Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of nitroglycerin and sodium nitroprusside in patients with acute myocardial infarction and signs of cardiac insufficiency was studied. These drugs reduced the increased pressure in the pulmonary artery. The systemic arterial pressure also reduced, but more markedly under the effect of nitroglycerin. Nitroglycerin often reduced the cardiac rhythm rate, whereas sodium nitroprusside caused no changes or increased it. Counterpulsation with an intra-aortic balloon was conducted in cardiogenic shock. The most marked positive changes in systemic arterial pressure occurred under the effect of counterpulsation. Changes in the cardiac output and pulmonoarterial pressure were much less conspicuous. The favourable dynamics disappeared in most patients after counterpulsation was discontinued.
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PMID:[Nitroglycerin, sodium nitroprusside and intra-aortic counterpulsation in acute myocardial infarct]. 678 24

The radioactive microsphere technique was used to trace regional blood flow and total cardiac output distribution in rats in heart failure secondary to biventricular volume overload during acute intravenous infusion of nitroglycerin. Data from rats with heart failure (chronic arteriovenous shunt) were compared to data obtained from rats subjected to sham surgical procedures. In both glycerin and normal saline (control). In heart failure, nitroglycerin slightly increased cardiac output at rest and during exercise, increased stroke volume, and reduced systemic vascular resistance at rest but not during exercise. In the heart failure group, exercise reduced flow to the renal, gastrointestinal, and cutaneous circulations but had little or no effect in the sham group. Nitroglycerin dramatically increased renal, gastrointestinal, and cutaneous blood flow during exercise in the heart failure group but had minimal effects on active hyperemia in the skeletal muscle bed. In the sham group, nitroglycerin decreased blood flow in the renal, gastrointestinal, and cutaneous beds and had no effect on skeletal muscle blood flow. Thus, in the renal, gastrointestinal, and cutaneous circulations during exercise, nitroglycerin increased flow in the heart failure group and decreased flow in the sham group to the extent that the respective values in the two groups were equal.
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PMID:Mechanism of action of nitroglycerin during exercise in a rat model of heart failure. Improvement of blood flow to the renal, splanchnic, and cutaneous beds. 678 98

Nitroglycerin (Ng) is a potent and short-acting coronary and systemic vasodilator, widely used in anginal pain treatment. When given to patients with pneumonia or chronic lung disease, Ng was found to cause a further decrease in arterial oxygen tension (PaO2) by increased perfusion of poorly ventilated territories in the lungs. In order to investigate the potential hazard in Ng decreasing the PaO2 in ischemic heart disease patients, who develop acute pneumonia, we administered 0.4 mg Ng sublingually to 11 patients who suffered concomitantly from ischemic heart disease and acute pneumonia. Arterial blood gases were monitored before, 2, 5 and 10 min following Ng administration, as well as a standard 12-lead electrocardiogram that was monitored as the same time. 8 out of the 11 patients showed a decrease in PaO2 which was mild to moderate, during the study period of time, none of them showed an increase, and there was tendency for the lower (less than 60 mm Hg) initial PaO2 to show a lesser decrease in the PaO2 in comparison to the higher (greater than 60 mm Hg) initial PaO2. There was no statistical significant correlation between the decrease in PaO2 and patients' age, sex, coexisting chronic obstructive lung disease and severity of systemic heart failure. Our conclusion is that the hazard in lowering PaO2 by Ng in ischemic heart disease patients who develop acute pneumonia is minimal, but the drug should be used with caution.
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PMID:Arterial hypoxemia following the administration of sublingual nitroglycerin in patients with ischemic heart disease and pneumonia. 679 69

Glyceryl trinitrate (GNT, 0.8 mg) was administered in a spray to 15 coronary patients of whom 7 had a pulmonary wedge pressure (PWP) greater than 16 mm Hg on exercise (subgroup I) and the others (subgroup II) had a normal PWP at rest and during exercise. At rest, GNT increased heart rate and decreased cardiac output, systolic index, stroke work index, right atrial pressure, pulmonary wedge and mean systemic pressures in all patients. Peripheral resistances did not change. During exercise, GNT lowered PWP, systemic arterial pressure and peripheral resistances in all cases. It increased cardiac output as well as systolic and stroke work indices only in patients of subgroup I. In subjects with coronary disease, no overt cardiac failure but elevated PWP on exercise, GNT in a spray can quickly improve exercise capacity and hemodynamic reserves and increase anginal threshold.
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PMID:Hemodynamic response to glyceryl trinitrate in a spray at rest and during exercise in a sitting position. 680 31

Effects of three representative vasodilators on peripheral and cardiac hemodynamics were studied in 20 patients with heart failure due to acute myocardial infarction (PCWP greater than 18 mmHg, C1 greater than 2.20 L/min/m2) using venous occlusion plethysmography and a Swan-Ganz catheter. Sublingual isosorbide dinitrate (ISDN) significantly increased calf venous capacitance (CVC) from 5 to 60 min (p less than 0.01) and calf blood flow (CBF) in the initial 15 min (p less than 0.05), while simultaneously lowering PCWP (p less than 0.05) and central venous pressure (p less than 0.05). Calf vascular resistance (CVR), cardiac index, blood pressure, and total systemic peripheral resistance (TSPR) were not affected significantly. Nitroglycerin ointment (NGO) significantly decreased CVR (p less than 0.05) and increased CVC (p less than 0.05) from 60 to 240 min, simultaneously with lowering of PCWP (p less than 0.01), central venous pressure (p less than 0.05), and TSPR (p less than 0.05). Oral prazosin (Pz) increased CBF (p less than 0.01) and CVC (p less than 0.05) from 60 to 240 min, simultaneously with significant lowering of PCWP (p less than 0.01) and TSPR (p less than 0.05), resulting in increased stroke work index (p less than 0.05). These data confirm that ISDN predominantly causes capacitance vessel dilatation and reduce excessive venous return, while Pz and NGO dilate not only capacitance vessels but also resistance vessels, consequently reducing systemic vascular resistance and resulting in increased peripheral blood flow and cardiac performance. It was observed that the higher the base-line calf vascular resistance rose, the better the response to the vasodilator treatment appeared in terms of a decrease in calf vascular resistance.
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PMID:Unloading effects of vasodilators on peripheral circulation and cardiac hemodynamics in patients with acute myocardial infarction. 681 69

Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF.
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PMID:[Effects of carperitide (alpha-human atrial natriuretic peptide) on acute congestive heart failure in dogs]. 851 7

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the reduction of venous tone by its nitrate properties. Nicorandil may prove to be useful in the treatment of acute ischemic heart failure.
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PMID:Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin. 989 Apr 2

Nitroglycerin (glyceryl trinitrate, GTN), originally manufactured by Alfred Nobel, has been used to treat angina and heart failure for over 130 years. However, the molecular mechanism of GTN biotransformation has remained a mystery and it is not well understood why "tolerance" (i.e., loss of clinical efficacy) manifests over time. Here we purify a nitrate reductase that specifically catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from GTN, leading to production of cGMP and relaxation of vascular smooth muscle both in vitro and in vivo, and we identify it as mitochondrial aldehyde dehydrogenase (mtALDH). We also show that mtALDH is inhibited in blood vessels made tolerant by GTN. These results demonstrate that the biotransformation of GTN occurs predominantly in mitochondria through a novel reductase action of mtALDH and suggest that nitrite is an obligate intermediate in generation of NO bioactivity. The data also indicate that attenuated biotransformation of GTN by mtALDH underlies the induction of nitrate tolerance. More generally, our studies provide new insights into subcellular processing of NO metabolites and suggest new approaches to generating NO bioactivity and overcoming nitrate tolerance.
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PMID:Identification of the enzymatic mechanism of nitroglycerin bioactivation. 1206 Jul 25

Glyceryl trinitrate (GTN) is used in the treatment of angina pectoris and cardiac failure, but the rapid onset of GTN tolerance limits its clinical utility. Research suggests that a principal cause of tolerance is inhibition of an enzyme responsible for the production of physiologically active concentrations of NO from GTN. This enzyme has not conclusively been identified. However, the mitochondrial aldehyde dehydrogenase (ALDH2) is inhibited in GTN-tolerant tissues and produces NO2- from GTN, which is proposed to be converted to NO within mitochondria. To investigate the role of this enzyme in GTN tolerance, cumulative GTN concentration-response curves were obtained for both GTN-tolerant and -nontolerant rat aortic rings treated with the ALDH inhibitor cyanamide or the ALDH substrate propionaldehyde. Tolerance to GTN was induced using both in vivo and in vitro protocols. The in vivo protocol resulted in almost complete inhibition of ALDH2 activity and GTN biotransformation in hepatic mitochondria, indicating that long-term GTN exposure results in inactivation of the enzyme. Treatment with cyanamide or propionaldehyde caused a dose-dependent increase in the EC50 value for GTN-induced relaxation of similar magnitude in both tolerant and nontolerant aorta, suggesting that although cyanamide and propionaldehyde inhibit GTN-induced vasodilation, these inhibitors do not affect the enzyme or system involved in tolerance development to GTN. Treatment with cyanamide or propionaldehyde did not significantly inhibit 1,1-diethyl-2-hydroxy-2-nitrosohydrazine-mediated vasodilation in tolerant or nontolerant aorta, indicating that these ALDH inhibitors do not affect the downstream effectors of NO-induced vasodilation. Immunoblot analysis indicated that the majority of vascular ALDH2 is present in the cytoplasm, suggesting that mitochondrial biotransformation of GTN by ALDH2 plays a minor role in the overall vascular biotransformation of GTN by this enzyme.
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PMID:Role of mitochondrial aldehyde dehydrogenase in nitrate tolerance. 1457 60

Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.
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PMID:Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. 1644 63


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