Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure

In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2--39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 +/- 1.3 (SEM) to 20.3 +/- 1.4 mm Hg (P less than 0.001), CO rose from 3.94 +/- 0.23 to 4.75 +/- 0.31 l/min (P less than 0.001), MAP fell from 87.5 +/- 3.8 to 77.9 +/- 4.1 mm Hg (P less than 0.001) and SVR from 1619 +/- 148 to 1252 +/- 137 dyne-sec-cm-5 (P less than 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 +/- 3.4 to 37.9 +/- 7.7 ng/ml/hr, P less than 0.05) but plasma norepinephrine fell (619.1 +/- 103.6 to 449.7 +/- 75.7, P less than 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.     

Systemic hemodynamics, vasoactive systems, and plasma volume in patients with severe Budd-Chiari syndrome

Budd-Chiari syndrome (BCS) causes postsinusoidal portal hypertension, which leads to complications similar to those observed in cirrhosis. However, no studies have investigated whether patients with BCS develop the hyperdynamic circulatory syndrome present in patients with cirrhosis who have portal hypertension. We evaluated systemic and cardiopulmonary hemodynamics, plasma renin activity, aldosterone and norepinephrine levels, and plasma volume in patients with BCS admitted for complications of portal hypertension. BCS patients had mean systemic and cardiopulmonary pressures and cardiac indices that were within the normal range but were significantly different from those of a group of patients with cirrhosis matched by sex, body surface, and liver function (cardiac index 3.1 +/- 0.7 vs. 4.9 +/- 1.2 L.min(-1).m(-2); P < .001; systemic vascular resistance [SVR] index, 2,189 +/- 736 vs. 1,377 +/- 422 dyne.s.cm(-5).m(-2), P < .001). Despite normal systemic vascular resistance, BCS patients had activation of the neurohumoral vasoactive systems, as evidenced by increased plasma renin activity, aldosterone and norepinephrine levels (15.0 +/- 21.5 ng/mL . h, 76.7 +/- 106.8 ng/dL, 586 +/- 868 pg/mL; respectively) and plasma volume expansion. The analysis of individual BCS patients identified that 7 of the 21 patients actually had reduced SVR index. These patients had the greatest plasma volume expansion. A significant inverse correlation between plasma volume and SVR index was observed. In conclusion, patients with BCS had activation of vasoactive neurohumoral systems and expanded plasma volume. This outcome was observed even though most of these patients did not exhibit systemic vasodilation and cardiac output was not increased, in marked contrast with what is observed in patients with cirrhosis.     

Hemodynamic effects of infused arginine vasopressin in congestive heart failure

The hemodynamic effects of exogenously administered arginine vasopressin were assessed in 11 patients with chronic congestive heart failure. Infusion rates of 0.1 to 0.8 pmol/kg per min increased plasma arginine vasopressin from 6.5 +/- 2.7 (SD) pg/ml at control to 63 +/- 39 pg/ml at the highest infusion rate. There were progressive decreases in cardiac output and stroke volume, with increases in systemic vascular resistance and pulmonary capillary wedge pressure, but only minimal changes in heart rate and blood pressure. Changes in cardiac output, stroke volume and systemic resistance were evident from the first infusion rate, which increased plasma arginine vasopressin from 6.5 +/- 2.7 to 9.9 +/- 4.6 pg/ml. A paired analysis of baseline hemodynamic data with those measured during infusions producing an arginine vasopressin level averaging 15 +/- 2.6 pg/ml yielded the following changes: cardiac output decreased from 4.6 +/- 1.2 to 4.2 +/- 0.96 liters/min (p less than 0.01), stroke volume decreased from 60 +/- 19 to 54 +/- 16 ml (p less than 0.005) and systemic vascular resistance increased from 1,329 +/- 396 to 1,443 +/- 395 dynes X s X cm-5 (p = 0.01). Thus, small increases in circulating arginine vasopressin cause modest but significant adverse circulatory effects in patients with congestive heart failure. A fall in cardiac output, probably as a result of increased afterload, is seen at levels of arginine vasopressin within the basal range found in congestive heart failure. These data demonstrate that circulating arginine vasopressin in physiologic concentrations is capable of influencing hemodynamics in patients with congestive heart failure and suggest that therapy for this condition directed at inhibition of the vascular effect of arginine vasopressin may be potentially useful.     

Neurohumoral consequences of vasodilator therapy with hydralazine and nifedipine in severe congestive heart failure

We evaluated the effects of intravenous hydralazine (5 to 30 mg) and oral nifedipine (20 to 80 mg) on plasma catecholamines, renin, and aldosterone in 18 patients with severe chronic heart failure. Both drugs resulted in a significant decrease in systemic vascular resistance and mean systemic blood pressure, and led to an increase in cardiac output. Baseline plasma norepinephrine concentration was elevated in most patients; however, augmentation of cardiac output with both drugs did not decrease the values of this hormone (from 870 +/- 128 to 946 +/- 161 pg/ml with hydralazine and from 1088 +/- 260 to 1106 +/- 187 pg/ml with nifedipine). Plasma epinephrine level was also elevated at baseline and did not change significantly following nifedipine therapy (164 +/- 44 vs 199 +/- 54 pg/ml), but increased in most patients following the administration of hydralazine (from 105 +/- 45 to 153 +/- 27 pg/ml, p less than 0.01). The renin-aldosterone system was activated in our patients and also demonstrated a different response to both drugs. Hydralazine therapy did not change either the plasma renin concentration (30 +/- 7 vs 28 +/- 7 ng/ml/hr) or the aldosterone level (24 +/- 7 vs 22 +/- 5 ng/dl). In contrast, nifedipine increased the plasma renin concentration (22 +/- 7 to 29 +/- 8 ng/ml/hr, p less than 0.05). This change did not correlate with changes in systemic blood pressure (r = 0.03) and was probably the result of previously shown calcium blockade-mediated stimulation of renin release from the juxtaglomerular cells of the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)     

The acute response of plasma norepinephrine, renin activity, and arginine vasopressin to short-term nitroprusside and nitroprusside withdrawal in patients with congestive heart failure

Activation of the sympathetic nervous system, manifested by an increase in heart rate and circulating plasma norepinephrine, can occur in normal subjects when they are given vasodilators. The extent to which this activation occurs in patients with congestive heart failure (CHF) and whether this activation could account for the hemodynamic rebound sometimes observed following abrupt withdrawal of nitroprusside in such patients are unclear. We prospectively and retrospectively studied the effects of nitroprusside on plasma norepinephrine in 38 patients with CHF to determine if acute vasodilator therapy activates this vasoconstrictor system during or following such treatment. Thirty-six of these patients also had plasma renin activity (PRA) measured and plasma arginine vasopressin was measured in 12 patients. Baseline supine plasma norepinephrine (714 +/- 72 pg/ml, +/- SEM), PRA (15 +/- 2 ng/ml/hr), and arginine vasopressin (10 +/- 1 pg/ml) were increased at least twofold in the CHF patients. Nitroprusside (96 +/- 11 micrograms/min) was infused for 63 +/- 5 minutes after achieving an optimal hemodynamic response: cardiac index increased (2.01 +/- 0.08 to 2.67 +/- 0.1 L/min/m2, p less than 0.001), pulmonary artery wedge pressure decreased (25 +/- 1 to 16 +/- 1 mm Hg, p less than 0.001), mean arterial pressure decreased (83 +/- 1 to 72 +/- 1 mm Hg, p less than 0.001), and heart rate was unchanged. Plasma norepinephrine (632 +/- 43 pg/ml), PRA (18 +/- 3 ng/ml/hr), and arginine vasopressin (11 +/- 1 pg/ml) did not change significantly for the group during peak effect of the vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of intravenous prostacyclin in stable angina pectoris

Prostacyclin (PGI2) is a naturally occurring vasodilator and inhibitor of platelet aggregation that produces vasodilatation of the systemic, pulmonary and coronary vascular beds in animal models. Because the endogenous production of PGI2 is reduced in those with coronary arterial disease (CAD), it may have a therapeutic role in patients with ischemic heart disease. To assess its safety and efficacy in this clinical setting, 17 patients with stable angina and CAD received an incremental intravenous infusion of either PGI2 (n = 10) to a maximum dose of 10 ng/kg/min (average 9.8 +/- 0.8 [mean +/- standard deviation]), or diluent buffer solution (placebo) (n = 7). All patients who received PGI2 became flushed, but experienced no other adverse effects PGI2 caused an increase in heart rate (66 +/- 11 to 80 +/- 11 beats/min, p less than 0.001) and cardiac index (2.88 +/- 0.65 to 3.97 +/- 1.17 liters/min/m2, p less than 0.001) and a decrease in mean femoral arterial pressure (96 +/- 18 to 86 +/- 11 mm Hg, p less than 0.001), but no change in mean pulmonary arterial or capillary wedge pressure. Total systemic and pulmonary vascular resistance decreased significantly (p less than 0.001). In response to PGI2, mean coronary sinus blood flow did not change significantly (100 +/- 40 to 121 +/- 52 ml/min), but coronary vascular resistance decreased (1.07 +/- 0.40 to 0.83 +/- 0.36 U, p less than 0.001). No variable was altered by placebo infusion. PGI2 caused a marked increase in 6-keto PGF1 alpha (the stable metabolite of PGI2) concentrations in both arterial (42 +/- 29 to 567 +/- 216 pg/ml, p less than 0.001) and venous (46 +/- 31 to 604 +/- 229 pg/ml, p less than 0.001) blood but no demonstrable change in plasma renin activity. Thus, intravenous PGI2 to a dosage of 10 ng/kg/min is a safe and effective systemic, pulmonary and coronary arterial vasodilator in patients with CAD and stable angina pectoris.     

Hemodynamic and clinical significance of the pulmonary vascular response to long-term captopril therapy in patients with severe chronic heart failure

Exercise capacity in patients with left heart failure is closely related to the performance of the right ventricle and the pulmonary circulation. To determine the significance of changes in pulmonary resistance during long-term vasodilator therapy, hemodynamic studies were performed before and after 1 to 3 months of treatment with captopril in 75 patients with severe chronic left heart failure. Patients were grouped according to the relative changes in pulmonary and systemic resistances during long-term therapy: patients in Group I (n = 24) showed greater decreases in pulmonary arteriolar resistance (PAR) than in systemic vascular resistance (SVR) (% delta PAR/% delta SVR greater than 1.0), whereas patients in Group II showed predominant systemic vasodilation (% delta PAR/% delta SVR less than 1.0). Despite similar changes in systemic resistance, patients in Group I showed greater increases in cardiac index, stroke volume index and left ventricular stroke work index (p less than 0.01 to 0.001) but less dramatic decreases in mean systemic arterial pressure (p less than 0.02) than did patients in Group II. Despite similar changes in left ventricular filling pressure, patients in Group I showed greater decreases in mean pulmonary artery and mean right atrial pressures (p less than 0.02 to 0.01) than did patients in Group II. Pretreatment variables in Groups I and II were similar, except that plasma renin activity was higher (8.7 +/- 2.1 versus 3.0 +/- 0.6 ng/ml per h) and serum sodium concentration was lower (133.1 +/- 0.9 versus 137.1 +/- 0.6 mEq/liter) in Group II than in Group I (both p less than 0.05). Both groups improved clinically after 1 to 3 months, but symptomatic hypotension occurred more frequently in Group II than in Group I (36 versus 8%) (p less than 0.005). These findings indicate that changes in the pulmonary circulation modulate alterations in both right and left ventricular performance during the treatment of patients with left heart failure. Hyponatremic patients are likely to experience symptomatic hypotension with captopril because they are limited in their ability to increase cardiac output as a result of an inadequate pulmonary vasodilator response to the drug.     

Hemodynamic and clinical correlates of endothelin-1 in chronic thromboembolic pulmonary hypertension.

BACKGROUND: In non-thromboembolic pulmonary hypertension, endothelin (ET)-1 levels are increased and correlate with the hemodynamic severity of the disease. Whether such correlations exist in chronic thromboembolic pulmonary hypertension (CTEPH) is unknown, nor whether ET-1 levels correlate with hemodynamic outcome after pulmonary endarterectomy (PEA). METHODS AND RESULTS: ET-1 levels were determined by ELISA. ET-levels were increased in 35 CTEPH patients (1.62+/-0.21 pg/ml) compared with healthy controls (n=11: 0.75+/-0.06 pg/ml, p<0.02). ET-1 levels correlated (all p<0.0001) with mean pulmonary artery pressure (mPAP) (r=0.70), cardiac index (r=-0.76), total pulmonary resistance (r=0.72), mixed venous oxygen saturation (r=-0.87), and the distance walked in the 6-min walk test (r=-0.59; p<0.005; n=23). Three months after PEA, ET-1 levels had decreased (p<0.002), and were similar between patients with and without residual pulmonary hypertension (p=0.4). Preoperative ET-1 levels, however, were higher in patients with bad postoperative outcome; that is, patients who either died because of persistent pulmonary hypertension or had residual pulmonary hypertension after PEA (2.68+/-0.48 pg/ml, and 1.13+/-0.15 pg/ml, respectively; p<0.002). The levels also correlated with hemodynamic outcome after PEA (mPAP: r=0.67, p<0.0001). By receiver-operator characteristic curve analysis, ET-1>1.77 pg/ml detected a bad postoperative outcome with a sensitivity and specificity of 79% and 85%, respectively, and a likelihood ratio of 5.2. CONCLUSION: ET-1 levels in CTEPH closely correlated with the hemodynamic and clinical severity of disease in a large cohort of patients. Preoperative ET-1 levels may be useful for better identification of patients at risk for persistent pulmonary hypertension after PEA.     

Endogenous catecholamine levels in chronic heart failure. Relation to the severity of hemodynamic abnormalities

Plasma free epinephrine, norepinephrine, and dopamine concentrations were determined in 48, 63, and 45 patients, respectively, with overt congestive heart failure, and compared with those in 26 patients with stable angina but without heart failure. Systemic hemodynamic values were determined to assess the severity of heart failure. Arterial epinephrine levels were not different between patients with heart failure (73 +/- 92 pg/ml) and patients without heart failure (55 +/- 73 pg/ml). In patients with congestive heart failure, norepinephrine (665 +/- 510 pg/ml, mean +/- SD) and dopamine (407 +/- 405 pg/ml) levels were significantly higher than in patients with stable angina without heart failure (norepinephrine 184 +/- 136 pg/ml, p less than 0.001, and dopamine 197 +/- 259 pg/ml, p less than 0.02). However, in patients with congestive heart failure, the plasma norepinephrine levels did not correlate with cardiac index (r = 0.21, p = NS), pulmonary capillary wedge pressure (r = 0.11, p = NS), mean arterial pressure (r = 0.11, p = NS), or systemic vascular resistance (r = 0.18, p = NS). Similarly, there was no correlation between dopamine levels and the hemodynamic abnormalities in patients with congestive heart failure. These findings suggest that although endogenous norepinephrine and dopamine levels are frequently elevated in patients with heart failure, reflecting enhanced sympathetic activity, catecholamine levels do not reflect the severity of heart failure.     

Does subclinical hypothyroidism affect cardiac pump performance?: Evidence from a magnetic resonance imaging study

OBJECTIVES: We sought to assess the effects of subclinical hypothyroidism (SHT) on the cardiac volumes and function. BACKGROUND: The cardiovascular system is one of the principal targets of thyroid hormones. Subclinical hypothyroidism is a common disorder that may represent "early" thyroid failure. METHODS: Thyroid profile was evaluated in 30 females with SHT and 20 matched control subjects. Left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), cardiac index (CI), and systemic vascular resistance (SVR) were calculated by cardiac magnetic resonance (CMR). Regional greatest systolic lengthening (E1) and greatest systolic shortening (E2) were calculated by tagging CMR. RESULTS: EDV was lower in SHT than in controls (64.3 +/- 8.7 ml/m(2) vs. 81.4 +/- 11.3 ml/m(2), p < 0.001), as well as SV [corrected] (38.9 +/- 7.5 ml/m(2) vs. 52.5 +/- 6.1 ml/m(2), p < 0.001) and CI (2.6 +/- 0.5 l/[min.m(2)] vs. 3.7 +/- 0.4 l/[min.m(2)], p < 0.001). SVR [corrected] was higher in SHT (12.5 +/- 2.5 mm Hg.min/[l.m(2)] vs. 8.6 +/- 1.1 mm Hg.min/[l.m(2)], p = 0.003). The E1 was higher in controls than in SHT at the basal (p = 0.007), equatorial (p = 0.05), and apical (p = 0.008) levels, as well as E2 at the equatorial (p = 0.001) and apical (p = 0.001) levels. All parameters normalized after replacement therapy. A negative correlation between TSH and EDV (p < 0.001), SV (p < 0.001), CI (p < 0.001), and E1 at the apical level (p < 0.001) and a positive correlation between TSH and SVR (p < 0.001) and E2 at the apical level (p < 0.001) were found. CONCLUSIONS: Subclinical hypothyroidism significantly decreased cardiac preload, whereas it increased afterload with a consequent reduction in SV and cardiac output. Replacement therapy fully normalized the hemodynamic alterations.     

The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy

The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.     

Androgen and estrogen response to adrenal and gonadal stimulation in idiopathic hemochromatosis: evidence for decreased estrogen formation

Gonadal function in idiopathic hemochromatosis (IHC) was evaluated by comparing clinical features and levels of sex hormones in 10 male patients with IHC (cirrhosis, 4; fibrosis, 6), 6 male patients with alcoholic cirrhosis (AC) and 10 healthy, age-matched controls. Impotence was present in 9 IHC and all AC patients and was associated with decreased plasma testosterone levels. However, gynecomastia, a feature in all patients with AC, was not present in IHC, and plasma sex hormone binding globulin was normal. Patients with IHC showed significantly lower basal estradiol levels (17.7 +/- 6.3 pg per ml) than did controls (28.5 +/- 8.5 pg per ml), and low LH levels (p less than 0.01), which were insufficiently stimulated by luteinizing hormone releasing hormone (n = 8) as well as a decrease in prolactin concentration (2.9 +/- 1.4 vs. 5.9 +/- 1.9 ng per ml in the controls) suggesting pituitary failure. Synthesizing capacity of sex hormones was determined by adrenocorticotropic hormone and human chorionic gonadotropin administration. Basal and stimulated levels of androstenedione and cortisol indicated normal function of the adrenals in IHC. However after adrenocorticotropic hormone, estrone levels increased to only 16.2 +/- 8.4 pg per ml (controls, 27.3 +/- 4.7 pg per ml; p less than 0.01). Increments of estrone (12.5 +/- 9.2 pg per ml) and estradiol (17.9 +/- 11.6 pg per ml) were also lower in IHC following human chorionic gonadotropin administration than in controls (26.0 +/- 7.2 and 37.5 +/- 11.4 pg per ml, respectively). In contrast, plasma human chorionic gonadotropin raised testosterone levels 3.3-fold in IHC and 2.2-fold in controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemodynamic effects of alpha human atrial natriuretic polypeptide in patients with congestive heart failure

Acute hemodynamic and humoral effects of synthesized alpha human atrial natriuretic polypeptide (alpha-hANP, 0.025 microgram/kg/min for 40 min) on 6 patients with severe congestive heart failure were assessed. Plasma alpha-hANP concentration was high in patients and increased further (from 463 +/- 360 to 1,282 +/- 670 pg/ml, mean +/- SD, p less than 0.01) following alpha-hANP infusion, but plasma norepinephrine (1,030 +/- 865 to 971 +/- 785 pg/ml) was not changed. Increases in urine output (1.0 +/- 0.8 to 2.6 +/- 2.3 ml/min) and Na+ excretion rate (87 +/- 89 to 257 +/- 211 mEq/min/m2) were statistically insignificant. A significant reduction was induced in mean aortic pressure (99 +/- 25 to 96 +/- 26 mmHg, p less than 0.05), mean right atrial pressure (11 +/- 9 to 7 +/- 8 mmHg, p less than 0.01), mean pulmonary arterial pressure (39 +/- 13 to 33 +/- 12 mmHg, p less than 0.05) and mean pulmonary capillary wedge pressure (27 +/- 8 to 20 +/- 7 mmHg, p less than 0.01). Heart rate, cardiac index, systemic vascular resistance and pulmonary vascular resistance were not altered. In conclusion, alpha-hANP induced decreases in left ventricular filling pressure and rightside heart pressure which were attributed to venodilatation rather than natriuresis in patients with congestive heart failure. Preserved cardiac output with decreased preload suggested that alpha-hANP improved cardiac function.     

Effects of intravenous and intracoronary nicardipine

The systemic and coronary hemodynamic effects of nicardipine, a calcium antagonist, were studied in 30 patients. Increased coronary blood flow (from 102 +/- 9 to 147 +/- 13 ml/min; p less than 0.001), heart rate (from 69 +/- 3 to 81 +/- 3 beats/min; p less than 0.001), stroke volume (108 +/- 6 to 123 +/- 6 ml; p less than 0.001) and cardiac output (from 7.3 +/- 0.5 to 9.9 +/- 0.5 liters/min; p less than 0.001) were demonstrated in 15 patients administered intravenous nicardipine (2 mg bolus given over 1 minute, followed by infusion of 50 micrograms/min to maintain 10 to 20 mm Hg decrease in systolic blood pressure). Systemic vascular resistance decreased (from 1,183 +/- 70 to 733 +/- 33 dynes s cm-5) as did coronary resistance (from 1.47 +/- 0.1 to 0.7 +/- 0.1 mm Hg/ml/min; p less than 0.001). Other hemodynamic parameters such as left ventricular end-diastolic pressure, stroke volume and work, aortic blood flow and acceleration, ejection and external power, myocardial oxygen consumption and time constant for left ventricular isovolumic relaxation also were evaluated. To distinguish between direct myocardial effects of nicardipine and peripheral effects, 15 patients were given intracoronary nicardipine (0.1 or 0.2 mg) during cardiac catheterization. Nicardipine produced slight depression of left ventricular contractile function and impairment of left ventricular relaxation; but these changes were mild and transient compared with the marked and sustained increase in coronary blood flow that persisted 7 minutes after administration. Thus, nicardipine is a relatively selective vasodilator with minimal direct myocardial depressant activity n humans.     

Evaluation of neurohumoral activation (adrenomedullin, BNP, catecholamines, etc.) in patients with acute myocardial infarction

OBJECTIVE: The object of our study was to identify the most useful predictor of patient prognosis in acute myocardial infarction (AMI), from 7 acute-phase cardiovascular peptides which take part in neurohumoral activation [brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), renin, aldosterone, adrenomedullin, epinephrine and norepinephrine]. METHODS: In 141 consecutive AMI patients, 24 hours from onset, we evaluated plasma concentration levels of the 7 types of cardiovascular peptides and the relationships between the values of these peptides and short-term clinical prognosis, including mortality. RESULTS: Plasma levels of all cardiovascular peptides were significantly higher in patients who suffered mortality than in surviving patients (BNP: 1,267+/-997 pg/ml vs. 293+/-327 pg/ml, p<0.0001; ANP: 164+/-186 pg/ml vs. 64+/-76 pg/ml, p<0.001; adrenomedullin: 13.61+/-3.29 Fmol/l vs. 3.45+/-1.52 Fmol/I, p<0.0001; renin: 8.79+/-7.15 ng/ml/h vs. 4.34+/-5.10 ng/ml/h, p<0.01; aldosterone: 249+/-210 pg/ml vs. 68+/-74 pg/ml, p<0.0001; epinephrine: 3,191+/-8,360 pg/ml vs. 68+/-74 pg/ml, p<0.0001; norepinephrine: 21.8+/-46.2 ng/ml vs. 0.9+/-0.8, ng/ml p<0.0001). Multivariate analysis identified only high levels of adrenomedullin as an independent related factor of cardiogenic shock (risk ratio: 5.84, 95% C.I.: 1.80-18.95, p=0.003), and as an independent predictor of short-term mortality (risk ratio: 16.16, 95% C.I.: 1.38-189.71, p=0.03). CONCLUSIONS: Acute-phase neurohumoral activation, involving renin, aldosterone, epinephrine, norepinephrine, BNP, ANP, and adrenomedullin may be closely related to poor patient outcomes, including mortality. Our results suggest that acute-phase plasma adrenomedullin concentrations may be the most useful predictor of patient prognosis in the setting of AMI, out of the 7 types of cardiovascular peptides involved in neurohumoral activation.     

Renal hemodynamic effects of vasodilation with nifedipine and hydralazine in patients with heart failure

The central and renal hemodynamic effects of nifedipine were evaluated in nine patients with severe chronic congestive heart failure. Oral nifedipine (34 +/- 22 mg, mean +/- standard deviation) was associated with a decrease in systemic vascular resistance from 1,748 +/- 436 to 1,321 +/- 302 dynes . s . cm-5 (p less than 0.001) and mean arterial blood pressure from 96 +/- 11 to 87 +/- 6 mm Hg (p less than 0.05) and with an increase in cardiac output from 4.2 +/- 1.1 to 4.9 +/- 1.2 liters/min (p less than 0.001). Although renal vascular resistance decreased from 11,988 +/- 2,256 to 10,286 +/- 3,011 dynes . s . cm-5 (p less than 0.05), no significant change was seen in renal blood flow (599 +/- 120 to 640 +/- 162 ml/min), glomerular filtration rate (62 +/- 18 to 62 +/- 17 ml/min), filtration fraction (18 +/- 5 to 17 +/- 6%), the ratio of renal/systemic vascular resistance (7.0 +/- 1.0 to 7.9 +/- 1.8) and the ratio of renal blood flow/cardiac output (0.15 +/- 0.02 to 0.13 +/- 0.03). Intravenous hydralazine (10 +/- 5 mg), given to eight of the patients in a randomized crossover design, resulted in a larger increase in cardiac output than did nifedipine (38 +/- 7 versus 19 +/- 10%, p less than 0.001) and in an increase in total renal blood flow from 570 +/- 152 to 645 +/- 174 ml/min (p less than 0.001). Renal vascular resistance decreased from 12,080 +/- 2,934 to 10,153 +/- 2,372 dynes . s . cm-5 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic data pattern in patients with acute pancreatitis

In 16 patients with necrotizing pancreatitis and in 6 patients with edematous-interstitial pancreatitis, hemodynamic studies were conducted between the first and the 12th day after the onset of illness. Patients with necrotizing pancreatitis had a high cardiac index of 4.47 +/- 0.75 L/min X m2 and a low total peripheral vascular resistance of 884 +/- 180 dyn X s/cm5, a low mean pulmonary vascular resistance of 84.3 +/- 25.7 dyn X s/cm5, and a high pulmonary shunt fraction of 24.2% +/- 6.6% of the cardiac output. This hyperdynamic vascular pattern was not found in patients with edematous-interstitial pancreatitis associated with gallstone disease. The group of patients with edematous-interstitial pancreatitis had a cardiac index of 3.21 +/- 0.8 L/min X m2, a total peripheral vascular resistance of 1337.8 +/- 248.2 dyn X s/cm5, a mean pulmonary vascular resistance of 130.7 +/- 48.2 dyn X s/cm5, and a pulmonary shunt fraction of 13.6% +/- 3.5% of the cardiac output. There was a significant difference between the patients with necrotizing pancreatitis and those with edematous-interstitial pancreatitis in the following hemodynamic parameters: heart rate (p less than 0.02), cardiac index (p less than 0.01), total peripheral vascular resistance (p less than 0.001), arteriovenous oxygen difference (p less than 0.02), and pulmonary shunt fraction (p less than 0.01). These findings in patients with necrotizing pancreatitis demonstrate an opening of intrapulmonary shunts and peripheral vasodilatation probably due to the release of pancreatitis-associated toxic agents in the early phase of the disease.     

Clinical, hemodynamic and neurohumoral effects of long-term therapy of patients with severe chronic heart failure with beta-adrenoblocker bisoprolol

The use of beta-adrenoblockers in conjunction with angiotensin converting enzyme inhibitors improves quality of life and prognosis of patients with chronic heart failure. However basic mechanisms of these positive effects in severe heart failure remain to be elucidated. METHODS: Patients (n=54) with NYHA class III-IV heart failure and left ventricular ejection fraction < or =35% were randomized either to treatment with bisoprolol (1.25-10 mg/day) (n=30) or in control group (n=24) and were followed up for 12 months. RESULTS: The use of bisoprolol was associated with significant improvement of heart failure functional class, lowering of heart rate (by 14%, p<0.01), elevation of systolic blood pressure (by 7.2+/-12.3 mm Hg, p<0.01) and increase of walking distance (by 30.1+/-29.0 m, p<0.01). No significant changes of these parameters occurred in control group. After 12 months increases of left ventricular end diastolic and end systolic volumes (by 85+/-69.2 and 71+/-51.5 ml, respectively, p<0.001) and of ejection fraction (by 5.7+/-7.3%, p<0.01) took place in bisoprolol treated patients. These changes were significantly (p<0.001) higher than those in control group. After 6 months of treatment with bisoprolol noradrenaline concentration fell from 533 to 402 pg/ml (p<0.05) while in controls it rose from 369 to 474 pg/ml, p<0.01). Decreases of plasma renin activity (from 1.2 to 0.42 ng/ml/h), plasma concentrations of angiotensin II (from 17.1 to 13.1 pg/ml) and aldosterone (from 173 to 148 pg/ml, p<0.05) were also observed in bisoprolol group. No substantial dynamics of activity of main components of renin angiotensin system took place in controls. There were no significant changes of atrial natriuretic peptide in both groups. Significant positive dynamics of parameters of heart rate variability was registered only in bisoprolol group: SDNN increased by 25% (p<0.05), high frequency spectrum by 106% (p=0.03), LF/HF ratio from 2.18+/-1.41 to 1.82+/-0.7. CONCLUSION: Long term use of bisoprolol was associated with improved clinical and hemodynamic status, increased systolic BP, blocked processes of pathological left ventricular remodeling, lowered activity of not only sympathetic-adrenal but also of main components of renin-angiotensin system and improved heart rate variability.     

Persistently increased serum concentrations of cardiac troponin in patients with acutely decompensated heart failure are predictive of adverse outcomes.

BACKGROUND: Persistently increased serum concentrations of cardiac troponin (cTn) are a prognostic marker in patients suffering from chronic congestive heart failure (CHF), but the significance in acute cardiac decompensation is unclear. METHODS AND RESULTS: Serial blood samples were collected from 52 patients presenting with acute cardiac decompensation in the absence of an acute coronary event. Serial serum concentrations of cTnI, creatine kinase (CK)-MB, and brain natriuretic peptide (BNP) were measured by rapid assay. BNP and CK-MB steadily decreased from 902+/-529 pg/ml and 2.3+/-1.6 ng/ml at baseline to 453+/-427 pg/ml and 1.2+/-1.6 ng/ml on day 7, respectively, (p<0.0001 for both comparisons). In contrast, cTnI did not decrease significantly and, in 17 patients (35%), increased from 0.063+/-0.047 ng/ml at baseline to 0.167+/-0.181 ng/ml on day 1 (p<0.05). By single variable regression analysis, systolic blood pressure (SBP), use of inotropes or inodilators, vasodilators, and an initially elevated cTnI were predictors of elevated cTnI on day 1. By multiple variable analysis, an elevated SBP (as a mitigating factor) (odds ratios (OR) 0.12; 95% confidence intervals (CI): 0.02-0.76; p=0.0248), and high baseline cTnI (OR 13.85; 95%CI: 1.97-97.54; p=0.0083) were significant predictors of an elevated cTnI on day 1. Patients with elevated cTnI on day 1 had higher rates of worsening CHF and death from CHF than patients without such an increase (p<0.05). CONCLUSIONS: Persistently increased serum concentrations of cTn in patients with acutely decompensated heart failure are predictive of adverse outcomes.