bluuebunny/crossref_metadata_2025 huggingface dataset:
Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids.
Authors: Leffler C W , Busija D W , Beasley D G , Fletcher A M
Published: June 2012

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-keto-PGF1 alpha production from 4.0 +/- 1.1 to 15.3 +/- 4.9 ng/100g X min (mean +/- SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF1 alpha and caused a decrease in blood flow (approximately equal to 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 +/- 0.3 ml/100 g X min to 1.5 +/- 0.3 ml/100 g X min 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 +/- 0.3 ml/100 g X min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 +/- 0.1 ml O2/100 g X min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn.
Prostaglandins contribute to cardiovascular reflexes evoked by static muscular contraction.
Authors: Stebbins C L , Maruoka Y , Longhurst J C
Published: June 2012

The purpose of this study was to determine the contribution of prostaglandins to the reflex cardiovascular responses induced by static contraction of the hind limb in cats, i.e., the exercise reflex. To accomplish this, the cardiovascular responses to hind limb contraction induced by electrical stimulation of spinal cord ventral roots L6-7 and S1 were compared before and after inhibition of prostaglandin synthesis (indomethacin, 2-6 mg/kg i.v., n = 5, or sodium meclofenamate, 2-6 mg/kg i.v., n = 5) or after injection of prostaglandin E2 into the hind limb arterial blood supply. Treatment with indomethacin attenuated the contraction-induced increase in mean arterial pressure and left ventricular dP/dt by 76% and 86%, respectively. Heart rate and average developed triceps surae muscle tension were unchanged. After administering sodium meclofenamate, the reflex response was attenuated to a similar degree. In the indomethacin-treated animals, injection of exogenous prostaglandin E2 (PGE2) partially restored the pressor and myocardial contractile responses. In 6 animals, treatment with exogenous PGE2 without prior inhibition of prostaglandin synthesis did not significantly augment the contraction-induced cardiovascular response. Using the radioactive microsphere technique, we measured skeletal muscle blood flow during contraction before and after treatment with indomethacin (n = 6) to determine if an indomethacin-induced alteration in blood flow could account for the attenuated contraction-induced cardiovascular response. Blood flow during static muscle contraction was not significantly altered by indomethacin. We conclude that prostaglandins contribute to the exercise reflex through an action on afferent nerve endings rather than through a regional vascular effect.
Cardiovascular, renal, and endocrine response to atrial natriuretic peptide in angiotensin II mediated hypertension.
Authors: Edwards B S , Schwab T R , Zimmerman R S , Heublein D M , Jiang N S , Burnett J C
Published: June 2012

Studies done in vitro have demonstrated that atrial natriuretic peptide (ANP) antagonizes angiotensin II-mediated contraction of vascular smooth muscle. The present studies were designed to examine the in vivo actions of ANP in acute angiotensin II-mediated hypertension. The cardiovascular, renal, and hormonal effects of intravenous ANP were evaluated in anesthetized normotensive (n = 6) and hypertensive (n = 6) dogs. In both groups, ANP (3.0 micrograms/kg bolus, 0.3 micrograms/kg/min continuous infusion) reduced arterial pressure and cardiac output without changing systemic vascular resistance. ANP specifically reduced renal vascular resistance and increased sodium excretion. The natriuresis observed was greater in hypertensive than in normotensive dogs. This occurred without a significant change in glomerular filtration rate or aldosterone. The ANP-mediated reduction in arterial pressure was associated with an increase in circulating arginine vasopressin and catecholamines but not in renin. These studies demonstrate that ANP-mediated hypotension results from a reduction in cardiac output without changing systemic vascular resistance, ANP acts as a specific renal vasodilator, ANP-mediated natriuresis can occur without alteration in glomerular filtration rate or aldosterone, and ANP specifically inhibits the release of renin without inhibiting the release of other circulating vasoconstrictors.
Ventricular Diastolic Suction at Normal Arterial Pressures
Authors: BRECHER GERHARD A. , KISSEN ABBOTT T.
Published: June 2012

It has been shown previously that an empty ventricle can suck in a small amount of fluid during diastole, but the question of whether a normal ventricle does so was not answered. In the present experiments it was demonstrated that even a ventricle with a more nearly normal endsystolic residual volume draws blood into its cavity and that this ventricular
vis a fronte
is augmented by the action of epinephrine.
Sodium Polyethylene Sulfonate Effects on Serum Lipids and Blood Coagulation
Authors: KUO PETER T. , HOPKINS F. THOMAS , WURZEL HAROLD
Published: June 2012

This investigation was undertaken in view of the interest lately aroused in the association of plasma lipids with atherosclerosis. Observations on the antilipemic and anticoagulant activities in man of sodium polyethylene sulfonate, a new drug with heparin-like properties, are presented. Alteration of the serum lipoprotein patterns of these patients observed during the course of the drug administration is also described.
Effect of Dietary Protein and Heated Fat on Serum Cholesterol and Beta-Lipoprotein Levels, and on the Incidence of Experimental Atherosclerosis in Chicks
Authors: NISHIDA T. , TAKENAKA F. , KUMMEROW F. A.
Published: June 2012

The present results indicate that dietary protein tends to depress the atherogenic effect of dietary cholesterol and fat. The substitution of heated oil for fresh oil depresses the serum cholesterol and β-lipoprotein levels, but the incidence of atherosclerosis is at least as high as with fresh oil, indicating that the serum cholesterol and β-lipoprotein levels are not necessarily proportional to the degree of experimental atherosclerosis.
Reflex Changes in Human Skeletal Muscle Blood Flow Associated with Intrathoracic Pressure Changes
Authors: RODDIE I. C. , SHEPHERD J. T. , WHELAN R. F.
Published: June 2012

Rapid alternating intrathoracic pressure changes caused by rapid breathing with partial obstruction to airflow caused a three to four fold increase in forearm blood flow whereas following the Valsalva maneuver the blood flow was decreased. Evidence is presented that these changes are brought about reflexly through alterations in vasoconstrictor tone. It is demontrated that the reflex changes are confined to skeletal muscle vessels, providing further evidence that the vasomotor centers controlling skin and muscle vessels can function independently.
A Simplified Method for the Resolution of the Orthogonal Electrocardiogram
Authors: PIPBERGER HUBERT V. , WOOD C. ROBERT
Published: June 2012

The question as to whether unipolar precordial electrocardiographic leads provide clinical information not contained in a 3-lead orthogonal electrocardiogram remains unanswered. A simple, inexpensive switching-type resolver was designed for the investigation of this problem.
Quantitative Studies of Triglyceride Lipolysis after Heparin Administration
Authors: ENGELBERG HYMAN
Published: June 2012

The extent of triglyceride lipolysis by postheparin lipemia clearing factor (lipoprotein lipase) was studied in vitro in 8 atherosclerotic individuals. Varying doses of heparin were injected intravenously and subcutaneously and blood was drawn at stated time intervals for analysis. The rate of splitting of human low density lipoproteins was then determined by measurement of the rate of release of unesterified fatty acids upon incubation of postheparin plasma plus lipoproteins in vitro at 37 C. The data obtained gives a range of the minimum in vivo removal of alimentary neutral fat following an injection of heparin.
Sitosterol Feeding
Authors: SHIPLEY R. E. , PEEIFFER R. R. , MARSH M. M. , ANDERSON R. C.
Published: June 2012

Sitosterol has previously been shown to block cholesterol absorption in both animals and man. Its clinical effectiveness in reducing hypercholesteremia has been repeatedly demonstrated. For periods exceeding 4 years, large amounts of sitosterol have been given daily for maintaining reduction of serum cholesterol concentration. The possibility of adverse side effects resulting from chronic administration has been considered. Long-term animal and clinical studies indicate that sitosterol has no detectable toxicity and does not accumulate or deposit in tissues.
Chromaffin Reacting Cells in Human Digital Skin
Authors: BURCH G. E. , PHILLIPS J. H.
Published: June 2012

These studies demonstrated the existence of chromaffin-reacting granules in the human skin. The chromaffin reaction was provided by bichromate fixation. Subsequent special staining by the modified Sevki procedure revealed these granules to be localized usually to characteristic long, eel-like cells with distinctive tinctorial features. Although the true significance of these cells is not certain, they are believed to represent the local source of a vasopressor material for the peripheral tissues. Much indirect physiologic evidence supports this belief.
Effect of the Energy to Protein Ratio on Serum and Carcass Cholesterol Levels in Chicks
Authors: KOKATNUR M. , RAND N. T. , KUMMEROW F. A.
Published: June 2012

"Soft" fats were found to depress significantly serum cholesterol levels in diets of high energy to protein (E/P) ratio but not in diets of low energy to protein ratios. A low (E/P) ratio depressed serum cholesterol values, regardless of the type of fat in the diet. The E/P ratio may represent the unknown factor in the equations of workers who have tried to relate the effect of dietary fats to serum cholesterol levels.
Effects of Dietary Protein and Carbohydrate Level on Cholesterolemia and Atherogenesis in Cockerels on a High-Fat, High-Cholesterol Mash
Authors: KATZ YALE J.
Published: June 2012

Renal lymphatic pressure was found to be increased either by partial occlusion of the renal vein or total occlusion of the ureter. Simultaneous measurement of interstitial and lymphatic pressure revealed that with compression of the renal vein the rise in interstitial pressure preceded the rise in lymphatic pressure.
Effect of Treated Polygalacturonic Acid on Blood Volume Loss in the Rat Following Traumatic Injury
Authors: BRAMBEL CHARLES E. , MURPHY DAVID
Published: June 2012

Evidence is presented that a polygalacturonic acid derivative (Stypturon) when administered intravenously to rats in an optimal dosage results in concomitant diminution of blood loss from experimental injury to the tail. Mortality rate associated with hemorrhagic shock was significantly reduced. Blood coagulation was inhibited at the site of injury by immersion of the traumatized tail in an anticoagulant solution at 37 C. for the duration of the experiment. The data for the enhancement of the normal hemostyptic mechanism by a polymeric substance without the apparent mediation of the blood coagulation system is discussed.
Renal Hemodynamics, Electrolyte Excretion and Water Metabolism in Pregnant Sheep Before and After the Induction of Toxemia of Pregnancy
Authors: ASSALI N. S. , HOLM LOUIS , HUTCHINSON DONALD L.
Published: June 2012

Renal hemodynamics, electrolyte excretion and plasma level of glucorticoids were studied in pregnant sheep before and after the experimental induction of toxemia. Marked renal ischemia occurred in the animals which developed toxemia. This abnormality occurred concomitantly with an increase in plasma corticoids. Despite the renal ischemia, arterial pressure remained the same. There are some similarities between the toxemia of the sheep and that of human pregnancy.
Effects of Sudden Aortic Occlusion on Heart Rate After Sino-Aortic Denervation
Authors: GILFOIL THOMAS M.
Published: June 2012

This study tests the possibility that pressoreceptors of the sinoaortic type may be located in thoracic vessels and innervated by thoracic afferent nerves. Heart rate and arterial pressure were recorded in anesthetized dogs with neural pathways intact, bilateral vagotomy and sinoaortic denervation before and after internal occlusion of the aorta just above the celiac artery. Results obtained indicate that after elimination of the sinoaortic mechanisms by vagotomy and isolation of the carotid sinuses no functional pressoreceptors of the sinoaortic type can be demonstrated in the arterial tree above the celiac artery.
The Effect of Atrial and Ventricular Tachycardia on Cardiac Output, Coronary Blood Flow and Mean Arterial Blood Pressure
Authors: WÉGRIA RENÉ , FRANK CHARLES W. , WANG HSUEH-HWA , LAMMERANT JACQUES
Published: June 2012

The effect of electrically induced auricular and ventricular tachycardia of various rates was studied in the anesthetized dog. When, the control heart ranging between 140 and 190 per minute, atrial tachycardia of a rate only slightly higher than the control rate was induced, a very temporary initial decrease in arterial blood pressure, cardiac output and coronary blood flow occurred, then all three parameters essentially returned to control level. With atrial tachycardia of a higher rate, blood pressure, cardiac output and coronary flow fell more markedly, then blood pressure and cardiac output rose to or toward control level, remaining below control level with higher rates of tachycardia, whereas the coronary flow rose to or above control level and only exceptionally remained below control level. Ventricular tachycardia had essentially the same effects as atrial tachycardia, but a ventricular tachycardia of a given rate had the same quantitative effect as an atrial tachycardia of a higher rate.
The Effect of Complete Ischemia on the Intracellular Electrical Activity of the Whole Mammalian Heart
Authors: KARDESCH MILTON , HOGANCAMP CHARLES E. , BING RICHARD J.
Published: June 2012

Spontaneous ventricular electrical potentials of whole mammalian hearts subjected to complete ischemia were investigated by means of the intracellular microelectrode. Spontaneous membrane action potentials persist for 20 min, following the onset of anoxia. Early, the duration of the action potential shortens, followed by a progressive fall in the amplitude of the spike. The resting potential shows a diminution to 65 per cent of the control value. The relationship of these effects to change in membrane ionic transports and metabolic processes are discussed.
The Development of Collateral Circulation in the Mouse's Ear
Authors: NORTH K. A. K. , SANDERS A. G.
Published: June 2012

As part of a larger study on the development of a collateral circulation, observations were made on the ear of the albino mouse. One or more arteries or veins were transected and the development of the resulting collateral circulation was followed.
Analysis of cranial neural crest distribution in the developing heart using quail-chick chimeras.
Authors: Phillips M T , Kirby M L , Forbes G
Published: June 2012

Previous studies have shown that ablation of cranial neural crest results in heart malformations in chick embryos. Cranial neural crest cells populate all of the pharyngeal arches and provide the mesenchymal walls of the aortic arch arteries. Neural crest cells migrate from the pharyngeal apparatus into the outflow region of the heart. However, it is not known which of the pharyngeal arches contribute ectomesenchyme to the developing heart nor has a pattern of distribution in the outflow region been established. In the present study, premigratory presumptive arch neural crest from quail embryos was grafted homotopically onto early chick embryos. On Day 6 of incubation, the chimeric embryos were fixed and processed for histological evaluation. The neural crest providing mesenchyme to pharyngeal arches 1 and 2 was not associated with the developing heart. Neural crest presumptive for arches 3, 4, and 6 was found distributed to the outflow region of the heart. Neural crest from arch 4 contributed the largest number of cells to the developing aorticopulmonary and conotruncal septa. This information indicates that ablations of neural crest presumptive for arches 3, 4, and 6 influence heart development directly while lesions of other areas of cranial neural crest probably influence heart development only secondarily with the primary effects occurring in the pharyngeal arches.
Influences on the distribution of blood flow during cardiac tamponade in the conscious dog.
Authors: Bernath G A , Cogswell T L , Hoffman R G , Klopfenstein H S
Published: June 2012

Cardiac tamponade is a spectrum ranging from pericardial effusions with minimal hemodynamic impairment to effusions causing circulatory collapse. In this study, we examined the roles played by the sympathetic nervous system and the renin-angiotensin system in controlling the distribution of blood flow in chronically instrumented conscious dogs during progressive cardiac tamponade. Fifty-one episodes of acute cardiac tamponade were induced to decompensation (decline in mean aortic blood pressure to 70% of the level present when the pericardium was free of fluid) in 6 dogs by intrapericardial infusion of warmed saline solution. Cardiac output (electromagnetic flow probe), intrapericardial pressure, aortic and right atrial blood pressures, and renal, coronary, and mesenteric artery blood flows (Doppler flow probes) were recorded during tamponade in the absence of blockade (control), during alpha-adrenergic blockade (phenoxybenzamine), beta-adrenergic blockade (propranolol), or angiotensin-converting enzyme blockade (captopril). Aortic and mesenteric artery blood flow decreased progressively during cardiac tamponade regardless of the presence or absence of blockade. Coronary artery blood flow did not significantly change during alpha-adrenergic blockade, suggesting that the continuous decline observed during cardiac tamponade in the absence of blockade was at least in part mediated by alpha-adrenergic mechanisms. Renal artery blood flow, in contrast, was well maintained in all situations, confirming the importance of autoregulation in this vascular bed during cardiac tamponade.
Endothelium-dependent modulation of cGMP levels and intrinsic smooth muscle tone in isolated bovine intrapulmonary artery and vein.
Authors: Ignarro L J , Byrns R E , Wood K S
Published: June 2012

The role of the endothelium in modulating cyclic nucleotide levels and intrinsic smooth muscle tone was studied in isolated rings of bovine intrapulmonary artery and vein. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were threefold to fourfold higher in unrubbed artery and vein than in vessels that had been denuded of endothelium. Cyclic 3',5'-adenosine monophosphate (cAMP) levels were twofold higher in unrubbed than in endothelium-denuded artery, but no differences were observed in veins. Methylene blue, an inhibitor of guanylate cyclase, decreased cGMP but not cAMP levels, and this was accompanied by increases in smooth muscle tone. M&B 22,948, an inhibitor of cGMP-phosphodiesterase, increased cGMP but not cAMP levels, and this was accompanied by decreases in smooth muscle tone. Unrubbed vessels were more sensitive than endothelium-denuded vessels to the actions of both methylene blue and M&B 22,948, and this may be attributed to endothelium-dependent increases in cGMP turnover. Moreover, unrubbed vessels were more sensitive than endothelium-denuded vessels to contractile responses to phenylephrine and potassium, and these responses were potentiated by methylene blue and attenuated by M&B 22,948. Although indomethacin lowered cAMP levels in unrubbed artery, no changes in tone or contractile responsiveness were observed. A consistent observation was that the smaller branches of unrubbed but not endothelium-denuded intrapulmonary artery and vein had higher levels of cGMP but not cAMP, were sensitive to endothelium-dependent vasodilators, were more sensitive to methylene blue, and would not maintain a steady level of submaximal tone to phenylephrine when compared with larger branches from a common vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse.
Authors: Rosenblum W I , Nelson G H , Povlishock J T
Published: June 2012

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.
Serotonin as an alternative transmitter in sympathetic nerves of large cerebral arteries of the rabbit.
Authors: Saito A , Lee T J
Published: June 2012

The distribution of serotonin (5-HT)-like immunoreactive (5-HT-LI) nerves and the potential role of 5-HT as a vasoconstrictor transmitter in large cerebral arteries of the rabbit were examined. 5-HT-LI fibers with weak immunofluorescence were observed in the anterior cerebral, middle cerebral, and basilar arteries when fixed by immersion after dissection from exsanguinated animals. The 5-HT-LI fibers, however, were not detected in these arteries when fixed either in vitro or in situ after first being perfused with Krebs solution in situ to flush the blood component from the lumen prior to dissection. In these arteries, 5-HT-LI nerve fibers with intense immunofluorescence, however, reappeared following incubation with 5-HT in vitro. The intensity of the 5-HT-LI fibers seemed to be proportional to the duration and 5-HT concentration during incubation. Following chronic surgical sympathectomy, 5-HT-LI fibers were not detected in arteries before or after incubation with 5-HT. Transmural nerve stimulation elicited constriction in 50% of the control arterial segments examined. The constriction was not affected by ketanserin but was prevented by guanethidine and chronic surgical sympathectomy. The remaining arterial segments that did not respond on transmural nerve stimulation, however, became constrictive on transmural nerve stimulation following incubation with 5-HT in vitro. The constriction was blocked by ketanserin and clonidine. These results demonstrate that the large cerebral artery of the rabbit brain has extremely sparse or no authentic 5-HT-LI nerves.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in myosin isoenzymes, ATPase activity, and contraction duration in rat cardiac muscle with aging can be modulated by thyroxine.
Authors: Effron M B , Bhatnagar G M , Spurgeon H A , Ruaño-Arroyo G , Lakatta E G
Published: June 2012

To determine whether the relative decline in cardiac myosin isoenzyme V1 with maturation continues progressively into senescence and whether thyroxine could reverse age-associated changes in the myosin isoenzyme profile and contraction, rats 2, 8, and 24 months old were treated with thyroxine, 6.4 mg/kg, for 7 days. Myosin isoenzymes, Ca2+-myosin ATPase activities, and isometric contractile function were measured in cardiac preparations from thyroxine-treated animals and age-matched controls. Right ventricular hypertrophy did not occur with aging in controls. Thyroxine increased right ventricular weight in each age group compared to the control group. Body weight decreased by 10% in all thyroxine-treated rats. The relative right ventricular V1 isoenzyme content progressively decreased from 75 +/- 1% to 54 +/- 1% and 14 +/- 1% in controls at 2, 8, and 24 months, respectively, and was associated with a reciprocal increase in V3 myosin isoenzyme. Ca2+-myosin ATPase activity also progressively declined monotonically with age in the control rats from 854 +/- 28 nmol Pi/mg prot/min at 2 months to 529 +/- 28 nmol Pi/mg prot/min at 24 months. Thyroxine administration increased right ventricular V1 at each age to 97 +/- 2%, 73 +/- 2%, and 59 +/- 2% at 2, 8, and 24 months, respectively. A thyroxine induced increase in the Ca2+-myosin ATPase activity could be detected only in the 24-month-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased capillary hydraulic conductivity induced by atrial natriuretic peptide.
Authors: Huxley V H , Tucker V L , Verburg K M , Freeman R H
Published: June 2012

The small molecular weight peptide, atrial natriuretic peptide (ANP), produces marked sodium and water excretion. The peptide, extracted from several species of vertebrate heart, also has been shown to increase glomerular filtration and reduce plasma volume. Several mechanisms have been proposed to account for the action of the peptide but remain undefined. In the present report, the ANP-induced alterations in transcapillary water movement were directly assessed. The modified Landis technique was used to measure single capillary hydraulic conductivity (Lp) of vessels from the frog mesenteric circulation. In 6 individual microvessels, Lp was measured under control conditions and again during perfusion with 10 X 10(-6) M ANP. The Lp increased in each vessel by a mean of 3.79-fold (+/- 2.09 SD). In 4 of these vessels, an additional measurement of Lp was repeated under control conditions; the capillary filtration coefficient returned to control levels. It was concluded that ANP directly and reversibly elevates capillary hydraulic conductivity; this response is independent of changes in capillary hydrostatic pressure or surface area.
Dissociation between calcium influx blockage and smooth muscle relaxation by nifedipine in spontaneously hypertensive rats.
Authors: Rinaldi G J , Amado Cattaneo E , Mattiazzi A , Cingolani H E
Published: June 2012

Aortic smooth muscle isolated from spontaneously hypertensive rats (SHR) and normotensive, age-matched Wistar Kyoto rats (WKY) was precontracted by potassium chloride. The relaxant effect of nifedipine (NIF) was much more pronounced in SHR than in WKY, while the relaxation produced by nitroglycerin (NTG) was similar in both tissues. EC50s were (in - log [M]) NIF:SHR 13.1 +/- 0.4 and WKY 9.4 +/- 0.2 (p less than 0.05); NTG:SHR 7.35 +/- 0.3 and WKY 7.26 +/- 0.18 (NS). Aortas from SHR were less sensitive to the contractile effect of Ca2+ than their WKY controls (EC50 was 3.18 +/- 0.03 in WKY and 2.76 +/- 0.13 in SHR, p less than 0.05). The relaxant effect of NIF was dissociated from its effect on Ca2+ influx in SHR aortas. NIF 10(-10) M relaxed the muscle by 100% without producing Ca2+ influx blockage, and NIF 10(-9) and 10(-8) M induced Ca2+ influx blockage while the muscle continued in the relaxed state. Chemically skinned aortic fibers from SHR were less sensitive to the contractile effect of Ca2+ than their normotensive (NR) controls (pCa for EC50 was 5.91 +/- 0.05 in SHR and 6.20 +/- 0.03 in NR, p less than 0.05). NIF 10(-10) M depressed the contractile response to Ca2+ significantly more in SHR than in NR skinned fibers (pCa for EC50 for 5.62 +/- 0.09 in SHR and 6.07 +/- 0.07 in NR, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of amiodarone on rat heart myosin isoenzymes.
Authors: Bagchi N , Brown T R , Schneider D S , Banerjee S K
Published: June 2012

The effects of amiodarone on heart weight, production of 14C-CO2 from labelled glucose, myosin ATPase activity, and myosin isoenzyme patterns were determined by comparing control and amiodarone-treated male Wistar rats. Since it has been suggested that amiodarone may interfere with thyroid hormone action on the heart, similar experiments were also carried out in hypothyroid and amiodarone-plus-triiodothyronine(T3)-treated rats, and the data were compared to those obtained in amiodarone-treated rats. Amiodarone treatment for 6 weeks resulted in lower heart weight, decreased atrial production of 14C-CO2 from labelled glucose, decreased myosin Ca-ATPase activity, and preferential synthesis of V3 isomyosin. These effects were similar to those observed in hypothyroid rats but were lesser in magnitude. T3 treatment of amiodarone-treated rats reversed all the changes induced by amiodarone. Serum thyroxine (T4) was higher in amiodarone-treated than in control rats, while serum T3 was similar. Serum T3 was higher in the amiodarone-plus-T3 than in the amiodarone-treated group. These results show that 1) amiodarone-induced changes resemble hypothyroidism with respect to cardiac myosin expression and atrial CO2 production, 2) amiodarone causes hypothyroid-like changes despite normal serum T3 and increased serum T4, and 3) T3 reverses the effects of amiodarone. These data support the hypothesis that amiodarone inhibits the action of thyroid hormone on the heart.
Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart.
Authors: Steenbergen C , Murphy E , Levy L , London R E
Published: June 2012

Changes in cytosolic free calcium concentration during myocardial ischemia were measured by 19F NMR in 5FBAPTA-loaded perfused rat hearts. The hearts were perfused with Krebs-Henseleit buffer containing 5 microM of the acetoxymethyl ester of 5FBAPTA, which was hydrolyzed by cytosolic esterases to achieve cytosolic concentrations of 5FBAPTA of 0.12 to 0.65 mM. Cytosolic free calcium concentrations were calculated as the product of the ratio of peak areas for bound and free 5FBAPTA in the NMR spectra and the dissociation constant (708 nM). The basal cytosolic calcium concentration, measured in potassium or magnesium arrested hearts, was 252 nM, and the time-average calcium concentration in beating hearts was 630 nM. Following the onset of total ischemia, there was no immediate substantial change in cytosolic calcium despite a rapid decline in creatine phosphate and ATP and a marked increase in inorganic phosphate as monitored by 31P NMR, but by 10 minutes, there was a substantial increase in free calcium concentration. The ratio of peak areas of bound and free 5FBAPTA returned to the preischemic value during reperfusion, and there was no detectable loss of 5FBAPTA from the heart. Creatine phosphate was also restored to its preischemic level during reperfusion. These results indicate that cytosolic free calcium increases during ischemia and is not immediately associated with lethal injury. This increase in cytosolic calcium may activate degradative enzymes that eventually could compromise myocyte viability.
Coronary artery hemodynamics in conscious dog during cardiac tamponade.
Authors: Klopfenstein H S , Bernath G A , Cogswell T L , Boerboom L E
Published: June 2012

We tested the hypothesis that coronary artery blood flow is sufficient to meet myocardial requirements throughout cardiac tamponade in a conscious euvolemic canine model recovered from surgery. Seven mongrel dogs were chronically instrumented to measure ascending aortic blood flow (electromagnetic flowmeter); intrapericardial, right atrial, and aortic blood pressures; regional myocardial blood flow (radionuclide labelled microspheres); and myocardial consumption of lactate, pyruvate, and oxygen. Data were collected during progressive cardiac tamponade induced by intrapericardial saline infusion to the point of hemodynamic decompensation. Decompensated cardiac tamponade (DCT) was defined as a decline in mean aortic blood pressure to 70% of the level present when the pericardial space was drained of fluid (baseline) and was produced in all animals within 25 minutes. Cardiac tamponade caused a continuous decline in coronary artery blood flow from 1.26 +/- 0.35 (baseline, mean +/- SD) to 0.53 +/- 0.15 ml/min/g (DCT, p less than 0.01), which was associated with a decrease in myocardial oxygen consumption from 1.26 +/- 0.35 (baseline) to 0.74 +/- 0.27 ml/min/g (DCT, p less than 0.05) and a slight increase in myocardial oxygen extraction from 71 +/- 3 (baseline) to 81 +/- 4% (DCT, p less than 0.05). This change in oxygen extraction occurred because of both an increase in arterial and a decrease in coronary venous oxygen content. At all degrees of cardiac tamponade, the lactate-pyruvate ratio did not change significantly from baseline (7.56 +/- 2.31), there was no evidence of lactate production, and the normal endocardial to epicardial blood flow ratio present at baseline (1.41 +/- 0.23) was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
Desensitization of postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses in rat harboring pheochromocytoma.
Authors: Tsujimoto G , Honda K , Hoffman B B , Hashimoto K
Published: June 2012

Prolonged stimulation of tissues by adrenergic agonists may lead to diminished responsiveness of the tissues to subsequent activation by catecholamines; this phenomenon has been termed desensitization or tachyphylaxis. We have examined the in vivo consequences of prolonged stimulation of vascular alpha-adrenergic receptors in rats harboring pheochromocytoma, a tumor that secretes catecholamines. In both early (3-4 weeks after implantation) and late (6-7 weeks after implantation) stages of tumor development, New England Deaconess Hospital rats with transplanted pheochromocytomas developed hypertension and tachycardia and had plasma dopamine and norepinephrine concentrations markedly greater than controls. In both these stages of pheochromocytoma, pressor responses to several vasoconstrictors were examined after pithing. Rats with the tumor were found to become progressively subsensitive to alpha-adrenergic agonists. In the early phase of pheochromocytoma, loss in sensitivity was found for both alpha 1- and alpha 2-adrenergic agonists, whereas responsiveness to the nonadrenergic vasoconstrictors Arg-vasopressin and angiotensin-II was intact (homologous desensitization). However, in the later stage of pheochromocytoma, pressor responses to all these vasoconstrictive agents and also to stimulation of the complex sympathetic outflow were found to be subsensitive (heterologous desensitization). In plasma membranes prepared from mesenteric arteries of early stage tumor-bearing rats, [3H]prazosin binding sites were significantly decreased to 150 +/- 12 fmol/mg vs. 234 +/- 19 fmol/mg in controls. [3H]Yohimbine binding sites were not significantly altered. Our results show that both postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses can be specifically attenuated in the presence of chronically elevated endogenous catecholamine levels produced by pheochromocytoma and that each alpha-receptor subtype may be differently regulated in the development of desensitization.
Role of right and left atria in natriuresis and atrial natriuretic factor release during blood volume changes in the conscious rat.
Authors: Garcia R , Cantin M , Thibault G
Published: June 2012

This study investigated whether excision of either the right or left atrial appendage of rats alters their natriuretic response and the release of atrial natriuretic factor during acute blood volume expansion or reduction. These animals were subjected to a thoracotomy and either had their right or left atrial appendages removed or underwent a right or left atrial sham appendectomy for comparative, control purposes. Intrajugular vein, intracarotid artery, and intravesical catheters were installed 3-4 weeks later under sodium pentobarbital anesthesia. Then, when the rats were conscious, blood volume was expanded using blood from donor rats once every 15 minutes in 3 increments of 10% of the calculated total blood volume at a rate of 5 ml/kg/min. Blood and urine samples were collected before volume expansion and at the end of each 15-minute period, with the withdrawn blood being replaced. A maximal fourfold increase in urinary volume, urinary sodium excretion, and plasma atrial natriuretic factor was observed in all but the right-atrial-appendectomized animals. Plasma atrial natriuretic factor, urinary volume, and urinary sodium excretion were correlated in all 4 groups. No significant changes in blood pressure or hematocrit were noted. Plasma vasopressin, measured at the end of volume expansion, was significantly lower in animals subjected to left atrial appendectomy. High-performance liquid chromatography of plasma from the control groups indicated that most of the released ANF during blood volume expansion corresponded to a high molecular weight peptide. Additional rats, processed as above, were subjected to 10% blood volume decrements.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoxia does not alter angiotensin converting enzyme activity in hamster pulmonary microvessels.
Authors: Shepard J M , Joyner W L , Gilmore J P
Published: June 2012

Studies were initiated to investigate the effects of hypoxia on the conversion of angiotensin I (AI) to angiotensin II (AII) in microvessels of the lung. Using the technique of allografting neonatal lung tissue into the cheek pouch of normal hamsters, the microvessels of the lung, pulmonary arterioles, and venules could be visualized and manipulated by direct in vivo microscopy. The microvessels of the lung were studied 7-10 days after allografting by anesthetizing the hamster with pentobarbital (6.0 mg/100 g body weight i.p.) and then preparing the lung tissue for observation. The tissue was suffused with a Ringer's bicarbonate solution bubbled with a normal (20% O2-5% CO2-75% N2) or a low (95% N2-5% CO2) oxygen mixture. After equilibration, a pulmonary arteriole or venule was selected for observation, and the vessel geometry was recorded. Then, a micropipette containing either AI or AII was positioned alongside the vessel, and the agent was delivered continuously for 2 minutes. Lumen diameter was recorded continually for 8-10 minutes. This procedure was repeated until both angiotensins were tested on pulmonary arterioles and venules under conditions of a normal and low oxygen environment. This protocol was repeated on cheek pouch microvessels that did not contain pulmonary allografts. Both AI and AII produced rapid decreases in the lumen diameters of all microvessels tested. This vasoconstriction was greater for AII, and the oxygen environment did not alter the response. Conversion of AI to AII was not altered by the oxygen environment, and the relative conversion was similar in the microvessels of the lung and cheek pouch.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle.
Authors: Kléber A G , Riegger C B , Janse M J
Published: June 2012

Extracellular and intracellular longitudinal resistances (ro and ri), transmembrane potentials, and conduction velocity were determined in arterially blood-perfused rabbit papillary muscles. Cable analysis was made possible by placing the muscle in a H2O-saturated gaseous environment, which acted as an electrical insulator. Ischemia was produced by exchanging the O2 in the atmosphere by N2 (94% N2-6% CO2) in addition to arresting coronary flow. The first 10-15 minutes of ischemia were characterized by an increase in ro, while ri remained constant. The early part of the increase in ro coincided with the drop in perfusion pressure and was probably due to the diminution of intravascular volume. Rapid electrical uncoupling, reflected by an increase in ri (threefold within 5 minutes), occurred thereafter. The dissociation between the early increase in ro and the delayed increase in ri produced an initial increase in the ratio ro:ri, which subsequently decreased. The decrease in conduction velocity was less than observed in intact hearts with ischemia. This difference is explained by the relatively small changes in resting membrane potential and action potential amplitude in the preparation used. Our results suggest that in the early, reversible phase of ischemia, the increase in ro contributes to a small but significant extent to the slowing of conduction. After 15-20 minutes, the rapid cellular uncoupling, which was most likely coincident with breakdown of cellular homeostasis, may contribute to the occurrence of arrhythmias during this phase of ischemia. Moreover, the early change in the ratio ro:ri will influence the amplitude of the extracellular electrograms following coronary occlusion (TQ-segment and ST-segment shifts).
Influence of heart rate on left ventricular performance in conscious dogs.
Authors: Freeman G L , Little W C , O'Rourke R A
Published: June 2012

The effects of atrial pacing on the left ventricular end-systolic pressure-volume relation, a relatively load-insensitive index of left ventricular performance, were studied in 8 chronically instrumented, conscious dogs. Six of the dogs were studied while autonomically intact, and 2 were studied after autonomic blockade with 2 mg/kg i.v. propranolol and 0.2 mg/kg i.v. atropine. Left ventricular pressure was measured with a micromanometer and left ventricular volume was determined from 3 ultrasonic orthogonal dimensions. Pressure was varied by caval occlusions at control heart rate and after atrial pacing at 100, 120, 140, 160, 180, and 200 bpm. The end-systolic pressure-volume relation was linear in every case (r = 0.97 +/- 0.03, SD). In the autonomically intact dogs, Emax, the slope of the end-systolic pressure-volume relation, was directly and monotonically related to heart rate in every dog, increasing to 238 +/- 99% of control at peak pacing rate (p less than 0.05). V0, the zero pressure intercept of the relation was also directly related to heart rate in every dog and increased 8.6 +/- 5.5 ml from control to peak pacing rate (p less than 0.05). Autonomic blockade did not attenuate these effects. This rightward shift of the end-systolic pressure-volume relation results in a reduced stroke volume from any end-diastolic volume, modulating the hemodynamic benefits of enhanced contractility. T, the time constant of isovolumic pressure fall during ventricular relaxation, was determined from beats with matched end-systolic pressures. T was related to heart rate, falling by 20 +/- 10.3% over the range of rates studied in the autonomically intact dogs and by 23.1 +/- 6.2% in the autonomically blocked dogs. Thus, the ventricle relaxes more rapidly at higher heart rates. We conclude that the frequency of contraction is concluded as an important determinant of overall pump function throughout the cardiac cycle in conscious dogs.
Forward and inverse electrocardiographic calculations using resistor network models of the human torso.
Authors: Walker S J , Kilpatrick D
Published: June 2012

An automated method of modelling the electrical properties of the human thorax from horizontal section data such as computerized tomographic scans has been used to develop both forward and inverse transformations between epicardial and body surface potential distributions. Eleven torso models with varying geometry and organ configurations have been studied. For the forward calculations, a standard dipole-like source is placed along the axis of the heart. Inverse calculations are performed using a measured body surface potential distribution and are based on a division of the surface of the heart into 25 source regions, producing epicardial potentials on these regions. A regularization method is used to stabilize the inverse solutions. Both forward and inverse solutions show substantial differences between models. These findings imply that matching models with patient geometry may be necessary in order to use such solutions in a clinical setting.
Electrical responses of smooth muscle cells during cholinergic vasodilation in the rabbit saphenous artery.
Authors: Komori K , Suzuki H
Published: June 2012

Isolated smooth muscle tissues of the rabbit saphenous artery precontracted with norepinephrine (NE) were relaxed by acetylcholine (ACh, greater than 10(-7) M) or oxotremorine (greater than 10(-7) M), through the activation of muscarinic receptors, only when the endothelial cells were intact. ACh (greater than 10(-7) M) transiently hyperpolarized the membrane (1-4 minutes) with an associated decrease in the membrane resistance, either in the presence or absence of NE, and these changes ceased during the continuous application of ACh. The ACh-induced transient hyperpolarization was not generated after mechanically removing the endothelium or by treatment with atropine. Oxotremorine (up to 10(-5) M) did not alter the membrane potential in the presence or absence of the endothelium. NE (10(-6) M) depolarized the smooth muscle membrane, which remained unchanged by additional application of ACh or oxotremorine for more than 5 minutes, or after removal of the endothelium. The excitatory junction potential generated by perivascular nerve stimulation was inhibited by ACh (greater than 10(-9) M) or oxotremorine (greater than 10(-9) M) in a concentration-dependent manner. These inhibitory actions of ACh or oxotremorine were blocked by atropine but were not affected by removal of the endothelial cells. These results suggest that the inhibitory actions of muscarinic agonists on electrical responses of smooth muscle cells of the rabbit saphenous artery were mainly indirect, i.e., a release of inhibitory substances from the endothelial cells and the inhibition of adrenergic transmission. The former required higher concentrations of ACh or oxotremorine, thereby suggesting that the latter may be more important for vasodilation related to cholinergic mechanisms.