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S J Pieper

Publications and source records attributed to S J Pieper.

9 recordsLinked to original sources
PubMed1999

Bradykinin modulates arginine vasopressin-induced calcium influx in vascular myocytes.

UNLABELLED: We investigated direct, endothelium-independent effects of bradykinin on arginine vasopressin-induced calcium influx in vascular smooth muscle cells. We studied cultured rat vascular smooth muscle cells by using the whole-cell voltage-clamp and calcium fluorescence imaging methods. Exposing cultured vascular smooth muscle cells (A7r5 cell line) to arginine vasopressin (100 nM) produced a transient increase in [Ca2+]i, followed by a sustained increase in [Ca2+]i. This was readily reversible (n=28). At a holding potential of -40 to -60 mV, arginine vasopressin induced a sustained inward current correlated with a sustained increase in [Ca2+]i. Bradykinin (30 nM to 30 microM) had no effect on arginine vasopressin-induced [Ca2+]i transients. However, during the sustained phase of increased [Ca2+]i, bradykinin reversibly attenuated relative fluorescence and inward current in the presence of arginine vasopressin (n=14). This was concentration dependent and inhibited by [D-Phe7]-bradykinin (30 microM), a kinin receptor antagonist. Also, sustained arginine vasopressin-mediated increases in [Ca2+]i and inward current were attenuated by Ca2+-free or La3+-supplemented perfusate but not by nifedipine (n=5). CONCLUSIONS: (1) Bradykinin can attenuate arginine vasopressin-induced and sustained Ca2+ influx and sustained inward current through a novel endothelium-independent process. (2) The direct effect of bradykinin on arginine vasopressin-induced increases in [Ca2+]i sustained Ca2+ influx in vascular smooth muscle cells is concentration dependent and kinin-receptor mediated. (3) Arginine vasopressin-induced sustained [Ca2+]i elevation correlates with the activation of a dihydropyridine-insensitive, Ca2+-conducting inward current.

Animals↗
PubMed1995

Heart rate variability: technique and investigational applications in cardiovascular medicine.

OBJECTIVE: To describe heart rate variability (HRV) analysis, especially time- and frequency-domain analyses, and some of its investigational applications in clinical cardiovascular medicine. DESIGN: We provide a brief introduction to the magnitude of sudden cardiac death and the factors that influence life-threatening ventricular arrhythmias as a backdrop to the potential importance of the autonomic nervous system and how this system might be assessed by the analysis of HRV. MATERIAL AND METHODS: We reviewed the literature from 1973 to 1994 that described beat-to-beat changes in heart rate, heart rate signal recording and processing, and investigational applications of HRV analysis to cardiovascular medicine. RESULTS: Beat-to-beat changes in heart rate are partly influenced by the autonomic nervous system. Briefly, changes in sympathetic input to the sinoatrial node affect low-frequency HRV, whereas changes in parasympathetic input affect high-frequency HRV. Multiple physiologic and nonphysiologic determinants of HRV exist, and therefore analysis of HRV as a direct "window" to autonomic tone is problematic. CONCLUSION: In selected patient populations, analysis of HRV yields important information about sinoatrial responsiveness to autonomic input and mortality risk stratification. Routine application of HRV analysis to clinical cardiovascular medicine awaits further investigation, however.

Autonomic Nervous System↗
PubMed1995

Narrow QRS complex tachycardias.

Regular narrow QRS complex tachycardias are a common problem encountered by general internists or family practitioners. Although such tachycardias often occur in patients with a normal heart and seldom represent life-threatening conditions, they may cause bothersome symptoms. The key to approaching the diagnosis of these arrhythmias is identifying atrial activity (P waves) on the surface electrocardiogram and classifying the tachycardia as long RP or short RP. On the basis of that information, a differential diagnosis can be generated, logical therapy can be delivered for termination of the tachycardia, and a plan can be developed to prevent recurrence. Because intravenously administered adenosine alleviates 90% of the episodes of supraventricular tachycardias and has minimal side effects, it has become the drug of choice for termination of most types of narrow QRS complex tachycardias.

Humans↗
PubMed1991

A new method for assessment of cultured cardiac myocyte contractility detects immune factor-mediated inhibition of beta-adrenergic responses.

BACKGROUND: Potentially reversible congestive heart failure accompanies disease states associated with an immune cell myocardial infiltrate such as cardiac allograft rejection and inflammatory myocarditis. We therefore examined the hypothesis that immune cells can produce noncytotoxic alterations in cardiac function. METHODS AND RESULTS: A novel system to evaluate cultured cardiac myocyte contractility was developed using neonatal rat cardiocytes grown on human amniotic membrane segments. Spontaneous synchronous cell beating produced macroscopic distortion of these membranes. Movement of free-floating membranes anchored within a perfusion chamber was visualized under low-power microscopy and measured from recordings of the rhythmic displacement of membrane-adherent markers. Additions of graded concentrations of isoproterenol to the perfusate produced up to threefold increases in the initial contractile phase velocity (contractile index), with an EC50 of 10(-7) M. When the extracellular Ca2+ concentration was increased from 0.9 to 3.6 mM, 2.43-fold increases in this index occurred. Myocytes incubated for 72 hours in the presence of dilutions of medium conditioned by activated rat splenic macrophages and lymphocytes exhibited an isoproterenol contractile index inhibited by 62% compared with control cells. In contrast, responses of supernatant-exposed and control cells to increased extracellular Ca2+ concentrations were not significantly different. Parallel studies of increases in myocyte intracellular adenosine 3':5'-cyclic monophosphate concentrations in response to isoproterenol stimulation demonstrated correlative inhibition that was specific for exposure to medium conditioned by immune cells. CONCLUSION: Thus, a new method of in vitro cardiac contractility assessment that has significant advantages over existing systems has been developed and characterized. This new method has enabled description of an inhibitor of cardiac contractile function produced by activated immune cells.

Animals↗
PubMed1989

Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness.

Reversible congestive heart failure can accompany cardiac allograft rejection and inflammatory myocarditis, conditions associated with an immune cell infiltrate of the myocardium. To determine whether immune cell secretory products alter cardiac muscle metabolism without cytotoxicity, we cultured cardiac myocytes in the presence of culture supernatants from activated immune cells. We observed that these culture supernatants inhibit beta-adrenergic agonist-mediated increases in cultured cardiac myocyte contractility and intracellular cAMP accumulation. The myocyte contractile response to increased extracellular Ca2+ concentration is unaltered by prior exposure to these culture supernatants, as is the increase in myocyte intracellular cAMP concentration in response to stimulation with forskolin, a direct adenyl cyclase activator. Inhibition occurs in the absence of alteration in beta-adrenergic receptor density or ligand binding affinity. Suppressive activity is attributable to the macrophage-derived cytokines interleukin 1 and tumor necrosis factor. Thus, these observations describe a role for defined cytokines in regulating the hormonal responsiveness and function of contractile cells. The effects of interleukin 1 and tumor necrosis factor on intracellular cAMP accumulation may be a model for immune modulation of other cellular functions dependent upon cyclic nucleotide metabolism. The uncoupling of agonist-occupied receptors from adenyl cyclase suggests that beta-receptor or guanine nucleotide binding protein function is altered by the direct or indirect action of cytokines on cardiac muscle cells.

Amnion↗
PubMed1988

Immune cytokine inhibition of beta-adrenergic agonist stimulated cyclic AMP generation in cardiac myocytes.

We hypothesize that reversible depression of cardiac function in cardiac allograft rejection and lymphocytic myocarditis reflects down modulation of the beta-adrenergic receptor system by a soluble product of activated immune cells. Thus, exposure of cultured cardiac myocytes to mixed lymphocyte culture or activated splenocyte supernatants produces 70% inhibition of isoproterenol-stimulated cAMP concentrations (Ki = 5% supernatant) in the absence of gross cellular injury or control media effects. This cAMP suppressive factor is not dialyzable and is ammonium sulfate precipitable. Beta-adrenergic receptor density, binding constant and affinity states are unaffected. These results demonstrate the existence of a cytokine inhibitor of cAMP accumulation that may mediate, in part, depression of cardiac contractility observed when immune cells invade the myocardium.

Animals↗
PubMed1984

Thermodynamic bases for fatty acid ethyl ester synthase catalyzed esterification of free fatty acid with ethanol and accumulation of fatty acid ethyl esters.

Myocardial homogenates rapidly synthesize fatty acyl ethyl esters from nonesterified fatty acid and ethanol in the absence of coenzyme A or ATP, and the enzyme catalyzing this reaction, fatty acid ethyl ester synthase, has been purified 5400-fold to homogeneity [Mogelson, S., & Lange, L. G. (1984) Biochemistry (preceding paper in this issue)]. To define the factors permitting this de novo synthesis of ester bonds and the consequent accumulation of fatty acyl ethyl esters in myocardium, we determined thermodynamic parameters relevant to the kinetics and equilibria of this reaction and specifically characterized (1) the rates of synthesis of ethyl oleate, in both the presence and absence of purified enzyme catalyst, and (2) the physical properties of the product, ethyl oleate, in an aqueous milieu. Compared to the reaction of ethanol and oleate in the absence of catalyst, fatty acid ethyl ester synthase enhanced the rate of ethyl oleate synthesis by reducing the free energy of activation (delta G) from 32.5 to 19.9 kcal/mol, effected in large part by a positive entropy shift, delta Senz - delta S uncat = 23.9 cal/(mol.deg). Rate constants in the presence and absence of enzyme at 37 degrees C were 6 X 10(-2) s-1 and 7.8 X 10(-11) M-1 s-1, respectively, indicating a catalytic power of at least 10(8)M for this enzyme. Kinetic data indicated an enzymatic Vmax of 1.25 nmol/(mg.s) (37 degrees C). The equilibrium constant was calculated for the reaction oleate + ethanol in equilibrium ethyl oleate and was 0.095 M-1 at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyltransferases↗
PubMed1984

Partial purification and product characterization of fatty acid ethyl ester synthases in rabbit myocardium.

Homogenates of rabbit ventricular myocardium synthesize fatty acid ethyl esters using as substrates nonesterified fatty acid and ethanol in the absence of coenzyme A and ATP. This catalytic activity resides in two soluble cytosolic enzymes accounting for 19 and 81% of total fatty acid ethyl ester synthetic capability. These enzymes have been separated and partially purified by anion exchange chromatography. Gas chromatographic/mass spectrometric analyses of the catalytic products formed by these enzymes from nonesterified fatty acid and ethanol confirm their identity as ethyl esters of fatty acids. Kinetic studies indicate apparent Km values for ethanol of 0.65 M and 0.75 M for the minor and major activities, respectively. These data confirm the presence of a myocardial pathway for nonoxidative ethanol metabolism and for a metabolism of fatty acids independent of coenzyme A.

Acyltransferases↗