摘要:

Cardiac mechanical function and coronary flow (CF) were measured in isovolumically beating hearts from neonatal piglets 0.5 to 12 days of age. The hearts were perfused retrogradely at 70 cm H2O with a recirculating modified Krebs-Henseleit solution containing washed adult pig red cells (hematocrit, 25%). They were electrically paced (180 beats/min), and left ventricular developed pressure (AP), maximum rate of rise of pressure (dP/dt), CF, and myocardial oxygen consumption were measured. These parameters were found to remain stable for at least 60 minutes. In one group, a single dose of amrinone was added to the perfusate to yield a concentration of 50 μg/ml. Within 5 minutes AP decreased from 104.0 ± 7.1 to 65.3 ± 8.6 mm Hg (p<0.001), and dP/dt fell from 1,160 ± 96 to 658 ± 78 mm Hg/sec (p<0.001). In a second group, successive doses of amrinone were added to yield concentrations ranging from 5 to 50 μg/ml. There was a progressive decrease in AP and dP/dt to 66.5 ± 4.2% and 57.6 ± 4.8% of initial values, respectively. CF increased progressively from 3.2 ± 0.2 to 6.8 ± 0.5 ml/min/g. In 3 experiments, amrinone was washed out after achieving the maximum concentration. Depressed mechanical function reversed and AP and dP/dt returned to control values in each heart. Additionally, CF decreased from 7.6 ± 0.3 to 5.0 ± 0.2 ml/min/g. It is concluded that amrinone has concentration-dependent negative inotropic actions in the neonatal piglet heart. Hence, the drug may not be useful in treating heart failure in the human neonate.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Myocardial fatty acid metabolism was studied in spontaneously-diabetic "BB" Wistar rats. The study involved 4 groups: control Wistar rats, nondiabetic littermates of "BB" Wistar rats, insulin-treated diabetic "BB" rats, and diabetic "BB" rats in which insulin treatment was removed 24 hours prior to study (uncontrolled diabetes). Hearts were perfused for 30 minutes as isolated working hearts in perfusate containing 1.2 mM (l-14C)-palmitate bound to 3% albumin, and 11 mM glucose. Palmitate oxidative rates, calculated as micromoles palmitate oxidized per gram dry weight per minute, were significantly decreased in both diabetic groups (0.447 ± 0.043 and 0.528 ± 0.038 in uncontrolled diabetic and treated diabetic versus 0.584 ± 0.032 and 0.629 ± 0.033 in nondiabetic littermate and control rats, respectively). This decrease was accompanied, however, by a significant decrease in the heart rate of these 2 groups when compared with control or nondiabetic animals. If the decreased heart function in the diabetic animals was accounted for, no decrease in palmitate oxidative rates occurred, suggesting that fatty acid oxidative metabolism is not impaired in the diabetic myocardium. In the uncontrolled diabetic rats, an increased rate of palmitate incorporation into myocardial triglycerides was seen compared with treated diabetic, nondiabetic littermates, and control rats (8.5 ± 0.3 μmol/g dry wt/30 min versus 4.8 ± 0.3, 5.9 ± 0.7, and 5.7 ± 0.3, respectively). Myocardial levels of coenzyme A were elevated in the uncontrolled diabetic rats compared with all other groups (647 ± 25 nmol/g dry wt versus 484 ± 27, 508 ± 56, and 534 ± 9, in treated diabetic, nondiabetic, and control rats, respectively). Combined with earlier studies in which high coenzyme A levels in control hearts also resulted in an increased rate of palmitate incorporation into triglycerides, the data suggest that high levels of myocardial coenzyme A contribute to the accumulation of myocardial triglycerides seen in poorly controlled diabetes. Similarly, contrary to earlier reports, a decrease in the rate of fatty acid oxidation was not observed in diabetic rat hearts.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To determine the characteristics of cardiac myosin in the conduction system, a pure Purkinje fiber preparation, consisting of atrioventricular nodes and the ventricular conduction system, was obtained from bovine hearts. Two types of myosin heavy chain isozymes, α-type and β-type, were fractionated by affinity chromotography using monoclonal antibodies CMA19 and HMC50, which are specific for the α-type heavy chain and β-type heavy chain, respectively. Competitive enzyme-linked immunosorbent assay demonstrated that the content of β-type in the atrioventricular node (30-40%) was higher than that in atrial ordinary myocardium (10-20%) and that of the α-type was 30-40% in the ventricular conduction system, which was much higher than that in the ventricular ordinary myocardium (less than 10%). By one- and two-dimensional electrophoresis of the peptides produced by partial and complete digestion, the peptide compositions of α-type and β-type in the conduction system were shown to be very similar to those of α-type and β-type in ordinary myocardium, respectively. The Ca2+-activated ATPase activity of myosin of the atrioventricular nodes was lower than that of ordinary atrial myosin (0.46 ± 0.03 versus 0.58 ± 0.02 μmol Pi/mg/min, mean ± SEM, p<0.05) and in contrast, that of ventricular specialized myocardium was higher than that of myosin in the ventricular ordinary working myocardium (0.32 ± 0.03 versus 0.22 ± 0.01 μmol Pi/mg/min, p<0.05). This was in good agreement with the relative proportion of myosin isozymes. We concluded that there were two distinctive myosin heavy chain isozymes in the conduction system and that they were closely related to heavy chain α and β of the ordinary working myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The objective of this study was to elucidate the close similarity in properties between endothelium-derived relaxing factor (EDRF) and nitric oxide radical (NO). Whenever possible, a comparison was also made between arterial and venous EDRF. In vascular relaxation experiments, acetylcholine and bradykinin were used as endothelium-dependent relaxants of isolated rings of bovine intrapulmonary artery and vein, respectively, and NO was used to relax endothelium-denuded rings. Oxyhemoglobin produced virtually identical concentration-dependent inhibitory effects on both endothelium-dependent and NO-elicited relaxation. Oxyhemoglobin and oxymyoglobin lowered cyclic guanosine monophosphate (cGMP) levels, increased tone in unrubbed artery and vein, and abolished the marked accumulation of vascular cGMP caused both by endothelium-dependent relaxants and by NO. The marked inhibitory effects of Oxyhemoglobin on arterial and venous relaxant responses and cGMP accumulation as well as its contractile effects were abolished or reversed by carbon monoxide. These observations indicate that EDRF and NO possess identical properties in their interactions with oxyhemoproteins. Both EDRF from artery and vein and NO activated purified soluble guanylate cyclase by heme-dependent mechanisms, thereby revealing an additional similarity in heme interactions. Spectrophotometric analysis disclosed that the characteristic shift in the Soret peak for hemoglobin produced by NO was also produced by an endothelium-derived factor released from washed aortic endothelial cells by acetylcholine or A23187. Pyrogallol, via the action of superoxide anion, markedly inhibited the spectral shifts, relaxant effects, and cGMP accumulating actions produced by both EDRF and NO. Superoxide dismutase enhanced the relaxant and cGMP accumulating effects of both EDRF and NO. Thus, EDRF and NO are inactivated by superoxide in a closely similar manner. We conclude, therefore, that EDRF from artery and vein is either NO or a chemically related radical species.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To define alterations in myocardial mitochondrial function due to hypoperfusion, oxidative phosphorylation was simultaneously studied in 17 control (stable perfusion pressure) rat hearts and 17 hypoperfused isolated rat hearts. Hypoperfusion for 30 minutes was achieved by a reduction in coronary perfusion pressure from 77.8 ± 1.2 mm Hg (mean ± SEM) to 20.2 ± 1.8 mm Hg in the experimental group (control perfusion pressure after 30 minutes 75.6 ± 1.2). Hypoperfusion caused a reduction in left ventricular developed pressure to 20.5 ± 1.5 mm Hg (versus control 74.8 ± 3.3, p<0.0001), a reduction of coronary flow rate to 4.9 ± 0.3 ml/min (versus control 19.4 ± 1.2, p<0.0001), and a drop in myocardial oxygen consumption to 0.06 ± 0.005 ml O2/min (versus control 0.17 ± 0.01, p<0.0001). Myocardial lactate production was increased by hypoperfusion (3.0 ± 0.6 μmol/min) compared with controls (0.7 ± 0.5, p<0.02), but myocardial creatine kinase release was similar in the hypoperfused and control groups. Hypoperfusion was associated with an augmentation of state 3 mitochondrial respiration with glutamate and malate as respiratory substrates (448.8 ± 14.0 ng atoms O/min/mg mitochondrial protein versus controls 290.7 ± 13.4, p<0.001). When rates were normalized for mitochondria) malate dehydrogenase (MDHm), state 3 respiration was still increased in hypoperfused hearts (24.1 ± 2.1 ng atoms O/min/IU MDHm) compared with controls (15.5 ± 1.6, p<0.02). The rates of dinitrophenol-uncoupled electron transport were similar to the rates of state 3 respiration in both the hypoperfused and control groups. No alterations in mitochondrial function were found with succinate as substrate. Therefore, moderate levels of hypoperfusion enhanced mitochondrial oxidative phosphorylation when glutamate and malate were the respiratory substrates, consistent with an augmentation of the activity of electron transfer complex I and/or the rates of mitochondrial glutamate/malate uptake. This enhancement may be an adaptive mechanism to maximize ATP synthesis during or following myocardial oxygen supply/demand imbalance.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Alterations in endothelium-dependent, sodium pump-mediated, and calcium-dependent responses of vascular smooth muscle were investigated in 5-7-, 24-26-, and 50-52-week-old male Sprague-Dawley rats. Age-dependent changes in systolic blood pressure were also determined. Although systolic blood pressure increased significantly with age, rats in all 3 age groups were considered normotensive. Initial studies on the passive force-response characteristics of strips of aortic and femoral arterial smooth muscle revealed that the level of passive force required for maximum active tension generation increased with increasing age. Subsequent studies were carried out using optimum passive force requirements. Endothelium-dependent relaxations of aortic smooth muscle induced by acetylcholine and the calcium ionophore A23187 decreased significantly with increasing age. An age-dependent decrease in the contractile response of aortic smooth muscle to ouabain and potassium-free physiological salt solution (PSS) was observed. Potassium relaxation of femoral smooth muscle following contraction to norepinephrine (NE) in a potassium-free PSS was also significantly attenuated with increasing age. No age-related alterations in calcium sensitivity (in the presence of 10-7M NE) or calcium relaxation (membrane stabilization) of femoral arterial smooth muscle was seen. These results show that endothelium-dependent and sodium pump-mediated responses are reduced in vascular smooth muscle of the rat with increasing age. However, no changes in calcium-dependent responses are apparent. These observations are discussed in relation to the vascular changes observed in hypertension.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Arterial smooth muscle myosin contains nonphosphorylated and phosphorylated light chains that appear as 4 spots on two-dimensional, Coomassie blue-stained gel electrophoretograms at the 20,000-molecular weight level (referred to as spots 4 through 1 in order of decreasing isoelectric points). Anti-light chain recognizes the proteins in all 4 light chain spots. Complete dephosphorylation of light chain in muscle homogenate, by inhibiting myosin light chain kinase and by adding phosphatase, leads to 2 spots on two-dimensional gel electrophoretograms; both spots are visible on immunoblots. Stimulation (K+or stretch) of smooth muscle results in increased light chain phosphorylation. Autoradiography of the gel electrophoretograms reveals that radioactive components are contained in spots 3, 2, 1, and in an additional spot with lower isoelectric point, referred to as spot 0. Phosphoamino acid analysis shows that spots 3 and 1 contain phosphoserine, whereas spots 2 and 0 contain phosphoserine and phosphothreonine. Two-dimensional phosphopeptide mapping of the trypsin-digested proteins from spots 3 and 1 shows predominantly 2 peptides; whereas from spots 2 and 0, it shows 5 peptides. Sodium dodecyl sulfate gel electrophoresis of the phosphopeptides obtained with Staphylococcus aureus V8 digestion gives identical maps for spots 3 and 2, which are different from the identical maps of spots 1 and 0. The results suggest that arterial smooth muscle myosin contains 2 nonphosphorylated 20,000-dalton light chain isoforms with different amino acid sequences and that each isoform can be mono- and diphosphorylated.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension (200 mm Hg for 10 seconds to 15 minutes). In open-chest anesthetized dogs, the left anterior descending coronary artery was perfused at constant pressure. Coronary diameter (D) was measured with piezoelectric crystals. At a control perfusion pressure of 80 mm Hg, serotonin produced dose-dependent constriction of the large coronary artery (mean ± SEM; ΔD= -22 ± 10μm at 5 μg/min; -108 ± 50 μm at 50 μg/min). Increasing perfusion pressure to 200 mm Hg increased flow 515 ± 79% and coronary diameter 509 ± 9 μm. After 15 minutes of hypertension, when coronary diameter had returned to baseline values, the constriction of the large artery to serotonin was potentiated (ΔD = -89 ± 33μm at 5 μg/min; - 207 ± 45 μm at 50 μg/min; p<0.05). Hypertension for 1-5 minutes potentiated constrictor responses of large coronary arteries for at least 2± hours. Removal of endothelium prevented effects of hypertension on constrictor responses of large arteries to serotonin. Hypertension did not alter constrictor responses to angiotensin II (1 and 2.5 μg/min) or methoxamine (50 and 100 μg/min) or the dilator response to acetylcholine (40 μg/min). Acute hypertension altered endothelial morphology. There were small endothelial craters following 10 seconds of hypertension, and disruption of endothelial junctions with leukocyte adherence following 1-15 minutes of hypertension. We conclude that acute hypertension alters constrictor responses of large coronary arteries to serotonin by impairing endothelial function and not by directly affecting vascular smooth muscle. These effects of acute hypertension on vascular reactivity are selective in that they do not involve non-endothelium-dependent agents or the endothelium-dependent agent, acetylcholine. The effect of hypertension also persists long after pressure is restored to normotensive levels.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Calcium-activated myosin adenosine triphosphatase (ATPase) activity has been measured in sections of rat ventricles that were rapidly frozen to preserve the structure and regulatory state of myosin occurring in vivo. These results were related to myosin isozyme composition measured in ventricles by native gel electrophoresis and by quantitative immunocytochemistry. Both total ATPase activity and percent α-heavy chain rapidly rise during the first month following birth. However, ATPase activity remains constant at a high level from 1 to 12 months following birth, even though percent a-heavy chain declines during this period. The ATPase activity of V1 myosin was specifically determined using sections in which V3 myosin had been completely inhibited by exposure to alkaline pH in the absence of adenosine 5'-triphosphate (ATP). Relative V1 specific activity, taken as the ratio of V1 ATPase activity to percent a-heavy chain, doubles in the first 2.0 months after birth and then remains approximately constant at this higher level until at least 4 months after birth. The specific activity of V1 can be further increased by the addition of adenosine-3',5'-cyclic monophosphate (cAMP). This effect of cAMP is age dependent, increasing threefold between 1 and 2 months following birth and then declining as V1 is replaced by V3.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

It is not clear what factors contribute to the prompt and reversible decrease in left ventricular diastolic chamber distensibility during angina pectoris that is induced by an increase in myocardial energy demand due to exercise or pacing tachycardia. To simulate the demand ischemia that occurs clinically during pacing-induced angina, we used isolated, blood-perfused rabbit hearts with restricted coronary flow and increased myocardial energy demand. A constant left ventricular balloon volume model was used to measure left ventricular diastolic chamber distensibility during 6 minutes of low-flow global ischemia, induced by a reduction in coronary perfusion pressure from 100 to 20 mm Hg. To investigate the influence of different levels of myocardial energy demand, the effects of two different heart rates were studied during low-flow global ischemia; pacing tachycardia (6.4 ± 0.2 Hz, n = 7) was compared with the rabbit's baseline heart rate of 4 Hz (n = 7). Low-flow ischemia caused a marked decrease in contractile function relative to the baseline preischemic state. In the pacing-tachycardia group, myocardial energy demand, as estimated by the rate ± systolic pressure product, was significantly greater than in the constant heart-rate group. When tachycardia was imposed during low-flow global ischemia, there was a transient and reversible increase in isovolumic left ventricular end-diastolic pressure from 14 ± 1 to 25 ± 4 mm Hg (measured during long diastoles obtained with transient cessation of pacing) in the pacing-tachycardia group, but there was no increase in left ventricular end-diastolic pressure during low flow ischemia in the constant heart-rate group with lower energy demand (p<0.01). The time constant of left ventricular relaxation also markedly increased in low-flow ischemia combined with pacing tachycardia. Glycolytic flux (as estimated by coronary venous-arterial lactate concentration difference) increased during low-flow ischemia at the baseline heart rate of 4 Hz but did not increase further during the elevated energy demand of pacing tachycardia. We conclude that in isolated, blood-perfused hearts, global myocardial ischemia due to a reduction in coronary flow alone is not associated with a decrease in diastolic chamber distensibility. However, when a pacing-induced increase in myocardial energy demand is superimposed on the ischemic myocardium and exceeds its capacity to generate high-energy phosphates, a rapid and reversible decrease in left ventricular diastolic chamber distensibility develops similar to that which occurs in response to pacing-induced angina in humans. This finding in isolated, blood-perfused hearts with global ischemia supports the hypothesis that the increase in left ventricular diastolic pressure that occurs during angina in humans is related to the effects of demand ischemia on myocardial relaxation per se and does not require dyssynchronous contraction of ischemic and nonischemic segments, nor does it depend on pericardial or right ventricular factors.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID