One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.

Baseline clinical and angiographic data in the Quinapril Ischemic Event (QUIET) Trial.

The QUinapril Ischemic Event Trial (QUIET) is the first prospective, double-blind, placebo-controlled trial to investigate the long-term antiatherosclerotic effects of angiotensin-converting enzyme inhibition. Normotensive, nonhyperlipidemic subjects (1,750) with normal left ventricular systolic function were randomly assigned to treatment or placebo at percutaneous transluminal coronary angioplasty (PTCA). The primary end point is time to first cardiac ischemic event. Baseline clinical characteristics are (mean +/- SD): age 58 +/- 9 years; blood pressure 123 +/- 15/74 +/- 10 mm Hg; low density lipoprotein cholesterol 124 +/- 27 mg/dL; high density lipoprotein cholesterol 37 +/- 10 mg/dL; and triglycerides 167 +/- 91 mg/dL. In addition, 81% are men; 22% are current smokers; 49% give a history of myocardial infarction. Baseline angiographic characteristics are (mean +/- SD): left ventricular ejection fraction 59% +/- 11%; per patient diameter stenosis (excluding the PTCA segment) 49% +/- 31%; 8.9 +/- 3.5 analyzable segments per patient (excluding the PTCA segment), 3.8 +/- 2.3 of which have visible stenosis. Including the PTCA segment, 52% have single vessel disease and 48% have multivessel disease. Baseline angiographic data for non-PTCA segments will be correlated with cardiac ischemic events which occur after 6 months. Up to 500 subjects will undergo follow-up angiography with quantitative coronary angiographic analysis (QCA) of baseline and follow-up films. The primary QCA end point will be per-patient categorical designation as progressor or nonprogressor based on the presence or absence of > or = 400 microns narrowing in > or = 1 vessels that did not undergo PTCA.

Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. METHODS AND RESULTS: Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). CONCLUSIONS: TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.

Delayed fatal pulmonary hemorrhage complicating use of a balloon flotation catheter.

A case of delayed fatal pulmonary hemorrhage caused by a balloon flotation catheter is described. The catheter was inserted preoperatively. The patient died on the 14th postoperative day from massive hemorrhage in the right pleural space after 12 days without any clinical symptoms. Pulmonary artery rupture is documented by the autopsy findings.

Tuberculous abscess of the pancreas.

A patient who presented with a prolonged febrile course was found to have a pancreatic abscess. Routine bacterial cultures of the abscess obtained at laparotomy were negative. The patient was treated with surgical drainage and antibiotics but did poorly. Following a second laparotomy 4 wk later, the tuberculous cause of the pancreatic abscess was recognized. Despite antituberculous therapy, the patient died; autopsy revealed generalized miliary tuberculosis. This case is unique in the accessible literature. We speculate that delayed diagnosis of the tuberculous pancreatic abscess contributed to the final dissemination of tuberculosis in this patient.

[Adaptation and disadaptation of the myocardium of rats trained to hypoxia]. / Adaptatsiia i dizadaptatsiia miokarda krys, trenirovannykh gipoksiei.

Adaptation to oxygen deficit resulted from training of rats to hypoxia (8--9% O2) at the normal atmospheric pressure, during 3 weeks. Subsequent 2-week training decreased the resistance to hypoxia (disadaptation). Perfusion of the isolated hearts of adapted and disadapted animals at anoxic regimen together with the recording of the systolic pressure in the left ventricle, the rhythm, glucose uptake, lactate excretion, coronary blood flow, and the histochemical data on SDH, MDH, LDH, and hydroxibutyric DH, as well as the electron microscopy of the left ventricle mitochondria, indicate that the range of compensation reactions increases in adapted rats and decreases in disadapted ones.

[Damage to the isolated heart due to adrenaline perfused with a saline solution]. / Povrezhdenie izolirovannogo serdtsa adrenalinom v usloviiakh perfuzii ego solevym rastvorom.

Perfusion of the isolated heart with Krebs solution containing 5 and 20 microgram/ml of adrenaline induced cardiocyte micronecrosis. Perfusion with 0.5 microgram/ml of adrenaline induced no micronecrosis. Dispersion analysis showed a statistically significant effect of adrenaline concentrations on the degree of the cardionecrotic effect. The fact of micronecrosis appearance in the isolated heart during its perfusion with saline solution requires revision of the hypothesis on the leading role of blood factor in the realization of the cardionecrotic effect of adrenaline. The appearance of micronecroses with the action of adrenaline in concentrations which activate the mechanism of amines uptake by the heart myocytes speaks in favour of the casual relationship between the accumulation of the biogenic amines by myocytes and the development of their necrosis.

[Myocardial resistance to adrenaline in rats adapted to hypoxia]. / Rezistentnost' miokarda k adrenalinu u krys, adaptirovannykh k gipoksii.

Expression of the damaging effect of adrenalin on the myocardium of rats adapted to hypoxia was studied under condition of adrenalin being injected into the integral body or in perfusion of an isolated heart. The damage was tested by the histoenzymatic reaction for the succinic dehydrogenase activity and staining for lipids. When the cardiotoxic dose (2.0 mg/kg) of adrenalin was injected intramuscularly to the adapted rats no damage of the myocardium was found, but perfusion of the isolated heart with adrenalin (20 microgram/ml) induced cardiocyte micronecrosis. The volume of these necroses was statistically less than in the isolated heart of the intact rats under analogous treatment. The difference between the sensitivity of the myocardium in vivo and in vitro indicated that in rats adapted to hypoxia the phenomenon of the myocardium protection from the damaging effect of adrenalin acted on the integral body level. An increased resistance of the myocardium proper seems to be caused by the increase of the metabolic system force during adaptation.

[Metabolic disorders and plasmorrhagia in myocardial cells following adrenalin damage]. / Metabolicheskie narusheniia i plazmorragii v miokardial'nye kletki pri ikh adrenalinovom povrezhdenii

The authors examined serial sections of the myocardium of rats sacrificed at periods of from 1 to 24 hours after adrenalin administration. The results of histoenzymatic reaction to succinic dehydrogenase (a test for cell injury) were compared with the data obtained in fibrin detection by Coons' method. Plasmorrhagia into the irreversibly injured muscle cells had a characteristic appearance in the test with nitro-BT; there proved to be no fibrin in the fibers with fatty dystrophy marked by macrogranular depositions of formazan. A supposition was put forward on different pathogenesis of the reversible and irreversible injuries of the myocardium caused by adrenalin administration.

[Enzymatic heterogeneity of the rat myocardium]. / Ob énzimaticheskoi geterogennosti miokarda krys

The histoenzymatic method was applied to the study of distribution of the activity of the redox enzymes in the myocardium of the ventricles in rats; distribution of the activity of lactic and malic dehydrogenase and of alpha-glycerophosphate proved to be the most manifest near the apex of the heart and was expressed in the presence of "spotty" areas of increased activity against the general homogeneous background of formazan deposits. The activity of mitochondrial upsilon-glycerophoric dehydrogenase was seen in all the portions of the ventricles and was characterized by an uneven distribution in the sarcoplasm with increase in the direction from the interdisc to the nucleus. Unevenness of distribution of the beta-oxybutyric dehydrogenase activity was detected in some of the animals and was pronounced in all the portions of the myocardium. The intensity of the reaction in detection of succinic dehydrogenase, NAD- and NADP-diaphorases varied but insignificantly.

[Histoenzymatic characteristics of fibroblasts during organization of myocardial micronecroses]. / Gistoénzimaticheskaia kharakteristika fibroblastov pri organizatsii mikronekrozov miokarda

The activity of dehydrogenase of succinate, lactate, glutamate, malate (NAD- and NADP dependent), alpha-glycerophosphate (NAD-dependent), glucoso-6-phosphate, NAD- and NADP-dyaphorase was studied in adult and old rats with the help of histoenzymatic methods in normal cardiac fibroblasts and under conditions of reparative regeneration developing in the places of foci of myocardial micronecroses caused by administration of adrenaline. Analysis of the activity of enzymes in normal fibroblasts revealed the predominance therein of an anaerobic way of metabolism. In the process of reparative regeneration the level of metabolism of fibroblasts rose with inclusion of the acitvity of pentose shunt and Krebs' cycle. No age differences in the activity of enzymes under study were revealed. The data obtained are discussed in connection with the problem of ascertaining inter-enzymatic relationships ensuring metabolism of the connective tissue in the process of its maturation.