ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The effects of coronary capacitance on instantaneous pressure-flow (P/F) relationships were analyzed using a theoretical model of coronary flow during diastole that included capacitance. The magnitude of the discrepancy between actual intramural and instantaneously derived P/F relationships was predicted to be dependent on the ratio of two natural decay constants (central aortic decay constant/intrinsic coronary decay constant). The effects of coronary capacitance are eliminated using constant pressure conditions. The instantaneous (dynamic) and constant pressure (static) P/F relationships were compared experimentally using a reservoir to provide constant pressure perfusion during prolonged diastoles in heart blocked dogs. In the presence of coronary tone, zero flow pressure intercepts (PZT) of 27.1 ± 6.6 and 11.0 ± 3.0 mm Hg were obtained under dynamic and constant pressure conditions respectively,P< 0.001. After maximal vasodilation, pzfof 14.2 ± 4.5 mmHg and 10.7 ± 2.4 mmHg were obtained under dynamic and constant pressure conditions, respectively,P= NS. Pzfderived under constant pressure conditions were independent of the state of coronary vasomotor tone with a value about 11 mmHg. The slopes of the dynamic P/ F relationships tended to be greater than those derived from constant pressure conditions. This may suggest an additional component of increasing coronary resistance during diastole that could not be readily assessed under dynamic conditions. We conclude that coronary capacitive effects and resistance changes during diastole severely limit the interpretation of instantaneous dynamic P/F relationships. Diastolic coronary perfusion ceases at about 11 mm Hg and is independent of coronary tone when capacitive effects are eliminated.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The extracellular epicardial potential fields produced by simple depolarization waves in the in situ canine left ventricular myocardium were analyzed. A mathematical model that included tissue anisotropy was developed to explain the observed fields. Values of intracellular (i), extracellular (o), longitudinal(L), and transverse (t) resistivity which gave the best fit between the model and experimental data were (in ohm-cm, mean ± SD): ro/= 852 ± 232, rol= 1247 ± 210,ri/=291 ± 38, rit= 1677 ± 331. The potential fields around simple stimulated waves on the epicardium can best be explained if the extracellular wavefront voltage is (mean ± SD) 74 ± 7 mV for a wave propagating parallel to the local muscle fibers, and 43 ± 6 mV for a wave propagating perpendicular to these fibers. We conclude that the anisotropy of the electrical conductivity of cardiac muscle has important effects on the propagation of waves of depolarization and on the potential fields produced by depolarization in the intact heart.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

In six open-chest, anesthetized dogs, segmental shortening was measured with one pair of ultrasonic dimension gauges placed in the subendocardium (used as a marker for regional ischemia) and two pairs in the epicardium. One of the epicardial crystal pairs was aligned parallel with the surface fibers and the other was oriented circumferentially, parallel with the short axis. During control conditions, with uniform transmural perfusion measured by microspheres (endo/epi ratio 1.17 ± 0.10), epicardial systolic shortening measured by parallel and circumferential segment pairs was comparable but significantly different (9.2 ± 2.4% and 7.3 ± 1.0%, respectively). Partial circumflex coronary artery narrowing produced subendocardial ischemia (blood flow reduced from 0.99 ± 0.24 to 0.29 ± 0.07 ml/min per g,P< 0.01 from control), characterized by elimination of subendocardial shortening (−1.3 ± 1.7%,P< 0.01) Outer myocardial perfusion remained unchanged [0.86 ± 0.17 to 1.00 ± 0.37 ml/min per g, not significant (NS)] and parallel epicardial shortening was not significantly reduced (8.4 ± 3.7%, NS); however, circumferential epicardial shortening was eliminated (−0.8 ± 2.2%,P< 0.01). With complete coronary occlusion, severe transmural ischemia was produced (including the subepicardial layer), and systolic lengthening was observed in the subendocardial as well as both epicardial segments. We conclude that circumferential and parallel epicardial shortening are comparable under conditions of uniform transmural perfusion (normal conditions and complete coronary occlusion), but that considerable nonuniformity of transmural contraction occurs during partial coronary narrowing associated with nonuniform transmural blood flow. Thus, unidimensional measurements of epicardial motion without regard to fiber orientation can lead to variable results under the latter conditions. Despite sustained epicardial blood flow, circumferential epicardial function correlated well with impaired subendocardial shortening during ischemia, indicating that a portion of the myocardium in the outer third of the wall is constrained from shortening during partial ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The effects of verapamil (1 mg/liter, 2 × 10−6mol/liter), quiescence, and cardioplegia (K+16 mmol/liter, Mg2+16 mmol/liter) on calcium exchange and mechanical function during ischemia and reperfusion have been investigated in the rabbit interventricular septum at 32°C. Calcium influx and efflux were recorded continuously with47Ca2+and45Ca2+. After 60 minutes of total ischemia and reperfusion for 30 minutes, there was a net calcium gain of 4.9 mmol/kg dry tissue. Verapamil given before total ischemia reduced net calcium gain to 1.5 mmol/kg dry tissue (n = 5,P< 0.03). When given only on reperfusion after total ischemia, or 10 minutes before reperfusion during low flow ischemia, verapamil did not affect calcium exchange. Cardioplegia begun 10 minutes before total ischemia reduced net calcium gain to 1.0 ± 0.26 mmol/kg dry tissue (n = 6, F < 0.001). Cardioplegia during the first 10 minutes of reperfusion, or lack of electrical stimulation during reperfusion, did not reduce calcium gain. Net calcium gain correlated with the maximum rise in resting tension and with the recovery of developed tension. In control experiments, neither verapamil nor cardioplegia altered influx or efflux of slowly exchanging calcium. The cardioprotective effects of cardioplegia and the calcium channel blocker verapamil appear to be due to a reduction of myocardial work rather than to any specific direct action on calcium fluxes across the myocardial cell membrane.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

A major advance in understanding how quinidine depresses maximum upstroke velocity (Vmax) is the Hondeghem-Katzung mathematical model which incorporates voltage-independent rate constants for binding to and unbinding from resting, open, and inactive Na channels, and a voltage shift of −40 mV for the Hodgkin-Huxley h-kinetics of quinidine-associated Na channels. Using a double microelectrode voltage clamp technique to control transmembrane voltage and apply conditioning pulses, we found that quinidine blockade increased as transmembrane voltage became more positive in the range −60 to +40 mV, and that the rate of quinidine dissociation increased as transmembrane voltage became more negative in the range −60 to −140 mV. The relationship of Vmaxto transmembrane voltage obtained at drive cycles from 500 msec to 20 seconds conformed to the model modified to include voltage-dependent rate constants without the postulated −40-mV shift for quinidine-associated channels. Thus binding of quinidine to inactive Na channels and unbinding from resting channels are both voltage-dependent and can explain frequency and voltage dependent actions of quinidine on Vmaxwithout any voltage shift for quinidine-associated channels.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Data derived from instantaneous diastolic coronary artery pressure-flow relationships in the dog have suggested that diastolic coronary vascular resistance may be constant and coronary vasoregulation unimportant during individual diastoles. We tested these hypotheses by using constant pressure perfusion to determine the pattern of coronary blood flow during single diastoles under steady state conditions and when coronary vascular resistance was actively changing. In 20 closed-chest, anesthetized dogs, long diastoles of constant cycle length were obtained by vagal nerve stimulation during simultaneous right ventricular pacing. Cholinergic vasodilation was prevented with intracoronary atropine. There were no differences between early and late diastolic flows (P> 0.8) for cycle lengths of 0.5 to 5 seconds and flows ranging from 40 to 125 ml/min per 100 g. When coronary resistance was actively altered with adenosine, brief coronary inflow occlusions, or abrupt changes in heart rate, diastolic flow varied continuously during each beat (13.0 ± 1.1 (SD) to 33.4 ± 5.4 ml/min per 100 g per sec). In 10 additional animals, instantaneous diastolic coronary artery pressure-flow relations obtained with initial diastolic resistance constant were compared with those obtained when resistance was actively changing. Despite a changing diastolic resistance, the resulting pressure-flow curves remained linear. Values for slope and zero flow pressure were increased during vasoconstriction (P< 0.001) and decreased during vasodilation (P< 0.001). We conclude that, during constant pressure perfusion, coronary vascular resistance is constant during diastole, and when coronary resistance is actively changing, regulation of coronary blood flow occurs continuously during individual diastoles. Furthermore, instantaneous diastolic coronary artery pressure-flow relations may be linear despite changes in coronary vasomotor tone, and thus cannot be used to estimate resistance or back pressure in such cases.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We studied the effects of a membrane-active antiarrhythmic agent, procainamide (PA), on cellular electrophysiological consequences of ischemic injury to cat ventricular muscle. The left ventricles of 90- to 120-minute acute myocardial infarctions (AMI) (n = 14), and 2- to 4-month healed myocardial infarctions (HMI) (n = 17), were studied by microelectrode techniques in isolated tissue bath. Control action potential duration at 90% repolarization (APD90) recorded from ventricular muscle cells in AMI areas were short (114 ± 4 msec) compared to recordings from cells in normal areas (136 ± 6 msec) (P< 0.001). In contrast, APD90of cells surviving ischemia in HMI preparations were longer than normals (159 ± 5 vs. 140 ± 5 msec,P< 0.001). After 60 minutes of exposure to PA, the APD90of all cells was prolonged, but the absolute and relative magnitudes of prolongation were greater in AMI cells (mean = +40 msec, +35%), than in HMI cells (mean = +19 msec, +13%),P< 0.001. The prolongation of APD90of normal cells was intermediate. Local refractory period changes paralleled APD90changes. In seven additional HMI preparations, sustained ventricular activity was induced by premature stimulation. APD90of HMI cells prolonged less than APD90of normal cells during exposure to PA in these preparations, and decreased differences of APD90between normal and HMI cells was associated with loss of inducibility of sustained ventricular activity. The effect of tetrodotoxin (TTX) was compared to the effect of PA in four HMI preparations to determine whether impaired delivery of test substances caused only an apparent decreased responsiveness to PA in HMI zones. TTX caused nearly identical prolongations of conduction times in HMI zones and normal zones, whereas PA caused different effects on APD90in the two zones. In conclusion, PA alters the time course of repolarization of AMI cells more than that of HMI cells, decreasing the dispersion of repolarization in a given AMI or HMI preparation. The decreased dispersion correlated with loss of ability to induce sustained ventricular activity. Finally, the decreased responsiveness of HMI cells to PA does not appear to be due to impaired delivery to cell membranes, but, rather, appears to be a membrane difference persisting in cells which have survived ischemic injury.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Recent work on vascular smooth muscle actomyosin has indicated that the Ca2+sensitivity of both ATPase and superprecipitation are affected by calmodulin (CaM) and cyclic AMP-dependent protein kinase (cPK). Using a “chemically skinned” arterial preparation, we have extended these observations to the intact structured contractile system. Media from hog carotid artery were skinned with 1% Triton X-100 followed by a 50% glycerol-ATP salt solution, in which the strips were stored at −25°C. Small strips (thickness between 0.1 and 0.2 mm) were mounted isometrically and relaxed in a Mg-ATP salt solution, pH 6.7, Ca2+10″8M, 30°C. Ca2+elicited a contraction with an ED50 of 10∼6M. Isometric force was between 1 and 4 miM, consistent with the force observed before skinning. With time, the preparation became less sensitive with an increase in ED50 to 10−57M. CaM (4 μM) reverses this loss, stabilizes the preparation, and sharply accelerates the rate of tension development. The ED50in the presence of 4 μM CaM shifts to about 10−7M. This effect is dose-dependent, with the half maximal effect at about 0.4 μM CaM. Submaximal Ca2+contractions can be reversibly depressed by preincubation of relaxed fibers with cPK catalytic subunit (300 U/ml), even in the presence of 4 μM CaM. An inhibition of about 50% of the contraction at 0.2 μM Ca2+was obtained, whereas only 20% inhibition was found at 6 μM Ca2+. Our findings suggest that changes in vascular contractility cannot be described solely in terms of changes in cytoplasmic Ca2+, and that changes in the sensitivity of the contractile protein to a given Ca2+concentration are also potential mechanisms for vasodilation.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Renin release was measured in the isolated rat kidney perfused with a recirculating artificial medium containing bovine serum albumin at 6.7 g per 100 ml or 11 g per 100 ml. At the higher concentration of albumin, glomerular filtration ceased and the rate of renin release over 70 minutes of perfusion was increased 6-fold. The addition of ouabain to the perfusate containing 11 g per 100 ml inhibited the release of renin, suggesting that inhibition of Na-K-ATPase or the related changes in cellular volume or composition prevented renin release. Lowering the osmolality of the perfusate by reducing the concentration of sodium chloride also prevented the increase in renin secretion produced by perfusion with 11 g per 100 ml albumin. Increasing the osmolality of the perfusate with mannitol restored the augmented renin release. These results are consistent with the hypothesis that alterations in the volume of certain cells, perhaps in the juxtaglomerular apparatus itself, can control renin release.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID