Dose Of Captopril Research Articles

Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na(+)/H(+) exchanger isoform 3 (NHE3), Na(+)/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 microg/min for 20 min) that increased PT flow rate approximately 20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng x kg(-1) x min(-1) for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H(+)-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.

Optimization of chitosan, sodium carboxy methyl celulose and magnesium stearat as mucoadhesive system in captopril tablet

Captopril is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of congestive heart failure. It has been reported that the duration of antihypertensive action after a single oral dose of captopril is only 6–8 h. Captopril is most stable at acidic condition and as the pH increases, it becomes unstable and undergoes a degradation reaction. These indicates a promising potential of the captopril mucoadhesive system as an alternative to the conventional dosage form. The objective of the current study was to find an optimum formula of mucoadhesive tablet for captopril using factorial design. Tablets were evaluated for mucoadhesive strength and drug release profile. The studies were perfomed to establish composition of chitosan, sodium CMC and Mg stearat. Such composition could produce mucoadhesive strength with a zero order release kinetics. A 23 factorial design has been applied to systematically optimize the formula. The amounts of chitosan (XA), sodium CMC (XB), and Mg stearat (XC) were selected as independent variables. Mucoadhesive strength and dissolution efficiency (DE480) were selected as dependent variables. According the contour plot suggested that optimum formula will be reach mucoadhesive strength (26-30 g) and DE480 (≥70 %) chitosan at low to middle level (20-35 mg), sodium CMC at middle to high level (150-200 mg), and Mg stearat at low to middle level (4-6 mg). Key words : mucoadhesive, factorial design, DE480 , chitosan, CMC Na, Mg stearat, contour plot

Synthesis, Synchrotron X-ray Diffraction, and Kinetic Studies on the Formation of a Novel Thiolatocobalamin of Captopril: Evidence for cis-trans Isomerization in the β-Axial Ligand.

The orally administered therapeutic captopril is widely used for treating hypertension, congestive heart failure, and cardiovascular disease. However, a number of undesirable side effects are associated with high doses of captopril. By coordinating a therapeutic to the upper (= beta) axial site of the naturally occurring macrocycle cobalamin (vitamin B(12)), the absorption and cellular uptake of the therapeutic can be significantly enhanced. We report the synthesis of captopril-cobalamin, a derivative of vitamin B(12) in which captopril is bound via its thiol group at the beta-axial site of cobalamin. Characterization of captopril-cobalamin by (1)H NMR spectroscopy and X-ray diffraction shows that captopril-cobalamin exists in both solution and the solid state as a mixture of geometric isomers. Kinetic studies on the formation of captopril-cobalamin have been carried out, and the data fits a model in which the thiol form (RSH, k(1) = 40.9 +/- 1.2 M(-1) s(-1)) and the thiolate form of captopril (RS(-), k(2) = 660 +/- 170 M(-1) s(-1)) react rapidly with aquacobalamin.

Long-Term Trophic Effect of Sodium Restriction on the Rat Adrenal Zona Glomerulosa. I. Its Partial Independence of the Renin-Angiotensin System

The mechanism of the trophic effect of chronic sodium restriction on the zona glomerulosa of the rat adrenals was investigated by combined morphometric and biochemical techniques. In the normal rats, prolonged sodium deprivation caused a significant hypertrophy of the zona glomerulosa and its parenchymal cells, coupled with a conspicuous rise in the plasma concentration of aldosterone. Analogous results were observed in animals simultaneously administered captopril and maintenance doses of angiotensin II. However, in this last case, the changes were significantly lower than those observed in the normal rats. These findings are compatible with the view that the activation of the renin-angiotensin system is not the sole mechanism involved in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa induced by chronic sodium restriction.

Antihypertensive Effect of a Polyphenol-Rich Cocoa Powder Industrially Processed To Preserve the Original Flavonoids of the Cocoa Beans

A natural flavonoid-enriched cocoa powder, commercially named CocoanOX and developed via a patented industrial process, was characterized and tested for a possible antihypertensive effect. The bioavailability of this polyphenol-rich cocoa powder developed at pilot scale was previously demonstrated in humans. The present results showed that this product was very rich in total procyanidins (128.9 mg/g), especially monomers, dimers, and trimers (54.1 mg/g), and mainly (-)-epicatechin (19.36 mg/g). The effect of a single oral administration of CocoanOX in spontaneously hypertensive rats (SHR) was evaluated at different doses (50, 100, 300, and 600 mg/kg). This product produced a clear antihypertensive effect in these animals, but these doses did not modify the arterial blood pressure in the normotensive Wistar-Kyoto rats. Paradoxically, the maximum effect in the systolic blood pressure (SBP) of SHR was caused by 300 mg/kg of CocoanOX. This dose brought about a decrease in this variable very similar to that caused by 50 mg/kg Captopril. It was also surprising that the maximum effect in the diastolic blood pressure (DBP) was caused by 100 mg/kg CocoanOX. The initial values of DBP and SBP were recovered in SHR, respectively, 24 and 48 h postadministration of the different doses of CocoanOX or Captopril. These results suggest that CocoanOX could be used as a functional ingredient with antihypertensive effect, although it would be also necessary to carry out bioavailability and clinical studies to demonstrate its long-term antihypertensive efficiency in humans.

Synergistic decrease in blood pressure by captopril combined with losartan in spontaneous hypertensive rats

This study was designed to examine the anti-hypertensive effect of the combination therapy of captopril with losartan by oral administration using both independent and cross-over experimental protocols. In independent experimental protocols, four different groups of spontaneous hypertensive rats (SHR) were treated for 1 or 2 weeks: control, captopril (20 mg/kg/day), losartan (20 mg/kg/day), and combination captopril (10 mg/kg/day) with losartan (10 mg/kg/day). In cross-over protocols, each SHR received all four treatments for 1 or 3 days with an interval of several days between each injection for washing-out and return to high blood pressure (BP) levels. BP and heart rate (HR) were measured in conscious telemetered SHR. According to the results from the independent protocol, regardless of a 1- or 2-week administration period, combination therapy with low doses of captopril and losartan had a greater anti-hypertensive effect than individual high-dose monotherapy. Similarly, results from the cross-over protocol showed that regardless of 1-day or 3-day administration, the decrease in BP in the 11(th) and 12(th) hour after administration was greatest with the combination of low-dose captopril and losartan. Therefore, combination therapy with low doses of captopril with losartan lowered BP to a greater extent than a high dose of either individual monotherapy.

Drug Dosing for Renoprotection

The maximum recommended therapeutic dose (MRTD) of a drug is an important limit not only for the manufacturer but also for physicians and their patients.1 Limits are derived from a dose-response curve that represents the combination of optimal efficacy and highest safety. The MRTD is established during the developmental phase of a drug. An error in that process may be very costly for both the manufacturer and patients. For example, when looking at the development of drugs altering the renin-angiotensin-aldosterone system (RAAS), there are interesting examples of “mistakes.” Captopril was the first practical drug to target the RAAS in the angiotensin-converting enzyme inhibitor (ACEI) class. During initial testing, the drug was given at dosages of 450 mg/d. Although BP was very effectively lowered, these dosages produced adverse effects such as decreases in renal function, increases in albuminuria, and skin rashes.2 Too high a dosage was later determined as the reason for these unwanted effects. Ironically, subsequent ACEIs, including lower dosages of captopril, were used to reduce albuminuria and provide renoprotection.3 When the first drug in a second new class targeting RAAS, the angiotensin II receptor blockers (ARBs), was launched, the manufacturer and regulators did not want to make the same mistake twice, and care was taken in establishing the MRTD for losartan at 50 mg/d. The choice of this dosage may have been too …

Lack of Interaction Between the Peptidomimetic Substrates Captopril and Cephradine

Intestinal peptide transporters, including hPEPT1, facilitate the absorption of cephalosporins and angiotensin-converting enzyme inhibitors, and have been investigated as a means to improve oral drug absorption. Renal peptide transporters including hPEPT2, may also facilitate renal reabsorption of such compounds. In vitro and animal studies suggest that co-administration of peptidomimetic compounds may alter oral pharmacokinetics, although this has not been well studied in humans. The purpose of this study was to determine whether co-administration of the hPEPT substrates captopril and cephradine alters the oral pharmacokinetics of either agent. Nine healthy male volunteers received a single oral 25-mg dose of captopril, a single oral 500-mg dose of cephradine, or concurrent ingestion of captopril and cephradine in a cross-over manner. Venous blood samples were taken and captopril and cephradine pharmacokinetics were determined using noncompartmental analyses. No significant differences were observed in captopril or cephradine pharmacokinetics when administered together as compared to each agent alone (a marginal decrease in C(max) was observed for both captopril and cephradine during co-administration [5-15%]; however, differences were not statistically significant). The results of our study suggest that hPEPT1 and hPEPT2 are unlikely to contribute to clinically important drug interactions in humans.

Isoflavone genistein inhibits the angiotensin-converting enzyme and alters the vascular responses to angiotensin I and bradykinin

Genistein produces antihypertensive and beneficial cardiovascular effects, although the mechanisms for these effects are not known. We examined whether genistein inhibits the in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetized rats as a result of angiotensin-converting enzyme inhibition. We have also studied the in vitro effects produced by genistein on the angiotensin-converting enzyme activity. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03 to 10 µg/kg, by angiotensin II in doses of 0.01 to 3 µg/kg, and to bradykinin in doses of 0.03 to 10 µg/kg in anaesthetized rats pretreated with vehicle (controls), or a single i.v. dose of genistein 25 mg/kg, or daily genistein 25 mg/kg i.v for two days, or a single i.v. dose of captopril 2 mg/kg. Plasma angiotensin-converting enzyme activity was determined in controls and genistein-treated rats using a fluorometric method. The effects of genistein (3–300 µmol/l) on in vitro angiotensin-converting enzyme activity were assessed by adding genistein to plasma samples and measuring angiotensin-converting enzyme activity. We found significant lower angiotensin-converting enzyme activity in plasma samples from rats pretreated with genistein compared with those found in the Control group (77.7 ± 8.1 his-leu nmol/min/ml and 108.7 ± 8.4 his-leu nmol/min/ml, respectively; P = 0.01). The incubation of genistein with plasma samples showed that genistein decreased the angiotensin-converting enzyme activity in plasma in a concentration-dependent manner ( P < 0.01). These findings indicate that genistein inhibits the angiotensin-converting enzyme in vivo and in vitro and may explain, at least in part, the antihypertensive and beneficial vascular effects produced by genistein.

Right atrial stretch alters fore‐ and hind‐brain expression of c‐fos and inhibits the rapid onset of salt appetite

The inflation of an intravascular balloon positioned at the superior vena cava and right atrial junction (SVC-RAJ) reduces sodium or water intake induced by various experimental procedures (e.g. sodium depletion; hypovolaemia). In the present study we investigated if the stretch induced by a balloon at this site inhibits a rapid onset salt appetite, and if this procedure modifies the pattern of immunohistochemical labelling for Fos protein (Fos-ir) in the brain. Male Sprague-Dawley rats with SVC-RAJ balloons received a combined treatment of furosemide (Furo; 10 mg (kg bw)(-1)) plus a low dose of the angiotensin-converting enzyme inhibitor captopril (Cap; 5 mg (kg bw)(-1)). Balloon inflation greatly decreased the intake of 0.3 m NaCl for as long as the balloon was inflated. Balloon inflation over a 3 h period following Furo-Cap treatment decreased Fos-ir in the organum vasculosum of the lamina terminalis and the subfornical organ and increased Fos-ir in the lateral parabrachial nucleus and caudal ventrolateral medulla. The effect of balloon inflation was specific for sodium intake because it did not affect the drinking of diluted sweetened condensed milk. Balloon inflation and deflation also did not acutely change mean arterial pressure. These results suggest that activity in forebrain circumventricular organs and in hindbrain putative body fluid/cardiovascular regulatory regions is affected by loading low pressure mechanoreceptors at the SVC-RAJ, a manipulation that also attenuates salt appetite.

Chronic high dose captopril decreases total heart rate variability and increases heart rate in C57BL/6J mice

The effects of high dose captopril, within the therapeutic range, on autonomic activity are unknown in those with normal cardiovascular function. Thus the study aims were to assess the effects of high dose captopril on autonomic function in mice. Autonomic activity was measured using heart rate variability (HRV). ECG recordings were obtained from 18 Male C57BL/6J mice (20–25 g) subdivided into control ( N = 8) or mice receiving oral captopril (0.688 mg/ml captopril in the drinking water for 6 weeks, N = 10). HRV results for linear and non-linear parameters were attenuated following chronic captopril for 6 weeks compared to control. Captopril was associated with a trend for an increase in average heart rate and approximate entropy (ApEn), a non-linear measure of HRV decreased significantly compared to control ( p < 0.05). In conclusion high dose captopril reduces total HRV and increases heart rate in normotensive mice with normal cardiac function.

Effect of Picrorrhiza Rhizoma Extracts on Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

The hypoglycemic effect of an aqueous extract of Picrorrhiza Rhizoma (PR) was investigated on diabetic nephropathy. The body weight of each of eight rats per group was measured 7 days after streptozotocin (STZ) treatment. The blood glucose levels 3 days after STZ treatment and the changes in body weight, kidney weight, blood glucose levels, and serum blood urea nitrogen (BUN) were also measured, and the histopathology of the kidney was examined. Body weight decreases and increases of kidney weight, blood glucose levels, and serum BUN and creatinine levels were detected in the diabetic control with histopathological changes related to diabetic nephropathy in the kidney. However, the level of hyperglycemia was significantly lowered in all groups given the PR extract. In addition, the changes related to diabetic nephropathy with the body weight were also significantly lower in the captopril and all PR extract-dosing groups than in the diabetic control. In conclusion, an aqueous extract of PR has relatively good inhibitory effects on STZ-induced diabetes with early diabetic nephropathy with a similar efficacy to an equal dose of captopril.

Side effects of angiotensin converting enzyme inhibitor (captopril) in newborns and young infants

To analyze the side effects of captopril, an angiotensin converting enzyme inhibitor (ACEI) in newborn and young infants. Retrospective analysis of side effects in 43 patients with congenital heart disease after cardiac surgery treated with captopril for heart failure during a two-year period. Median age of the patients was 26 days (range 6-310 days), median weight 3.5 kg (range 1.9-7.9 kg). Initial median dose of captopril was 0.17 mg/kg/day (range 0.05-0.55 mg/kg/day), slowly increased over 3-33 days to a maximal median dose of 1.86 mg/kg/day (range 0.2-2.3 mg/kg/day). All patients were additionally treated with diuretics. Side effects occurred in 17 patients (renal impairment or failure in 6, low blood pressure in 8, and oxygen saturation deficit in 3) requiring cessation or interruption in seven patients with renal impairment/failure (n=4), hypotension (n=1) and aorto-pulmonary shunting with low pulmonary perfusion (n=2). The six children who developed renal impairment or failure did so following a median delay of nine days after reaching the final dose and weighed on average 500 g less than the other patients (P=0.046). All side effects were fully reversible. Side effects due to captopril were not dose-related in newborns and infants in this study. However, renal side effects occurred more often in smaller infants. Routine monitoring of infants on ACEI should include renal function tests, blood pressure and transcutaneous oxygen saturation measurements.

Effect of L-5-Hydroxytryptophan on drinking behavior in Coturnix japonica (Temminck and Schlegel, 1849) (Galliformes: Aves): involvement of renin-angiotensin system

The purpose of this study was to explore the role of L-5-hydroxytryptophan (L-HTP) and its relationship with the renin-angiotensin system (RAS) on the drinking behavior in Japanese quails. Normally-hydrated quails that received injections of L-HTP (12.5; 25 and 50 mg.kg-1) by the intracoelomic route (ic) expressed an increase in water intake, which was inhibited by captopril, an angiotensin converting enzyme (ACE) inhibitor. In addition, captopril also induced such a response in birds under previous fluid deprivation. High doses of captopril (35-70 mg.kg-1, sc) in normally-hydrated quails decreased the spontaneous water intake while low doses of captopril (2-5 mg.kg-1, sc) did not prompt water intake after L-HTP administration. Losartan, an AT1 receptor antagonist in mammals, did not change the water intake levels in normally-hydrated or water-deprivated birds. Serotonin (5-HT) injections did not provoke its known dipsogenic response.

Serotonergic receptor blockade in the lateral parabrachial nucleus: Different effects on hypertonic and isotonic NaCl intake

Hypertonic NaCl intake is produced by serotonin receptor antagonism in the lateral parabrachial nucleus (LPBN) of dehydrated rats or in rats pretreated with a mineralocorticoid, for example deoxycorticosterone (DOCA), that receive an intracerebroventricular injection (icv) of angiotensin II (ang II). The objective of the present work was to find out whether these two mechanisms are also involved with isotonic NaCl intake. Serotonin receptor blockade by methysergide in the LPBN (4 μg/0.2 μl bilaterally) had no effect on 0.15 M NaCl (methysergide: 19.3 ± 5.2 ml/60 min; vehicle: 19.3 ± 4.2 ml/60 min; n = 7) or water (methysergide: 3.4 ± 1.4 ml/60 min; vehicle 2.2 ± 0.6 ml/60 min) intake induced by systemic diuretic furosemide combined with low dose of captopril (Furo/Cap). Methysergide treatment 4 days later in the same animals produced the expected enhancement in the 0.3 M NaCl intake induced by Furo/Cap (methysergide: 16.6 ± 3.5 ml/60 min; vehicle: 6.6 ± 1.5 ml/60 min). Similar result was obtained when another group was tested first with 0.3 M NaCl and later with 0.15 M NaCl. Isotonic NaCl intake induced by icv ang II was however enhanced by prior DOCA treatment. A de novo hypertonic NaCl intake was produced in another group by the same combined treatment. The results suggest that a facilitatory mechanism like the mineralocorticoid/ang II synergy may enhance NaCl solution intake at different levels of tonicity, while the action of an inhibitory mechanism, like the LPBN serotonergic system, is restricted to the ingestion at hypertonic levels.

Therapeutic Actions of Allylmercaptocaptopril and Captopril in a Rat Model of Metabolic Syndrome

Hypertension often coexists with hyperlipidemia, insulin resistance, and glucose intolerance in metabolic syndrome. Allylmercaptocaptopril is a conjugate of the angiotensin-converting enzyme inhibitor captopril with allicin, an active principle in garlic with multiple beneficial actions on metabolic-syndrome abnormalities. We sought to test the hypothesis that the conjugation of allicin to captopril may confer additional therapeutic actions in metabolic disease. We compared allylmercaptocaptopril (53.5 mg/kg/day orally for 60 days) to an equimolar dose of captopril (40 mg/kg/day) in the spontaneously hypertensive, obese rat (SHROB) model. Allylmercaptocaptopril prevented progressive weight gain, without a detectable effect on food intake. Both captopril and allylmercaptocaptopril lowered blood pressure, but allylmercaptocaptopril was more effective. Allylmercaptocaptopril, but not captopril, improved cardiac hypertrophy, as indicated by heart weight and ventricular-wall thickness. Allylmercaptocaptopril improved, whereas captopril impaired, oral glucose tolerance after a fast. Triglycerides were decreased by both captopril and allylmercaptocaptopril. Total cholesterol and non-HDL cholesterol were reduced by captopril but not by allylmercaptocaptopril. The SHROB rats developed severe glomerulosclerosis and renal failure. Allylmercaptocaptopril showed significant nephro-protection, as indicated by reductions in urinary protein loss, urinary protein-to-creatinine ratio, and plasma creatinine. Captopril showed the same trends and also prevented the decline of creatinine clearance. Finally, both allylmercaptocaptopril and captopril reduced the basal level of lipolysis in isolated abdominal adipocytes, and restored the response to catecholamine stimulation. Both captopril and allylmercaptocaptopril are effective in attenuating multiple abnormalities of metabolic syndrome. Allylmercaptocaptopril may have additional effectiveness on improving glucose tolerance, further lowering blood pressure, reducing cardiac hypertrophy, preventing weight gain, and protecting against renal disease.

Variations in captopril formulations used to treat children with heart failure: a survey in the United kingdom

Background and objective: Different liquid formulations of a drug prepared for use in children cannot be assumed to have therapeutic equivalence. The objective of this study was to ascertain the...

Therapeutic actions of allylmercaptocaptopril (BL‐2040) in the SHROB rat model of metabolic syndrome and glomerulosclerosis

The spontaneously hypertensive obese (SHROB) rat is a model of obese hypertension which spontaneously develops end stage renal disease. BL-2040 is a conjugate of the ACE inhibitor captopril with allicin, an antioxidant in garlic. We compared BL-2040 (53.5 mg/kg/d orally for 60d) to an equimolar dose of captopril (40 mg/kg/d). Both agents lowered blood pressure, but BL-2040 was more effective. Triglycerides were decreased by both captopril and BL-2040. Total and non-HDL cholesterol were reduced by captopril but not BL-2040. BL-2040 showed significant nephroprotection, as indicated by reductions in urinary protein loss (control: 179±26; captopril: 134±29; BL-2040: 86±17mg/d), urinary protein/creatinine, and plasma creatinine. Finally, both BL-2040 and captopril reduced the basal level of lipolysis in isolated abdominal adipocytes and restored the response to catecholamine stimulation. Both captopril and BL-2040 are effective in attenuating metabolic syndrome. BL-2040 may have additional effectiveness on improving glucose tolerance, lowering blood pressure, reversing cardiac hypertrophy and retarding renal disease.

Treatment of Combined Aortic Regurgitation and Systemic Hypertension: Insights From an Animal Model Study

Hypertension (HT) and aortic valve regurgitation (AR) often coexist but the specific impacts of AR + HT on the left ventricle (LV) are still unknown. The best treatment strategy for this combination of diseases is also unclear. The objectives of this study were 1) to evaluate LV function, remodeling and 2) to assess the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril (C) in rats with AR +/- HT in spontaneously hypertensive rats (SHR). Animals were grouped as follows: normotensive (NT) Wistar-Kyoto, NT + AR, hypertensive SHR (HT), and HT + AR receiving or not captopril (150 mg/kg/d). Hearts were evaluated in vivo by echocardiography and harvested for tissue analysis after 6 months of evolution. The HT + AR rats had the worst LV hypertrophy (LVH), subendocardial fibrosis, and lowest ejection fraction. Captopril normalized BP in HT and HT + AR, but could not prevent LVH in HT + AR as well as it did in isolated HT. The LV ejection fraction remained below normal in HT + AR + captopril compared to HT alone + captopril. Cardiomyocyte hypertrophy remained in HT + AR + captopril but was normalized in HT + captopril. Subendocardial fibrosis was reduced by captopril in HT + AR. The AR + HT rats had the most severe myocardial abnormalities. High dose captopril was effective to slow LVH and preserve normal LV ejection fraction in isolated HT or AR, but was less effective when both pathologies were combined. Prohypertrophic stimuli clearly remain active in HT + AR despite ACE inhibition. These results suggest that a very aggressive medical treatment strategy may be required to optimize LV protection when AR and HT co-exist.

Recovery of Left Ventricular Systolic Function After Biventricular Resynchronization Pacing in a Child With Repaired Tetralogy of Fallot and Severe Biventricular Dysfunction

A 5-year-old child had undergone surgical repair of a ventricular septal defect and pulmonary stenosis at the age of 4 months. The repair required a total of 3 episodes of cardiopulmonary bypass and was complicated by complete atrioventricular block. Subsequently, a permanent dual-chamber pacemaker was implanted, with epicardial leads on the right atrium and the right ventricular outflow tract. Late postoperative complications included atrial ectopic tachycardia, controlled with amiodarone, and progressive left ventricular systolic dysfunction, treated with increasing doses of digoxin, captopril, furosemide, and hydrochlorothiazide-spironolactone. The patient was referred to our center for ongoing …