ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Action potentials and membrane currents were recorded from isolated single ventricular cells from rabbit hearts using the suction pipette whole-cell clamp method. Action potentials elicited after short diastolic intervals of < 2 seconds showed an increase and prolongation of the plateau compared to those elicited after a 10-second rest period. The recovery of the tetrodotoxin-insensitive secondary inward current revealed a transient increase at short diastolic intervals above the level of full recovery (after 10 seconds). The increased secondary inward current recovery, however, was voltage-dependent, and the period of its increase did not cover the entire diastolic intervals of the action potential overshoots, suggesting the contribution of another ionic current to the changes in potential. During depolarizing voltage steps, from + to - 20 mV, a rapid activating and then inactivating outward current was elicited, which overlapped the calcium current. This outward current exhibited time- and voltage-dependent properties similar to those of the transient outward current in Purkinje and other cardiac preparations. The recovery of the transient outward current was slow, achieving only 75% of its full level at 2 seconds, whereas the same level of calcium current recovery was achieved at 200 milliseconds. The application of 4-aminopyridine suppressed most of the transient outward current, and the rest of the current was abolished by caffeine or Co2+. The 4-aminopyridine sensitive transient outward current exhibited slow recovery kinetics compared to those of the other or calcium current, and its inhibition caused elimination of the augmented plateau during electrical restitution. The application of verapamil or Co2+ for inhibition of secondary inward current also abolished the action potential overshoot. These results indicate that an increase and prolongation of the plateau at short diastolic intervals are produced by the slower recovery from inactivation in the 4-aminopyridine-sensitive transient outward current than that in the calcium current.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Previous studies have shown that ablation of cranial neural crest results in heart malformations in chick embryos. Cranial neural crest cells populate all of the pharyngeal arches and provide the mesenchymal walls of the aortic arch arteries. Neural crest cells migrate from the pharyngeal apparatus into the outflow region of the heart. However, it is not known which of the pharyngeal arches contribute ectomesenchyme to the developing heart nor has a pattern of distribution in the outflow region been established. In the present study, premigratory presumptive arch neural crest from quail embryos was grafted homotopically onto early chick embryos. On Day 6 of incubation, the chimeric embryos were fixed and processed for histological evaluation. The neural crest providing mesenchyme to pharyngeal arches 1 and 2 was not associated with the developing heart. Neural crest presumptive for arches 3,4, and 6 was found distributed to the outflow region of the heart. Neural crest from arch 4 contributed the largest number of cells to the developing aorticopulmonary and conotruncal septa. This information indicates that ablations of neural crest presumptive for arches 3,4, and 6 influence heart development directly while lesions of other areas of cranial neural crest probably influence heart development only secondarily with the primary effects occurring in the pharyngeal arches.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

This study was designed to determine whether the endothelium-derived relaxing factor induced by acetylcholine (1 μ.M) in rabbit thoracic aorta inhibits agonist-induced calcium mobilization, specifically calcium influx. Force generated in rings of rabbit thoracic aorta by norepinephrine (1 μM) was measured under isometric conditions. At the appropriate time during 1 fiM acetylcholine-induced relaxation of 1 μM norepinephrine-contracted rabbit thoracic aorta, the rings were pulse-labelled with calcium-45 to measure calcium influx. When measured in this fashion, 1 μM acetylcholine decreased the 1 μ.M norepinephrine-induced increase in calcium influx. This effect was eliminated by removal of the endothelium and by atropine (1 μM), but not by indomethacin (14 μM). Acetylcholine (1 fiM) also blocked the 60 mM potassium-chloride-induced increase in calcium influx without dramatically affecting force. The phasic contraction produced by norepinephrine (1 μM) with 2 mM lanthanum pretreatment, which is caused by release of intracellular calcium, was inhibited by acetylcholine (1 μM) in a fashion similar to 1 μM nitroglycerin. The tonic contraction produced by norepinephrine (1 μM) after depletion of the agonist-releasable pool of intracellular calcium, which is thought to be due to calcium influx, was depressed by acetylcholine (1 μM). These data suggest that endothelium-derived relaxing factor relaxes 1 μM norepinephrine-contracted rings of rabbit thoracic aorta by decreasing calcium entry and by producing an extracellular calcium-independent relaxant effect.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The actin binding and ATPase kinetics of cardiac myosin subfragment-1 were compared with prior studies on skeletal myosin subfragments. Previous kinetic studies on rabbit skeletal subfragment-1 (S-l) have revealed two important features of the actomyosin ATPase activity. First, hydrolysis of ATP by myosin subfragment-1 proceeds both when S-l is bound to actin and when it is dissociated from actin. Second, the actin concentration required to reach half the maximum ATPase activity, Ka(ATPase), is considerably lower than the actin concentration required to bind half the subfragment-1 during steady state hydrolysis of ATP, Ka(binding). These kinetic facts require that skeletal myosin hydrolyze ATP without dissociating from actin; therefore, a “nondissociating” pathway for ATP hydrolysis exists. The studies reported here show that porcine cardiac S-l is very similar to rabbit skeletal S-l. Under identical conditions to prior work on skeletal S-l, the Ka(ATPase) of porcine cardiac S-l is approximately equal to that reported for skeletal S-l. This is also true for Ka(binding). Comparison of Ka(ATPase) and Ka(binding) shows that for cardiac proteins Ka(ATPase) is fourfold to sixfold stronger than Ka(binding), i.e., half maximal ATPase activity is achieved at about one fifth the actin necessary to reach 50% binding. The extrapolated maximum ATPase activity at saturating actin concentration for cardiac S-l is consistently slower than skeletal S-l by about a factor of 2.5. Furthermore, studies of the actoS-1 ATPase activity at high actin concentrations as well as with crosslinked actoS-1 show no significant inhibition, implying the requirement of a “nondissociating” pathway for ATP hydrolysis by cardiac myosin subfragment-1.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Purified synthetic products from the cytochrome P450 pathway of arachidonate metabolism were applied to the intestinal serosa. Arteriolar blood flow was calculated using video microscopy. After a steady-state baseline, a bolus containing 10–60 μg 14,15-epoxyeicosatrienoic acid/ml (14,15-EET) had no detectable effect on blood flow. However, 25 ±3 μg 11,12-EET/ml and 36 ±2 μg 8,9-EET/ml caused increases (134 ± 8% and 127 ± 6%) that were similar to those elicited by 8 ± 2 μg adenosine/ml (138 ± 12%). Furthermore, the increases (275 ± 38%) produced by 32 ± 6 μg 5,6-EET/ml exceeded those elicited (160 ± 10%) by a similar concentration (27 ± 3 μg/ml) of adenosine. Thus, a structure-activity relationship is suggested. Nevertheless, these values probably underestimate the potency of the EETs because the vasoactivity was reduced by contact with water. The activity of the cyclooxy-genase pathway seemed to limit the formation of vasoactive quantities of EETs, or other nonprosta-noids, from exogenous arachidonate in the serosa but not the mucosa. A bolus (1.3 ± 0.2 mg/ml) or continuous application (122 ± 45 μg/ml) of arachidonate caused blood flow increases (236 ± 14% or 229 ± 27%) that were almost eliminated (129 ± 5% or 121 ± 9%) by a cyclooxygenase inhibitor; the residual response was abolished by a cytochrome P450 inhibitor. However, cytochrome P450 inhibitors alone did not attenuate the arachidonate response. In contrast, a continuous application of 194 fig arachidonate/ml to the mucosa caused a markedly smaller blood flow increase (119 ± 8%) and cyclooxygenase inhibitors potentiated (132 ± 8%), rather than reduced, this response. We conclude that EETs are a labile class of vasodilators with a potency comparable to adenosine in the intestinal microcirculation. Indirect evidence suggests regional differences in the formation of vasoactive quantities of arachidonate metabolites within the intestinal wall.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

This study examined the relation between left ventricular (LV) function and the severity of acute myocardial ischemia in a conscious dog model. The LV ejection fraction (EF) was measured by multigated equilibrium radionuclide angiography, and regional myocardial blood flow was measured with radioactive microspheres before and 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD, 13 dogs) or left circumflex (LC, 13 dogs) coronary artery. Two methods were used to evaluate the extent of ischemia. The first method determined the mass of myocardium that was ischemic based on different degrees of reduced blood flow. The second method estimated the severity of ischemia expressed as blood flow deficit resulting from each coronary occlusion. Global LV function was very sensitive to ischemia, and the relation between change in function and the degree of ischemia were described best by linear functions. The best linear correlation between mass of ischemic myocardium and percent reduction in EF resulted from the ischemic region defined as all tissue with 25% or greater reduction in blood flow, r=0.84 for LAD (Y = 0.96X + 1.8) and r = 0.75 for LC (Y = 0.53X + 2.0) occlusions. Defining ischemic mass by more severe reduction in blood flow resulted in exclusion of ischemic myocardium that affected function. The myocardial blood flow deficit also correlated linearly with percent reduction in EF, r = 0.89 for LAD (Y = 1.3LY + 2.7) and r = 0.81 for LC (Y = 0.83X - 0.1) occlusions. The slope of the regression lines using both analyses of ischemia were significantly greater (p< 0.01) for LAD than LC occlusions, indicating that for comparable degrees of ischemia LAD as compared to LC occlusion decreased EF to a greater extent. Calculation of EF from attenuated corrected volumes resulted in small changes in LAD, but not LC, EF and did not account for the disproportionate effects of LAD and LC ischemia. In a separate group of studies (n = 18) EF measured by radionuclide angiography after LAD or LC occlusions correlated well with biplane contrast angiography r= 0.93, SEE 5.1. These data suggest that disportionately greater effects of LAD compared to LC ischemia on global EF in the dog are due primarily to different pathophysiologic responses to ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Cardiac tamponade is a spectrum ranging from pericardia! effusions with minimal hemodynamic impairment to effusions causing circulatory collapse. In this study, we examined the roles played by the sympathetic nervous system and the renin-angiotensin system in controlling the distribution of blood flow in chronically instrumented conscious dogs during progressive cardiac tamponade. Fifty-one episodes of acute cardiac tamponade were induced to decompensation (decline in mean aortic blood pressure to 70% of the level present when the pericardium was free of fluid) in 6 dogs by intrapericardial infusion of warmed saline solution. Cardiac output (electromagnetic flow probe), intrapericardial pressure, aortic and right atrial blood pressures, and renal, coronary, and mesen-teric artery blood flows (Doppler flow probes) were recorded during tamponade in the absence of blockade (control), during α-adrenergic blockade (phenoxybenzamine), β-adrenergic blockade (pro-pranolol), or angiotensin-converting enzyme blockade (captopril). Aortic and mesenteric artery blood flow decreased progressively during cardiac tamponade regardless of the presence or absence of blockade. Coronary artery blood flow did not significantly change during a-adrenergic blockade, suggesting that the continuous decline observed during cardiac tamponade in the absence of blockade was at least in part mediated by α-adrenergic mechanisms. Renal artery blood flow, in contrast, was well maintained in all situations, confirming the importance of autoregulation in this vascular bed during cardiac tamponade.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The role of the endothelium in modulating cyclic nucleotide levels and intrinsic smooth muscle tone was studied in isolated rings of bovine intrapulmonary artery and vein. Cyclic 3′,5′-guanosine mono-phosphate (cGMP) levels were threefold to fourfold higher in unrubbed artery and vein than in vessels that had been denuded of endothelium. Cyclic 3,5-adenosine monophosphate (cAMP) levels were twofold higher in unrubbed than in endothelium-denuded artery, but no differences were observed in veins. Methylene blue, an inhibitor of guanylate cyclase, decreased cGMP but not cAMP levels, and this was accompanied by increases in smooth muscle tone. M&B 22,948, an inhibitor of cGMP-phosphodiesterase, increased cGMP but not cAMP levels, and this was accompanied by decreases in smooth muscle tone. Unrubbed vessels were more sensitive than endothelium-denuded vessels to the actions of both methylene blue and M&B 22,948, and this may be attributed to endothelium-depen-dent increases in cGMP turnover. Moreover, unrubbed vessels were more sensitive than endothelium-denuded vessels to contractile responses to phenylephrine and potassium, and these responses were potentiated by methylene blue and attenuated by M&B 22,948. Although indomethacin lowered cAMP levels in unrubbed artery, no changes in tone or contractile responsiveness were observed. A consistent observation was that the smaller branches of unrubbed but not endothelium-denuded intrapulmonary artery and vein had higher levels of cGMP but not cAMP, were sensitive to endotheli-um-dependent vasodilators, were more sensitive to methylene blue, and would not maintain a steady level of submaximal tone to phenylephrine when compared with larger branches from a common vascular bed. These data indicate that endothelium-derived factors in intrapulmonary artery and vein markedly influence intrinsic cGMP levels, sensitivity to endothelium-dependent vasodilators, smooth muscle tone, and contractile responsiveness.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We have studied the individual and combined effects of elevated external potassium concentration (8 mM [K+], metabolic acidosis (pH = 6.8), and hypoxia at different stimulation rates (BCL = 1,000 or 400 milliseconds) on Purkinje (P) and ventricular (V) conduction velocities and on Purkinje-ventricu-lar junctional conduction delay (PVJ delay) in in vitro preparations from canine ventricles. Elevated [K+] had opposite effects on P and V velocities, increasing V velocity by 8% while reducing P velocity by 7%. Acidosis reduced P velocity by 9% while reducing V velocity by only 4%. Hypoxia and rapid stimulation rates had no significant effect on either P or V velocities. All test solutions (except hypoxia alone) significantly increased the PVJ delay. The magnitude of the increase in PVJ delay was much greater than the effects on either P or V velocity. In addition, hypoxia and rapid stimulation augmented the increase in PVJ delay in the presence of elevated [K+] and/or acidosis. The special features of conduction at the PV junctional sites may produce altered pathways of excitation of the ventricles during myocardial ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID