Potassium channel activators cromakalim and celikalim (WAY-120,491) fail to decrease myocardial infarct size in the anesthetized canine.

The cardioprotective effects of the K channel activator drugs celikalim (WAY-120,491) and cromakalim were studied in a canine model of myocardial infarction consisting of 90 min of ischemia and 5 h of reperfusion. Intracoronary infusion of cromakalim and celikalim at 0.2 microgram/kg/min beginning 10 min before occlusion of the left circumflex coronary artery and continuing throughout the duration of the reperfusion period appeared to exacerbate ischemic injury. Infarct size (percent of risk area) was 27.7 +/- 5.6% in vehicle control animals (n = 5), 40.3 +/- 6.2% for cromakalim (n = 5) and 55.7 +/- 6.4% (p less than 0.05 vs. vehicle) for celikalim-treated animals (n = 5). When these compounds were administered intravenously, using doses shown to increase total coronary flow in nonoccluded control animals, no exacerbation of ischemic injury was observed. Anatomic infarct size was 32.8 +/- 7.1% for vehicle animals (n = 5) and 32.6 +/- 13.3 and 30.9 +/- 9.8% for cromakalim- (n = 6) and celikalim-treated (n = 5) animals, respectively. Intravenous diltiazem decreased myocardial infarct size to 16.3 +/- 7.3% (n = 5) of area at risk (p = NS vs. vehicle). The anatomic area at risk was similar in all three treatment groups, and no significant differences in rate-pressure product were observed. Results of this study suggest that K-channel-activating drugs such as cromakalim and celikalim may not be effective agents in the acute therapeutic management of myocardial ischemic injury.

Antithrombotic activity of the phosphodiesterase III inhibitor pelrinone in a canine model of coronary artery thrombosis: enhancement of efficacy with concurrent alpha 2-adrenergic antagonism.

The purpose of this study was to determine if idazoxan, an alpha 2-adrenergic antagonist, could enhance the antithrombotic activity of pelrinone, a PDE III inhibitor, in a canine model of coronary thrombosis that uses electrical current to injure the coronary endothelium. Thrombus mass in vehicle-treated animals was 37.9 +/- 8 mg. Pelrinone, 0.625 and 2.5 mg/kg decreased thrombus size by 46 and 21%, respectively, while idazoxan, 0.75 mg/kg decreased thrombus mass by 43%. When this dose of idazoxan was combined with pelrinone, 0.625 and 2.5 mg/kg, thrombus mass was decreased by 71 and 91%, respectively. Antithrombotic efficacy correlated with the ability of these treatments to inhibit epinephrine-sensitized, collagen-induced platelet aggregation. Sixty minutes following drug administration, idazoxan, 0.50 mg/kg inhibited aggregation by 50%, while pelrinone, 0.625 and 2.5 mg/kg inhibited aggregation by 55 and 68%, respectively. Combined administration of idazoxan with pelrinone, 0.625 and 2.5 mg/kg resulted in 80 and 95% inhibition of aggregation, respectively. Similar trends in inhibiting platelet aggregation to epinephrine-sensitized ADP and arachidonic acid were also observed. Experimental treatments did not affect hematocrit or circulating platelet count, although pelrinone was observed to prolong prothrombin time slightly. To examine the effect of drug-induced increases in coronary blood flow on thrombus formation, the potassium channel activator drug cromakalim was studied at a dose (0.1 mg/kg) that increased coronary blood flow by 25-35 ml/min above baseline in sham control animals. Animals treated with cromakalim showed a shorter time to coronary occlusion (103 +/- 11 min) vs. vehicle (173 +/- 24 min) and developed larger thrombi (53.7 +/- 19 mg). These results demonstrate that coronary vasodilation does not contribute to antithrombotic activity in this model. Results from the study also show that alpha-adrenergic inhibition of platelet function can potentiate phosphodiesterase inhibitor antiaggregatory and antithrombotic activity.

Carotid artery: percutaneous transbrachial selective arteriography with a 4-F catheter.

Bilateral selective common carotid artery catheterization was attempted in 72 patients by means of percutaneous placement of a 4-F catheter from a right brachial artery puncture site in the antecubital fossa. The success rate was high (95.8%) and the complication rate low (6.9%), and there were no instances of brachial artery spasm or thrombosis. The experience, while small, suggests that selective common carotid arteriography can be done safely and efficaciously from the right brachial artery approach.

Class II antigens on retinal vascular endothelium, pericytes, macrophages, and lymphocytes of the rat.

Class II histocompatibility complex antigens on the retinal vascular endothelium may allow these cells to function as antigen-presenting cells to circulating T cells. The present study investigated induction of class II antigens in vitro to characterize the response under controlled conditions. Retinal vascular endothelium from Lewis and Brown Norway rats (high versus low responders in experimental autoimmune uveitis) were exposed in vitro to recombinant rat gamma interferon, interleukin-1, interleukin-2, or Concanavalin-A spleen supernatant. Retinal pericytes, macrophages and lymphocytes were studied in comparison. A newly adapted ELISA technique was used to assay levels of antigen expression. Class II antigens (I-A OX6, I-E OX17, polymorphic I-A OX3), class I antigens (OX18), macrophage marker (OX42), macrophage and T helper cell marker (W3/25), and T suppressor/cytotoxic cell marker (OX8) were studied. Results showed that retinal vascular endothelium normally expresses very little class II antigen. However, high levels of I-A and I-E were induced by interferon or spleen supernatant. The levels of class II antigen approached that of the traditional antigen-presenting cell (macrophage) and were much higher than levels for pericytes and lymphocytes. The same doses of interferon showed larger increases in the Lewis rat compared to Brown Norway. No effect was seen with interleukin-1 or -2. Therefore, retinal vascular endothelium may be induced by gamma interferon to express class II antigens with degree of induction greater than or equal to the macrophage, and higher levels of induction were seen in the high responder strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Ontogenic corticosteroidogenesis of the domestic fowl: response of isolated adrenocortical cells.

Ontogenic adrenocortical function of the domestic was investigated using adrenocortical cells isolated from embryonic chicks (18, 19, 20, and 21 days old) and male and female posthatch birds (1 day, 1 week, and 3 weeks old). Production of the predominant corticosteroids secreted by the chicken adrenal gland, corticosterone, cortisol, and aldosterone, was measured by radioimmunoassay after 2-hr incubation of cells with or without steroidogenic agents. Approaching hatch, basal and maximal ACTH-(1-24) (ACTH)-induced corticosteroid production increased steadily and peaked around 1 day posthatch (5-18 times and 3-9 times, respectively, the production values at 18 days embryonic life). Thereafter, corticosteroid production values decreased steadily to 3 weeks posthatch. Corticosterone predominated over the ages studied: Maximal ACTH-induced corticosterone production averaged 52 and 115 times the production values of aldosterone and cortisol, respectively. In addition, maximal ACTH-induced aldosterone production was roughly 2.2 times greater than cortisol production over the ages studied except for a short-lived, disproportionately greater aldosterone production at 1 day posthatch. In addition to perihatch and age-related differences in cellular corticosteroid production, there were also differences in cellular sensitivity to steroidogenic agents as indicated by the differences in half-maximal steroidogenic concentration values (ED50 values) of the steroidogenic agents. Sensitivity to ACTH increased 2.7 times from Day 18 of embryonic life to 1 day posthatch and then decreased steadily to 3 weeks posthatch. In addition, sensitivity to 8-bromo-cAMP (8-Br-cAMP) increased abruptly at 1 day posthatch (nearly 3 times) but then remained constant thereafter. However, a consistent change in cellular sensitivity to 25-hydroxycholesterol was not observed until 3 weeks posthatch (an increase in sensitivity of 3 times that at Day 18 of embryonic life). These data of cellular sensitivity suggest that there were distinct development and maturational alterations in the cellular loci at which ACTH, 8-Br-cAMP, and 25-hydroxycholesterol acted. Thus, during the transition from embryonic to postembryonic life of the domestic fowl, there are alterations in adrenocortical cell steroidogenic capacity and in the function of some cellular loci comprising the corticosteroidogenic pathway.

Neurogenic hyperacute ascites in mice.

Four groups of mice were subjected to controlled fatal head trauma and then evaluated for the presence of ascites (neurogenic hyperacute ascites, NHA). The animals died virtually instantaneously and without evidence of maintained pain or suffering. The volume of ascites was determined in one group of animals. Two of the traumatized groups were pretreated, one with the beta-blocker propranolol and the other with the alpha-blocker phentolamine. A fifth, non-traumatized, group which was killed with either inhalation served as a control group. Two more groups of non-traumatized mice were administered either the alpha-adrenergic agonist methoxamine hydrochloride or the beta-agonist isoethrane mesylate before killing by ether inhalation, and then evaluated for ascites. Transudative ascitic fluid was found in 87-100% of untreated traumatized mice and in no control animals. Pretreatment with phentolamine had no effect on the prevalence of ascites. Pretreatment with propranolol produced a significant decrease in the prevalence of ascites compared with trauma alone (P less than 0.001). Isoethrane (beta-agonist) administration caused ascites in 100% of the treated animals. Methoxamine (alpha-agonist) administration did not cause ascites. A previously undescribed consequence of acute brain trauma is described (NHA) which appears to be mediated by beta-sympathetic activity of central origin. NHA is inhibited by beta-blockade and can be simulated with beta-agonist administration.

Increased biosynthesis of pyruvate kinase under hypoxic conditions in mammalian cells.

The rate of biosynthesis of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) was compared in cells maintained under normoxic or hypoxic conditions. L8 cells (a myoblast cell line) were pulse-labeled with [3H]leucine and incorporation of radioactivity into pyruvate kinase was measured after quantitative affinity separation with anti-pyruvate kinase monoclonal antibody. During chronic hypoxia there is an increased rate of biosynthesis of pyruvate kinase leading to an increase in enzyme content and augmented glycolytic capacity. An inhibitor of the electron transport chain, antimycin A, was used to determine whether changes in pyruvate kinase content occurring during hypoxia are a result of reduction in molecular oxygen directly or an indirect consequence of oxygen depletion. Pyruvate kinase activity increased during chronic antimycin A exposure under normoxic conditions. The increase was quantitatively accounted for by an increase in cellular pyruvate kinase enzyme content. This suggested that decreases in the levels of molecular O2 are not the direct stimulus for the increased content of pyruvate kinase. It is more likely that the increased pyruvate kinase content results from depressed rates of electron transport through the mitochondrial electron transport chain.

LDHk, the lactate dehydrogenase associated with transformation by the Kirsten sarcoma virus: a re-evaluation.

A lactate dehydrogenase isozyme designated "LDHk" has recently been described in cells transformed by the Kirsten murine sarcoma virus. Several unusual properties were felt to distinguish this LDH isozyme from previously described LDH isozymes. These properties include cathodic electrophoretic migration in acrylamide gels using an imidazole/borate buffer system, inhibition of activity by oxygen and GTP, and stimulation of activity by cyanide. However, this report demonstrates that the muscle-type mammalian LDH isozyme, LDH 5, also exhibits these unusual properties when it is isolated and detected by the same methods previously used to demonstrate LDHk. The unusual properties attributed to LDHk are not intrinsic properties of the enzyme itself but rather result from the methods employed to demonstrate LDHk activity. Numerous similarities exist between LDH 5 and LDHk including electrophoretic mobility, substrate requirements, similar Michaelis constants for lactate, pyruvate, NAD, and NADH, and identical tissue distribution, indicating that LDHk represents mammalian LDH 5.

Hormonal manipulation of pulmonary metastases from carcinoma of the prostate.

Chest roentgenograms and medical records were reviewed on 91 consecutive patients having orchiectomy for advanced carcinoma of the prostate during a 4-year period. Our purpose was to investigate the potential of antiandrogen therapy for inducing regression of prostate pulmonary metastases and respiratory difficulty accompanying lymphangitic spread. Patients encountered during the study period who had lung metastases but refused orchiectomy and were treated with oral estrogens were also included. Antiandrogen therapy was found to be effective in inducing regression of prostatic pulmonary metastases and respiratory distress accompanying lymphangitic spread in those patients who had no prior hormonal manipulation.

Contrast enhancement of the soft tissues of the abdomen.

In summary, TBO in adults is generally not performed as a separate examination, but it is an important part of the excretory urogram. It permits detection, definition, and characterization of mass lesions outside of the urinary tract, extending the diagnostic yield of excretory urography. It can raise the diagnostic confidence level by providing direct visualization of a mass, minimizing reliance on indirect radiographic signs. TBO can reliably characterize a mass as hypovascular or avascular. While this does not guarantee benignity, such information can be helpful in distinguishing cystic and mixed lesions from solid lesions.

Acetylcholinesterase and fetal malformations: modified qualitative technique for diagnosis of neural tube defects.

A single-blind study involving amniotic-fluid samples from 214 pregnancies of known outcome confirms that an electrophoretically distinct isoenzyme of acetylcholinesterase is associated with fetal open neural tube defects. Furthermore, only one of 13 amniotic-fluid samples with false-positive results for alpha-fetoprotein showed the characteristic isoenzyme, indicating that qualitative acetylcholinesterase assessment can decrease the proportion of false positives from the alpha-fetoprotein assay. We have also identified this characteristic isoenzyme in amniotic fluids from pregnancies in which other serious fetal defects occurred. A detailed electrophoresis protocol for identifying this characteristic isoenzyme is described.

Diffuse enlargement of gastric folds as a manifestation of secondary syphilis.

A case of gastric lues with diffuse enlargement of gastric rugae is presented. Confirmation of the etiological role of the spirochete in producing this very unusual roentgen manifestation of syphilitic gastropathy was provided by recovery of the organism from the gastric mucosa and reversal of the clinical and roentgenographic aberrations by penicillin therapy alone. Diffuse hyperrugosity and erosive gastritis occurring in a patient with a reactive serologic test for syphilis should raise the possibility of luetic gastritis.

Solitary nonparasitic hepatic cyst causing obstructive jaundice.

Solitary nonparasitic hepatic cysts are rarely associated with jaundice and abnormalities of liver function have been attributed to hepatocellular disease in the absence of a separate obstructing lesion of the biliary tree. This case represents the first cholangiographic documentation of a solitary nonparasitic hepatic cyst compressing biliary radicles resulting in obstructive jaundice. The implication for treatment is discussed.

Ultrasound detection of a carcinoid tumor.

The intraluminal component of symptomatic malignant carcinoid tumors of the small bowel is typically small relative to the extension in the mesentery, and barium examinations are occasionally normal. This case report illustrates the diagnostic value of abdominal ultrasonography in the detection of extraluminal component of a carcinoid tumor.

The influence of hydration and bladder distension on the sonographic diagnosis of hydronephrosis.

Renal sonography is frequently employed to exclude obstructive uropathy in patients with uremia. Sonographic findings of moderate bilateral hydronephrosis were encountered in a dehydrated patient undergoing rehydration. Subsequent excretory urography and a follow-up renal sonogram were normal. To investigate the possibility that hydration and bladder distension in an otherwise normal and unobstructed collecting system could result in hydronephrosis detectable by ultrasound, 23 apparently normal volunteers underwent renal sonography in the hydrated and basal states. The filled urinary bladder in a patient undergoing hydration frequently results in the sonographic appearance of hydronephrosis.

Colonic ileus. Indication for prompt decompression.

Eleven cases of colonic ileus were associated with a variety of clinical conditions. The dominant roentgenographic finding was severe cecal dilation. Its recognition and prompt management are required to prevent possible disastrous perforation.