Neocuproine, a selective Cu(I) chelator, and the relaxation of rat vascular smooth muscle by S-nitrosothiols

1. A study has been made of the effect of neocuproine, a specific Cu(I) chelator, on vasodilator responses of rat isolated perfused tail artery to two nitrosothiols: S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and S-nitroso-glutathione (GSNO). 2. Bolus injections (10 microl) of SNAP or GSNO (10(-7)-10(-3) M) were delivered into the lumen of perfused vessels pre-contracted with sufficient phenylephrine (1-7 microM) to develop pressures of 100-120 mmHg. Two kinds of experiment were made: SNAP and GSNO were either (a) pre-mixed with neocuproine (10(-4) M) and then injected into arteries; or (b) vessels were continuously perfused with neocuproine (10(-5) M) and then injected with either pure SNAP or GSNO. 3. In each case, neocuproine significantly attenuated vasodilator responses to both nitrosothiols, although the nature of the inhibitory effect differed in the two types of experiment. We conclude that the ability of exogenous nitrosothiols to relax vascular smooth muscle in our ex vivo model is dependent upon a Cu(I) catalyzed process. Evidence is presented which suggests that a similar Cu(I)-dependent mechanism is responsible for the release of NO from endogenous nitrosothiols and that this process may assist in maintaining vasodilator tone in vivo.     

BASEMENT LITHOLOGY AND ITS CONTROL ON SEDIMENTATION, TRAP FORMATION AND HYDROCARBON MIGRATION, WIDURI-INTAN OILFIELDS, SE SUMATRA

The Widuri-Intan oilfields produce from late Oligocene sandstones of the Talang Akar Formation, which were deposited in a fluvial-to-deltaic setting on the NW side of the Asri Basin, offshore SE Sumatra. The Asri Basin is of rift origin and formed during the early Oligocene, with its axis oriented in a NE-SW direction. Approximately 310 million brls of oil have been produced from the fields within the 12-by-12 mile (20-by-20 km) study area. The oil occurs in a series of structural and stratigraphic traps within slightly sinuous to meandering channel sandstone bodies. The reservoir sequence (sandstone interbedded with minor mudstone and coal) overlies basement rocks, which are predominantly Cretaceous in age. Forty-nine well penetrations have shown that the basement is composed of one of four lithologies: (1) hornblende granodiorite; (2) metamorphic rocks, mainly mica schist; (3) plugs of metabasalt and related volcanic rocks; or (4) dolomitic limestone. A combination of drill cuttings, sidewall and conventional cores and FMS/FMI images has been used to identify and map the distribution of basement rock type. The basement was subjected to exposure and deep weathering prior to the formation of the Asri Basin, as evidenced by the zones of surface alteration encountered during drilling. The basement palaeotopography had a strong influence on the later distribution of major fluvial channels and sand pinch-outs. Several major faults appear to be controlled by basement lithology, especially at the boundaries of granodiorite and metabasalt intrusives. An important shear zone, oriented NW-SE, appears to have offset the basement between the main Widuri and Intan fields, and was subsequently the site of silicification of the mica schists in the basement. The Lidya field is situated where the reservoir pinches out onto eroded areas of basement silicification along this shear zone. Palaeocurrents in the upper 34–2 and 34–1 channel sandstones in the Widuri field were controlled by the orientation of this basement feature. Drape and compaction of Oligocene Talang Akar Formation sediments over eroded volcanic plugs have defined or enhanced a number of structural/stratigraphic plays, including the Widuri and Chesy fields. From seismic and well evidence, the reservoir sequence at the Indri field is underlain by dolomitic limestone and exhibits a series of unusual karst-related sinkhole and collapse structures. These are circular to slightly elliptical in shape, and extend from basement level to over 900 ft vertically into the overlying Talang Akar Formation.     

Clinical and economic outcome of patients undergoing tracheostomy for prolonged mechanical ventilation in New York state during 1993: analysis of 6,353 cases under diagnosis-related group 483

OBJECTIVE: To examine and describe the relation between age and disposition in patients undergoing tracheostomy. DESIGN: Retrospective analysis of a statewide database. SETTING: All acute care hospitals in New York state. PATIENTS: All patients (n = 6,353) > or = 18 yrs of age who were discharged from the hospital during 1993 with a final diagnosis-related groups code of 483. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final disposition, according to six disposition codes (other acute care facility, residential healthcare facility, other healthcare facility, home, home healthcare services, and death) was examined for the entire population. Cost per case was assumed to equal the average statewide Medicaid rate. An inverse relation between survival rate and age was observed, which resulted in an age-related increased cost per survivor. Also, survivors in older age groups had an increased rate of discharge to residential healthcare facilities. There was a negative, albeit less marked, effect of older age on the rates of survivors discharged to home and to other healthcare facilities. CONCLUSIONS: Care of patients who undergo tracheostomy for prolonged mechanical ventilation is expensive. The older the patient, the less satisfactory the outcome from an economic, clinical, and possibly social perspective.     

Hypothermic circulatory arrest does not increase the risk of ascending thoracic aortic aneurysm resection

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of a period of deep hypothermic circulatory arrest (DHCA) during elective replacement of the ascending thoracic aorta. SUMMARY BACKGROUND DATA: DHCA has been implemented in ascending thoracic aortic aneurysm resection whenever the anatomy or pathology of the aorta or arch vessels prevents safe or adequate cross-clamping. Profound hypothermia and retrograde cerebral perfusion have been shown to be neurologically protective during ascending aortic replacement under circulatory arrest. METHODS: The authors conducted a retrospective analysis of 91 consecutive patients who underwent repair of chronic ascending thoracic aortic aneurysms from 1986 to present. The authors hypothesized that patients undergoing DHCA with or without retrograde cerebral perfusion during aneurysm repair were at no greater operative risk than patients who received aneurysm resection while on standard cardiopulmonary bypass. RESULTS: There were no significant differences in hospital mortality, stroke rate, or operative morbidity between patients repaired on DHCA when compared to those repaired on cardiopulmonary bypass. CONCLUSIONS: DHCA with or without retrograde cerebral perfusion does not result in increased morbidity or mortality during the resection of ascending thoracic aortic aneurysms. In fact, this technique may prevent damage to the arch vessels in select cases and avoid the possible complications associated with cross-clamping a friable or atherosclerotic aorta.     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

Susceptibility to atrial fibrillation: a study in an ovine model of pacing-induced early heart failure

INTRODUCTION: The development of susceptibility to atrial fibrillation (AF) is a common consequence of many forms of cardiovascular disease, especially heart failure. In this study we used a sheep model of pacing-induced stable early heart failure to describe, quantify, and relate the level of susceptibility to AF to changes in structural and electrophysiologic parameters. METHODS AND RESULTS: Epicardial electrodes were implanted on the atria and right ventricles of nine sheep. The AF threshold, atrial vulnerability period, atrial effective refractory period (ERP), and interatrial conduction time were examined during control and over a 6-week period of ventricular pacing at 190 beats/min. Left atrial (LA) area and left ventricular (LV) fractional shortening were monitored using echocardiography. There were significant increases in LA susceptibility to AF (P < 0.0003), LA area (P < 0.0002), and LA ERP400 (P < 0.0002). Rate of increase in LA area was related positively to AF susceptibility (P = 0.02) and inversely to LA ERP400 (P = 0.002). LV fractional shortening decreased to approximately 50% of control value (P < 0.00001). No changes were observed in right atrial electrophysiology. CONCLUSION: In this study, susceptibility (the ability of an extrastimulus to induce AF) was rigorously measured within a predetermined format. Significant relationships were found to exist between susceptibility, certain of the observed changes in atrial electrophysiology and structure.     

The connection between the structure and activity of enkephalins in the realization of their cardiotropic effects in cats

In experiments on anesthetized cats the ability of natural enkephalins to affect baseline heart rate, the magnitude of vagal chronotropic effect and its components, inhibitory tonic and synchronizing, was compared with activity of synthetic analogs and short fragments of enkephalins. Substitutions of met-enkephalin structure in second and fifth positions did not modify its cardiac activity. When Tyr1 was removed the peptide lost ability to affect baseline heart rate and the magnitude of synchronizing vagal component, but modulatory influence on inhibitory tonic vagal effect still persisted. The conclusion has been made that various parts of amino acid chain of met-enkephalin have different significance in realization of cardiac effects evoked by this peptide.     

Comparison of polysomnography with ResCare Autoset in the diagnosis of the sleep apnoea/hypopnoea syndrome

BACKGROUND: Increasing referral numbers make the development of simplified accurate methods of diagnosing the sleep apnoea/hypopnoea syndrome highly desirable. The accuracy of one such system--the ResCare Autoset--has been examined. METHODS: Thirty one consecutive patients assessed by polysomnography had simultaneous monitoring of their respiratory pattern using the Autoset system. The Autoset detects episodes of flattening of the flow/time profile using nasal cannulae. RESULTS: There was a good correlation (r = 0.85) between the number of apnoeas+hypopnoeas/hour in bed recorded using polysomnography and the Autoset system. The median difference in such events was 3.1 (95% confidence interval 8.4 to -1.6)/hour in bed. In two patients the Autoset scored 70 apnoeas+hypopnoeas/hour in bed compared with 34 apnoeas+hypopnoeas with 35 arousals/hour in bed by polysomnography; however, this did not alter the diagnostic category of either patient. Autoset gave a sensitivity of 100%, specificity of 92%, positive predictive value of 92%, and negative predictive value of 100%, which was better than oximetry alone. A sleep study using the Autoset system costs 14 pounds compared with 126 pounds for polysomnography. CONCLUSIONS: The Autoset is clinically useful for diagnosing the sleep apnoea/hypopnoea syndrome.