Hypertension: Feldman J

Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, Doctor A, Davis A, Duff J, Dugas MA, Duncan A, Evans B, Feldman J, Felmet K, Fisher G, Frankel L, Jeffries H, Greenwald B, Gutierrez J, Hall M, Han YY, Hanson J, Hazelzet J, Hernan L, Kiff J, Kissoon N, Kon A, Irazuzta J, Irazusta J, Lin J, Lorts A, Mariscalco M, Mehta R, Nadel S, Nguyen T, Nicholson C, Peters M, Okhuysen-Cawley R, Poulton T, Relves M, Rodriguez A, Rozenfeld R, Schnitzler E, Shanley T, Kache S, Skache S, Skippen P, Torres A, von Dessauer B, Weingarten J, Yeh T, Zaritsky A, Stojadinovic B, Zimmerman J, Zuckerberg A. · No affiliation provided · Crit Care Med. · Pubmed #19325359 No free full text.

Abstract: BACKGROUND: The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and to improve patient outcomes. OBJECTIVE: 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. PARTICIPANTS: Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001-2006). METHODS: The Pubmed/MEDLINE literature database (1966-2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. RESULTS: The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%-3% in previously healthy, and 7%-10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. CONCLUSION: The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill <or=2 secs, and 2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3-6.0 L/min/m.

Feldman J, Bousquet P. · No affiliation provided · J Hypertens. · Pubmed #12714859 No free full text.

This publication has no abstract.

Bousquet P, Dontenwill M, Greney H, Feldman J. · Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France. · J Cardiovasc Pharmacol. · Pubmed #11346216 No free full text.

Abstract: The site of the hypotensive action of imidazoline compounds, such as clonidine, was first identified within the rostroventrolateral part of the brainstem. Afterwards, it was shown that imidazolines reduced blood pressure when applied in this area, whereas no catecholamine was capable of such an effect. These data led us to suggest the existence of receptors specific for imidazolines different from the alpha-adrenergic receptors. Soon after, the existence of imidazoline binding sites (IBS) was reported in the brain and in a variety of peripheral tissues including pancreatic gland and kidney. As expected, these specific binding sites do not bind the catecholamines. The IBS are classified in two groups: the I1 type, sensitive to clonidine and idazoxan; and the I2 type, sensitive to idazoxan and largely insensitive to clonidine. Imidazoline receptors were shown to be involved in several physiological regulations and pathological processes such as hypertension, diabetes mellitus and some mood disorders. Evidence for their implication in the nervous regulation of blood pressure and in the insulin secretion control will be presented. The hypotensive effects of clonidine-like drugs involve imidazoline receptors (I1Rs), while their most frequent side-effects only involve alpha2-adrenergic receptors. A new class of centrally acting antihypertensive drugs selective for I1Rs is now available. At hypotensive doses, these drugs are devoid of significant side effects. It was shown that the good acceptability of these drugs is likely due to their selectivity for I1Rs.

Feldman J, Berenbeim D. · Pulmonary Hypertension Program, St. Joseph's Hospital, Phoenix, USA. · Manag Care Interface. · Pubmed #17274478 No free full text.

Abstract: In this two-part white paper from The Pharmacy and Therapeutics Society, the authors have described a number of potent oral therapies available or in late clinical development for the treatment of pulmonary arterial hypertension (PAH). They assert that for optimal clinical efficacy and cost efficiency, patients with PAH should be managed, and treatment initiated, within specialist tertiary referral centers. Combination therapy using oral agents with complementary mechanisms of action may offer increased clinical efficacy over monotherapy and reduce the need for parenteral therapy; however, combination therapy may be limited by clinically significant interaction between these agents, such as in the case of bosentan and sildenafil. Newer treatments may offer less potential for liver damage and more favorable interaction profiles.

Feldman J, Berenbeim D. · Pulmonary Hypertension Program, St. Joseph's Hospital, Phoenix, USA. · Manag Care Interface. · Pubmed #17137242 No free full text.

Abstract: Pulmonary arterial hypertension (PAH) represents a significant challenge to physicians, particularly because of its etiology and nonspecific presentation. Unfortunately, the majority of patients are not diagnosed until the condition is at an advanced stage. In this two-part White Paper from The Pharmacy and Therapeutics Society, prostanoids, administered as continuous intravenous or subcutaneous infusions, are the most effective treatments but are inconvenient and costly, owing to complex parenteral administration. The endothelin-receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil are currently the only oral therapies licensed for PAH; however, bosentan has an identified risk of liver toxicity. Newer PAH treatments may offer benefits over existing therapies in terms of less potential for liver damage and more favorable interaction profiles.

Sy GY, Bruban V, Bousquet P, Feldman J. · Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France. · Hypertension. · Pubmed #11230279 links to  free full text

Abstract: NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct action on presynaptic nerve terminals, stimulating the release of gamma-aminobutyric acid, glutamate, and norepinephrine. Our aim was to study the possible role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmenidine, and alpha-methyl-norepinephrine (alpha-MNA). Sites and mechanisms of the hypotensive action of these drugs were different; clonidine and rilmenidine acted on imidazoline receptors in the nucleus reticularis lateralis, whereas alpha-MNA acted upon alpha(2)-adrenoceptors in the nucleus tractus solitarius. The influence of N:(G)-nitro-L-arginine, an NO synthase inhibitor, on the central hypotensive effects of these drugs was investigated in pentobarbital-anesthetized rabbits. The intracisternal (IC) administration of alpha-MNA (30 microg/kg) induced hypotension (79+/-2 versus 103+/-4 mm Hg) and bradycardia (222+/-8 versus 278+/-4 bpm) (P:<0.05) (n=5). Clonidine (0.07 microg/kg IC) also induced hypotension (69+/-5 versus 99+/-4 mm Hg) and bradycardia (266+/-7 versus 306+/-10 bpm) (P:<0.05) (n=5). In addition to clonidine, rilmenidine (1 microg/kg IC) induced hypotension (64+/-4 versus 97+/-4 mm Hg) and bradycardia (264+/-11 versus 310+/-4 bpm) (P:<0.05) (n=5). Pretreatment with N:(G)-nitro-L-arginine (900 microg/kg IC) completely prevented the hypotensive effect of alpha-MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the catecholamine alpha(2)-adrenoceptor agonist alpha-MNA, have distinct mechanisms of action.