Right ventricular overload causes the decrease in cardiac output after nitric oxide synthesis inhibition in endotoxemia

OBJECTIVE: To determine whether the decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased left ventricular afterload or right ventricular afterload. DESIGN: Prospective, randomized, unblinded study. SETTING: Research laboratory at an academic, university medical center. SUBJECTS: Nonanesthetized, sedated, mechanically ventilated pigs. INTERVENTIONS: Pigs were infused with 250 microg/kg of endotoxin over 30 mins. Normal saline was infused to maintain pulmonary artery occlusion pressure (PAOP) at a value not exceeding 1.5 times the baseline value. Left ventricular dimensions and function were studied using echocardiography. Right ventricular volumes and ejection fraction were determined via a rapid thermistor pulmonary artery catheter. We also measured mean arterial pressure (MAP), cardiac output, pulmonary arterial pressure, and calculated pulmonary and systemic resistances. Gastric tonometry was used as an index of gastric mucosal oxygenation and peripheral oxygenation. When MAP had decreased to < or =60 mm Hg or had decreased 30 mm Hg from baseline, nine animals received NG-nitro-L-arginine methyl ester (L-NAME) at 15 mg/kg to restore MAP to baseline. A second group of animals (n = 6) continued to receive normal saline, ensuring that PAOP did not exceed 1.5 times its baseline value. A third group of pigs (n = 5) did not receive endotoxin and served as the time control. In this group, a balloon was used to occlude the descending thoracic aorta and to increase MAP by approximately the same amount as in the L-NAME group. MEASUREMENTS AND MAIN RESULTS: Endotoxin caused an increase in pulmonary arterial pressure and right ventricular volumes, and a decrease in gastric mucosal pH. Cardiac output was maintained in the animals receiving the saline infusion. By 2 hrs, pulmonary arterial pressure had decreased but was still notably higher than baseline. However, by this time, MAP had decreased to < or =60 mm Hg. L-NAME administration restored MAP to its baseline value but resulted in worsening pulmonary hypertension, increased right ventricular volumes, and decreased cardiac output, compared with the saline group. Three animals that received L-NAME died of right ventricular failure. We did not observe any evidence of left ventricular dysfunction with increased left ventricular afterload. Moreover, the restoration of MAP with L-NAME infusion did not correct gastric mucosal acidosis. No changes were noted in the time-control group. Occlusion of the thoracic aorta increased MAP but did not change cardiac output. This finding demonstrates that increases in left ventricular afterload of the magnitude seen with the infusion of L-NAME do not lead to decreases in cardiac output. CONCLUSION: The decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased right ventricular afterload and not to left ventricular afterload.     

Overcoming right ventricular failure with left ventricular assist devices

BACKGROUND: Right ventricular failure can lead to circulatory collapse while on left ventricular assist device support. By shunting blood from the femoral vein to the left ventricular assist device, cardiac output can be increased, but arterial oxygen saturation will decrease. METHODS: To determine the effects on O2 delivery, a model was developed on the basis of O2 uptake in the lungs and whole body O2 consumption. An equation was derived that related cardiac output, pulmonary venous O2 saturation, O2 consumption, and the ratio of shunt-to-systemic blood flow to systemic O2 delivery. RESULTS: When total cardiac output increases, the shunt will increase systemic O2 delivery while decreasing arterial O2 saturation and leaving systemic venous O2 saturation unaltered. When total output does not increase, the shunt will decrease systemic O2 delivery, arterial O2 saturation, and systemic venous O2 saturation. CONCLUSIONS: The analysis suggests that measuring systemic venous oxygen saturation may be a useful way to monitor patient safety. A decrease in systemic venous O2 saturation when creating the shunt implies an inadequate increase in cardiac output.     

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.     

Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance

BACKGROUND: In patients with left ventricular (LV) dysfunction, inhaled nitric oxide (NO) decreases pulmonary vascular resistance (PVR) but causes a potentially clinically significant increase in left atrial pressure (LAP). This has led to the suggestion that inhaled NO may reach the coronary circulation and have a negative inotropic effect. This study tested an alternative hypothesis that LAP increases because of volume shifts to the pulmonary venous compartment caused by NO-induced selective pulmonary vasodilation. METHODS AND RESULTS: The Thermo Cardiosystems Heartmate is an LV assist device (LVAD) that can be set (by controlling pump rate) to deliver fixed or variable systemic blood flow. Eight patients (between 1 and 11 days after LVAD implantation) were administered inhaled NO (20 and 40 ppm for 10 minutes), and LAP, systemic flow, and pulmonary arterial pressure were measured in both fixed and variable pump flow modes. In both modes, inhaled NO lowered PVR (by 25 +/- 6% in the fixed mode, P < .001, and by 21 +/- 5% in the variable mode, P < .003). With fixed pump flow, LAP rose from 12.5 +/- 1.2 to 15.1 +/- 1.4 mm Hg (P < .008). In the variable flow mode, LAP did not increase and the assist device output rose from 5.3 +/- 0.3 to 5.7 +/- 0.3 L/min (P < .008). CONCLUSIONS: A selective reduction in PVR by inhaled NO can increase LAP if systemic flow cannot increase. These data support the hypothesis that with LV failure, inhaled NO increases LAP by increasing pulmonary venous volume and demonstrate that inhaled NO has beneficial hemodynamic effects in LVAD patients.     

Hemodynamic effects of intravenous prenalterol in severe heart failure

Nine patients with chronic severe low output heart failure (radionuclide left ventricular ejection fraction 17 +/- 5 percent [mean +/- standard deviation], left ventricular filling pressure 26 +/- 6 mm Hg, cardiac index 1.9 +/- 0.4 liters/min per m2, left ventricular stroke work index 18 +/- 6 g-m/m2) from various causes were treated with intravenous prenalterol (a new catecholamine-like inotropic agent) in doses of 1,4 and 8 mg. Significant hemodynamic improvement occurred as measured by increased left ventricular ejection fraction (to 26 +/- 4 percent), decreased left ventricular filling pressure (to 21 +/- 8 mm Hg) and increased cardiac index (to 2.4 +/- 0.6 liters/min per m2) and left ventricular stroke work index (to 25 +/- 8 g-m/m2). Significant increases in heart rate (from 87 +/- 18 to 91 +/- 18 beats/min) and mean systemic arterial pressure (from 87 +/- 8 to 92 +/- 7 mm Hg) also occurred. Peak hemodynamic response occurred at various doses. Significant adverse effects associated with prenalterol consisted of increased ventricular ectopic beats in two patients and asymptomatic ventricular tachycardia in two patients. Thus, intravenous prenalterol produces hemodynamic improvement in patients with a chronic severe low output state but may be associated with increased ventricular ectopic activity.     

Scorpion venom leads to gastrointestinal ischemia despite increased oxygen delivery in pigs

OBJECTIVES: Scorpion envenomation may be accompanied by metabolic acidosis even in the absence of hypoxia and cardiovascular derangement. We tested the hypothesis that venom causes ischemia of the gastrointestinal tract rather than failure of delivery of oxygen to the periphery. DESIGN: Repeated measures, prospective study in experimental animals. SETTING: University-affiliated hospital research laboratory. INTERVENTIONS: In ten spontaneously breathing, intubated, sedated pigs, purified dried venom (Leiurus quinquestriatus), 0.05 mg/kg, was administered intravenously. Measurements were obtained before (baseline), and 5, 15, 30, 60, 120, 180, and 240 mins after injection. MEASUREMENTS AND MAIN RESULTS: Variables measured included: mean arterial pressure (MAP), heart rate (HR), mean pulmonary arterial pressure, pulmonary artery occlusion pressure, cardiac output, stroke volume, right ventricular ejection fraction (rapid thermistor), left ventricular dimensions (echocardiography), arterial gas tensions, lactate and catecholamine concentrations, gastric interstitial mucosal pH (tonometry), as well as systemic and pulmonary vascular resistances. Within 5 mins after venom injection, there was a hyperdynamic state accompanied by significantly increased MAP (97 +/- 18 to 136 +/- 47 mm Hg, p < .0003), HR (70 +/- 12 to 121 +/- 24 beats/min, p < .00006), and cardiac output (1.88 +/- 0.35 to 2.95 +/- 0.53 L/min, p < .0003), with no change in stroke volume, or pulmonary artery occlusion pressure. Right ventricular ejection fraction increased from 38.1 +/- 4.3 to 48.6 +/- 9.0% (p < .0009) by 15 mins. No change in left ventricular function was observed. There were significant decreases in systemic vascular resistance and pulmonary vascular resistance following envenomation. Arterial and gastric mucosal pH significantly decreased from 7.40 +/- 0.04 to 7.25 +/- 0.07 (p < .0001) for arterial pH, and 7.33 +/- 0.08 to 7.17 +/- 0.13 (p < .00001) for gastric mucosal pH by 30 mins after envenomation. The decrease in arterial pH was not sufficient to account for the change in gastric mucosal pH, indicating gastric mucosal ischemia. Arterial lactate increased from 2.6 +/- 1.4 to 7.4 +/- 1.9 (p < .05 x 10(-8)). There were significant increases in serum epinephrine and norepinephrine values by 5 mins. All hemodynamic variables and catecholamine concentrations returned to baseline by 4 hrs. However, there was persistent arterial and gastric mucosal acidosis and increased lactate concentrations even at 4 hrs. Oxygen delivery remained normal or supernormal for 4 hrs following envenomation. However, despite this finding, systemic and gastric mucosal pH changes indicate impaired gastrointestinal oxygen delivery. CONCLUSIONS: Despite increased peripheral oxygen delivery, scorpion envenomation was associated with evidence of ischemia of the gastrointestinal tract. This association could be due to shunting of blood from metabolically active areas, possibly associated with massive catecholamine release, or a direct toxic effect of the venom on regional oxygen transport at the cellular level.     

Propranolol in mitral stenosis during sinus rhythm

Patients with early symptomatic mitral stenosis usually suffer from pulmonary congestion on the basis of left atrial and pulmonary venous hypertension. They are often in sinus rhythm, and cardiac output is usually well maintained. Symptoms occur most often when heart rate, cardiac output, or both are increased. In this study, intravenous propranolol administered to patients with pure mitral stenosis in sinus rhythm resulted in significant reductions in mitral diastolic gradient (-7.1 mm. Hg +/- 1.6 SED), mean pulmonary wedge pressure (--6.9 mm. Hg +/- 1.2) and mean pulmonary artery pressures (--9.0 mm. Hg +/- 1.2). This was due to simultaneous reduction of heart rate (--13.0 beats/minute +/- 2.6 and cardiac output (--0.5 L./minute +/- 0.2). A small associated reduction of left ventricular systolic pressure (--5.1 mm. Hg +/- 2.6) was not accompanied by adverse clinical effects. A potential role for propranolol in medical management of pure mitral stenosis in the presence of sinus rhythm is suggested.     

In vitro evaluation of a pulsatile assist device for a centrifugal pump using a new principle

To induce a pulsatile flow in a centrifugal pump, we developed a new device (pulsatile assist device for centrifugal pump: PADCP) using a new concept. This device consists of a flexible polyurethane tube with an air chamber which is connected to the arterial side of the centrifugal pump circuit directly. A mock circulation system was used for evaluation of this PADCP. Thirty to 40 mm Hg of pulse pressure was obtained under 3-6 L/min of flow rate. By increasing the driving pressure of the PADCP from 200 to 600 mm Hg in a mock system, 4-48 mm Hg of pulse pressure was gained accompanied by a decrease in pump flow and increased left atrial pressure. The decreased pump flow and increased left atrial pressure were recovered easily by increasing the flow rate of the centrifugal pump. Pressures at the proximal site of the PADCP were less than 500 mm Hg. The PADCP was useful to induce a pulsatile flow in a centrifugal pump.     

Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.     

Unidirectional valve patch for repair of cardiac septal defects with pulmonary hypertension

BACKGROUND: Congenital septal defects with a large left-to-right shunt often cause pulmonary hypertension, which complicates surgical repair of the defects. METHODS: Twenty-four patients with congenital cardiac septal defects and severe pulmonary hypertension had operation to close the septal defect using a unidirectional valve patch during a 3-year period. The ratio of systolic pulmonary artery pressure to systolic arterial blood pressure was near to or more than 1.0 in all patients. RESULTS: Two patients died in the hospital after operation, and there have been no deaths during intermediate term follow-up. Mean pulmonary artery pressure decreased from 80 +/- 12 mm Hg to 56 +/- 18 mm Hg. The ratio of pulmonary artery pressure to systemic arterial pressure dropped from 1.1 +/- 0.1 mm Hg to 0.7 +/- 0.1 mm Hg. The unidirectional valve patch functioned allowing right to left shunting in 4 patients with a systolic pulmonary artery pressure more than systolic arterial blood pressure immediately after closure of a septal defect. The patch sealed or was effectively closed by the third postoperative day. There was impressive improvement in symptoms and exercise tolerance after operation during the 3-month to 3-year (mean, 1.1 year) follow-up period. CONCLUSIONS: The unidirectional valve patch is useful for management of patients having operation to close cardiac septal defects in the presence of severe pulmonary hypertension.     

MR guidance of laser disc decompression: preliminary in vivo experience

BACKGROUND: The mechanism of atrial natriuretic peptide (ANP) release has been difficult to demonstrate in patient studies because of inaccuracies in measuring atrial volumes using conventional techniques. METHODS: Magnetic resonance imaging was performed in 28 clinically stable patients (New York Heart Association class 3) with chronic heart failure to determine right atrial (RA), left atrial (LA), and ventricular volumes. In addition, right heart catheterization was serially performed and plasma ANP levels (in picograms per milliliter) were drawn from the right atrium. RESULTS: Five patients had to be excluded from data analysis for technical reasons. The remaining 23 patients had the following hemodynamic measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p < 0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r = 0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of controls) revealed a stronger relation between ANP and RA volumes than between ANP and LA volumes. CONCLUSIONS: These data suggest that increased right heart volume with subsequent increased atrial stretch is the major determinant for ANP release in patients with stable CHF.     

Fibroelastolytic papulosis of the neck: a report of 20 cases

BACKGROUND: Reports of pulmonary edema complicating inhaled nitric oxide therapy in patients with chronic heart failure and pulmonary hypertension have raised the concern that inhaled nitric oxide may have negative inotropic effects. METHODS AND RESULTS: We investigated the effect of multiple doses of inhaled nitric oxide (20, 40 and 80 ppm) on left ventricular contractile state in 10 open-chest pigs. Pressure-volume loops were generated during transient preload reduction to determine the end-systolic pressure-volume relationship and the stroke work-end-diastolic volume relation. Inhaled nitric oxide had no effect on systemic vascular resistance, cardiac output, end-systolic pressure volume relationship or stroke work-end-diastolic volume relation under normal conditions. After induction of pulmonary hypertension (intravenous thromboxane A2 analog), inhalation of nitric oxide (80 ppm) resulted in a reduction in pulmonary vascular resistance (mean +/- standard error of the mean) from 10.4 +/- 3 to 6.5 +/- 2 Wood units (p < 0.001) and in pulmonary artery pressure from 44 +/- 4 to 33 +/- 4 mm Hg (p < 0.05). Left ventricular end-diastolic volume rose from 53 +/- 9 ml to 57 +/- 10 ml (p = 0.02). No statistically significant change in cardiac output or systemic vascular resistance was observed. Inhaled nitric oxide had no effect on end-systolic pressure-volume relationship or stroke work-end-diastolic volume relation. CONCLUSIONS: In a porcine model of pulmonary hypertension, inhaled nitric oxide does not impair left ventricular contractile function. Therefore the cause of pulmonary edema observed in some patients receiving inhaled nitric oxide is not due to a negative inotropic action of this therapy.     

Angiotensin-converting enzyme (ACE) inhibitors revert abnormal right ventricular filling in patients with restrictive left ventricular disease

OBJECTIVES: Our aim was to determine mechanisms underlying abnormalities of right ventricular (RV) diastolic function seen in heart failure. BACKGROUND: It is not clear whether these right-sided abnormalities are due to primary RV disease or are secondary to restrictive physiology on the left side of the heart. The latter regresses with angiotensin-converting enzyme inhibition (ACE-I). METHODS: Transthoracic echo-Doppler measurements of left- and right-ventricular function in 17 patients with systolic left ventricular (LV) disease and restrictive filling before and 3 weeks after the institution of ACE-I were compared with those in 21 controls. RESULTS: Before ACE-I, LV filling was restrictive, with isovolumic relaxation time short and transmitral E wave acceleration and deceleration rates increased (p < 0.001). Right ventricular long axis amplitude and rates of change were all reduced (p < 0.001), the onset of transtricuspid Doppler was delayed by 160 ms after the pulmonary second sound versus 40 ms in normals (p < 0.001) and overall RV filling time reduced to 59% of total diastole. Right ventricular relaxation was very incoordinate and peak E wave velocity was reduced. Peak RV to right atrial (RA) pressure drop, estimated from tricuspid regurgitation, was 45+/-6 mm Hg, and peak pulmonary stroke distance was 40% lower than normal (p < 0.001). With ACE-I, LV isovolumic relaxation time lengthened, E wave acceleration and deceleration rates decreased and RV to RA pressure drop fell to 30+/-5 mm Hg (p < 0.001) versus pre-ACE-I. Right ventricular long axis dynamics did not change, but tricuspid flow started 85 ms earlier to occupy 85% of total diastole; E wave amplitude increased but acceleration and deceleration rates were unaltered. Values of long axis systolic and diastolic measurements did not change. Peak pulmonary artery velocity increased (p < 0.01). CONCLUSIONS: Abnormalities of RV filling in patients with heart failure normalize with ACE-I as restrictive filling regresses on the left. This was not due to altered right ventricular relaxation or to a fall in pulmonary artery pressure or tricuspid pressure gradient, but appears to reflect direct ventricular interaction during early diastole.     

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A double-blind, placebo-controlled, randomized crossover trial

BACKGROUND: The pharmacological effects of infusion of human brain natriuretic peptide (hBNP) in patients with severe congestive heart failure have not been characterized previously. METHODS AND RESULTS: Twenty patients with severe congestive heart failure were randomized in a double-blind, placebo-controlled, crossover trial to receive incremental 90-minute infusions of hBNP (0.003, 0.01, 0.03, and 0.1 microgram/kg per minute) or placebo on 2 consecutive days. At the highest completed dose of the hBNP, mean pulmonary artery pressure decreased from 38.3 +/- 1.6 to 25.9 +/- 1.7 mm Hg; mean pulmonary capillary wedge pressure decreased from 25.1 +/- 1.1 to 13.2 +/- 1.3 mm Hg; mean right atrial pressure decreased from 10.9 +/- 1 to 4.8 +/- 1.0 mm Hg; mean arterial pressure decreased from 85.2 +/- 2.0 to 74.9 +/- 1.7 mm Hg; and cardiac index increased from 2.0 +/- 0.1 to 2.5 +/- 0.1 L/min per square meter (all P < .01 versus placebo). Urine volume and urine sodium excretion increased significantly during hBNP infusion when compared with placebo infusion (90 +/- 38 versus 67 +/- 27 mL/h and 2.6 +/- 2.4 versus 1.4 +/- 1.2 mEq/h, respectively, both P < .05 versus placebo), whereas creatinine clearance and urinary potassium excretion did not change. CONCLUSIONS: Infusion of incremental doses of hBNP is associated with favorable hemodynamic and natriuretic effects in patients with severe congestive heart failure.     

Effects of cardiomyoplasty on right ventricular filling during volume loading

BACKGROUND: Although cardiomyoplasty (CMP) is thought to improve ventricular systolic function, its effects on ventricular diastolic function are not clear. Especially the effects on right ventricular diastolic filling have not been fully investigated. Because pericardial influences are more pronounced in the right ventricle than in the left ventricle, CMP with its external constraint may substantially impair right ventricular diastolic filling. METHODS: Fourteen purebred adult beagles were used in this study. Seven underwent left posterior CMP, and 7 underwent a sham operation with a pericardiotomy and served as controls. Four weeks later, the hemodynamic effects of CMP were evaluated by heart catheterization before and after volume loading (central venous infusion of 10 mg/kg of 4.5% albumin solution for 5 minutes). RESULTS: In the CMP group, mean right atrial pressure and right ventricular end-diastolic pressure increased significantly from 3.1 +/- 1.2 mm Hg to 6.1 +/- 2.0 mm Hg (p < 0.001) and from 4.0 +/- 1.8 mm Hg to 9.6 +/- 2.5 mm Hg (p < 0.001), respectively. Volume loading in the control group did not significantly increase either variable. Right ventricular end-diastolic volume and stroke volume did not change significantly (from 53 +/- 9.3 mL to 60 +/- 9.0 mL and from 20 +/- 2.3 mL to 21 +/- 3.2 mL, respectively) in the CMP group. In the control group, however, right ventricular end-diastolic volume and stroke volume increased significantly from 45 +/- 7.7 mL to 63 +/- 14 mL (p < 0.05) and from 18 +/- 4.3 mL to 22 +/- 4.2 mL (p < 0.05), respectively. CONCLUSIONS: These results suggest that CMP may reduce right ventricular compliance and restrict right ventricular diastolic filling in response to rapid volume loading because of its external constraint.     

Assessing risk by hemodynamic profile in patients awaiting cardiac transplantation

A profile of hemodynamic abnormalities in patients listed for cardiac transplantation was related to survival during the first year after listing. After a patient is listed for cardiac transplantation, the waiting period for a suitable donor heart is often long; therefore, objective criteria to determine risk would be helpful in identifying the group at highest risk of dying before receiving a transplant. Several studies have suggested certain hemodynamic parameters to be related to a poor prognosis. However, no 1 variable has emerged as an adequate predictor of survival in patients awaiting cardiac transplantation. One-year outcomes were examined in 138 consecutive patients listed for cardiac transplantation, who were grouped according to a hemodynamic risk score (HRS) based on abnormalities in baseline measures of right atrial pressure, pulmonary artery systolic pressure, transpulmonary gradient, cardiac output, cardiac index and pulmonary vascular resistance. Right atrial pressure alone was the most significant predictor of survival (p < 0.05). Patients with a right atrial pressure > 12 mm Hg had a 47% 1-year survival as compared with the 68% survival for those with a right atrial pressure < 12 mm Hg. HRS was the next strongest predictor of survival. The 66% survival in group I (HRS = 0) and the 69% survival in group II (HRS = 1 to 3) were significantly (p < 0.03) higher than the 41% survival in group III (HRS = 4 to 6) at 1 year after listing. Differences in survival for the HRS groups could not be explained by left ventricular ejection fraction, left ventricular end-diastolic diameter or status at listing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.     

New aspects of the treatment of left ventricular failure: Nitroglycerin (author's transl)

The effectiveness of Nitroglycerin and its derivates in angina pectoris is well-known. One of the main effects is the reduction of left ventricular filling pressure. Therefore in patients with left ventricular failure after acute myocardial infarction or with chronic coronary heart disease the indication for Nitroglycerin has to be proved. In 51 patients with 76 measurements Nitroglycerin sublingual, intravenous Nitroglycerin, Isosorbide-Dinitrate and Myocardon were investigated. All substances decreased pulmonary artery pressure especially left ventricular filling pressure. Cardiac output increased or decreased in dependence to the height of left ventricular enddiastolic pressure. In the patients with myocardial infarction and left ventricular failure with filling pressures over 20 mm Hg a significant increase in cardiac output was observed. On the contrary in patients without left ventricular failure cardiac output decreased slightly. Nitroglycerin sublingual is especially useful in the most severe form of left ventricular failure: in pulmonary oedema. 0.8 mg of Nitroglycerin 3 to 4 times in 5 to 10 minutes distance is necessary dependent on the severity of the pulmonary oedema and the height of the blood pressure. The permanent intravenous infusion of Nitroglycerin (3 to 6 mg per hour) is very efficient in the treatment of congestive failure in acute myocardial infarction. The left ventricular filling pressure decreased from 28 to 16 mm Hg with an increase in cardiac output from 3.5 to 4.01/min. The mean arterial pressure dropped about 10 mm Hg. Also with oral derivates of Nitroglycerin (Isosorbide-Dinitrate and Myocardon) an extensive decrease in left ventricular filling pressure and an increase in cardiac output has been observed in patients with left heart failure.     

An intracorporeal (abdominal) left ventricular assist device. Initial clinical trials

We have initiated clinical trials with an intracorporeal (abdominal) partial artificial heart and ten preterminal postcardiotomy patients have been studied. During profound left ventricular failure, the device captures the entire cardiac output from the apex of the left ventricle at low pressures (20 to 40 mm Hg) and ejects (at 80 to 150 mm Hg) into the infrarenal abdominal aorta; the biological aortic valve opens only intermittently and the entire systemic circulation is pump generated. The device is six to ten times more effective than intra-aortic balloon pumping in man and has maintained systemic perfusion during clinical asystole and ventricular fibrillation. We have documented that the profoundly depressed postcardiotomy left ventricle, initially incapable of ejection, can recover during total left ventricular unloading with the abdominal left ventricular assist device support over a seven-day period.