摘要:

The aggregation of red blood cells in blood flowing through small tubes at very low shear rates leads to the two-phase flow of an inner core of rouleaux surrounded by a cell-depleted peripheral layer. The formation of this layer is known to be accompanied by a decrease in hydrodynamic resistance to flow. To quantitate this effect, we measured the pressure gradient, flow rate, and the radius of the red blood cell core in suspensions flowing through tubes of 172-μm radius at mean linear flow rates (Ū) from 50 to 0.15 tube diameters · sec−1. Washed red blood cells were suspended in 1.5% buffered dextran 110 at hematocrits of 34–52%. Using syringe pumps, blood flowed from a stirred reservoir through a vertical 12-cm length of tube in either the upward or downward direction. The pressure drop was measured with transducers. Mean values in distributions in the core radius were obtained by analyzing cine films of flow taken through a microscope with flow in the upward direction, measuring the core radius at five equally spaced axial positions of the tube in each of 100 frames. At 34% and 46% hematocrit, the hydrodynamic resistance increased as Ū decreased from 50 sec−1, reaching a maximum at Ū∼2 sec−1. It then decreased to a minimum at Ū<0.5 sec−1as the red blood cell core formed in the tube, and the mean core radius/tube radius ratio decreased from 0.98 to 0.74 with marked axial fluctuations at the lower Ū. At higher hematocrits, both the increase and decrease in hydrodynamic resistance were greater. In a red blood cell albumin–saline suspension, where there is no aggregation of red blood cells and no two-phase flow, hydrodynamic resistance increases linearly with decreasing Ū. The experimental results were compared with the predictions of a two-phase steady-flow model, assuming axisymmetric flow of a core surrounded by cell-free suspending medium. Two models were considered, one in which the core is solid, the other in which the rheological properties of the suspension in the core are given by the Quemada equation. The effects of sedimentation of the core resulting in a zero net flow pressure gradient were taken into account. Provided that an experimentally extrapolated value for the zero pressure gradient was used, the Quemada-fluid model gave good agreement with the experimentally observed core radius as a function of Ū and hematocrit.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Oxygen free radicals have the ability to oxidize cholesterol. However, nothing is known about the effects of cholesterol oxidation on ion transport in isolated myocardial membranes. The purpose of the present study was to investigate the effects of in situ oxidative modification of sarcolemmal cholesterol on Ca2+flux. Cholesterol oxidase was used to oxidatively modify membrane cholesterol. After incubation of cardiac sarcolemmal vesicles with cholesterol oxidase, cholest-4-en-3-one (cholestenone) was the predominant species of oxidated cholesterol produced. Cholesterol oxidase inhibited sarcolemmal Na+-Ca2+exchange in a concentration-dependent manner. Both the Vmax. andKmof the reaction were altered after cholesterol oxidase treatment. Extensive treatment of the sarcolemmal membranes with cholesterol oxidase increased the passive permeability characteristics of the membrane. Passive Ca2+efflux from the sarcolemmal vesicles was stimulated by increasing the concentration of cholesterol oxidase. ATP-dependent Ca2+uptake was also inhibited after cholesterol oxidase treatment, but it was not as sensitive as the Na+-Ca2+exchange. Conversely, passive Ca2+binding to sarcolemmal vesicles was strikingly stimulated by cholesterol oxidase treatment. The results demonstrate that oxidative modification of sarcolemmal membrane cholesterol can directly affect ionic interactions with the sarcolemmal vesicle and provide potentially important mechanistic information for the molecular basis of the effects of free radicals on ion flux and function in the heart.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To characterize the mechanisms involved in the formation of the myosin heavy chain (MHC) heterodimer V2(αβ-MHC) and the homodimers V3(ββ-MHC) and V1(αα-MHC), 82 5-week-old normotensive rats with homogeneous V1were made hypothyroid with propylthiouracil (0.8%, drinking water), and the proportion of V2, V3, and V1was determined by pyrophosphate gel electrophoresis in multicellular specimens of the left and right ventricles. After the switch from α-MHC to β-MHC, the p-MHC occurred initially in the form of the heterodimer. After 4 and 6 days, V2was greater (p<0.05) than V3. At day 8, V2was smaller than V3, and at day 10, V2was not statistically different from V3. From day 12 onward, V2was smaller than V3. After 21 days, the propylthiouracil treatment was stopped, and the remaining 34 hypothyroid rats were injected with a daily dose of thyroxine (average, 0.1 mg/kg body wt), resulting in a switch from β-MHC to α-MHC. After 1 day, V2still was greater than V1; however, already from day 3 onward, V2was smaller than V1. This characteristic but unexplained heterodimeric and homodimeric organization of the thick filament was analyzed by mathematical models involving probability calculations. Two principally different models were established that assume either the exchange of MHC dimers or of single MHC in the thick filament. The parameters of the models were estimated by minimization routines using the squared discrepancies between the experimental and predicted isoenzyme populations. Based on goodness of fit and crucial model parameters, we concluded that the characteristic organization of the thick filament can be accounted for by an exchange involving predominantly MHC dimers and not single MHC. The fact that V2was lower than expected if formation of heterodimers and homodimers were random was attributed to the preferred homodimerization of 35% of the newly synthesized MHC.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Ouabain-induced arrhythmias are a well-known model used to study triggered activity resulting from delayed afterdepolarizations. In the intact heart, initiation of these arrhythmias is promoted by pacing, especially at fast rates. However, the relevance of the number of stimuli is unknown. In conscious dogs with formalin-induced atrioventricular block, we investigated the effect of variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at progressive levels of ouabain intoxication, and 2) the induction of sustained ventricular tachycardia (VT). Twenty experiments were analyzed. Ouabain was administered as a bolus of 40 μg/kg followed by continuous infusion. Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until completion or induction of VT. When VT could not be initiated, the experiment was repeated at least 1 week later, adding 5-10 μg/kg ouabain to the bolus and increasing the infusion rate correspondingly. This was repeated until VT could be induced. Four interstimulus intervals (200, 400, 600, and 800 msec) and seven numbers of stimuli (5, 10, 20, 35, 50, 100, and 150) were given in two pacing protocols. The effect of these protocols on 1) the number of induced beats per stimulation train, 2) their first postpacing interval, and 3) induction of VT were studied. Initiation of VT occurred after 75±42 minutes. The bolus of ouabain needed to induce VT was inversely related to the body weight of the animals. Progression of ouabain intoxication resulted in 1) a significant increase in the number of induced beats per stimulation train and 2) a significant shortening of the first postpacing interval. Stimulation at a faster rate and/or more stimuli resulted in 1) a significantly pronounced increase in the number of induced beats at the higher levels and 2) a significantly shorter first postpacing interval at successive levels of ouabain intoxication. As a result, VT induction was more frequently observed after pacing with a high number of stimuli (≥50 stimuli, 88%) using short interstimulus intervals (≤400 msec, 100%). In conclusion, VT induction in the presence of ouabain is promoted by pacing using shorter intervals and a higher number of stimuli.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]itransients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]itransients fell severely and was associated with a high diastolic [Ca2+]iin cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]ihomeostasis.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The endothelium releases substances controlling vascular tone and platelet function. We investigated mediators of endothelium-dependent responses in human internal mammary arteries and saphenous veins. The inhibitor of nitric oxide formation,NG-monomethyl L-arginine, enhanced the sensitivity to norepinephrine (fivefold) and evoked more pronounced endothelium-dependent contractions in internal mammary arteries (19±6% of 100 mM KCl) than in saphenous veins (2±1%;p<0.005). In internal mammary arteries,NG-monomethyl L-arginine, but not indomethacin, markedly reduced endothelium-dependent relaxations to acetylcholine (from 95±2% to 39±7%;p<0.005) and prevented those to histamine (78±6% to 4±3%;p<0.005). In saphenous veins, endothelium-dependent relaxations to acetylcholine were weak (24±11%), while nitric oxide caused comparable relaxations (85±3%) as in internal mammary arteries (80±5%; NS).NG-Monomethyl L-arginine prevented the relaxations to acetylcholine and unmasked endothelium-dependent contractions (30±10%). Indomethacin and the thromboxane synthetase inhibitor CGS-13080 augmented relaxations of saphenous veins to acetylcholine from 24±11% to 46±91% (p<0.05). Histamine-evoked contractions were converted to endothelium-dependent relaxations by indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ-30741 (38±3% and 40±6%;p<0.05) but not CGS-13080. Thus, 1) nitric oxide mediates endothelium-dependent relaxations in human arteries and veins; 2) internal mammary arteries release more nitric oxide than do saphenous veins, and 3) in saphenous veins, the effects of nitric oxide are reduced by endothelium-derived contracting factors originating from the cyclooxygenase pathway.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary occlusion in the rat. There is little data available on whether ischemic preconditioning (PC) of hearts can reduce the incidence of such arrhythmias. The effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on development of arrhythmias after a subsequent 5-minute coronary artery occlusion and reperfusion was studied. Rats (n=16 each group) underwent 5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion, and biopsies were taken for creatine phosphate and adenosine triphosphate in ischemic and nonischemic zones of the left ventricle. PC reduced the incidence of ventricular tachycardia (VT) during occlusion (81% control versus 13% PC,p<0.001). On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC animals versus 13 (81%) of controls (p<0.001), and irreversible VF in zero of PC versus seven (44%) of controls (p=0.007). VT occurred in four (25%) of PC versus all (100%) of controls (p<0.001). PC reduced mean duration of VT plus VF from 320±54 to 5±1 seconds (p<0.001) and delayed arrhythmia onset from 8±2 to 85±35 seconds after reperfusion. There was no difference in creatine phosphate levels in the ischemic zone at the end of reperfusion in PC animals compared with controls without irreversible VF (16.2 ±4.1 versus 15.5 ±3.9 nmol/mg protein,p=NS). There was no relation between creatine phosphate levels and occurrence of VT or VF (14.0±5.6 nmol/mg protein VF versus 16.7±3.3 no VF; 16.4±3.5 VT versus 15.4±4.5 no VT;p=NS). Adenosine triphosphate levels in the ischemic zone were unaffected by PC (15.5±2.1 versus 14.5±1.9 nmol/mg protein, PC versus control). When a coronary occlusion of 5 minutes duration is preceded by PC, the usually severe reperfusion arrhythmias are markedly attenuated. This protective effect of PC is not likely to be related to alterations in high-energy phosphate compounds.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Acidosis leads to mechanical alternans (i.e., alternation of large and small contractions) in ferret papillary muscles. This alternation in the size of the contraction is paralleled by alternation in the size of the intracellular Ca2+transient (monitored using the photoprotein aequorin). In isolated myocytes, the large contraction is accompanied by a prolonged action potential. Mechanical alternans also can be induced by acidosis in isolated myocytes during a train of voltage-clamp pulses. Thus, it appears unlikely that the mechanical alternans is secondary to changes in action potential duration; it is more likely that the observed changes in action potential duration are secondary to changes in the size of the Ca2+transient. The observation that a Ca2+-activated inward current also shows alternation during mechanical alternans provides a possible mechanism for the link between Ca2+and action potential duration. The alternation in the size of the Ca2+transient may be secondary to the slowed mechanical restitution observed in papillary muscles during acidosis. This also could explain the observation that decreasing stimulation rate can abolish the alternans.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The mechanism by which isoproterenol (ISO) prevents the prolongation of action potential duration (APD) and refractory period (RP) by the class III antiarrhythmic agent E-4031 was studied. E-4031 (1 μM) increased RP by 501% with no effect on contractile force in papillary muscles isolated from guinea pig heart. ISO (1 μM) increased force of contraction more than fivefold and decreased RP by 25%. The prolongation of RP by E-4031 was prevented by pretreatment of muscles with ISO. The prolongation of APD in isolated guinea pig ventricular myocytes by 5 1 μM E-4031 also was antagonized by prior exposure of the cells to 1 μM ISO. Instantaneous currents and delayed rectifier K+currents, IK, were measured in isolated myocytes using the suction microelectrode voltage-clamp technique. Currents were measured in response to 225 -msec depolarizing pulses from a holding potential of -40 mV. Previous studies have demonstrated that IKin these cells results from activation of two distinct outward K+currents, IKsand IKr(specifically blocked by E-4031). ISO doubled the magnitude of IKS without significant effect on IKr. The instantaneous current, putatively identified as a Cl−current, also was doubled by ISO but was unaffected by E-4031. The augmented conductance of IKS and instantaneous current by ISO results in a decrease in RP. The small effect of E-4031 on APD and RP in the presence of ISO results from the smaller contribution of IKrrelative to the augmented repolarizing currents.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The relation between reflected waves and features of ascending aortic pressure waveforms and impedance patterns was investigated with a modified T-tube model of the systemic arterial circulation. Ascending aortic pressure and flow and descending aortic flow were measured in 10 dogs under basal conditions and under the effect of an agent (methoxamine) that caused vasoconstriction and an increase of mean aortic pressure. A broad range of aortic pressure amplitudes and features was obtained. These waveshapes were classified into four groups. Under basal conditions, cases for which a prominent diastolic fluctuation was present (n=8) were grouped in A. Cases for which this fluctuation was absent (n=2) were grouped in B. Groups C (n=4) and D (n=3) included cases that, under vasoconstricted conditions, did or did not display, respectively, a diastolic fluctuation in pressure. Arterial T-tube model parameters were estimated by simultaneously fitting the model to both ascending and descending aortic flows with aortic pressure as input. A good fit was obtained in any case considered. After parameter estimation, forward and reflected waves and impedance patterns at the entrance of head circulation (head and upper limbs) and body circulation (trunk and lower limbs) as well as their merger in the ascending aorta were determined. T-tube input impedance compared well with impedance data points obtained from the ratio of corresponding harmonics of ascending aortic pressure and flow. In some cases (group A), modulus and phase spectra displayed two distinct minima, in the range from 0 to 10 Hz. In some other circumstances, these minima were less distinct (groups B and C) and could even appear as one (group D). Whether one or two minima appeared in the ascending aortic impedance spectra at low frequency and whether a prominent diastolic fluctuation did or did not appear in aortic pressure, pressure and flow waveshapes proximal to the heart were explained by the presence of two effective reflecting sites in the systemic circulation. In group B, a diastolic fluctuation in pressure was absent despite the fact that head-end and body-end reflected waves were distinct. This happened because body-end reflected waves peaked corresponding to a minimum of the head-end reflected wave. In group D, a diastolic fluctuation in aortic pressure was absent because the body-end reflected wave moved into systole and superimposed on the head-end reflected wave. This superimposition was due to increased pulse wave velocity in the body transmission path as a result of decreased arterial distensibility. After comparing our T-tube model with a single-tube model representation of systemic circulation, we concluded that, in cases like those grouped in D, two effective reflecting sites appear as one to the heart.

ISSN:0009-7330    

出版商:OVID    

年代:1991

数据来源: OVID