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L J Rubin

Publications and source records attributed to L J Rubin.

At least 91 records · Page 5Linked to original sources
PubMed1995

Inhibition of cytochrome P-450 reduces voltage-gated K+ currents in pulmonary arterial myocytes.

Cytochrome P-450 (P-450) is a NADPH-requiring and O2-dependent monooxygenase system. It is present in lung and has been postulated to act as an O2 sensor in hypoxic pulmonary vasoconstriction. To determine whether P-450 is involved in the regulation of voltage-gated K+ (KV) channel activity in pulmonary artery (PA) myocytes, we used the whole cell patch-clamp technique to evaluate the effects of P-450 inhibitors on KV channel currents (IKV) and membrane potential (Em). Bath application of the P-450 inhibitors clotrimazole, miconazole, and 1-aminobenzotriazole (1-ABT) significantly and reversibly inhibited steady-state IKV (IKss) and depolarized PA cells bathed in either Ca(2+)-containing (1.8 mM) or Ca(2+)-free [0.5-1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid present] bath solution. Clotrimazole (1 microM), miconazole (10 microM), and 1-ABT (1 mM) reversibly reduced IKss, elicited by a test potential of +80 mV, by 40, 70, and 31%, respectively. Pretreatment of PA smooth muscle cells with 10 mM 4-aminopyridine (4-AP) prevented the subsequent inhibitory effect of clotrimazole on IKV. However, pretreatment of the cells with 1 mM tetraethylammonium negligibly altered the effects of miconazole on IKV and Em. In current-clamp (I = 0) measurements, clotrimazole depolarized PA myocytes by 9 and 11 mV during perfusion with Ca(2+)-containing and Ca(2+)-free bath solution, respectively. 1-ABT also caused a 9-mV depolarization in PA myocytes bathed in Ca(2+)-free solution. These effects are similar to those induced by hypoxia, reduced glutathione, and 4-AP. Clotrimazole also decreased IKV and depolarized mesenteric arterial myocytes. These data raise the possibility that the P-450 system, due to its influence on IKV and sensitivity to O2 tension and NADPH, may play a role in linking the regulation of pulmonary vascular tone to the alteration of cellular redox status through a common pathway of KV channel activity.

Animals↗
PubMed1995

Inhibition of glycolysis by 2-DG increases [Ca2+]i in pulmonary arterial smooth muscle cells.

Inhibition of glycolysis depolarizes single pulmonary arterial smooth muscle cells (PASMC) and potentiates hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs. Whether glycolytic inhibition causes an increase in the intracellular Ca2+ concentration ([Ca2+]i) in PASMC was determined in this study. [Ca2+]i was measured in primary cultured rat PASMC using the Ca2+ -sensitive fluorescent indicator, fura 2, and quantitative fluorescence microscopy. Extracellular application of the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), significantly and reversibly increased [Ca2+]i in PASMC. Removal of extracellular Ca2+ and application of the Ca2+ channel blocker, verapamil (10 microM), attenuated, but did not eliminate, the 2-DG-induced rise in [Ca2+]i. In the absence of extracellular Ca2+, however, depletion of inositol triphosphate-sensitive intracellular Ca2+ stores by 10 microM cyclopiazonic acid (CPA) completely abolished the 2-DG-induced increase in [Ca2+]i. The data suggest that 2-DG-induced increases in [Ca2+]i result from both Ca2+ influx through the verapamil-sensitive voltage-gated Ca2+ channels and Ca2+ release from the CPA-sensitive intracellular Ca2+ stores.

Animals↗
PubMed1995

Endotoxin-induced myocardial dysfunction: is there a role for nitric oxide?

Nitric oxide has been implicated in the regulation of cardiac contractile function as well as the depressed myocardial contractility associated with sepsis and endotoxemia. We examined the effects of nitric oxide synthase (NOS) inhibitors and a nitric oxide generator on contractile responses of left atrial preparations and ventricular myocytes isolated from endotoxemic guinea pigs, which exhibit depressed myocardial contractile function. The NOS inhibitor L-NAME had no effect on contractile tension developed by control atria or atria isolated from guinea pigs 4 or 16 h after an intraperitoneal injection of endotoxin. Similarly, contraction of ventricular myocytes isolated from control or endotoxemic guinea pigs (4 h after endotoxin injection) was unchanged by exposure to several NOS inhibitors. In addition, neither Ca(2+)-dependent nor Ca(2+)-independent ventricular NOS activity was affected by endotoxemia. These data suggest that nitric oxide alone is not responsible for the cardiac contractile dysfunction of endotoxemic guinea pigs.

Animals↗
PubMed1994

Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin.

OBJECTIVE: To evaluate the effects of long-term-intravenous infusion of prostacyclin on exercise capacity, hemodynamics, and survival in patients with primary pulmonary hypertension. DESIGN: Open, multicenter, uncontrolled trial. SETTING: Four referral centers. PATIENTS: 18 patients with primary pulmonary hypertension: 1 New York Heart Association (NYHA) class II patient, 13 NYHA class III patients, and 4 NYHA class IV patients. INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pumps. All patients were treated with anticoagulant agents. MEASUREMENTS AND MAIN RESULTS: With the 6-minute walk used to evaluate exercise capacity, patients could walk on average more than 100 meters farther after prostacyclin therapy was initiated (distance at 6 months, 370 +/- 119 meters compared with 264 +/- 160 meters at baseline; P < 0.001; distance at 18 months, 408 +/- 138 meters; P = 0.02 compared with baseline). Hemodynamics were improved at 6 months: The cardiac index increased 18% (95% CI, 0.1% to 36.7%; P = 0.02), and mean pulmonary artery pressure and total pulmonary resistance decreased 9% (CI, 1.4% to 15.7%; P = 0.03) and 26% (CI, 6.1% to 46.3%; P = 0.02), respectively, compared with baseline. The improvements in cardiac index and total pulmonary resistance were maintained at 12 months (27% increase [CI, 1.3% to 51.9%; P = 0.05] and 32% decrease [CI, 9.7% to 53.6%; P = 0.02] compared with baseline, respectively). Survival was improved in NYHA class III and IV patients who received continuous prostacyclin (n = 17; follow-up, 37 to 69 months) when compared with historical controls who received standard therapy (National Institutes of Health Primary Pulmonary Hypertension Registry, n = 31, P = 0.045). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates for the patients treated with prostacyclin were 86.9%, 72.4%, and 63.3%, respectively, compared with 77.4%, 51.6%, and 40.6% for the historical control group (hazard ratio, 2.9 [CI, 1.0 to 8.0; P = 0.045]). Serious complications attributable to the drug and delivery system included two deaths and seven episodes of nonfatal sepsis in three patients. CONCLUSIONS: Continuous intravenous prostacyclin resulted in sustained clinical and hemodynamic improvement and probably in improved survival in patients with severe primary pulmonary hypertension. Despite potentially serious complications, long-term prostacyclin may be especially helpful in seriously ill patients awaiting transplantation.

Adult↗
PubMed1994

Contractile dysfunction of ventricular myocytes isolated from endotoxemic guinea pigs.

Mechanisms responsible for the decline in cardiac function following sepsis or endotoxemia are unclear but may result from indirect effects of cardiodynamic readjustments to diminishing venous return or to direct effects of endogenous factors on myocardial function. We examined contractile properties of ventricular myocytes isolated from endotoxemic guinea pig hearts to 1) verify and characterize inotropic dysfunction in the absence of immediate influences from extrinsic neurohumoral agents, and 2) assess the ability of beta-adrenergic receptor activation to modulate contractility. Myocytes were isolated by enzymatic dispersion from hearts 4 h following an intraperitoneal injection of Escherichia coli endotoxin. Contractility was assessed using a computer-driven image analysis system. Inotropic responsiveness of endotoxemic myocytes to changes in frequency of stimulation (.2-2.0 Hz) or increases in extracellular calcium ([Ca2+]o, 1.8-8.0 mM) was significantly less than control myocytes, even with maximally effective frequencies or [Ca2+]o. These data demonstrate that the endotoxin-induced dysfunction is intrinsic to ex vivo cardiac myocytes and independent of immediate influence from extracardiac factors by 4 h in vivo exposure to endotoxemia. Inotropic responsiveness to beta-adrenergic receptor activation remained intact in endotoxemic myocytes; maximally effective concentrations (> 10 nM) reversed the endotoxin-induced contractile dysfunction. These data confirm that E. coli endotoxemia incorporates intrinsic contractile dysfunction of myocardial cells, while sparing their ability to respond to inotropic mechanisms activated by beta-adrenoceptor agonists.

Analysis of Variance↗
PubMed1994

Cardiodynamic response to Escherichia coli endotoxemia: effects of fluid resuscitation.

We tested the influence of in vivo volume resuscitation on intrinsic contractile properties of left ventricular (LV) preparations of endotoxemic guinea pigs. Escherichia coli endotoxin (LPS)-injected animals were divided into nonresuscitated and resuscitated groups. Volume resuscitation improved cardiac output and stroke volume, increased arterial pH and body temperature, and decreased mortality. In isovolumetric LV preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) of LPS with (42 +/- 3) and without (42 +/- 2) fluid resuscitation were consistently less than control values (70 +/- 3). LV end-diastolic pressure-volume (compliance) decreased in LPS-nonresuscitated hearts, while LV compliance of LPS-resuscitated hearts was similar to control. Thus, intravascular volume expansion selectively improved LV diastolic compliance of LPS hearts without affecting LV systolic function. These findings suggest that LV systolic and diastolic dysfunctions associated with endotoxemia and Gram-negative sepsis may involve separate pathogenic mechanisms.

Analysis of Variance↗
PubMed1994

Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells.

Hypoxia-induced pulmonary vasoconstriction (HPV) is triggered by a rise in cytosolic Ca2+ concentration ([Ca2+]i) that is partially controlled by voltage-gated Ca2+ channels. Hypoxia inhibits voltage-gated K+ (KV) channels in pulmonary artery (PA) myocytes. This depolarizes the cells, opens voltage-gated Ca2+ channels, thereby increases [Ca2+]i, and initiates HPV. In intact animals and isolated perfused lungs, metabolic inhibitors and reducing agents augment HPV. We compared the effects of hypoxia with the glycolysis inhibitor, 2-deoxy-D-glucose (2-DOG), and the reducing agent, reduced glutathione (GSH), on voltage-gated steady-state K+ currents (IK,ss) and membrane potential (Em) in cultured rat pulmonary and mesenteric arterial (MA) smooth muscle cells. Bath application of 10 mM 2-DOG (glucose-free) or 5-10 mM GSH reversibly reduced IK,ss by 25-35% in PA myocytes, with 5 mM ATP present in the pipette solution. Neither hypoxia nor 2-DOG significantly affected IK,ss in MA myocytes, but GSH did reduce IK,ss in these cells. Furthermore, hypoxia, 2-DOG, and GSH depolarized PA cells in the absence as well as in the presence of external Ca2+. Hypoxia, 2-DOG, and GSH also evoked action potentials on the top of the steady depolarization in 36-50% of PA myocytes but not in any MA myocytes; removal of external Ca2+ abolished the action potentials without affecting the steady depolarization. These effects were comparable to those produced by 4-aminopyridine (5-10 mM), a blocker of KV channels. This implies that the action potentials are attributable to Ca2+ influx through voltage-gated Ca2+ channels opened by the steady depolarization due to KV channel inhibition. In the presence of 2-DOG or GSH, hypoxia had no further effect on IK,ss or Em in PA cells; this implies that hypoxia, 2-DOG, and GSH all block the same K+ channels. The data suggest that 1) the hypoxia-induced decrease of IK,ss and the resultant depolarization in PA myocytes may be related to a local decrease of intracellular ATP level and/or a change in redox status of the membrane or cytosol and 2) extracellular Ca(2+)-dependent action potentials may be responsible for at least part of the increase in [Ca2+]i during HPV. Similarities between the effects of hypoxia, 2-DOG, and GSH on IK,ss and Em in PA myocytes, along with the dissimilar responses of PA and MA myocytes, suggest that a common mechanism may underlie the responses of PA cells to these treatments.

Animals↗
PubMed1994

Escherichia coli endotoxin inhibits agonist-mediated cytosolic Ca2+ mobilization and nitric oxide biosynthesis in cultured endothelial cells.

Altered release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) has been proposed as a final common pathway underlying the abnormal vasodilator responses to gram-negative lipopolysaccharide (endotoxin). However, mechanisms responsible for lipopolysaccharide-induced changes in EDRF/NO release from endothelial cells have not been clarified. We evaluated direct effects of Escherichia coli endotoxin on agonist-stimulated cytosolic Ca2+ mobilization and NO biosynthesis in cultured bovine and porcine aortic endothelial cells (ECs). Two methods were used to assay for NO: (1) analysis of NO-induced endothelial levels of cGMP as a biological indicator of NO generation and (2) direct quantitative measurement of NO release (chemiluminescence method). Cytosolic free Ca2+ ([Ca2+]i) was evaluated using fura 2 fluorescence methodology (340/380-nm ratio excitation and 500-nm emission). Incubation of ECs with endotoxin (0.5 microgram/mL, 1 hour plus 1-hour wash) significantly inhibited bradykinin (100 nmol/L)- and ADP (10 mumol/L)-mediated increases in endothelial cell cGMP to 37% and 22% of control responses, respectively. In contrast, endotoxin failed to inhibit the increase in cGMP produced by the non-receptor-dependent Ca2+ ionophore A23187 (1 mumol/L) or sodium nitroprusside (1 mmol/L). Similarly, incubation with endotoxin inhibited ADP-stimulated increases in NO release and EDRF bioactivity to 55% and 56% of control values, respectively, but did not affect A23187-stimulated increases in NO release or EDRF bioactivity. Endotoxin produced significant decreases in both transient and sustained [Ca2+]i responses of ECs to bradykinin and ADP. For example, the initial rapid increase in bovine EC [Ca2+]i in response to bradykinin was reduced to 31% of the initial increases in control cells, and the secondary plateau phase was reduced to only 3% of respective control responses. Concentration-response relation to endotoxin (10(-3)) to 10(0) micrograms/mL) indicated high correlation and similar IC50 values (0.025 and 0.021 micrograms/mL, respectively) for inhibitory effects on cGMP and [Ca2+]i. Endotoxin had no effect on inositol trisphosphate formation ([3H]myo-inositol incorporation) and intracellular Ca2+ release ([Ca2+]i responses in Ca(2+)-free medium) induced by bradykinin. However, agonist-stimulated Mn2+ quenching (index of Ca2+ influx) was significantly attenuated by endotoxin treatment. These studies demonstrate that endotoxin directly decreases agonist (bradykinin and ADP)-mediated biosynthesis and release of EDRF/NO from ECs. These effects can be explained by altered [Ca2+]i mobilization mechanisms, which in turn produce subsequent decreases in activity of the Ca(2+)-calmodulin-dependent constitutive isoform of NO synthase and, ultimately, impairment of agonist-mediated NO release and endothelium-dependent vasodilation.

Adenosine Diphosphate↗
PubMed1993

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals.

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.

Animals↗
PubMed1993

Characterization of a Mg-dependent, Na-inositol co-transport process in cardiac sarcolemmal vesicles.

[3H]-myo-Inositol transport into cardiac sarcolemmal vesicles is both a time- and Na(+)-dependent process. Transport was stimulated 3-fold by 1 microM valinomycin suggesting the process is electrogenic. myo-Inositol transport was dependent upon the presence of Mn2+ or Mg2+ but not Ca2+. Kinetic analysis revealed a high affinity transport process that was saturable (Vmax, 650 +/- 71 pmoles myo-inositol/mg protein/min; Km, 37.7 +/- 1.3 microM) and a low affinity process that was unsaturable up to 1.0 mM substrate. Transport was not inhibited by 1.0 mM of either L-glucose, D- or L-galactose. However, D-glucose and L-fucose at 1.0 mM were inhibitory. Higher concentrations (30 mM) of each of the sugars inhibited transport. myo-Inositol transport was also inhibited by the inositol isomers (1.0 mM), D-chiro-inositol, epi-inositol and scyllo-inositol with scyllo-inositol being most effective. Kinetic analysis established scyllo-inositol as a competitive inhibitor of cardiac myo-inositol transport, increasing the Km for substrate three-fold (122 +/- 21 microM). These data indicate that inositol transport across cardiac sarcolemma is a Mg(2+)-dependent Na+ co-transport process that is electrogenic and stereospecific.

Animals↗
PubMed1993

Ionic currents in rat pulmonary and mesenteric arterial myocytes in primary culture and subculture.

The electrophysiological properties of cultured single vascular smooth muscle (VSM) cells from rat pulmonary (PA) and mesenteric (MA) arteries were studied using the whole cell patch-clamp technique. Cells were studied at 3-7 days as primary cultures, or were replated after 10-20 days and subcultured for 2-5 days. In the standard physiological bath solution (containing 1.8 mM Ca2+), and with 125 mM K+ + 10 mM ethylene glycol-bis(beta-aminoethyl ether)- N,N,N',N'-tetraacetic acid (EGTA)-filled pipettes, both PA and MA primary cultured cells had high input resistances (mean = 2-3 G omega) and resting membrane potentials of about -40 mV. The cells were clamped at a holding potential of -70 mV. Depolarization to -20 mV or more evoked a transient inward current (Iin) that was eliminated in Ca(2+)-free bath solution; this indicates that Iin was carried by Ca2+. Iin was substantially smaller in subcultured cells from both PA and MA. Depolarization also activated three components of outward current (Iout) in primary cultured PA and MA cells: a rapidly inactivating transient component (Irt), a slowly inactivating transient component (Ist), and a steady-state (noninactivating) component (Iss). All three components of Iout were inhibited to varying degrees by 5 mM 4-aminopyridine and were eliminated by replacing intracellular K+ with Cs+, but were only minimally affected by removal of extracellular Ca2+. These results suggest that this Iout was carried by K+ and was voltage gated. Little external Ca(2+)-dependent Iout was observed under these conditions, but a substantial Ca(2+)-dependent component was seen when the EGTA concentration in the pipettes was reduced to 0.1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1993

Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes.

To explore possible mechanisms underlying hypoxia-induced pulmonary vasoconstriction, the effect of hypoxia on outward K+ current (Iout) was evaluated in primary cultured rat pulmonary (PA) and mesenteric (MA) arterial smooth muscle cells using the whole cell patch-clamp technique. When the cells were bathed in standard physiological salt solution and the patch pipettes contained Ca(2+)-free media with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), virtually all of the Iout, including both the rapidly inactivating component (Irt) and the steady-state (noninactivating) component (Iss), was mediated by voltage-gated K+ channels. Reduction of O2 tension in the bath solution from 155 Torr to < 74 Torr with sodium dithionite reversibly inhibited both Irt and Iss in PA myocytes, but not in MA myocytes. The hypoxia-sensitive Iss was activated at about -50 mV; thus, some of the channels responsible for this current may be open at the resting membrane potential (-40 +/- 1 mV) of PA cells used in this study. Hypoxia also significantly depolarized PA cells bathed in PSS (1.8 mM Ca2+) from -40.7 +/- 1.3 to -24.0 +/- 2.4 mV, and PA cells bathed in Ca(2+)-free PSS (0.1 mM EGTA) from -38.4 +/- 1.3 to -26.1 +/- 3.9 mV. The hypoxia-induced inhibition of Iout in PA cells was accompanied by an apparent increase in inward Ca2+ current.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

NG-monomethyl-L-arginine paradoxically relaxes preconstricted canine intrapulmonary arteries.

We studied the effects of NG-monomethyl-L-arginine (LMMA), a nitric oxide (NO) synthesis inhibitor, in canine intrapulmonary arteries constricted with phenylephrine. Isolated vessels were suspended in organ chambers containing modified Krebs solution, and isometric tensions were recorded. In contrast to the expected constriction predicted from other studies, LMMA instead caused dose-dependent vasorelaxation in phenylephrine-constricted canine pulmonary arteries. LMMA (1 and 10 microM) reduced the phenylephrine contraction by 5 and 23%, respectively. Similar dose-dependent relaxations were observed with NG-monomethyl-D-arginine (DMMA) but not with L-arginine (L-Arg), N epsilon-methyl-L-lysine, and another NO synthesis inhibitor, N omega-nitro-L-arginine (LNA), suggesting that a methyl group positioned at the guanidino-nitrogen is important in these responses. Vasorelaxation induced by LMMA and DMMA was not affected by pretreatment with the NO precursor L-Arg; however, responses were abolished by dissimilar cyclooxygenase inhibitors indomethacin (10 microM) and meclofenamate (2 microM). Pretreatment of vessels with LNA (100 microM) augmented LMMA-induced relaxations but attenuated DMMA-induced responses. LMMA- and DMMA-induced vasorelaxations were also observed in endothelium-rubbed vessels; DMMA-induced vasorelaxations were similar in vessels with and without endothelium, whereas LMMA-induced relaxations were increased in endothelium-rubbed vessels. These data suggest that LMMA and DMMA induced vasorelaxation by causing synthesis of dilator prostaglandins, which was independent of the presence of endothelial cells and the L-Arg-NO pathway. In addition, both endothelium removal and LNA pretreatment augmented LMMA-induced but not DMMA-induced relaxations, suggesting that inhibition of NO synthesis by LMMA opposes its cyclooxygenase-dependent vasorelaxant effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Ontogeny of neonatal pulmonary vascular pressure-flow relationships.

Previously we reported that pulmonary vascular pressure gradients determined by vascular occlusion varied as a function of neonatal age. The purpose of this study was to evaluate the effect of blood flow on pressure gradients during normoxia (inspired O2 28%) and hypoxia (inspired O2 4.2%) in isolated, indomethacin-treated lungs obtained from lambs at less than 1, 2-4, 12-14, and 30-32 days of age (n = 6 at each age). The total pulmonary pressure gradient was partitioned into pressure gradients across relatively indistensible arteries and veins and relatively compliant vessels in the middle region (delta Pm) by inflow and outflow occlusions at flows of 25, 50, 75, and 100 ml.kg-1.min-1. During normoxia, lungs from lambs less than 1 day of age had significantly greater pressures at each flow than lungs from older lambs, due primarily to a significantly greater delta Pm in this age group. During hypoxia, the greatest vasoconstriction occurred in the youngest group, also due mostly to an increased delta Pm. This enhanced response to hypoxia in the younger age groups was due to inhibition of prostaglandin synthesis; without indomethacin treatment, the older age groups had a greater hypoxic pressor response than the younger groups. The arterial vascular resistance at all ages was relatively constant as a function of blood flow during both normoxia and hypoxia, whereas the total and middle vascular resistances generally decreased as a function of flow. The venous resistance initially decreased and then was constant. These results suggest that the neonatal pulmonary circulation h as a fixed arterial resistance, a slightly distensible venous region at low flows, and a more distensible middle region.

Aging↗
PubMed1992

Primary pulmonary hypertension. Practical therapeutic recommendations.

Primary pulmonary hypertension (PPH) is a rare disease of unknown aetiology which typically results in right heart failure and death within several years of the onset of symptoms. While there is no cure for PPH, several pharmacological and surgical approaches to treatment have been developed over the past decade which proved useful in a significant proportion of patients. In particular, vasodilator therapy may produce sustained haemodynamic and symptomatic improvement in up to approximately two-thirds of patients; in the remaining patients, vasodilators may either produce no benefit or result in deterioration. The calcium channel blocking agents are the most widely used oral vasodilators; continuous intravenous infusions of epoprostenol (prostacyclin; prostaglandin I2) have been used in some patients who are refractory to oral therapy, particularly as a bridge to transplantation. While combined heart-lung transplantation has been considered the surgical procedure of choice for severe pulmonary hypertension, single lung transplantation has been performed successfully in a small number of patients, and may be the preferred approach in patients with reasonably preserved right heart function.

Anticoagulants↗