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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-eclampsia and 'essential' hypertension in pregnancy require to be studied separately. Their haemodynamic characteristics need to be determined and the effects of antihypertensive therapy and blood volume expansion explored. Diuretics should be used in pre-eclampsia only to treat cardiac failure. Hydrallazine may be contraindicated if cardiac failure is imminent. The role of propranolol remains undecided and a controlled trial is required. Studies of the renin-angiotensin system which take into account the various factors that alter renin secretion may prove useful.
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PMID:The haemodynamic pathophysiology of pre-eclampsia. 699 61

Neural control of renin secretion is an important physiologic mechanism, but alterations in the central nervous system feedback and control of renin release in heart failure have not been investigated. Accordingly we studied conscious dogs after volume overload (arteriovenous fistula) or chronic myocardial infarction. Acute infusion of nitroprusside was used to test the renin response to arterial hypotension and decreased central blood volume. Hydralazine and prazosin administration were used to test the response to chronic vasodilator administration. After 4 weeks of volume overload or 3 weeks after myocardial infarction, the renin response to a graded hypotensive stimulus was blunted. After 7 days of hydralazine or prazosin administration, plasma renin activity remained elevated and blood volume increased from baseline values. Our results indicate a decrease in the neural feedback control of renin release after chronic volume overload or myocardial infarction. However, chronic vasodilator administration still resulted in sustained augmented renin secretion and an increase in blood volume.
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PMID:Changes in control of renin release in congestive heart failure in dogs: response to acute and chronic vasodilator therapy. 704 41

Arterial oxygen transport (cardiac output x arterial oxygen content) may be decreased in heart failure. We studied the determinants of arterial oxygen transport in 15 patients with chronic, severe myocardial failure at rest and during cycle ergometry. During control therapy at rest, arterial oxygen tension was normal (81 +/- 8 mm Hg, mean +/- SD) and increased slightly during exercise (90 +/- 14 mm Hg). During hydralazine therapy at rest, arterial oxygen tension was slightly higher (87 +/- 9 mm Hg) and also increased during exercise (92 +/- 15 mm Hg). Hydralazine did not increase arterial oxygen tension (0.10 greater than p greater than 0.05), but exercise did (p less than 0.02). Arterial oxygen saturation and content were normal and did not change under any condition or treatment. During control therapy at rest, arterial oxygen transport was low (313 +/- 74 ml/min . m2) and remained abnormally low during exercise (434 +/- 124 ml/min . m2). During hydralazine therapy, arterial oxygen transport was higher at rest (457 +/- 100 ml/min . m2) and during exercise (577 +/- 131 ml/min . m2). Hydralazine increased arterial oxygen transport (p less than 0.01) because it increased stroke volume at rest and during exercise, but it did not change arterial oxygenation. Arterial oxygenation is normal in chronic heart failure patients at rest and during exercise. Hydralazine increases cardiac output and arterial oxygen transport without changing arterial oxygenation.
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PMID:Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment. 708

Hydralazine and isosorbide dinitrate can increase the cardiac output during submaximal exercise in patients with heart failure but whether this increase improves oxygen delivery to underperfused exercising muscle is uncertain. To investigate this question, we measured three systemic markers of skeletal muscle oxygen availability--exercise VO2, mixed venous lactate concentration and oxygen debt--during submaximal exercise in 15 patients with heart failure both before after hydralazine (nine patients) or isosorbide dinitrate (eight patients) administration. Hydralazine increased the cardiac output during exercise from 4.9 +/- 1.2 liter/min to 6.5 +/- 1.8 liter/min (p less than 0.01) but had no effect on exercise VO2 (control, 531 +/- 135 ml/min; hydralazine, 489 +/- 102 ml/min), peak lactate concentration (control, 18.3 +/- 4.2 mg/dl; hydralazine, 17.9 +/- 3.6 mg/dl) or oxygen debt (control, 474 +/- 213 ml; hydralazine, 465 +/- 170 ml) (all p greater than 0.10). Isosorbide dinitrate increased the cardiac output during exercise from 4.6 +/- 0.9 liter/min to 5.3 +/- 0.8 liter/min (p less than 0.01) but also did not change exercise VO2 (control, 488 +/- 62 ml/min; isosorbide, 473 +/- 44 ml/min), peak lactate concentration (control, 19.2 +/- 6.0 mg/dl; isosorbide, 21.4 +/- 8.2 mg/dl) or oxygen debt (control, 522 +/- 154 ml; isosorbide, 445 +/- 147 ml) (all p less than 0.10). We conclude that short-term administration of hydralazine or nitrates to patients with heart failure can substantially improve circulatory function during exercise but that this improvement probably does not enhance skeletal muscle nutritional flow.
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PMID:Circulatory improvement after hydralazine or isosorbide dinitrate administration in patients with heart failure. Effect on metabolic responses to submaximal exercise. 728 52

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and branchial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (+/- standard deviation) cardiac output at rest from 3.5 +/- 0.5 to 4.9 +/- 1.0 liters/min (p less than 0.01) and decreased arm oxygen extraction from 39 +/- 8 to 33 +/- 10 percent (probability [p] less than 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 +/- 4, hydralazine 60 +/- 12 percent; p = not significant [NS]) or venous lactate during exercise (control 16.6 +/- 7.8, hydralazine 17.1 +/- 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 +/- 0.7 to 4.5 +/- 0.7 liters/min (p less than 0.01) but had no effect on arm oxygen extraction at rest (control 40 +/- 11, isosorbide dinitrate 38 +/- 11 percent; p = NS) and during exercise (control 66 +/- 5, isosorbide dinitrate 64 +/- 8 percent; p = NS) or on venous lactate during exercise (control 17.9 +/- 6.4, isosorbide dinitrate 17.1 +/- 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.
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PMID:Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure. 730 41

Cardiac phenotypic modulation and remodeling appear to be involved in the pathophysiology of cardiac hypertrophy and heart failure. We undertook this study to examine whether angiotensin II (Ang II) in vivo, independent of blood pressure, contributes to cardiac phenotypic modulation and remodeling. A low dose (200 ng/kg per minute) of Ang II was continuously infused into rats by osmotic minipump for 24 hours or 3 or 7 days to examine the effects on the expression of cardiac phenotype-related or fibrosis-related genes. This Ang II dose caused a small and gradual increase in blood pressure over 7 days. Left ventricular mRNAs for skeletal alpha-actin, beta-myosin heavy chain, atrial natriuretic polypeptide, and fibronectin were already increased by 6.9-, 1.8-, 4.8-, and 1.5-fold, respectively, after 24 hours of Ang II infusion and by 6.9-, 3.3-, 7.5-, and 2.5-fold, respectively, after 3 days, whereas ventricular alpha-myosin heavy chain and smooth muscle alpha-actin mRNAs were not significantly altered by Ang II infusion. Ventricular transforming growth factor-beta 1 and types I and III collagen mRNA levels did not increase at 24 hours and began to increase by 1.4-, 2.8-, and 2.1-fold, respectively, at 3 days. An increase in left ventricular weight occurred 3 days after Ang II infusion. Treatment with TCV-116 (3 mg/kg per day), a nonpeptide selective angiotensin type 1 receptor antagonist, completely inhibited the above-mentioned Ang II-induced increases in ventricular gene expressions and weight. Hydralazine (10 mg/kg per day), which completely normalized blood pressure, did not block cardiac hypertrophy or increased cardiac gene expressions by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats. 776 70

In recent years, vasodilator drugs are considered a standard therapy for patients with symptomatic heart failure. Isosorbide dinitrate, venodilator, shows a striking fall in cardiac filling pressure. Hydralazine, arterially active vasodilator, decreases afterload and increases cardiac output. The combined use of nitrates and hydralazine shows synergistic effect in increasing cardiac output, lowering cardiac filling pressure and improving exercise tolerance and life expectancy. Prazosin showed no favourable effect on survival in a V-HeFT trial. Although calcium antagonists have been expected to improve hemodynamics in the patients with heart failure, there have been no controlled large trial to prove that the hemodynamic effect is accompanied by any improvement in exercise tolerance or quality of life. At the present, it is considered to be reasonable to use nitrates and hydralazine combined with ACE inhibitors, in patients with chronic heart failure.
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PMID:[Vasodilator therapy in cardiac failure]. 810 Dec 37

We compared the effects of Hydralazine and Isosorbide dinitrate (ISDN) with those of an angiotensin-converting-enzyme inhibitor, captopril on mortality in patients with chronic congestive heart failure (NYHA class III and IV). Patients receiving conventional treatment with digoxin and diuretics were randomly assigned to receive either placebo (n = 51), hydralazine-ISDN. (n = 50) or captopril (n = 52) in a double blind trial. At the end of 6 months there were 14 deaths in the placebo group (27.4%) as compared with 11 deaths in the hydralazine-ISDN group (22%)--a mortality reduction of 20% (P > 0.05) and 10 deaths in the captopril group (19.2%)--a mortality reduction of 30% (p > 0.05). At the end of one year, mortality was 50%, 42% and 30% in the placebo, hydralazine-ISDN and captopril groups respectively with a mortality reduction of 16% in the hydralazine-ISDN group (p > 0.05) and 40% in the captopril group (p < 0.05) compared to the placebo group. The mortality reduction was mainly due to reduction in deaths attributed to progressive heart failure. The data suggests that the addition of captopril to conventional treatment significantly reduces mortality in patients with severe congestive heart failure. Hydralazine-isorobide dinitrate also reduced mortality but statistically this was not significant.
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PMID:Effect of vasodilator therapy on mortality in chronic congestive heart failure. 830 Apr 56

1. The purpose of this study was to elucidate the cellular mechanism of the positive inotropic effect of hydralazine, a vasodilator widely used for afterload reduction in patients with heart failure that has also been reported to have positive inotropic effects on the heart. After isolation, right ventricular papillary muscles from the ferret were maintained in bicarbonate-buffered salt solution (30 degrees C). A concentration-response relationship was obtained for hydralazine (10(-6) to 10(-3) M). In order to mimic different levels of catecholamine release found in heart failure, we utilized two methods of stimulation: (a) threshold punctate pulses and (b) suprathreshold punctate stimulation with voltage approximately 10% above threshold. 2. In a first group of muscles (n = 16), a maximally effective concentration of hydralazine (10(-3) M) increased peak isometric tension by 39 +/- 9% (P < 0.05). Doses lower than 10(-5) M had no significant effect. The bioluminescent Ca2+ indicator, aequorin, was loaded into a subset of these muscles (n = 7). A significant increase in peak light (i.e., intracellular Ca2+) developed, concurrently with an increase in peak tension (38 +/- 5% to 66 +/- 8%). This inotropic response was associated with a decrease in time to peak tension (ms), 221 +/- 7 to 186 +/- 5 (P < 0.05), and time to peak light, 65 +/- 4 to 52 +/- 2 (P < 0.05). These effects were markedly attenuated by pretreatment with autonomic blocking agents. 3. In a second group of muscles (n = 12), histamine was used to stimulate cyclic AMP production in the presence of propranolol. Hydralazine (3 x 10-4 M) led to a shift in the pD2 (i.e. the negative log of the concentration of histamine producing 50% of the maximal response) from 6.1 +/- 0.1 to 5.9 +/- 0.1(P <0.05), thus increasing the sensitivity of the muscles to histamine. Hydralazine also increased maximum tension from 160 +/- 77% to 195 +/- 57% (P <0.05) above baseline. Thus, hydralazine altered the potency and efficacy of histamine despite the presence of beta-adrenoceptor blockade.4. A third group of muscles were chemically skinned to examine the effects of hydralazine on myofilament Ca2+ responsiveness. Pretreatment of ferret papillary muscles with hydralazine (10-3 M)before skinning did not shift the force-pCa curve after skinning (n = 16). However, hydralazine added to previously skinned fibres desensitized the myofilaments, as indicated by a rightward shift of the force-pCa curve (n = 12). Maximum tension development was not changed.5. The pharmacological effects of hydralazine are characteristic of inotropic drugs that act mainly via cyclic AMP; however, the increase in peak tension demonstrated with histamine in the presence of hydralazine also suggests an effect on cyclic AMP-independent second messenger pathways. These data are consistent with reports that large doses of hydralazine may increase cellular levels of cyclic AMP, as well as other second messengers, by direct cardiac and indirect neuronal mechanisms.
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PMID:Cellular mechanism of the positive inotropic effect of hydralazine in mammalian myocardium. 835 64

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


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