ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Prostaglandin E1, 4 μg/min, infused locally intra-arterially (ia) for 80 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (⋍ 1 g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 μg base/min, or bradykinin, 10 μtg base/min, infused locally ia for 30 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin Ei, 4 μg/min, together with histamine, 16 μg base/min, or bradykinin, 10 μg base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E, and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin Ei, 4 μg/min, together with bradykinin, 10 μg base/min, was even more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 μg base/min, or bradykinin, 0.8 μg base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases In lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 μg base/min, and bradykinin, 0.8 μg base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Responses of isolated adult rat heart cells to conditions that emphasize various aspects of ischemia have been evaluated. Cells maintained in hypoxic media with limited gubstrate deteriorate mort rapidly than aerobic controls supplemented with glucose. Two distinct irreversible pathways for cell alteration can be distinguished as follows: (1) continued anaerobic aging in the absence of glucose results in the production of large numbers of cells which retain the rod-shaped morphology of heart cells in situ, but which have lost saxcolemmal integrity, and (2) after a period of anaerobic aging, reaeration of the cells produces large numbers of rounded cells in irreversible contracture. These cells maintain an intact sarcolemma and are indistinguishable from those produced by addition of 1 mM Ca2+to Na+-loaded, aerobic cells. Contracture of isolated cells on re-aeration is at least superficially analogous to the oxygen paradox in situ, but since the isolated cells maintain an intact sarcolemma, there is no loss of creatine phosphokinase or other components of the cytosol. Incubation of isolated heart cells at acid pH (pH 8.8 to 6.2) largely prevents both Ca2+-dependent contracture and a Ca2+- dependent loss of respiratory capacity. The acidic conditions virtually eliminate the net influx of40Ca2+into isolated cells that occurs at neutral pH, and the inhibition appears to be localized at the sarcolemma.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

This study was performed to determine the early and delayed metabolic effects of myocardial ischemia on the major membrane phospholipids and to reassess the potential role of lysophospholipids In the genesis of malignant dysrhythmias induced by ischemia. Samples taken from in situ hearts before and at various intervals up to 40 minutes after abrupt ligation of LAD were extracted by the classical Folch technique with modifications to avoid artlfactual lysophospholipid production and losses. Following thin layer chromatography of lipid extracts, phospholipid fractions were quantified by phosphorus estimation and lysophospholipids by a more sensitive method employing gas liquid chromatography. The total phospholipid content with the exception of lysophospholipids remained essentially constant throughout the early phases of acute ischemia, but fell by 6 and 14% after 8 and 24 hours, respectively. At 8 minutes, lysophospholipid levels in ischemic myocardium were significantly increased by 60% compared to pre-occlusion controls in tbe ischemic zone and by 25% in post-occlusion controls. They changed little thereafter. The molecular species of lysophospholipids remained unchanged throughout the period of ischemia gtudied. The mole fraction of other phospholipids as well as their fatty acyl and aldehyde profiles also were unchanged. Despite significant elevations in lysophoapholiplds levels, their absolute quantities were very small (0.6% of total phospholipid P) and 15-fold smaller than that reported in vitro to simulate elcctrophysiological manifestation of ischemia. However, such small amounts in vivo, if produced in the microenvironment of certain membrane-bound enrymes along with acidosis, hypoxia, and fatty acids, could be potentially deleterious to cell functions.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

[3H](±)Carazolol, a newly available β-adrenergic receptor antagonist, has been used to characterize β-adrenergic receptor subtypes present in membrane vesicles derived from canine ventricular myocardium and canine lung. [3H](±)Carazolol binding is saturable, of high affinity, and in displaceable by β-adrenergic agents in accordance with their known pharmacological potencies. The interaction of carazolol with β-adrenergic receptors is stereospeclflc; the (−) stereoisomer demonstrates greater potency than the (+) stereoisomer. Kinetic analysis of [JH}(±)carazolol interaction with β-adrenergic receptors suggests the presence of two phases of interaction, consistent with initial rapidly reversible “low” affinity association of ligand with receptor, followed by Isomerization to form a high affinity, slowly reversible complex. Through use of a [3H](±)carazolol binding assay based on the high affinity complex, pharmacological specificities of £-adrenergic receptor populations of canine myocardium and lung were quantified. Analysis using computer-assisted techniques suggests a β1/β2receptor ratio of approximately 85%/15% for canine myocardium and 5%/95% for canine lung. In the absence of added guanine nucleotides, comparison of potencies of β-adrenergic agonists in the two membrane systems suggests significant β, selectivity of l-isoproterenol and l-eplnephrine, and nonselectivity of norepinephrine. In the presence of saturating levels of guanine nucleotides, comparison of agonist potencies confirms the non-selectivity of l-isoproterenol and l-epinephrine, and β1selectivity of norepinephrine. These results demonstrate that the state of guanine nucleotide regulation of receptors should be defined when examining agonist selectivities for β-adrenergic receptor subtypes in vitro.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled with Krebs-Ringer solution. Acetylcholine depressed contractile responses to electric activation of the sympathetic nerve endings significantly more than those to exogenous norepinephrine; the relaxations caused by the cholinergic transmitter were antagonized by atropine. Helical strips were incubated with [3H]norepinephrine and mounted for superfusion. Electric stimulation augmented the fractional release of labeled norepinephrine. Acetylcholine caused a depression of the evoked3H release which was antagonized by atropine but not by hexamethonium. TTiese experiments demonstrate that, as in animal cutaneous veins, there are prejunctional inhibitory muscarinic receptors on the adrenergic nerve endings in the human saphenous vein. By contrast, the human vein also contains postjunctional inhibitory muscarinic receptors.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We evaluated a technique to measure small vessel pressures and diameters in the right ventricle of a beating rabbit heart. The method allowed free motion of the heart while these measurements were performed. This was accomplished with a strobed light source synchronized with the heart. Thus the observer “sees” the vessels only at the same point in the cardiac cycle. By slowly advancing the Btrobe pulse, we were able to visualize an entire cardiac cycle. We performed pressure measurements with an electromechanical micromanipulator that was programmed to synchronize the motion of a micropipette to the motion of a small vessel. For comparison, another technique was also used which fixed a portion of the right ventricle and allowed motion to be centered around this fixed point. Pressures in veins by our use of the free-motion and fixed techniques were compared and found to be statistically different (6.8 ± 0.7 compared to 13.5 ± 4.7 mm Hg, P< 0.01) with the free-motion technique recording the lower values. The phasic relationship between venous diameter variation and left ventricular pressure also was determined. This relationship was variable between venous networks but quite consistent within a network. The relationship between vessel pressure and vessel diameter revealed significant declines in pressure in relatively large vessels (< 140 μn). This free-motion technique can be used to provide information concerning not only the normal physiology of the coronary circulation, in terms of pressure distributions and the effects of extravascular pressure, but also the changes in vascular pressure which occur in ischemic myocardium and other tissues with inherent motion.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Lysophosphogiycerides and long-chain acyl carnitines accumulate in igchemic myocardium soon after coronary occlusion. Since both are amphiphi.cs and have some structural similarities, we studied their clectrophysiological effects on transmembrane action potentials (AP) of isolated canine Purkinje fibers. Lysophosphatidyl choline (LPC) in the absence of albumin induced concentration-dependent (75–300 μM) and reversible decreases in maximum diastolic potential (MDP), AP amplitude, maximum upstroke velocity of phase 0 (Vmax.,) and action potential duration (APD). These responses were identical to those elicited by LPC in the presence of albumin at 10-fold higher concentrations (750–300 μM). Palmitoyl carnitine induced similar concentration-dependent (75–300 JIM) decreases in MDP1Vmax, AP amplitude, and APD. In addition, at concentrations >100 μM, both compounds induced additional alterations characteristic of ischemic tissue in vivo: triangularization of the AP configuration, increased threshold for extracellular stimulation, conduction delay, non-uniform phase 0 depolarization and electrical alternans. Neither FFA, glycerophosphoryl choline, nor carnitine, all possible catabolites of LPC or acyl carnitine, induced any significant electrophysiological alterations analogous to those caused by LPC. The derangements induced by LPC and palmitoyl carnitine were additive. Acidosis comparable to that seen during early ischemia in vivo (pH «= 6.7) led to a 2- to 3-fold leftward shift in the concentration-response curve for LPC and palmitoyl carnitine. Acidosis alone without the amphiphile during the 10-minute superrusion period failed to alter MDP or AP amplitude, although Vmaxwas reduced (517 to 429 V/sec) and APO was prolonged rather than shortened. Thus, both lysophosphoglycerides and long-chain acyl carnitines increase in ischemic tissue and induce profound electrophysiological derangements closely analogous to those seen in ischemic myocardium In vivo, implicating both metabolites as potential progenitors of dysrhythmias during ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We divised a method to determine tissue osmolality in intact beating hearts. After occlusion of the left anterior descending coronary artery (LAD) of isolated porcine hearts, tissue osmolality in the ischemic myocardium increased within 50 minutes by about 40 mOsm/kg. This rise in osmolality could be accounted for by metabolic processes, notably the conversion of glycogen into lactate, and the hydrolysis of high energy phosphates. Concomitant with the rise in osmolality, the ischemic myocardium during the 1-hour period of LAD occlusion took up fluid and increased tistue water volume by an average of 16.5%. We demonstrated that the osmolality of fixatives used for morphological studies markedly influences ischemic cell morphology. Thus, normotonic fixation of the ischemic myocardium accentuates cell swelling, whereas nearly normal cell volumes result from hypertonic fixation, adjusted according to the rise hi ischemic tissue osmolality. Normotonic reperfusion of the ischemic area after 1 hour of LAD occlusion resulted in the “no-refiow” phenomenon in the mldmural and subendocardial regions. Epicardial and intramural DC-electrograms showed persistent ischemic changes, i.e., T-Q depression, S-T elevation, and monophasic potentials. Tissue resistivity, which during ischemia had risen twofold, remained high. Lacate levels remained high, creatinephosphate (CP) and adenosinetriphosphate (ATP) levels remained low. Selective hypertonic reperfusion of the LAD, followed by a gradual return to normotonic perfnsion, resulted in a normalization of DC extracellular elcctrograms, restoration of electrical resistivity to near normal, low levels of lactate, and higher levels of CP and ATP although control values were not reached. Cell morphology was correspondingly normalized following this procedure. We conclude that ischemic cells become hyperosmotic and consequently take up additional fluid when exposed to normotonic blood. This increased cell swelling compresses capillaries, prevents reperfusion, and may be a major factor in causing reperfusion damage. This damage can be prevented to a large extent by selective hypertonic reperfusion.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Acute shifts in the pressure-volume relationship of the left ventricle occur under several conditions. One potential mechanism for this phenomenon is ventricular interdependence, that is, the influence of right ventricular filling on the left ventricle. TTiis mechanism was studied in an isolated cross-circulated ejecting canine heart preparation with balloons sewn into both right and left ventricles and connected to volumetric chambers allowing continuous and accurate simultaneous measurement of right and left ventricular pressures and volume. Seta of left ventricular pressure-volume loops were obtained under a variety of right ventricular volumes. Experiments were repeated with and without the pericardium. Both diastole and systole were studied. We show that in the pericardium-free heart working over a normal range of volumes, the right ventricle exerts little influence on left ventricular pressure. With the pericardium present, there is a small but significant effect of right ventricular volume on left ventricular pressure during systole and diastole. Over a wider range of volumes imposed in the arrested heart, the right ventricle does influence left ventricular pressure even without the pericardium. Thus we have demonstrated that ventricular interdependence is not likely to lead to large acute pressure-volume shifts, either during diastole or systole, except in the presence of considerably above normal right ventricular volumes.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID