摘要:

We studied the relationship between the repetitive (two or more) extrasystole threshold (RET) and ventricular fibrillation threshold (VFT) in 38 pentobarbital anesthetized dogs. A 100-Hz train of 16 4-msec stimuli was delivered to the right ventricle during the T wave of every 12th paced supraventricular beat. Current was increased in 1-mA steps until ventricular fibrillation occurred. Five measurements were made in each dog at 15-minute intervals. In 10.3% of the VFT determinations, VF was not preceded by a repetitive extrasystolic activity. For the remainder regression analysis of the correlation between RET and VFT revealed an r = 0.37 (P< 0.001). The average RET was 54.6% of the VFT (5.4 ± 1.6 vs. 10.2 ± 2.4 mA); however, it ranged from 5% to 98%. Five animals received a 90- minute lidocaine infusion (0.3 mg/kg per min). Although lidocaine significantly increased both RET and VFT as a linear function of log lidocaine plasma concentration (Cp), the mean slope of the VFT vs. log lidocaine Cpregression line was significantly different from that of RET vs. log lidocaine Cpregression line (P< 0.05). Nine dogs infused with the /S-blocker acebutolol (0.5 mg/kg in five and 2 mg/ kg in four dogs) showed a concentration-dependent increase of VFT without significant increase of RET, and the mean slopes of the response vs. log Cpregression lines were significantly different (P<0.01). We conclude that in the control state the RET may be related to the VFT. However, during pharmacological studies, VFT and RET do not necessarily change in parallel. Circ Res 46:599-605,1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Studies were performed to determine the role of the dorsal motor nucleus (DMN) and nucleus ambiguus (NA) in cardiac control in cats. Heart rate (HR), mean arterial blood pressure (MABP), ventricular contractility, left ventricular end-diastolic pressure (LVEDP), and right ventricu- lar end-diastolic pressure (RVEDP) were monitored in anesthetized, paralyzed and /J-blocked animals. The rate of rise of the rising limb of the left ventricular pressure curve (dP/dt) and the output of a strain gauge sutured to the right ventricle (SGF) served as indices of ventricular contractility. Pacing electrodes were inserted into the ventricular myocardium and stimulating electrodes were stereotaxi- cally placed in the DMN and NA. The nuclei were stimulated with and without cardiac pacing, before and after ipsilateral vagotomy. DMN stimulation produced decreases in MABP, dP/dt, and SGF, no HR change, and increases in LVEDP and RVEDP. HR and MABP decreased and dP/dt, SGF, LVEDP, and RVEDP increased with NA stimulation. The responses to NA stimulation were abolished by ventricular pacing. The responses to stimulating either nucleus were abolished by ipsilateral vagotomy. The decreases in dP/dt and SGF with DMN activation were not secondary to preload decreases since LVEDP and RVEDP increased during stimulation. However, since the dP/dt and SGF changes during NA stimulation were abolished by cardiac pacing, the responses were secondary to bradycardia. The data suggest cardiac vagal preganglionic somata are organized according to physiological function. Cell bodies of the DMN control ventricular contractility whereas NA somata are involved in HR control.Circ Res 46: 606-611, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the effect of therapeutic of lidocaine, procainamide, quinidine, propranolol, and diphenylhydantion on two models of depressed conduction and unidiectional block peoduced by asymmetric focal cooling and crushing in sheep Purkinje fibres. All drugs were shwon to induce reversible deterioration of conduction. Unidirectional block was converted to bidirectional block to bidirectional conduction never was observed. These experiments suggest that all five drgus may act by a uniform mechanism of action of some reetrant ventricular arrhythmias involving a zone of depressed conduction or unidirectional block within the Purkinje network. Circ Res 46: 612-619, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the possible contribution of increased vascular reactivity to the development of deoxycorticosterone acetate (DOCA) hypertension in rats. Changes in vascular reactivity were studied in isolated, constant-flow perfused kidneys of male Sprague-Dawley rats post unilateral nephrectomy which received a single subcutaneous implant of Silastic containing 100 mg/kg of DOCA and were given 0.9% NaCl plus 0.2% KC1 solution to drink. Age- and sex-matched control rats (CR) received Silastic implants. The hypertensive rats were studied at 4 days (prehypertensive stage) and 61 days (chronic hypertensive stage) after implantation. At an average of 4 days, blood pressure in DOCA- treated rats did not differ significantly from that measured prior to implantation, and renal vascular resistance was similar to that in the matched controls. However, renal vascular reactivity to norepi- nephrine (NE), vasopressin (ADH), and angiotensin II (A II) was enhanced in the DOCA-treated rats. Dose-response curves for kidneys of these prehypertensive rats showed a parallel leftward shift, reduced EDso, and decreased threshold dose. After an average period of 61 days, blood pressure in the DOCA-treated rats was 189.2 ± 3.5 mm Hg, and renal vascular resistance at maximal vasodilation was significantly greater (P< 0.0001) than in CR. Renovascular reactivity to NE, ADH, and A II was markedly enhanced. Dose-response curves were characterized by a leftward shift, steeper slopes, increased maximal responses, decreased ED50, and threshold doses. Hence, enhanced vascular reactivity clearly precedes and may initiate the rise in arterial pressure in DOCA-treated rats. The initial increase in response to vasoconstrictor substances is attributed to an enhanced sensitivity of vascular smooth muscle, whereas, in the chronic stage of hypertension, structural changes in the resistance vessels, secondary to the rise in arterial pressure, are the main mechanisms responsible for the intensified reactivity. Circ Res 46: 619-624, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Heparin inhibits the proliferation of intimal smooth muscle cells which occurs after denudation of endothelium by air-drying injury in the rat carotid artery. We determined (1) whether the antiproliferative effect of heparin is secondary to effects on platelet adherence to subendothelium or endothelial regeneration and (2) whether the antiproliferative and anticoagulant activities of heparin are related. Morphometric observations by scanning electron microscopy showed that heparin did not alter platelet adherence 5 days after arterial injury and had little or no effect on endothelial regener- ation at 5 and 10 days. To study the relationship between the antiproliferative and anticoagulant effects, we fractionated heparin by affinity chromatography on antithrombin-Sepharose into purified anticoagulant and nonanticoagulant fractions. These heparin fractions were administered to rats in doses which were equivalent either in terms of anticoagulant activity or in terms of mass to the dosage of unfractionated heparin known to inhibit myointimal growth. Additionally, some rats received nonanticoagulant heparin at a dose which was greater in terms of mass than the highest dose of unfractionated heparin which could be administered without inducing fatal hemorrhage. Inhibition of myointimal growth, determined by morphometric analysis of total plaque volume 2 weeks after arterial injury, correlated with total mass of heparin administered but not with anticoagulant activity. Non- anticoagulant heparin given at high dose caused 77% inhibition of myointimal growth(P= 0.02 vs. controls). Heparin inhibition of arterial smooth muscle cell proliferation does not appear to be mediated either by effects on other cells at the level of the arterial wall or by antithrombin. This study should direct attention toward a potential growth regulatory role for arterial glycosaminoglycans.Circ Res 46: 625-634, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

DC electrograms and transmembrane potentials were recorded from isolated perfused pig hearts.Regional ischemia was produced by clamping the left anterior dascending artery (LOD), and after a reperfusion period, regional hypoxic, glucose-free solutions (with or without acidification, or high K+) or with normoxic high K+ solutions. In transmural biosies, nucleotides, lactate, and K+ were determined. During ischemia, resting potential decrease (T-Q depression), action potential amplitude and upstroke velocity decrease, and local activation is markedly delayed (S-T elevation, late intrinsic deflection, high R wave). A high K+ concentration, up to 13 mM, decrease resting potential (T-Q depression) and shortens the action potential (positive T wave) but has minor effect on amplitude (no S-T elevation) and activation (no delay). Hypoxin (Poz=7 mm Hg, no glucose) causes a moderate decrease in resting potential, marked action potential shortening, and some of loss of amplitude but no or only minor delay in activation (slight T-Q depression and S-T elevation, positive T waves). Acidle perfusate does not influence changes fin transm,embrane potential during hypoxia. Potentials of similar configuration to those seen during ischemia could be obtained by LAD perfusion with hypoxic, glucose-free, high K+(10 mM), acidic (pH 6.8) solutions. Most surprising was improvement of potentials after 20 minutes of perfusion, like that seen during maintained LAD occlusion. The time course of metabolic changes was the same in hypoxia and ischemia. Results indicate (1) that there is no direct relationship between metabolic and electrical changes, (2)that electrical changes during ischemia are caused by a combination of lack of perfusion (hypoxia, no substrate) and lack of washout (hyperkalemia, acidosis), and (3) that action potentils of ischemic cells are more “depressed” than those of normoxic cells, at similar reduced levels of resting membrane potential. Circ Res 46: 634-646, 1980.

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We measured cardiac output (CO), renal blood flow (RBF), renal plasma flow (RPF), and afferent arteriolar diameter by the microsphere method, and inulin clearance (GFR) simultaneously in awake rats given an infusion of exogenous angiotensin II (100 ng/min per kg). Angiotensin II did not affect the CO, whereas both RBF and RPF decreased significantly in rats infused with angiotensin II (RBF, 2.88 ± 0.11, mean ±SE; RPF, 1.78 ± 0.09,n= 6) when compared to control animals given saline (RBF, 4.58 ± 0.31; RPF, 2.80 ± 0.24 ml/min per 100 g,n= 6, bothP< 0.005, respectively). Both mean arterial pressure (MAP) and renal vascular resistance (RVR) were significantly higher in rats infused with antiogensin II than in controls. The decrease in GFR did not parallel the reduction of RPF in rats infused with angiotensin II as reflected by their higher values of mean filtration fraction (41.1 ± 1.6%,n= 6) than that of controls (33.7 ± 2.4%,n= 6,P< 0.05). Despite significant elevations of MAP and RVR in rats infused with angiotensin II, their mean afferent arteriolar diameter (19.6 ± 0.24 /im) was not different from that of controls (20.1 ± 0.39 /im). We conclude that angiotensin II preferentially acts at the site of postglomerular vasculature but not at the afferent arteriole. Circ Res 46: 646-650, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We used a double-labeling technique to compare the metabolism of complex carbohy- drates by skin fibroblasts from patients with rheumatic heart disease and from age- and sex-matched normal controls. Fibroblasts were subcultured through a similar number of passages prior to their growth in the presence of "C- or3H-labeled glucosamine, a precursor of complex carbohydrates. At the preconfluent, confluent, and postconfluent stages of growth, the culture medium and trypsin digest of the3H- oruC-labeled fibroblasts were combined, incubated with Protease, then successively fraction- ated on Biogel P-2, Biogel P-100, and DE-52 cellulose. Individual fractions were assayed for radioactiv- ity, and the radioactive elution profiles of labeled complex carbohydrates were compared. These profiles showed that trypsin digestion releases quantitatively more high molecular weight complex carbohydrates and proportionately less heterogeneous glycopeptides from normal fibroblasts, as compared to fibroblasts from rheumatic patients. Chemical analysis of the components of these complex carbohydrates revealed that complex carbohydrates of fibroblasts from rheumatic patients contained more glycoproteins and proportionately less hyaluronic acid than complex carbohydrates of normal fibroblasts. In addition, normal fibroblasts secreted significantly more high molecular weight complex carbohydrates into the medium than fibroblasts from rheumatic patients. These differences were confined to the medium recovered from fibroblast cultures grown to post confluency but not to earlier stages of growth. These findings suggest the possible presence of a biochemical alteration in the synthesis of complex carbohydrates by fibroblasts of rheumatic individuals. The basis and exact nature of this alteration remain to be defined.Circ Res 46: 651-659, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the role of the anticholinergic properties of disopyramide and quinidine in mediating the electrophysiological effects of these agents on isolated cardiac tissue. In right atria, disopyramide, quinidine, and procainamide administered alone elicited negative chronotropic responses. However, after cholinergic stimulation with physostigmine (1 × 10"6M), disopyramide and quinidine produced a positive chronotropic response. Procainamide, when administered under the same conditions of increased cholinergic stimulation, elicited negative chronotropic responses similar to those observed when it was given alone. In Purkinje fibers, disopyramide, quinidine, and procainamide superfused alone for 5 minutes significantly prolonged action potential duration (APD). When administered to Purkinje fibers pretreated with isoproterenol (1 × 10−7M) plus acetylcholine (3 × 10−7M), disopyramide and quinidine shortened APD. Atropine also shortened APD of fibers exposed to both isoproterenol and acetylcholine. In these experiments, isoproterenol consistently shortened APD, and acetylcholine consistently blunted these effects of isoproterenol. Thus, disopyramide and quinidine, alone, prolong APD, but when given in the setting of increased adrenergic-cholinergic stimulation, they shorten APD. Procainamide, when administered to Purkinje fibers pretreated with isoproterenol and acetylcholine, prolongs APD as when it is administered alone. These data demonstrate that disopyramide and quinidine exert important anticholinergic electrophysiologic effects on the atria and the ventricular conducting systems. These anticholinergic effects may contribute to the antiarrhythmic and arrhythmogenic properties of these compounds. Circ Res 46: 660-668, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

From venous tracer-dilution curves, after 57 pulse injections of "NaCl and [13II]albumin (RISA) into the arterial inflow of nine isolated canine lung lobes perfused with blood (hematocrit = 0.24-0.44) under zone III conditions, we calculated area-weighted fractional extractions (E3) and capillary permeability (P)-surface area (S) products (PS) for24Na at plasma flows (Fp) ranging from 4.1 to 40.1 ml»min"1«g"1dry weight. In six of the lobes, 35 separate injections of RISA and [l25I]iodoanti- pyrine permitted calculation of pulmonary blood volume (PBV) and extravascular lung water (EVW). Our experimental preparation allowed us to evaluate, independently, the effects of flow and perfusion pressure on the measurements of PS, PBV, and EVW. PS increased as Fpwas raised, but at any given Fp, PS remained constant despite large changes in pulmonary arterial (PA, range 5-38 mm Hg) and venous (Pv, range 2-30 mm Hg) pressures. Mean EVW (2.8 ± 1.5 ml/g,n= 35) was unaffected by changes in Fp, PA, or Pv. An increase of 52% in PBV occurred as mean PAincreased from 11 to 33 nun Hg. This increase in PBV was due to disterition of small intrapulmonary vessels. Since EVW remained unchanged, there was no evidence for vascular recruitment in these lobes (that is, no change in S), and assuming no change in permeability, we concluded that the flow-dependent changes in PS are related to underestimates of E3and PS at low Fp. At high Fp, mean PS was 3.6 ml»min∼1«g∼Idry weight. If S for the lung is 3000 cm2/g, then pulmonary capillary permeability for sodium is about 3.8 × 10∼6cm/sec, which is considerably lower than the 3.1 × 10"5cm/sec that we have reported for myocardial capillaries.Circ Res 46: 669-680, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID