C-type natriuretic peptide of rainbow trout (Oncorhynchus mykiss): primary structure and vasorelaxant activities

Natriuretic peptides (NPs) play important roles in osmoregulatory and cardiovascular systems of vertebrates. For functional studies of NPs, rainbow trout (Oncorhynchus mykiss), a euryhaline fish, is an interesting model. The information on homologous NPs of salmonid fish is, however, still incomplete with respect to C-type NP (CNP). In this study, we isolated cDNAs encoding the precursor of CNP from the brain of trout. Predicted mature CNP (CNP-22) sequence was identical to that of killifish Fundulus heteroclitus, and only one amino acid was different from that of the eel Anguilla japonica, demonstrating a greater conservation among different teleost species than is found with atrial NP (ANP) and ventricular NP (VNP). While the preprosegment of trout CNP retained 57% similarity to the eel sequence, similarities were low to those of sharks and tetrapods. The major site of expression identified by RT-PCR was the brain with minor expression in the atrium. The putative mature CNP-22 was synthesized and its biological activity was compared with other trout NPs (ANP and VNP) using trout ventral aorta, efferent branchial and celiacomesenteric arteries and anterior cardinal vein in vitro. Synthetic trout CNP-22 relaxed all pre-contracted vessels with potencies comparable to trout ANP and VNP.     

A method for large-scale, high-yield isolation of canine pancreatic islets of Langerhans

A modified collagenase digestion method is described for the isolation of large numbers of islets from the canine pancreas (approximately 3,500 islets/g). The islets isolated by this technique remained viable and released insulin in response to secretagogues after one week of maintenance in tissue culture. Islets isolated from a single donor pancreas were re-implanted into the spleen of the same animal made diabetic by subtotal pancreatectomy and two injections fo streptozotocin. Hyperglycemia was corrected in two dogs and decreased in a third dog followed for 30 days. The islet isolation method is described, therefore, provides a sufficiently large yield of viable islets from one donor pancreas to correct or improve diabetes in a recipient animal.     

Pump dysfunction after myocardial infarction: Importance of location,extent and pattern of abnormal left ventricular segmental contraction

To delineate the relative effects on left ventricular function of the site, extent and nature of abnormal left ventricular segmental contraction (dyssynergy) and thereby determine the mechanism by which anterior myocardial infarction results in greater depression of left ventricular performance than does inferior infarction, 43 patients with remote myocardial infarction of similar extent (average 38 percent of left ventricular systolic perimeter) and associated hypokinesia or dyskinesia confined to either the anterior or inferior wall were compared; 10 additional patients were evaluated who exhibited generalized dyssynergy (72 percent of left ventricular perimeter). When the pattern of dyssynergy and extent of infarction were similar, the location alone of dyssynergy did not influence variables of left ventricular function. However, paradoxical outward systolic movement (dyskinesia) of the anterior or inferior wall resulted in greater depression (P < 0.05) of measures of left ventricular performance than did diminished inward systolic motion (hypokinesia) associated with infarction of similar extent and location. All measures of left ventricular performance were considerably more depressed (P < 0.05) in the 10 patients with generalized dyssynergy than in the 43 patients with localized dyssynergy. Thus, the location of infarction is not a unique determinant of left ventricular performance. Instead, the size of infarction is the principal characteristic of dyssynergy that impairs left ventricular function; the severity of the pattern of dyssynergy is significant but of lesser importance. It is therefore concluded that the greater reduction of left ventricular function in anterior than in inferior myocardial infarction is largely the result of the more extensive area of necrosis rather than of the location of the infarction.     

Effects of oxygen, calcium ionophore, and arachidonic acid on prostaglandin production by monolayer cultures of mixed cells and endothelial cells from rat fetal lungs

Prostaglandins (PGs) synthesized by fetal and neonatal lungs play pivotal roles in pulmonary physiology, especially during the transition from uterine to independent life. One regulator of prostaglandin synthesis at this time may be oxygen. We examined the effects of 1% O2, 21% O2 and 50% O2 in 5% CO2, balance N2 (PO2 values in medium = 30 +/- 4, 142 +/- 4, and 260 +/- 3 mm Hg, respectively), on prostaglandin production from monolayer cultures of mixed or endothelial cells prepared from day 20 gestation rat fetal lungs. Cells were untreated or stimulated to produce prostaglandins by the addition of the calcium ionophore, A23187 (10(-5) M), or the prostaglandin precursor, arachidonic acid (AA, 1 microgram/ml). Prostaglandins 6-keto F1 alpha (6KF, the hydrolysis metabolite of prostacyclin, PGI2), E2, F2 alpha and 13,14-dihydro-15-keto PGF2 alpha (FM, the enzymatic metabolite of PGF2 alpha) were measured by radioimmunoassay. The basal release of 6KF from mixed cells into serum-free medium was approximately 2 ng/10(6) cells/3 days. The levels of 6KF were 10-fold greater than those of the other prostaglandins. Basal endothelial cell release of 6 KF was 30 ng/10(6) cells/3 days, and this was 15- to 100-fold greater than that of the other prostaglandins measured. In mixed cells, oxygen treatment for 3 days had no effect upon the basal release of any prostaglandin, nor was there any effect of oxygen upon the basal 6KF or PGE2 production in endothelial cells. However, both PGF2 alpha and PGFM production by endothelial cells was decreased (p less than 0.05) in 50% O2 compared to 1% O2. Both A23187 and AA enhanced prostaglandin release from mixed and endothelial cells. Ionophore-stimulated 6KF net production in mixed cells was greater in 21% O2 than in 1% O2 (p less than 0.05). Calcium ionophore stimulated the net production of 6KF and PGE2 in endothelial cells in 21% O2 versus 1% O2 (p less than 0.05), and AA enhanced the net production of 6KF, PGE2 and PGF2 alpha in endothelial cells in 21% O2 versus 1% O2. We conclude that rat fetal pulmonary cells produce prostaglandins from endogenous and exogenous substrates, that prostaglandin production is sensitive to Ca2+-mobilizing agents, and that the production of the vasodilators PGI2 and PGE2 increases in the presence of 21% O2 and a stimulating factor.     

Effects of beta-blocker therapy on ventilatory responses to exercise in patients with heart failure

BACKGROUND: Ventilatory efficiency is the increase in ventilation relative to carbon dioxide production during exercise. Congestive heart failure (CHF) is associated with decreased ventilatory efficiency. beta-blockers improve hemodynamics, prolong survival, and improve functional class in patients with CHF, though peak exercise performance may not improve. We hypothesized beta-blockers increase ventilatory efficiency in patients with CHF. METHODS AND RESULTS: The study group comprised 614 subjects with left ventricular ejection fraction < or = 40% referred for cardiopulmonary exercise testing. Clinical and exercise data were reviewed and recorded. For comparison, subjects were divided into those treated with beta-blockers (n = 195) and those not treated (n = 419). Subjects on beta-blockers had lower minute ventilation (12 +/- 4 versus 14 +/- 4 L/min, P < .001) at rest, which remained lower during submaximal and maximal exercise, by 4 and 6 L/min, respectively (P = .001). Ventilatory efficiency was increased in subjects treated with beta-blockers at submaximal (32 +/- 6 versus 34 +/- 7, P = .002) and maximal (34 +/- 7 versus 37 +/- 10, P = .005) exercise. Differences between treatment subgroups remained significant by covariate analysis; beta-blockers were also independently associated with decreased minute ventilation by multiple regression. CONCLUSION: Beta-blockers may be associated with increased ventilatory efficiency in CHF patients, which may contribute to improved functional class and quality of life.     

The Cameriere,Haavikko, Demirjian,and Willems methods for the assessment of dental age in Croatian children

International Journal of Legal Medicine - This study aimed to evaluate the accuracy and precision of the Cameriere European formula, Demirjian, Haavikko, and Willems methods for estimating dental...     

MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction

Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myocardium is beneficial for cardiac function over time, nor which regulatory pathways play a crucial role in this process. To address these questions, transgenic (TG) mice engineered to overexpress modulatory calcineurin-interacting protein-1 (MCIP1) in the myocardium were used to achieve cardiac-specific inhibition of calcineurin activation. MCIP1-TG mice and their wild-type (WT) littermates, were subjected to MI and analyzed 4 weeks later. At 4 weeks after MI, calcineurin was activated in the LV of WT mice, which was significantly reduced in MCIP1-TG mice. WT mice displayed a 78% increase in LV mass after MI, which was reduced by 38% in MCIP1-TG mice. Echocardiography indicated marked LV dilation and loss of systolic function in WT-MI mice, whereas TG-MI mice displayed a remarkable preservation of LV geometry and contractility, a pronounced reduction in myofiber hypertrophy, collagen deposition, and beta-MHC expression compared with WT-MI mice. Together, these results reveal a protective role for MCIP1 in the post-MI heart and suggest that calcineurin is a crucial regulator of postinfarction-induced pathological LV remodeling. The improvement in functional, structural, and molecular abnormalities in MCIP1-TG mice challenges the adaptive value of post-MI hypertrophy of the remote myocardium. The full text of this article is available online at http://circres.ahajournals.org.     

N-dimethylisopropyl propranolol. Effects on myocardial oxygen demands.

N-Dimethylisopropyl propranolol (DMP) is a quaternary derivative which lacks significant beta-adrenergic blocking and local anesthetic effects. It has been reported, nonetheless, to be effective in treating experimental arrhythmias and in limiting the extent of ST-segment elevations following experimental coronary occlusion. The present study examined the effects of DMP on the hemodynamics and myocardial oxygen demands of anesthetized dogs. After a single dose of 3 mg/kg, heart rate fell from 146 +/- 8 to 124 +/- 6 beats/min (P less than 0.0025), and aortic systolic pressure fell from 151 +/- 11 to 141 +/- 9 mm Hg (0.05 less than P less than 0.10), resulting in a 16.8% reduction in the tension-time index. Stroke volume was reduced by 10% despite a 54% increase in left ventricular end-diastolic pressure, suggesting a negative inotropic effect. This was supported by a decrease in maximum extrapolated contractile element velocity from 9.10 +/- 1.05 to 6.61 +/- 65 units/sec (P less than 0.0025). Myocardial oxygen consumption was reduced from 12.0 +/- 1.4 to 9.9 +/- 1.5 ml/min/100 g tissue (P less than 0.05). Myocardial oxygen extraction was unchanged, indicating that the decrease in oxygen consumption resulted from a reduction in myocardial oxygen demand. When heart rate and systolic pressure were artificially restored to control levels, after the administration of DMP, myocardial oxygen consumption remained significantly below the control level. DMP, therefore, appeared to reduce myocardial oxygen demands primarily by its negative inotropic effect. This drug may have application in the treatment of ischemic heart disease.