Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review of the clinical studies of thromboxane synthase inhibitors (TXSIs) and thromboxane receptor blocking drugs (TXRBs) covers the years 1981 to the present. Clinical studies on TXSIs include those in normal volunteers as well as those in patients with angina, peripheral vascular disease and Raynaud's syndrome, pulmonary hypertension, cerebral vasospasm, hepatorenal syndrome, adult respiratory distress syndrome, and those on cardiopulmonary bypass and hemodialysis. The compounds studied include dazoxiben, dazmagrel, CGS 13080, CV 4151, OKY 1581, OKY 046, and U 63557A. In volunteers, single-dose studies have demonstrated inhibition of thromboxane A2 (TXA2) formation, with some small increases in bleeding time but no marked effect on platelet aggregation. In general, the compounds tested were ineffective in both chronic stable angina and vasospastic angina but caused symptomatic improvement in patients with unstable angina. The TXSIs studied were found to produce no consistent effects in any of the other clinical conditions. Since none of the compounds tested produced a sustained inhibition of TXA2 synthesis, the disappointing clinical results with this class of drugs may be due to an incomplete blockade of thromboxane synthase with the dosage regimens used. Possible alternative or additional reasons for the general lack of success with TXSIs could be that some of the diseases studied do not involve TXA2 or that accumulating prostaglandin endoperoxides in the presence of thromboxane synthase inhibition substitute for TXA2 in causing platelet aggregation. TXRBs rely for their efficacy only on blockade of the TXA2 receptor and antagonize the deleterious effects of both TXA2 and prostaglandin H2 equally, so they represent a simpler pharmacological approach than TXSIs. Such drugs include AH 23848, GR 32191, BM 13.177, BM 13.505, and SQ 28668. All of these compounds are inhibitors of platelet aggregation induced by TXA2 or by its stable mimetic, U-46619. AH 23848 was ineffective in patients with stable angina but did benefit patients with peripheral vascular disease. BM 13.177 has also proven effective in preventing restenosis after angioplasty, occlusion of coronary artery bypass grafts, and the deleterious effects of TXA2 in renal disease. From these preliminary studies, it would appear that TXRBs may offer greater clinical potential than TXSIs. Further studies currently underway with TXRBs to resolve this question include those in unstable angina, angioplasty, peripheral vascular disease, renovascular hypertension, and cyclosporine nephrotoxicity.
 ...
PMID:Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review. 213 20

In 10 patients with adult respiratory distress syndrome, we studied the effects on respiratory system mechanics of two levels of positive end-expiratory pressure (PEEP), best PEEP (BP) and half of this value (HBP), using a respiratory inductive plethysmograph (RIP) combined with a super syringe. We found the following. 1) Inflation compliance of pressure-volume (PV) curves did not change significantly. 2) End-expiratory volume increased with HBP and further with BP (278 +/- 186 and 464 +/- 313 ml, respectively, P less than 0.01). This increase was positively correlated with inflation compliance for HBP and BP (r = 0.794, P less than 0.01 and r = 0.876, P less than 0.01, respectively). 3) No dynamic hyper-inflation was detected on mechanical ventilation at zero end-expiratory pressure (ZEEP), and the time constant of the respiratory system was in the normal range (0.79 +/- 0.21 s). 4) Hysteresis of PVrip curves, which were corrected for gas exchange, decreased significantly with PEEP (P less than 0.05). We conclude that PEEP does not change inflation PV curve but induces an increase in intrathoracic volume whose magnitude is related to compliance and PEEP level. The reduction of hysteresis with PEEP suggests less gas trapping and thus a functional improvement.
 ...
PMID:Mechanical effects of PEEP in patients with adult respiratory distress syndrome. 218 53

In adult respiratory distress syndrome (ARDS), the pulmonary artery hypertension is followed by increases in right ventricular diastolic and systolic volumes and a decreased ejection fraction. The stroke volume is preserved by the Frank-Starling mechanism as preload increases, even in the presence of severe pulmonary artery hypertension. In contrast, if there coexists a depression of the right ventricle contractility, as during right ventricular contusion, septic shock or a viral myocarditis, the compensatory Frank-Starling mechanism, that maintains right ventricular pump function, seems limited. Thus, it appears that the contractile state of the right ventricle can influence the clinical course of ARDS. In addition, patients with ARDS require mechanical ventilation with positive end-expiratory pressure (PEEP), which has a detrimental effect on right ventricular loading conditions. Most investigators agree that the most important effect is a decreased right ventricular preload, secondary to the increased pleural pressure due to PEEP. However, in patients with severe pulmonary artery hypertension, the PEEP-induced increase in right ventricular afterload may become more preponderant, and inotropic support to maintain right ventricular stroke volume may be necessary.
 ...
PMID:Right ventricular performance in adult respiratory distress syndrome. 227 9

The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists.
 ...
PMID:Ranitidine compared to cimetidine in multiagent pharmacological treatment of porcine Pseudomonas ARDS. 231 Dec 2

The aim of this study was to establish a stable and reproducible model of pulmonary artery hypertension with concomitant ARDS-like changes of lung function and lung morphology. In eight anesthetized and ventilated dogs, 0.01 ml/kg oleic acid (OA) was given i.v. followed by repetitive injections of 100 microns glass beads (GB) into the right atrium until a mean pulmonary artery pressure of 35-40 mmHg was reached. Mean right ventricular (RVP) and pulmonary artery (PAP) pressures, pulmonary vascular resistance (PVR), lung compliance and resistance, PaO2, intrapulmonary shunt and colloidosmotic pressure (COP) were closely monitored for 150 min. PAP, RVP, and PVR considerably increased subsequent to OA/GB injection, and stabilized at a high level within 70 min, showing only a minimal decrease (PAP, RVP) or no change (PVR) during the following 80 min. A significant decrease of PaO2 and pulmonary compliance as well as an increase of resistance and intrapulmonary shunt were found as early as 30 min after the last embolization and they remained unchanged for 120 min. Reduction of COP suggested transcapillary leakage of macromolecules. Histology revealed an interstitial and intraalveolar edema. We conclude that the combined injection of oleic acid and glass beads provokes microvascular lung injury and results in stable pulmonary artery hypertension with concomitant ARDS-like changes of lung function. Thus, an acute model is provided in the dog allowing for the study of cardiac function in ARDS complicated by pulmonary artery hypertension.
 ...
PMID:A new experimental model of ARDS and pulmonary hypertension in the dog. 248 70

Pulmonary artery hypertension associated with adult respiratory distress syndrome (ARDS) may increase microvascular filtration pressure by increasing pulmonary capillary pressure (PCP). To evaluate the potential to reverse this consequence of pulmonary artery hypertension, the effects of short-term vasodilator treatment were compared with prostaglandin E1 (PGE1) or nitroglycerin (NTG) on pulmonary hemodynamics and gas exchange. The two vasodilators were infused in ten patients with mild or moderate ARDS at a dosage rate achieving a 20% reduction of the mean arterial pressure. PCP was estimated by graphic analysis of the pulmonary artery occlusion curve, and continuous ventilation-perfusion (VA/Q) distributions were assessed using the multiple inert gas technique. At the given dosages both drugs induced equivalent reductions of the mean pulmonary artery pressure (PAP) from 28.2 +/- 3.6 to 23.7 +/- 3.2 with PGE1 and to 23.4 +/- 3.2 mmHg with NTG. The right atrial and pulmonary artery wedge pressure (PAWP) were also decreased to the same extent associated with the expected decrease in PCP from 17.4 +/- 2.6 to 15.1 +/- 3.3 with PGE1 and to 15.6 +/- 2.7 mmHg with NTG. The estimated PCP values were closely correlated with the values calculated according to Gaar's equation (r = 0.822. n = 23, P less than 0.001) with a regression close to the identity line. The contribution of pulmonary venous resistances to the resistance of the whole pulmonary vascular bed computed as the ratio (PCP- PAWP)/(PAP-PAWP) was 0.28 and remained unchanged during vasodilator infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prostaglandin E1 and nitroglycerin reduce pulmonary capillary pressure but worsen ventilation-perfusion distributions in patients with adult respiratory distress syndrome. 249 9

In order to examine the prognostic value of pulmonary arterial hypertension (PAH) in patients with moderate and severe acute respiratory failure (ARF), 225 patients with ARF who had been treated with mechanical ventilation and admitted to our ICU during a 3-yr period (January, 1983 to January, 1986) were prospectively studied. All 70 (31%) patients with moderate and severe ARF also had some form of hemodynamic or pulmonary instability, and were monitored with a pulmonary artery catheter. Of these 70 patients, 38 (54%) had PAH (mean BP 29 +/- 6 mm Hg); their mortality was 79% (30/38). The rest of the patients (n = 32) did not have PAH (mean BP was 15 +/- 3 mm Hg) and their mortality was 44% (14/32) (p less than .01). Thirty patients met all the criteria for adult respiratory distress syndrome (ARDS), and their mortality was 70% (21/30); all of them were included among the 38 PAH patients. ARDS patients who died had a significantly higher pulmonary vascular resistance and a significantly lower cardiac index than patients who survived (p less than .001). We conclude that PAH (present in all our ARDS patients) is a good predictor of mortality in ARF of diverse causes.
 ...
PMID:Pulmonary hypertension in acute respiratory failure. 272 Dec 10

1. A 38-year-old previously healthy worker accidentally spilled phenol-formaldehyde resin over a large area of his skin. 2. Several days later he was hospitalized with extensive necrotic skin lesions, fever, hypertension, adult respiratory distress syndrome (ARDS), proteinuria and renal functional impairment. 3. All symptoms improved progressively and eventually disappeared. 4. We propose that toxic materials originating from the necrotic skin lesions and the continued facilitated absorption of the resin and/or its components via the skin lesions were the main factors responsible for this alarming multisystem involvement. 5. Workers handling this material should be instructed to take appropriate precautions and physicians should be alerted to the potential pathophysiological consequences.
 ...
PMID:Acute resin phenol-formaldehyde intoxication. A life threatening occupational hazard. 274 83

A persistent pulmonary artery hypertension, increased airways resistance, increased vascular permeability to protein, and hypoxia are characteristic of sepsis-induced ARDS in humans and are present in the late phase injury response seen in sheep after endotoxin. Our purpose was to determine the role of serotonin, 5-HT, in the steady-state pulmonary hypertension and decreased arterial oxygen tension seen beginning approximately 3 h after Escherichia coli endotoxin injury (2 micrograms/kg) in the adult sheep. Plasma 5-HT levels remained constant, whereas lung lymph values increased from a baseline of 60 +/- 40 to 180 +/- 70 and 270 +/- 90 ng/ml at 1-h and at 3- to 5-h periods, respectively, after endotoxin. Platelet count decreased significantly only at the 3-h time period. Ketanserin, a 5-HT antagonist, was infused (0.15 mg/kg/h) in 7 sheep during endotoxin injury. The degree of early pulmonary hypertension and hypoxia was not affected by ketanserin. Mean values for pulmonary artery pressure and arterial oxygen tension were 40 +/- 8 mmHg and 70 +/- 8 torr for endotoxin alone and 38 +/- 7 mmHg and 72 +/- 7 torr for the ketanserin group. Steady-state, protein-rich pulmonary perfusion was also not altered, being increased 3-fold in both groups. Pulmonary hypertension and hypoxia were significantly attenuated, however, at the 3- to 5-h period with ketanserin, compared with endotoxin alone, the pulmonary artery pressure decreasing from 29 +/- 5 to 22 +/- 4 mmHg and the PaO2 increasing from 75 +/- 4 to 83 +/- 5 torr.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Relationship of increased lung serotonin levels to endotoxin-induced pulmonary hypertension in sheep. Effect of a serotonin antagonist. 293 13

Recent work suggests that oxygen radicals may be important mediators of damage in a wide variety of pathologic conditions. In this review we consider the evidence supporting the participation of oxygen radicals in the adult respiratory distress syndrome, in ischemia reperfusion injury in the myocardium, and in cerebral vascular injury in acute hypertension and traumatic brain injury. In the adult respiratory distress syndrome there is active sequestration of polymorphonuclear neutrophils in the pulmonary vascular system. There is evidence that activation of these neutrophils results in the production of oxygen radicals which injure the capillary membrane and increase permeability, leading to progressive hypoxia and decreased lung compliance which are hallmarks of the syndrome. In acute arterial hypertension or experimental brain injury oxygen radicals are important mediators of vascular damage. The metabolism of arachidonic acid is the source of oxygen free radical production in these conditions. In myocardial ischemia and reperfusion injury, the ischemic myocyte is "primed" for free radical production. With reperfusion and reintroduction of molecular oxygen there is a burst of oxygen radical production resulting in extensive tissue destruction. Myocardial ischemia--reperfusion injury shares in common with the other two syndromes activation of the arachidonic acid cascade and acute inflammation. Thus it would appear that the generation of toxic oxygen species may represent a final common pathway of tissue destruction in several pathophysiologic states.
 ...
PMID:Oxygen radicals in the adult respiratory distress syndrome, in myocardial ischemia and reperfusion injury, and in cerebral vascular damage. 298 21


<< Previous 1 2 3 4 5 6 7 8 9 Next >>