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Isolated right ventricular cardiomyopathy in a dog.

Right-sided heart failure was diagnosed in a young dog with clinical and pathologic features of isolated right ventricular cardiomyopathy. This disorder, also referred to as right ventricular dysplasia, is an infrequent cause of heart failure and sudden death in people. Echocardiography of this dog revealed right ventricular and right atrial dilatation and severe right ventricular systolic dysfunction. Left ventricular size and function were normal. Electrocardiography revealed ventricular bigeminy. The configuration of the ectopic beats was similar to that seen with left bundle branch block. The dog died suddenly, and histologic examination of the heart revealed fibroadipose replacement of right atrial and right ventricular myocardium.

Animals↗

Neonatal autoperfused working heart-lung preparation: assessment of factors determining survival.

The function and survival of the autoperfused working heart-lung preparation in the newborn period was studied in six newborn pigs (3 to 5 days old). Normothermic autoperfusion was maintained by a closed blood-primed circuit. Left ventricular afterload was determined by positioning the blood reservoir, and the venous return was adjusted to maintain a right atrial pressure of 6 to 8 mm Hg. Left ventricular function was assessed by a conductance catheter in the left ventricle and was determined by the slope of the end-systolic pressure-volume relationship. Left ventricular diastolic compliance was measured from the end-diastolic pressure-volume relationship. Serial measurements at 60, 120, 180, and 240 minutes showed no change in the end-systolic pressure-volume relationship, whereas there was a significant leftward shift of the end-diastolic pressure-volume relationship after 240 minutes (0.42 +/- 0.02 ml-1 to 0.66 +/- 0.04 ml-1, p less than 0.05). Cessation of effective cardiac function occurred at 268 +/- 10 minutes (+/- SEM). This followed progressive deterioration in pulmonary function based on measurement of arterial blood gases and peak airway resistance. This study shows the feasibility of maintaining systolic cardiac function in a newborn autoperfused working heart-lung preparation. Extended survival beyond 4 hours will require improved methods to preserve left ventricular diastolic function and especially pulmonary function.

Animals↗

Mechanism of atrial natriuretic peptide release with increased inspiratory resistance.

Elevated plasma atrial natriuretic peptide (ANP) levels and concomitant increases in renal sodium and water excretion are often encountered in respiratory diseases associated with increased airway resistance such as obstructive sleep apnea. The present study utilized an anesthetized rat model to determine the principal mechanism(s) responsible for stimulation of ANP release in this clinical syndrome. A 10-minute increase in external resistive loading, which reduced peak tracheal pressure to -15 to -17 mm Hg produced a significant increase in both central venous pressure and right atrial transmural pressure. This maneuver subsequently resulted in significant transient increases in glomerular filtration rate; urine flow; urinary Na+, K+, and Cl- excretion; and urinary cyclic guanosine monophosphate (cGMP) excretion, which was taken as an index of increased circulating levels of ANP. Similar changes in renal function and cGMP excretion occurred when arterial PO2 was lowered to a degree equivalent to that seen with increased resistive loading. Lowering arterial PO2 also significantly increased mean central venous pressure and right atrial transmural pressure. Conversely, the resistive loading-induced changes in renal function and cGMP excretion did not occur when the reduction in arterial PO2 was prevented by breathing a high O2 gas mixture during the resistive loading. Additionally, O2 supplementation prevented the increases in both mean central venous pressure and right atrial transmural pressure caused by increased resistive loading. These data indicate that the elevated ANP release that results from an acute increase in external resistive loading is not caused by a decrease in intrathoracic pressure but rather suggest that the elevated ANP release is primarily caused by an increased right atrial transmural pressure resulting from hypoxia-induced pulmonary vasoconstriction.

Airway Resistance↗

An alternative surgical technique in orthotopic cardiac transplantation.

Forty patients underwent orthotopic cardiac transplantation at Wythenshawe Hospital between May 1991 and November 1992. Twenty patients had transplantation using an alternative technique that preserves the shape of the left atrium and leaves the right atrium intact (group A). The remaining twenty had conventional transplantation using the technique described by Lower and Shumway (group B). The patients were randomized to either the new or the conventional technique on an alternate basis. There was no mortality in group A, but two patients in group B developed right ventricular failure and died. Two patients in each group developed nodal rhythm and all four recovered sinus rhythm. Echocardiography and Doppler velocimetry at the transvalvular level confirmed normal atrial function in group A with erratic atrial contraction wave in group B. There was also slightly lower incidence of mitral and tricuspid valve regurgitation in group A than in group B. The improved atrial function in group A may play a part in the prevention of right sided failure following cardiac transplantation.

Echocardiography↗

Effect of patient age at surgical intervention on long-term right ventricular performance in atrial septal defect.

Controversy exists about the influence of patient age on the benefit of surgery in atrial septal defect (ASD). Tissue Doppler echocardiography (TDE) when applied to atrioventricular annuli provides variables reliably reflecting the performance of the corresponding ventricle. We sought to investigate the effect of timing of surgery on biventricular functions by comparing the conventional echocardiography variables and TDE profiles of right and left atrioventricular annuli in patients treated at various ages. Conventional echocardiography and TDE analysis of mitral and tricuspid annuli were performed in 20 controls and 61 patients who underwent surgical ASD closure 2.8 +/- 2.5 years before the study. Standard parameters included were right and left-sided dimensions, estimated pulmonary artery pressure, ejection fraction, and tricuspid annular motion amplitude. TDE variables were systolic, early and late diastolic peak velocities at tricuspid lateral-and mitral-annulus at lateral and septal corners. Two subsets of patients who underwent surgery before (group 1, n = 20) and after 25 years (group 2, n = 41) formed our subgroups. Peak systolic TDE velocity and tricuspid annular motion amplitude had the lowest value in group 2 (P < 0.01 and <0.02, respectively). Late diastolic TDE velocity was significantly lower in group 2 compared to group 1 (P < 0.05). Increased right ventricular and atrial dimensions (P < 0.001 for both) and the estimated pulmonary artery pressure (P < 0.03) were the conventional measurements discriminating group 2 from group 1. The TDE profile of the mitral annulus was similar between the groups. These results suggest that delayed ASD closure is a relatively less effective procedure to restore secondary right ventricular dysfunction, as demonstrated by significantly different TDE measurements reflecting right ventricular longitudinal contraction and relaxation.

Adult↗

Streptokinase dissolution of a right atrial thrombus.

A critically ill 20-month-old white male with severe bronchopulmonary dysplasia, cor pulmonale, and intolerance to enteral feeds, required a left percutaneous subclavian Broviac catheter. Echocardiogram showed a right atrial thrombus, resolution of which was demonstrated after infusion of streptokinase through the Broviac catheter for 16 hours. The catheter remained in place, functioning well, for a further 4 months. The patient suffered no bleeding complications, and was spared the prohibitive risk of right atrial thrombectomy. This use of streptokinase has not previously been reported.

Cardiac Catheterization↗

Effects of carbon dioxide and pH on myocardial function in dogs with acute left ventricular failure.

The present study was undertaken to examine the effects of changes in PaCO2 and pHa on myocardial blood flow and central hemodynamics during acute ischemic left ventricular failure. Six closed-chest dogs anesthetized with pentobarbital were hyperventilated, and CO2 was added to the inspiratory gas to induce: a) normocapnia, b) hypocapnia, c) hypercapnia, and d) hypercapnia with sodium carbonate given to correct pH. Embolization of the left coronary artery with 50-microns microspheres resulted in deterioration of left ventricular function, as indicated by increased left ventricular end-diastolic pressure and mean pulmonary arterial pressure, while cardiac output decreased. During hypocapnia with left ventricular failure, the central hemodynamics remained unchanged, while a minor but nonsignificant decrease in myocardial blood flow was observed. Hypercapnia aggravated the heart failure, as indicated by increased left ventricular end-diastolic pressure, mean right atrial pressure, and mean pulmonary arterial pressure; however, the pump function of the heart was unchanged, as demonstrated by the unaltered cardiac output, heart rate, and mean aortic blood pressure. The changes in the central hemodynamics were reversed when pH was normalized during hypercapnia. Thus, in the present study pH, and not PaCO2, was responsible for the hemodynamic deterioration observed during hypercapnia in the failing heart.

Acute Disease↗

A functional study of the development of the cardiac sympathetic neuroeffector junction in the SHR.

We studied the function of the cardiac sympathetic nerve varicosity in isolated right atrial preparations of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 4, 9, 14, 20 and 50 weeks of age. Cumulative concentration-atrial period response (C-R) curves to isoprenaline showed similar maximum response and sensitivity (EC50) at all ages but there was an age-related fall in resting atrial rate. Similar results were found for methoxamine (alpha 1-adrenoceptor agonist) although the maximum response was significantly less than for isoprenaline. The time-dependent recovery (T 1/2) of the fall in atrial period in response to sympathetic nerve stimulation from electrical field pulses (1-32 at 1 Hz) was enhanced by neuronal uptake inhibition by desipramine (0.1-1 mumol/l), to a similar degree at all ages. Pre-junctional alpha 2-adrenoceptor stimulation by clonidine caused progressively more inhibition of the number of field pulses-fall in period relationship with age. SHR atria were similar to WKY rat atria at all ages except for a further impairment of the development of pre-junctional alpha 2-adrenoceptors. These studies indicate that the function of the cardiac sympathetic varicosity matures early (by 4 weeks) and overall there is very little impairment in SHR versus WKY rat atria.

Aging↗

Role of functional block extension in lesion-related atrial flutter.

BACKGROUND: A line of block in the right atrium (RA) between the venae cavae is necessary to obtain classic atrial flutter (AFL). We tested the hypothesis that the location of that line of block would determine whether the AFL reentrant circuit would be due to single-loop reentry or figure-of-8 reentry. METHODS AND RESULTS: Simultaneous mapping from 392 sites (both atria and the atrial septum) was performed in 13 normal dogs before and after creating a linear lesion on the RA free wall. The lesion was 1 to 1.5 cm anterior and parallel to the crista terminalis (7 dogs) or posterior and close to the crista terminalis region (6 dogs). Sustained AFL (>2 minutes) was then induced. In 4 dogs with an anterior lesion, the AFL reentrant circuit traveled around the lesion (lesion reentry). In 9 dogs (3 with anterior lesions and 6 with posterior lesions), the AFL reentrant circuit included the anterior RA free wall, the atrial septum, and Bachmann's bundle (single-loop reentry). In these 9 dogs, the fixed line of block was extended to the superior and/or inferior vena cava by a functional line of block, thereby preventing lesion reentry. No figure-of-8 reentry was induced. CONCLUSIONS: In this model, the location of a fixed line of block and its functional extension determine the type of AFL reentry. These data provide an explanation for the chronic AFL that occurs in some patients after surgical repair of congenital heart lesions.

Animals↗

[Current developments on the physiology of the cardiac atrial pacemaker an excitation conduction of the left atrium].

According to recent developments the atrial pacemaker area and the right atrium show a peculiar morpho-functional organization, i.e.: 1) The pacemaker area is formed of clusters of cells containing relatively few myofibrils and showing embryologic characteristics. Such cells are known as nodal cells and between these and the atrial muscles are in general situated transitional cells. Each cluster is separated from the other by collagenous boundaries. The resistance of the membranes to the current flow seems to be relatively low between the cells of the same cluster but the collagenous boundaries are, according to TRAUTWEIN e UCHIZONO (1963), very poor conductors. The pacemaker activity seems to originate inside the various clusters. 2) The functional relationships between the sinoatrial node and the atrioventricular node as well as the interatrial relationship would take place through preferential pathways. These pathways corresponding approximately to the tracts described by JAMES (1966) (anterior, posterior and middle internodal tracts) and to the interatrial or Bachmann bundle, seems to show a higher velocity conduction. In general the fibres of which the tracts are composed are neither morphologically nor functionally isolated from the atrial muscle. The functional consequences of the above mentioned nodal and atrial organization seems to be: a) The possible conditioning of the pacemaker functions by the various clusters activity i.e. the dominance of one cluster over another. b) The shifting of the pacemaker activity from one cluster to anothr due to the arrival of nervous stimuli or chemical substances, etc. According to some Authors as a consequence of the shift the pacemaker area can sometimes move out side the nodal tissue and settle inside an area belonging to the internodal pathways. c) Another consequence of the shift can be the different involvement of the conducting pathways which can lead to a change in the dynamics of the atrial invasion by the excitement.

Acetylcholine↗

Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation.

OBJECTIVE: Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS: Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox's MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. RESULTS: L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. CONCLUSIONS: Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.

Aged↗

Muscarinic cholinoceptors in the human heart: demonstration, subclassification, and distribution.

In human atrial and ventricular myocardium, the muscarinic cholinoceptor (M-cholinoceptor) populations were characterized by means of radioligand binding (with [N-methyl-3H]-scopolamine ([3H]-NMS) as the ligand) and functional experiments (negative inotropic effect of carbachol on isolated electrically driven right atrial and left papillary muscle preparations). (1) Binding of [3H]-NMS to human atrial and ventricular membranes was rapid, reversible and saturable (KD-values: 0.5-1.0 nmol/l). The maximal number of [3H]-NMS binding sites, however, was approximately 2.5-fold higher in right and left atrial membranes (200-250 fmol [3H]-NMS specifically bound/mg protein) than in right and left ventricular membranes (80-100 fmol/mg protein). (2) M-cholinoceptor antagonists inhibited [3H]-NMS binding to right atrial and left ventricular membranes with steep, monophasic competition curves indicating interaction with a single class of binding sites. In both tissues the order of potency was: atropine greater than AF-DX 116 greater than hexahydrosiladifenidol (HHSiD) greater than pirenzepine. (3) On isolated electrically driven right atrial and left papillary muscle preparations (with force of contraction enhanced by 10(-5) mol/l isoprenaline), carbachol (10(-8)-10(-4) mol/l) caused concentration-dependent decreases in force of contraction; the pD2-value for carbachol was 6.65 +/- 0.09 (n = 8, atria) and 6.62 +/- 0.08 (n = 10, papillary muscles). In both tissues M-cholinoceptor antagonists antagonized the negative inotropic effect of carbachol with an order of potency: atropine greater than AF-DX 116 greater than HHSiD greater than pirenzepine, identical to that obtained in radioligand binding experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbachol↗

Online Quantification of Cardiovascular Function in Children.

Echocardiography is the most valuable diagnostic tool in evaluating congenital anatomic pathology. Improvements in transducer resolution and development of color Doppler echocardiography have resulted in the ability to delineate cardiac anatomy in detail. Online quantification of cardiovascular function represents a similar advance in terms of evaluating physiology. Performing an online quantification examination requires attention to technical factors such as avoiding chamber foreshortening, optimizing endocardial tracking, ensuring patient cooperation, and accounting for the effects of respiration. A typical examination consists of performing acoustic quantification on the left ventricle in both short-axis and apical four-chamber views and on the left atrium from the apical four-chamber view. From these views, ventricular systolic and diastolic function, as well as atrial systolic function, can be assessed. As in adult patients, acoustic quantification indices in children correlate well with similar indices measured off line. Acoustic quantification data in children show that, unlike adults, the left ventricular filling is almost exclusively dependent on passive filling, with minimal atrial contribution. Acoustic quantification indices have also been useful in monitoring left ventricular function in intensive care and emergency department settings to evaluate the acute effects of a clinical manipulation. Acoustic quantification can also be used to assess the function of ventricles of unusual geometry such as in hypoplastic left and right heart, double-inlet single ventricle, and unbalanced atrial ventricular septal defect. In these types of ventricles, systolic and diastolic systemic ventricular function has been shown to be markedly altered compared with a normal left ventricle. Acoustic quantification can also be used to assess diastolic function in a variety of pediatric diseases, such as transplant rejection and insulin-dependent diabetes mellitus. In summary, online quantification of cardiovascular function represents a significant advance in the ability to understand cardiovascular physiology in children.

Journal Article↗

Right ventricular function in chronically anemic fetal lambs.

OBJECTIVE: Our purpose was to determine whether the increase in extravascular fluid in chronic fetal anemia occurs either because of heart failure or despite successful cardiac adaptation. STUDY DESIGN: Right ventricular function curves were obtained in five ovine fetuses at the start, midpoint, and end of 5 to 8 days of anemia induced by isovolemic daily hemorrhage. Least-squares fit of the ascending and plateau lines of stroke volume versus right atrial pressure were used to establish breakpoints (intersection of the ascending and plateau lines), which were compared by analysis of variance for repeated measures. Myocardial blood flow was measured by microspheres. RESULTS: Carotid arterial oxygen content was reduced from 7.0 +/- 0.3 to 2.1 +/- 0.1 ml/dl and the hematocrit from 29% +/- 1.8% to 13% +/- 0.6%. Breakpoint analysis of function curves showed that although right atrial pressure remained unchanged (3.4 +/- 0.7 and 3.6 +/- 0.6 mm Hg) stroke volume increased from 1.03 +/- 0.14 to 1.62 +/- 0.25 ml/kg. Both right and left ventricular coronary blood flow were increased, 1351 +/- 313 and 1166 +/- 264 ml/min per 100 gm. Excess fluid was present in abdomen and chest of most animals at autopsy. CONCLUSION: Tissue edema during severe anemia occurs despite normal right atrial pressure, increased stroke volume, and markedly increased coronary blood flow, markers of successful cardiac adaptation.

Anemia↗

Use of M-mode and Doppler echocardiography to investigate the cardiotoxicity of minoxidil in beagle dogs.

Doppler and M-mode echocardiography (EC) were used to investigate the effects of minoxidil on the cardiac function of the dog and potentially to clarify the pathogenesis of cardiac lesions, in particular the necrotic lesion in the left ventricle and the haemorrhagic lesion in the right atrium. Groups of three dogs were treated with a single oral dose of 0.5 or 2 mg/kg minoxidil or control vehicle, and M-mode and Doppler parameters were recorded at different time points before as well as 1, 3 and 24 h after treatment. The treatment produced a number of changes in M-mode parameters that indicate an increase in left ventricle contractility, in particular, increases in the percentage of thickening of the left ventricle wall during systole and in ejection fraction, and decrease of systolic volume. There was also a decrease in diastolic volume, which indicates a decrease in filling of the left ventricle probably due to the tachycardia and subsequent decrease in inter-systolic time. Doppler EC showed an increase in the velocity of the aortic flow, which indicates an increase in cardiac contractility. There was also a mild increase in stroke volume, which together with the tachycardia resulted in a marked increase in cardiac output. Together, Doppler and M-mode recordings gave evidence of an increase in the contractility of the left ventricle. This change is consistent with the generally accepted mechanism for the development of the left ventricle lesion induced by minoxidil. Minoxidil also produced changes in atrio-ventricular flows. The velocity and/or acceleration of E- and A-waves of the mitral and tricuspid flows increased, and the E/A ratio decreased. The changes in the E-wave indicate a faster diastole of the ventricle probably to compensate for the decrease in inter-systolic time. The changes in A wave are characteristic of an increased amplitude and velocity of the atrial contraction. This latter change is much more marked for tricuspid than for mitral flow. For both flows the E/A ratio decreased, which indicates that the contraction of the atria plays an increased role in ventricle filling after minoxidil treatment. This stimulation of atrial contraction that we evaluate with Doppler EC may play a key role in the development of the atrial lesion produced by minoxidil. The fact that the change is more marked in the right than in the left atrium may explain why the lesion occurs only in the right atrium in dogs. This study showed, therefore, that Doppler EC associated with M-mode EC is a useful method for obtaining pertinent information on the pathogenesis of the left ventricle lesion induced by haemodynamic mechanisms. Moreover, Doppler EC allowed the assessment of changes in the function of the right atrium that may be involved in the development of the right atrial lesion.

Animals↗

Immunosuppression switch in pediatric heart transplant recipients: cyclosporine to FK 506.

OBJECTIVES: We studied rejection, allograft function and side effects, such as hypertension, renal dysfunction and hypercholesterolemia, in seven patients switched from cyclosporine-based triple-drug immunosuppression to FK 506. BACKGROUND: A subset of pediatric heart transplant recipients treated with triple-drug immunosuppression consisting of cyclosporine, azathioprine and prednisone experience either persistent rejection when attempts are made to taper corticosteroids or morbidity from cyclosporine and corticosteroids. Experience with the new immunosuppressive agent FK 506 has demonstrated its effectiveness as a single agent in heart transplant recipients, and anecdotal evidence has shown that side effects such as hypertension and hypercholesterolemia may be lower. METHODS: Seven patients whom we deemed corticosteroid dependent were switched to FK 506-based therapy. Allograft function, episodes of rejection, need for corticosteroids and incidence of side effects from FK 506 were monitored. The switch to FK 506 was performed using an established protocol. Follow-up time has ranged from 15 to 41 months. Serial right heart catheterizations and endomyocardial biopsies were performed after each reduction of corticosteroid dosing. RESULTS: Catheterization data showed no significant change in pulmonary wedge pressure, mean right atrial pressure or cardiac index, indicating no decline in allograft function. Serial echocardiographic variables of allograft function were also stable. At present, all seven patients are free of the corticosteroid portion of their immune suppression. There have been only two episodes of significant acute rejection requiring treatment with intravenous corticosteroids. Antihypertensive medications have been discontinued in five of six patients previously treated with these drugs. Plasma cholesterol, low density lipoprotein and triglyceride levels were decreased, and renal function was stable. CONCLUSIONS: Preliminary studies suggest that FK 506 may be an alternative immunosuppressive agent for pediatric and adolescent patients experiencing ongoing rejection or significant morbidity from cyclosporine and corticosteroids and in those patients dependent on corticosteroids for immune suppression.

Adolescent↗

Effects of pharmacologic autonomic blockade on atrial electrophysiologic properties in normal subjects and in patients with sinus node disease.

In order to elucidate the influence of autonomic nervous system on atrial electrophysiologic properties, we studied 10 patients with sinus node dysfunction and 10 age-matched normal subjects. In each of them effective and functional refractory periods of the right atrium (near its junction with the superior caval vein) were measured, during atrial pacing (100/min) and using variable current strengths (2, 3, 4, 5, 7, 10, and 15 mA), before and after pharmacologic autonomic blockade (using intravenous propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Mean values of effective and functional refractory periods at each current strength were significantly higher in patients with sinus node disease than in normal subjects both before and after autonomic blockade. Blockade did not significantly modify mean values of effective and functional refractory periods at any current strength, either in patients with sinus node disease or in normal subjects. Furthermore, autonomic blockade did not change the effects of the increase of current strength on atrial refractoriness in either group. We conclude that our data indicate a prolonged refractoriness to be present in patients with sinus node disease even in the absence of influences from the autonomic nervous system. Thus, we can suggest a "primary" involvement of atrial fibers in this pathophysiological condition. Propranolol together with atropine did not induce changes of atrial refractoriness. Indeed, they probably exerted an opposite effect. The effects of the increase of current strength on atrial excitability do not seem to be mediated by autonomic humoral agents.

Aged↗

Cardiac phosphocreatine deficiency induced by GPA during postnatal development in rat.

The effect of chronic administration of beta-guanidinopropionic acid (GPA) on the protein profiling, energy metabolism and right ventricular (RV) function was studied in the rat heart during the weaning and adolescence period. GPA was given in tap water (1-1.5%) using pair drink controls. The feeding of animals with GPA solution for a six week period resulted in elevation of heart to body weight ratio due to body growth retardation. GPA accumulated in the myocardium up to 67.37 +/- 5.3 mumoles.g dry weight and the tissue content of total creatine, phosphocreatine and ATP was significantly decreased to 15%, 9% and 65% of control values respectively. Total activity of creatine kinase (CK) was not changed, but the proportion of mitochondrial (Mi) CK isoenzyme was decreased; the percentage of MB isoenzyme of CK was significantly higher. GPA treatment resulted in an elevation of the content of cardiac collagenous proteins and decrease of non-collagenous proteins in the heart; in parallel, a decrease of the collagen I to collagen III ratio was detected. The function of the RV was assessed using an isolated perfused heart with RV performing pressure-volume work. As compared to pair-drink controls, RV function was significantly impaired the GPA group: at any given right atrial filling pressure, the RV systolic pressure and the rate of pressure development were decreased by almost a factor of two. Elevation of the RV diastolic pressure with increasing pulmonary artery diastolic pressure was also significantly steeper in the GPA group which also showed decrease of cardiac output, especially at high outflow resistance. It may be assumed that chronic administration of GPA deeply influenced metabolic parameters, protein profiles and contractile function of the developing heart. On the other hand, concentrations of glucose, total lipids and triglycerides in blood plasma were not affected. All these data confirm the concept that the CK system is of central importance both for heart function and for the regulation of normal growth of cardiac myocytes.

Animals↗