摘要:

Carbocyclic thromboxane A2(10−9to 10−7M) produced a concentration-dependent contraction of helical strips of dog cerebral, coronary, mesenteric, renal, and femoral arteries and of monkey cerebral, coronary, and mesenteric arteries. Contractions induced by low concentrations of carbocyclic thromboxane A2tended to be greater in cerebral arterial strips. Even after 60 minutes of exposure to Ca++-free media, approximately one-half of the contractile response of dog cerebral and mesenteric arteries to 10−8M carbocyclic thromboxane A2was retained. The contractile response was attenuated by diphloretin phosphate, a prostaglandin antagonist, and was potentiated by aspirin. In dog cerebral arterial strips contracted with carbocyclic thromboxane, the relaxant response to prostaglandin I2was less than the response seen in mesenteric and coronary arteries, whereas, in contrast, the response to verapamil was greater in cerebral arteries. Concentration-relaxation curves for papaverine did differ appreciably. It may be concluded that contractions induced by carbocyclic thromboxane are associated with the release of Ca++from intracellular storage sites and, in addition, the increase in transmembrane Ca++influx. Greater susceptibility of cerebral arteries to verapamil may indicate that the Ca++antagonist is of use to relieve the persistent contraction of cerebroarterial smooth muscle. Prostaglandin I2appears to counteract effectively the action of potent vasoconstrictors, such as thromboxane A2and its carbocyclic analog, in various vascular beds.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Transmural histological changes were determined morphometrically in the left ventricular free wall of 20 pigs after Iigation of distal left anterior descending coronary artery for 10, 20, 40, and 120 minutes. Hemodynamics were recorded and regional blood flow distribution was measured in the ischemic zone. Coronary occlusion produced regional transmural ischemia without producing significant systemic hemodynamic change. The microsphere blood flow technique revealed that blood flow was less than 0.05 ml/min per g in all layers of the ischemic zone, i.e., inner, middle, and outer thirds. Ischemic cellular damage was classified and quantified from grade O to grade 5 (0 being normal and 5 being the most severe damage) with light microscopy and confirmed by electron microscopy. Layers of 200 μm immediately beneath the endocardium and epicardium showed minimal ischemic damage of less than grade 1.4 regardless of duration of ischemia in all hearts. In the ischemic left ventricular wall, except for the above layers, a definite transmural gradient of the cellular damage existed from the inner third (grade 2.3 ± 0.1) to the outer third (grade 1.3 ± 0.2) at 20 minutes of ischemia and at 40 minutes of ischemia (grades 3.6 ± 0.1 and 1.9 ± 0.3, respectively). The transmural ischemic damage gradient disappeared at 120 minutes of ischemia, where the inner and outer third ischemic grades were both 5.0 ± 0.1. The data suggest that the limited ischemic damage which occurs in the few cell layers beneath endocardium and epicardium may be explained by regional collateral blood flow. An early ischemic damage wavefront phenomenon does exist in the pig myocardium and is independent of myocardial blood flow and its distribution. The transmural cell damage gradient may be the result of transmural gradients of wall stress and intramyocardial pressure in vivo. Therefore, it appears that factors other than blood flow are the major determinants of ischemic cellular damage in the left ventricular wall of hearts lacking a collateral blood supply.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We report a model of prostaglindin depletion induced in rats by fasting for 11 days, followed by institution of an essential fatty acid-deficient diet. Urinary prostaglandin E, 2 weeks after this diet had been implemented, was 22 ± 2 ng/24 hours compared to 113 ± 8.5 ng/24 hours in controls (P< 0.01). There was no difference in 24-hour urine volume or solute excretion in controls and essential fatty acid-deficient rats. Five hours after administration of NaCl, 10 mM/kg, essential fatty acid-deficient diet rats excreted 1.85 ± 0.78 ml urine compared to 6.42 ± 2.26 ml in control (P< 0.01) with Na+excretion 447 ± 273 μEq in essential fatty acid-deficient rats vs 1483 ± 366 μEq in control (P< 0.01). Intravenous isotonic NaCl, 1.5% body weight, resulted in increased urine flow rate in control rats from 8.3 ± 2 μ/min to 28.7 ± 8.8 μ/min, with sodium excretion increasing from 0.19 ± 0.2 to 3.3 ± 0.9 μEq/min. In the essential fatty acid-deficient diet animals, there was no significant change in flow rate, 6.07 ± 2.43 to 9.85 ± 4.29 μ/min, or sodium excretion, 0.09 ± 0.03 to 0.40 ± 0.24 μEq, after saline infusion. There was no difference in the glomerular filtration rate or plasma aldosterone in the two groups after the salt load. When given a water load, 3 ml/100 g body weight, essential fatty acid-deficient diet rats excreted 2.5 ± 0.7 ml in 5 hours compared to 6.3 ± 1.4 ml in controls (P< 0.01). The defect in water excretion was not due to increased sensitivity to antidiuretic hormone, since similar sensitivity to this hormone was demonstrated in the essential fatty acid-deficient diet and control rats during a water diuresis. When isotonic saline was substituted for drinking water, there was an increase in systolic blood pressure in essential fatty acid-deficient diet rats from 124 ± 2 to 142 ± 3 mm Hg over 9 days (P< 0.01) compared to 122 ± 2 before and 122 ± 2 mm Hg after saline drinking in controls. The administration of linoleic acid for 4 days increased urinary prostaglandin E excretion to 114 ± 15 ng/24 hours from 23 ± 4 (P< 0.01), and the alterations in the ability to excrete a sodium and water load were reversed. In essential fatty acid-deficient diet animals made hypertensive by 9 days of saline drinking, the institution of linoleic acid to the diet normalized the blood pressure despite the continued administration of saline. These studies demonstrate that essential fatty acid-deficient diet animals develop salt-sensitive hypertension with a combined defect in both sodium and water excretion which is reversed following correction of the essential fatty acid deficiency.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Although the hemodynamic effects of diuretics have been studied extensively, their effects on inner medullary blood flow remain unknown. In the present study, renal hemodynamics, including papillary plasma flow measured by the albumin accumulation technique, and associated alterations in papillary tissue solute content were determined in anesthetized, hydropenic dogs and during euvolemic diuresis induced by furosemide (3 mg/kg plus 2 mg/kg per hr, iv), ethacrynic acid (3 mg/kg plus 2 mg/kg per hr, iv) or chlorothiazide (10 mg/kg plus 10 mg/kg per hr, iv). Renal blood flow increased significantly after furosemide and ethacrynic acid and decreased significantly after chlorothiazide. Sixty minutes after diuretic administration, papillary plasma flow was 10.8 ± 1.0 (mean ± SE) in six furosemide- and 11.3 ± 2.6 ml/min per 100 g in six ethacrynic acid-treated dogs, both significantly lower than in eight normal or eight chlorothiazide-treated dogs [26.4 ± 2.6 and 26.7 ± 2.7 ml/min per 100 g, respectively (P<0.01)]. A similarly low papillary plasma flow was also noted 10 minutes after diuretic administration in five furosemide and four ethacrynic acid dogs (13.6 ± 2.3 and 13.4 ± 1.8 ml/min per 100 g, respectively). In furosemide and ethacrynic acid dogs, papillary osmolaliry and sodium content were significantly lower than those in normal or chlorothiazide dogs. In normal and chlorothiazide dogs, papillary sodium content was similar, with a significantly reduced papillary osmolality in the latter. At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P<0.01) and remained unchanged in normal and chlorothiazide dogs. Furthermore, papillary plasma flow was restored to normal (25.3 ± 3.9 ml/min per 100 g) in five dogs in which furosemide was infused during angiotensin II blockage with saralasin, despite a similar diuresis and natriuresis as the other furosemide group. These data demonstrate that after administration of furosemide, ethacrynic acid and chlorothiazide, regulation of papillary plasma flow is independent of renal blood flow, and suggest that angiotensin II may play a role in the reduced papillary plasma flow in furosemide and ethacrynic acid dogs.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

To investigate the relative contributions of alterations in blood flow, capillary density, and tissue PO2to elevated oxygen delivery in working muscle, we conducted experiments on the suffused hamster cremaster muscle, using in vivo microscopic techniques. Muscle PO2was measured during striated muscle twitch contraction at 1 Hz. Tissue oxygenation was changed by using suffusion solutions equilibrated with 0%, 5%, 10%, 21%, or 50% oxygen. Contraction caused an increase in capillary density (capillary recruitment), whose magnitude was related to the equilibration gas and, thus, to the suffusate PO2. Capillary recruitment first increased as the oxygen content was raised, peaked with 10% oxygen, and then diminished with higher oxygen content. Arteriolar functional dilation was also observed; when oxygen was raised above 21%, dilation was decreased. The data suggest that oxygen supply is increased primarily by arteriolar conductance changes with low suffusion solution oxygen (0% to 5%), and by capillary recruitment and increased PO2gradients above 10% oxygen. When vasomotor tone was increased by addition of norepinephrine to the suffusion medium, the changes observed were similar to those observed when oxygen was increased. Therefore, we propose that the altered microvascular responses during vasoconstriction are a function of vascular tone rather than the levels of tissue PO2. A model is proposed which may partially explain the relations among vascular tone, functional dilation, and capillary recruitment. Our data also suggest that tissue PO2may not be precisely regulated about a narrowly defined set point in this striated muscle but that, instead, tissue PO2is a dependent variable controlled by the integrated effects of capillary recruitment, functional vasodilation, and altered metabolism.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We studied the cardiac effects of amantadine, an antiviral and anti-Parkinson drug. Amantadine hydrochloride (100–800 μM) produced significant changes in the electrophysiological properties of isolated ventricular muscle preparations from frog, rabbit, cat, dog, and calf. At relatively low concentrations (100–300 μM), the drug increased action potential duration, decreased action potential amplitude and maximum diastolic potential, and induced phase 4 depolarization. Amantadine also caused subthreshold diastolic depolarizations, apparent upon cessation of stimulation in all preparations studied. The amplitude of the diastolic depolarizations increased as a function of time and/or concentration of drug, eventually reached threshold, and spontaneous activity ensued. In the steady state, amantadine-induced spontaneous activity was rather stable, and the rate was dependent upon the amantadine and external potassium concentrations, as well as the membrane potential. In the absence of stimulation, amantadine-induced spontaneous activity occurred abruptly or could be triggered by a single stimulus, often occurring in a “bursting” fashion that appeared to originate from multiple discrete foci. All actions of amantadine were rapidly reversed upon washout. Propranolol had no effect on the actions of the drug. Amantadine-induced spontaneous activity was unaffected by lidocaine, diminished by TTX, and reduced or abolished by verapamil. The results indicate that amantadine can directly alter the membrane properties of ventricular muscle, possibly due to an effect on potassium conductance. Furthermore, amantadine can be used as a tool to study the ionic basis of ventricular automaticity and to model cellular mechanisms of ventricular rhythm disturbances.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We performed experiments to determine whether or not extracardiac factors are involved in the increase of the glycogen phosphorylase activity after coronary artery ligation in dog hearts. A branch of the left anterior descending coronary artery (LAD) was ligated for 1.5 minutes. The glycogen phosphorylase activity was determined in the endo- and epicardial layers. LAD ligation sigificantly increased the glycogen phosphorylase activity in both LAD (ischemic) and circumflex (nonischemic) areas. Pretreatment with reserpine (1 mg/kg, im, 24 hours before experiments) or hexamethonium (3 mg/kg, iv) prevented the LAD ligation-induced increase in the glycogen phosphorylase activity, but adrenalectomy did not. In the heart-lung preparation and stellectomized dogs, LAD ligation did not increase the glycogen phosphorylase activity in both ischemic and nonischemic areas. Changes in the glycogen phosphorylase activity in the endocardial layers were not essentially different from those in the epicardial layers. In other dogs, metabolic intermediates and ST segment of the surface electrocardiogram were measured. LAD ligation significantly decreased the tissue level of creatine phosphate and increased that of lactate in the ischemic but not in the nonischemic area. An elevation of ST segment occurred only in the ischemic area. Thus ischemic and nonischemic areas were confirmed. The ATP level, however, did not change in any of the ischemic and nonischemic areas. It is suggested that LAD ligation increases the glycogen phosphorylase activity in both ischemic and nonischemic areas probably by an increase in the efferent cardiac sympathetic nerve activity.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The relative capacity for metabolizing [14C]arachidonic acid into biologically active products was studied in microsomes prepared from both normal and infarcted regions of myocardium at three different times after circumflex coronary artery occlusion in the dog. At 3 days after infarction, when polymorphonuclear leukocytes were the predominant invading cell, the ability of infarcted left ventricle microsomes to produce arachidonic acid metabolites was greater than that of microsomes from normal areas of the same hearts. At 3 weeks after infarction, when macrophages were the predominant infiltrating cell and there was a proliferation of blood vessels and fibroblasts, there continued to be significant increases in the production of both prostacyclin (measured as 6- keto PGFio) and thromboxane (measured as TXB2). This enhanced production was still seen at 3 months after infarction at a time when histological examination of the tissue showed that it was still healing with both blood vessels and fibroblasts present. The production of 6-keto PGFiQ was 31.7 ± 4 picomoles per milligram protein per hour (pmol/mg per hr) in noninfarcted regions of left ventricle, whereas the production was significantly increased to 71.7 ± 15 at 3 days, 64.1 ± 10 at 3 weeks, and 67.2 ± 15 even at 3 months after infarction. The thromboxane synthetase activity rose significantly from 30.1 ± 5 pmol mg per hr in noninfarcted regions to 73.7 ± 18 at 3 days, 71.2 ± 5 at 3 weeks, and 92.4 ± 40 at 3 months. The enhanced ability to metabolize arachidonic acid may result from the inflammatory cell invasion or fibroblast activation which accompany healing of acute infarcts.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Electrical responses induced by perivascular nerve stimulation were recorded intracellularly from the smooth muscle of dog middle cerebral artery. With nerve stimulation, the muscle membrane produced excitatory junction potential and then a slow hyperpolarization. The excitatory junction potential showed facilitation and the slow hyperpolarization showed depression phenomena, when the nerves were stimulated with twin pulses. Generation of the slow hyperpolarization was associated with an increase in the potassium conductance of the membrane and was suppressed by tetraethylammonium, which depolarized the membrane, reduced the membrane conductance, and increased the amplitude of the excitatory junction potential. Treatment with 6-hydroxydopamine abolished the excitatory junction potential, but not the slow hyperpolarization; the latter was suppressed by tetrodotoxin. The amplitude of slow hyperpolarization was decreased by application of tetraethylammonium or ATP, but was not affected by application of atropine, neostigmine, theophylline, apamin, ouabain, norepinephrine, propranolol, or guanethidine. ATP produced transient depolarization of the membrane with associated decrease in the membrane resistance. The excitatory junction potential was attributed to activation of the noradrenergic nerves, whereas the slow hyperpolarization was not generated by activation of adrenergic, cholinergic, or purinergic receptors. Inasmuch as the electrogenic Na-K pump, cAMP, and ATP were not involved in the generation of slow hyperpolarization, the possibility of an unidentified chemical transmitter should be given attention.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We studied the effects of intravenous ouabain administration (15 /ig/kg) and vagal stimulation on instrumented conscious dogs. In these dogs, a special electrode was implanted on the epicardial surface over the sinus node and plaque electrodes were placed on the superior vena cava and left atrial appendage. Unipolar sinus electrograms were recorded through the terminals of the sinus electrode paired with the superior vena caval electrode. An electrode also was implanted around the desheathed cervical vagosympathetic trunk, and a coiled polyethylene tube with side holes was implanted cranial to it. Ouabain administration resulted in: (1) an increase in the sinus cycle lengths and sinoatrial intervals and increase in beat-to-beat variation of the sinus cycles and sinoatrial intervals, and (2) periods of sinus pacemaker shift, sinus arrest and sinoatrial block that occurred spontaneously or after atrial overdrive stimulation delivered through the electrode on the left atrial appendage. These effects of ouabain were abolished by intravenous administration of atropine (2 mg). Prior to vagal stimulation, intravenous propranolol (0.5 mg/kg) was administered to block sympathetic responses and 0.75% bupivacaine was injected through the polyethylene tube to block afferent transmission. Vagal stimulation in conscious dogs resulted in two types of responses: (1) slowing of sinus pacemaker rate accompanied by a decrease in diastolic slope and followed by sinus pacemaker shifts, and (2) gradual prolongation of the sinoatrial intervals followed by failure of sinoatrial conduction. An intravenous bolus of acetylcholine (0.1 mg) resulted in a response of type 2 in dogs in which vagal stimulation produced a response of type 1. The marked similarity between the effects of ouabain and vagal stimulation on sinus function and the abolition of the effects of ouabain by atropine suggest that the ouabain effects are vagally mediated.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID