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您现在的位置：首页>美国卫生研究院文献>American Journal of Physiology - Heart and Circulatory Physiology

期刊信息

  • 期刊名称：

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  • 刊频： Twice monthly, Feb. 2012-
  • NLM标题： Am J Physiol Heart Circ Physiol
  • iso缩写： -
  • ISSN： -

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  • 1.

    【2hr】Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase

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    机译 缺乏脂肪酸酰胺水解酶的小鼠的血流动力学特征，对anandamide的反应性和压力反射敏感性
    摘要：The endocannabinoid anandamide exerts neurobehavioral, cardiovascular, and immune-regulatory effects through cannabinoid receptors (CB). Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the in vivo degradation of anandamide. Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising novel approach for the treatment of anxiety, inflammation, and hypertension. In this study, we compared the cardiac performance of FAAH knockout (FAAH−/−) mice and their wild-type (FAAH+/+) littermates and analyzed the hemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters, systolic and diastolic function at different preloads, and baroreflex sensitivity were similar in FAAH−/− and FAAH+/+ mice. FAAH−/− mice displayed increased sensitivity to anandamide-induced, CB1-mediated hypotension and decreased cardiac contractility compared with FAAH+/+ littermates. In contrast, the hypotensive potency of synthetic CB1 agonist HU-210 and the level of expression of myocardial CB1 were similar in the two strains. The myocardial levels of anandamide and oleoylethanolamide, but not 2-arachidonylglycerol, were increased in FAAH−/− mice compared with FAAH+/+ mice. These results indicate that mice lacking FAAH have a normal hemodynamic profile, and their increased responsiveness to anandamide-induced hypotension and cardiodepression is due to the decreased degradation of anandamide rather than an increase in target organ sensitivity to CB1 agonists.
  • 2.

    【2hr】Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations

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    机译 慢性炎性疼痛导致血脑屏障通透性增加和紧密连接蛋白改变
    摘要：The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freund’s adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and infrared paw-withdrawal latency. At 72 h postinjection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [14C]sucrose while rats were under pentobarbital anesthesia demonstrated that CFA treatment significantly increased brain sucrose uptake. Western blot analysis of BBB TJ proteins showed no change in expression of zonula occludens-1 (an accessory protein) or actin (a cytoskeletal protein) with CFA treatment. Expression of the transmembrane TJ proteins occludin and claudin-3 and -5 significantly changed with CFA treatment with a 60% decrease in occludin, a 450% increase in claudin-3, and a 615% increase in claudin-5 expression. This study demonstrates that during chronic inflammatory pain, alterations in BBB function are associated with changes in specific transmembrane TJ proteins.
  • 3.

    【2hr】Increased superoxide leads to decreased flow-induced dilation in resistance arteries of Mn-SOD-deficient mice

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    机译 增加的超氧化物导致Mn-SOD缺陷小鼠的阻力动脉血流诱导的扩张减少
    摘要：The role of mitochondrial manganese-superoxide dismutase (Mn-SOD) in the maintenance of vascular function has not yet been studied. Thus we examined flow- and agonist-induced dilations in isolated mesenteric arteries (~90 µm in diameter) of Mn-SOD heterozygous (Mn-SOD+/−) and wild-type (WT) mice. Increases in flow elicited dilations in all vessels, but the magnitude of the dilation was significantly less in vessels of Mn-SOD+/− mice than in those of WT mice (64 vs. 74% of passive diameter). Nω-nitro-l-arginine methyl ester inhibited the dilation in vessels of WT mice but had no effect on vessels of Mn-SOD+/− mice. Tempol or tiron (superoxide scavengers) increased flow-induced dilation in vessels of Mn-SOD+/− mice. Acetylcholine- and sodium nitroprusside-induced, but not adenosine-induced, dilations were also decreased in arteries of Mn-SOD+/− mice. Superoxide levels in the arteries of Mn-SOD+/− mice were significantly increased. Western blot analysis confirmed a 50% reduction of Mn-SOD protein in the vessels of Mn-SOD+/− mice. A 41% reduction in endothelial nitric oxide synthase (eNOS) protein and a 37% reduction in eNOS activity were also found in the vessels of Mn-SOD+/− mice. Whereas there was no difference in eNOS protein in kidney homogenates of WT and Mn-SOD+/− mice, a significant reduction of nitric oxide synthase activity was found in Mn-SOD+/− mice, which could be restored by the administration of tiron. We conclude that an increased concentration of superoxide due to reduced activity of Mn-SOD, which inactivates nitric oxide and inhibits eNOS activity, contributes to the impaired vasodilator function of isolated mesenteric arteries of Mn-SOD+/− mice. These results suggest that Mn-SOD contributes significantly to the regulation of vascular function.
  • 4.

    【2hr】The Molecular Correlates of Altered Expression of Potassium Currents in Failing Rabbit Myocardium

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    机译 衰竭心肌中钾电流表达改变的分子相关性
    摘要：Action potential (AP) prolongation is a hallmark of failing myocardium. Functional down regulation of K currents is a prominent feature of cells isolated from failing ventricles. The detailed changes in K current expression differ depending upon the species, the region of the heart and the mechanism of induction of heart failure. We used complementary approaches to study K current down regulation in pacing-tachycardia induced heart failure in the rabbit. The APD at 90% repolarization was significantly longer in cells isolated from failing hearts compared to controls (539 ± 162 ms failing versus 394 ± 114 control, p < 0.05). The major K currents in the rabbit heart, IK1, Ito and IK were functionally down regulated in cells isolated from failing ventricles. The mRNA levels of Kv4.2, Kv1.4, KChIP2 and Kir2.1 were significantly down regulated, while the Kv4.3, Erg, KvLQT1 and minK were unaltered in the failing compared with the control left ventricles. Significant down regulation in the long splice variant of Kv4.3 but not total Kv4.3, Kv4.2 and KChIP2 immunoreactive protein was observed in cells isolated from the failing ventricle with no change Kv1.4, KvLQT1, and in Kir2.1 immunoreactive protein levels. Multiple cellular and molecular mechanisms underlie the down regulation of K currents in the failing rabbit ventricle.
  • 5.

    【2hr】PPAR-γ activation fails to provide myocardial protection in ischemia and reperfusion in pigs

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    机译 PPAR-γ激活无法在猪缺血和再灌注中提供心肌保护
    摘要：Peroxisome proliferator-activated receptor (PPAR)-γ modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-γ activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-γ activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both α-tocopherol and thiazolidinedione moieties, whether PPAR-γ activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg·kg−1 ·day−1), rosiglitazone (3 mg·kg−1 ·day−1), or α-tocopherol (73 mg·kg−1 ·day−1, equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-γ, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or α-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an α-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-γ activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its α-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest interspecies differences in the response to PPAR-γ activation in the heart.
  • 6.

    【2hr】Dynamic model for ventricular junctional conductance during the cardiac action potential

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    机译 心脏动作电位期间心室连接传导的动态模型
    摘要：The ventricular action potential was applied to paired neonatal murine ventricular myocytes in the dual whole cell configuration. During peak action potential voltages >100 mV, junctional conductance (gj) declined by 50%. This transjunctional voltage (Vj)-dependent inactivation exhibited two time constants that became progressively faster with increasing Vj. Gj returned to initial peak values during action potential repolarization and even exceeded peak gj values during the final 5% of repolarization. This facilitation of gj was observed <30 mV during linearly decreasing Vj ramps. The same behavior was observed in ensemble averages of individual gap junction channels with unitary conductances of 100 pS or lower. Immunohistochemical fluorescent micrographs and immunoblots detect prominent amounts of connexin (Cx)43 and lesser amounts of Cx40 and Cx45 proteins in cultured ventricular myocytes. The time dependence of the gj curves and channel conductances are consistent with the properties of predominantly homomeric Cx43 gap junction channels. A mathematical model depicting two inactivation and two recovery phases accurately predicts the ventricular gj curves at different rates of stimulation and repolarization. Functional differences are apparent between ventricular myocytes and Cx43-transfected N2a cell gap junctions that may result from posttranslational modification. These observations suggest that gap junctions may play a role in the development of conduction block and the genesis and propagation of triggered arrhythmias under conditions of slowed conduction (<10 cm/s).
  • 7.

    【2hr】Reciprocal splanchnic-thoracic blood volume changes during the Valsalva maneuver

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    机译 瓦尔萨尔瓦（Valsalva）动作期间内脏胸廓血流量的相互变化
    摘要：The Valsalva maneuver is frequently used to test autonomic function. Previous work demonstrated that the blood pressure decrease during the Valsalva maneuver relates to thoracic hypovolemia, which may preclude pressure recovery during phase II, even with normal resting peripheral vasoconstriction. We hypothesized that increased regional blood volume, specifically splanchnic hypervolemia, accounts for the degree of thoracic hypovolemia during the Valsalva maneuver. We studied 17 healthy volunteers aged 15–22 yr. All had normal blood volumes by dye dilution. Subjects also had normal vascular resistance while supine as well as normal vasoconstrictor responses during 35° upright tilt. We assessed changes in estimated splanchnic, pelvic-thigh, and lower leg blood volume, along with thoracic blood volume shifts, by impedance plethysmography before and during the Valsalva maneuver performed in the supine position. Early increases in splanchnic blood volume dominated the regional vascular changes during the Valsalva maneuver. The increase in splanchnic blood volume correlated well (r2 = 0.65, P < 0.00001) with the decrease in thoracic blood volume, there was less correlation of the increase in pelvic blood volume (r2 = 0.21, P < 0.03), and there was no correlation of the increase in leg blood volume (r2 = 0.001, P = 0.9). There was no relation of thoracic hypovolemia with blood volume or peripheral resistance in supine or upright positions. Thoracic hypovolemia during the Valsalva maneuver is closely related to splanchnic hyperemia and weakly related to regional changes in blood volume elsewhere. Changes in baseline splanchnic vascular properties may account for variability in thoracic blood volume changes during the Valsalva maneuver.
  • 8.

    【2hr】Sex modifies exercise and cardiac adaptation in mice

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    机译 性别改变小鼠的运动和心脏适应能力
    摘要：How an individual’s sex and genetic background modify cardiac adaptation to increased workload is a topic of great interest. We systematically evaluated morphological and physiological cardiac adaptation in response to voluntary and forced exercise. We found that sex/gender is a dominant factor in exercise performance (in two exercise paradigms and two mouse strains) and that females of one of these strains have greater capacity to increase their cardiac mass in response to similar amounts of exercise. To explore the biochemical mechanisms for these differences, we examined signaling pathways previously implicated in cardiac hypertrophy. Ca2+/calmodulin-dependent protein kinase (CaMK) activity was significantly greater in males compared with females and increased after voluntary cage-wheel exposure in both sexes, but the proportional increase in CaMK activity was twofold higher in females compared with males. Phosphorylation of glycogen synthase kinase-3β (GSK-3β) was evident after 7 days of cage-wheel exposure in both sexes and remained elevated in females only by 21 days of exercise. Despite moderate increases in myocyte enhancer factor-2 (a downstream effector of CaMK) transcriptional activity and phosphorylation of Akt with exercise, there were no sex differences. Mitogen-activated protein kinase signaling components (p38 mitogen-activated protein kinase and extracellular regulated kinase 1/2) were not different between male and female mice and were not affected by exercise. We conclude that females have increased exercise capacity and increased hypertrophic response to exercise. We have also identified sex-specific differences in hypertrophic signaling within the cardiac myocyte that may contribute to sexual dimorphism in exercise and cardiac adaptation to exercise.
  • 9.

    【2hr】Characterization of embryonic cardiac pacemaker and atrioventricular conduction physiology in Xenopus laevis using noninvasive imaging

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    机译 非洲爪蟾胚胎心脏起搏器和房室传导生理特性的无创成像
    摘要：Congenital heart defects often include altered conduction as well as morphological changes. Model organisms, like the frog Xenopus laevis, offer practical advantages for the study of congenital heart disease. X. laevis embryos are easily obtained free living, and the developing heart is readily visualized. Functional and morphological evidence for a conduction system is available for adult frog hearts, but information on the normal properties of embryonic heart contraction is lacking, especially in intact animals. With the use of fine glass microelectrodes, we were able to obtain cardiac recordings and make standard electrophysiological measurements in 1-wk-old embryos (stage 46). In addition, a system using digital analysis of video images was adapted for measurement of the standard cardiac intervals and compared with invasive measurements. Video images were obtained of the heart in live, pharmacologically paralyzed, stage 46 X. laevis embryos. Normal values for the timing of the cardiac cycle were established. Intervals determined by video analysis (n = 53), including the atrial and ventricular cycle lengths (473 ± 10 ms and 464 ± 19 ms, respectively) and the atrioventricular interval (169 ± 5 ms) were not statistically different from those determined by intrathoracic cardiac recordings. We also present the data obtained from embryos treated with standard medications that affect the human conduction system. We conclude that the physiology of embryonic X. laevis cardiac conduction can be noninvasively studied by using digital video imaging. Additionally, we show the response of X. laevis embryonic hearts to chronotropic agents is similar but not identical to the response of the human heart.
  • 10.

    【2hr】Regional Blood Volume and Peripheral Blood Flow in the Postural Tachycardia Syndrome

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    机译 姿势性心动过速综合征的局部血容量和外周血流量
    摘要：Variants of postural tachycardia syndrome (POTS) are associated with increased (“high flow” POTS, HFP), decreased (“low flow POTS”, LFP) and normal (“normal flow POTS”, NFP) blood flow measured in the lower extremities while supine. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 years: 14 LFP, 15 NFP and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured supine by venous occlusion strain gauge plethysmography of the forearm and calf in order to subgroup patients. Using indocyanine green techniques we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while supine compared to control subjects. Blood volume tended to be decreased in LFP compared to control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased while splanchnic, pelvic and leg blood volumes increased for all subjects during orthostasis, but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of [at least] three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.
  • 11.

    【2hr】Dynamic remodeling of K+ and Ca2+ currents in cells that survived in the epicardial border zone of canine healed infarcted heart

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    机译 在犬心肌梗死后的心外膜边缘区中存活的细胞中K +和Ca2 +电流的动态重塑
    摘要：Action potentials (APs) of the epicardial border zone (EBZ) cells from the day 5 infarcted heart continue to be altered by day 14 postocclusion, namely, they shortened. However, by 2 mo, EBZ APs appear “normal,” yet conduction of wave fronts remains abnormal. We hypothesize that the changes in transmembrane APs are due to a change in the distribution of ion channels in either density or function. Thus we focused on the changes in Ca2+ and K+ currents in cells isolated from the 14-day (IZ14d) and 2-mo (IZ2m) EBZ and compared them with those occurring in cells from the same hearts but remote (Rem) from the EBZ. Whole cell voltage-clamp techniques were used to measure and compare Ca2+ and K+ currents in cells from the different groups. Ca2+ current densities remain reduced in cells of the 14-day and 2-mo infarcted heart and the kinetic changes previously identified in the 5-day heart begin to, but do not recover to, cells from noninfarcted epicardium (NZ) values. Importantly, ICa,L in both the EBZ and Rem regions still show a slowed recovery from inactivation. Furthermore, during the remodeling process, there is an increased expression of T-type Ca2+ currents, but only regionally, and only within a specific time window postmyocardial infarction (MI). Regional heterogeneity in β-adrenergic responsiveness of ICa,L exists between EBZ and remote cells of the 14-day hearts, but this regional heterogeneity is gone in the healed infarcted heart. In IZ14d, the transient outward K+ current (Ito) begins to reemerge and is accompanied by an upregulated tetraethylammonium-sensitive outward current. By 2-mo post-occlusion, Ito and sustained outward K+ current have completed the reverse remodeling process. During the healing process post-MI, canine epicardial cells downregulate the fast Ito but compensate by upregulating a K+ current that in normal cells is minimally functional. For recovering ICa,L of the 14-day and 2-mo EBZ cells, voltage-dependent processes appear to be reset, such that ICa,L “window” current occurs at hyperpolarized potentials. Thus dynamic changes in both Ca2+ and K+ currents contribute to the altered AP observed in 14-day fibers and may account for return of APs of 2 mo EBZ fibers.
  • 12.

    【2hr】Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats

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    机译 减少老年大鼠肠系膜动脉中一氧化氮释放至切应力
    摘要：We hypothesized that aging is characterized by a reduced release of nitric oxide (NO) in response to shear stress in resistance vessels. Mesenteric arterioles and arteries of young (6 mo) and aged (24 mo) male Fischer 344 rats were isolated and cannulated. Shear stress (15 dyn/cm2)-induced dilation was significantly reduced and shear stress (1, 5, 10, and 15 dyn/cm2)-induced increases in perfusate nitrite were significantly smaller at all shear stress levels in vessels of aged rats. Inhibition of NO synthesis abolished shear stress-induced release of nitrite. Furthermore, shear stress (15 dyn/cm2)-induced release of nitrate was significantly higher and total nitrite (nitrite plus nitrate) was significantly lower in vessels of aged rats. Tiron or SOD significantly increased nitrite released from vessels of aged rats, but this was still significantly less than that in young rats. Superoxide production was increased and the activity of SOD was decreased in vessels of aged rats. There were no differences in endothelial NO synthase (eNOS) protein and basal activity or in Cu/Zn-SOD and Mn-SOD proteins in vessels of the two groups, but extracellular SOD was significantly reduced in vessels of aged rats. Maximal release of NO induced by shear stress plus ACh (10−5 M) was comparable in the two groups, but phospho-eNOS in response to shear stress (15 dyn/cm2) was significantly reduced in vessels of aged rats. These data suggest that an increased production of superoxide, a reduced activity of SOD, and an impaired shear stress-induced activation of eNOS are the causes of the decreased shear stress-induced release of NO in vessels of aged rats.
  • 13.

    【2hr】Transmural mechanics at left ventricular epicardial pacing site

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    机译 左心外膜起搏部位的透壁力学
    摘要：Left ventricular (LV) epicardial pacing acutely reduces wall thickening at the pacing site. Because LV epicardial pacing also reduces transverse shear deformation, which is related to myocardial sheet shear, we hypothesized that impaired end-systolic wall thickening at the pacing site is due to reduction in myocardial sheet shear deformation, resulting in a reduced contribution of sheet shear to wall thickening. We also hypothesized that epicardial pacing would reverse the transmural mechanical activation sequence and thereby mitigate normal transmural deformation. To test these hypotheses, we investigated the effects of LV epicardial pacing on transmural fiber-sheet mechanics by determining three-dimensional finite deformation during normal atrioventricular conduction and LV epicardial pacing in the anterior wall of normal dog hearts in vivo. Our measurements indicate that impaired end-systolic wall thickening at the pacing site was not due to selective reduction of sheet shear, but rather resulted from overall depression of fiber-sheet deformation, and relative contributions of sheet strains to wall thickening were maintained. These findings suggest lack of effective end-systolic myocardial deformation at the pacing site, most likely because the pacing site initiates contraction significantly earlier than the rest of the ventricle. Epicardial pacing also induced reversal of the transmural mechanical activation sequence, which depressed sheet extension and wall thickening early in the cardiac cycle, whereas transverse shear and sheet shear deformation were not affected. These findings suggest that normal sheet extension and wall thickening immediately after activation may require normal transmural activation sequence, whereas sheet shear deformation may be determined by local anatomy.
  • 14.

    【2hr】Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo

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    机译 再灌注时给予释放CO的分子可减少体内的梗塞面积
    摘要：Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro (glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 ± 3.5% vs. 36.5 ± 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 ± 4.9% of the region at risk (n = 13) vs. 47.7 ± 3.8% (n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.
  • 15.

    【2hr】Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits

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    机译 尼古兰地诱导清醒家兔抗心肌梗塞的晚期预处理
    摘要：Nicorandil has been shown to induce an infarct-limiting effect similar to that induced by the early phase of ischemic preconditioning (PC). The goals of this study were to determine whether nicorandil induces a delayed cardioprotection that is analogous to the late phase of ischemic PC and, if so, whether nicorandil-induced late PC is associated with upregulation of cardio-protective proteins. Chronically instrumented, conscious rabbits received vehicle (intravenous normal saline; control group, n = 10), nicorandil (100 μg/kg bolus + 30 μg·kg−1·min−1 iv for 60 min; nicorandil group, n = 10), or ischemic PC (6 cycles of 4-min coronary occlusion/4-min reperfusion; PC group, n = 8). Twenty-four hours later, rabbits underwent a 30-min coronary occlusion, followed by 3 days of reperfusion. Myocardial infarct size was significantly reduced in rabbits pretreated with nicorandil (27.5 ± 5.3% of the risk region) or with ischemia (30.3 ± 4.2%) versus controls (59.1 ± 4.7%, P < 0.05 vs. both). Furthermore, the expression of cyclooxygenase-2 (COX-2) and Bcl-2 was significantly elevated (+38% and +126%, respectively; P < 0.05) in myocardium of rabbits given nicorandil 24 h earlier versus controls. We conclude that nicorandil induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by upregulating COX-2 and Bcl-2.
  • 16.

    【2hr】Transmural left ventricular mechanics underlying torsional recoil during relaxation

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    机译 放松过程中扭转后坐力的透壁左心室力学
    摘要：Early relaxation in the cardiac cycle is characterized by rapid torsional recoil of the left ventricular (LV) wall. To elucidate the contribution of the transmural arrangement of the myofiber to relaxation, we determined the time course of three-dimensional fiber-sheet strains in the anterior wall of five adult mongrel dogs in vivo during early relaxation with biplane cineangiography (125 Hz) of implanted transmural markers. Fiber-sheet strains were found from transmural fiber and sheet orientations directly measured in the heart tissue. The strain time course was determined during early relaxation in the epicardial, midwall, and endocardial layers referenced to the end-diastolic configuration. During early relaxation, significant circumferential stretch, wall thinning, and in-plane and transverse shear were observed (P < 0.05). We also observed significant stretch along myofibers in the epicardial layers and sheet shortening and shear in the endocardial layers (P < 0.01). Importantly, predominant epicardial stretch along the fiber direction and endocardial sheet shortening occurred during isovolumic relaxation (P < 0.05). We conclude that the LV mechanics during early relaxation involves substantial deformation of fiber and sheet structures with significant transmural heterogeneity. Predominant epicardial stretch along myofibers during isovolumic relaxation appears to drive global torsional recoil to aid early diastolic filling.
  • 17.

    【2hr】Mechanical compression elicits NO-dependent increases in coronary flow

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    机译 机械加压引起冠状动脉血流的NO依赖性增加
    摘要：Our previous studies have demonstrated that a decrease in arteriolar diameter that causes endothelial deformation elicits the release of nitric oxide (NO). Thus we hypothesized that cardiac contraction, via deformation of coronary vessels, elicits the release of NO and increases in coronary flow. Coronary flow was measured at a constant perfusion pressure of 80 mmHg in Langendorff preparations of rat hearts. Hearts were placed in a sealed chamber surrounded with perfusion solution. The chamber pressure could be increased from 0 to 80 mmHg to generate extra-cardiac compression. To minimize the impact of metabolic vasodilatation and rhythmic changes in shear stress, nonbeating hearts, by perfusing the hearts with a solution containing 20 mM KCl, were used. After extracardiac compression for 10 or 20 s, coronary flow increased significantly, concurrent with an increased release of nitrite into the coronary effluent and increased phosphorylation of endothelial NO synthase in the hearts. Inhibition of NO synthesis eliminated the compression-induced increases in coronary flow. Shear stress-induced dilation could not account for this increased coronary flow. Furthermore, in isolated coronary arterioles, without intraluminal flow, the release of vascular compression elicited a NO-dependent dilation. Thus this study reveals a new mechanism that, via coronary vascular deformation, elicited by cardiac contraction, stimulates the endothelium to release NO, leading to increased coronary perfusion.
  • 18.

    【2hr】N-acetyl-seryl-aspartyl-lysyl-proline stimulatesangiogenesis in vitro and in vivo

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    机译 N-乙酰基-丝氨酰-天冬氨酰-赖氨酰脯氨酸刺激体内外血管生成
    摘要：N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a natural inhibitor of pluripotent hematopoietic stem cell proliferation, has been suggested as capable of promoting an angiogenic response. We studied whether Ac-SDKP stimulates endothelial cell proliferation, migration, and tube formation; enhances angiogenic response in the rat cornea after implantation of a tumor spheroid; and increases capillary density in rat hearts with myocardial infarction (MI). In vitro, an immortal BALB/c mouse aortic endothelial 22106 cell line was used to determine the effects of Ac-SDKP on endothelial cell proliferation and migration and tube formation. In vivo, a 9L-gliosarcoma cell spheroid (250–300 μm in diameter) was implanted in the rat cornea and vehicle or Ac-SDKP (800 μg · kg−1 · day−1 ip) infused via osmotic minipump. Myocardial capillary density was studied in rats with MI given either vehicle or Ac-SDKP. We found that Ac-SDKP 1) stimulated endothelial cell proliferation and migration and tube formation in a dose-dependent manner, 2) enhanced corneal neovascularization, and 3) increased myocardial capillary density. Endothelial cellproliferation and angiogenesis stimulated by Ac-SDKP could be beneficial incardiovascular diseases such as hypertension and MI. Furthermore, becauseAc-SDKP is mainly cleaved by ACE, it may partially mediate the cardioprotectiveeffect of ACE inhibitors.
  • 19.

    【2hr】Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure

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    机译 慢性容量超负荷心力衰竭时心室几何结构异常的透壁结构的时间依赖性重塑
    摘要：To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 ± 2 wk (means ± SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 ± 0.030; P < 0.05), whereas the apical site did not [P = not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 ± 0.003 at 2 wk and 0.054 ± 0.021 at final; both P < 0.05), which contributed to a significant increase in wall thickness at the final study (0.181 ± 0.047; P < 0.05), whereas the apical site did not (P = NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.
  • 20.

    【2hr】Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure

    包量

    机译 晚期衰老相关心力衰竭大鼠模型中的左心室压力-容积关系
    摘要：Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old (young) and 24- to 26-mo-old (old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/dt), and its relation to end-diastolic volume (+dP/dt-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, maximal slope of the diastolic pressure decrement, +dP/dt-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats.
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