Sustained haemodynamic action of nitroglycerin ointment.

Intravenous vasodilators have been shown to improve the haemodynamic status of patients in congestive heart failure. However, neither intravenous nor sublingual preparations are suitable for chronic administration or use in ambulatory patients. In this study, nitroglycerin ointment bas administered to 11 patients in congestive heart failure. Mean pulmonary wedge and arterial pressures, as well as systemic blood pressures and heart rate were then monitored for 2 to 5 hours and compared with baseline values. Pulmonary wedge and arterial pressures, as well as systemic systolic arterial pressure, decreased significantly at 15 minutes after application and remained depressed for up to 5 hours. Systemic diastolic pressures fell significantly at 30 minutes and also remained significantly reduced for up to 5 hours. Thus, nitroglycerin ointment may be suitable for chronic vasodilator therapy of congestive heart failure.     

Sleep apnea-hypopnea syndrome and the heart

Cardiovascular and cerebrovascular diseases are the most common diseases in industrialized societies. The main objectives of this article were to summarize the physiological effects of sleep apnea on the circulatory system and to review how treatment of this condition influences cardiovascular disease. Acute sleep apnea has a number of hemodynamic consequences, such as pulmonary and systemic hypertension, increased ventricular afterload and reduced cardiac output, all of which result from sympathetic stimulation, arousal, alterations in intrathoracic pressure, hypoxia and hypercapnia. When chronic, sleep apnea-hypopnea syndrome is associated with systemic hypertension, ischemic heart disease, congestive heart failure, and Cheyne-Stokes respiration in patients with congestive heart failure. Nocturnal treatment with continuous positive airway pressure decreases both the number of central apneic episodes and blood pressure in patients with sleep apnea-hypopnea syndrome and arterial hypertension.     

Glycyl-prolyl-p-nitroanilidase (GPNAase) activity in cardiovascular diseases.

We have studied serum glycyl-prolyl-p-nitroanilidase (GPNAase) activity and its distribution in various parts of the body in patients with acute myocardial infarction, chronic ischemic heart disease, valvular heart disease with or without congestive heart failure and essential hypertension. Serum GPNAase activity in patients with acute myocardial infarction was significantly lower as long as 12 days after the onset as compared with normal controls. The serum enzyme activity in patients with congestive heart failure was also significantly lower than that of controls and there was a tendency of its gradual decrease with the progress of the disease. There was no significant difference between the activity in control group and that in age-matched patients with essential hypertension. There was no significant change of the activity in patients with chronic ischemic heart disease. The GPNAase activities in sera obtained from various parts of the body by cardiac catheterization were essentially similar.     

Treatment of heart failure in older persons. Dilemmas with coexisting conditions: diabetes mellitus,chronic obstructive pulmonary disease,and arthritis

Diabetes mellitus is a risk factor for congestive heart failure. Diabetics with congestive heart failure should have good glycemic control, treatment of hypertension and dyslipidemia, and treatment with diuretics, angiotensin-converting enzyme inhibitors, and beta blockers as well as digoxin, if the left ventricular ejection fraction is abnormal. Patients with chronic obstructive pulmonary disease may have left ventricular failure because of a coexistent cardiac disorder or right ventricular failure from pulmonary hypertension. An acute respiratory tract infection may precipitate right ventricular failure and should be treated. Alveolar hypoxia should be corrected by improving alveolar ventilation through relieving airflow obstruction with bronchodilators and by increasing inspired oxygen concentration. Loop diuretics should be used cautiously. Beta blockers may be given to patients with chronic obstructive pulmonary disease and left ventricular failure if bronchospasm is not present. Angiotensin-converting enzyme inhibitors should be used to treat left ventricular failure. Digitalis should not be used in patients with right ventricular failure due to chronic obstructive pulmonary disease. Nonsteroidal anti-inflammatory drugs are contraindicated in patients with congestive heart failure. There are controversial data about the negative interaction between aspirin and angiotensin-converting enzyme inhibitors in patients with congestive heart failure. Patients with arthritis and congestive heart failure needing large doses of aspirin for pain relief may be treated instead with acetaminophen, tramadol, or Percocet if necessary for chronic severe pain.     

Hemodynamic advantage of combined administration of oral ibopamine and nitroprusside in patients with ischemic and idiopathic congestive cardiomyopathy

The hemodynamic effects of combined administration of ibopamine (Ib) (150 mg orally) with nitroprusside (NP) (50-150 micrograms/min intravenously) were compared with those of NP alone in 17 patients with severe congestive heart failure due to coronary artery disease (7 patients) or idiopathic cardiomyopathy (10 patients). Hemodynamic measurements were obtained using a Swan-Ganz thermodilution catheter and a bedside thermodilution cardiac output computer. Nitroprusside alone produced a significant decrease (-12.4%) in mean arterial pressure, mean pulmonary arterial pressure (-28.3%), and systemic vascular resistance (-22.6%), and a significant increase in stroke volume index (23.1%). The administration of combined NP and Ib produced a further significant increase of stroke volume index (20.1%) with a concomitant and significant reduction of systemic vascular resistance (-19.4%); heart rate, mean systemic and pulmonary arterial pressures did not change significantly from the values observed with NP alone. Moreover, stroke work index, although not significantly modified with the vasodilator alone, was significantly increased over control values with NP + Ib association. Although NP alone induced similar effects in both the ischemic and idiopathic cardiomyopathies, the association of Ib gave a more favorable, though not significant, hemodynamic response in the subjects with primitive cardiomyopathy than in the ischemic ones. Thus, the association of Ib to NP therapy, in patients with congestive heart failure, further increases stroke volume index and stroke work index with a concomitant reduction of systemic vascular resistance, without any significant change in mean systemic and pulmonary arterial pressures, or heart rate. These results point out the possibility of associating Ib with other orally active vasodilators in the chronic treatment of congestive heart failure.     

Diastolic function in hypertension

Diastolic dysfunction in patients with hypertension may present as asymptomatic findings on noninvasive testing, or as fulminant pulmonary edema, despite normal left ventricular systolic function. Up to 40% of hypertensive patients presenting with clinical signs of congestive heart failure have normal systolic left ventricular function. In this article we review the pathophysiologic factors affecting diastolic function in individuals with diastolic function, current and emerging tools for measuring diastolic function, and current concepts regarding the treatment of patients with diastolic congestive heart failure.     

Therapy for diastolic heart failure

There is little objective to guide the therapy of patients with diastolic heart failure. Because of the similarities of pathophysiology abnormalities in diastolic and systolic heart failure, it is a reasonable inference to suggest that the proven therapy for systolic heart failure may also be of benefit in patients with diastolic heart failure. Treatment of underlying or exacerbating conditions in diastolic heart failure, such as hypertension, left ventricular hypertrophy, ischemia, diabetes, anemia, obesity and pulmonary disease is an important means of managing diastolic heart failure. Control of systolic blood pressure is effective in improving and preventing the development of diastolic heart failure. Treatment of diastolic heart failure is most effective when it is associated with hypertension. Production of systolic arterial pressure acutely reduces pulmonary congestion, ischemia, and chronically may lead to regression of left ventricular hypertrophy. Patients with diastolic heart failure in the absence of hypertension are very difficult to treat.     

Calcium antagonists in heart failure

Clinical experience with calcium antagonists in congestive heart failure has, to date, been mainly restricted to the use of nifedipine but there is either no or only a limited extent of information available on diltiazem and verapamil. In patients with acute and chronic congestive heart failure, single-dose administration of nifedipine was seen to lead to a decrease in systemic vascular resistance, left ventricular filling pressure and ventricular volumes as well as to an increase in stroke volume, ejection fraction and mean velocity of circumferential fiber shortening. These favorable effects could not be detected in eight patients during a three-week treatment phase with 80 mg nifedipine daily: resting blood pressure, cardiac volumes, echocardiographically-dimensions and exercise tolerance were unchanged as compared with placebo. In patients with ischemic heart disease and impaired ventricular function, in addition to an improvement in systolic function, single-dose nifedipine administration led to favorable effects on diastolic function with a shift of the diastolic pressure-volume relationship downward and to the diastolic pressure-volume relationship downward and to the left. In patients with severe aortic regurgitation, the observed increase in effective cardiac output affected by nifedipine was primarily attributable to an increase in heart rate. In the presence of an initially-elevated systemic vascular resistance, the regurgitation fraction decreased. In pulmonary hypertension, favorable hemodynamic effects have been reported after acute administration of verapamil as well as diltiazem and nifedipine. In individual cases, promising results in patients with primary pulmonary hypertension have been reported during long-term therapy with nifedipine provided that a favorable initial response could be documented.     

前列地尔脂微球载体制剂对AECOPD合并慢性肺源性心脏病肺动脉高压疗效的临床研究

目的评价前列地尔脂微球载体制剂（L ipo PGE1）治疗AECOPD合并慢性肺源性心脏病肺动脉高压患者的疗效。方法 60例AECOPD合并慢性肺源性心脏病肺动脉高压患者随机分为治疗组和对照组,治疗组在常规治疗的基础上加用L ipoPGE1 10μg,对照组仅常规治疗。治疗前后检测肺动脉收缩压（SPAP）、肺动脉平均压（MPAP）、肺动脉舒张压（DPAP）、动脉血氧分压（PaO2）、动脉二氧化碳分压（PaCO2）、肺功能FEV1和FEV1/FVC。结果治疗后SPAP、MPAP、DPAP、PaCO2较治疗前明显降低,PaO2、FEV1和FEV1/FVC较治疗前显著增加,与对照组相比有显著差异（P〈0.05）。结论 PGE1治疗AECOPD合并慢性肺源性心脏病肺动脉高压能降低肺动脉压力,改善动脉血气和肺功能。     

Peritoneal ultrafiltration for refractory fluid overload and ascites due to pulmonary arterial hypertension

Pulmonary hypertension is a common finding in patients with advanced liver disease. Similarly, among patients with advanced pulmonary arterial hypertension, right heart failure leads to congestive hepatopathy. Diuretic resistant fluid overload in both advanced pulmonary hypertension and chronic liver disease is a demanding challenge for physicians. Venous congestion and ascites-induced increased intra-abdominal pressure are essential regarding recurrent hospitalization, morbidity and mortality. Due to impaired right-ventricular function, many patients cannot tolerate extracorporeal ultrafiltration. Peritoneal dialysis, a well-established, hemodynamically tolerated treatment for outpatients may be a good alternative to control fluid status. We present a patient with pulmonary arterial hypertension and congestive hepatopathy hospitalized for over 3 months due to ascites induced refractory volume overload treated with peritoneal ultrafiltration. We report the treatment benefits on fluid balance, cardiorenal and pulmonary function, as well as its safety. In conclusion, we report a case in which peritoneal ultrafiltration was an efficient treatment option for refractory ascites in patients with congestive hepatopathy.     

Use of invasive ergometric exercise to assess the hemodynamic response to nicardipine

The calcium antagonists are potent vasodilators. This physiologic property suggests that these agents have a potential role in the treatment of patients with hypertension and congestive heart failure. Although the clinical response to calcium antagonism in hypertension is promising, the response in patients with congestive heart failure is less than hoped for; this is due to the fact that this class of agents may induce a hemodynamically important degree of negative inotropic effect.

To test the hemodynamic response to nicardipine, a second-generation dihydropyridine, the hemodynamic response to maximal ergometric exercise was evaluated in a group of patients with moderate to severe chronic congestive heart failure. One week of nicardipine therapy was associated with a significant reversal of vasoconstriction at rest and during peak exercise with a secondary increase of cardiac index, and a decrease in pulmonary wedge pressure. The reversal of vasoconstriction was associated with a decrease in mean arterial pressure, with no change in the heart rate. There was no change in oxygen consumption or carbon dioxide production; however, there was a decrease in arteriovenous oxygen difference, consistent with a reduction of oxygen extraction. This short-term study identified the potent vasodilator properties of nicardipine in patients with chronic congestive heart failure; a hemodynamically significant negative inotropic effect could not be identified. Although the use of calcium antagonists for the treatment of congestive heart failure may have a limited role, this study nonetheless suggests that nicardipine may have a favorable vasodilator effect without an overt negative inotropic effect. This would be of considerable advantage in the treatment of hypertension, when compared with β-adrenergic blocking agents.     

A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease

The hearts obtained at autopsy of 67 patients with hypertension, diabetes mellitus, or both were examined microscopically and histochemically, and the amount of fibrosis was determined. Significant differences in heart weight, interstitial fibrosis, replacement fibrosis, and perivascular fibrosis were found among the groups. The mean heart weight of the hypertensive-diabetic patients was significantly greater than that of the hypertensive patients and the diabetic patients. The amount of microscopic fibrosis increased between the groups, the lowest in hypertensive hearts, midrange in diabetic hearts, and highest in hypertensive-diabetic hearts. Total fibrosis correlated with heart weight among diabetic and hypertensive-diabetic patients and was significantly greater among patients with congestive heart failure, most of whom had histories of both hypertension and diabetes. The microscopic grade of fibrosis correlated significantly (p less than 0.01) with a quantitative, histochemical determination of the amount of collagen per milligram of total noncollagenous protein in the heart tissue. Myocardial fibrosis may contribute to the diastolic dysfunction typical of hypertensive-diabetic cardiomyopathy, in which congestive heart failure is a common sequela. The importance of hypertension in the pathogenesis of severe diabetic heart disease is discussed.     

Clinical significance of changes in the serum level of endogenous digitalis-like factor in patients with chronic congestive heart failure

Determination of serum endogenous digitalis-like factor (EDF) concentration was carried out in 52 patients with chronic congestive heart failure with radioimmunoassay. The results showed that concentration of serum EDF in patients with chronic congestive heart failure was significantly lower than that in normal subjects (P less than 0.001). The lowering of serum EDF concentration was significantly negatively correlated with the severity of heart failure, r = 0.6475, P less than 0.001. Age had no significant effect on serum EDF concentration (P greater than 0.05). Serum EDF concentration rose after the heart failure was treated, but was still lower than that in normal subjects (P less than 0.01). Serum EDF concentration in patients with coronary heart disease was the lowest and in patients with hypertension the highest.     

Fenestrated occluders for treatment of ASD in elderly patients with pulmonary hypertension and/or right heart failure

Atrial septal defect (ASD) occlusion in adult patients with advanced age and left or right heart diastolic or systolic heart failure and in patients with pulmonary arterial hypertension bears a considerable risk of deterioration of heart failure. Therefore, we conducted this feasibility trial in 15 ASD patients with pulmonary hypertension and/or right heart failure using a fenestrated Amplatzer septal occluder (AGA Medical Corporation, Golden Valley, MN), allowing an overflow of blood in both directions in case of univentricular diastolic or systolic heart failure. In all patients, the device could be implanted without complications. All symptomatic patients showed an improvement in the New York Heart Association (NYHA) class, and no right or left heart decompensation occurred. On echocardiography, right ventricular end diastolic dimension (RVEDD) and pulmonary artery pressure (PAP) decreased significantly, whereas left ventricular end diastolic dimension (LVEDD) increased. Our series of 15 patients with fenestrated ASD occlusion shows that high-risk ASD occlusion can safely be accomplished with excellent clinical results and without complications by a fenestrated occluder.     

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes

AIMS: Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. METHODS AND RESULTS: Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). CONCLUSION: In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.     

Regulation of circulation in congestive heart failure

Regulation of extremity (limb) circulation was studied in 21 patients suffering from congestive heart failure. In 11 cases the peripheral circulation was intact, while 10 patients also suffered from peripheral obliterative arterial disease. Data of 75 patients with normal cardiac condition served as control: 35 subjects with intact peripheral circulation and 40 patients suffering from peripheral obliterative arterial disease. Limb blood flow was measured by using venous isotope dilution technique. Cardiac output was determined by the dye dilution method. In chronic heart failure the limb circulation characteristically deviated from the normal; the limb blood flow and the limb oxygen consumption slightly decreased, while the limb vascular resistance markedly increased. The diminution of the limb blood flow and the increase in the limb vascular resistance due to obliterative arterial disease were more pronounced in patients suffering from congestive heart failure. The pathological increase in the peripheral vascular resistance due to chronic heart failure proved mostly reversible; on the administration of vasodilator drugs the elevated limb vascular resistance markedly decreased and the limb blood flow significantly increased.     

Relation between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure

The cause of exercise intolerance in congestive heart failure is unclear. Hemodynamic and ventilatory responses were measured during symptomatic maximal upright bicycle exercise in 28 patients with chronic severe left ventricular failure who achieved a maximal oxygen uptake of only 12 +/- 4 ml/min/kg (+/- standard deviation). All patients reached anaerobic metabolism as the respiratory exchange ratio rose and arterial pH fell significantly. Pulmonary capillary wedge pressure increased from 20 +/- 10 mm Hg at rest to 38 +/- 9 mm Hg at peak exercise and cardiac index increased from 2.51 +/- 0.73 to 4.54 +/- 1.65 liters/min/m2 (both p less than 0.001). Systemic vascular resistance decreased, but pulmonary vascular resistance did not change during exercise. Despite the marked pulmonary venous hypertension at peak exercise, blood gases were unchanged (PaO2, 96 +/- 15 mm Hg; PaCO2, 35 +/- 7 mm Hg). Systemic arterial oxygen content increased from 16 +/- 2 to 17 +/- 2 vol% (p less than 0.01). Changes in pulmonary capillary wedge pressure did not correlate with changes in arterial oxygen content. Results were similar whether patients were limited by dyspnea or fatigue. Thus, exercise intolerance in patients with severe left ventricular failure is associated with marked elevation of pulmonary capillary wedge pressure and anaerobic metabolism without hypoxemia or altered carbon dioxide tension. These findings suggest that exercise ability in congestive heart failure is more dependent on cardiac output than on ventilatory consequences of pulmonary congestion.     

Cardiovascular disorders and obstructive sleep apnea syndrome

The first polysomnographic recordings with concomitant monitoring of cardiocirculatory parameters demonstrated that obstructive apneas arising during sleep are accompanied by a marked increase in pulmonary and systemic arterial pressure and severe alveolar hypoventilation. Apneas also may give rise to cardiac arrhythmias, namely potentially life-threatening bradyarrhythmias. The long-term repercussions of these nocturnal cardiocirculatory changes on subsequent cardiovascular diseases and the patient's life expectancy are more controversial. There is little doubt that patients with obstructive sleep apnea syndrome (OSAS) have systemic arterial hypertension, ischemic heart disease, transient ischemic attacks, or stroke more often than control populations and have a shorter life expectancy. However, these clinical manifestations may be at least partly due to myriad other risk factors almost always present in OSAS patients (in particular obesity, diabetes, alcoholism, and cigarette smoking). Few multivariate epidemiological surveys have addressed all these confounding factors. The effectiveness of continuous positive airway pressure treatment in reducing the incidence of cardiovascular comorbidity in OSAS patients is not disputed, even though controlled epidemiological surveys on large populations are scant. This overview of cardiovascular disorders and OSAS examines the latest literature findings aimed at establishing the true impact of nocturnal apneas on cardiocirculatory disease (systemic arterial hypertension, ischemic heart disease, stroke, pulmonary hypertension and right heart failure and mortality).     

Hypertension and the older diabetic

Hypertension is a common comorbidity in persons with diabetes mellitus, and its prevalence increases with advancing age. Both diabetes mellitus and hypertension are independent risk factors for development in older persons of coronary artery disease, ischemic stroke, peripheral arterial disease, and of congestive heart failure. This article reviews studies addressing the implications of hypertension and the older diabetic.     

Flosequinan, a new vasodilator: systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure.

OBJECTIVES. The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure. BACKGROUND. Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure. METHODS. Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment. RESULTS. The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow. Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics. CONCLUSIONS. Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system.