摘要:

Fetal ventricular performance has been considered limited because ventricular output does not increase with rapid volume expansion above mean left atrial pressures (mLAPs) of 5–7 mm Hg. To explore relations between preload, afterload, and stroke volume (SV) in the fetal left ventricle, we instrumented 126–129 days gestation fetal lambs with ascending aortic electromagnetic flow transducers, vascular catheters, and inflatable occluders around the aortic isthmus (n=8) or descending aorta (n=7). At 24–48 hours after surgery, blood was withdrawn or infused to reach various mLAPs. The aorta was then slowly occluded as aortic flow and mean arterial pressure (MAP) were measured continuously. Isthmus constriction produced linear decreases in SV as MAP increased; mLAP was unchanged. Descending aortic constriction produced no decrease in SV until high MAPs were reached. SV decreased as MAP increased further, and mLAP rose significantly. The curve relating mLAP and SV before constriction showed little increase in SV above mLAPs of 5–7 mm Hg; however, when curves were derived relating SV and mLAP at relatively constant MAPs, SV continued to increase even above an mLAP of 8–10 mm Hg. Our studies indicate that the fetal left ventricle responds to progressive increases in mLAP to at least 10 mm Hg. The lack of increase in SV above an mLAP of 5–7 mm Hg with rapid volume expansion is related to the concomitant increase in MAP and afterload. {Circulation Research 1989;65:127–134)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In seven conscious, chronically instrumented dogs, left ventricular volume was calculated with an ellipsoidal model from the anteroposterior, septal-free wall, and base-to-apex left ventricular dimensions, measured by implanted ultrasonic transducers. Matched micromanometers measured left and right ventricular transmural and transseptal pressures. Ventricular pressures and volumes were varied by inflation of implanted vena caval and pulmonary arterial occluders. When compared with vena caval occlusion at matched left ventricular end-diastollc volumes, graded pulmonary arterial occlusions were associated with higher right ventricular systolic pressures, reduced left-to-right transseptal systolic pressure gradients, and leftward systolic septal displacement, with increased septal-free wall segment shortening (all p<0.05). Graded pulmonary arterial occlusions, like vena caval occlusions, reduced left ventricular end-diastolic volume, but left ventricular stroke work at a given end-diastolic volume was greater during pulmonary arterial occlusions (2,674 ± 380 10−3erg) than during vena caval occlusion (l,886 ± 450 10−3erg, < 0.05). These data indicate that, while transient pulmonary arterial occlusion reduces left ventricular preload, the concomitant increase in right ventricular systolic pressure, which is the pressure external to the interventricular septal segment of the left ventricle, augments septal shortening and assists left ventricular pump function at a given preload through direct systolic ventricular interaction. {Circulation Research 1989;65:135–145)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The objective of this study was to determine whether reactive oxygen intermediates (e.g., singlet oxygen and the superoxide radical) can rapidly induce eiectrophysiological disturbances leading to the genesis of arrhythmias, even in the absence of ischemia and reperfusion. Rat hearts (n = 6 per group) were perfused aerobically at 37° C for 10 minutes without rose bengal and for 5 minutes with rose bengal (250 nmol/l), during which time no changes in coronary flow or heart rate were observed. Hearts were then uniformly illuminated for 20 minutes with green light (530–590 nm) from 200 fiber optic cables. With light and without rose bengal, or vice versa, all hearts remained stable. However, in the illuminated rose bengal group, eiectrophysiological changes (inversion of the terminal portion of the T wave and an increase in Q-T interval) were observed within 11.8 ± 2.1 seconds (i.e., less than 60 beats). All hearts exhibited ventricular premature beats (within 2.2 ± 0.7 minutes) and ventricular tachycardia (within 2.8 ± 0.7 minutes) before the occurrence of complete atrioventricular block (within 5.5 ± 0.9 minutes). During the illumination period, coronary flow progressively fell in the rose bengat-perfused hearts from 11.6 ± 0.5 ml/min to 2.0 ± 0.4 ml/min (< 0.05 when compared with any control group). When a similar progressive reduction in coronary flow was mimicked (with or without rose bengal), no arrhythmias occurred. Photosensitization of the rose bengal solution in the cannula at a point close to the heart did not induce any eiectrophysiological disturbances or arrhythmias, indicating that it was the short-lived reactive oxygen intermediates rather than the rose bengal product that were responsible for the observed effects. The addition of histidine (100 nmol/l) as a quenching agent to the rose bengal solution significantly delayed the occurrence of the eiectrophysiological changes and arrhythmias. Our results provide evidence that reactive oxygen intermediates can rapidly induce eiectrophysiological changes and arrhythmias even in the absence of ischemia or reperfusion. {Circulation Research 1989;65:146–153)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

[3H]LY186126, an analogue of the cardiotonic agent indolidan, was shown to bind reversibly and with high affinity (Kd=4 nM) to a single class of binding sites within canine myocardial vesicles. Binding site density measured in various cardiac membrane fractions correlated well with Ca2+-ATPase activity (r=0.94; p<0.01), but not with Na+,K+-ATPase or azide sensitive ATPase, indicating a localization of these sites within sarcoplasmic retlculum membranes. Divalent cations were required for binding and displayed the following order of activation: Zn2++ Mn2+Mg2+Ca2+. Differential activation of [3H]LY186126 binding by various divalent cations was due to alterations in binding site density, rather than affinity. cGMP and selective inhibitors of type IV membrane-bound phosphodiesterase (SR-PDE), for example, indolidan, milrinone, imazodan, and enoxlmone, selectively displaced bound [3H]LY186126; caffeine, theophylline, and rolipram were relatively impotent as inhibitors of radiolabel binding. Kdvalues from displacement corves were highly correlated with IC50values for inhibition of SR-PDE (r=0.92; p<0.001). In addition, Kdvalues correlated well with published ED50values for increases in cardiac contractility in pentobarbital-anesthetized dogs (r=0.94; p<0.001). The results support the hypothesis that [3H]LY186126 labels the pharmacological receptor for the class of positive inotropic agents characterized as isozyme-selective phosphodiesterase inhibitors. Furthermore, the data suggest that the identity of the site labeled by [3H]LY186126 is SR-PDE, the type IV isozyme of cardiac phosphodiesterase located in the sarcoplasmic retlculum.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Different aspects of the intrinsic regulation of rate-induced variations of functional refractory period of atrioventricular node (FRPN) were studied in isolated rabbit heart preparations. First, the hypothesis that these variations originate from the net interaction between facilitation and fatigue was tested. For a constant fast rate, selective effects of facilitation and of steady-stage fatigue were independently shown to shorten and prolong, respectively,FRPNwhile their combined effects were shown to result in intermediate changes corresponding to the sum of their individual effects. Second, selective and combined effects onFRPNwere shown to start for rates corresponding to the upper hah* of the 1:1 nodal conduction range and to reach their maximums at the fastest rate tested. Third, the time-courses of fatigue-induced prolongations in nodal conduction time andFRPNwere shown to be closely linked. Facilitation effects on conduction time andFRPNwere confirmed, as previously shown for in situ dog hearts, to be linked, but time-independent. Fourth,FRPNwas shown not to correspond to particular limits in its subintervals, but to be, nevertheless, related to nodal refractoriness. Fifth, it was demonstrated that, in conditions of combined facilitation and transient fatigue such as those prevailing in current endocavitary investigations of nodal function,FRPNcould be shortened, left unchanged or prolonged by a constant fast rate depending on its duration. In conclusion, the present study demonstrates the dual origin of rate-inducedFRPNvariations, their rate and time dependence, their relation to changes in nodal refractoriness, and their involvements in various nodal responses.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To characterize adenosine-mediated vascular responses, synthetic A1and A2receptor agonists (N-ethyl carboxamido adenosine [NECA], 2-chloro adenosine [2CA], or cyclohexyl adenosine [CHA]), the parent compound (adenosine [ADO]), an uptake inhibitor (dipyridamole [DIPYRID]) or a nonselective, competitive antagonist (8-phenyl theophylline [8pTHEO]) were topically applied to 20–60 μm arterioles in the subcutaneous microcirculation of the hamster. Blood flow was calculated from arteriolar diameter and red blood cell velocity using intravital microscopy. At >10−8M, the potency order for vasodilation (maximum, 170–190% of control) was NECA>2CA>ADO; these responses were attenuated by 10−5M 8pTHEO. From 10−8to 10−6M, 2CA evoked vasodilation whereas ADO, which has an identical affinity at A1and A2receptors, evoked lesser responses. ADO-induced vasodilation was potentiated by 10−5M DIPYRID; this response was similar to that evoked by 2CA alone or 2CA+DIPYRID. In contrast to ADO, 2CA is a poor substrate for cellular uptake, which suggests that uptake reduces the A2effect of exogenous ADO. From 10−10to 10−8M, CHA and ADO were equipotent for causing vasoconstriction (minimum, 80–90% of control); these responses were completely antagonized by SpTHEO. Norepinephrine was a more potent vasoconstrictor and 8pTHEO did not alter these responses. Since ADO is a metabolic substrate and a nonselective receptor agonist, while CHA is Arselective and a poor substrate for cellular uptake, neither A2activation nor cellular uptake altered expression of the A1effect of exogenous ADO. Furthermore, DIPYRID had no effect on the A1response. Thus, depending on agonist concentration, stimulation of high affinity A1receptors or low affinity A2receptors can cause opposite responses in the skin microcirculation. The precise location or physiological role of these receptors is unknown.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The hypothesis that cocaine has Class I-type antiarrhythmic drug effects was tested in tissues isolated from rabbit heart with standard microelectrode methods. Propranolol (1 μM) was used to block 0-adrenergic effects. The actions of cocaine on cellular electrophysiology were concentration- and time-dependent and were reversible. In paced right atrial (RA) and right ventricular papillary (RVP) tissues, cocaine produced a profound prolongation of the effective refractory period (ERP) assessed by either premature stimulation or minimum pacing interval. ERP was increased up to eightfold in RA tissue and doubled in RVP tissue by 60 μM cocaine. This concentration of cocaine depressed action potential phase 0 depolarization 80% in RA tissue and 53% in RVP tissue but had no effect on resting membrane potentials. Automaticity was moderately depressed in sinus node (34% decrease in rate) but not in tricuspid valve cells. Phase 0 depolarization was not altered hi these spontaneously active slow-response cells. Repolarization was depressed in RA, tricuspid valve, and sinus node cells leading to a twofold increase in action potential duration during exposure to cocaine. Evidence from the effects on cellular action potentials suggests that cocaine affects both fast Na+channels and repolarizing K+but not Ca2+channels. We conclude that cocaine has Class I-type activity and the effects on ERP are extreme.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

When exposed to an increasing transmural pressure, middle cerebral arteries of tbe cat exhibit reduction of internal diameter which is mediated by vascular muscle cell depolarization. This laboratory has recently demonstrated that this "pressure-induced" activation is dependent upon the presence of an intact endothelium. The present studies were undertaken to determine if this phenomenon is due to inhibition of tonically released endothelium-derived relaxing factors (EDRF) or release of a contractile substance. When cerebral arterial segments were pressurized to between 40 and 160 mm Hg there was 13.2% reduction in internal diameter accompanied by significant muscle cell depolarization from -53 ± 2.7 to -22 ± 1.4 mV. There was a significant positive correlation between the A E, and step increases in transmural pressure. These excitatory responses were lost and vessels dilated to pressure when the endothelium was removed. Upon exposing the denuded vessel to a pressurized intact donor, the denuded vessel recovered its ability to contract and depolarize suggesting that a contractile substance might be released from the vascular endothelium upon pressurization. The EDRF antagonist oxyhemoglobin did not alter the excitatory response to pressure in these isolated cerebral arteries further suggesting that the reduction in diameter and muscle cell depolarization results from the release of a contractile substance from the vascular endothelium and not inhibition of EDRF. {Circulation Research 1989;65:193–198)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Experimeats were performed to study the cellular mechanism of endothelium-derived relaxing factor (EDRF) on vascular smooth muscle. Rat femoral arteries were cannulated and pressurized to 100 mm Hg. Vascular smooth muscle membrane potential (Em) and diameter responses to perfusion with 5times10−6M acetyicholine (ACh) were measured in vessels precontracted with 5times10−6M norepinephrine (NE). Hyperpolarization (−35 ± 1.2 to -66 ± 2.0 mV) and dilation were observed during ACh administration. Both responses were abolished on removal of the endothelium with collagenase. A bioassay was developed in which two vessel segments from the same artery were connected in series. The downstream vessel was deendothelialized while the endothelium of the upstream vessel remained intact. The protocol used was the same as in the first set of measurements. Hyperpolarization and dilation were observed in both vessels during ACh perfusion. However, when the direction of the perfusate flow in the bioassay system was reversed so that the deendothelialized vessel was upstream, only the "endothelium-intact" vessel demonstrated vascular smooth muscle hyperpolarization. To examine the ionic mechanism underlying the hyperpolarization presumably by released EDRF, the Em was measured as a function of increasing extracellular potassium ([K+]o). In the presence of ACh (but not NE) the maximum depolarization produced by a decade increase of [K+]o(10- 100 mM) was 50 mV. In the deendothelialized vessel, this depolarization was decreased significantly to 39 mV. Addition to the superfusate of 10 mM tetraethylammonium, a K+channel blocker, significantly reduced the hyperpolarization caused by ACh-induced EDRF release. In conclusion, this bioassay represents a useful method for measuring the biomechanical and electrophysiological effects of EDRF. In addition, the data obtained using this methodology support the hypothesis that the EDRF-induced hyperpolarization is mediated, at least in part, by an increase in K conductance.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The Syrian cardiomyopathic (CM) hamster (BIO 14.6) develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, and, eventually, cardiac dilatation and congestive heart failure. Several lines of evidence implicate cellular calcium overload as an Important etiologic factor. We previously reported an increased number of receptors for calcium antagonist drugs, which block voltage-dependent calcium channels, in heart, skeletal muscle, and brain tissue of these hamsters in the early necrotic stage of the disease. To better characterize the pathophysiological significance of this abnormality we evaluated calcium antagonist receptor binding and Na+-Ca2+exchange in CM and control hamsters at different stages of disease as documented by quantitative histopathologic assessment. In CM hamsters as young as 10 days, an age previously thought to be before the onset of disease, we identified cardiac myocyte hypertrophy, a twofold increase in calcium antagonist receptor binding in heart and brain, and a 50% increase in skeletal muscle. Overt histological lesions were present in skeletal muscle at 25 days and in heart between 28–30 days. The size of cardiac lesions increased over time and changed from necrotic foci with cellular infiltration to fibrotic or calcined lesions by 360 days. Myocardial cellular hypertrophy persisted through the late stages of the disease (360 days), but increased calcium antagonist binding was present in heart only to 6 months of age, in skeletal muscle to 90 days, and in brain to 30 days. Na+-Ca2+exchange in heart was normal until 15 days and then increased by 400% at 30 days suggesting that this augmentation might be a secondary response to the earlier increase in calcium antagonist receptors. At 360 days cardiac Na+-Ca2+exchange was decreased by 50%, likely reflecting progressive cardiac damage. The increase in calcium antagonist receptors in CM animals as young as 10 days supports the hypothesis that abnormalities in voltage-dependent calcium channels play a role in the pathophysiology of CM hamsters.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID