: a correlation of blood flow and microvasculature.

The effects of exercise conditioning on the myocardium were studied in seven instrumented pigs strenuously exercised for 12 wk by treadmill running. Data were compared with eight instrumented untrained pigs. O2 consumption measured during maximum exercise effort was significantly elevated in the trained pigs (71.7 +/- 4.0 vs. 56.3 +/- 3.0 ml X ml-1 X kg-1). Absolute right and left ventricular mass increased by 20 and 13%, respectively, in response to exercise. Myocyte cross-sectional area increased by 21% in the trained hearts compared with the untrained hearts. Transmural left ventricular myocardial blood flow (ml X min-1 X g-1) was not significantly different at rest, during maximum exercise, or during exercise with adenosine infusion. However, training caused an elevation of the regional epicardial blood flow noted during exercise and exercise with adenosine. In the trained pigs mean aortic pressure during maximum exercise with adenosine infusion was not significantly different compared with untrained pigs. Coronary resistance during exercise with adenosine infusion was the same in both animal groups. In the trained group capillary numerical (no./mm2) and length (mm/mm3) densities were reduced, whereas arteriolar numerical and length densities were significantly increased compared with the untrained group. Measurements of capillary luminal surface density (mm2/mm3) in the trained group were unchanged compared with the untrained group. These results suggest that strenuous exercise does not stimulate the production of new capillaries, but this is modified by the ability of existing capillaries to increase their luminal surface area to parallel increases in myocyte growth. The arteriolar data suggest that exercise promotes the formation of new arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Validation of a respiratory mask for measuring gas exchange in exercising swine.

A respiratory mask was developed for resting and exercising swine. The lightweight, low-dead-space design fits airtight against the animals' snouts to provide breath-by-breath measurements of respiration and metabolism. Validation of the mask was carried out using the Fick principle with dye-dilution cardiac outputs and arterial and mixed venous O2 content measurements. Linear regression analysis of O2 consumption (VO2) measurements by the two techniques revealed a slope of 1.07 and a Y-intercept of -1.06 ml X kg-1 X min-1. The standard error of the estimate of VO2 was 3.5 ml X kg-1 X min-1. The mask design permits rapid measurements of ventilation and metabolism in response to acute and chronic exercise.

Animals↗
PubMed1986

The pig as a model for myocardial ischemia and exercise.

The pig has been well characterized as an appropriate model for the study of coronary physiology, the coronary collateral circulation and exercise physiology. We compared both Yucatan miniature swine and young farm pigs in experiments involving myocardial ischemia, infarction and exercise. The Yucatan pig was vigorous, docile and proved to be an appropriate model of coronary physiology and exercise in man. The exercise capacity of the Yucatan pig was greater than that of the similar weight Hampshire pig, apparently because of the higher hematocrit and larger heart size. Both breeds were able to increase their maximal oxygen consumption (VO2 max) by approximately 25% after 10 weeks of training. Experiments measuring maximal coronary capacity suggest that the vascular capacity was similar to that of man, but less than that of the dog. Acute occlusion of the coronary artery in pigs infarcted most of the tissue of the vascular bed at risk. The collateral circulation of the pig is less than one fourth that of the dog and is similar to that of man. Slow occlusion of the left circumflex coronary artery produces an ischemic vascular bed which is collaterally dependent with only 5% infarction. Collateral flow is sufficient to meet resting conditions, but during exercise, severe ischemia is unmasked. This ischemia is present for up to 16 weeks following occlusion. The observation of limited infarction in conjunction with limited collateral vessel development suggests that this is a good model for investigating the growth and development of coronary collateral circulation in man.

Animals↗
PubMed1984

Decreased systolic wall thickening in myocardium adjacent to ischemic zones in conscious swine during brief coronary artery occlusion.

The purpose of this study was to examine wall thickening in normally perfused myocardium adjacent to acutely ischemic zones. Regional wall thickening (%WT), internal minor axis diameter, and hemodynamics were monitored in nine conscious swine during temporary occlusion of the left circumflex coronary artery (LCCA). Animals were chronically instrumented with ultrasonic dimension gauges for measuring left ventricular (LV) wall thickness and minor axis, catheters in the left atrium and aorta, and a pneumatic occluder around the proximal LCCA. During a 2-minute occlusion of the LCCA, radiolabeled tracer microspheres (10 micron) were injected into the left atrium to determine regional myocardial blood flow (RMBF). Within the ischemic zone, reduction of %WT was related linearly (Y = 24.9 X -4.1, p less than 0.001) to reduced RMBF and endocardial/epicardial blood flow ratio was reduced from 1.30 +/- 0.12 (mean +/- SE) to 0.87 +/- 0.11 (p less than 0.01). In zones adjacent to the ischemic zones RMBF was unchanged by LCCA occlusion. RMBF and %WT were poorly correlated (r = 0.38) and endocardial/epicardial blood flow ratio was unchanged from preocclusion values. Therefore, myocardium adjacent to ischemic zones may have reduced thickening despite no apparent blood flow changes. We conclude that such dysfunction may be due to either mechanical tethering effects or a reduction of global LV function due to the presence of an acutely ischemic zone.

Animals↗
PubMed1984

Effects of exercise on collateral development in myocardial ischemia in pigs.

To study the effects of exercise on collateral development in myocardial ischemia, we induced coronary arterial stenosis of the left circumflex coronary artery (LCCA) in 18 of 30 pigs. During that surgery, we identified the coronary bed at risk. Nine of these pigs were then subjected to 5 mo of exercise training on a treadmill. After exercise training, we determined regional collateral and myocardial blood flow using radiolabeled microspheres. At autopsy, all animals had complete occlusion of the LCCA. Infarct size in the exercise-trained pigs was significantly less than in the sedentary pigs (5.9 +/- 1.0 vs. 11.7 +/- 1.0% of the left ventricle). The exercise-trained animals had a greater increase in collateral flow, 35.1 +/- 3.0 vs. 28.7 +/- 4.1 ml X min-1 X 100 g-1, in the noninfarcted jeopardized zone of the LCCA bed. The major findings of the study were the following: 1) chronic coronary artery stenosis progressing to occlusion stimulated development of the collateral circulation and salvaged tissue in the jeopardized myocardium of an animal model with sparse collaterals; 2) development of the collateral circulation and tissue salvage is increased by exercise training; 3) collaterals develop primarily in or near the ischemic zone; and 4) all collateral beds develop a circumferential flow gradient following occlusion.

Animals↗
PubMed1984

Effects of a calcium-entry blocker (diltiazem) on regional myocardial flow and function during exercise in conscious dogs.

We examined the effects of diltiazem, a calcium-entry blocker, on exercise-induced myocardial ischemia in nine conscious dogs with chronic coronary stenoses. An ameroid constrictor, Doppler flow probe, and hydraulic occluder were placed around the left circumflex coronary artery, and left ventricular pressure was measured (Konigsberg micromanometer). Pairs of ultrasonic crystals were implanted for measuring left ventricular systolic wall thickening (% delta WTh) in control (left ventricular anterior wall) and ischemic (left ventricular posterior wall) regions, and regional myocardial blood flow was measured with the microsphere method. Eighteen days (average) after surgery mean coronary blood flow velocity had decreased and reactive hyperemic flow velocity after 10 sec of coronary occlusion was markedly reduced, but % delta WTh at rest remained normal, indicating collateral development. Control treadmill exercise was performed for 3.7 min (average), and 2 hr later administration of 0.3 mg/kg diltiazem was followed by an identical exercise bout. Control exercise increased % delta WTh in the normal region, while in the ischemic region % delta WTh decreased markedly and ischemia was evident (subendocardial flow, 0.29 +/- 0.12[SD] ml/min/g). After diltiazem hemodynamic and % delta WTh values at rest were not changed; during exercise the heart rate was significantly lower (204 +/- 24 vs 227 +/- 33 beats/min, p less than .01), but values for other hemodynamic measures were similar to those during the control run. % delta WTh in the control region was not changed during exercise after diltiazem, but compared with control exercise in the ischemic zone there was less dysfunction and subendocardial flow was greater. Recovery from exercise-induced dysfunction in the ischemic region occurred within 5 min, compared with over 30 min after control exercise. Thus, in a preparation of chronic coronary stenosis, the calcium-entry blocker improved the relationship between regional myocardial flow and function during exercise and led to more rapid recovery of regional myocardial dysfunction.

Animals↗
PubMed1984

Myocardial characteristics of pressure overload hypertrophy. A structural and functional study.

The effects of pressure overload hypertrophy were studied in the left ventricular myocardium of young adult cats. Hypertrophy was induced by a 90% constriction of the ascending aorta, and animals were studied 4, 7, 30, 120, and 248 days after constriction. Cardiac hypertrophy, as determined by heart weight, was evident at each experimental time period. Ultrastructural data indicate that during the early stages of hypertrophy (4 and 7 days) there is an enhancement of the myofibrillar volume relative to the mitochondrial volume. After 30 days the normal balance between the myofibrillar and mitochondrial volumes has been reestablished. The later stages of hypertrophy (120 and 248 days) are characterized by a reduced mitochondrial volume relative to the myofibrillar volume. This late stage of hypertrophy (248 days) is also characterized by reduced surface densities of the T-tubular and diadic junctional systems. Analysis of the microvasculature indicated that capillary density decreased with increasing time of hypertrophy. The effects of chronic hypertrophy on myocardial blood flow were also measured. In hypertrophied hearts, coronary reserve, measured as the percentage increase in blood flow from control to near maximal flow during adenosine infusion, was reduced. Left ventricular minimal coronary resistance (per gram) was elevated during hypertrophy. These results indicate that the alterations in flow reserve are largely due to the reduced capillary density. This, combined with the inability of the myocardium at the cellular level to maintain normal structural parameters, may play an important role in the transition of a compensated heart to a failing heart.

Animals↗
PubMed1983

The physiologic effects of oxygen transport by hemoglobin solutions.

Two chronic animal models and one acute animal model were used to evaluate exchange transfusion with stroma-free hemoglobin solutions. A direct comparison was made between stroma-free hemoglobin solutions having differing oxygen offloading characteristics as well as a colloid solution consisting of 7% bovine albumin. These studies involved a partial exchange involving approximately 50% of the animal's blood volume to simulate a clinically more appropriate partial blood replacement situation. We noted a consistent increase in the arterial oxygen content of animals exchanged with the stroma-free hemoglobin solutions and some modest improvement in oxygen dynamics. Our studies examining myocardial contractility, especially those carried out in the right heart bypass swine preparation failed to substantiate any difference between an exchange with albumin or stroma-free hemoglobin solutions. The conscious animal models examined both at rest and at exercise demonstrated marked differences in exercise response. Animals exchanged transfused with stroma-free hemoglobin solutions often had an almost normal exercise response while those animals exchanged with non-oxygen carrying albumin solution frequently failed to exercise on a treadmill. Blood flow measurements using radiolabeled microspheres were performed in chronically instrumented swine. These animals had a normal variation in organ blood flow during exercise which was noted both during the control period as well as following exchange with stroma-free hemoglobin solutions. Animals exchanged transfused with albumin had a marked derangement in organ blood flow apparently reflecting the decreased oxygen availability. Results from these three studies substantiate a significant benefit to animals undergoing a 50% exchange when that exchange is done with an oxygen carrying solution such as stroma-free hemoglobin solutions as opposed to a non-oxygen carrying but oncotically active solution such as albumin solution. These studies seem to offer encouragement to the continued investigation and ultimate clinical utilization of hemoglobin solutions as an appropriate blood substitute.

Animals↗
PubMed1982

Effect of acute exercise stress in cardiac hypertrophy. II. Quantitative ultrastructural changes in the myocardial cell.

Stereological techniques were used to determine quantitatively the changes in subcellular organelles in the hypertrophied swine heart. Hypertrophy was induced by aortic stenosis. In addition, the animals were stressed by exercising twice weekly on the treadmill for 30 days. The controls were normal animals which were neither exercised nor had aortic stenosis. Tissue samples from the left ventricle and interventricular septum were processed for electron microscopy. Relative volumes of myofibrils, mitochondria, transverse tubular system (T-system) sarcoplasmic reticulum (SR), and clear intracellular space (ICS) were measured. Significant differences in the volumes of all the components except the T-system were found between experimental and control animals in the epicardial and endocardial regions of the left ventricle and interventricular septum. Mitochondria and myofibrils were significantly decreased in the exercise stressed hypertrophied hearts as reported in ischemia, while SR and ICS were significantly increased. These findings suggest that ischemic injury occurs in all regions of the hypertrophied heart wall subjected to acute exercise stress, not solely the endocardial region as previous qualitative studies suggested.

Animals↗
PubMed1982

Comparative physiological responses to exercise stress.

We determined the effect of exhaustive exercise on the acid-base balance, O2 consumption, and cardiac output in dogs and pigs to examine which species was comparable with humans in its physiological response to exercise. We ran 11 dogs and 11 pigs on a motor-driven treadmill at steady-state (heart rate 75% maximum) and exhaustive (maximum heart rate) exercise levels. Measuring heart rate, cardiac output, and aortic pressure via implanted probes we obtained arterial and venous blood samples before, during, and after exercise to determine hematocrit, blood gas tensions, pH, and lactic acid levels. Dogs had a twofold greater work capacity than the pigs, but the dogs could not run at maximal heart rate as long as the pigs did. Although O2 consumption correlated well with cardiac output and total work in both species, dogs were capable of a greater range of values. The acid-base studies showed that exhaustive exercise in the pigs resulted in a severe metabolic acidosis, whereas this did not occur in dogs. Respiratory alkalosis was noted in dogs. This suggested that the supply of O2 to the working muscles of the pig was insufficient to maintain aerobic metabolism. The pigs' responses to exercise conformed to those found by others in the human, suggesting that the pig is a more appropriate model for some exercise studies.

Acid-Base Equilibrium↗
PubMed1981

Histologic, ultrastructural, and enzymatic measurements of infarct size following coronary artery stenosis and occlusion.

Coronary artery narrowing (CAN), which reduced resting coronary blood flow (BF) by 50%, was induced in 10 conscious dogs and was maintained for 4 hours. Five additional dogs (group 1) with complete coronary artery occlusion were compared to the dogs with CAN. Serum isoenzymes of creatine phosphokinase (CK) and lactate dehydrogenase (LD) were monitored hourly in all groups. After 36 hours, samples were obtained for regional myocardial BF, quantitative histology, and quantitative ultrastructural (EM) morphology. Six dogs with CAN had small infarcts (MI) of less than 1 gm and persistent myocardial cell injury (group 2). The other four dogs with CAN has only persistent myocardial cell injury by ultrastructural criteria (group 3). Peak serum CK activities in groups 2 and 3 were similar, as well MI sizes calculated from serum CK and myocardial depletion. MB CK was of diagnostic value in group 1 but not in groups 2 and 3. The ratio of LD 1/LD 2 had diagnostic value in all three groups. MI size by enzyme estimates was consistently higher than planimetered MI size at autopsy in both groups 1 and 2. All three groups had significant amounts of ultrastructural damage outside of histologically demonstrated. MI. These findings suggest that (1) gross and histologic MI size determination of 36 hours after ischemia underestimate extent of damage, and (2) ultrastructural cell changes cause significant release of CK and LD in coronary disease (CAD).

Animals↗
PubMed1981

Effects of experimental volume-overload hypertrophy on myocardial blood flow and cardiac function.

To examine the effects of volume-overload hypertrophy on regional myocardial perfusion, we determined myocardial blood flows with microspheres at rest, during exercise, and during exercise with adenosine infusion in dogs with aortocaval fistulas for 12 wk (group 2) and sham-operated controls (group 1). A subgroup of six animals (group 3) was studied both before and after shunt closure in order to separate the influences of hypertrophy from the hemodynamic effects of the fistula. Epicardial blood flows in animals with patent fistulas were significantly greater than in controls under all conditions (P less than 0.05). However, endocardial blood flows were lower at maximal exercise and with adenosine, so that the endocardial-to-epicardial blood flow ratios were reduced 36 and 28%, respectively(P less than 0.05). These flow abnormalities were reversed by closing the fistula prior to regression of hypertrophy. Moreover, coronary resistance per unit of myocardium was not different for the three groups. These results suggest that the blood-flow abnormalities seen in the exercising dog with an aortocaval fistula are secondary to hemodynamic considerations and not to hypertrophy itself. Low aortic diastolic pressures and high myocardial oxygen demands during exercise may combine to produce subendocardial hypoperfusion in this model.

Animals↗
PubMed1981

Correlation of regional myocardial blood flow and function with myocardial infarct size during acute myocardial ischemia in the conscious pig.

Regional myocardial function and blood flow were determined for 48 hours after permanent occlusion of the left circumflex coronary artery in conscious swine. Systolic wall thickening and end-diastolic wall thickness (EDWTh) were correlated with regional myocardial flow (RMBF) at 15 minutes, 24 and 48 hours after occlusion. Both regional function and blood flow were compared with the extent of myocardial necrosis (determined histologically) after 48 hours in functionally distinct zones. Group 1 (control zones) was characterized by increased systolic wall thickening, EDWTh, RMBF and had no necrosis. Group 2 (marginal zones) had depressed systolic wall thickening (35 +/- 3% [mean +/ SEM] of preocclusion level at 48 hours) and RMBF (64 +/- 6% of preocclusion values), transiently decreased EDWTh and 46 +/- 5% necrosis. In Group 3 (ischemic zones), all values were greatly reduced: systolic wall thickening was 3.6 +/- 1.2%, EDWTh 76 +/- 8% and RMBF 25 +/- 9% preocclusion values; necrosis was 90 +/- 5%. Groups 2 and 3 had increased RMBF at 24 and 48 hours from that at 15 minutes after occlusion; however, in neither case was systolic wall thickening greater than that at 15 minutes after occlusion. We conclude that there is close correlation between RMBF, systolic wall thickening and the extent of necrosis present after 48 hours of coronary artery occlusion in the conscious swine; subsequent increases in RMBF to the marginal zone after occlusion are not accompanied by improved regional function.

Animals↗
PubMed1981

Myocardial morphometric characteristics in swine.

We have quantified the ultrastructure of myocardial cells in tissue samples obtained from six adult normal Yucatan swine. Tissue samples were obtained from 20 different sites in the left ventricle, right ventricle, and interventricular septum. The samples were processed for electron microscopy and quantitative morphometric analysis. The percent relative volumes of myofibrils, mitochondria, transverse tubular system, sarcoplasmic reticulum, and clear intracellular space were determined using stereological morphometric methods. Overall, the data were distributed homogeneously among the 20 individual sites. However, when certain subcellular components were examined regionally, some differences appeared. The mitochondrial:myofibril volume ratios were significantly increased in the left ventricle and interventricular septum compared to the right ventricle. They also were greater in the endocardial region compared to the epicardium, which is consistent with higher metabolic activity of these zones. Similarly, the sarcoplasmic reticulum:myofibril ratio was greater in the endocardial region vs. the epicardial region and the basal layer compared to the mid-layer, suggesting the greater need for provision of calcium ions in these particular zones. Since the swine is a convenient large animal for physiological studies, the results indicate that swine can also be used for quantitative morphometric measurements of myocardial changes in normal and pathologic hearts, and for the study of regional changes in various layers and regions of heart walls.

Animals↗
PubMed1981

The effect of prolonged physical training on the properties of long bone: a study of Wolff's Law.

UNLABELLED: Five one-year-old immature swine were subjected to twelve months of exercise training. Four matched swine with no training served as controls. After they were killed, four-millimeter-wide strips of bone taken from the anterior, medial, posterior, and lateral quadrants of the central femoral diaphysis were subjected to four-point bending tests to failure. It was found that although exercise did not change the mechanical properties of the cortical bone, it resulted in significant increases in the averaged femoral cross-sectional properties: 17 per cent in cortical thickness, 23 per cent in cortical cross-sectional area, and 21 per cent and 27 per cent in maximum and minimum area moments of inertia, respectively. These changes were due primarily to reduction in the diameter of the medullary canal. The analyses of bone composition showed that the bone density and biochemical contents of the control and exercised animals were similar, but the total volume and the dry, ash, and calcium weights of the exercised bone were significantly higher. These combined results suggest that prolonged exercise has a significant effect on the quantity of the bone, but not on its quality. CLINICAL RELEVANCE: It has long been recognized that stress deprivation from immobilization in plaster casts results in profound bone atrophy, and it is generally accepted that a minimum level of activity is necessary for homeostasis of bone. These results show that exercise at a level comparable to that prescribed in running fitness programs for humans (65 to 80 per cent of maximum heart rate) can not only maintain homeostasis, but produce actual hypertrophy of bone. This work further suggests the importance of graduated, prolonged, supervised rehabilitation programs in overcoming osteoporotic states.

Animals↗
PubMed1979

Redistribution of pulmonary blood flow in the dog with PEEP ventilation.

The effects of positive end-expiratory pressure (PEEP) at 20 cmH2O on the distribution of pulmonary blood flow was studied in intact dogs and isolated lung preparations. Measurements were made of a) the continuous distribution of ventilation-perfusion ratios (VA/Q), b) the vertical distribution of pulmonary blood flow, and c) the dimensions of the microvasculature. Without PEEP the distributions of ventilation and perfusion were unimodal and centered on a VA/Q close to one. Dependent regions received 5-10 times more of cardiac output than uppermost regions. With PEEP the distribution showed a bimodal character, one mode of normal VA/Q and the other comprising one-third of ventilation, lying between VA/Q of 10 and 100. Cardiac output was reduced two- to threefold and blood flow in the uppermost regions was grossly reduced but not eliminated. Bimodal distributions were also found in isolated lungs with PEEP, and histological examination of rapidly frozen lung tissue showed that alveolar capillaries were closed in the uppermost, poorly perfused regions, whereas alveolar corner vessels remained open. We suggest that the blood flow through these corner vessels is responsible for the additional, high VA/Q mode during PEEP.

Animals↗
PubMed1979

Spatial distribution of pulmonary blood flow in the dog with PEEP ventilation.

The effects of mechanical ventilation without and with a positive end-expiratory pressure (PEEP) of 20 cmH2O and, after hemorrhage, on the spatial distribution of lobar lung blood flow were studied by means of iv injections of radioactive microspheres in supine dogs. The lungs were excised and dried at an inflation pressure of 30 cmH2O. Each lobe was cut into slices. In five slices from each lobe, 30--60 samples were punched out. The activity was measured in a gamma counter. By this means distribution of lobar blood flow could be described three-dimensionally. In dogs awake and spontaneously breathing or anesthetized and mechanically ventilated, blood flow distribution was rather even, except for a vertical gradient. PEEP caused a) a two- to threefold reduction in total lung blood flow, b) a redistribution from the right to the left lung, and c) a redistribution from the core to the periphery of the lung. This pattern of redistribution could not be reproduced by reducing cardiac output by hemorrhage during mechanical ventilation without PEEP.

Animals↗