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Biomedical subjects

L G Ribeiro

Publications and source records attributed to L G Ribeiro.

At least 19 recordsLinked to original sources
PubMed1988

Effects of two nonsulfhydryl angiotensin-converting enzyme inhibitors, CGS 14831 and CGS 16617, on myocardial damage and left-ventricular hypertrophy following coronary artery occlusion in the rat.

The present study was designed to examine the effects of two new angiotensin-converting enzyme (ACE) inhibitors, CGS 14831 and CGS 16617 (3 mg/kg i. v. 1 min prior to occlusion and 4 and 24 h after occlusion), on myocardial ischemic (MI) damage and left-ventricular hypertrophy in rats. Administration of CGS 14831 or CGS 16617 inhibited angio-tensin-I-induced pressor responses by 40-100% for 4 h after each dose. Myocardial creatine phosphokinase (CK) levels were 10.6 +/- 0.6 U/mg protein in sham-MI animals, and following coronary artery occlusion for 48 h were decreased to 4.1 +/- 0.2 U/mg protein in MI + vehicle animals (p less than 0.01). CGS 14831 and CGS 16617 attenuated the decrease in CK content and resulted in 47 and 40% sparing, respectively, of the left-ventricular free wall. Neither agent attenuated the left-ventricular hypertrophy which developed following coronary artery occlusion. These data indicate that the nonsulfhydryl ACE inhibitors CGS 14831 and CGS 16617 have a significant cardioprotective effect in rats surviving 48 h, and suggest a potential therapeutic usefulness of these agents for the treatment of ischemia-induced heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Increased survival in rats with congestive heart failure treated with enalapril.

Vasodilating drugs such as angiotensin converting enzyme (ACE) inhibitors may extend life expectancy in patients with congestive heart failure (CHF). The purpose of this study was to evaluate whether long-term therapy (365 days) with enalapril (ENAL, an ACE inhibitor), would prolong life in rats with a healed myocardial infarction (MI), an experimental model with hemodynamic characteristics of CHF. Seven days after sham or coronary ligation, when the healing phase of MI was well underway, 132 rats (75 sham, 57 MI) were randomized to receive either enalapril in the drinking water (17-25 mg/L, approximately 1.0 mg/kg/day) or tap water. The date of spontaneous death was recorded, and heart weight and MI size (by planimetry) were determined. Serum ENAL, total ACE concentration, and angiotensin and methoxamine pressor responses were quantified in 12 survivors. Long-term enalapril prolonged survival (p = 0.014) with a median 50% survival of 164 (164-165) days, compared to 84 (64-104) days in rats receiving tap water. There were twice as many MI rats alive at the end of one year on angiotensin converting enzyme inhibition (ACEI) therapy as compared to the untreated group. The average MI size (39-40%) was not different between groups, and there was a significant inverse correlation between date of death and MI size (r = 0.7-0.8) in both treatment groups. Cardiac hypertrophy was evident in all MI rats. Serum ENAL levels, after one year, were at the clinically relevant concentration (2.3 ng/ml) and total serum ACE (inhibitor removed) doubled to 4,300 nmol/h/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Limitation of myocardial infarct size by metabolic interventions that reduce accumulation of fatty acid metabolites in ischemic myocardium.

The effects on myocardial damage of metabolic interventions by nicotinic acid, oxfenicine, or a combination of the two were assessed in open-chest dogs exposed to coronary artery occlusion for 6 hours. The accumulation of metabolites of free fatty acids (FFAs) was studied in tissue samples of the left ventricle taken 60 minutes after coronary occlusion in separate animals. The percentage of the hypoperfused zone that evolved to infarction was 96 +/- 3% (mean +/- SEM) in control dogs, 74 +/- 4% in dogs treated with nicotinic acid (p less than 0.05 vs control dogs), 72 +/- 2% in dogs treated with oxfenicine (p less than 0.05 vs control dogs), and 54 +/- 5% in dogs with combined nicotinic acid and oxfenicine (p less than 0.05 vs control dogs, p less than 0.05 vs nicotinic acid and oxfenicine). Arterial FFA concentration was markedly reduced in dogs treated with nicotinic acid and those treated with combination nicotinic acid and oxfenicine. The accumulation of long-chain acyl carnitine was substantially reduced in the ischemic myocardium after nicotinic acid, oxfenicine, and a combination of the two, whereas the lowering of long-chain acyl CoA was less pronounced. Thus, nicotinic acid and oxfenicine, which depress myocardial FFA metabolism by different mechanisms, both reduce myocardial infarct size and their effects are additive.

Acetylcarnitine↗
PubMed1986

Enalapril in experimental hypertension and acute heart failure: comparison with calcium channel blockers.

The hemodynamic effects of enalaprilat (MK-422) and lisinopril (MK-521) were compared with the calcium channel blocker felodipine in dogs with ischemic left ventricular (LV) failure. The combination of nitrendipine plus enalapril was also examined in ischemic failure and in rats with spontaneous hypertension. In anesthetized dogs coronary embolization with 50 micron plastic microspheres reduced cardiac output and LV dP/dt max by approximately 40%, and LV end-diastolic pressure increased to greater than 13 mm Hg. Enalaprilat and lisinopril reduced mean arterial pressure by a maximum of 20 mm Hg and total peripheral resistance by approximately 30%. Left ventricular dP/dt:LVP, which was substantially decreased by embolization, was slightly increased by both angiotensin converting enzyme (ACE) inhibitors. The calcium entry blockers felodipine and nitrendipine qualitatively produced many of the same hemodynamic effects as the ACE inhibitors, but, in addition, they markedly reduced coronary resistance, increased myocardial blood flow, and did not alter cardiac contractility (LV dP/dt max). In spontaneously hypertensive rats single doses of nitrendipine (1.25 to 5.0 mg/kg per os) and enalapril (0.3 and 3.0 mg/kg per os) reduced mean arterial pressure, but differences were observed in the onset (enalapril 2 h versus nitrendipine 0.5 h), the duration of action, and magnitude of effect. In terms of blood pressure lowering, nitrendipine, 5.0 mg/kg per os, was clearly additive to 3.0 mg/kg per os of enalapril, but other combinations (enalapril, 3 mg/kg per os plus 0.625 mg/kg of nitrendipine or enalapril, 0.3 mg/kg per os plus 0.625 mg/kg nitrendipine) were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Effects of lisinopril, a new angiotensin converting enzyme inhibitor in a cryo-injury model of chronic left ventricular failure.

The angiotensin converting enzyme inhibitor, lisinopril, was studied in a cryo-injury model of chronic heart failure. This model is characterized by a progressive decrease in cardiac output starting six weeks after cryo-injury to a 30% decrease in cardiac output 10 weeks after injury. Although histological damage to the myocardial tissue, particularly in the epicardial area, was observed, no significant changes occurred in body weight, mean arterial blood pressure, heart rate or central venous pressure. Daily intraperitoneal injection of 3 mg/kg lisinopril was instituted starting four weeks after injury for a duration of six weeks. Lisinopril completely restored the cardiac output to normal values at the end of this six week period. Thus, converting enzyme inhibition appears to be an effective therapeutic agent in this model of chronic cardiac failure.

Animals↗
PubMed1985

Hemodynamic effects of synthetic atrial natriuretic factor (ANF) in dogs with acute left ventricular failure.

The hemodynamic and renal electrolyte/function effects of a synthetic peptide (ANF) corresponding to the sequence of the 26 amino acids contained in atrial natriuretic factor (ANF) were assessed in closed-chest dogs in which acute left ventricular failure was produced by coronary artery embolization with 50 micron plastic microspheres. Coronary embolization produced a sustained reduction in cardiac contractility (LV dP/dtmax) and cardiac output which averaged 42 and 44%, respectively. Following a 45 min equilibration period after heart failure induction, most of the hemodynamic functions stabilized. At this time, ANF infused intravenously at 100 pmol/kg per min X 30 min (n = 9) did not lower mean arterial pressure although it increased cardiac output (P less than 0.05) by 17% at only one time period. With the exception of a fall in coronary resistance and an increase in myocardial blood flow, a higher dose of ANF (200 pmol/kg per min) did not consistently alter hemodynamic function. Fractional excretion of sodium (FE Na%) increased 3.4-fold with ANF at 100 pmol/kg per min and 1.8-fold with the 200 pmol/kg per min dose. Neither dose of ANF produced significant effects on renal blood flow (RBF) or glomerular filtration rate (GFR). Plasma angiotensin II which was 91 +/- 20 fmol/ml at baseline increased to 175 +/- 25 fmol/ml (P less than 0.05) 45 min after heart failure induction. However, neither dose of ANF significantly reduced these high circulating angiotensin II levels. These results demonstrate that an infusion of a synthetic ANF stimulated saluresis without altering RBF or GFR, and improved cardiac output in dogs with acute left ventricular failure.

Angiotensin II↗
PubMed1985

Preservation of ischemic myocardium by a new converting enzyme inhibitor, enalaprilic acid, in acute myocardial infarction.

Enalaprilic acid (MK-422), the biologically active diacid of the converting enzyme inhibitor enalapril, was studied in myocardial ischemia (MI). Acute left coronary artery ligation was produced in 62 male Sprague-Dawley rats, and infarct size was determined by left ventricular free wall (LVFW) creatine kinase (CK) activity. Administration of enalaprilic acid (2 mg/kg) 2 minutes and 24 hours after MI significantly blunted the reduction in LVFW CK activity at 48 hours after ligation, when compared to the MI rats given vehicle (6.4 +/- 0.5 vs 4.7 +/- 0.2 IU/mg protein, respectively; p less than 0.01). The percentage of LVFW spared was significantly (p less than 0.01) increased from 28 +/- 2% to 45 +/- 5% by MK-422. MK-422 also significantly blunted the loss of LVFW CK activity 48 hours after a coronary ligation (10 minutes) followed by reperfusion, when compared to vehicle (10.1 +/- 0.6 vs 8.3 +/- 0.6 IU/mg protein, respectively; p less than 0.05). This represents a significant increase in the percentage of LVFW spared, 65 +/- 5% vs 85 +/- 6% (p less than 0.05). These data indicate a significant protective action afforded by MK-422 in two different protocols of ischemic damage to the myocardium and suggest a role for the renin-angiotensin system in the extension of ischemic damage.

Angiotensin II↗
PubMed1985

Regional myocardial lidocaine concentration determines the antidysrhythmic effect in dogs after coronary artery occlusion.

Ischemic ventricular dysrhythmias were produced in 40 of 47 anesthetized mongrel dogs by high ligation of the left anterior descending coronary artery. Dysrhythmias were treated with a single iv bolus of 20, 40, 80, or 120 mg of lidocaine (L) in order to determine the dose at which approximately 50% of animals had an antidysrhythmic response. Cardiac output and regional myocardial blood flow (RMBF) were measured by using radionuclide labeled microspheres. Lidocaine concentration [( L]) was measured from samples of arterial and venous blood and normal and ischemic myocardium. All dogs treated with 40, 80, or 120 mg of L had an antidysrhythmic effect. However, with 20 mg of L the dysrhythmia persisted in 12 and resolved in 14. With 20 mg of L, ischemic myocardial [L] was greater in dogs with an antidysrhythmic effect than in those with persistent dysrhythmias (1.14 +/- 0.12 vs. 0.76 +/- 0.04 micrograms X g-1), but no difference was seen for arterial, venous, and normal myocardial [L]. Ischemic RMBF was higher in the dogs that had an antidysrhythmic effect than in those that did not, 9.8 +/- 1.5 versus 6.9 +/- 1.3% of normal. With 20 mg of L, [L] in ischemic myocardium correlated well with ischemic RMBF. The antidysrhythmic response to L had a threshold at a tissue concentration of greater than or equal to 1.0 microgram X g-1 (chi-square = 8.55, P less than 0.005). For this model, the [L] in ischemic myocardium during acute ischemia correlates with the antidysrhythmic response to L, while the concentration in normal myocardium or blood does not.

Animals↗