摘要:

Propagation in cardiac muscle is faster in the longitudinal than in the transverse axis of the cells. Yet, as a result of the larger upstroke velocity of action potentials propagating transversely, it has been suggested that longitudinal propagation is more vulnerable to block. To study the relation between conduction velocity and maximal upstroke velocity (±max), as well as the time course of conduction delay and block in the transverse vs. longitudinal direction, thin square pieces of sheep epicardial muscle were superfused with the cellular uncoupler heptanol (1.5 mM). Action potentials were recorded with microelectrodes at opposite corners of the preparation while stimulating alternately in the longitudinal or transverse direction with bipolar electrodes located at contralateral corners. In all cases, block occurred more promptly for transverse than for longitudinal propagation. The decrease in conduction velocity was greater than expected for ±maxdecay and, in some cases, ±maxincreased while conduction velocity decreased. In the presence of high grade conduction impairment, foot potentials appeared and the upstrokes became ''notched.'' We conclude that when intercellular coupling is impaired, transverse propagation is more vulnerable to block, and need not be dependent on changes in ±max.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Isolated perfused paced hearts from rats rendered hypothyroid by chronic administration of propylthiouracil have a delayed onset of ischemia-induced myocardial contracture in contrast to hearts from control rats. In addition, the time to reach maximum contracture is delayed, and the magnitude of the contracture pressure is reduced. Preischemia myocardial adenosine triphosphate (ATP) values in the hypothyroid rat hearts are similar to those of control, but the rate of decrease in ATP is slower in the hearts of hypothyroid rats. Thus, it appears that in the hypothyroid state the development of ischemic contracture is associated with a slower fall of ATP.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Serotonin (5-HT) uptake by bovine pulmonary artery endothelial cells in culture was stimulated several fold by exposure of cells for 24 hours to 0–3% O2. The cells appeared normal morphologically, excluded trypan blue dye, showed normal levels of release of lactate dehydrogenase, and contained normal amounts of adenosine triphosphate (ATP). Incubation of cells with iodoacetate (3–5 μM), an inhibitor of glycolytic metabolism, prevented the stimulation of 5-HT uptake but did not impair cellular proliferation. A similar, but less pronounced, effect was produced by 1 mM deoxyglucose. On the other hand, the mitochondrial inhibitors antimycin A, sodium azide, potassium cyanide, and 2,4-dinitrophenol inhibited cellular replication similar to the effect of anoxia but did not alter the stimulation of 5-HT uptake. 5-HT uptake correlated strongly with lactate production by the cells exposed to anoxia (r= 0.98). We conclude that stimulation of 5-HT uptake by prolonged exposure of the endothelial cell to hypoxia/anoxia causes alteration of a membrane function (serotonin transport) of the endothelial cell. This alteration is associated with enhanced glycolytic activity of the cell during exposure to hypoxia. The mechanism for translation of enhanced glycolysis to later stimulation of 5-HT uptake remains to be determined. Endothelial cellular replication is dependent on aerobic metabolism.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The coronary efflux of radioactive3',5'-cyclic adenosine monophosphate (cAMP) and adenosine from isolated guinea pig hearts was measured following selective prelabelling of coronary endothelial adenine nucleotides with 10 nM [2,8,5'-3H] adenosine. Intracoronary infusion of adenosine and its derivatives5'-N-ethyl-carboxamide-adenosine (NECA), (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA), and (+)-N6-(S-phenyl-isopropyl)-adenosine (S-PIA) caused dose-dependent parallel increases in both coronary flow and the coronary efflux of radioactive cAMP with a rank order of potency: NECA > R-PIA > adenosine > S-PIA. In contrast, adenosine receptor stimulation of isolated cardio-myocytes in primary culture decreased the cellular release of cAMP below control levels with a rank order of potency: R-PIA > NECA. Under control conditions, coronary efflux of adenosine and cAMP was 34.3 ± 2.3 and 3.9 ± 0.8 pmol/min (mean ± SEM,n= 6), respectively. NECA (12 μM) caused an increase in cardiac cAMP release of 3.8 times and elevated the specific radioactivity of cAMP 5 times to 63.7 ± 6.0 Ci/mol, a value 11 times greater than the specific radioactivity of tissue ATP; Based on these findings, it was concluded that the coronary endothelium possesses adenosine A2 receptors linked to adenylate cyclase, which are activated in parallel with increases in coronary flow and that cardiomyocyte adenosine receptors are predominantly of the A1 subtype. In addition, the contribution of the coronary endothelium to total cardiac adenosine release was calculated to be 14% using the specific radioactivities of adenosine and cAMP released into the effluent perfusate.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Doprost (0.1–100 μM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Doprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5ain each of the groups was control 13.3 ± 1.8 units/g tissue (n= 12) and iloprost 6.5 ± 0.9 units/g (n= 12),p<0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 ± 3.1 % of the area at risk(n= 15) compared with 42.4 ± 3.3% of control (n= 13),p<0.01. Doprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the Interface between infarcted and noninfarcted tissue: control(n= 9) 9.0 ± 1.8 units/g tissue, iloprost (n= 6) 2.0 ± 0.4 units/g,p<0.01. The ability of iloprost to reduce Infarct size may be related both to a reduction in arterial blood pressure and to a modulation of neutrophil infiltration and activation at the site of tissue injury.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effect of acute myocardial ischemia on the myocardial elastic modulus has been a matter of controversy. To evaluate this question, diastolic elastic modulus was assessed by finite element analysis of left ventricular geometry using three-dimensional echocardiographic reconstructions and right and left ventricular pressure recordings. Elastic properties were estimated before and after coronary occlusion in 6 open-chest dogs. Elastic modulus values were derived by means of a computer program that determined the global elastic modulus that best predicted the diastolic changes in left ventricular geometry. In the finite element analysis after coronary occlusion, two analyses were performed: one utilizing the control elastic modulus for all segments of the left ventricle and one in which ischemic (dyskinetic) segments were assigned a higher elastic modulus. Results showed that the control elastic modulus was a poor predictor of diastolic left ventricular expansion after coronary occlusion. The finite element analysis in which the ischemic segments were assigned a higher elastic modulus better predicted ischemic diastolic wall motion patterns. Error values (difference between predicted and actual left ventricular segmental diastolic motion) were: control, 1.9 ± 0.3 mm (mean ± SD), ischemia, 2.9 ± 0.5 mm, and 2.2 ± 0.4 mm using the stiffer elastic modulus for ischemic segments. Error values were significantly higher (p< 0.05) under ischemic conditions when the control elastic modulus was uniformly applied compared with control and ischemia with dyskinetic segments assigned a higher elastic modulus. From these data, it is concluded that the myocardial diastolic elastic modulus is increased by ischemia and that this approach may allow clinical assessment of intrinsic muscle stiffness.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To determine whether calcium channel agonists and antagonists bind to distinct pharmacologically active sites, the binding of dihydropyridine calcium channel agonists and antagonists was related to calcium flux and contractile state in primary monolayer cultures of spontaneously contracting chick embryo ventricular cells. Equilibrium binding studies using the antagonist (+)-[3H]PN200–110 demonstrated equilibrium binding to intact, beating cells consistent with a single class of binding sites (KD, 1.1 nM; Bmax, 40 fmol/mg protein). Membrane depolarization of the intact cells by incubation in 30 mM potassium caused a 91 % increase in the apparent number of (+)-PN200–110 binding sites (Bmax76 fmol/mg protein), but no significant change in the KD(1.2 nM). The (+)-PN200–110 produced a concentration-dependent decrease in calcium uptake (IC502.2 nM) and contractile amplitude (IC505.6 nM). The calcium channel agonist, (±)-[3H]BAY k 8644, bound to two distinct binding sites with high affinity (KD1.0 nM) and low affinity (KD1.9 μM). The (±)-BAY k 8644 produced biphasic modulation of calcium flux and contractile state. At concentrations of 100 nM or less, (±)-BAY k 8644 increased calcium flux and contractile amplitude, consistent with drug interaction with the high affinity agonist site. However, at higher concentrations, the stimulatory effect of (±)-BAY k 8644 on calcium flux and contractile amplitude was abolished, a finding that is consistent with drug interaction with the low affinity antagonist site. Ligand binding studies using (±)-BAY k 8644 to displace (+)-[3H]PN200–110 demonstrated that these ligands compete at a single site with KDfor (±)-Bay k 8644 of 1.7 μM, which is consistent with binding at the low-affinity antagonist site. It was concluded that in intact cultured myocytes, voltage-sensitive calcium channels have at least 2 distinct dihydropyridine binding sites. Binding of dihydropyridines to these sites mediates opposing effects on calcium flux and contractile function.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The in vivo synthesis rates of myosin isozyme heavy chainsβandαwere measured in right ventricular (RV) muscle at 2 and 4 days following pulmonary artery constriction in rabbits, together with measurements of their relative mRNA levels. The synthesis rate ofβ-myosin heavy chains was elevated in 2-day (0.27 ± 0.06 day−1or 2.5 ± 0.7 mg/g RV/day, mean ± SD) and in 4-day (0.25 ± 0.08 day−1or 2.8 ± 1.0 mg/g RV/day) pressure overload, when compared to untreated rabbits (0.15 ± 0.04 day−1or 1.5 ± 0.4 mg/g RV/day). However, the synthesis rates ofα-myosin heavy chains in the same hearts were not altered significantly. There was a differential increase in the fractional synthesis rate ofβvs.αheavy chains in 2-day and 4-day pressure overload and in 2-day shams, suggesting switching towardβheavy chain synthesis had occurred at these time points.βheavy chain synthesis, as a proportion of total (α+β) heavy chain synthesis, was significantly higher in 4-day pressure overload (78 ± 9%) than in 4-day sham rabbits (63 ± 6%). This increase in relativeβ-synthesis was associated with a significant increase in the relative proportion ofβheavy chain mRNA level (76 ± 13% vs. 56 ± 7%). Furthermore, relativeβ-synthesis and theβ-mRNA levels correlated linearly with each other in all experimental groups. We conclude that during the early stages of pressure overload 1) the synthesis rate ofβ-myosin heavy chains is accelerated without a reciprocal decrease in a-myosin heavy chain synthesis, and 2) an increase inβ-myosin heavy chain expression appears to be achieved mainly by modulation of pretranslational events.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Changes in cytosolic free calcium concentration during myocardial ischemia were measured by19F NMR in 5FBAPTA-loaded perfused rat hearts. The hearts were perfused with Krebs-Henseleit buffer containing 5 μM of the acetoxymethyl ester of 5FBAPTA, which was hydrolyzed by cytosolic esterases to achieve cytosolic concentrations of 5FBAPTA of 0.12 to 0.65 mM. Cytosolic free calcium concentrations were calculated as the product of the ratio of peak areas for bound and free 5FBAPTA in the NMR spectra and the dissociation constant (708 nM). The basal cytosolic calcium concentration, measured in potassium or magnesium arrested hearts, was 252 nM, and the time-average calcium concentration in beating hearts was 630 nM. Following the onset of total ischemia, there was no immediate substantial change in cytosolic calcium despite a rapid decline in creatine phosphate and ATP and a marked increase in inorganic phosphate as monitored by31P NMR, but by 10 minutes, there was a substantial increase in free calcium concentration. The ratio of peak areas of bound and free 5FBAPTA returned to the preischemic value during reperfusion, and there was no detectable loss of 5FBAPTA from the heart. Creatine phosphate was also restored to its preischemic level during reperfusion. These results indicate that cytosolic free calcium increases during ischemia and is not immediately associated with lethal injury. This increase in cytosolic calcium may activate degradative enzymes that eventually could compromise myocyte viability.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Solute and water uptake were studied in isolated perfused rat lungs with airspaces filled with the perfusion fluid. The albumin in this solution was labelled with Evans blue (T-1824), and uptake of fluid from the airspaces was documented by an increase in T-1824 concentration in airway fluid of 6.5 ± 1.6% (n= 5, SEM) at 1 hour and 12.2 ± 0.9% (n= 10) at 2 hours. The only detectable osmotic force that could have contributed to a loss of fluid from the alveolar fluid was a decrease in airspace glucose concentrations, which fell much more rapidly (from 150 mg/dl to 58.7 ± 7.1 mg/dl,n= 10, after 2 hours) than plasma glucose (from 150 mg/dl to 128.9 ± 3.7 mg/dl). Addition of 5 ± 10−5M terbutaline to the perfusate and airspace solutions nearly doubled fluid reabsorption at 1 hour, an effect that was inhibited by propranolol and did not appear to be related to glucose consumption. Exposure to terbutaline for 2 hours increased epithelial permeability to3H-mannitol and22Na+. These observations suggest that active sodium transport and epithelial metabolism or transport of glucose in airway fluid may each play a role in the reabsorption of edema fluid.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID