Browsing by Author "CORBALAN, R"
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- ItemCHANGES IN CYCLIC-AMP-DEPENDENT PROTEIN-KINASE AND ACTIVE STIFFNESS IN THE RAT VOLUME OVERLOAD MODEL OF HEART HYPERTROPHY(ELSEVIER SCIENCE BV, 1993) LAVANDERO, S; CARTAGENA, G; GUARDA, E; CORBALAN, R; GODOY, I; SAPAGHAGAR, M; JALIL, JEObjective: The aim was to clarify the role of cyclic AMP dependent protein kinase (PKA) and changes in mechanical heart function during development of cardiac hypertrophy induced by volume overload. Methods: Protein and DNA contents, PKA activity, and peak systolic stress-strain relationships in hearts from animals submitted to aortocaval shunt were assessed as a function of time. Sham operated (control) rats were used as controls. Results: Heart weight to body weight ratio and cardiac protein content per heart increased from d 7 (p<0.005 and p<0.01, respectively) reaching their highest values by d 56; the same occurred with cardiac DNA content. PKA activity.g-1 tissue in soluble extracts of hearts from rats with aortocaval shunt increased by 2.7-fold on d 2 (p<0.005), reached a ninefold peak increase by d 7 (p<0.0001) and declined to fourfold by d 56 with respect to control values. The end peak systolic stress-strain relation slopes were: control, 368(SEM 14) g.cm-2 (n=16); aortocaval shunt values: 2 d, 514(28) g.cm-2 (n=6); 7 d, 579(10) g.cm-2 (n=7); and 56 d, 554(28) g.cm-2 (n=7). The force generating capacity at 0% strain was also significantly higher in the shunt groups as compared to sham operated controls (p<0.01). Early activation of PKA was also confirmed through endogenous cardiac protein phosphorylation. SDS-PAGE gel electrophoretogram and autoradiography showed more heavily phosphorylated bands in aortocaval shunt hearts than in the control group. Conclusions: PKA activity and the slope of systolic stress-strain regression line followed a similar trend throughout the study, with an early increase in both variables by d 2 in the shunt group, reaching a peak at d 7, and decreasing thereafter but remaining higher than in controls. PKA activity appears to be related to increased force generating capacity rather than to hypertrophy or increased cardiac protein content. Thus PKA activation is an early biochemical event after aortocaval shunt, followed later by cardiac hypertrophy. Changes in PKA activity showed a similar trend to mechanical heart function over time. These findings help to explain the changes in the mechanical properties of the heart preceding the development of cardiac hypertrophy in the rat model of volume overload.
- ItemEFFECT OF A CALCIUM INHIBITOR, NIFEDIPINE, ON EXERCISE TOLERANCE IN PATIENTS WITH ANGINA-PECTORIS - A DOUBLE-BLIND-STUDY(1981) CORBALAN, R; GONZALEZ, R; CHAMORRO, G; MUNOZ, M; RODRIGUEZ, JA; CASANEGRA, PThe effect of nifedipine on exercise tolerance was studied in 30 patients with stable angina and positive graded exercise testing. Treadmill exercise testing was performed on each of 5 consecutive days. Placebo or nifedipine, 10 mg sublingually, was given 30 min before exercise on the 3rd day. The following day the intervention was reversed in a double-blind manner. Angina was abolished by nifedipine but not by placebo in 12 patients (40%). The time to onset of angina in the remaining patients increased from 4.1 .+-. 0.4 (SEM [standard error of mean]) to 6.7 .+-. 0.6 min (P < 0.001). Time to ST depression .gtoreq. 2 mm increased from 4.0 .+-. 0.3 to 5.4 .+-. 0.5 min, while duration of exercise increased from 6.3 .+-. 0.3 to 8.2 .+-. 0.4 min (P < 0.001). The maximum heart rate was 145 .+-. 3.3 with nifedipine and 122 .+-. 3.8 min-1 with placebo (P < 0.01). Resting systolic blood pressure decreased 30 min after nifedipine administration from 131 .+-. 3.4 to 106 .+-. 2.9 mm Hg (P < 0.01). Maximal systolic blood pressure during exercise was lower with nifedipine (127 .+-. 4.8 mm Hg) than with placebo (155 .+-. 8.6 mm Hg, P < 0.01). Nifedipine significantly improves the exercise tolerance of patients with stable angina pectoris by decreasing peripheral vascular resistance and myocardial O2 demand.
- ItemEFFECTS OF CAPTOPRIL VERSUS MILRINONE THERAPY IN MODULATING THE ADRENERGIC NERVOUS-SYSTEM RESPONSE TO EXERCISE IN CONGESTIVE HEART-FAILURE(1990) CORBALAN, R; JALIL, J; CHAMORRO, G; CASANEGRA, P; VALENZUELA, PThe potential adverse consequences of increased adrenergic nervous system activity in patients with heart failure are now recognized. Modulation of the plasma noradrenaline response to submaximal exercise should be desirable. The long-term (9 weeks) effects of milrinone (10 mg 4 times a day) or captopril (50 mg 3 times a day) compared to placebo were evaluated in a double-blind crossover study, in 16 patients with stable, congestive heart failure receiving digoxin and furosemide. After treatment, clinical status (score range 0 to 14 points) improved significantly with both milrinone (4.4 .+-. 0.5, p < 0.01) and captopril (4.1 .+-. 0.4, p < 0.01). Plasma noradrenaline at rest was similar with both drugs and not significantly different from placebo. During submaximal exercise it increased significantly to 1,295 .+-. 174 pg/ml with milrinone; this response was reduced significantly with captopril, to 820 .+-. 100 pg/ml (p < 0.01). Thus, long-term therapy with both captopril and milrinone improved the clinical score, but only captopril reduced the plasma noradrenaline response to submaximal exercise. These findings suggest that angiotensin-enzyme inhibition with captopril will modulate the adrenergic system response to daily activities in patients with chronic congestive heart failure and therefore could have additional salutary effects beyond vasodilatation.
- ItemEFFECTS OF NIFEDIPINE DURING LOW, NORMAL AND HIGH INTAKES OF SODIUM IN PATIENTS WITH ESSENTIAL-HYPERTENSION(1982) VALDES, G; SOTO, ME; CROXATTO, HR; BELLOLIO, T; CORBALAN, R; CASANEGRA, P
- ItemRISK-FACTORS FOR SYSTEMIC EMBOLISM IN PATIENTS WITH PAROXYSMAL ATRIAL-FIBRILLATION(MOSBY-ELSEVIER, 1992) CORBALAN, R; ARRIAGADA, D; BRAUN, S; TAPIA, J; HUETE, I; KRAMER, A; CHAVEZ, AThe purpose of this study was to define the risk factors for systemic embolism in patients with recently diagnosed paroxysmal atrial fibrillation. We therefore studied 63 consecutive patients with symptomatic nonvalvular paroxysmal atrial fibrillation and performed a clinical and noninvasive cardiac, peripheral vascular, and neurologic evaluation that included two-dimensional echocardiography, 24-hour Holter monitoring, and computed tomographic brain scan. Patients with predisposing clinical conditions for systemic embolism (valvular heart or coronary artery disease) or paroxysmal atrial fibrillation (sick sinus disease, preexcitation, or thyroid dysfunction) were excluded. At entry 34 patients had idiopathic paroxysmal atrial fibrillation and 29 had hypertension. Fourteen patients had a recent systemic embolic complication: nine had a recent occlusive nonlacunar cerebrovascular accident, two had transient ischemic attacks, and three had peripheral systemic emboli that required surgery. In addition, five patients had evidence of old cerebrovascular accident on the computed tomographic scan (group 1). Forty-four patients had no systemic embolism (group 2). Results of univariate analysis showed that patients in group 1 were older (72 +/- 9 vs 63 +/- 13 years, p < 0.05), had a higher incidence of hypertension (70% vs 35%, p < 0.01), and had an increased left atrial diameter (4.1 +/- 0.7 vs 3.6 +/- 0.5 cm, p < 0.05). Multiple stepwise logistic regression analysis showed that a history of hypertension and left atrial enlargement on two-dimensional echocardiography were significant independent risk factors for systemic embolism in patients with symptomatic nonvalvular paroxysmal atrial fibrillation.
- ItemROLE OF PROGRAMMED ELECTRICAL-STIMULATION OF THE HEART IN RISK STRATIFICATION POST-MYOCARDIAL INFARCTION(1988) GONZALEZ, R; ARRIAGADA, D; CORBALAN, R; CHAMORRO, G; FAJURI, A; RODRIGUEZ, JA