The hemostatic effect of packed red cell transfusion in patients with anemia

BACKGROUND: The hemostatic effect of platelets has been well established, but the possible role of red cells in hemostasis has not yet been well studied. An evaluation of the hemostatic effect of packed red cell transfusion in patients with chronic anemia was the purpose of this study. STUDY DESIGN AND METHODS: In a prospective study, bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) were measured before and after the transfusion of allogeneic packed red cells in 42 patients with chronic anemia. The results were compared and analyzed. RESULTS: APTT and BT decreased significantly after transfusion, by a mean of 1.3 seconds (p = 0.01) and 2.6 minutes (p < 0.01), respectively. PT did not change significantly after transfusion (p = 0.65). Factors studied (patient's age, sex, and renal function measurements; pretransfusion and posttransfusion hemoglobin levels, platelet counts, and PTs; change in platelet count [delta platelet count] and PT [delta PT] after transfusion) did not independently affect the change in BT (delta BT) or in APTT (delta APTT). The delta BT was not affected by the pretransfusion or posttransfusion levels of APTT or by the delta APTT. The delta APTT was not affected by the pretransfusion or posttransfusion levels of BT or by the delta BT. Diagnosis of malignant or benign diseases was found to affect delta APTT, but not delta BT. Patients with pretransfusion hemoglobin < or = 60 g per L had a 4.07 times greater chance of posttranfusion increase in BT than the patients with hemoglobin > 60 g per L (p = 0.04). CONCLUSION: Red cell transfusion might decrease the APTT and BT in some anemic patients, though the actual cause of the decrease was not determined in the present study.     

Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease

OBJECTIVE: To study in anemic patients with chronic obstructive pulmonary disease (COPD) whether blood transfusion reduces minute ventilation and work of breathing (WOB). DESIGN: We prospectively evaluated the minute ventilation and WOB in 20 anemic adults (hemoglobin of <11 g/dL). Ten patients had severe COPD and ten patients were without lung disease. Measurements were made before and after receiving red blood cell transfusion; post-transfusion measurements were made 24 to 36 hrs after the last transfusion. SETTING: The study was performed in the intensive care unit of a tertiary referral center for home mechanical ventilation and for patients considered difficult to wean from mechanical ventilation. PATIENTS: Twenty clinically stable patients (12 female, eight male) with chronic anemia were studied. Ten patients with COPD (mean forced expiratory volume in 1 sec: 0.55+/-0.1 [SD] L) were compared with ten patients without lung disease. All participants had adequate renal and left ventricular function. INTERVENTIONS: Patients received 1 unit of packed red blood cells for each g/dL that their hemoglobin value was less than an arbitrarily defined target value of 11.0 to 12.0 g/dL. Each unit was transfused over 2 hrs and < or =3 units in total was given. MEASUREMENTS AND MAIN RESULTS: Esophageal pressure was measured from a catheter which was positioned in the middle of the esophagus. Flow was measured using a pneumotachygraph connected to a mouthpiece while a nose clip closed the nostrils during the measurements. From these data, respiratory rate, minute ventilation, and inspiratory resistive WOB were computed. Arterial blood gas values, oxygen saturation, hemoglobin, and hematocrit were also measured, and oxygen content was calculated before and 24 to 36 hrs after transfusion. In patients with COPD, hemoglobin increased from 9.8+/-0.8 to 12.3+/-1.1 g/dL due to a mean transfusion of 2.2+/-0.4 (SD) units of red blood cells. There was a reduction in the mean minute ventilation from 9.9+/-1.0 to 8.2+/-1.2 L/min (p < .0001); correspondingly, WOB decreased from 1.03+/-0.24 to 0.85+/-0.21 WOB/L (p< .0001). The capillary P(CO2) increased from 38.1+/-6.0 to 40.7+/-6.8 torr (5.1+/-0.8 to 5.8+/-0.9 kPa) (p < .05). Similarly, capillary P(O2) changed from 56.9+/-8.9 to 52.8+/-7.0 torr (7.6+/-1.2 to 7.0+/-0.9 kPa) (p < .05). In anemic patients without lung disease, minute ventilation, WOB, and the capillary blood gas values did not change after increase of the hemoglobin by a similar degree. CONCLUSIONS: We conclude that red blood cell transfusion in anemic patients with COPD leads to a significant reduction of both the minute ventilation and the WOB. In these patients, transfusion may be associated with unloading of the respiratory muscles, but it may also result in mild hypoventilation.     

A retrospective audit of blood loss in total hip joint replacement surgery at Middlemore Hospital

AIMS: To quantify the level of inappropriate red cell transfusion in primary and complex hip replacement surgery. METHODS: Data extraction was by retrospective review of patients records. Calculation of total red cell volume loss was by use of pre and postoperative (day 7) haematocrit levels, patient weight and number of units transfused. Transfusion was accepted as justified only if instituted for a 30% red cell volume loss or loss sufficient to drop the haematocrit below 0.28. RESULTS: Of 104 patients having primary hip joint replacement, 58 were transfused with a total of 157 units of red cells; 37 (24%) of these units were given inappropriately. Of 38 patients having complex hip replacement operations, 32 were transfused with a total of 139 units of red cells; 12 (9%) of these were given inappropriately. CONCLUSIONS: Inappropriate transfusion occurs in hip replacement surgery. A concurrent audit of red cell usage is required to better define the magnitude of the problem. Two unit transfusion is commonly given when one unit would have been sufficient.     

Preload and incident angle independent index of left ventricular contractility determined by continuous wave Doppler echocardiography

BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated blood and conventionally stored blood on oxygen consumption in acutely anemic dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1 hour they were transfused to a hematocrit of 18% with control or phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin P50 measurements allowed calculation of oxygen consumption during anemia, and posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with phosphoenolpyruvate-treated blood allowed greater O2 consumption than control (8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or venous PO2 or pH; there were marked differences in HOA, measured by posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation. CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen consumption at a similar hematocrit when compared with untreated banked blood.     

Left ventricular diastolic pressure-volume relations in man

Diastolic function of the left ventricle was analysed in patients with different cardiac diseases: acute and chronic volume overload (in aortic and mitral incompetence), pressure overload and inappropriate ventricular hypertrophy (aortic stenosis and hypertrophic cardiomyopathy), congestive cardiomyopathy, and constrictive pericarditis. Most patients were receiving digitalis therapy at the time of study. A constant exponential relation between pressure and volume was assumed, and pressure-volume curves were constructed from two points: the instantaneous pressure-volume relation at beginning-diastole and at end-diastole. The determinants of left ventricular end-diastolic pressure were studied. Left ventricular end-diastolic pressure depended on the beginning-diastolic pressure and volume (O point), the slope of the pressure-volume curve (m), and the volume which distended the ventricle in diastole. In chronic volume loading and in congestive cardiomyopathy the curves were flatter than normal, so that left ventricular end-diastolic pressure was only slightly increased despite the large volume filling the ventricle. In pressure overload and in constrictive pericarditis the curves were steeper than normal. Acute changes in volume were accomplished by a shift up or down the pressure-volume curve but in these patients the slope was not altered: the ventricle had not had time to adapt and end-diastolic pressure was greatly increased.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.     

Effect of dextran loading on left ventricular performance in chronic obstructive pulmonary disease

The status of left ventricular function in patients with chronic obstructive pulmonary disease remains controversial. With a radionuclide technique left ventricular ejection fraction, left ventricular end-diastolic volume, cardiac output, and stroke volume were measured at rest and following infusion of dextran in 23 men with severe COPD. Resting, mean LVEF was normal in 19 subjects with COPD alone; four with COPD and coronary artery disease had a depressed mean LVEF. Left ventricular end-diastolic volume index and pulmonary capillary wedge pressure were both normal at rest indicating that the left ventricle was not volume underloaded. There was a normal response to dextran infusion (750 ml.) with no deterioration in LVEF and a significant increase in cardiac index, stroke volume index, LVEDVI, and PCW. These data suggest that at rest and following volume loading with dextran left ventricular function is normal in patients with COPD.     

Intraoperative extra strong electrical stimulation in the treatment of peripheral nerve injury

OBJECTIVE: To explore the Yinji Capsule (YJC) in improving the left ventricular systolic function of angina pectoris patients with Blood Stasis Syndrome. METHODS: The systolic function of left ventricle (LV) in cardiac cycle of 28 angina pectoris patients with Blood Stasis Syndrome was examined with three-dimensional echocardiograph (3-DE) before and after treatment with YJC. RESULTS: The total symptomatic effective rate was 85.7%. The changes of LV systolic function were those: left ventricle ejection fraction (LVEF) increased from 45.0 +/- 4.9% to 48.2 +/- 3.5% (P < 0.05); EF on early stage and late stage increased from 22.6 +/- 2.1%, 8.3 +/- 1.2% to 28.1 +/- 3.0% and 10.3 +/- 0.9% respectively (P < 0.01, P < 0.05), myocardial region with segment systole (SS) < 5% decreased significantly (P < 0.01). CONCLUSION: YJC could improve LV systolic function on early stage and late stage in cardiac cycles, and mainly improve the systolic function of the region with low SS of LV.     

Intralesional cytokine therapy in cancer: a pilot study of GM-CSF infusion in mesothelioma

Most cases of left ventricular aneurysms undergo operation through resection of the exteriorized dyskinetic area with longitudinal suturing of the opening and this technique has been considered by cardiologists (Froehlich et al) to bring no improvement to the morphology and performance of the left ventricle. Some technical modifications have been adopted, such as the septal plicature (Cooley) or circular suturing of the opening (Jatene). Since 1984 our team has used an endoventricular patch, sutured over the contractile area and excluding the akinetic non-resectable scars, bringing a significant and calculable improvement to the left ventricular function. This technique of left ventricular reconstruction (LVR), called endoventricular circular patch plasty (EVCPP) has been already used on more than 750 patients (May 97). Clinical and echographic data for each case are completed by right catheterisation with measurement of the cardiac output, pulmonary arterial pressures (PAP) and programmed ventricular stimulation (PVS), in order to detect eventual ventricular tachycardia (IVT). During left heart catheterisation, the morphology of the left ventricle (LV) is studied on right and left anterior oblique incidences and the LV ejection fraction (EF) is checked globally (GEF) and especially in its contractile portion (CEF). After surgery, a hemodynamic study associated with a PVS, is carried out during the first post-operative month, and again after one year. Results were clinically satisfactory in more than 90% of cases (8.9% of NYHA III-IV), and in more than 90% of cases with ventricular arrhythmia with the hemodynamic persistent EF at one year, superior to the pre-operative CEF. Thus we have to propose the following indications: Elective: This ventricular reconstruction can be recommended for ventricular aneurysms or akinesias with angina, arrhythmias or attacks of cardiac insufficiency, when GEF > 30% and CEF > 40%. The operative mortality rate varies from 1,5 to 3%, which is better than allowing natural evolution. Mandatory: In emergency, when safe immediate circulatory assistance or a cardiac transplant is unavailable, LVR can give hope for survival to more than 80% of patients, whereas natural evolution is without hope. Finally the operative indication is uncertain in two contrasting circumstances: In asymptomatic patients when hemodynamic and angiographic examinations after myocardial infarction show left ventricular dyskinesia. If GEF is below 40% and CEF below 50%, it seems wise to propose LVR in order to prevent unfavourable evolution. In end-stage ischemic cardiomyopathies, if the EF is below 20%, CEF is below 30%, cardiac output is below 1.5 l, and the mean pulmonary pressure is above 25, then a cardiac transplant should be considered. EVCPP with septal exclusion is a safe technique and easily reproduced when associated with coronary revascularization as far as practicable, then EVCPP improves the ventricular function. When associated with sub-total endocardectomy, then EVCPP allows excellent control of VA.     

A clinical and economic evaluation of red blood cell transfusions in patients receiving cancer chemotherapy

A clinical and economic evaluation of red blood cell (RBC) utilization in cancer patients during chemotherapy is described. Using a randomized sampling process, 100 patients who had received chemotherapy with or without cisplatin were selected (50 in each group). Multiple logistic regression was then used to identify risks factors for transfusion requirements. Twenty-five percent of patients in the cisplatin and 12% in the noncisplatin group received at least one blood transfusion during chemotherapy (p = .09). Depressed hemoglobin levels and cisplatin dosage were identified as risk factors for transfusion requirements. Combining all transfused patients revealed an overall cost of Can $599 (95% CI: $513-$683) per transfusion. The results of the current study indicated that anemia is a common complication of cancer chemotherapy that can be costly to manage.     

Myocardial performance in critically ill patients: response to whole blood transfusion as a prognostic measure

The standardized stroke work, which is derived from the left ventricular stroke work (LVSW) and the pulmonary capillary wedge pressure (WP), is presented as a convenient index for tracking changes in the overall cardiac function and relating these changes to other cardiorespiratory variables. This index and its response to whole blood transfusion were used to assess cardiac function in 102 critically ill patients with hemorrhagic or traumatic shock. Survivors had greater mean values of the standardized stroke work before, during, and after transfusion than did the nonsurvivors (p < 0.05). Moreover, the maximal change in standardized stroke work in response to transfusion was greater in survivors than in nonsurvivors (p < 0.05): this response was found to be dependent on the stage of shock. The experience of the authors with this index suggests that it is a useful way to follow changes in myocardial performance in critically ill patients over time, and in quantitating changes in myocardial function after whole blood transfusion or other forms of volume therapy.     

Adaptational behaviour of peripheral and central acoustic responses in guinea pigs under the influence of various fractions of an extract from Gingko biloba (author''s transl)

Cardiopulmonary function studies at rest and during submaximal and maximal exercise were performed in 21 children and adolescents who had undergone surgical correction of tetralogy of Fallot. Maximal oxygen uptake of the patients was 84.6% of healthy peers matched for age and height. The reduced aerobic capacity can mainly be attributed to a reduction in stroke volume. In the presence of a reduced stroke volume normal cardiac output during submaximal exercise was achieved and maintained by an increase in heart rate. During maximal exercise, however, the heart rate did not exceed that of the healthy controls and the results for the children in this series are about 20% higher than those reported in the literature for adults who had undergone surgical repair of a tetralogy. Persistent impairment of cardiac function in patients with tetralogy of Fallot who have undergone corrective surgery may represent a residual outflow tract obstruction in the right ventricle, impaired function of the left ventricle or the result of restricted physical activity.     

Further studies of the relationships among strains classified as taxon 15, taxon 18, taxon 20, (Pasteurella) granulomatis or the (Pasteurella) haemolytica-complex in ruminants using quantitative evaluation of phenotypic data

Congestive heart failure (CHF) patients share several similar features, such as reduced cardiac contractility and neurohumoral activation to compensate the impaired cardiac function. In CHF patients, the cardiac renin-angitensin (RA) system, receptors, GTP-binding proteins, and their effector molecules are inevitably exposed to chronically elevated neurohumoral stimulation. A widely recognized concept is that a chronic increase in such stimulation can desensitize target cell receptors and the post-receptor signal transducing pathway. Recently, reports of several studies have indicated that the inhibitory GTP-binding protein (Gi) can be increased in CHF patients and animal models. Although direct evidence for a change in catalytic protein of adenylyl cyclase has not been found, limited information has suggested a reduced catalytic activity in terminally failing hearts. In this paper, we have assessed the changes in beta AR, GTP-binding protein, catalytic protein and beta ARK. We also examined angiotensinogen mRNA expression in failing heart. It was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Immunohistochemical studies revealed a stronger reaction in the endocardial layer of the human left ventricle than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. Our experiments revealed a widespread immunopositive reaction for angiotensinogen in the left ventricle of diseased hearts. In the non-diseased heart, ACE and AT1 receptor RNA are present in ventricular muscles. Renin and Ao mRNA could not be detected in the subendocardium of non-diseased left ventricle, but both were present in the left ventricle of diseased hearts. These data indicate that the cardiac RA system plays an important role in the deterioration of cardiac function.     

Ventricular interdependence: significant left ventricular contributions to right ventricular systolic function

This article reviews diastolic and systolic ventricular interaction, and clinical pathophysiological conditions involving ventricular interaction. Diastolic ventricular interdependence is present on a moment-to-moment, beat-to-beat basis, and the interactions are large enough to be of physiological and pathophysiological importance. Although always present, ventricular interdependence is most apparent with sudden postural and respiratory changes in ventricular volume. Left ventricular function significantly affects right ventricular systolic function. Experimental studies have shown that about 20% to 40% of the right ventricular systolic pressure and volume outflow result from left ventricular contraction. This dependency of the right ventricle on the left ventricle helps to explain the right ventricular response to volume overload, pressure overload, and myocardial ischemia. The septum and its position are not the sole mechanism for ventricular interdependence. Ventricular interdependence causes overall ventricular deformation, and is probably best explained by the balance of forces at the interventricular sulcus, the material properties, and cardiac dimensions.     

3-Methoxytyramine as an indicator of impulse-induced dopamine release in rat brain in vivo

Autotransfusions were performed in 80 patients operated upon for thyroid diseases at the Department of Surgery, Institute of Haematology in Warsaw. For autotransfusions patients were selected in good general condition and with haematological indices in the range accepted for blood donors. Planning of autotransfusion is purposeful only in these cases of thyroid disease in which the necessity of blood transfusion can be predicted in advance (e.g. Graves-Basedov-disease, retrosternal goitre, mediastinal goitre). The transfused volume may cover completely or partly the intraoperative blood loss. Autotransfusion protects the patients against possible isoimmunization which may develop after transfusion of blood from donors. Protection of patients against possible immunization is a problem of considerable value. It is important particularly in young subjects, especially young women who may become mothers. Operations connected with blood loss up to 500 ml do not require supplementary transfusions. Intraoperative blood loss in the range from 500 to 1000 ml requires supplementation. The risk of posttransfusion complications is lowest when autotransfusion is done.     

Asynchronous volume changes of the two ventricles after Fontan operation in patients with a biventricular heart

Coordinated contraction of the ventricle is an important determinant of pump function, which seems to be particularly important in Fontan circulation with one pumping ventricle. We analyzed the synchronism of contraction of the two ventricles in 11 patients with a biventricular heart who had undergone Fontan operation. Curves representing ventricular volume changes in a cardiac cycle measured on angiograms were smoothed and divided into 20 segments. We calculated the number of segments of the same directional volume changes (synchronous changes) between the two ventricles (synchronous ratio). We also calculated the total volume of the two ventricles (the two as one whole ventricle) by adding their volumes in each segment and calculated the ratio (stroke volume ratio) of the aortic stroke volume from the whole ventricle to the sum of stroke volumes of the morphological right and left ventricles. If the two ventricles ejected the blood in a completely synchronous manner, these ratios should be 1.0. In seven patients with synchronous ratios of 0.75 or greater and a stroke volume ratio of greater than 0.95, the cardiac index was 3.2 +/- 0.3 l/min/m2, the maximum total volume (corresponding to end-diastolic volume) was 106 +/- 45% normal, and the ejection fraction was 0.44 +/- 0.10. In four patients with ratios of less than 0.70 and 0.95, respectively, the parameters were 2.4 +/- 0.5 (P < 0.05), 193 +/- 92%, and 0.33 +/- 0.08, respectively. The synchronous ratio was inversely correlated with cardiac output. In conclusion, synchronism of the cardiac cycle of the two ventricles affects Fontan circulation in patients with a biventricular heart.     

Right ventricular function: physiological and physiopathological features

Sinus and conus constitute the two cavities of the right ventricle. They are anatomically and functionally different. The sinus is a flow-generator and the conus a pressure-regulator. The coronary circulation of the right ventricle is provided by the right coronary artery and the left anterior descending artery. The right ventricle is perfused during systole and diastole. When oxygen demand increases, coronary arteries dilate and oxygen extraction rises. As for the left ventricle, right ventricular performance depends upon heart rate, rhythm, contractility and loading conditions. Ventricular interactions are very important for right ventricular function. Loading conditions and contractility of the left ventricle are of major significance for right ventricular performance. For the right ventricle, the end of the ejection is different from the end of the active contraction. The time between them allows to achieve ventricular emptying. This duration is linked to afterload. Presently, it is impossible to accurately and simply assess these conditions. Pressure and volume overloadings result in right ventricular failure. They are responsible for ventricular dilation and ischaemia with a decrease in cardiac output, generating a vicious circle. Treatment includes the removal of the cause, and the maintenance of systemic arterial pressure and biventricular contractility. It is difficult to assess the effects of intravenous vasodilators on right ventricular afterload.     

Red blood cell transfusion practices in patients undergoing orthopedic surgery: a multi-institutional analysis

This retrospective review analyzed and compared transfusion practices in patients undergoing orthopedic surgery in five Massachusetts hospitals with current practice guidelines; opportunities for improvement were identified. Patient-specific clinical information and data about transfusion practices were obtained from the medical records of 384 Medicare patients undergoing orthopedic surgery between January 1992 and December 1993. The number of patients who donated autologous blood preoperatively differed significantly among hospitals as did the number of autologous units that were unused. The number of blood units transfused at each transfusion event also differed significantly; some surgeons transfused > or =2 units in the majority of their patients, while others transfused 1 unit at a time. This variation in practice was not explained by differences in patients' clinical status. The mean pretransfusion hematocrit was higher for autologous versus allogeneic blood, suggesting more liberal criteria to transfuse autologous blood. Nearly half of all transfusion events were determined to have been potentially avoidable. Avoidable transfusions were also three to seven times more likely with autologous than with allogeneic blood. Significant inter-hospital differences existed in the number of elective surgery patients exposed to allogeneic blood. The major determinant of allogeneic blood use in these patients was the availability of autologous blood. Each additional autologous blood unit available decreased the odds of allogeneic blood exposure twofold. Differences in intraoperative and postoperative blood salvage use also were noted. These findings indicate that significant variations in practice exist. Comparative data enabled hospitals to identify and target specific areas for improvement.     

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart

BACKGROUND: The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure. METHODS AND RESULTS: The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression. CONCLUSIONS: The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Ten patients with preserved inotropic function having a dual-chamber (right atrium and right ventricle) pacemaker placed for complete heart block were studied. They performed static one-legged knee extension at 20% of their maximal voluntary contraction for 5 min during three conditions: 1) atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HR fixed at the resting value (DOO-Rest; 73 +/- 3 beats/min), and 3) HR fixed at peak exercise rate (DOO-Ex; 107 +/- 4 beats/min). During control exercise (DDD mode), mean arterial pressure (MAP) increased by 25 mmHg with no change in stroke volume (SV) or systemic vascular resistance. During DOO-Rest and DOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of a SV-dependent increase in cardiac output (+1.3 and +1.8 l/min, respectively). The increase in SV during DOO-Rest utilized a combination of increased contractility and the Frank-Starling mechanism (end-diastolic volume 118-136 ml). However, during DOO-Ex, a greater left ventricular contractility (end-systolic volume 55-38 ml) mediated the increase in SV.