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Biomedical subjects

F C Messineo

Publications and source records attributed to F C Messineo.

At least 37 records · Page 2Linked to original sources
PubMed1985

Effects of fatty acids on Na/Ca exchange in cardiac sarcolemmal membranes.

Three structurally distinct amphiphiles palmitic acid, oleic acid, and palmityl carnitine were studied to determine their effects on sodium dependent calcium uptake by purified cardiac sarcolemmal vesicles (PSL). Sodium dependent calcium uptake by PSL when studied over a 20 min reaction period was composed of an initial rapid uptake (20.9 +/- 0.93 nmol/mg X 30 s, mean +/- S.E. n = 20) a plateau in calcium content (42.4 +/- 3.2 nmol/mg, mean +/- S.E. n = 20) and a slow spontaneous release characterized by a first order rate constant of 0.68 +/- 0.08/h (mean +/- S.E. n = 18). Both palmityl carnitine and palmitic acid inhibited, whereas oleic acid stimulated initial calcium uptake. All three amphiphiles shortened the time to peak calcium content, inhibited peak calcium content and increased the rate constant for calcium release. All these effects were observed at fatty acid: membrane phospholipid mole ratios of 0.67 : 1 to 1.67 : 1 for oleic acid and palmityl carnitine and 0.02 : 1 to 0.42 : 1 for palmitic acid. These effects do not reflect disruption of membrane vesicle structure and may be explained, at least in part, by amphiphile induced increases in sarcolemmal membrane ion permeability. Although amphiphile accumulation has been implicated in the pathogenesis of cellular abnormalities in the ischemic myocardium, this study has shown that large amounts of amphiphile relative to membrane lipid are required to alter sarcolemmal membrane function in vitro.

Animals↗
PubMed1985

Interaction of amphiphilic molecules with biological membranes. A model for nonspecific and specific drug effects with membranes.

The nonspecific interactions of propranolol, timolol, and ethanol with model and sarcoplasmic reticulum membranes were determined utilizing radioisotopic association differential scanning calorimetry, and neutron diffraction. Differential scanning calorimetry performed on mixtures of these amphiphilic compounds and model membrane bilayers composed of dimyristoyllecithin showed that propranolol was approximately 25 times more lipid-soluble than timolol and at least 100 times more lipid-soluble than ethanol. Neutron diffraction showed that the solvation of propranolol was within the fatty acyl chain region of the lipid bilayer. This solvation correlated with the effect of propranolol to inhibit ATP-dependent calcium transport in isolated rabbit skeletal muscle sarcoplasmic reticulum, a membrane that lacks beta-adrenergic receptors. In contrast, the major site of interaction of ethanol was within the aqueous compartment hydrating the sarcoplasmic reticulum membrane. A model for nonspecific drug interaction with the sarcoplasmic reticulum membrane based on the site of interaction of these amphiphiles and their relative potencies to inhibit calcium transport by these membranes is proposed. In principle, this model could be extended to specific drug interactions with membranes.

Animals↗
PubMed1984

Cellular actions and pharmacology of the calcium channel blocking drugs.

The calcium channel blockers represent a group of diverse chemical structures that block calcium-selective channels in the plasma membranes of a variety of excitable cells. As the calcium fluxes carried by these channels allow the calcium ion (Ca2+) to gain access to the cell interior, where calcium serves as an activator messenger, calcium channel blockers generally act to inhibit cell function. By reducing the depolarizing currents caused by the entry of positively charged Ca2+ into the negatively charged interior of resting cells, the calcium channel blockers also inhibit excitatory processes that depend on calcium entry across the plasma membrane. These principles account for most of the effects of calcium channel blockers on the cardiovascular system. The calcium channel blockers inhibit contractile function in the heart and vascular smooth muscle and, because the initial depolarizing currents in the sinoatrial and atrioventricular nodes are carried by calcium channels, slow the heart rate and prolong atrioventricular conduction. The negative inotropic and vasodilatory effects of the calcium channel blockers, both of which can reduce systemic blood pressure, offer a theoretic basis for their potential use in the treatment of hypertension. The tissue specificity exhibited by some of the calcium channel blockers may enhance their therapeutic value in selected hypertensive patients. Of the three calcium channel blockers now available for use in the United States (diltiazem, nifedipine, and verapamil), diltiazem and verapamil are approximately equipotent in inhibiting calcium channel function in the heart and vascular smooth muscle, whereas nifedipine is more potent in smooth muscle. This tissue specificity can be used to advantage in the management of hypertension. These pharmacologic principles underlie the growing appreciation of the potential value of the calcium channel blockers in the treatment of hypertension.

Action Potentials↗
PubMed1984

Mechanisms of fatty acid effects on sarcoplasmic reticulum. III. The effects of palmitic and oleic acids on sarcoplasmic reticulum function--a model for fatty acid membrane interactions.

The mechanism by which palmitic and oleic acids modify calcium sequestration by sarcoplasmic reticulum vesicles was investigated by examining the effects of these fatty acids on calcium-dependent ATPase activity, on the phosphoenzyme intermediates found during calcium sequestration reactions, and on passive membrane permeability to calcium. The calcium sequestered in the presence of these fatty acids was also characterized by determining the amount exchangeable with the extravesicular pool or released by the ionophore A23187. In the presence of 50 microM ATP, 18 microM palmitic acid enhanced and 18 microM oleic acid inhibited calcium sequestration, whereas both fatty acids stimulated ATPase activity. Neither fatty acid had significant effects on the amount or distribution of the phosphoenzyme formed during the calcium transport reaction. Palmitic acid stimulated calcium sequestration only when ATP was present. Oleic acid caused the release of a portion of the accumulated calcium during ATP-supported calcium sequestration and also enhanced the release observed in ATP-depleted reactions. A portion of the calcium sequestered in the presence of palmitic acid appears to be incorporated into a nonexchangeable and ionophore-insensitive calcium pool, although the latter was estimated to be considerably larger than the nonexchangeable pool. These data support the hypothesis that oleic acid inhibits calcium sequestration by increasing membrane permeability to calcium, whereas palmitic acid appears to stimulate calcium sequestration by interacting with a portion of the calcium within the vesicles to form a separate, poorly exchangeable calcium pool.

Adenosine Triphosphate↗
PubMed1984

Mechanisms of fatty acid effects on sarcoplasmic reticulum. I. Calcium-fatty acid interaction.

To elucidate the mechanism for the previously reported increase in calcium sequestration by sarcoplasmic reticulum vesicles in the presence of palmitic acid, the ability of this fatty acid to bind calcium was investigated by dual wavelength spectrophotometry using the calcium indicator arsenazo III,, and by Millipore filtration using 45CaCl2. In the presence of 120 mM KCl, 1 mM MgCl2, 15 microM CaCl2, and 40 mM histidine (pH 6.8, 25 degrees C), calcium binding to 10-80 microM palmitic acid occurred slowly (approximately 3-7 min halftime) and was accompanied by an increase in turbidity (measured by difference spectrophotometry) and a decrease in exchangeable calcium. The stoichiometry of calcium binding to palmitic acid under this condition was 0.15 mol of calcium/mol of palmitate, but increased to approximately 0.4 mol of calcium/mol of palmitate in the presence of 0.03-3 mM calcium. The rate of calcium binding to palmitic acid also increased with calcium concentration such that in the presence of 1-3 mM calcium, palmitic acid bound approximately 0.4 mol of calcium/mol of palmitate within 15 s. Thus, palmitic acid may represent a calcium-precipitating anion in regions of the cell, such as the lumen of the sarcoplasmic reticulum, where calcium concentration is high. Analyses of sarcoplasmic reticulum calcium sequestration in the presence of various palmitic acid concentrations support this hypothesis and suggest that 10% of the palmitic acid is accessible to luminal calcium.

Adenosine Triphosphate↗
PubMed1984

Mycotic aneurysm of the sinus of Valsalva due to Eikenella corrodens bacterial endocarditis.

A patient with a left sinus of Valsalva aneurysm secondary to bacterial endocarditis involving an unusual pathogen, Eikenella corrodens, is presented. This case and a review of previous reports on mycotic sinus of Valsalva aneurysm are analyzed. The distinctive M-mode and two-dimensional echocardiographic patterns of a sinus of Valsalva aneurysm as well as the usefulness and limitations of echocardiography in this condition are discussed. This rare complication of bacterial endocarditis can be diagnosed and clinically followed by serial echocardiographic studies, and its presence alone does not necessitate surgical intervention.

Adult↗
PubMed1984

Beta blockers: the extended family.

Beta-Adrenergic blocking drugs, by occupying beta receptors without stimulating adenylate cyclase, interfere with the physiologic responses mediated by the sympathetic nervous system. This property has led to their application in the cardiovascular disorders on which sympathetic tone either underlies or contributes to the pathogenesis of the process. Lipid solubility, selective beta-receptor blockade, and intrinsic sympathomimetic activity are three additional characteristics of beta blockers that modify the pharmacodynamics and pharmacologic effects of each agent. As the role of the sympathetic nervous system in the pathogenesis of heart disease is better defined, the development of beta blockers with particular pharmacologic profiles and fewer side effects may provide more specific treatment.

Adrenergic beta-Agonists↗
PubMed1983

The possible role of endogenous amphiphiles in the membrane abnormalities of ischemic and reperfused myocardium.

Calcium entry into cardiac cells is believed to be controlled by transmembrane-voltage dependent, protein regulated "channels." The sarcoplasmic reticulum participates in the regulation of cytosolic calcium by ATP dependent Ca2+ sequestration during diastole, and by action potential stimulated calcium release. Massive calcium overloading occurs during reperfusion following myocardial ischemia. Calcium overloading activates phospholipases, which may activate another mechanism involved in lethal cellular injury, that is, the accumulation of long chain fatty acids and their derivatives. These compounds are soluble amphiphiles, and once liberated, they may insert into biological membranes and change membrane composition, physiology, and response to ions and drugs. Sarcoplasmic reticulum vesicles were used as an in vitro model to study the effects of palmitic acid, oleic acid, and palmitylcarnitine on the ability of this membrane system to sequester calcium within the vesicles. In the absence of phosphate, palmitic acid enhanced the ability of the vesicles to sequester calcium. Oleic acid and palmitylcarnitine inhibited calcium sequestration. In the presence of phosphate palmitic acid also inhibited the sequestration of calcium by sarcoplasmic reticulum, although not as severely as oleic acid and palmitylcarnitine. These results suggest that the disturbances in cellular calcium homeostasis following ischemia may be due, in part, to the incorporation of accumulated long chain fatty acids into membranes.

Animals↗
PubMed1982

Fatty acid effects on calcium influx and efflux in sarcoplasmic reticulum vesicles from rabbit skeletal muscle.

Low concentrations of fatty acids inhibited initial Ca uptake by sarcoplasmic reticulum vesicles, the extent of inhibition varying with chain length and unsaturation in a series of C14-C20 fatty acids. Oleic acid was a more potent inhibitor of initial Ca uptake than stearic acid at 25 degrees C, whereas at 5 degrees C there was less difference between the inhibitory effects of low concentrations of these fatty acids. When the fatty acids were added later, during the phase of spontaneous Ca release that follow Ca uptake in reactions carried out at 25 degrees C 1-4 microM oleic and stearic acids caused Ca content to increase. This effect was due to marked inhibition of Ca efflux and slight stimulation of Ca influx. At concentrations of greater than 4 microM, both fatty acids inhibited the Ca influx that occurs during spontaneous Ca release; in the case of oleic acid, this inhibition resembled that of initial Ca uptake at 5 degrees C. The different effects of fatty acids at various times during Ca uptake reactions may be explained in part if alterations in the physical state of the membranes occur during the transition from the phase of initial Ca uptake to that of spontaneous Ca release.

Animals↗
PubMed1982

Effects of palmitic acid and palmityl carnitine on calcium sequestration by rabbit skeletal sarcoplasmic reticulum vesicles.

A number of long-chain fatty acids and fatty acid derivatives accumulate in the cytosol of ischemic myocardium. Although the functional significance of this accumulation in vivo remains unclear, these amphiphilic compounds may alter the functional properties of a variety of biological membranes in vitro. In this study, we investigated the effect of palmitic acid and palmityl carnitine on calcium sequestration by sarcoplasmic reticulum vesicles in the absence of calcium-precipitating anions. Palmitic acid, at micromolar concentrations, enhanced calcium sequestration in a concentration-dependent manner when present from the onset of the reaction or when added to calcium-filled vesicles. Under identical conditions, similar concentrations of palmityl carnitine inhibited calcium sequestration when present at the onset of the reaction and caused a rapid release of accumulated calcium when added to calcium-filled vesicles. Low concentrations of palmitic acid decreased the sensitivity of the sarcoplasmic reticulum to the inhibitory effects of palmityl carnitine. These results suggest that calcium pump function in the sarcoplasmic reticulum can be altered by the presence of amphiphilic compounds and that this alteration is dependent on both the structure and number of amphiphiles present.

Animals↗
PubMed1982

The interaction of drugs with the sarcoplasmic reticulum.

Efforts to determine the mechanisms by which drugs interact with membranes can be facilitated by studies of the SR, which has a relatively simple structure. The fact that the SR lacks most of the specific receptors found on other membranes, notably the sarcolemma, is an advantage, as well as a limitation, in that "nonspecific" drug effects can be evaluated readily in the SR. The presence in the SR of a well-characterized calcium pump protein allows the effects of a given drug on membrane function to be analyzed, and drug effects on the functional properties of the SR can now be correlated with their probable sites of action within the membrane. Equally important is the ability to acquire information regarding the relation between the structure of an amphiphilic drug and its mechanism of interaction with the SR membrane, because these interactions depend on the structural properties of both the membrane and the added agent. The potential sites of interaction of amphiphiles schematically portrayed in Figure 3 may be relevant to membranes other than the SR, as the overall structural properties of this membrane appear not to be unique. For this reason, the interaction of drugs with the sarcoplasmic reticulum membrane may provide structural models that are applicable to other biological membranes.

Adrenergic beta-Antagonists↗
PubMed1982

Ion channels in membranes.

The membranes that separate the myocardial cell interior from the extracellular space and delimit compartments within the myocardial cell represent ion-impermeable phospholipid barriers. Embedded in these phospholipid membranes are intrinsic membrane proteins, some of which serve as ion channels. The voltage-sensitive ion channels that control the sarcolemmal action potential appear to be highly regulated intrinsic membrane proteins that contain "gates" that respond to changing membrane potential by opening and closing an ion-selective "pore" that allows specific ions to cross the membrane. Pharmacologic blockade of the sarcolemmal ion channels is selective, not only for individual classes of ion channels, but also for specific states of a given type of channel. The basis for this selectivity remains unclear, but may derive from a preferential interaction between a given drug and a specific type of ion-channel protein, or a selective drug action on a structurally specific region of the membrane phospholipid that is in intimate contact with the ion-channel protein.

Animals↗
PubMed1981

Lipids and membrane function: implications in arrhythmias.

Increasing attention is being devoted to the relevance of lipid-membrane interactions to arrhythmias and their therapy. Particular emphasis is placed on alterations of transmembrane ion transport that can result from closure of protein channels, perhaps mediated by chemically induced changes in the phospholipid membrane bilayer. Such alterations may underlie antiarrhythmic drug actions.

Action Potentials↗
PubMed1981

The relationship between frequent and complex ventricular ectopy during 24 h ambulatory electrocardiographic monitoring.

Complex and frequent ventricular ectopy have been associated with an increased risk of sudden death in certain patient groups. The evaluate the relationship between complexity and frequency of ventricular ectopy, 275 consecutive 20- to 24-hour ambulatory electrocardiograms were analyzed. The unselected study population included 56% males and the average age was 56. Prior myocardial infaraction was present in 28%. Dizziness, palpitations and syncope were present in 16, 30 and 13%, respectively. Complex ventricular ectopy (complexity) was definced as multiformity, bigeminy, couplets or salvos, ventricular tachycardia (VT), and R on T. Premature ventricular depolarizations (PVDs) were observed in 230 of 275 records and exhibited one or more criteria for complexity in 164 (71%). Of the 164 records with complexity, 71% had multiformity, 35% bigeminy, 32% couplets, 5% VT, and 22% R on T. Of 159 records with average PVD frequency less than or equal to 30/h, 98 (61%) exhibited complexity, whereas 66 of 71 (93%) records with greater than 30 PVD/h had complexity. Of 113 records with greater than 100 PDVs/24h, 102 (90%) exhibited complexity, whereas 60 of 99 (61%) records with between 2 and 100 PDVs on the entire record showed complexity. Of the 164 records with complexity, 43 had 'rare PVDs' (less than 30/24 h), but exhibited 72% multiformity, 5% begeminy, 25% couplets, 2% VT, and 14% R on T. This study demonstrates a high prevalence (50-60) of complexity in patients with 'infrequent' PDVs defined as less than 30/24 h, less than 30 average per h, or less than 30 per any 1 h. In approximately 25% of patients with infrequent PDVs, complexity included repetitive ventricular beating (couplets, salvos, or VT). These findings indicate that infrequent PVDs are often complex.

Adult↗