Right-sided Congestive Heart Failure Research Articles

Short-term effects of naloxone hemodynamics and baroreflex function in conscious dogs with pacing-induced congestive heart failure

Objective. The purpose of this study was to determine the effects of naloxone on systemic hemodynamics and reflex function in dogs with congestive heart failure induced by rapid pacing.Background. We have shown previously that naloxone, an opiate receptor antagonist, improves cardiac output, aortic blood pressure, systolic performance and the baroreflex function in conscious dogs with chronic right-sided congestive heart failure. However, whether endogenous opioids also play a role in mediating the reduction of myocardial and baroreflex function in animals with left heart failure remains controversial.Methods. We administered naloxone (1 mg/kg body weight) and normal saline solution to 15 dogs with pacing-induced congestive heart failure (225 beats/min for 8 weeks) and 11 control dogs. In addition to systemic hemodynamic measurements, the slope of pressure-area relation obtained from echocardiography with intravenous bolus injection of phenylephrine was taken as a load-independent index of myocardial contractility. Baroreflex function was estimated by the slope of the regression line relating systolic aortic pressure and RRE interval.Results. Plasma beta-endorphin levels were elevated in dags with congestive heart failure. Naloxone administration increased heart rate, mean aortic pressure, first derivative of left ventricular pressure, cardiac output and myocardial contractility in pacing-induced congestive heart failure. These changes correlated significantly with basal plasma beta-endorphin levels and were accompanied by increases in plasma beta-endorphin and catecholamines after naloxone administration. However, unlike the hemodynamic and cardiac effects of naloxone, baroreflex function did not change after naloxone in dogs with congestive heart failure.Conclusions. The increase in basal plasma beta-endorphin suggests that the endogenous opiate system is activated in lef-tsided congestive heart failure. Because naloxone improves the systemic hemodynamics and myocardial contractile function under this condition, the endogenous opioids appear to play an important role in mediating the myocardial depression that occurs in heart failure. However, the endogenous opiate system has no apparent effect on the regulation of baroreflex control in heart failure induced by rapid pacing.

Use of a modified open patch-graft technique and valvulectomy for correction of severe pulmonic stenosis in dogs: eight consecutive cases.

A modified open patch-graft technique was used to correct congenital pulmonic stenosis in 8 dogs. Pulmonary valve dysplasia was moderate to severe in all cases, based upon clinical and echocardiographic criteria, and 3 dogs were in right-sided congestive heart failure at the time of surgery. Seven of the 8 dogs survived the surgery. One surviving dog displayed cerebral cortical dysfunction, the remaining 6 had no detectable neurological sequelae. Right ventricular failure was alleviated in all 7 surviving dogs, but right ventricular dilatation persisted post-operatively. Pulmonary valvulectomy and open patch-grafting provides an effective means of alleviating signs of congestive heart failure caused by pulmonary valve dysplasia, even in the presence of severe infundibular hypertrophy and dynamic outflow obstruction.

O-039 - Hemodynamic effects of orally administered OPC-21268 in conscious dogs with right-sided congestive heart failure

O-039 - Hemodynamic effects of orally administered OPC-21268 in conscious dogs with right-sided congestive heart failure

Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

The reductions of myocardial beta-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by beta-receptor blockade. We administered the oral beta-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of beta-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure. Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.

Attenuation of pressor responses to arginine vasopressin in right-sided congestive heart failure

Although arginine vasopressin (AVP) is elevated in heart failure, inhibition of the vasopressinergic V1-receptor produces minimal changes in blood pressure. To determine whether the V1 vasoconstrictor effect is attenuated in heart failure, we randomly administered three increasing doses of AVP and methoxamine intravenously to 11 dogs with right-sided congestive heart failure (RHF) and 7 sham-operated dogs. Plasma AVP was elevated in RHF (21 +/- 3 pg/ml) compared with sham-operated dogs (3.8 +/- 0.6 pg/ml). While the pressor response to methoxamine was similar in the two groups, AVP caused a smaller increase in mean aortic pressure in RHF dogs than sham-operated dogs. To determine whether the difference in the pressor response to AVP was caused by greater reflex withdrawal of the sympathetic activity in RHF than sham-operated dogs, we also administered AVP after these animals had been pretreated with prazosin and propranolol. Adrenoceptor blockade exaggerated the pressor response to AVP; however, the increase in mean aortic pressure was still smaller in RHF than sham-operated dogs. The diminished pressor response in adrenoceptor-blocked RHF dogs was associated with a smaller increase in total peripheral vascular resistance compared with similarly treated sham dogs. Thus, although the pressor response to AVP was offset by baroreflex activation, the attenuated pressor effect of AVP in heart failure cannot be explained by sympathetic withdrawal alone. AVP probably exerts a smaller direct vasoconstrictor effect when the vasopressinergic system is chronically activated in heart failure.

Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure.

The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Opiate receptor antagonism in right-sided congestive heart failure. Naloxone exerts salutary hemodynamic effects through its action on the central nervous system.

Opiate receptor inhibition causes adrenergic receptor-mediated increases in aortic pressure, cardiac output, and left ventricular contractile function in right heart failure. To study whether the effects of opiate receptor inhibition are mediated by means of an action on the central opiate system, we administered equimolar doses of naloxone hydrochloride and naloxone methobromide (MeBr) and normal saline to heart failure dogs. Chronic stable right heart failure was produced by progressive pulmonary artery constriction and tricuspid valve avulsion. Naloxone hydrochloride caused an increase in mean aortic pressure, cardiac output, left ventricular dP/dt and dP/dt/P, plasma catecholamines, and regional blood flows to the myocardium, quadriceps muscle, kidneys, and splanchnic beds. Plasma beta-endorphin and adrenocorticotropin also increased. In contrast, neither normal saline nor naloxone MeBr (which does not cross the blood-brain barrier) affected the systemic or regional hemodynamics or neurohormones. Naloxone hydrochloride was also administered to anesthetized heart failure dogs. Pentobarbital anesthesia removed cortical perception of nociceptive stimulation, reduced the increase in plasma epinephrine, and abolished vasodilation in skeletal muscle that occurred in conscious dogs after naloxone hydrochloride administration but had no major effects on responses of plasma norepinephrine, systemic hemodynamics, or other regional blood flows to opiate receptor inhibition. Naloxone hydrochloride had no effect in sham-operated dogs. The results indicate that the hemodynamic effects of naloxone are mediated by an action within the central nervous system. Furthermore, since pentobarbital anesthesia did not markedly alter the hemodynamic responses to naloxone hydrochloride, the acute salutary effects of opiate receptor inhibition probably are not caused by removal of the antinociceptive effect of endogenous opioids in heart failure.

Short-term hemodynamic effects of vasopressin V1-receptor inhibition in chronic right-sided congestive heart failure.

Arginine vasopressin is elevated in congestive heart failure. To determine the effect of arginine vasopressin upon systemic hemodynamics and regional blood flows, we administered the specific inhibitor of the vascular action of vasopressin [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)-tyrosine]-arginine vasopressin [d(CH2)5Tyr(Me)AVP] to 15 dogs with chronic right-heart failure produced by tricuspid avulsion and progressive pulmonary artery constriction. The animals exhibited increased plasma arginine vasopressin and norepinephrine levels. Vasopressin inhibition increased cardiac output and left ventricular dP/dt and dP/dt/P, and it decreased total peripheral vascular resistance, whereas mean aortic pressure did not change significantly. Simultaneously, blood flow increased to skeletal muscle, kidneys, skin, and right and left ventricular myocardium. Plasma catecholamines also increased. Pretreatment with propranolol and prazosin abolished the increases in cardiac output and left ventricular function produced by vasopressin inhibition. Pretreatment also led to a decrease in mean aortic pressure after vasopressor inhibition. In contrast, administration of d(CH)2)5Tyr(Me)AVP to 11 sham-operated animals or administration of normal saline to nine sham-operated and eight heart-failure dogs was without effect either in the absence or in the presence of adrenergic receptor blockade. Thus, arginine vasopressin participates in the control of the circulation in right-sided congestive heart failure, with both a direct constrictor action on blood vessels and an indirect action by inhibition of the sympathetic nervous system.

Patterns of lactate dehydrogenase isoenzymes in serum of patients with acute pulmonary edema.

Total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum and proportions of LD isoenzymes were quantified on admission and discharge in 170 selected (from 240) patients with acute pulmonary edema (APE). The patients were divided into group A, 75 patients with normal LD values (less than 225 U/L); and groups B-E, with increased LD activity in serum: group B, 40 patients with increase in the proportion of LD-3 (greater than 38%); group C, 12 patients with increased LD-5; group D, 36 patients with an isomorphic pattern of LD isoenzymes; and group E, seven patients with LD-1/LD-2 greater than 0.75. Nine patients in group C (75%) had also signs of right-sided congestive heart failure, 30 in group D (83%) had hypotension on admission, and six in group E (86%) had signs of recent myocardial infarction. Evidently, half of patients with APE may show increased total LD activity in serum at the time of admission. LD isoenzyme proportions should be determined in such patients, because there is no one typical pattern of LD isoenzymes and some LD isoenzyme patterns may be associated with specific clinical situations.

Canine cardiomyopathy after whole heart and partial lung irradiation

The late radiation response of the heart is of concern because of many reports of heart disease following radiation therapy of thoracic tumors. This study was done because of the clinical relevance of the pathophysiology of cardiopulmonary irradiation and because the heart is a good model for late effects of vasculoconnective tissue due to its lack of acutely responding parenchymal cells. Thoracic irradiation of adult beagle dogs including the heart and one third of the lung volume produced an early response in the heart at 1 and 3 months which consisted of an increase in left ventricle and septal wall thickness, decreased left ventricle ejection fraction, increased heart rates, intraventricular conduction disturbances and a high probability for pericardial effusion at 3 months. Radiation doses were 36, 44, or 52 Gy given in 4 Gy fractions in 4 weeks. Premature atrial contractions, paroxysmal atrial tachycardia, sustained atrial tachycardia and atrial fibrillation occurred at all dose levels. Evidence suggests that both early and late responses were due, at least in part, to direct injury to the cardiac microvasculature. The later effects appeared to be enhanced by injury to the lung. The early response appeared to resolve in 6 to 9 months, after which there was thinning of the myocardium at higher doses and resolution of pericardial effusions. At 12 months, elevations in right atrial pressure, but not pulmonary wedge pressure, were suggestive of right-sided congestive heart failure. Pulmonary hypertension was also present at 12 months presumably due to partial lung irradiations, and may have exacerbated right-sided congestive heart failure. The radiation injury may continue to increase with time leading to serious deficits in cardiopulmonary function. The functional studies may aid in predicting late effects and evaluating residual injury.

Intravenous isosorbide dinitrate during open-heart surgery and its role in the treatment of right-sided congestive heart failure

Recent awareness of the importance of the functional integrity of the right ventricle and the effect of raised pulmonary vascular resistance on cardiac output after cardiopulmonary bypass has focused attention on means of protecting right ventricular myocardium and reducing right ventricular afterload during open-heart surgery. A study of the acute effects of bolus intravenous isosorbide dinitrate (ISDN) has shown that after cardiopulmonary bypass, bolus intravenous ISDN produced highly significant (p <0.001) decreases in mean pulmonary arterial pressure (13%), pulmonary vascular resistance (23%) and the ratio of pulmonary to systemic vascular resistance (20%), indicating that active pulmonary vasodilation had occurred in the absence of other hemodynamic changes. The results suggest that possibly the acute effect of low-dose ISDN after cardiopulmonary bypass is predominantly exerted on the right ventricular afterload if systemic arterial pressure is not elevated. Two different clinical situations are described in which intravenous ISDN proved beneficial, one being acute pulmonary hypertension after protamine sulphate and the second being acute right-sided congestive heart failure with systemic hypotension unresponsive to conventional therapeutic measures. Thus, ISDN may prove a useful agent for alleviating right ventricular dysfunction at a time of not infrequent cardiovascular instability, the period after bypass.

The role of endogenous opioids in congestive heart failure: effects of nalmefene on systemic and regional hemodynamics in dogs.

We studied the role of endogenous opiates and their interrelationships with the sympathetic nervous system in an experimental preparation of right-sided congestive heart failure (CHF) produced by surgical tricuspid avulsion and progressive pulmonary arterial constriction. Three groups of dogs with CHF and one group of sham-operated dogs were studied. One group of dogs with CHF was given normal saline as pretreatment, while the other two groups were pretreated with either propranolol alone (beta-blockade) or propranolol plus prazosin (alpha- plus beta-blockade). CHF was characterized by weight gain, ascites, elevated right atrial pressure, tachycardia, and reduced cardiac output. Compared with sham-operated animals, animals with CHF exhibited significantly higher baseline levels of plasma beta-endorphin and cortisol. Furthermore, only the animals with CHF responded to the opiate receptor-antagonist nalmefene with significant increases in plasma beta-endorphin, cortisol, and adrenocorticotropic hormone. Administration of nalmefene increased aortic blood pressure, cardiac output, left ventricular dP/dt and dP/dt/P, and blood flow to the myocardium, skeletal muscle, and kidneys in dogs with CHF, but had no appreciable effects in sham-operated dogs. beta-Receptor blockade abolished the increase in cardiac output, left ventricular performance, and blood flow produced by nalmefene, but had no effect on the pressor response to nalmefene. The increase in mean aortic pressure in the beta-blockade group was accompanied by an increase in skeletal muscle vascular resistance. Addition of prazosin in the alpha- plus beta-blockade group abolished the increases in mean aortic pressure and skeletal muscle vascular resistance, suggesting that the changes after propranolol probably resulted from unmasking of alpha-receptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary Manifestations of Heartworm Disease

The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.

The heart in massive (more than 300 pounds or 136 kilograms) obesity: Analysis of 12 patients studied at necropsy

Observations are described in 12 massively obese patients (5 women, 7 men), aged 25 to 59 years (mean 37), who weighed 312 to more than 500 pounds (mean 381). Seven patients had had systemic hypertension, 4 hypersomnia or sleep apnea, 2 diabetes mellitus, and 1 patient symptomatic coronary artery disease. Five patients died suddenly from undetermined causes, 2 from right-sided congestive heart failure, 1 patient from acute myocardial infarction; 1 from aortic dissection; 1 from intracerebral hemorrhage; 1 from a drug overdose, and 1 soon after an ileal bypass. The heart weight was increased in all 12 patients. The heart weight to body weight ratio expressed as a percent ranged from 0.22 to 0.61 (mean 0.37) (normal for men 0.42 to 0.46 [mean 0.43], normal for women 0.38 to 0.46 [mean 0.40]). The left ventricular cavity was dilated in 11 patients and the right ventricular cavity in all 12. Only 2 patients (aged 42 and 59 years) had 1 or more major epicardial coronary arteries narrowed greater than 75% in cross-sectional area by atherosclerotic plaque, 1 of whom had no symptoms of myocardial ischemia. Of 664 five-millimeter segments from the 4 major epicardial coronary arteries from 11 patients (mean 60 per patient), 431 (65%) were narrowed 0 to 25% in XSA, 143 (21%) were narrowed 26 to 50%, 73 (11%) were narrowed 51 to 75%, and 17 (3%) were narrowed 76 to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical Approach to Intracardiac Renal Cell Carcinoma

Renal cell carcinoma frequently extends into the vena cava, and the tumor thrombus occasionally continues into the right atrium. Patients often have symptoms of right-sided congestive heart failure of recent onset and signs of inferior vena cava obstruction. Previous reports have documented the value of very aggressive operative management in these situations; the present patient and the literature surveyed support this therapeutic approach.

Digoxin pharmacokinetics in congestive heart failure.

The steady-state pharmacokinetics of oral digoxin in eight hospitalized patients was compared upon their admission with marked right-sided congestive heart failure and later when they were compensated. Large intersubject variations in the serum digoxin concentration profiles were observed. However, over a 24-hour dosing interval, digoxin concentrations in each patient studied during heart failure were either similar or higher than those observed when the patient became compensated. There were no significant differences in digoxin half-life of elimination between the two states. In contrast, the mean ratio of the fraction of digoxin dose absorbed to its apparent volume of distribution was increased by 37 per cent (P less than 0.05) in heart failure. Contrary to the prevailing notion, we found that the oral administration of supplemental doses of digoxin only on the basis of its reduced serum concentration in patients with congestive heart failure is unwarranted.

Right atrial myxoma: unusual clinical presentation and atypical glandular histology.

A 57-year-old black female presented with a 1-month of right-sided congestive heart failure and clinical evidence of pulmonic and tricuspid valvular stenosis and insufficiency. The echocardiographic examination and ventriculography demonstrated a large right atrial tumor interfering with the function of both right-sided valves. The patient underwent successful surgical resection of the tumor. Histologically, the tumor had cellular areas typical of myxoma, as well as glandular areas, a feature which has been described very rarely in this lesion. Electron microscopy of the glandular zones, which has never been reported previously, shown cells having essential homology with the usual myxoma elements. The atypical histopathology of this lesion supports the theory that atrial myxomas are true neoplasms, and are not derived from unusually organized mural thrombi.

Modified technique for production of experimental right-sided congestive heart failure.

Experimental heart failure was produced by tricuspid insufficiency accomplished by digital avulsion of the anterior leaflet of the tricuspid valve and progressive pulmonary stenosis by progressive distension of a periarterial hydraulic occluder implanted at the base of the pulmonary artery. This technique is advantageous because it allows external regulation of the degree of pulmonary occlusion and is associated with a negligible operative mortality and consistently produces dogs with heart failure which remain otherwise healthy for many months.

Kinetocardiographic changes as the result of mitral commissurotomy

The twenty patients in this study were selected from a group in whom valvulotomy was performed for mitral stenosis at the University Hospital, and Veterans Administration Hospital, Birmingham, Alabama. These patients were chosen because kinetocardiographic records were obtained before and after the operation. The majority of patients in the group have been followed up for approximately two years after mitral surgery. In addition, several patients were included because of their unusual clinical and kinetocardiographic findings, although the follow-up period has not been as long. Table I represents the classification of the various patients into special groups to facilitate subsequent discussion. As this is a small and select series, analysis of the clinical features will not be undertaken, and only the data relevant to the interpretation of the kinetocardiograms are presented in Table I. The functional class of patients, as listed, is based upon that of the American Heart Association, and the presence of right-sided congestive heart failure is noted in each instance (indicated by the presence of pedal edema, enlarged liver, and an elevation in venous pressure). It is obvious from Table I that many of the patients in all groups were of the same functional class before surgery for mitral stenosis, while the results following the procedure varied considerably. TECHNICS

Increased aldosterone secretion in dogs with right-sided congestive heart failure and in dogs with thoracic inferior vena cava constriction.

Studies (1-5) of patients with congestive heart failure, decompensated hepatic cirrhosis and nephrosis have provided evidence of increased amounts of aldosterone or aldosterone-like substances in urine during edema or ascites formation. More recently, it has been demonstrated (6) that increased urinary excretion of aldosterone occurs in association with sodium retention in dogs with right heart failure and in dogs with ascites secondary to constriction of the thoracic inferior vena cava. The data in both man and dog imply that the blood level of aldosterone is elevated. Numerous attempts have been made to elucidate the mechanism regulating aldosterone secretion in clinical states associated with the formation of edema, but no data have been reported to show that increased circulating aldosterone results from increased secretion rather than from a decreased rate of inactivation. The purpose of this study was to determine the relative rates of secretion of aldosterone in 1) dogs with cardiac failure produced by stenosis of the pulmonary artery, 2) dogs with thoracic inferior vena cava constriction and ascites, and 3) normal dogs.