Cardiac atria of BIO 14.6 hamsters are deficient in natriuretic factor.

The hearts of 220-day-old hamsters of the BIO 14.6 strain are deficient in atrial natriuretic factor; saline extracts of atria produce one-third the natriuretic and diuretic effects of extracts of atria from age-matched normal hamsters. BIO 14.6 hamsters are known to develop congestive heart failure with edema when they are about 200 days old, and the venous congestion and edema are preventable by parabiosis with normal hamsters. The humoral mediator, the deficiency of which causes venous congestion and edema in BIO 14.6 hamsters, may be atrial natriuretic factor.

Augmented coronary blood flow response to intracoronary norepinephrine after ventricular sympathectomy.

BACKGROUND: Ventricular sympathetic denervation may occur as a result of myocardial infarction or heart transplantation. The present study examined the time-dependent effects of surgical ventricular sympathectomy on coronary flow and myocardial contractile responses to intracoronary norepinephrine administration in conscious dogs. METHODS: Adult mongrel dogs (18-26 kg), were either ventricular sympathectomized or served as a sham-operated control. Animals were studied 2, 4, and 8 weeks after surgery. Measurements of left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure generation (dP/dtmax), maximum negative rate of segmental shortening (-dL/dtmax), heart rate, and mean circumflex flow velocity (CFV) were obtained before and after bolus administration of norepinephrine into the circumflex artery in doses ranging from 0.01 to 0.50 microgram. RESULTS: Intracoronary norepinephrine administration caused significant increases in LVSP, dP/dtmax, -dL/dtmax, heart rate, and CFV. After reaching a peak or maximum response, these variables returned to their respective preinjection values, except for CFV, which exhibited a biphasic response. CFV continued to decline below control levels, indicating a vasoconstrictor response to norepinephrine, before returning back to preinjection levels. With the 0.5-microgram dose of intracoronary norepinephrine, the percent increases in CFV were 124% +/- 25% and 105% +/- 15% (P < 0.05) at 2 and 4 weeks respectively, compared with the sham-operated controls, which only increased 56% +/- 15%. The response to the 0.5-microgram dose of norepinephrine at 8 weeks (61% +/- 6%) was not significantly different from control. Elevated myocardial contractile responses in the sympathectomized hearts were also evident at 2 and 4 weeks, but not at 8 weeks. The vasoconstrictor response to norepinephrine administration was not significantly different between sympathectomized and sham-operated hearts. Finally, there was no difference in the change in LVSP, dP/dtmax, or heart rate between any of the groups at any of the doses. CONCLUSIONS: These results suggest that a supersensitivity to the coronary functional hyperemic response after intracoronary norepinephrine is present in ventricular sympathectomized hearts, but a coronary constrictor supersensitivity does not exist.

Exercise training reduces ischemic myocardial dysfunction.

PURPOSE: This study tested the hypothesis that exercise training improves myocardial blood flow and regional myocardial contractile function in a lateral border zone located adjacent to the ischemic zone during coronary artery occlusion. METHODS: Fourteen dogs were subjected to either 12 wk of dynamic exercise training or cage rest. Dogs were anesthetized and instrumented to assess regional myocardial contractile function (percent segment length shortening and rate of shortening) and regional myocardial blood flow (tracer microspheres) in the central ischemic, lateral border, and nonischemic zones. Measurements were made preocclusion and at 2 min and 3 h after occlusion of the left anterior descending coronary artery (CAO). RESULTS: Contractile function and regional myocardial blood flow were not affected by CAO in the nonischemic zone in both cage-rested and exercise trained dogs. Regional myocardial contractile function and blood flow in the lateral border zone were significantly higher in exercise trained dogs compared with cage-rested dogs, both at 2 min and 3 h after CAO. Ischemic dysfunction was similar in the central ischemic zone in both cage-rested and exercise trained dogs both at 2 min and 3 h after CAO. Regional myocardial blood flow was similarly reduced in the ischemic zone in both groups after 2 min of CAO, but was significantly higher in the inner (subendocardial) region of the exercised trained hearts after 3 h (P < 0.05). CONCLUSION: These data suggest that there was greater border zone perfusion in exercise trained animals during prolonged CAO, which was associated with significantly improved myocardial contractile function.

Endurance training alters arterial baroreflex function in dogs.

The present study was designed to determine whether 12 wk of daily exercise alter autonomic neural control of the heart during baroreflex stimulation in healthy dogs. We studied 16 untrained and 12 endurance-trained anesthetized dogs which were instrumented to measure arterial blood pressure (AP), carotid sinus baroreceptor pressure (CBP), electrocardiogram (ECG), heart rate (HR), and R-R interval (RR). The arterial baroreflex was studied during hypertension caused by i.v. bolus infusion of phenylephrine, hypotension caused by i.v. bolus infusion of nitroprusside, and bilateral carotid occlusion (BCO) in which carotid sinus pressure was reduced to 41 +/- 2 mm Hg (mean +/- SEM). Arterial baroreflex sensitivity, which was assessed by determining the change in heart interval (i.e., change in RR) per unit change in systolic AP (delta RR/delta AP), was significantly lower during the hypertensive challenge in the trained dogs compared to the untrained dogs (2.2 +/- 0.3 vs 6.8 +/- 1.5 ms.mm Hg-1, respectively). Similarly, the delta RR/delta AP was substantially lower during the hypotensive challenge in trained dogs vs the untrained dogs (1.2 +/- 0.3 vs 1.8 +/- 0.4 ms.mm Hg-1, respectively). In addition, the HR response to the BCO was significantly less in trained dogs (22 +/- 2 bpm) vs untrained dogs (32 +/- 5 bpm). The open-loop gain (Go), which was used to quantitate the effectiveness of the carotid baroreflex to increase mean systemic AP during BCO, was similar in both untrained and trained dogs (2.9 +/- 0.6 and 2.4 +/- 0.5, respectively). These data indicate that, while endurance training significantly reduces the HR component of the arterial baroreflex, the arterial pressure response apparently is not altered.

Follow the leader: a learning exercise.

This manuscript presents an alternate method for students' acquisition of leadership concepts. It also invites the students to become actively invoLved in their own learning. "Follow the Leader: A Learning Exercise" enables students to observe leadership in action, and to analyze and assimilate leadership/management theories. After observing leaders, the students discuss how they would use what they learned to become better nursing leaders. The exercise covers these key nursing management concepts: principles of delegation of authority and responsibility, communication patterns, group process, decision making, and evaluation. In order to do the exercise, students need background knowledge of basic management procedures of planning, organizing, directing and controlling.

How to make conflict work for you.

Fostering an environment of collaboration allows staff room to solve conflicts among themselves.

Caring leadership: secret and path to success.

Combining insights from both care theory and leadership theory, nursing leaders can develop a work environment which fosters autonomy and creativity in nursing practice through valuing and empowering the caregivers. Caring leadership affirms the uniqueness and importance of each individual. Experiencing justice, equity and respect, nurses are motivated to contribute their unique talents to a common goal.

Taxonomic and diagnostic markers for identification of Coccidioides immitis and Coccidioides posadasii.

The ribosomal Internal Transcribed Spacer (ITS) regions of the two recognized species of Coccidioides were studied using a reference set of strains that had been previously identified with species defining microsatellite polymorphisms. Unambiguous identification of the two species proved to be possible by amplifying and sequencing the ITS region. PCR-reactions are sensitive to amplification conditions requiring their careful optimization. Stable amplification and sequencing was achieved with primers ITS3 and 4, enabling species diagnosis. Alternatively, Restriction Fragment Length Polymorphism (RFLP) of the entire ITS region using an annealing temperature of 52 degrees C with the restriction enzymes BsrI and XcmI can also distinguish the species. Three strains typifying the species, Glenospora meteuropaea, G. metamericana and Geotrichum louisianoideum, were analyzed and found to be conspecific with C. posadasii. Although these species have nomenclatural priority over C. posadasii, the latter will be proposed for conservation as it has been included in the US select agent list. In addition, Coccidioides immitis is neotypified in this report. Results of antifungal susceptibility testing did not reveal differences between the two species.

In vivo and in vitro studies of a putative inhibitor of cyclic guanosine 3',5'-monophosphate production.

Our main objective was to test the efficacy of 6-anilino-5,8-quinolinedione (LY83583) in vivo, a putative inhibitor of cyclic guanosine 3',5'-monophosphate (cGMP) production. If the drug proved capable of lowering plasma, vascular, and kidney levels of cGMP and of inhibiting the hypotensive effect of sodium nitroprusside and methacholine, then LY83583 could be of potential use in exploring the contribution of cGMP to cardiovascular and renal physiology. We found that when administered to trained conscious rats, LY83583 (1-mg/kg bolus, followed by a 2-hr infusion of 3 mg/kg.hr) decreased plasma cGMP concentration by 36% (P less than 0.01). Doubling the dosage of drug (2-mg/kg bolus, 6 mg/kg.hr) decreased plasma cGMP by 46% (P less than 0.05). We next measured tissue levels of cGMP ex vivo from rats that had received LY83583 or vehicle for 2 hr. The cGMP content of aortic segments when LY83583 was infused at the low dose, or renal cortical tissue when LY83583 was infused at both doses, was not significantly different from the cGMP content of tissue from rats that had received vehicle. LY83583 in doses up to 10-mg/kg bolus, followed by 6 mg/kg.hr infusion also failed to attenuate the hypotensive response to sodium nitroprusside or methacholine in conscious rats. Last, we tested whether, in our hands, LY83583 could reduce cGMP of aortic segments and kidney cortical slices in vitro. We found that after 10 min of incubation, 10(-5) M LY83583 decreased intracellular cGMP by approximately 65% and 50% in aortic and kidney tissues, respectively. In order to ascertain whether LY83583 lowered cGMP by stimulating phosphodiesterase, we incubated tissues with 10(-4) M 3-isobutyl-1-methylxanthine to inhibit the enzyme. In the presence of 3-isobutyl-1-methylxanthine LY83583 still exerted an inhibitory effect on cGMP production by aortic and kidney tissues. In conclusion, although LY83583 is a useful agent to lower renal and vascular tissues levels of cGMP in vitro, its efficacy in vivo seems doubtful.

The interaction of cardiolipin with rat liver carbamoyl phosphate synthetase I.

A selective interaction of rat liver carbamoyl phosphate synthetase I with cardiolipin, and other anionic phospholipids, has been demonstrated. The enzymatic activity of the synthetase is inhibited by cardiolipin and, to a lesser extent, by phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine. This group of anionic phospholipids also induced a conformational change in the synthetase, yielding a species with increased exposure of the linkages between independently folded domains of the enzyme, as determined by limited proteolysis under nondenaturing conditions. The interaction of cardiolipin with carbamoyl phosphate synthetase I was a fairly slow process, with complex kinetics, and was apparently irreversible. The inclusion of Mg2+ or of MgATP in the incubation mixture prevented the cardiolipin effects. The zwitterionic phospholipids phosphatidylcholine and phosphatidylethanolamine had negligible effects on the structure and activity of the synthetase. This interaction between cardiolipin and carbamoyl phosphate synthetase I potentially constitutes one of the mechanisms by which the synthetase forms its loose association with the inner mitochondrial membrane. Multiple mechanisms, including synthetase conformational changes, cardiolipin phase changes, and ATP/ADP binding site involvement, are possibly involved in the phospholipid/synthetase interaction and the resulting potential regulatory mechanism(s) for urea cycle activity.

Plasma atrial natriuretic peptide in conscious rats with reduced renal mass.

The effect of salt intake and reduction of renal mass (RRM) on plasma immunoreactive atrial natriuretic peptide (iANP) levels in conscious rats was studied. Rats were divided into RRM and sham-operated groups, and then further subdivided into groups infused with 1 or 6 mEq of sodium per day. Plasma urea nitrogen increased in the groups with RRM. Plasma sodium, sodium balance, and heart rate did not differ between the sham and RRM groups. Rats with RRM maintained on 1 mEq of sodium per day did not have an elevation of water intake, arterial pressure, or plasma iANP. Rats with RRM maintained on 6 mEq of sodium per day had significantly (P less than 0.05) elevated water intake, arterial pressure, and plasma iANP. Arterial pressure and plasma iANP were correlated (r = 0.800) for rats with RRM on either 1 or 6 mEq of sodium per day. Increased plasma iANP in the RRM group on 6 mEq per day was not caused by either RRM or high sodium alone; it was an effect of RRM plus high salt intake. The increase in plasma iANP in the RRM group may be caused by the increase in arterial pressure, possibly due to an increase in extracellular fluid volume. ANP may not be responsible for the sustained increase in fractional sodium excretion observed in RRM.

Augmentation of coronary flow improves myocardial function in exercise.

We compared the effects of increasing coronary blood flow (CBF) by intracoronary alpha 1-adrenergic blockade or by a direct vasodilator in six chronically instrumented dogs undergoing submaximal exercise. On different days, CBF, left ventricular pressure (LVP), regional myocardial segment length (SL), and arterial blood pressure (ABP) were measured at rest, during strenuous exercise before administration of vasodilating agents, and during exercise after administration of the vasodilating agents prazosin (0.5 mg) or adenosine (10-100 micrograms/min continuous infusion) through an indwelling circumflex artery catheter. Exercise resulted in a significant increase in CBF, which was accompanied by significant increases in maximum rate of LVP generation (dP/dtmax), percentage of SL shortening (%SL) and maximum rate of SL shortening (dL/dtmax) in both the anterior and posterior regions of the left ventricle. As compared with the exercise level alone, prazosin administration or adenosine infusion during exercise significantly increased CBF by 22 and 26%, respectively. Furthermore, these increases in CBF were followed by significant increases in both dP/dtmax and dL/dtmax over exercise levels without prazosin administration or adenosine infusion. These results suggest that myocardial contractile function may be flow-limited under conditions of submaximal exercise and that coronary vasodilation, either by alpha 1-adrenergic blockade or by a direct vasodilator, improves contractile function.

Atriopeptin II lowers cardiac output in conscious sheep.

Atrial natriuretic peptides cause natriuresis, kaliuresis, diuresis, and hypotension. They relax vascular smooth muscle in vitro, and they dilate renal vessels in vivo. Hence, we tested the hypothesis that they produce hypotension by lowering total peripheral resistance. The studies were performed in conscious chronically instrumented sheep standing quietly in their cages. Atriopeptin II (AP II) was infused into the right atrium for 30 min at 0.1 nmol X kg-1 X min-1. Atriopeptin II lowers arterial pressure (9%, P less than 0.05) by lowering cardiac output (18%, P less than 0.05), stroke volume (28%, P less than 0.05), and right atrial pressure (2.3 mmHg, P less than 0.05). Heart rate and total peripheral resistance increase (16 and 13%, respectively, P less than 0.05). Partial ganglionic blockade with trimethaphan camsylate during AP II infusion prevents the increases in heart rate and total peripheral resistance. The changes in right atrial pressure, stroke volume, and cardiac output persist, and arterial pressure falls further (27%, P less than 0.05). These hemodynamic data are consistent with direct AP II-induced relaxation of venous smooth muscle with reduction of venous return, right atrial pressure, stroke volume, cardiac output, and arterial pressure, followed by reflex activation of the sympathetic nervous system to increase heart rate and total peripheral resistance. Because partial ganglionic blockade alone and AP II alone cause similar reductions in right atrial pressure (2.1 and 2.3 mmHg, respectively) but AP II causes a greater fall in stroke volume (28 vs. 13%), it is possible that AP II also causes coronary vasoconstriction.

Elevation of intrarenal adenosine by maleic acid decreases GFR and renin release.

Maleic acid administration produces a defect in tubular reabsorption resembling that seen in the Fanconi syndrome and also causes a decrease in glomerular filtration rate (GFR). The mechanism by which maleic acid alters renal function is uncertain, though the tubular defect is known to be associated with decreased ATP levels. Because of this alteration in nucleotide metabolism the present study was undertaken to determine the role of elevated endogenous adenosine in mediating the maleic acid-induced changes in renal function. Since the renal effects of exogenous adenosine are enhanced by sodium-depletion and attenuated by sodium-loading, the present study compared the time course of the effects of maleic acid on renal function in 10 dogs maintained on a low sodium diet, and 10 dogs maintained on a high sodium diet. In addition, we examined the effect of maleic acid on adenosine levels in renal venous plasma, on the urinary excretion of adenosine, and the effect of the adenosine antagonist, theophylline, on the maleic acid-induced changes in renal function. After 100 min of maleic acid, GFR was decreased significantly by 55 +/- 4% of control in the sodium-depleted dogs, and by 39 +/- 4% of control in the sodium-loaded dogs. In the sodium-depleted dogs, renin release was also significantly depressed (12 +/- 8% of control) during the infusion of maleic acid. The fractional excretion of sodium was significantly increased in both groups. The renal venous concentration of adenosine and the urinary excretion of adenosine were both significantly increased during maleic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA.

OspA is a protective antigen of the Lyme disease spirochete Borrelia burgdorferi. Expression of the full-length B. burgdorferi B31 OspA gene in Escherichia coli produces a protein that is processed posttranslationally by signal peptidase II and contains an attached lipid moiety. The recombinant OspA lipoprotein has been purified by detergent extraction and ion-exchange chromatography. Priming and boosting with OspA lipoprotein, either with no adjuvant or adsorbed to alum, elicited a strong, dose-dependent immunoglobulin G response. Serum from vaccinated mice inhibited spirochetal growth in vitro. Mice immunized twice with as little as 0.4 micrograms of OspA lipoprotein were protected against an intradermal challenge with 10(4) infectious spirochetes. The ability of the purified recombinant lipoprotein to induce a strong protective response in the absence of toxic adjuvants makes it an excellent candidate antigen for a human vaccine against Lyme disease. By contrast, no serum immunoglobulin G or growth inhibitory response to OspA nonlipoprotein was seen at any dose. The difference in immunogenicities of the lipoprotein and nonlipoprotein forms of OspA is not due to any difference in the antigenicities of the two proteins. These results suggest that posttranslational lipid attachment is a critical determinant of the immunogenicity of the OspA protein.