Loading...
(1/563) Inhibition of beta-myosin heavy chain gene expression in pressure overload rat heart by losartan and captopril.

AIM: To study the effects of losartan and captopril on beta-myosin heavy chain (MHC), and alpha-MHC gene expression. METHODS: Pressure overload was produced by abdominal aortic coarctation (AAC) in rats. alpha- and beta-MHC mRNA were measured by Northern blot. RESULTS: In left ventricular myocardium of sham-operated rats, the alpha-MHC mRNA predominated, while the beta-MHC mRNA was only detectable. In response AAC, there was a 70-fold increase in the beta-MHC mRNA (P < 0.01), while alpha-MHC mRNA reduced to 26% (P < 0.01). Losartan (3 mg.kg-1.d-1, i.g. for 11 d) to AAC rats caused inhibitions of beta-MHC by 96% and alpha-MHC by 86% gene expression without lowering blood pressure. A reduction in beta-MHC mRNA was also seen in captopril-treated rats (30 mg.kg-1.d-1, i.g. for 11 d), but the inhibitory effect of captopril on alpha-MHC mRNA was less than that of losartan (44% vs 86%, P < 0.05). CONCLUSIONS: The shift of MHC isoform induced by pressure overload is due to up-regulation of beta-MHC and down-regulation of alpha-MHC gene expression. Inhibition of beta-MHC gene expression by losartan is achieved primarily by direct blockade of angiotensin II type I receptors in the myocardium, independent on hemodynamics.  (+info)

(2/563) Biventricular repair approach in ducto-dependent neonates with hypoplastic but morphologically normal left ventricle.

OBJECTIVES: Increased afterload and multilevel LV obstruction is constant. We assumed that restoration of normal loading conditions by relief of LV obstructions promotes its growth, provided that part of the cardiac output was preoperatively supported by the LV, whatever the echocardiographic indexes. BACKGROUND: Whether to perform uni- or biventricular repair in ducto dependent neonates with hypoplastic but morphologically normal LV (hypoplastic left heart syndrome classes II & III) remains unanswered. Echocardiographic criteria have been proposed for surgical decision. METHODS: Twenty ducto dependent neonates presented with this anomaly. All had aortic coarctation associated to multilevel LV obstruction. Preoperative echocardiographic assessment showed: mean EDLW of 12.4 +/- 3.03 ml/m2 and mean Rhodes score of -1.73 +/-0.8. Surgery consisted in relief of LV outflow tract obstruction by coarctation repair in all associated to aortic commissurotomy in one and ASD closure in 2. RESULTS: There were 3 early and 2 late deaths. Failure of biventricular repair and LV growth was obvious in patients with severe anatomic mitral stenosis. The other demonstrated growth of the left heart. At hospital discharge the EDLVV was 19.4+/-3.12 ml/m2 (p = 0.0001) and the Rhodes score was -0.38+/-1.01 (p = 0.0003). Actuarial survival and freedom from reoperation rates at 5 years were 72.5% and 46%, respectively. CONCLUSIONS: Biventricular repair can be proposed to ducto dependent neonates with hypoplastic but morphologically normal LV provided that all anatomical causes of LV obstruction can be relieved. Secondary growth of the left heart then occurs; however, the reoperation rate is high.  (+info)

(3/563) A family study of coarctation of the aorta.

Families of 100 patients with coarctation of the aorta and 50 controls for age, sex, and social status were studied to assess the influence of genetic and environmental variables in the aetiology. A tendency to familial aggregation of the condition and other congenital heart defects compatible with multifactorial inheritance was discerned. Recurrence risk for sibs is approximately 1 in 200 for coarctation of the aorta, and 1% for any form of congenital heart defect. The heritability of coarctation is estimated at 58%. The tendency for other non-cardiac defects to occur in the patients with coarctation does not appear in their sibs and is not so pronounced as in some other congenital heart conditions. Of the several environmental variables examined, there was no definitive association with any other than season of birth, which implies a possible association with maternal infection; there is also a suggestion of a paternal age effect, but these require investigation in a prospective survey.  (+info)

(4/563) Long-term effects of balloon angioplasty on systemic hypertension in adolescent and adult patients with coarctation of the aorta.

AIMS: To define the long-term effect of balloon angioplasty of aortic coarctation on hypertension, in adolescent and adult patients. METHODS: Balloon angioplasty of discrete, native aortic coarctation was performed on 50 patients (34 male) aged 23+/-8 (mean+/-standard deviation) years. In 42 of these patients cardiac catheterization and angiography were repeated 1 year later, and on the basis of sphygmomanometric blood pressure determination at that time, they were divided into 31 patients (group A) with normalized blood pressure and 11 patients (group B) who still needed antihypertensive medication. Both groups were followed annually thereafter for 12-123 (66+/-37) months. RESULTS: Coarctation gradient values before, immediately after and 1 year after angioplasty were 69+/-24 mmHg, 12+/-8 mmHg (P<0.001) and 7+/-6 mmHg. The corresponding systolic blood pressure values were 165+/-17 mmHg, 128+/-12 mmHg (P<0.001) and 115+/-10 mmHg (P<0.001) in group A; 182+/-21 mmHg, 141+/-24 mmHg (P<0.001) and 134+/-18 mmHg (P<0.001) in group B. Echocardiographic left ventricular mass index before angioplasty and at follow-up was 130+/-31 g x m-2 and 105+/-23 g x m-2 in group A; 157+/-38 g x m-2 and 132+/-35 g x m-2 in group B (P<0.001 for both comparisons). CONCLUSION: Normalization of blood pressure without medication occurred in 74% of patients after angioplasty for aortic coarctation, with subsequent long-term regression of left ventricular hypertrophy. In comparison to reported surgical results, balloon angioplasty should be considered as first line treatment for native, discrete aortic coarctation in adolescent and adult patients.  (+info)

(5/563) Effects of aminopeptidase P inhibition on kinin-mediated vasodepressor responses.

We studied in anesthetized rats whether aminopeptidase P (AMP) may be involved in bradykinin (BK) metabolism and responses. For this we inhibited AMP with the specific inhibitor apstatin (Aps). Studies were done with Aps alone or together with the angiotensin-converting enzyme inhibitor lisinopril (Lis). Aps increased the vasodepressor response to an intravenous bolus of BK (400 ng/kg): vehicle, -3.0 +/- 0.7 mmHg; Aps, -7.8 +/- 0.7 mmHg (P < 0.01 vs. vehicle); Lis, -23.8 +/- 1.8 mmHg; Aps + Lis, -37.5 +/- 1.9 mmHg (P < 0.01 vs. Lis). Aps did not affect the vasodepressor response to BK given into the descending aorta. Plasma BK increased only in Aps + Lis-treated rats (in pg/ml): control, 48.0 +/- 1.4; Lis, 57.5 +/- 7.6; Aps + Lis, 121. 8 +/- 30.6 (P < 0.05 vs. control or Lis), whereas in rats infused with BK (400 ng. kg-1. min-1 for 5 min), Aps increased plasma BK (in pg/ml): control, 51.9 +/- 2.5; Aps, 83.5 +/- 20.5; Lis, 725 +/- 225; Aps + Lis, 1,668 +/- 318 (P < 0.05, Aps vs. control and Lis vs. Aps + Lis). In rats with aortic coarctation hypertension, the acute antihypertensive effects of Aps plus Lis were greater than Lis alone (P < 0.01). Hoe-140, a BK B2-receptor antagonist, abolished the difference. We concluded that in the rat AMP contributes to regulation of BK metabolism and responses.  (+info)

(6/563) Critical pathways for postoperative care after simple congenital heart surgery.

OBJECTIVE: To evaluate the clinical, financial, and parent/patient satisfaction impact of critical pathways on the postoperative care of pediatric cardiothoracic patients with simple congenital heart lesions. STUDY DESIGN: Critical pathways were developed by pediatric intensive care nurses and implemented under the direction of pediatric cardiothoracic surgeons. PATIENTS AND METHODS: Critical pathways were used during a 12-month study on 46 postoperative patients with simple repair of atrial septal defect (ASD), coarctation of the aorta (CoA), and patent ductus arteriosus (PDA). Using the study criteria, a control group of 58 patients was chosen from 1993. Prospective and control group data collected included postoperative intubation time, total laboratory tests, arterial blood gas utilization, morphine utilization, time in the pediatric intensive care unit, total hospital stay, total hospital charges, total hospital cost, and complications. Variances from the critical pathway and satisfaction data were also recorded for study patients. RESULTS: Resource utilization was reduced after implementation of critical pathways. Significant reductions were seen in total hours in the pediatric intensive care unit, total number of laboratory tests, postoperative intubation times, arterial blood gas utilization, morphine utilization, length of hospitalization (ASD, 4.9 to 3.1 days; CoA, 5.2 to 3.2 days; and PDA, 4.1 to 1.4 days; all P < 0.05), total hospital charges (ASD, $16,633 to $13,627; CoA, $14,292 to $8319; and PDA, $8249 to $4216; all P < 0.05), and total hospital costs. There was no increase in respiratory complications or other complications. Patients and families were generally satisfied with their hospital experience, including analgesia and length of hospitalization. CONCLUSIONS: Implementation of critical pathways reduced resource utilization and costs after repair of three simple congenital heart lesions, without obvious complications or patient dissatisfaction.  (+info)

(7/563) Stent implantation in an adult with coarctation of the aorta in the presence of advanced secondary heart failure.

We report the case of a 56-year-old woman with congenital coarctation of the aorta, who presented in critical clinical condition with advanced secondary cardiomyopathy and heart failure. We successfully applied an unusual technique to pass the aortic obstruction, and then implanted a PALMAZ stent. The procedure resulted in prompt clinical improvement and completely resolved the coarctation. The patient's improved clinical condition was still evident 11 months after the procedure.  (+info)

(8/563) Cyclooxygenase-2 inhibition decreases renin content and lowers blood pressure in a model of renovascular hypertension.

It has been proposed that the macula densa participates in the regulation of increased renin expression in renovascular hypertension (RVH) and that prostaglandins may be among the mediators of macula densa function. We have previously shown that in renal cortex, cyclooxygenase-2 (COX-2) expression is localized to the macula densa and surrounding cortical thick ascending limb and increases in high-renin states, such as salt restriction and angiotensin-converting enzyme inhibition. In the present studies, we examined the effect of the selective COX-2 inhibitor SC58236 on plasma renin activity (PRA) and renal renin expression in RVH in rats. The aorta was coarcted between right and left renal arteries, and animals received either SC58236 or vehicle for 1 week. At day 8, vehicle-treated coarcted rats were hypertensive (mean carotid arterial blood pressure: 138+/-3 versus 87+/-2 mm Hg in sham-operated controls; n=9 to 11; P<0.001) and exhibited a disparity of kidney size (ratio left/right kidney: 0.78+/-0.04 versus 1.02+/-0.02; n=9 to 10; P<0.001). PRA increased significantly (84.6+/-6.5 versus 9.0+/-1.4 ng angiotensin I [Ang I] per milliliter per hour; n=8 to 9; P<0.01). In the coarcted rats, neither renin mRNA expression nor renin activity of the right kidney was altered (renin/GAPDH mRNA: 1.12+/-0.05-fold levels in control rats; n=6; P=NS; renin activity: 23.4+/-1.8 versus 27.1+/-3.4 ng Ang I per hour per milligram protein; n=8 to 9; P=NS). However, the renin mRNA of the left kidney increased to 3.0+/-0.6-fold of control (n=6), and the renin activity increased to 189.0+/-28.6 ng Ang I per hour per milligram protein (n=8; P<0.01). Expression of COX-2 mRNA and immunoreactive protein increased in the affected left kidney but was not different from control in the unaffected right kidney. SC58236 treatment to coarcted rats did not affect kidney size (ratio left/right kidney: 0.79+/-0.06; n=9). However, PRA was significantly decreased compared with the vehicle-treated coarcted rats (19.8+/-2. 8 ng Ang I per milliliter per hour; n=9; P<0.01). The left kidney renin mRNA and renin content were also decreased (1.7+/-0.3-fold control; n=6; P<0.05; and 45.7+/-7.6 ng Ang I per hour per milligram protein; n=9; P<0.01, respectively), while renin mRNA and renin content of the right kidney were not altered. SC58236 lowered mean arterial blood pressure (122+/-5 mm Hg; n=14; P<0.05 compared with vehicle). A significant correlation was observed between PRA and mean blood pressure (r=0.75; P<0.01). In summary, these studies indicate that the selective COX-2 inhibitor SC58236 decreases renin production and release in RVH and suggest an important role for COX-2 regulation of the renin-angiotensin system.  (+info)