摘要:

We studied atrial flutter due to circus movement in chronically instrumented conscious dogs to identify the mechanism by which class I and class III antiarrhythmic drugs terminate reentrant excitation. We used a crossover experimental design administering five class I agents and one class III agent, by intravenous bolus followed by intravenous infusion. The class I agents other than lidocaine were almost uniformly effective in terminating the arrhythmia (disopyramide in six of seven dogs, propafenone in six of six, flecainide in seven of seven, and SC-40230 in seven of seven). Termination was preceded by a marked increase in cycle length (ranging from +78% with propafenone to +55% with disopyramide), but with the exception of disopyramide, class I agents did not significantly shorten the excitable gap. With disopyramide the gap decreased from 49 ± 3% to 28 ± 3% of the cycle length. With no class I agent did the wavelength of effective refractoriness increase to approach the cycle length of the arrhythmia. Lidocaine, used as a negative control, terminated the reentry in one dog with modest prolongation of the cycle length. Terminations with class I agents correlated with depression of conduction rather than prolongation of refractoriness. In contrast with class I agents, D-sotalol prolonged the cycle length minimally (+10%) and terminated the arrhythmia in six of seven dogs. It decreased the excitable gap from 42 ± 4% to 26 ± 6% of the cycle, but it still did not cause the wavelength of effective refractoriness to equal the cycle length. Terminations by D-sotalol seemed to result from either failure of the lateral boundaries of the circus path or reflection within the path.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Intracoronary administration of acetylcholine or efferent vagal stimulation causes coronary vasodilation in dogs. However, in baboons it has been reported that intracoronary acetylcholine results in a fall in coronary blood flow and that stimulation of the vagi is without effect. The dose response of intracoronary acetylcholine and the effect of efferent vagal stimulation on the coronary circulation were reinvestigated in closed-chest, anesthetized dogs and baboons. The left main coronary artery was cannulated and perfused at constant pressure. o-Adrenergic and 0-adrenergic receptors were pharmacologically blocked with phenoxybenzamine and propranolol. Heart rate was held constant by right ventricular pacing. In dogs, intracoronary infusion of acetylcholine (1-300 μg/min) elicited a dose-dependent increase in steady-state coronary blood flow and coronary sinus oxygen tension, without a change in myocardial oxygen consumption. Vagal stimulation caused a coronary vasodilation that was attenuated by a metabolically mediated decrease in flow. In baboons, acetylcholine increased steady-state coronary blood flow in the dose range of 1-10 μg/min, caused little change at 30 /tg/min, and decreased flow at 100-300 μg/min. Coronary sinus oxygen tension increased in a dosedependent manner up to 10 μg/min. Myocardial oxygen consumption was unchanged in the dose range of 1-10 μg/min and declined between 30 and 300 μg/min. Efferent stimulation of the vagi resulted in coronary dilation obscured by a metabolic reduction of flow. It is concluded that 1) low doses of acetylcholine elicit a primary coronary vasodilation in both species, but in baboons high doses of acetylcholine cause a reduction of both myocardial oxygen consumption and coronary blood flow below control values and 2) vagal stimulation causes a competition between coronary vasodilation and metabolic reduction of flow in dogs and baboons.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Having found the regional differences in right atrial action potentials shown in an accompanying article, we tested two seemingly paradoxical hypotheses: 1) The spatial pattern of repolarization provides a protective mechanism against reentry, and 2) repolarization inhomogeneities interact with anisotropic discontinuous propagation to produce reentry. Measurement of multidimensional refractory periods demonstrated an anisotropic distribution within large bundles with the longest refractory periods in the medial upper crista terminalis (sinus node area), a distribution similar to that of action potential durations. Also, discontinuities of repolarization were found at muscle bundle junctions. Early premature impulses originating in the sinus node area propagated throughout the right atrial preparations without conduction disturbances or reentry. Conversely, early premature impulses that originated at sites distal to the sinus node area resulted in localized conduction block at multiple sites, which frequently produced complex conduction changes and reentry. The critical nature of the site of origin of a premature impulse in initiating reentry was related to locations where the steepest repolarization gradients occurred: within anisotropic bundles in the direction of highest axial resistance (across fibers) and at muscle bundle junctions that represented localized discontinuities of axial resistance. The multiple conduction abnormalities at localized sites interacted to produce different types of reentry at a larger size scale (25 mm2to several cm2). In each case, neither repolarization inhomogeneities (leading circle concept) nor anisotropic discontinuous propagation was the only "mechanism" involved. That is, reentry at a macroscopic size scale occurred as a result of a combined repolarization-anisotropic discontinuous propagation mechanism.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have previously reported that α2-adrenoceptor stimulation enhances adenosine-induced coronary vasodilation. In the present study, we tested the hypothesis that α2-adrcnoceptor activity exerts beneficial effects on myocardial ischemia through augmentation of vasodilatory effects of released adenosine. In open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Propranolol was infused into the bypass tube to exclude the metabolic effects of norepinephrine. When clonidine (0.24 μg/kg/min i.e.) was infused for 10 minutes after reduction of coronary blood flow by partial occlusion of the bypass tube, coronary blood flow was increased by 43% from 27 ± 1 ml/100 g/min despite no changes in coronary perfusion pressure (38 ± 5 mm Hg) and a slight decrease in adenosine release. Both fractional shortening and lactate extraction ratio of the perfused area were significantly improved (fractional shortening, 1.8 ± 1.0 to 10.9 ± 1.5%, p<0.001; lactate extraction ratio, −57.8 ± 6.5 to −31.9 ± 2.4%, p<0.005). Identical results were observed in the denervated hearts, indicating that the beneficial effect of clonidine is not attributed to the prevention of norepinephrine release from the sympathetic nerve terminals. The beneficial effects of clonidine were prevented by yohimbine, an α2-adrenoceptor blocking agent. An adenosine receptor antagonist, 8-phenyltheophylline, also prevented the beneficial effects of clonidine, indicating that these beneficial effects are mediated by effects of adenosine. Furthermore, the extent of augmentation of coronary flow in the ischemic heart was coincided with that of augmentation of exogenous adenosine-induced hyperemic flow (40%) by clonidine. Production of cyclic AMP in the coronary artery during myocardial ischemia was augmented by clonidine. In 12 other dogs, myocardial ischemia was produced by intracoronary embolization of microspheres (15 μm in diameter). Clonidine enhanced (39%) the hyperemic coronary flow and improved both fractional shortening and lactate extraction ratio. Thus, we conclude that α2-adrenoceptor stimulation can ameliorate myocardial ischemia mainly due to enhancement of vasodilatory effects of adenosine released from the ischemic myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The multiple indicator dilution technique was used to study transfer of labeled HCO3∼ across the hepatocyte membrane in the anesthetized mongrel dog. A bolus of H['4C]O3∼, JICr-labeled erythrocytes, [36CI−] and/or [3H]sucrose, and [3H]OH was injected through a catheter in the portal vein, and timed anaerobic blood samples were obtained from a catheter in the hepatic vein. Experiments were carried out in untreated controls and after intravenous infusion of acetazolamide (100 mg/kg). In the controls, the H[14C]O3curve was very similar to the [3H]OH curve. The dilution curves were all linear transformations of each other, indicating that HCO3∼, as had previously been shown for the other diffusible tracers, undergoes delayed-wave flow-limited distribution. The distribution space for H[14C]O3∼ in the control situation includes the blood plasma and interstitial spaces, the erythrocyte interior modified by a Donnan equilibrium, and the available liver cellular space. The calculated HCO3∼ concentration in the liver cells was somewhat lower than that in the plasma space; the difference implied a cellular pH lower than that of plasma by approximately 0.08 pH units. When the carbonic anhydrases were inhibited with acetazolamide, the dilution curve for H[HC]O3∼ changed radically, approaching that for [36Cl], which does not enter the liver cells. The change indicates that although HCO3∼, like Cl", is rapidly exchanged between plasma and erythrocytes, it also does not readily penetrate hepatocytes unless previously transformed to carbon dioxide by the carbonic anhydrases.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A number of genetic disorders in humans are associated with defects in the synthesis and metabolism of collagen, which are accompanied by multiple cardiovascular disease processes. To determine whether genetically determined cross-linking abnormalities of collagen may alter cardiac function, left ventricular papillary muscles of mice with a genetic defect in the cross-linking of collagen (Movbr) were studied in vitro. With respect to controls, increases in time to peak tension, from 102 ± 1.4 to 125 ± 5.4 msec (p<0.001), and time to one-half relaxation, from 76 ± 3.0 to 98 ± 6.1 msec (/J<0.05), were measured. Moreover, resting tension at the length associated with maximum developed isometric force (L) was elevated, from 11.1 ± 1.7 to 19.3 ± l.l mN/mm2(p<0.001), and a similar difference was also seen throughout the physiological range of muscle lengths. In contrast, developed tension was depressed at 93-97% of L. Peak rate of tension rise and decay were diminished whereas time to peak rate of tension rise was prolonged. Isotonically, a decrease in the magnitude of peak shortening at L, from 4.0 ± 0.5 to 2.0 ± 0.2% (p<0.04), and an increase in time to peak shortening, from 100 ± 2.3 to 129 ± 2.8 msec (p< 0.001), were seen. In addition, peak velocities of shortening and relengthening were diminished in the Movbrmouse heart. In conclusion, the impairment in collagen cross-linking alters cardiac mechanics by a reduction in force-generating ability and a prolongation of the timing parameters of the systolic and diastolic phases of contraction in vitro.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The heart is the first functioning organ in the embryo and provides blood flow during cardiac morphogenesis from a muscle-wrapped tube a few cells thick to the four-chambered pump. We described the hemodynamics of the chick embryo from stage 12 (50 hours of a 21-day incubation) to stage 29 (6 days), during which the embryo weight increased 120-fold. We measured ventricular, embryo and extraembryonic vascular bed wet weights, dorsal aortic blood flow with a directional pulsed-Doppler velocity meter, and ventricular and vitelline arterial blood pressures witfa a servo-null micropressure system. The data are reported as mean ± SEM. With rapid development and morphogenesis, dorsal aortic blood flow increased from 0.015 ± 0.004 to 2.40 ± 0.20 mm3/sec parallel to the geometric increase of wet embryo weight from 2.22 ± 0.10 to 267.5 ± 9.7 mg. Dorsal aortic blood flow normalized for embryo and extraembryonic weight remained relatively constant (Y=2.13+0.02X, r=0.23, SEE=0.03). Stroke volume increased from 0.01 ± 0.003 to 0.69 ± 0.03 mm3, and heart rate doubled from 103 ± 2 to 208 ± 5 beats/min. Systolic, diastolic, and mean vitelline arterial pressure increased linearly from 0∼32 ± 0.01, 0.23 ± 0.01, and 0.28 ± 0.01 mm Hg at stage 12 to 2.00 ± 0.06, 1.22 ± 0.03, and 1.51 ± 0.04 mm Hg, respectively, at stage 29. Ventricular peak systolic and end-diastolic pressure increased from 0.95 ± 0.04 and 0.24 ± 0.02 at stage 12 to 3.45 ± 0.10 and 0.82 ± 0.03 at stage 29, respectively. The hemodynamic waveforms were similar to those found in the four-chamber heart of the mature animal. These data are integral to understanding the interrelation of function and form during cardiac development.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study was carried oat to examine the effects of atrial natriuretic peptide on coronary collateral blood flow. Studies were performed in nine adult mongrel dogs 3.4 months after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study the anterior descending coronary artery was cannulated to allow estimation of interarterial collateral flow from measurements of retrograde blood flow. Injection of radioactive microspheres during retrograde flow collection allowed simultaneous determination of continuing tissue flow for evaluation of microvascular collateral communications. Atrial natriuretic peptide in doses of 20 and 200 μg administered into the left atrium resulted in 17 ± 3.0% and 34 ± 4.5% increases in retrograde flow, respectively (each<0.01). Tissue flow in the collateral dependent myocardial region did not change in response to atrial natriuretic peptide. After the larger dose of atrial natriuretic peptide, the administration of nitroglycerin (10 μg/kg into the left atrium) caused no further increase of retrograde blood flow, and no further decrease of collateral vascular resistance. These data indicate that atrial natriuretic peptide causes vasodilation of moderately welldeveloped interarterial coronary collateral vessels. 1671 1678

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To study the pathogenesis of platelet activation in ischemic stroke, ionized calcium ([Cai2+]) was measured in aequorin-loaded gel-filtered platelets in the basal and stimulated state. Basal [Cai2+] was increased in stroke patients maximally 36-72 hours after onset. The increase in [Cai2+] after stimulation with thrombin, collagen, and platelet-activating factor were also greater in stroke patients, but the profiles of these [Cai2+] changes were parallel to control. Cross incubation of control platelets with plasma from stroke patients resulted in raised basal [Cai2+] and caused the release of serotonin from platelets. These results indicate that the higher platelet basal [Cai2+] in stroke patients represents a lowered threshold for activation and that this may be due to a plasmatic factor rather than a primary platelet defect.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study was carried out to test the hypothesis that adrenergic coronary vasoconstriction limits blood flow to hypoperfused regions of myocardium during exercise. The vasoconstrictor influence of α-adrenergic receptor subtypes was assessed by use of selective adrenergic blocking agents. Dogs chronically instrumented with a circumflex coronary artery hydraulic occluder and an intra-arterial catheter underwent treadmill exercise in the presence of a coronary stenosis that decreased distal perfusion pressure to 40 mm Hg. Myocardial blood flow was measured with radioactive microspheres (15 μm) before and during selective α1- or α2afcadrenergic receptor blockade produced by intracoronary infusion of prazosin (1 /tg/kg/min×lO min) or idazoxan (1 μg/kg/min × lO min), respectively. Coronary perfusion pressure was held equal before and during receptor blockade with the hydraulic occluder. Compared with control exercise, subendocardial blood flow increased during α2-receptor blockade with prazosin from 0.60 ± 0.14 to 1.12 ± 0.17 ml/min/g (p<0.05), and mean transmural flow increased from 1.07 ± 0.19 to 1.60 ± 0.22 ml/min/g (p<0.05). In contrast, subendocardial and mean transmural blood flow were not different from control during selective α2-adrenergic receptor blockade with idazoxan (0.48 ± 0.10 vs. 0.67 ± 0.14 ml/min/g, p=0J3, and 0.82 ± 0.15 vs. 1.02 ± 0.2© ml/min/g, p-Q.45, respectively). These data indicate that even in the presence of a coronary stenosis that causes substantial myocardial underperfusion during exercise, residual coronary vasoconstrictor tone is present in iscbemic myocardium, and this vasoconstriction is mediated predominantly by the α1-adrenergic receptor.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID