bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of rat arterial smooth muscle cell proliferation by heparin. II. In vitro studies.
Authors: Hoover R L , Rosenberg R , Haering W , Karnovsky M J
Published: June 2012

We studied in vitro the effects heparin on the growth of rat aortic smooth muscle cells. Measurements of growth were monitored by [3H]thymidine uptake and changes in cell number over a period of 3 days. Our results show that heparin-highly anticoagulant or nonanticoagulant-significantly inhibits growth of smooth muscle cells. We also show that this is a highly specfic interaction with regard to molecule and cell type: i.e., other polyanions, except for a low molecular weight dextran sulfate, do not have the same effect on growth, and not all cells are inhibited by heparin; e.g., endothelial cell growth actually is enhanced. After removing antithrombin from our media, we carried out experiments which show that heparin is effective even though thrombin, a potent mitogenic agent, is still present and active. We also found that passing the platelet extract over a heparin column did not remove all of the motogenic activity of the platelet preparation. Both experiments indicate an inhibitory role for the heparin molecule, per se. Our results support the findings of a recent paper (Guyton et al., 1980) showing that heparin can limit the size of myointimal plaques in rats after carotid injuries by inhibiting smooth muscle cell proliferation.
Intra- and extracellular K+ and Na+ activities and resting membrane potential in sheep cardiac purkinje strands.
Authors: Sheu S S , Korth M , Lathrop D A , Fozzard H A
Published: June 2012

K+- and Na+-selective liquid ion-exchanger microelectrodes were used to measure intracellular K+ activity (aK i) and intracellular Na+ activity (aNa i) of sheep cardiac Purkinje strands in different solutions. In Tyrode's solution with an extracellular K+ concentration ([K+]o) of 5.4 mM, aK i was between 80 and 140 mM and averaged 109.6 +/- 4.0 mM (mean +/- SE, 20 strands). The measured aK i was closely correlated with the resting membrane potential, so that the K+ equilibrium potential was always about 10 mV more negative. When [K+]o was lower than 5.4 mM, aK i fell, and when [K+]o was higher than 5.4 mM it increased, aNa i was between 4 and 12 mM, and averaged 6.6 +/- 0.6 mM (14 strands). Its variation was also correlated with resting potential. Over a wide range of [K+]o and extracellular Na+ concentrations ([Na+]o), the aiNa changes were such that Na+ equilibrium potential remained between +70 and +80 mV. The quiescent membrane behaved as a K+-electrode when [K+]o was higher than 5.4 mM. When [K+]o was low and [Na+]o was zero, then Ca2+ and perhaps Cl- contributed to the resting potential.
Anticholinergic effects of disopyramide and quinidine on guinea pig myocardium. Mediation by direct muscarinic receptor blockade.
Authors: Mirro M J , Manalan A S , Bailey J C , Watanabe A M
Published: June 2012

We studied the interaction of disopyramide, quinidine, and procainamide with cardiac muscarinic receptors. In electrophysiological experiments, the effects of disopyramide, quinidine, procainamide, and atropine were determined on spontaneously depolarizing guinea pig right atria (GPRA) both in the presence and absence of pharmacologically induced (physostigmine) cholinergic stimulation. All four agents demonstrated a concentration-dependent antagonism of the negative chronotropic effects of physostigmine. The order of anticholinergic potency was atropine greater than disopyramide greater than quinidine greater than procainamide. The ability of disopyramide to antagonize the physostigmine induced slowing was stereoselective, (+)disopyramide greater than (-)disopyramide. In contrast, the ability of quinidine to antagonize the negative chronotropic effects of physostigmine was non-stereoselective, quinidine = quinine. In parallel experiments, we studied the ability of disopyramide, quinidine, procainamide, and atropine to compete with the radiolabeled muscarinic receptor antagonist [3H] quinuclidinyl benzilate ([3H]QNB) for binding to muscarinic receptors in crude homogenates of GPRA and membrane vesicles from canine ventricular myocardium. All four agents inhibited [3H]QNB binding to muscarinic receptors. The order of anticholinergic potency determined by the receptor binding studies was identical to that determined by the physiological studies. The interaction of disopyramide with muscarinic receptors was stereoselective, (+)disopyramide > (-)disopyramide. Quinidine was only slightly more potent than quinine in inhibiting [3H]QNB binding to muscarinic receptors. Interaction of antiarrhythmic drugs with muscarinic receptors satisfied criteria for a competitive interaction. The data from this study localize the anticholinergic effects of disopyramide and quinidine to the muscarinic receptor.
Nuclear uptake of sex steroid hormones in the cardiovascular system of the baboon.
Authors: McGill H C , Sheridan P J
Published: June 2012

Cardiac and arterial tissues of six male and six female adult baboons were examined for nuclear uptake of tritiated 5-alpha-dihydrotestosterone (3H-DHT) or tritiated estradiol-17 beta (3H-E2) by autoradiography. 3H-DHT uptake occurred in nuclei of most atrial and ventricular myocardial fibers, no cardiac interstitial tissues, some arterial endothelial cells, most smooth muscle cells of the intima and inner arterial media, and a few smooth muscle cells of the outer arterial media. 3H-E2 uptake occurred in nuclei of a few atrial and ventricular myocardial fibers, many cardiac interstitial cells, occasional arterial endothelial cells, a few smooth muscle cells of the intima and inner arterial media, smooth muscle cells of the outer arterial media, and nearly all adventitial cells. These observations are consistent with other autoradiographic and biochemical findings which indicate that the heart and major arteries of several mammalian species contain androgen and estrogen receptors in distinctive patterns of distribution among muscle and connective tissue cells.
Angiotensin-converting enzyme activity and its modulation by oxygen tension in the guinea pig fetal-placental unit.
Authors: Davidson D , Stalcup S A , Mellins R B
Published: June 2012

Angiotensin-converting enzyme (ACE) activity in the guinea pig fetal-placental unit was assessed at the different oxygen tensions found in utero, during labor, and at birth. To determine fetal-placental ACE activity, we separately perfused in situ term guinea pig fetuses and their placentas via the umbilical vessels under controlled conditions of flow, temperature, and pH. ACE activity was defined as the percent of angiotensin I (AO) or bradykinin (BK) in Krebs-Henseleit solution cleared by a single passage through the placenta or fetus. Peptide concentrations were measured by radioimmunoassay (RIA). Using BK as substrate, we found that placental and fetal ACE activities were reflected by 45% (SD = 10) and 24% (SD = 7) clearances, respectively, at a perfusate PO2 of 29 mm Hg. Maternal hypoxia (PaO2 = 28 mm Hg) decreased placental ACE activity to 16% (SD = 8) and maternal hyperoxia (PaO2 = 191 mm Hg) increased placental ACE activity to 56% (SD = 9). Using a perfusate PO2 of 95 mm Hg, fetal and placental ACE activity increased in less than 5 minutes to 75% (SD = 10) and 77% (SD = 9), respectively. Similar results were obtained using AI as substrate. We conclude that: fetal-placental ACE activity exhibits a chronically reduced level of activity appropriate to the low oxygen tension found in the fetal-placental unit; the placenta is the primary site of ACE activity in the fetus; maternal oxygenation modulates fetal-placental ACE activity; and fetal ACE activity acutely increases with increased fetal oxygenation and thus may play an important physiological role in the regulation of circulating levels of BK and AII and the circulatory adjustments at birth.
Relaxation properties of mammalian atrial muscle.
Authors: Couttenye M M , De Clerck N M , Goethals M A , Brutsaert D L
Published: June 2012

The properties of relaxation, particular the sensitivity of relaxation to load, were analyzed in isolated intact atrial muscle and in manually dissected, detergent-treated cellular preparations from cat, dog, and rat atria. Force and length traces under increasing afterloads and following load clamps were obtained using an electromagnetic lever-force transducer system for the intact muscles and a capacitance transducer system for the cellular preparations. In both types of preparations, the time course of relaxation was hardly affected by the load or by alterations in load (load clamps), unlike intact mammalian ventricular muscle. This load independence of relaxation, which was hardly influenced by variations of initial muscle length, resembled relaxation in intact frog ventricular muscle and in detergent-treated mammalian ventricular single cells. As relaxation of these ventricular preparations with poorly developed (frog) or absent (detergent-treated single cells) calcium-sequestering systems was shown to be governed by the dissipation of activation, these results suggest a similar control mechanism for relaxation in mammalian atrial muscle. Furthermore, load independence of relaxation of mammalian atrial muscle in late diastole may promote optimal filling of the ventricle.
Adrenergic coronary vasoconstriction in the presence of coronary stenosis in the dog.
Authors: Buffington C W , Feigl E O
Published: June 2012

Previous studies have demonstrated competition between sympathetic alpha receptor-mediated coronary vasoconstriction and local metabolic vasodilation during sympathetic activation. The present study tested if this competition also occurs in the presence of coronary stenosis. In closed-chest dogs, the left coronary artery was cannulated, and blood flow from the aorta was restricted by a moderate stenosis (70% area reduction). Intracoronary norepinephrine infusion produced coronary vascular alpha receptor and myocardial beta receptor activation. Norepinephrine infusion was repeated following alpha receptor blockade with phenoxybenzamine (0.25 mg/kg, injected into the coronary artery). Myocardial oxygen and lactate extraction, coronary sinus blood oxygen tension, and coronary resistance were compared at equal levels of myocardial oxygen consumption before and after coronary alpha receptor blockade. In the presence of coronary stenosis, intracoronary norepinephrine infusion decreased coronary sinus oxygen content and increased myocardial oxygen extraction. At comparable myocardial oxygen consumptions coronary vascular resistance was greater with alpha receptors intact than after alpha receptor blockade. The increase in myocardial oxygen extraction was prevented by alpha receptor blockade. We conclude that a sympathetic alpha receptor-mediated coronary vasoconstrictor influence operates, even in the presence of coronary stenosis, to limit oxygen delivery to the heart and increase myocardial oxygen extraction up to the point of cardiac failure, but that this vasoconstrictor effect does not result in net myocardial lactate production.
The relationship between myocardial blood flow and contraction by myocardial layer in the canine left ventricle during ischemia.
Authors: Weintraub W S , Hattori S , Agarwal J B , Bodenheimer M M , Banka V S , Helfant R H
Published: June 2012

We investigated the relationship between regional myocardial blood flow (MBF) and segmental shortening in 17 open-chest dogs. The left anterior descending coronary artery was cannulated and perfused from the left carotid while measuring perfusion pressure. Graded occlusion was produced by a screw clamp. Extent of occlusion was monitored by perfusion pressure. Percent systolic shortening (% delta L) was measured using ultrasonic crystals implanted in normal and ischemic endocardium and ischemic epicardium. MBF was measured in ischemic and normal endocardium and epicardium with tracer microspheres. Dogs underwent 1 to 4 grades of coronary stenosis. Myocardial blood flow both to endocardium and epicardium was found to be linearly related to diastolic perfusion pressure below 50 mmHg (r = 0.803 and 0.748, respectively). Normalized % delta L (N% delta L) was best related to fraction normal zone MBF in the endocardium by the sigmoidal equation, N% delta L = e9.01 MBF-4.03/1 + e9.01 MBF-4.03. % delta L was only weakly related to myocardial blood flow in the epicardium (r = 0.584), and, in four dogs, % delta L was zero in the epicardium despite normal regional blood flow. However, % delta L in the epicardium was linearly related to % delta L in the endocardium (r = 0.78). Thus, endocardial wall motion is related to MBF by a sigmoidal relationship while epicardial wall motion is tethered to endocardial wall motion.
Blood flow and in vivo apparent viscosity in working and non-working skeletal muscle of the dog after high and low molecular weight dextran.
Authors: Gustafsson L , Appelgren L , Myrvold H E
Published: June 2012

We studied the effect of high and low molecular weight dextran on blood flow and in vivo apparent viscosity in the vasodilated vascular bed of working and non-working skeletal muscle. In 12 mongrel dogs, the calf muscle of one hindlimb was isolated. Vasodilation was induced either by sciatic stimulation setting the muscle at rhythmic work or by intraarterial infusion of papaverine. Blood flow was measured electromagnetically at different perfusion pressures. In vivo apparent viscosity was calculated by comparing pressure-flow relationship for blood and a reference solution. Viscosity in vitro was determined in a cone-plate viscometer. A hyperviscous state was induced by intravenous infusion of high molecular weight dextran (HMWD). Hemodilution subsequently was produced by administration of low molecular weight dextran (LMWD). After HMWD, blood flow decreased to 30% of control values in the non-working group and to 45% of control values in the working group. After subsequent infusion of LMWD, blood flow returned to 60% of control values in the non-working group and to 70% of control values in the working group. In vivo apparent viscosity increased to values 250% above control in the non-working group and to 120% above control in the working group following HMWD. After subsequent infusion of LMWD in vivo, apparent viscosity decreased, but remained at values 65% above control in the non-working group and 45% above control in the working group. Thus, the flow impairment induced by HMWD was less pronounced in the working muscle, indicating a flow-preserving effect of rhythmic muscle contractions in this state of disturbed blood rheology. In contrast, the flow-improving effect of LMWD by hemodilution was more pronounced in the non-working muscle.
Uneven distribution of postjunctional alpha 1-and alpha 2-like adrenoceptors in canine arterial and venous smooth muscle.
Authors: De Mey J , Vanhoutte P M
Published: June 2012

We studied isolated canine arteries and veins to compare the pharmacological properties of their postjunctional alpha-adrenoceptors. Rings of femoral and splenic arteries and of femoral and saphenous veins were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer bicarbonate solution. The four blood vessels contracted when exposed to methoxamine, norepinephrine, phenylephrine, and tramazoline; clonidine failed to induce contraction only in the splenic artery. The relative sensitivity to methoxamine was comparable in the arteries and veins, but that for phenylephrine was larger in the former. The veins, but not the arteries, were more sensitive to clonidine and tramazoline than to phenylephrine or methoxamine. Phentolamine was a competitive antagonist against norepinephrine in the arteries and the veins. Prazosin was a competitive antagonist arteries. The competitive antagonistic properties of yohimbine were more pronounced in the veins than in the arteries. Verapamil depressed to the same extent the contractile responses of saphenous veins to clonidine and norepinephrine, but reduced the contractions caused by methoxamine more than those due to norepinephrine. These results indicate the presence of both alpha 1- and alpha 2-like adrenoceptors on venous smooth muscle cells, whereas arterial smooth muscle cells contain mainly postjunctional alpha 1-adrenoceptors.
Myosin isoenzyme changes in several models of rat cardiac hypertrophy.
Authors: Mercadier J J , Lompré A M , Wisnewsky C , Samuel J L , Bercovici J , Swynghedauw B , Schwartz K
Published: June 2012

We studied the effect of chronic mechanical overloading on the isoenzyme composition of rat cardiac myosin in several experimental models: aortic stenosis (AS), aortic incompetence (AI), aortocaval fistula (ACF), overload of the non-infarcted area after left coronary ligation (INF), and overload of the spontaneously hypertensive rats (SHR). Samples of the left and right ventricles were isolated from these hearts, and myosins were analyzed by electrophoresis in non-dissociating conditions. The myosin isoenzymes were called V1, V2, and V3 in order of decreasing mobility, according to the nomenclature of Hoh et al. Controls of the Wistar and Wistar Kyoto (WKY) strains were almost exclusively V1, A slow age-dependent shift toward V3 was observed in the left ventricles of adult Wistar rats, which at 30 weeks of age (body weight 600 g) contained approximately 15% of this form. In all models of cardiac hypertrophy, an isoenzymic redistribution was observed with a significant increase in V3. The level of V3 was statistically correlated with the degree of hypertrophy in the AS, (n = 11, r - 0.6, P less than 0.05), the AI (n = 14, 4 = 0.88, P less than 0.001), and the AS + AI(n = 14, 4 = 0.69, P less than 0.01) but not in the ACF (n = 16, r = 0.46). The isoenzymic changes could account for the decreases in both myosin ATPase activity and cardiac contractility described previously in our laboratory and by others. They also demonstrate that changes in myosin isoenzymes represent a general response of the rat heart, to chronic mechanical overloading.
Mechanical and structural correlates of canine pericardium.
Authors: Wiegner A W , Bing O H , Borg T K , Caulfield J B
Published: June 2012

We have assessed viscoelastic properties of pericardium within the physiological range of stresses and related mechanical behavior to fiber direction as defined by scanning electron microscopy. Stiffness, stress relaxation, and creep were measured in samples taken from the anterior surface of 14 canine pericardia. Stress-strain relations generally were not exponential; stiffness at a stress of 1 g/mm2 ranged from 12.9 to 239 g/mm2 during stretch and varied both from pericardium to pericardium and with the orientation of the strip within the sample (anisotropy). The strips exhibited hysteretic behavior which was not promotional to rate of strain. Following a rapid increase in stress, creep averaged less than 1% and stress relaxation, 34% in a 30-minute test period. The orientation of the strip with the greatest stiffness was consistent from pericardium to pericardium, and correlated with a layer of collagen fibers oriented along the major axis of te strip.
Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study.
Authors: Gorza L , Pauletto P , Pessina A C , Sartore S , Schiaffino S
Published: June 2012

We have used affinity-purified antibodies reacting with guinea pig soleus muscle and ventricular myosin heavy chains to analyze the distribution of specific isomyosin in the ventricular myocardium of normal and renal hypertensive rats. Immunofluorescent staining of cardiac tissue sections with the two antimyosins revealed striking variations in reactivity among ventricular muscle fibers, reactive fibers being more numerous in the left compared to the right ventricle and in subendocardial compared to subepicardial layers. The response of the ventricular myocardium changed during development: all fibers were stained in the newborn rat, whereas most fibers were unreactive in 1-month-old animals. The number of reactive fibers increased again in subsequent stages leading to a mixed pattern in adult animals. The normal mixed pattern of reactivity was transformed into a uniformly positive pattern in hypertensive rats 2 months after surgery. This complete transformation was observed in 20 out of 23 hypertensive animals examined. These findings indicate that the two antimyosins cross-react with a particular type of ventricular myosin heavy chain, whose distribution varies in different muscle cells and whose relative concentration changes during development and during cardiac hypertrophy induced by systemic hypertension. We suggest that differences in pressure load may be responsible for both regional variations in isomyosin distribution and for isomyosin changes in hypertensive animals.
Paradoxical rise in left ventricular filling pressure in the dog during positive end-expiratory pressure ventilation. A reversed Bernheim effect.
Authors: Darsee J R , Mikolich J R , Walter P F , Schlant R C
Published: June 2012

Controversy exists whether positive end-expiratory pressure (PEEP) ventilation lowers cardiac output by reducing left ventricular preload, or by a combination of mechanisms. Sixteen open-chest dogs were instrumented for measurement of left and right ventricular pressure, aortic flow, and left ventricular dimensions. With the pericardium intact, PEEP caused the interventricular septum to bulge toward the left ventricular chamber, increased right and left ventricular end-diastolic pressures, but decreased the average of the three left ventricular dimensions. When right ventricular filling pressure was suddenly reduced, the interventricular septum moved back toward the right ventricle, and left ventricular filling pressure fell. With the pericardium removed, PEEP was associated with a decrease in all three left ventricular end-diastolic dimensions but no significant change in left ventricular filling pressure. Although several indices of contractility were decreased during PEEP, all returned to baseline values when left ventricular preload was normalized during PEEP by a rapid infusion of heparinized blood into the left atrium. In conclusion, PEEP decreases preload and significantly alters the shape and compliance of the left ventricle with the pericardium intact. With the pericardium removed, PEEP produces proportional decreased in major and minor axis dimensions, does not appear to affect left ventricular contractility independent of preload, and alters left ventricular compliance to only a small degree.
Effects of hypoxia on the closing pressure of the canine systemic arterial circulation.
Authors: Sylvester J T , Gilbert R D , Traystman R J , Permutt S
Published: June 2012

We studied the relationships among closing pressure (Pc) and indices of systemic arterial resistance (Ra) and compliance (Ca) during hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) in anesthetized dogs with cardiac bypass and constant ventilation. Closing pressure was measured as the lowest level to which arterial pressure (Pa) fell after inflow to the arterial bed was reduced suddenly to zero. Since the fall of Pa to Pc could be well-described as a single exponential function of time and since Pc was always greater than outflow (venous) pressure. Ra and CA were determined by applying a "vascular waterfall" model to the arterial bed. During HH, Pc increased while Ra and Ca decreased. During COH, Pc and Ra decreased, but Ca did not change. The Pc results indicate that during HH, but not COH, a large portion of the systemic arterial bed experienced a marked increase in vasomotor tone, a qualitative difference that would have been missed if Pc had not been measured. The relationship among Pc, Ra, and Ca during hypoxia suggest these indices may have been determined largely by different portions of the arterial bed in which tone changed independently.
Contracture in isolated adult rat heart cells. Role of Ca2+, ATP, and compartmentation.
Authors: Haworth R A , Hunter D R , Berkoff H A
Published: June 2012

Isolated intact quiescent myocytes from the adult rat were used as a model system for investigating the determinants of contracture induced by metabolic deprivation. The model simulated the pattern of contracture and ATP decline seen in the intact heart during ischemia. Three new insights into the contracture process were gained: (1) in the quiescent cell system, the rate of onset of contracture was independent of external Ca2+, supporting the view that the Ca2+ dependence of the rate of onset in the whole heart is related to beat-dependent substrate utilization; (2) the second phase of ATP decline was paralleled by a decline in the percentage of cells which had not undergone contracture, suggesting that-in any cell-contracture is immediately preceded by a total loss of ATP; and (3) oligomycin delayed the onset of contracture by 55 +/- 12%, suggesting that mitochondrial ATPase activity is a significant drain on energy resources in the quiescent ischemic heart.
Membrane electrical mechanism of basilar artery constriction and pial artery dilation by norepinephrine.
Authors: Harder D R , Abel P W , Hermsmeyer K
Published: June 2012

To study the mechanism by which norepinephrine acts on vascular muscle cell membrane, we recorded membrane potential with intracellular microelectrodes in isolated cat basilar and pial arteries. On addition of norepinephrine concentrations less than 1 microM, pial arteries hyperpolarized and relaxed while basilar arteries depolarized and contracted. Relaxation and hyperpolarization of the pial arteries occurred without the need for addition of any other drug, which indicates the relaxation of spontaneous tone. The relaxation and hyperpolarization could be completely blocked by addition of propranolol before exposure to norepinephrine. The depolarization and contraction of both basilar and pial arteries was blocked by the previous exposure to phentolamine. Electrical spikes were not found spontaneously, but could be induced in both arteries by tetraethylammonium and subsequent addition of norepinephrine, blockable by phentolamine. We conclude that membrane property differences between basilar and pial arteries result in qualitatively different effects of norepinephrine.
Sympathetic cross-innervation of SHR and genetic controls suggests a trophic influence on vascular muscle membranes.
Authors: Abel P W , Hermsmeyer K
Published: June 2012

We have attempted to differentiate neural from humoral environmental factors as the cause of altered arterial muscle membrane properties in spontaneously hypertensive rats (SHR). This laboratory has previously reported that alterations in membrane electrical properties appear to be responsible for increased NE sensitivity in caudal arteries from SHR. In this study, caudal arteries were transplanted into innervated or denervated anterior eye chambers of the same (KNR in KNR, SHR in SHR) or the opposite (KNR in SHR, SHR in KNR) strain. Seven weeks later, we measured membrane potential (Em) and norepinephrine (NE) contractile sensitivity (EC50) in both transplanted and host caudal arteries. Caudal arteries from 2-week-old donor animals transplanted into hosts reinnervated and developed Em and NE EC50 values characteristic of the host strain, interconverting between SHR and KNR characteristics in cross-transplantations. In other experiments, the superior cervical ganglion ipsilateral to the transplanted eye chamber was removed 1 day before transplantation to eliminate the influence of sympathetic nerves. Em values were the same in transplants denied sympathetic innervation whether the arteries were transplanted into the same or opposite strains. Although denervation increased NE sensitivity of KNR caudal arteries, sensitivity of arteries from the SHR strain was unchanged. Therefore, without sympathetic reinnervation, there was no interconversion of Em or NE EC50 characteristics between SHR and KNR by cross-transplantation. These results suggest that neural factors control the development of membrane properties of vascular muscle. It appears that the sympathetic nervous system of the SHR has altered trophic influences that contribute importantly to altered membrane properties in hypertension.
Effect of Oral Anticoagulant (Marcumar) on Prothrombin and Related Components in Blood Coagulation
Authors: JOHNSON SHIRLEY A. , CALDWELL M. JUNE , PRIEST EDWARD MCCALL
Published: June 2012

Marcumar has been considered as an excellent anticoagulant for long term management. It was found that the effect of the drug on plasma levels of prothrombin and autoprothrombin I and autoprothrombin II differed from that of the drugs previously studied using the technics described. Autoprothrombin II was not reduced by Marcumar. This clotting factor, autoprothrombin II, has been found to have no influence on the Quick prothrombin time which is the test generally used to follow the effect of anticoagulants on the clotting mechanisms. The two coagulation factors which were found to decrease following the administration of Marcumar, prothrombin and autoprothrombin I, both influence the Quick prothrombin time.
Dynamics of the Circulation in Acute Hypertension Produced by Stimulation of the Cerebral Cortex
Authors: LANGFORD HERBERT G. , PATTERSON JOHN L. , PORTER RENO R.
Published: June 2012

Electric stimulation of motor areas of the cerebral cortex of the dog is followed by a prompt rise in systemic blood pressure, without significant changes in heart rate or cardiac output. Small increases occurred in lesser circuit pressures.
Estimation of Clotting Accelerator Activity in Plasma after Ingestion of Fat
Authors: TILDEN JOHN H. , SHIPLEY R. E.
Published: June 2012

A relatively simple method is presented which permits a quantitative estimation of a "coagulation accelerator activity" which appears in plasma of human and dog blood after oral ingestion of various fats. Accelerator activity and increased plasma turbidity were observed after ingestion of cream, peanut oil, cocoanut oil, linseed oil, or sodium oleate. Peak responses were seen between 3 and 5 hours after fat intake with gradual return toward control levels in 7 hours.
Effects of Adenine Nucleotides on the Contractility and Membrane Potentials of Rat Atrium
Authors: HOLLANDER PHILIPS B. , WEBB LEYDEN
Published: June 2012

Adenine nucleotides and nucleosides depress the contractility of the rat atrium as has been shown previously for cardiac tissue of other species. It was found that this depression was accompanied by a marked shortening of the action potential, clue to a more rapid rate of repolarization, without marked effects on other atrial characteristics. The evidence points to the site of action as the cell membrane rather than the intracellular contractile systems. The purine-riboside moiety is the basic unit required for activity and combination of this group with sites in the membrane apparently leads to an increased permeability to potassium following depolarization.
Quantitation of Collagen in Human Myocardium
Authors: OKEN DONALD E. , BOUCEK ROBERT J.
Published: June 2012

The collagen concentrations of the four cardiac chambers of normal hearts were determined chemically. Right ventricles and atria contained significantly higher collagen concentrations than did left ventricles and atria. The atria contained twice the collagen concentration of the ventricles. Severe atherosclerosis, hypertrophy and coronary occlusion did not necessarily increase the concentration of collagen in the left ventricle of diseased hearts.
Effect of pH Change upon Systemic Large and Small Vessel Resistance
Authors: FLEISHMAN MALCOLM , SCOTT JERRY , HADDY FRANCIS J.
Published: June 2012

In the dog foreleg acute increase and decrease of hydrogen ion concentration is associated with active small vessel dilatation and constriction, respectively, through some direct effect upon vascular smooth muscle. These small vessel resistance changes do not affect total resistance in the intact leg because of directionally opposite active changes in artery resistance. The latter response appears to be related to central nervous connections and perhaps to circulating or locally released epinephrine, norepinephrine or unknown vasoactive substances.
A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs.
Authors: Pagani M , Pizzinelli P , Bergamaschi M , Malliani A
Published: June 2012

The role of pressor sympathetic reflexes in circulatory control was investigated in conscious dogs. Animals were previously instrumented with a 6- to 8-cm rigid core cannula covered by an inflatable rubber cylinder in the thoracic aorta, a pressure catheter implanted in the aorta above the cannula, and a second catheter inserted into the aorta below the cannula through a femoral artery. Two piezoelectric crystals were positioned at opposing adventitial sites to measure aortic distension with ultrasound techniques. After recovery from surgery, the diameter of the aortic segment surrounding the cannula was increased by 9.6 +/- 0.4% from 16 +/- 1 mm by inflating the rubber cylinder, without obstructing blood flow. Mean aortic pressure rose 31 +/- 3% from 100 +/- 3 mm Hg and heart rate 20 +/- 3% from 91 +/- 3 beats/min (P less than 0.01). The pressor response was abolished by alpha-adrenergic blockade (phentolamine 1 mg/kg, iv). The heart rate response was reduced either by beta-blockade (propranolol 1 mg/kg, iv) or muscarinic blockade (atropine 0.2 mg/kg, iv) and abolished by their combination. During aortic stretch, the sensitivity of the baroreflex was reduced 57 +/- 7% from 18 +/- 2 msec/mm Hg (P less than 0.01). The pressor response was increased by 49 +/- 8% after bilateral carotid sinus nerve section and vagotomy. These excitatory reflex responses were obtained in absence of any pain reaction. Thus, in the conscious dog, aortic distension within physiological ranges induces a potent pressor sympathetic reflex with positive feedback characteristics. Such a pressor reflex not only occurs in the presence of functioning baroreflexes, but is also capable of reducing their sensitivity.
Mechanical interactions between four heart chambers with and without the pericardium in canine hearts.
Authors: Maruyama Y , Ashikawa K , Isoyama S , Kanatsuka H , Ino-Oka E , Takishima T
Published: June 2012

By using excised postmortem hearts obtained from 15 mongrel dogs with the pericardium intact, we investigated mechanical interactions between the four heart chambers from the standpoint of ventricular pressure-volume relationships. The interactions investigated were those between (1) the atrium and the ventricle, (2) the right ventricle and left ventricles, (3) the atrium and one ventricle vs. the other ventricle, and finally (4) the left and right atrium and the right ventricle vs. the left ventricle. For these purposes, we inserted compliant balloons into the four heart chambers without injuring the pericardium, i.e., we incised the base of the atria which was not covered with the pericardium. We obtained the right and/or left ventricular pressure-volume relationships under a constant pressure in three other heart chambers by changing the height of the reservoir connected to each balloon. As a result, both ventricular pressure-volume relationships were hardly affected by an increase in the atrial pressure ranging from 5 to 30 cm H2O with the pericardium removed, although the ventricle became less compliant due to an increase of the same magnitude of the opposite ventricular pressure. On the other hand, the effect of an increase in atrial pressure was distinct with the pericardium intact. Also, all mechanical interactions were enhanced dramatically with the intact pericardium. Thus, the pericardium plays an important role in these mechanical interactions, especially when the filling pressures of all heart chambers increase simultaneously. Clinically, these findings may be important to understanding ventricular functions as related to various heart disease-especially acute heart failure.
Verapamil preserves myocardial contractility in the hereditary cardiomyopathy of the Syrian hamster.
Authors: Rouleau J L , Chuck L H , Hollosi G , Kidd P , Sievers R E , Wikman-Coffelt J , Parmley W W
Published: June 2012

We attempted to alter the inherited myocardial damage and loss of contractility of the cardiomyopathic Syrian hamster (strain U-MX7-1) by giving cardiac drugs that altered intracellular calcium and myocardial workload. Thirty-seven 21-day-old cardiomyopathic and thirty-seven 21-day-old normal hamsters were divided into five groups each: verapamil-, propranolol-, digoxin-, hydralazine-, and saline-injected. On their 90th day of life, the hamsters were killed. Of the five cardiomyopathic groups, only verapamil reduced myocardial damage. When both "control" and cardiomyopathic hamsters were treated with saline, digoxin, or propranolol, the cardiomyopathic hamsters had significantly less contractile force, maximal rate of force development, and maximum velocity of unloaded shortening. When both groups were treated with verapamil or hydralazine, there were no significant group differences in the indices of contractility. However, when saline-treated cardiomyopathic hamsters were compared with drug-treated cardiomyopathic hamsters, only verapamil preserved myocardial contractility. There was also a weak correlation between the Vmax and the actin-activated ATPase activity of the cardiomyopathic hamsters (r = 0.63, P less than 0.001). We conclude that verapamil helped protect the myocardium of genetically cardiomyopathic hamsters against structural damage, and helped preserve myocardial contractility.
Limited maximal vasodilator capacity of forearm resistance vessels in normotensive young men with a familial predisposition to hypertension.
Authors: Takeshita A , Imaizumi T , Ashihara T , Yamamoto K , Hoka S , Nakamura M
Published: June 2012

The study was performed to determine whether there is a structural vascular abnormality in normotensive subjects with hypertensive relatives. We examined maximal vasodilator capacity of forearm resistance vessels in 23 normotensive young men (mean blood pressure 94 +/- 0.4 mm Hg, mean +/- SE) with hypertensive relatives (age 24 +/- 0.1 years) and in 17 normotensive subjects (mean blood pressure 85 +/- 0.4 mm Hg) with no family history of hypertension (age 24 +/- 0.1 years). Maximal vasodilator capacity was examined by measuring minimal vascular resistance during peak reactive hyperemia after release from 10 minutes of arterial occlusion. Minimal forearm vascular resistance after release from 10 minutes of arterial occlusion was 25% higher (P less than 0.02) in subjects with hypertensive relatives (2.0 +/- 0.02 units) than that in subjects with no family history (1.5 +/- 0.01) units. We confirmed the previous findings that increasing metabolic vasodilator stimulus by performing intermittent handgrip exercise during 10 minutes of arterial occlusion did not augment peak dilation. This suggests that 10 minutes of arterial occlusion produced maximal vasodilation. Forearm vascular responses to ice on the forehead was greater in subjects with hypertensive relatives than those in subjects with no family history. These results suggest that there may be a structural abnormality in the forearm resistance vessels in normotensive subjects with family history of hypertension.
Regional myocardial blood flow and coronary vascular reserve in unanesthetized young calves exposed to a simulated altitude of 3500 m for 8--10 weeks.
Authors: Manohar M , Parks C M , Busch M A , Tranquilli W J , Bisgard G E , McPherron T A , Theodorakis M C
Published: June 2012

We determined regional myocardial blood flow (15-micrometer tracer microspheres) and hemodynamics in nine normal calves, seven calves with right ventricular (RV) hypertrophy induced by pulmonary artery banding (PAB) at sea level, and five calves exposed to simulated high altitude (HA) of 3,500 m (PB = 500 mm Hg) for 8--10 weeks. Progression of RV hypertrophy was very rapid in HA calves. RV weight:body weight ratio of 2.74 +/- 0.20 g/kg at 8--10 weeks of sojourn at HA significantly exceeded that in PAB calves (1.98 +/- 0.11 g/kg) 20 weeks post-banding. All calves were studied unanesthetized at sea level before (control) and during maximal coronary vasodilation (iv adenosine; 4 microM/kg per min). Normal and HA calves were also studied during acute hypoxemia (PaO2: 42 +/- 1 mm Hg) induced by administration of 12--13% O2 + N2 in the inhaled gas. RV myocardial blood flow was significantly increased only in PAB calves, whereas in HA calves it was similar to that in normal calves. Left ventricular (LV) mass and blood flow were identical in three groups of calves. Polycythemia did not occur in HA calves. Minimal coronary vascular resistance per unit weight of the hypertrophied RV was identical to that in the normal RV myocardium. This suggested that, despite very fast progression of RV hypertrophy in HA calves, functional cross-sectional area of the RV coronary vascular bed kept pace with the increase in cardiac mass. Minimal coronary vascular resistance per unit weight of the left ventricular myocardium was also identical in three groups of calves. This suggested that chronic hypoxemia by itself did not cause an increase in the functional cross-sectional area of the LV coronary vascular bed. Acute hypoxemia resulted in a significant increase in myocardial blood flow in all calves, but in HA calves, RV endo:epi perfusion ratio decreased below 1.00. Transmural RV myocardial blood flow and RV systolic pressure in HA calves during acute hypoxemia significantly exceeded that in normal calves.
Relationship between beta-adrenergic receptor numbers and physiological responses during experimental canine myocardial ischemia.
Authors: Mukherjee A , Bush L R , McCoy K E , Duke R J , Hagler H , Buja L M , Willerson J T
Published: June 2012

In the present study, we evaluated the physiological responsiveness of the increased numbers of beta-adrenergic receptors in ischemic canine myocardium to in vivo stimulation by (-)-isoproterenol and epinephrine. After 1 hour of temporary proximal left anterior descending coronary artery occlusion and during a 15-minute period of reflow, dogs received (1)-isoproterenol intravenously at a rate sufficient to increase their heart rates 20--40 beats/min. Following the infusion of isoproterenol, myocardial tissue was obtained from the LV ischemic and nonischemic regions for measurement of beta-adrenergic receptor numbers, cyclic AMP content, and phosphorylase b to a conversion. beta-Adrenergic receptor numbers were significantly increased in the left ventricular (LV) ischemic tissue. The administration of (-)-isoproterenol was associated with significant increases in cyclic adenosine monophosphate content and phosphorylase b to a conversion in the LV ischemic tissue. Also, the administration of (-)-epinephrine significantly increased the phosphorylase b to a conversion in ischemic tissue over the nonischemic tissue and this conversion was blocked by pretreatment with (+/-)-propranolol. These data suggest that, in this experimental model, the increased numbers of beta-adrenergic receptors in canine LV ischemic tissue are capable of translating physiological responses when they are activated with an appropriate agonist in vivo.
Effect of histamine on the energy metabolism of K+-depolarized hog carotid artery.
Authors: Peterson J W
Published: June 2012

In a previous study (Peterson and Glück, 1982), activation of hog carotid artery with high-K+ medium caused no increase in aerobic glycolysis (lactic acid production). In contrast, histamine alone is found to stimulate aerobic glycolysis in a tension-dependent fashion (GLück and Paul, 1977). In this study, the addition of histamine to the already K+-depolarized hog carotid artery induced additional contraction, elevated tissue cyclic adenosine 3',5'-monophosphate [cAMP] levels, coupled the rate of aerobic glycolysis to external [Ca++] and isometric tension, and caused suprabasal energy utilization to exceed that required to support the contraction alone by approximately 25%. Increased cytoplasmic free-[Ca++] per se does not stimulate aerobic glycolysis. In the presence of histamine, however, aerobic glycolysis is Ca++-sensitive. Whereas a cycle of Ca++ depletion and restoration has only a small effect on basal metabolic rates in arteries activated with high-K+ alone, the same procedure with arteries stimulated by high-K+ with added histamine causes a dramatic shift in basal metabolic rates toward higher levels of glycolysis.
Quantitative structural changes of the rat thoracic aorta in early spontaneous hypertension. Tissue composition, and hypertrophy and hyperplasia of smooth muscle cells.
Authors: Olivetti G , Melissari M , Marchetti G , Anversa P
Published: June 2012

The thoracic aorta of 21-, 28-, 35-, and 45-day-old spontaneously hypertensive (SH) and Wistar Kyoto (WK) rats was analyzed morphometrically to evaluate the cellular hypertrophy and proliferation of medial smooth muscle cells during the development of genetically determined hypertension. The absolute increase in volume of collagen and ground substance, and elastic tissue was also measured. In SH animals, cellular hypertrophy was found to be the dominant mechanism of muscle growth in the 21- to 28-day and 35- to 45-day intervals, resulting in an overall 68% enlargement of the mean cell volume from 21 to 45 days. The total number of smooth muscle cells increased only 21% (not statistically significant) and the tendency toward hyperplasia was restricted to the 28- to 35-day period. Normotensive controls showed cell proliferation mainly from 21 to 28 days and cellular hypertrophy from 35 to 45 days with an absolute 33% increase in the number of cells and a 26% larger volume of the mean smooth muscle cell at 45 days of age. from 21 to 45 days, the above changes in cell size and number provoked an overall 104% and 67% growth of the muscle mass in SH and WK rats, respectively. The initial response phase of spontaneous hypertension was also characterized by an increase of collagen and ground substance, 184%, which was slightly greater than that of the elastic component, 168%. Changes in mural concentration of fibrous proteins that were similar to but of less magnitude than those of controls, were seen. These results demonstrate that short-term spontaneous hypertension determines a simultaneous growth adaptation in every component structure of the media of the thoracic aorta leading to a disproportionate accumulation of scleroproteins that markedly exceeds that of the contractile component of the vessel wall. At a cellular level, smooth muscle cell hypertrophy is the prevailing process that underlies the tissue response of the aorta in early hypertension.