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Biomedical subjects

D G Penney

Publications and source records attributed to D G Penney.

At least 55 records · Page 3Linked to original sources
PubMed1988

The effects of carbon monoxide on persistent changes in young rat heart: cardiomegaly, tachycardia and altered DNA content.

Newborn rat pups that inhale 500 ppm carbon monoxide (CO) for 32 days and develop increased heart mass (i.e. cardiomegaly) show persistent cardiomegaly and elevated resting heart rate as adults. Studies were carried out to explore the relationship of these phenomena to CO concentration and initial cardiomegaly using exposures of 350, 500 and 700 ppm CO. Initial cardiomegaly was greater in the right ventricle free wall (RV) than in the left ventricle plus interventricular septum (LV + S) at all three CO concentrations, and RV mass excess increased with CO concentration. Initial RV cardiomegaly was greater at 350 and 700 ppm CO in females than in males. Persistent cardiomegaly in the RV also increased with CO concentration, and was significantly greater in the females. Persistent cardiomegaly in the RV increased with initial cardiomegaly but at a decreasing rate at the higher CO concentrations, and when expressed as a percentage of initial cardiomegaly (i.e. 'efficiency'), the relative response was greatest at 500 ppm CO. For LV + S, efficiency of development of persistent cardiomegaly was greatest at 350 ppm CO. Persistent tachycardia increased with CO concentration in males but failed to do so in females, and was only weakly correlated with degree of persistent cardiomegaly. Thus, persistent cardiomegaly and persistent tachycardia (in males) are related to CO concentration. Myocardial DNA content of 32-day-old juveniles was significantly increased at 350 and 700 ppm CO. Adult DNA content of the RV was significantly elevated at 350 ppm CO (females) and continued to rise with CO concentration. DNA concentrations of the RV and LV were increased at 700 ppm CO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Time course of blood volume change with carbon monoxide inhalation and its contribution to the overall cardiovascular response.

Adult male Sprague-Dawley rats inhaled 500 ppm CO continuously for 42 days in order to examine the blood volume response in a time course manner. Plasma volume as measured by Evan's blue dye dilution technique did not change significantly from the control value of 3.96% of body weight (BW). Total blood volume estimated using plasma volume and hematocrit increased steadily from 7.34% of BW to 11.69%, almost entirely as the result of a more than 2-fold increase in erythrocyte mass (3.42% increased to 7.55%). Absolute blood volume increased from 28.51 ml to 58.26 ml; normal growth contributed to this increase, i.e. BW increased from 350.0 g to 499.1 g. "Real hematocrit" determined by dye dilution increased from 46.5% to 64.6%, reaching a near-equilibrium level within 15 days. Hemoglobin concentration increased from 13.68 g/dl to 20.07 g/dl, and erythrocyte count increased from 6,150,000 per cubic mm to 9,140,000 per cubic mm. Minor changes in erythrocyte indices (i.e. mean corpuscular hemoglobin concentration and mean corpuscular volume) occurred during the 42 days. Concurrently, the weight of right ventricle increased more than left ventricle + septum, reflecting somewhat greater right-sided cardiomegaly. Increases in both ventricles were correlated with changes in blood volume and hematocrit. Plasma atrial natriuretic peptide activity increased 2.5 fold after 15 and 30 days of CO exposure, possibly reflecting increasing atrial stretch caused by increased blood volume. Like the polycythemic hypervolemic state of chronic hypoxic hypoxia, blood volume in CO hypoxia increases solely through addition of erythrocytes.

Animals↗
PubMed1988

Hyperglycemia exacerbates brain damage in acute severe carbon monoxide poisoning.

It is hypothesized that hyperglycemia naturally induced by stress and/or produced by intravenous trauma therapy adversely effects neurologic outcome following acute severe carbon monoxide poisoning, and the higher the blood glucose the greater the degree of brain dysfunction. Increased availability of glucose presumably increases cerebral glycolytic flux, and elevates intracellular and interstitial lactate level, which in turn induces acidosis and edema, resulting in brain damage. In a retrospective study of blood glucose and other data obtained from patients upon hospital admission for CO poisoning, a mean value of 409 mg/dL was associated with "brain death", a value of 215 mg/dL with "minimal to substantial brain damage," and a value of 165 mg/dL with "normal" recovery.

Blood Glucose↗
PubMed1988

Hemodynamic response to carbon monoxide.

Historically, and at present, carbon monoxide is a major gaseous poison responsible for widespread morbidity and mortality. From threshold to maximal nonlethal levels, a variety of cardiovascular changes occur, both immediately and in the long term, whose homeostatic function it is to renormalize tissue oxygen delivery. However, notwithstanding numerous studies over the past century, the literature remains equivocal regarding the hemodynamic responses in animals and humans, although CO hypoxia is clearly different in several respects from hypoxic hypoxia. Factors complicating interpretation of experimental findings include species, CO dose level and rate, route of CO delivery, duration, level of exertion, state of consciousness, and anesthetic agent used. For example, tachycardia is commonly observed, although bradycardia also can result from myocardial and/or central nervous system (CNS) hypoxemia at high carboxyhemoglobin (COHb) saturations, as can electrocardiographic abnormalities. Augmented cardiac output usually observed with moderate COHb may be compromised in more severe poisoning for the same reasons, such that regional or global ischemia result. The hypotension usually seen in most animal studies is thought to be a primary cause of CNS damage resulting from acute CO poisoning, yet the exact mechanism(s) remains unproven in both animals and humans, as does the way in which CO produces hypotension. This review briefly summarizes the literature relevant to the short- and long-term hemodynamic responses reported in animals and humans. It concludes by presenting an overview using data from a single species in which the most complete work has been done to date.

Animals↗
PubMed1987

Frogs and turtles: different ectotherm overwintering strategies.

The ability of frogs and turtles to overwinter and to survive hypoxia and anoxia has long been a topic of interest. While data remains scant, the emerging picture shows fundamentally different approaches to overwintering in these two groups of ectotherms. Frogs are far more limited by availability of oxygen than are turtles, even at near-freezing ambient temperatures. The reasons for this probably involve the vastly greater cutaneous permeability of the former. With their extreme tolerance of anoxia and profound suppression of metabolism, overwintering in turtles should not be viewed as simply prolonged diving but rather as ectotherm hibernation. Their incredible diving capabilities are merely a spin-off of a successful overwintering strategy. The following discussion reviews the major physiological mechanisms involved in the overwintering strategies of these two ectotherm groups.

Acclimatization↗
PubMed1987

Carboxyhemoglobinemia, polycythemia, cardiomegaly, and cardiovascular function in the anesthetized rat.

The effects of carbon monoxide (CO), polycythemia (PC), and cardiomegaly (CM) on cardiovascular function were investigated in adult rats in which the latter two conditions were induced by 500 ppm CO inhalation for 5-6 weeks. Using an anesthetized open-chest preparation, these rats were compared with normal rats. With CO + PC + CM present, resting cardiac index, stroke index, stroke work, and minute work were elevated (heart rate also in the conscious state), while left ventricle end-diastolic pressure (LVDP) was normal. With PC + CM after CO washout, cardiac index and stroke index returned to normal at normal LVDP. Minute work, peripheral resistance, heart rate, and blood pressure, however, remained above normal. With CM alone, minute work, +dP/dtmax, +dF/dtmax, peripheral resistance, blood pressure, and LVDP declined from the condition with PC + CM. Although most cardiovascular parameters increased in the three conditions above with acutely increased LVDP, only with CM alone was performance augmentation normal. The results (i) reveal several characteristics of the hemodynamic response to chronic carboxyhemoglobinemia, (ii) suggest that the transient hypertension attending CO elimination in the presence of PC results from rapid reversal of peripheral vasodilatation, (iii) demonstrate decreased cardiac functional reserve with CO and (or) polycythemia upon preload challenge, and (iv) provide evidence for the benign nature of CO-induced cardiomegaly alone, on heart function.

Anesthesia↗
PubMed1987

Effect of litter size (i.e. nutrition) on carbon monoxide-induced persistent heart changes.

It was hypothesized that manipulation of litter size, thus nutrition, which has been shown to alter the neonatal response to cardiovascular stress (i.e. carbon monoxide) might also alter persistent post-stress changes. Rat pups reared in litters of 4 and 16 inhaled 500 ppm CO for 32 days ("CO"), or served as controls ("AIR"). Some pups were killed at 14-15 days of age to assess initial cardiomegaly. As adults, right ventricle (RV) mass was greater in CO/4 males (123 days of age) and females (113 days of age) than in same sex CO/16 rats. Persistent RV cardiomegaly was present in CO/4 males and females compared to AIR's of the same litter size and sex, whereas this was the case only in females comparing CO/16 and AIR/16 rats. RV mass was significantly larger in AIR/4 males than in AIR/16 males. Plots of initial cardiomegaly (both ventricles) versus persistent cardiomegaly (RV) for large and small litters produced similar slopes for the two sexes, with females lying above males. Resting heart rate, monitored in males (66-121 days of age) and females (81-109 days of age), was increased by small litter size, and also by CO, particularly in the males. Resting heart rate was significantly correlated with RV weight. RV DNA content and concentration were increased by small litter size in the males, and concentration also by CO. The male CO/4 rats had the highest DNA content and concentration. In the females, DNA content was increased by small litter size and was greatest in the CO/4 group. Thus, the effects of small litter size have lasting effects: i.e. augmented persistent cardiomegaly, persistent tachycardia, and myocardial DNA content and concentration.

Aging↗
PubMed1986

Cardiomegaly due to myocyte hyperplasia in perinatal rats exposed to 200 ppm carbon monoxide.

Exposure to carbon monoxide (CO) during the fetal and neonatal period was used to evaluate cardiac ventricular regional weight and myocyte growth response to an increased hemodynamic load. Date-mated Sprague-Dawley rats inhaled 200 ppm CO from day 7 of pregnancy until parturition; another group of pregnant rats inhaled room air. At birth, pups from these two groups were subdivided into four groups: (1) control group (AIR/AIR), that was maintained in room air in utero and post-partum; (2) AIR/CO group, which received CO only after birth; (3) CO/CO group, which received CO exposure in utero and post-partum; and (4) CO/AIR group, which received CO exposure in utero but was maintained in room air post-partum. Rats were removed from litters at selected intervals from birth to 28 days of age and used to determine regional ventricular weights and ventricular dry weights, and to obtain isolated myocyte preparations for measurement of cell size characteristics and allow calculation of cell numbers. Compared with AIR raised control animals, right ventricular weight was increased in animals exposed to CO during the fetal period. Post-natal CO exposure caused an increase in left ventricular weight. Heart weight to body weight ratio of animals exposed to CO post-natally only (AIR/CO) gradually increased to reach that of the CO/CO group by 12 days of age, while animals exposed to AIR post-natally following fetal CO exposure gradually decreased their heart weight to body weight ratio toward that of the control animals by 28 days of age. Binucleated cells first appeared at 4 days of age in all groups. Myocyte volume was similar in both groups at birth and increased from six through 28 days of age. Left ventricle plus septum and right ventricle cell volumes of the CO/CO group were smaller than the controls at 28 days of age in spite of heavier wet and dry weights in the CO-exposed rats. At birth, the CO-exposed animals had more myocytes in the RV compared to AIR-exposed controls. Carbon monoxide exposure after birth resulted in left ventricular myocyte hyperplasia. The results of this study indicate that increased hemodynamic load due to CO exposure during the fetal period results in cardiomegaly because of increased myocyte hyperplasia. This cellular response is sustained through the early neonatal period in animals exposed to CO both in utero and post-partum.

Aging↗
PubMed1985

Cardiomegaly and haemodynamics in rats with a transplantable growth hormone-secreting tumour.

To investigate cardiovascular changes in experimental acromegaly, a growth hormone-secreting tumour (MtT-W-15) was implanted in adult female rats. Somatic and tumour growth occurred steadily during the 8 week study period, as did an increase in serum growth hormone titre. Weight of left ventricle and right ventricle increased directly with tumour growth, both on an absolute basis and when compared with normal rats of equal body weight. Atrial weight also increased substantially. Haematocrit declined sharply at first, and more slowly later with increasing tumour weight. Haemodynamic measurements were made on these animals at two stages of tumour growth using an anaesthetised open-chest preparation. Cardiac index (per g body wt), stroke index, stroke work, left ventricle +dP/dtmax, and dF/dtmax of aortic flow were greatly elevated in rats with the largest tumours (longer duration), and to a lesser extent in those with smaller tumours (shorter duration). Systemic peripheral resistance and heart rate were depressed. Ventricular weight increased non-linearly with increases in cardiac index. Cardiac output, stroke volume, stroke work and dF/dtmax normalised per g left ventricle weight were also elevated. Splenomegaly accompanied tumour growth; however, splenectomy of tumour-bearing animals failed to prevent development of anaemia and cardiomegaly. While a direct effect of elevated growth hormone provides the best explanation for development of cardiomegaly in this model, volume work overloading due to anaemia and water retention may be a contributory cause.

Acromegaly↗
PubMed1985

Effects of thyroid and growth hormone deficiency, and food restriction on heart mass, with and without added stress (carboxyhemoglobinemia).

The roles of thyroid and growth hormone, and food restriction in maintenance of heart mass and in carbon monoxide-stimulated cardiac growth were examined. First, thyroidectomized and normal adult male rats inhaled up to 500 ppm CO in air for 42 days. Combined ventricular weights of thyroidectomized rats inhaling CO and air were 12 and 23% smaller than predicted, respectively, while the combined ventricular weight of normal rats inhaling CO was 29% larger than predicted. Thyroidectomy increased the mass of the left ventricle relative to the right ventricle; this was reversed by CO treatment. While the hematocrit increased in thyroidectomized-CO rats, it was lower than in normal-CO rats: likewise the hematocrit of thyroidectomized-AIR rats was lower than that of normal rats in air. Body weights of the thyroidectomized rats were 57% that of normals. As additional controls, two groups of normal rats (one AIR, one CO) were maintained at the same body weight as the thyroidectomized rats, by adjusting food intake. Combined ventricular weight was less than predicted in AIR rats and failed to increase in CO animals, while hematocrits were the same as normals in air and in CO. Serum thyroxine (T4) and growth hormone levels assayed in thyroidectomized rats were less than 15 and 25% of normal rats, respectively. Growth hormone levels were not altered by CO inhalation in thyroidectomized and in normal rats. Levels of both hormones were normal in food-restricted rats. While thyroidectomy produced cardiac atrophy, cardiac growth was stimulated by CO inhalation, although heart mass then only approached that of normals in air. Food restriction also produced cardiac atrophy, but CO inhalation failed to stimulate heart growth.

Animals↗
PubMed1984

Cardiac compliance and dimensions in carbon monoxide-induced cardiomegaly.

Adult male rats inhaled 500 ppm CO continuously for 38 to 47 days to produce significant cardiomegaly. In a first experiment in which heart wall stiffness was examined, haematocrit rose 45.1% and the ratio of the sum of right ventricle (RV) and left ventricle (LV) to body weight (mg X g-1) increased from 2.69 to 3.34. Compliance (ml X mmHg-1) of CO LV's and RV's studied from 0 to 25 mmHg intraluminal pressure, was generally greater than that of LV's and RV's from controls at the same pressure. These differences were greater for RV's. There was no difference between control RV's and LV's at the same distending pressure. The differences between treated and control groups disappeared when compliance was normalised per g heart weight. In a second experiment in which heart dimensions were examined, haematocrit ratio increased 48.6% and 2V (RV + LV) to body weight ratio (mg X g-1) increased from 2.77 to 3.45. Atrial weight was also greater. LV apex to base length increased 6.4% and LV outside diameter increased 7.3. No significant differences in LV, RV or interventricular septum (S) thickness resulted from CO exposure, as measured at three sites in each, in four cross-sections of the heart between the apex and base. In general, LV wall was slightly thicker than S, while RV was about 35% that of LV. The findings suggest that chronic carboxyhaemoglobinaemia produces largely eccentric cardiomegaly, and that there is no intrinsic change in wall stiffness.

Animals↗
PubMed1984

Persistent cardiomegaly induced by carbon monoxide and associated tachycardia.

To explore the effect of persistent cardiomegaly on cardiovascular function, groups of newborn rats inhaled up to 500 ppm CO for 33 days, after which development continued in ambient air. In the first two experiments hemodynamics were assessed by use of an anesthetized open-chest preparation; in the third experiment heart rate (HR) and arterial systolic blood pressure (BP) were monitored by auscultation in the conscious state. In all three experiments weights of left ventricle (LV) plus interventricular septum (S), both ventricles (2V), and right ventricle (RV) were significantly greater by prediction on the basis of body weight (BW) than for normal rats at 87-97, 166-176, and 337-339 days of age in females and 98-108, 177-183, and 337-339 days of age in males. 2V/BW ratio was significantly greater than littermate controls in all six instances. In all but one case (male, 177-183 days) the RV/(LV+S) weight ratios were significantly greater than the respective control groups. In experiments 1 and 2 unconscious HR was significantly elevated in females at 87-97 days and in males at 98-108 and 177-183 days. The first derivative of LV pressure rise was also increased. There was no significant change in BP or other hemodynamic parameters. In experiment 3 awake HR was elevated above controls in previously CO-treated males and females at six monitoring points between 78 and 200 days, whereas BP was not altered. BW of previously CO-exposed males was depressed and returned to normal only after 290 days. A similar decrement in BW was not seen in females. Neonatal CO inhalation and cardiomegaly causes persistent cardiomegaly and tachycardia, lasting a significant fraction of the maximal life span of the rat in both sexes.

Animals↗
PubMed1984

Growth of the young heart: influence of nutrition and stress.

Newborn rat pups reared in litters of 4 and 16 inhaled up to 500 ppm carbon monoxide for 14 days, while others in litters of equal size remained in room air. Body weight, combined ventricle weight, hemoglobin concentration, hematocrit, and myocardial DNA content were measured. Differences in hemoglobin concentration and hematocrit between the four groups of pups were small. Cardiomegaly resulting from CO-stress was intensified in pups from small, as opposed to large litters. Relative combined ventricle weight was unaltered by change in litter size in the absence of CO-stress, although combined ventricle weight and body weight were increased with small litter size. Ventricular DNA content, indicative of cellularity, was increased in small litters and with CO-stress. Exacerbated postnatal anemia is not responsible for the differential effects of litter size and stress on the heart.

Animal Nutritional Physiological Phenomena↗
PubMed1983

Cardiac response of the fetal rat to carbon monoxide exposure.

Groups of pregnant rats were exposed to 200, 166, and 157 ppm CO for the last 17 out of 22 days of gestation. The number of fetuses per dam or live young per litter were unaffected. Neonatal red blood cell count was depressed, whereas mean corpuscular hemoglobin and volume were elevated. Birth weight was reduced; heart weight, heart weight-to-body weight ratio, placental weight, and placental weight-to-body weight ratio were elevated. Identical results were obtained in studies of fetuses examined daily during the final 4 days of gestation at 200 ppm. Cardiomegaly present at birth was not due to elevated myocardial water content, as dry heart weight and wet heart weight increased proportionately. Heart DNA content (microgram) was increased at both 157 and 200 ppm CO in neonates and fetuses, whereas DNA concentration (microgram/mg dry wt) was similar to the controls. Cardiac hydroxyproline concentration (microgram/mg dry wt) and content (microgram) were unaffected in neonates by fetal CO exposure at 157 and 200 ppm, although the hydroxyproline content was elevated in fetuses at 157 ppm CO. Cardiac lactate dehydrogenase (LDH) M subunit composition was elevated from 4 days before birth, until birth, at 200 ppm CO, whereas total LDH activity was unchanged. Although neonatal myocardial cytochrome c was unaltered by fetal CO exposure, myoglobin concentration (mg/g) and content (mg) were elevated. Prolonged maternal CO inhalation thus exerts significant effects on fetal body and placental weight, heart weight, enzyme constituents, and composition.

Animals↗
PubMed1983

Hemodynamic responses to acute carboxyhemoglobinemia in the rat.

The effects of carbon monoxide on the hemodynamics of the adult rat were investigated. A number of parameters were measured using an open-chest, chloralose-urethan anesthetized preparation. Our experiments showed this anesthetic agent to have several advantages over pentobarbital sodium. One group inhaled 150 ppm CO for 0.5-2 h, carboxyhemoglobin (HbCO) reaching 16%. Heart rate, cardiac output, cardiac index, dF/dtmax (aortic), and stroke volume rose significantly; mean arterial pressure, total peripheral resistance, and left ventricular systolic pressure fell, whereas stroke work, left ventricular dP/dtmax, and stroke power changed little. These effects were evident at a HbCO saturation as low as 7.5% (0.5 h). A second group inhaled 500 ppm CO for 5-48 h, HbCO reaching 35-38%. The same parameters changed in the same direction as in the first group, with mean arterial pressure and peripheral resistance remaining depressed, while heart rate, cardiac output, cardiac index, and stroke volume remained elevated. Heart rate and arterial systolic pressure were also monitored in conscious rats; rats in one group inhaled 500 ppm CO for 24 h, and rats in a second group were injected with a bubble of pure CO ip. In both cases heart rate was sharply elevated and blood pressure depressed as HbCO saturation increased. Both parameters recovered on CO washout. There was no significant difference between the response to inhaled vs. injected CO.

Animals↗
PubMed1982

Postnatal carbon monoxide exposure: immediate and lasting effects in the rat.

Groups of newborn rats inhaled 500 ppm CO for 32 days, after which they continued development in ambient air. The ratio of heart weight to body weight increased sharply after birth, peaked at 14 days of age, and then fell progressively but remained above that of normal rats at 68 and 107 days of age. At 14 days of age, the weight of the left ventricle plus interventricular septum (LV + S) exceeded the controls by 80%, whereas the weight of the right ventricle (RV) was 100% greater. RV weight remained significantly greater than that of the controls at 68, 107, and 217 days of age. The ratio of RV weight to LV + S weight remained higher than that of the controls both during and after CO exposure. Myocardial deoxyribonucleic acid (DNA) concentration (microgram/mg dry wt) declined more rapidly in the CO-exposed groups during the first 2 wk. DNA content (microgram/LV + S + RV) was not significantly different. There were no differences in DNA concentration or content after CO exposure. Hydroxyproline, used as an index of collagen content, was unaffected by postnatal cardiomegaly. Hydroxyproline concentration was depressed only during the first 3 wk. Cardiac cytochrome c concentration was depressed and lactate dehydrogenase M subunit composition elevated only during CO exposure. Neither lactate dehydrogenase specific activity nor myoglobin concentration was altered during or after CO treatment. Neither the DNA nor hydroxyproline data provide an explanation for "persistent cardiomegaly."

Animals↗
PubMed1982

A study of free lung cells from young rats chronically exposed to carbon monoxide from birth.

Carbon monoxide (CO) is a well know constituent of cigarette smoke and automobile exhaust. The purpose of this study was to determine the effect of CO on the first line of lung defense, the alveolar macrophage (AM). Free lung cells were obtained by bronchoalveolar lavage with Dulbecco's phosphate buffered saline from rats exposed to 500 ppm CO from birth until 33 days of age and from littermate controls. Morphological and functional parameters of the exposed cells showed minor changes. Hemoglobin concentration and hematocrit were significantly elevated in the CO-exposed group. Recovery yield of lavage fluid, wet lung weight, and lung displaced volume were identical to controls. Neither number of AM, viability, maximal diameter, surface area nor acid phosphatase activity of exposed AM appeared to be different from controls. However, in a test with fluorescent latex spheres, the phagocytic ability of AM was found to be enhanced in CO-exposed rats and was correlated with an increased percentage of spread forms of AM adhering to glass coverslips. The surface features of the AM were somewhat modified. Number and percentage of granular leukocytes were statistically increased in lavages following chronic exposure to CO. These alterations contrast with the effects of diesel exhaust and cigarette smoke.

Aging↗