Search PubMed⌕ Search

Biomedical subjects

G W Moe

Publications and source records attributed to G W Moe.

At least 37 records · Page 2Linked to original sources
PubMed1993

Dual natriuretic peptide system in experimental heart failure.

OBJECTIVES: The objectives of this study were 1) to define in an experimental model of heart failure the time course of changes in plasma brain natriuretic peptide concentrations during the development of and recovery from heart failure, and 2) to relate the changes to changes in atrial natriuretic peptide concentration and hemodynamic status. BACKGROUND: Brain natriuretic peptide is a circulating peptide with homology to atrial natriuretic peptide. However, unlike the latter, its changes during heart failure and its relation to cardiac filling pressures have not been studied. METHODS: Eight male mongrel dogs underwent right ventricular pacing at 250 beats/min for 3 weeks until heart failure occurred and were followed up during recovery for 4 weeks after cessation of pacing. RESULTS: Heart failure was characterized by an increase in both left ventricular and end-diastolic pressure (6.6 +/- 4.1 mm Hg at the control measurements to 35.1 +/- 5.9 mm Hg at 3 weeks, p < 0.01) and right atrial pressure (6.7 +/- 1.1 to 11.4 +/- 2.1 mm Hg, p < 0.01). Recovery was accompanied by a return of cardiac filling pressures to control level. The time course of change of arterial plasma brain natriuretic peptide concentration was similar to that of atrial natriuretic peptide. Plasma concentrations of both peptides increased after 1 week of pacing (16 +/- 4 pg/ml at the control measurement to 59 +/- 20 pg/ml at 1 week, p < 0.001 for brain natriuretic peptide and 84 +/- 55 to 856 +/- 295 pg/ml, p < 0.001 for atrial natriuretic peptide). The level of both peptides then stayed level with no further increase at 3 weeks and returned to the control value by 4 weeks of recovery. There was an excellent correlation between plasma concentrations of the two peptides (r = 0.86, p < 0.001) and between the two peptides and cardiac filling pressures. However, compared with atrial natriuretic peptide, plasma brain natriuretic peptide concentration had a smaller percent increase during evolving heart failure and a slower rate of decline at recovery. CONCLUSIONS: Brain and atrial natriuretic peptide constitute a dual natriuretic system and are both responsive to changes in cardiac filling pressures in heart failure. However, brain natriuretic peptide appears to be less responsive than atrial natriuretic peptide.

Analysis of Variance↗
PubMed1993

Medical advances in the treatment of congestive heart failure.

The increased incidence and prevalence of congestive heart failure place a high priority on novel treatment strategies. Left ventricular ejection fraction remains the single most valuable measurement providing both diagnostic and prognostic insights. The most systematic approach to heart failure involves an objective assessment of functional disability, to include exercise tests such as a 6-minute walk under standardized conditions. Left ventricular dysfunction incites a host of neurohumoral compensations that are of fundamental importance in the heart failure syndrome expression. Both vasoconstrictor and vasodilator neurohormones are stimulated and provide new therapeutic opportunities. The therapeutic approach to heart failure begins with a strong emphasis on prevention, patient education, and self-participation in therapy with respect to both its monitoring and adjustment. Diuretics remain a mainstay of therapy but, in the face of severe heart failure, may become ineffectual, requiring constant infusion of loop-active diuretics, combination diuretics, or diuretics in association with concomitant low-dose dopamine infusion. Vasodilator therapy has been an important advance: combination hydralazine and nitrate therapy was initially shown to be efficacious in improving survival, and more recently, angiotensin-converting enzyme (ACE) inhibitors, in the form of enalapril, have shown incremental benefit on survival over this combination. Interestingly, there is now evidence from both SOLVD and SAVE to demonstrate an unexpected and, as yet, unexplained reduction in the frequency of both unstable angina and myocardial infarction. Although, on balance, the weight of evidence concerning the long-term efficacy of inotropic agents has been disappointing, especially as it relates to their unfavorable effects on survival, recent information on vesnarinone, an agent with a complex and diversified mechanism of action, suggests that with appropriate doses, improved symptoms and survival are possible. A substantial amount of new information from randomized placebo-controlled trials attests to the symptomatic relief, hemodynamic improvement, and gain in exercise performance achieved by digoxin. A long-term survival study is ongoing to assess its effects on mortality. beta-Blockers, especially metoprolol, appear beneficial in some patients with heart failure, possibly related to their reduction in sympathetic nervous activity and restoration of beta-receptor population, with resultant improved contractile performance, enhanced myocardial relaxation, and overall increase in cardiac efficiency. Based on available evidence, the best contemporary approach to treatment involves the use of ACE inhibitors coupled with diuretic therapy, either continuous or intermittent, to relieve central or peripheral congestion. The addition of digoxin or a hydralazine nitrate combination is a logical next step, with commencement of low-dose beta-blocker a reasonable option.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Left ventricular myocardial blood flow, metabolism, and effects of treatment with enalapril: further insights into the mechanisms of canine experimental pacing-induced heart failure.

Left ventricular myocardial blood flow and metabolic parameters were studied in dogs with severe heart failure induced by rapid ventricular pacing. The impact of early administration of enalapril was also evaluated. Seventeen dogs were randomly assigned in a blinded fashion to receive enalapril at a dose of 10 mg orally per day or a matching placebo commencing 1 week after initiation of pacing. Six dogs underwent sham operations and served as a control for the myocardial blood flow and metabolic studies. In general, there was no significant difference in myocardial blood flow among the control dogs, the placebo-treated, and the enalapril-treated, paced dogs. However, tissue adenosine triphosphate was markedly reduced in both the enalapril-treated, paced dogs (2.43 +/- 0.55 mumol/gm wet weight, mean +/- SD) and the placebo-treated, paced dogs (2.79 +/- 0.39 mumol/gm) compared with the level in control dogs (4.77 +/- 0.88 mumol/gm, both p < 0.01). Tissue glycogen and lactate levels were similar in the three groups. The time to development of severe heart failure tended to be longer in the enalapril-treated dogs (33 +/- 12 days) than in the placebo-treated dogs (24 +/- 10 days, p = 0.07). In pacing-induced heart failure, therefore, an imbalance between energy supply and demand may contribute to the left ventricular dysfunction, myocardial ischemia does not play a major role, and early treatment with enalapril may prolong the time to development of severe heart failure.

Animals↗
PubMed1992

Myocardial myoglobin deficiency in various animal models of congestive heart failure.

Myoglobin is known to protect the mechanical function of the heart from hypoxia by acting as a sarcoplasmic oxygen reservoir and shuttle. We postulated a role for myoglobin in the pathogenesis of congestive heart failure. Several models of congestive heart failure were employed to test the hypothesis, including spontaneous inherited dilated cardiomyopathy in Doberman Pinschers, and heart failure produced by rapid ventricular pacing in dogs, volume overload in chickens and furazolidone toxicity in turkeys. Myocardial myoglobin was decreased by approximately 50% for all models (P less than 0.05). In Doberman Pinschers dogs which are predisposed to the development of dilated cardiomyopathy and have mild subclinical depression of cardiac performance, myocardial myoglobin (1.05 +/- 0.22 mg/g) is approximately 50% decreased compared to healthy mongrel dogs (2.15 +/- 0.52 mg/g), approximately twice as much as dobermans with heart failure (0.47 +/- 0.25 mg/g) but similar to the concentration found in dogs paced to heart failure (1.09 +/- 0.34 mg/g). Myocardium from poultry had remarkably decreased myoglobin compared to mammals (34 +/- 4 micrograms/g) with heart failure produced either by furazolidone or salt toxicity causing a further 50% reduction. In the canine models of heart failure, myocardial myoglobin concentration was demonstrated to be correlated with biochemical and physiological indicators of myocardial performance, namely, mitochondrial and sarcoplasmic reticular ATPase activities, and cardiac output, systemic vascular resistance, pulmonary capillary wedge pressure and mean arterial pressure, respectively. Our data implicates a role for myoglobin deficiency in the pathogenesis of congestive heart failure and in the predisposition of doberman pinschers to dilated cardiomyopathy.

Animals↗
PubMed1992

Evaluation of indices of left ventricular contractility and relaxation in evolving canine experimental heart failure.

OBJECTIVE: The aim was to evaluate changes in indices of left ventricular contractility and relaxation in relation to changes in loading conditions in dogs with rapid pacing induced heart failure. METHODS: 14 conscious male mongrel dogs were paced at 250 beats.min-1 to severe heart failure, which occurred at 4.2(SD1.9) weeks. Six sham operated dogs served as controls. Right sided pressures were obtained by a thermodilution catheter. Left ventricular pressure and its derived variables were obtained by a high fidelity manometer tipped catheter. Rate corrected velocity of circumferential fibre shortening--end systolic wall stress relations were obtained by simultaneous haemodynamic and echocardiographic studies. RESULTS: In the paced dogs, baseline right atrial pressure, 6.4(2.0) mm Hg, and pulmonary capillary wedge pressure, 7.1(2.5) mm Hg, increased to 13.3(3.1) mm Hg and 34.5(7.1) mm Hg respectively at severe heart failure (both p less than 0.0001). The peak first derivative of left ventricular pressure dP/dt decreased from 1515(274) mm Hg.s-1 at baseline to 975(321) mm Hg.s-1 at severe heart failure (p less than 0.05) while baseline left ventricular end diastolic pressure, 4.4(3.7) mm Hg, and relaxation time constant tau, 18.0(4.5) ms, increased to 37.2(6.6) mm Hg (p less than 0.01) and 51.9(21.4) ms (p less than 0.05) respectively. The shortening-wall stress relation was markedly displaced downward from baseline. Furthermore, weekly studies revealed a major downward displacement of this relation by one week of pacing with no significant further shift at severe heart failure, whereas both end diastolic diameter (preload) and end systolic wall stress (afterload) increased significantly further from one week. In the sham operated dogs, there was no change over time in any of these study variables. CONCLUSIONS: In pacing induced heart failure, there is impairment of left ventricular contractility and relaxation. The major downward shift of the shortening-wall stress relation at one week suggests that left ventricular contractility is impaired early and may be the initiating mechanism of heart failure in this model.

Animals↗
PubMed1992

Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure.

The pharmacokinetics of synthetic atrial natriuretic factor (ANF) and its effects on cyclic GMP, urinary sodium excretion, and hemodynamics were compared in 18 control subjects with normal hemodynamics and 12 patients with severe heart failure. Human 99-126 ANF was administered intravenously (0.2 micrograms/kg i.v. followed by 0.07 micrograms/kg/min for 30 min). As compared with controls, baseline plasma ANF concentration was higher in the heart failure group (329.2 +/- 166.1 vs. 33.6 +/- 17.3 pg/ml in controls, means +/- SD, p less than 0.01). Synthetic ANF increased plasma ANF concentration by similar amounts, but the elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure group (6.5 +/- 2.6 vs. 3.8 +/- 0.8 min, p less than 0.05). Baseline plasma cyclic GMP concentration was higher in the heart failure group (13.8 +/- 6.8 vs. 4.2 +/- 2.2 pmol/ml, p less than 0.01) but ANF increased plasma cyclic GMP concentration to a lesser degree (14.4 +/- 7.6 pmol/ml, p less than 0.05 vs. 24.9 +/- 10.1 pmol/ml, p less than 0.001). Baseline urinary sodium excretion was less in the heart failure group (13.3 +/- 14.0 vs. 53.7 +/- 37.3 mumol/min, p less than 0.01) and ANF induced a smaller increase in urinary sodium excretion (22.1 +/- 32.3 mumol/min, p less than 0.05 vs. 305.7 +/- 242.9 mumol/min, p less than 0.001). Baseline plasma norepinephrine (NE), renin, and aldosterone were higher in the heart failure group. Synthetic ANF increased plasma NE only in the control group, had no effect on renin, and decreased aldosterone in both groups. Hemodynamic responses were similar in both groups except the decreased arterial blood pressure (BP) was accompanied by increased heart rate (HR) only in the controls. Therefore, in heart failure, the t 1/2 of ANF is prolonged and there appears to be a limit for further increase in cyclic GMP. These changes may explain in part the blunted renal response to ANF.

Adult↗
PubMed1991

Sequential echocardiographic-Doppler assessment of left ventricular remodelling and mitral regurgitation during evolving experimental heart failure.

STUDY OBJECTIVE: The aim was to study the nature, magnitude, and time course of left ventricular structural adaptations to evolving heart failure. DESIGN: 17 male mongrel dogs, weight 24.9(SD 3.7) kg, underwent rapid ventricular pacing (250 beats.min-1) until severe heart failure developed. Two dimensional echocardiographic and Doppler studies were performed at control, then weekly to severe heart failure. Haemodynamic measurements were made at control and severe heart failure. All studies were performed with the animals conscious during temporary sinus rhythm. MEASUREMENTS AND MAIN RESULTS: Left ventricular diastolic volume gradually increased and the left ventricle assumed a more globular shape associated with significant wall thinning. Both the change in diastolic volume after one week of pacing and at the time of severe heart failure correlated with the time to peak heart failure. Mitral regurgitation was mild after one week of pacing, became moderate in most animals at severe heart failure, and lagged temporarily behind the increase in cardiac dimensions. The percentage increase in mitral annular size was significantly less than the increase in left ventricular cross sectional area. CONCLUSIONS: In pacing induced heart failure (1) marked left ventricular remodelling occurs, (2) the extent of left ventricular dilatation, both early and late, correlates directly with the time required for the development of severe heart failure, (3) mitral regurgitation is an epiphenomenon and is most likely to be caused by the increase in left ventricular cross sectional area.

Animals↗
PubMed1991

Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation-contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure.

The development of muscle fatigue due to exhaustive exercise is associated with impaired sarcoplasmic reticulum (SR) Ca-transport activity. This study tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue owing to relative functional overload regardless of the method of induction: excessive stimulation, diminished performance capacity, or excessive excitation-contraction coupling. The Ca-transport activity was determined using three unique models of muscle fatigue: chronic and rapid ventricular pacing in dogs; metabolic inhibition caused by global cardiac ischemia in swine; and the hypermetabolic syndrome of porcine malignant hyperthermia (MH). Both pacing- and ischemia-induced fatigue resulted in reduction of SR Ca-transport ATPase activity: from 275 +/- 58 to 159 +/- 57 nmol.min-1.mg-1 (mU/mg) and from 577 +/- 82 to 177 +/- 133 mU/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95 +/- 2.4 to 3.11 +/- 0.67 nM/s at 300 nM Ca and 38.7 +/- 10.5 to 16.3 +/- 8.0 nM/s at 1500 nM Ca, respectively (all p less than 0.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r = 0.76; p less than 0.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration.

BACKGROUND: This study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure. METHODS AND RESULTS: The effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/min), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32 +/- 12 to 168 +/- 153 pg/ml (p less than 0.05) and from 32 +/- 9 to 137 +/- 113 pg/ml (p less than 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 +/- 295 pg/ml (p less than 0.05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332 +/- 121 to 407 +/- 113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2 +/- 2.5 versus 16.1 +/- 10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62 +/- 0.31 versus 0.24 +/- 0.16 pg/mg) was increased compared with that of controls (both p less than 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls. CONCLUSIONS: These data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF.

Animals↗
PubMed1991

Sequential changes in atrial pressures, dimensions, and plasma atrial natriuretic factor concentrations during volume loading in hemodynamically normal human subjects.

The effects of volume loading on atrial pressures and dimensions, plasma levels of atrial natriuretic factor (ANF), and other neurohormonal variables were studied in 11 patients with normal hemodynamics with the patients in a supine -15 degree left decubitus posture by infusing 750 ml of normal saline solution over 30 minutes. Right and left atrial areas were measured by two-dimensional echocardiography. Plasma ANF level was sampled simultaneously from the pulmonary artery, aorta, and femoral artery and vein. At 30 minutes into the infusion, pulmonary capillary wedge pressure and right atrial pressure increased from 5.6 +/- 2.8 mm Hg (mean +/- SD) and 6.4 +/- 2.2 mm Hg to 10.2 +/- 3.2 and 9.5 +/- 2.2 mm Hg, respectively (both p less than 0.01). Left atrial area increased from 12.6 +/- 2.2 cm2 to 15.0 +/- 2.1 cm2 (p less than 0.05), whereas right atrial area did not change. Plasma ANF levels from all sampling sites increased significantly (e.g., 43 +/- 21 pg/ml to 71 +/- 62 pg/ml in the femoral artery, p less than 0.05). Plasma norepinephrine and renin levels were unchanged, whereas aldosterone level declined significantly. At 30 minutes after termination of the infusion, atrial pressures declined to baseline values in all patients. However, left atrial area remained significantly increased, and a trend for systemic arterial plasma ANF level to remain increased was seen. Plasma aldosterone level remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Response of atrial natriuretic factor to postural change in patients with heart failure versus subjects with normal hemodynamics.

The response of atrial natriuretic factor to an acute increase in atrial pressures produced by changing from a 45 degrees upright to a -15 degrees Trendelenburg tilt was examined in 21 patients with heart failure and 8 control subjects with normal hemodynamics. In the control subjects, baseline (45 degrees upright tilt) pulmonary capillary wedge and right atrial pressures increased from 3.1 +/- 0.9 (mean +/- SEM) and 4.4 +/- 0.3 mm Hg to 6.9 +/- 1.9 and 8.5 +/- 0.4 mm Hg, respectively (p less than 0.05 for both), 30 min after the -15 degrees tilt. Baseline arterial plasma atrial natriuretic factor concentration increased from 34 +/- 4 to 44 +/- 1 pg/ml (p less than 0.05) 30 min after the tilt, with an increase observed in every patient. In the group with heart failure, baseline pulmonary capillary wedge and right atrial pressures increased from 17.5 +/- 2.0 and 5.3 +/- 1.2 mm Hg to 24.6 +/- 1.8 and 9.7 +/- 1.3 mm Hg, respectively (p less than 0.01 for both), 30 min after the tilt. Plasma atrial natriuretic factor concentration was 326 +/- 38 pg/ml at baseline and 347 +/- 34 pg/ml (p = NS) 30 min after tilt. Compared with the 7 patients with heart failure who had increased atrial natriuretic factor concentrations after the tilt (responders), the 14 patients with unchanged or decreased atrial natriuretic factor concentrations after the tilt (nonresponders) had a higher baseline right atrial pressure and atrial natriuretic factor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function↗
PubMed1990

Pathophysiological role of changing atrial size and pressure in modulation of atrial natriuretic factor during evolving experimental heart failure.

STUDY OBJECTIVE: The aim was to study the interactions between pulmonary capillary wedge pressure (an estimate of left atrial pressure), left atrial dimension, and atrial natriuretic factor during evolving heart failure. DESIGN: Sequential simultaneous measurements of haemodynamic variables, left atrial dimension, and plasma atrial natriuretic factor concentrations were obtained during evolving experimental pacing induced heart failure. EXPERIMENTAL MATERIAL: Eight male mongrel dogs were paced (250 beats.min-1) to severe heart failure over 4.9(SD 1.8) weeks. MEASUREMENTS AND RESULTS: The development of heart failure was characterised by a progressive increase in pulmonary capillary wedge pressure and left atrial cross sectional area, from 5.6(1.3) mm Hg and 7.9(1.2) cm2 respectively at control, to 25.3(4.9) mm Hg and 14.2(2.5) cm2 respectively (both p less than 0.01) at severe heart failure. In contrast to the progressive increase in pulmonary capillary wedge pressure and left atrial area, plasma atrial natriuretic factor concentration increased from 98(51) ng.litre-1 at control to a peak of 422(110) ng.litre-1 (p less than 0.01) at 1 week, then plateaued and reached 354(108) ng.litre-1 at severe heart failure (p less than 0.05 v control). Plasma atrial natriuretic factor correlated with pulmonary capillary wedge pressure and left atrial area at 1 week (r = 0.73, r = 0.71 respectively, both p less than 0.01), but not at the time of severe heart failure. CONCLUSION: The divergent time course of the changes in plasma atrial natriuretic factor concentration, pulmonary capillary wedge pressure, and left atrial dimension suggests that in this model, the release of atrial natriuretic factor becomes attenuated as severe heart failure develops.

Animals↗
PubMed1990

Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies.

Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 +/- 7.6 vs. 50.5 +/- 5.1%) and cardiac index (81 +/- 22 vs. 178 +/- 48 mL.min-1.kg-1), 287% higher pulmonary capillary wedge pressure (27.5 +/- 6.8 vs. 7.1 +/- 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 +/- 3.7 vs. 11.2 +/- 1.3 cm2) (all p less than 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 +/- 139 vs. 747 +/- 220 ng/g protein), (ii) 25-50% lower activities of myofibrillar Ca ATPase (0.188 +/- 0.026 vs. 0.253 +/- 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 +/- 0.074 vs. 0.288 +/- 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 +/- 10.0 and 47.7 +/- 15.8 U/g), (iii) 32% higher activity of the beta-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 +/- 1.48 vs. 8.67 +/- 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 +/- 0.77 vs. 1.81 +/- 0.95 U/g) (all p less than 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Fibrillar collagen and remodeling of dilated canine left ventricle.

To test the hypothesis that in the failing volume-overloaded ventricle, the extracellular matrix and fibrillar collagen in particular are major determinants of the architectural remodeling of the myocardium, this histopathological study of the dilated, postmortem canine left ventricle secondary to rapid ventricular pacing or aortocaval fistula was undertaken. Using the picrosirius-polarization technique to enhance collagen birefringence, we sought to examine the structural integrity of the collagen matrix and interstitium. In the dilated failing ventricle secondary to rapid pacing, we found 1) interstitial edema and a disruption or disappearance of collagen fibers that were apparent within 6 hours of pacing, persisted for weeks, and subsequently were associated with muscle fiber disorganization within the endomyocardium, 2) interstitial fibrosis that was present in the midwall and epimyocardium with chronic pacing, and 3) an early remodeling of intramyocardial coronary arteries that included medial swelling with smooth muscle degeneration followed by proliferative lesions involving fibroblasts and a subsequent perivascular and medial fibrosis. Many of these findings were still evident 48 hours after pacing had been discontinued. In contrast, the collagen matrix and interstitium seen with ventricular dilatation secondary to the circulatory overload that accompanies an aortocaval fistula were indistinguishable from that in sham-operated controls. Thus, we conclude that unlike the chamber enlargement and preserved ventricular function that accompany an aortocaval fistula, ventricular dilatation and failure caused by rapid pacing are based on an architectural remodeling of the myocardium. This structural dilatation involves the extracellular matrix and interstitium and appears to be related to altered permeability of intramyocardial coronary arteries. The mechanism or mechanisms involved in the pathogenesis of myocardial remodeling with rapid ventricular pacing require further investigation.

Animals↗
PubMed1990

Pharmacokinetics, hemodynamic, renal, and neurohormonal effects of atrial natriuretic factor in experimental heart failure.

The hemodynamic, renal, neurohormonal effects and pharmacokinetics of synthetic atrial natriuretic factor (ANF) were studied in six conscious dogs with severe heart failure induced by right ventricular pacing at 250 beats/min for 5.0 +/- 0.6 weeks. Severe heart failure was characterized by a low cardiac output (2.1 +/- 0.1 L/min, elevated pulmonary capillary wedge pressure (26.8 +/- 2.8 mmHg) and right atrial pressure (14.5 +/- 2.2 mmHg). Synthetic ANF (human 99ser-126tyr ANF) was administered intravenously as 2 consecutive 30 min infusions (0.02 and 0.10 microgram/kg.min respectively); and each infusion was preceded by a priming dose of 1 microgram/kg. In contrast to the potent vasorelaxant, natriuretic and renin-lowering effects previously reported in normal dogs, these effects were not observed in the dogs with heart failure with either dose of ANF. The plasma half-life was 10.0 +/- 2.6 min, significantly longer than that reported previously in normal dogs. These data suggest that in this model of heart failure, the pharmacokinetics of ANF are altered and there is generalized target organ resistance to the actions of ANF.

Animals↗
PubMed1990

A new method for hemodynamic and echocardiographic assessment of conscious dogs: comparison with thiopental-morphine anaesthesia.

A method allowing assessment of cardiac structure and function in the conscious dog using readily available instrumentation is desirable and should provide physiologic advantages when compared to anaesthesia. Accordingly, we studied 19 dogs (22 +/- 2.5 kg), using two-dimensional echocardiographic and Swan-Ganz and femoral artery catheterization; ten were conditioned to permit conscious studies and nine received anaesthesia. Dogs receiving anaesthesia were induced with intravenous thiopental (16 +/- 4 mg/kg), followed by a maintenance dose (7 +/- 1 mg/kg/h) plus morphine sulphate (213 +/- 5 micrograms/kg/h). Cardiac index, mean blood pressure, and systemic vascular resistance were similar between groups. However, anaesthesia as compared to conscious studies resulted in a marked tachycardia (147 +/- 30 bpm, vs 98 +/- 19 bpm, p less than 0.0005), significantly lower right atrial pressure (5 +/- 2 mmHg vs 8 +/- 2 mmHg, p less than 0.05), and a trend towards a lower pulmonary capillary wedge pressure (6 +/- 5 mmHg vs 9 +/- 3 mmHg). Simultaneous echocardiography showed left ventricular diastolic cross sectional area to be smaller in the anaesthesia group (8.5 +/- 1.7 cm2 vs 10.4 +/- 1.5 cm2, p less than 0.05); however, ejection fraction in the two groups was similar. Velocity of circumferential fiber shortening (Vcf), normalized for heart rate and preload, was significantly lower in the anaesthetised dogs (0.63 +/- 0.22 circ/sec vs 0.89 +/- 0.26 circ/sec, p less than 0.05); this decline in Vcf, in association with a lower systolic wall stress (85 +/- 29 10(3) dynes/cm2 vs 119 +/- 23 10(3) dynes/cm2, p less than 0.05) indicates that thiopental-morphine anaesthesia depresses contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗