Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.

OBJECTIVES: The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND: Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS: One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS: The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

Observation unit treatment of heart failure with nesiritide: results from the proaction trial.

This was a multicenter, randomized, double-blind, placebo-controlled pilot study, evaluating the safety and efficacy of a standard care treatment regimen with the addition of either nesiritide or placebo (SCP) in 237 Emergency Department (ED)/Observation Unit (OU) patients with decompensated heart failure (HF). Efficacy measures included initial admission, length of hospital stay (LOS), and inpatient rehospitalization through 30 days. Compared to the standard care group, patients who also received nesiritide had 11% fewer inpatient hospital admissions at the index ED visit (55% SCP, 49% nesiritide, p = 0.436), and 57% fewer inpatient hospitalizations within 30 days after discharge from the index hospitalization (23% SCP, 10% nesiritide, p = 0.058). The duration of rehospitalization was shorter for nesiritide patients (median LOS 2.5 vs. 6.5 days, p = 0.032). The incidence of symptomatic hypotension was low and did not differ between the groups. This study showed that nesiritide is safe when used in the emergency department, observation units, or similar settings.

Comparison of the occurrence of ventricular arrhythmias in patients with acutely decompensated congestive heart failure receiving dobutamine versus nesiritide therapy.

Ventricular arrhythmias are common in patients with congestive heart failure (CHF) and may be exacerbated by positive inotropic therapy. Because human B-type natriuretic peptide (nesiritide), an arterial and venodilator, inhibits sympathetic activity, it may decrease the incidence of arrhythmias. Our investigation compares the arrhythmogenicity of dobutamine with nesiritide. A total of 305 patients with decompensated CHF requiring intravenous vasoactive therapy were randomized to receive standard therapy (n = 102) or nesiritide (0.015 microg/kg/min [n = 103] or 0.030 microg/kg/min [n = 100]) to gain additional data on the relative safety and efficacy of nesiritide compared with standard parenteral care. Dobutamine was chosen as the standard care agent in 58 subjects. During study drug infusion, all patients had continuous clinical hemodynamic and electrocardiographic monitoring. The dobutamine and nesiritide groups were similar with respect to baseline use of antiarrhythmic agents, including beta blockers. Serious arrhythmias and the incidence of cardiac arrest were more common in patients who received dobutamine than in those taking nesiritide: sustained ventricular tachycardia, 4 (7%) versus 2 (1%), respectively (p = 0.014); nonsustained ventricular tachycardia, 10 (17%) versus 23 (11%), respectively (p = 0.029); cardiac arrest, 3 (5%) versus 0, respectively (p = 0.011). We conclude that among patients with decompensated CHF for whom dobutamine is selected as standard therapy, the incidence of serious ventricular arrhythmias and cardiac arrest is significantly greater than the incidence of these events in patients randomized to nesiritide.

Nontraumatic fat embolism syndrome in sickle cell anemia.

A 14-year-old girl with sickle cell disease and nephrotic syndrome developed bone pain, followed by pulmonary edema, seizures, coma, and bilateral flaccid paralysis. Fat embolism syndrome was diagnosed by cranial magnetic resonance imaging and an exchange transfusion was performed. Within 3 months, all symptoms had resolved. It is concluded that fat embolism syndrome must be considered as a possible cause of acute neurologic deterioration in patients with sickle cell anemia.

Ischemia: a cause of hepatic telangiectasis in cattle.

We histologically examined (i) 73 bovine livers condemned by packing house inspectors for telangiectasis, (ii) 15 bovine livers passed by the same inspectors as normal, and (iii) 8 livers from cattle given an injection into their mesenteric veins: 6 with a suspension of agar particles containing viable Haemophilus somnus and 2 with diluent only. The injected cattle were killed and necropsied 2 to 12 days after the inoculations. Of the 73 telangiectatic livers, 57 (78%) had thrombosed and occluded or contracted and empty portal veins (venopathies), whereas 1 of the 15 normal livers contained one microscopic focus of telangiectasis and nearby venopathy. Of the 6 livers injected with suspended particles, all had venopathies and telangiectasis and the 2 control livers had neither.

Bulling among yearling feedlot steers.

In a survey to determine the cause of illness and deaths among yearling feedlot cattle, bulling was found to be one of the major problems. During the years 1971-1974, 54,913 (2.88%) steers became bullers and represented an annual loss of around +325,000. Some of the causes of bulling were found to be hormones, either as implants or in the feed. In 1974, from 1,988 necropsies, it was determined that 83 steers died from riding injuries.

Embolic pulmonary aneurysms in yearling feedlot cattle.

Throughout all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. Of 1,988 cattle necropsied, 25 (1.3%) had ruptured pulmonary aneurysms and an additional 4 had gross pulmonary emboli without rupture. The emboli originated from thrombi in the caudal vena cava where that vessel closely applies to the left border of the liver and where parenchymal abscesses had developed. The emboli had lodged in the pulmonary artery, weakened its wall, and led to saccular aneurysms. Infection weakened and blood pressure ruptured the saccule and opened the adjacent bronchi. Extravasated blood dissected the tunica adventitia, formed hematomas, poured into the bronchus, and was expelled from the larynx. A portion was swallowed into the rumen, and some was coughed and blown from the nose and mouth. Deaths were attributed to exsanguination and pulmonary incapacitation.

Diseases of yearling feedlot cattle in Colorado.

During all of 1974 we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. The morbidity was 5.1%, with a case mortality of 18.9% and a population mortality of 1.0%. Both morbidity and mortality were higher during fall and winter than during spring and summer. Of the 3,943 dead cattle, 1,988 were necropsied. The most prevalent diseases were: pneumonia, 48%; diphtheria, 6%; brisket disease, 6%; hemorrhagic colitis, 5%; riding injury, 4%; bloat, 3%; calculosis, 2%; endocarditis, 2%; abomasal ulcers, 2%; bovine viral diarrhea, 2%; embolic pulmonary aneurysm, 1%; and pulmonary edema, 1%.

Atypical interstitial pneumonia in yearling feedlot cattle.

During each week of 1974, we surveyed, for illnesses and deaths, a constantly changing population of yearling feedlot cattle that, for the year, totaled 407,000 animals. From 3,943 fatalities, 1,988 necropsies were made; of this number, 106 (5.3%) had atypical interstitial pneumonia. The death rate was higher during summer and fall than during the other seasons and was evenly distributed throughout each of the 4 stages of fattening. Gross pulmonary lesions involved both lungs and were prominent throughout the caudal (diaphragmatic) lobes. Epithelialization, hemorrhage, fibrin, hyaline membranes, emphysema, bronchiolitis, and interstitial edema were common, whereas chromatin strands, bronchiolar edema, interstitial emphysema, and obliterating bronchiolitis were less common histopathologic features.

Fetal abomasal ulcers in yearling feedlot cattle.

During all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. From the 3,943 dead cattle, 1,988 necropsies were made; of this number, 31 (1.6%) had ulcers with fatal perforations or hemorrhages; a similar additional number of necropsied cattle had innocuous ulcers as incidental findings. Ulcers developed during all seasons and all stages of fattening, but were more common during the first 45 days of winter-initiated fattening than during other times. Perforations of the abomasal wall resulted in spillage of abomasal contents into the abdominal cavity and the development of peritonitis.

Sudden deaths in yearling feedlot cattle.

A survey of the causes for fatal diseases of yearling feedlot cattle was conducted on more than 407,000 cattle during a 14-month period. Of the 4,260 (1%) cattle that died during this period, 1,358 (32%) were categorized as cases of "sudden death syndrome." Of the 11 most frequent causes of the syndrome, as determined at necropsy, only 4--bloat, pulmonary aneurysms, riding injury, and hemopericardium--were considered as short-course problems and true causes of sudden death. The largest number of cases of sudden death were attributed to pneumonia (113 animals). Consequently, the sudden death syndrome is a misnomer for many long-course diseases and, in some instances, a mask for neglect because, as clinically used, the name frequently includes cattle that have been sick, often with pneumonia, for several days.

Bronchiectasis in yearling feedlot cattle.

Thoughout all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle. From the 3,943 dead cattle, 1,988 necropsies were made; of the cattle necropsied, 32 (1.6%) had bronchiectasis. In this disease, the permanently dilated small bronchi and bronchioles, located in ventral parts of the lungs, were filled with accumulations of exudate and microorganisms, including Pasteurella hemolytica, Pasteurella multocida, Corynebacterium pyogenes, Escherichia coli, Salmonella anatum, Staphylococcus spp, and Mycoplasma arginini.

Cause and pathogenesis of middle ear infection in young feedlot cattle.

Two populations of feedlot cattle--weaned calves and yearlings--suffered otitis media. In calves the disease was acute and epizootic and had a prevalence of about 400 cases per 2000 cattle, whereas in yearlings, it was chronic and sporadic and had a prevalence of 1 case per 2000 cattle. Clinical signs were facial paralysis, otorrhea, and head tilt. The middle ears from 64 dead calves and 22 dead yearlings were examined. Calf ears had acute infection, with exudate in air cells and rupture of tympanic membranes. Yearling ears had chronic infection, with exudate in air cells, rupture or destruction of tympanic membranes, and necrosis of air cell partitions. Mixtures of Pasteurella multocida and Corynebacterium pseudotuberculosis were isolated from diseased ears, but Pasteurella multocida predominated in acute infections and Corynebacterium pseudotuberculosis predominated in chronic infections.

Brisket disease in yearling feedlot cattle.

During all of 1974, we surveyed, for illnesses and deaths, about 407,000 yearling feedlot cattle maintained at 1,600 m altitude. Of 1,988 cattle necropsied, 116 (5.8%) had brisket disease. The malady occurred during all seasons but was most common throughout fall and winter. The gross changes were hypertrophy and dilatation of the right ventricle and generalizaed passive congestion. The postulated causative factors were high genetic susceptibility, rapid growth rate, previous mountain grazing, and hypoventilation with airway hypoxia.

Shipping fever pneumonia in yearling feedlot cattle.

During each week of 1974, we surveyed, for illnesses and deaths, a continually changing population of yearling feedlot cattle that, for the year, totaled 407,000 animals. About 5.1% of the cattle sickened and, of these, 18.9% died. From the 3,943 fatalities, 1,988 necropsies were made. About 75% of the clinical diagnoses and 64% of the necropsy diagnoses were respiratory tract diseases; of the fatalities from respiratory tract diseases, 75% were attributed to shipping fever pneumonia. Nearly 72% of fatal cases of shipping fever pneumonia occurred during the first 45 days on feed. In the lungs of most cattle with shipping fever pneumonia, bronchiolitis, fibrinous exudate, colonies of microorganisms, lymphatic clots, intravascular clots, thromboses, and foci of necrosis were found. Pasteurella spp, Mycoplasma spp, and infectious bovine rhinotracheitis virus were isolated from pneumonic tissues. It was hypothesized that pathogenic Pasteurella spp and other microorganisms in nasal secretions transfer from the nasopharynx into the lungs by draining along the tracheal floor into ventral bronchi, bronchioles, and alveoli, and that pasteurella endotoxin, formed in infected lobules, thromboses and occludes lymphatics, capillaries, and veins and thereby causes ischemic necrosis.

Laryngeal contact ulcers in feedlot cattle.

Of 30,444 larynges from fattened cattle at three companies, 3,985 (13.1%) had contact ulcers or ulcer scars in the mucous membranes over the vocal processes and medial angles of the arytenoid cartilages. The incidence was higher in cattle fed during fall than in cattle fed during other seasons. We hypothesize: 1. that some feedlot cattle develop acute mucositis from mixed infections with species of Pasteurella, Haemophilus, Mycoplasma, and viruses in the nose, pharynx, and larynx; 2. that reflex coughing and swallowing accelerate the rate of larynx closure; and 3. that the closures erode the swollen membrane over the vocal processes and medial angles of the arytenoid cartilages and thus produce primary contact ulcers.

Limb arthropathies and periarticular injuries in feedlot cattle.

Beginning summer 1977 and continuing through 4 consecutive seasons, we examined samples of at least 25, and a total of 106, lame limbs or joints from slaughtered beef cattle. Of this number about 64 (60%) were articular and 42 (40%) periarticular lesions. Fifty-three were caused by trauma and 9 by osteochondrosis. Stifle joints (40) and digital joints (19) were the most frequently affected articulations, and the humerus and femur were the most frequently fractured bones. Twenty joints, mostly stifles, had fibrinous arthritis, and Mycoplasma spp. were isolated from 11.

Laryngeal diphtheria and papillomatosis in feedlot cattle.

In a random sample of 30,444 larynges from slaughtered beef cattle, 441 (1.4%) had chronic diphtheria and 1,345 (4.4%) had papillomatosis. Both types of lesions were centered in mucous membranes over the vocal processes and medial angles of the arytenoid cartilages. Since they are found in the same anatomical locations as laryngeal contact ulcers, we hypothesize that ulcers are primary and diphtheria and papillomatosis are secondary.