摘要:

To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that it would be unlikely to cause substantial chemical changes in the contractile proteins and that most of the effects would be due to changes in the level of activation. The effects of a digitalis analogue (acetylstrophanthidin), an adrenergic agent (isoproterenol), and a methylxanthine (caffeine) were then compared with those of postextrasystolic potentiation. The conditions were chosen so that each agent caused a twofold increase in twitch force. Acetylstrophanthidin and postextrasystolic potentiation caused twitch force to increase with only a slight (11%) decrease in time to peak force. Isoproterenol caused the peak of the twitch to occur substantially (40%) earlier with marked abbreviation of the twitch. Caffeine had the opposite effect: time to peak force was delayed (by 60%), and the twitch was markedly prolonged. In contrast to the marked differences in the time course of the twitch, there was no significant difference between the instantaneous force-velocity curves obtained with the different interventions. All four interventions caused maximum velocity to increase slightly (1-9%) and maximum power to increase only slightly more than twitch force (5-21%). All of the changes observed can be accounted for by changes in activation, either by an increase in the amount of calcium released into the myonlament space or by a change in the sensitivity of the myonlaments to calcium. There was no need to postulate direct changes in the contractile machinery to account for these results.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To clarify the characteristics of the phasic blood velocity pattern in small arteries and veins on the left atrial surface, we used our newly developed fiber-optic laser Doppler velocimeter. We intended particularly to examine the Influence of atrial contraction and relaxation on velocity waveforms to obtain some insight into the nature of the mechanical force acting on the atrial intramyocardial vascular beds. In 14 anesthetized open-chest dogs, the left atrial appendage was gently displaced to expose small branches of the artery and vein. Vessels with an outer diameter of about 150-500 μm were chosen for the measurements because their walls are transparent to laser light. The fiber tip (velocity sensor) was fixed on the vessel surface with a drop of cyanoacrylate when good-quality Doppler signals were consistently observed. Additional experiments with three dogs were performed to observe the blood velocities in the atrial artery and vein during arrhythmia. The blood velocity waveform in the artery was similar to the pattern of aortic pressure during ventricular ejection (peak velocity, 18.8 ± 7.8 cm/sec) but was characterized by a pronounced dip during atrial contraction. The temporal coincidence between the dip formation and atrial contraction was confirmed during atrial flutter with an atrioventricular block. After isoproterenol administration (2 μg i.v.), the acceleration rate of the forward flow velocity increased by 176% (p<0.05), and reverse flow appeared during atrial contraction in five cases out of eight (p=0.013). The blood flow velocity in atrial small veins, on the other hand, was predominant during atrial contraction (peak velocity, 15.6 ± 5.8 cm/sec). Isoproterenol increased the acceleration rate of this forward flow velocity by 121% (p<0.01). Nitroglycerin did not change the blood velocity waveform significantly in atrial arteries or in veins. The phase opposition between arterial inflow into and venous outflow from the atrial myocardium indicates that a large portion of the coronary inflow to the atrial myocardium may be stored due to the presence of atrial myocardial vascular capacitance. We conclude that atrial myocardial contraction impedes atrial inflow and promotes venous outflow from atrial capacitance vessels.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To determine whether anemia-induced cardiac hypertrophy affects ventricular size and shape and the component structures of the capillary network of the left and right ventricles, young male rats were fed an iron- and copper-deficient diet for 7 weeks. By that time, blood hemoglobin content fell to 5 ± 1 g/dl, and packed cell volume fell to 18 ± 3%. To further characterize the implications of anemia, red blood cell number, hemoglobin corpuscular content, systemic arterial pressure, heart rate, and blood viscosity were measured. Moreover, the changes in ventricular weights were analyzed in terms of the alterations in ventricular wall area and ventricular wall thickness to establish the impact of the elevation in load associated with a high cardiac output state on ventricular remodeling. The quantitative properties of the capillary circulation were also examined biventriculariy by low power electron microscopic morphometry to evaluate the adaptive growth potential of the coronary microcirculation in this form of cardiac hypertrophy. Anemia was found to interfere with the production of red blood cells and their mean corpuscular hemoglobin content and resulted in a 40% reduction in blood viscosity and a 12% and 27% decrease in systolic and diastolic blood pressure, respectively. The changes in heart rate were not statistically significant. In comparison with control animals, heart weight increased by 50%, but the enlargement in right ventricular mass (65%) was greater than that of the left ventricle (47%). Ventricular hypertrophy occurred with increases in wall area and wall thickness although the former increased consistently more than the latter in either ventricle. Tissue growth was accompanied by a 60% lengthening of the capillary network, which in combination with an increase in capillary diameter resulted in a 65% and 34% expansion in capillary luminal volume and 56% and 20% larger luminal surface density in the left and right sides of the heart, respectively. In conclusion, hypochromic microcytic anemia leads to eccentric ventricular hypertrophy with a significant amount of capillary proliferation that may tend to protect the myocardium from the increased potential for ischemic injury.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The goal of the present study was to evaluate the effects of endothelin, a newly discovered very potent vasoconstrictor secreted by endothelial cells, on the coronary vascular bed. For this purpose, the effects of endothelin injected intracoronarily were tested in open-chest anesthetized dogs with the circumflex coronary artery cannulated and perfused at a constant pressure of 100 mm Hg. Circumflex blood flow, transmural distribution of coronary blood flow (radioactive microspheres), circumflex coronary artery diameter (piezoelectric crystals), and circumflex luminal surface area were measured. Endothelin decreased coronary blood flow by 30% and 61% with doses of 1 and 3 μg, respectively. A dose of 10 μg was lethal. The decrease of coronary blood flow was larger in the subepicardium than in the subendocardium, which explains that the endocardiai-epicardia] blood flow ratio increased from 1.27 ± 0.05 to 1.98 ± 0.23 (p<0.001) with a dose of 3 μg endothelin. Circumflex surface area decreased by 7% (p=NS) and 20% (p<0.01) with doses of 1 and 3 μg endothelin, respectively. The action of endothelin was not modified by the concomitant o^adrenergic blockade, serotonergic blockade, angiotensin converting enzyme inhibition, or cyclooxygenase inhibition. We conclude that endothelin is a potent coronary vasoconstrictor with a selective effect on the subepicardium. At least part of the increase of coronary vascular resistance is due to a constriction of the large coronary arteries. Further studies are required to determine the physiopathological role of endothelin, especially in coronary vasospasm.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The purpose of the present study was to characterize adenosine receptors in human atrial and ventricular myocardium. In isolated electrically driven preparations, adenosine produced „direct” negative inotropic effects in atrial myocardium (AT). In ventricular myocardium (VE), it only had negative Inotropic properties when force of contraction had been stimulated with isoprenaline (“indirect” effect), but it has no inotropic effect alone. The adenosine receptor antagonist 8-phenyltheophylline antagonized the „direct” and „indirect” effects; these findings indicated that both effects were mediated by adenosine receptors. In cardiac membranes from human AT and VE, adenosine receptors were characterized with [3H]-8-cyclopentyl-l,3-dipropylxanthine (DPCPX) binding. The effects of agonists.R-(-)-N6-phenylisopropyladenosinc (R-PIA),S-(+)-N6-phenylisopropyladenosuie (S-PIA), and 5′-(N-ethylcarboxamido)adenosine (NECA) and the effects of guanine nucleotides [Gpp(NH)p] were studied also. The antagonist affinities as judged from the apparent affinity, Kd, of [3H] DPCPX were similar in AT (2.2 nmol/1; 95% confidence limits, 1.4–3.7) and VE (1.8 nmol/1; 95% confidence limits, 1.0–3.0). The number of adenosine receptors was 1.7 times greater in AT (26.9 ± 2.33 fmol/mg protein;n=5) than in VE (16.2 ± 23 fmol/mg protein;n=5). High and low affinity states of adenosine receptors evaluated with the influence of Gpp(NH)p on agonist competition withR-PIA were similar in AT or VE. The rank orders of potency for agonists (R-PIA>S-PIA>NECA) and antagonists (DPCPX>8-phenyltheophylline>theophylline) were characteristic for the A, receptor subtype. It is concluded that A, adenosine receptors exist in the human myocardium. Since binding properties were similar in AT and VE, the same A1adenosine receptor probably couples to different effectors in a similar guanine nucleotide-dependent way. [3H] DPCPX is the first radiolabeled antagonist ligand that allows detection of A, adenosine receptors and their coupling in the human myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The heart contains superficial cardiac nerves whose effects may be modulated by pericardial fluid bathing the epicardium. We tested this hypothesis In open-chest dogs anesthetized with secobarbital. Oxygenated normal Tyrode's solution (NT) or NT containing hexamethonium, a ganglionic blocker (500 μM), or tetrodotoxin, a blocker of axonal neurotransmission (5 μM, TTX), was instilled into the pericardial cavity to superfuse the epicardium of the whole heart. During each superfusion, effective refractory period (ERP) was determined in deep intramyocardium (≥4 mm in depth from the epicardium) of anterior and posterior left ventricle and in the subendocardium of the right ventricle in the baseline state and during bilateral cervical vagal stimulation (VS) or ansae subclaviae stimulation (SS). Lengthening of ERP induced by VS during superfusion with NT (6.9 ± 0-3 msec, mean ± SEM, n-36) was eliminated during subsequent superfusion with hexamethonium (0.9 ± 0.5 msec,p<0.001). Hexamethonium also prevented sinus arrest induced by VS but did not affect shortening of ERP induced by SS (17.3 ± 1.3 to 16.6 ± 1.0 msec,n=26). TTX suppressed VS-induced changes in ERP (6.3 ± 0.3 to 1.5 ± 0.5 msec,n=32, p < Q.OQ1) and SS-induced changes in ERP (18.8 ± 1.6 to 6.0 ± 0.9 msec,n=23,p<0.001) but did not affect changes in ERP induced by intravenous administration of norepinephrine or methacholine. This indicates that the suppresslve effect of TTX on neurauy induced changes in ERP was due to an inhibition of neurotransmission and not on the response of the effector site to the neurotransmitter. We conclude that 1) vagal ganglia that innervate both ventricles as well as sinus node are distributed superficially and are blocked by epicardial superfusion with hexamethonium, 2) the epicardium lacks sympathetic ganglia, and 3) both vagal and sympathetic axons at some point travel superficially during their course in the heart and are blocked by TTX. These results suggest that substances in the pericardial fluid, whether normally secreted or present due to disease, have the potential to modulate autonomic neural transmission to the heart. {Circulation Research1989;65:1212-1219)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Activated polymorphonuclear leukocytes (PMNs) contribute to myocardial injury during ischemia and reperfusion. There is evidence that activation of the complement pathway may be one of the mechanisms of PMN activation during ischemia. Intracoronary infusion of complement C5a during normal perfusion pressure is associated with decreased coronary Bow, contractile dysfunction, and PMN accumulation. The mechanisms responsible for these changes have not been identified. Thromboxane A2 (TXA2) is a potential mediator of this myocardial ischemic response. Activated PMNs produce TXA2, a known coronary vasoconstrictor, and TXA] was shown to be a mediator of the pulmonary hypertensive response to activated complement. The goal of the present study was to determine if an enhanced TXA2production is associated with the myocardial response to C5a and whether cyclooxygenase blockade would reduce the myocardial ischemia. In open-chest pigs, intracoronary C5a (500 ng) caused reversible reductions in blood flow (50.0% of control), regional contractile function (25.8% of control), leukocyte trapping (1.0 × 106cells/g myocardium or a peak artery-coronary venous difference of 5.3 × l03cells/μl blood), and increased coronary venous TXB2(the TXA2breakdown product) from 1.6 pmol/ml to a peak of 6.9 pmol/ml. Cyclooxygenase blockade with aspirin or indomethacin, which prevented TXB2production, did not alter the response in flow, function, or PMN trapping. Ibuprofen, a known direct inhibitor of PMNs in addition to Its cyclooxygenase blockade effect, reduced the response slightly. The pig coronary vascular bed was responsive to the TXA2agonist U46619, which reduced flow and function without PMN trapping. Mechanical reductions in coronary flow to levels equivalent to those during the C5a infusions did not increase coronary venous TXB2nor cause PMN trapping but did cause equivalent contractile dysfunction. Incubation of whole blood with C5a at concentrations equivalent to those achieved in vivo did not cause TXB3production. We conclude that 1) TXA2is produced in response to intracoronary C5a and 2) cyclooxygenase blockade does not prevent the C5a-induced myocardial ischemia, contractile dysfunction, and PMN trapping. The TXA2production likely involves a vascular site or a blood cell-vascular interaction. This model system indicates the potential for persistently activated PMNs to cause continued ischemia during myocardial reperfusion.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Using mice transgenic for the growth hormone gene (TGHM), we have studied the effects of a systemic elevation of growth hormone on vascular growth with the aim of investigating the role of vascular mass changes in producing hypertension. In contrast to human acromegaly or gigantism, there was no elevation of blood pressure in TGHM, but there were significant increases in vascular wall mass. In accordance with a presumably Increased perfusion of larger organs, the medial cross-sectional areas of thoracic aorta and mesenteric resistance vessels were greater in the TGHM. These differences could be normalized in the aorta by body weight and in the mesenteric vessel by small intestine weight. Furthermore, the brain was not significantly heavier in the TGHM, and their carotid and cerebral vessels also were not larger. Wallto- lumen ratios were similar in the aorta, carotid, and middle cerebral arteries suggesting that wall stress was the controlling factor in wall thickness. Surprisingly, the mesenteric vessels had increased wall-to-lumen ratio, which was similar to that seen in hypertensive vascular remodeling but in a normotensive animal. In an attempt to explain this finding it was noted that the pattern of mesenteric vascular networks and even organized structure within the vessel wall itself appeared to be fixed, perhaps by genetic mechanisms. Thus, vascular network structure may be a potentially limiting factor in the ability of the vessel wall to remodel and may have been responsible for the greater wall-to-lumen ratio in TGHM mesenteric vessels. A similar situation in human acromegaly or gigantism could result in a circulation marginally able to correct for other demands on blood flow resulting in about one third of cases being hypertensive.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have isolated a full length complementary DNA clone (pCTnCl) from a 19-day embryonic chicken heart library corresponding to cardiac troponin C (TnC). Sequence analysis demonstrated varying homologies with TnC complementary DNA clones isolated from developing chick skeletal muscle. Using pCTnCl as a hybridization probe, we have determined that cardiac TnC is constitutively expressed in both atria and ventricles of the developing and adult heart. These data along with previous immunochemical studies of TnC expression demonstrate that the slow skeletal and cardiac muscle Isofonn is the only TnC expressed in the heart. In contrast, expression of slow skeletal and cardiac muscle TnC is developmentally regulated in skeletal muscles of the chicken. The tightly controlled expression of slow skeletal and cardiac muscle TnC in the varying myocyte types of the heart suggests a physiologically significant role of this regulatory protein.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The mechanism of interaction of lidocaine with cardiac sodium channels during use-dependent block is not well denned. We examined the blockade of single cardiac sodium channels by lidocaine and its hydrophobic derivative RAD-242 in rabbit ventricular myocytes. Experiments were performed in cell-attached and inside-out patches. Use-dependent block was assessed with trains of ten 200 -msec pulses with interpulse intervals of 500 msec and test potentials of -60 to -40 mV. Single-channel kinetics sometimes showed time-dependent change in the absence of drug. During exposure to 80 μM lidocaine, use-dependent block during the trains was associated with a decrease in the average number of openings per step. At -60 mV, mean open time was not significantly changed (control, 1.4 ± 0.6 msec; lidocaine, 1.2 ± 03 msec, P > 0.05). Greater block developed during trains of 200 -msec pulses compared with trains of 20-msec pulses at the same interpulse interval at test potentials during which openings were uncommon later than 20 msec (−50 and -40 mV). Prolonged bursts of channels showing slow-gating kinetics were observed both in control and the presence of 80 μM lidocaine. However, lidocaine may decrease the late sodium current by altering the kinetics of slow gating. The hydrophobic lidocaine derivative RAD-242, which has a 10-fold greater lipid solubility than lidocaine, decreased the peak averaged current during pulse train stimulation by 60% without a change in the mean open time. Our results suggest that the major effect of lidocaine during use-dependent block involves the interaction with a nonconducting state of the sodium channel followed by a failure to open during subsequent depolarization. {Circulation Research1989;65:1247-1262)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID