Marked Reduction In Cardiac Output Research Articles

Acute Heart Failure: Diagnostic-Therapeutic Pathways and Preventive Strategies-A Real-World Clinician's Guide.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.

Physiological changes during low- and high-intensity noninvasive ventilation

In a physiological randomised cross-over study performed in stable hypercapnic chronic obstructive disease patients, we assessed the short-term effects of two settings of noninvasive ventilation. One setting was aimed at maximally reducing arterial carbon dioxide tension (P(a,CO(2))) (high-intensity (Hi) noninvasive positive pressure ventilation (NPPV)): mean ± SD 27.6 ± 2.1 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 22 breaths · min(-1). The other was performed according to the usual parameters used in earlier studies (low-intensity (Li)-NPPV): 17.7 ± 1.6 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 12 breaths · min(-1). Both modes of ventilation significantly improved gas exchange compared with spontaneous breathing (SB), but to a greater extent using Hi-NPPV (P(a,CO(2)) 59.3 ± 7.5, 55.2 ± 6.9 and 49.4 ± 7.8 mmHg for SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater reduction in the pressure-time product of the diaphragm per minute from 323 ± 149 cmH(2)O · s · min(-1) during SB to 132 ± 139 cmH(2)O · s · min(-1) during Li-NPPV and 40 ± 69 cmH(2)O · s · min(-1) during Hi-NPPV, while in nine out of 15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked reduction in cardiac output (CO) measured noninvasively with a Finometer PRO (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV. We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in CO, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.

Impairment of cardiac insulin signaling and myocardial contractile performance in high-cholesterol/fructose-fed rats

Although insulin resistance is recognized as a potent and prevalent risk factor for coronary heart disease, less is known as to whether insulin resistance causes an altered cardiac phenotype independent of coronary atherosclerosis. In this study, we investigated the relationship between insulin resistance and cardiac contractile dysfunctions by generating a new insulin resistance animal model with rats on high cholesterol-fructose diet. Male Sprague-Dawley rats were given high cholesterol-fructose (HCF) diet for 15 wk; the rats developed insulin resistance syndrome characterized by elevated blood pressure, hyperlipidemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. The results show that HCF induced insulin resistance not only in metabolic-response tissues (i.e., liver and muscle) but also in the heart as well. Insulin-stimulated cardiac glucose uptake was significantly reduced after 15 wk of HCF feeding, and cardiac insulin resistance was associated with blunted Akt-mediated insulin signaling along with glucose transporter GLUT4 translocation. Basal fatty acid transporter FATP1 levels were increased in HCF rat hearts. The cardiac performance of the HCF rats exhibited a marked reduction in cardiac output, ejection fraction, stroke volume, and end-diastolic volume. It also showed decreases in left ventricular end-systolic elasticity, whereas the effective arterial elasticity was increased. In addition, the relaxation time constant of left ventricular pressure was prolonged in the HCF group. Overall, these results indicate that insulin resistance reduction of cardiac glucose uptake is associated with defects in insulin signaling. The cardiac metabolic alterations that impair contractile functions may lead to the development of cardiomyopathy.

Chronic β-agonist administration affects cardiac function of adult but not old rats, independent of β-adrenoceptor density

Although beta-adrenoceptor agonists have clinical merit for attenuating the age-related loss of skeletal muscle mass and strength (sarcopenia), potential cardiac-related side effects may limit their clinical application. The aim of this study was to determine whether chronic beta-agonist administration impairs cardiac function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats were treated with fenoterol (1.4 mg.kg(-1).day(-1) ip) or vehicle for 4 wk. Heart function was assessed in vitro before analyses of cardiac structure and beta-adrenoceptor density. Heart mass increased 17% and 25% in fenoterol-treated adult and aged rats, respectively. The increased heart mass in aged, but not adult, rats was associated with a relative increase in collagen content. Cardiac hypertrophy in adult rats was associated with an increase in left ventricular developed pressure, a marked reduction in cardiac output, and a reduction in coronary flow per unit heart mass. In contrast, negligible differences in ventricular function were observed in fenoterol-treated aged rats. The differential effect on contractile function was not associated with age-related differences in beta-adrenoceptor density but, rather, an age-related increase in downregulation after treatment. Our results show that chronic beta-agonist treatment impairs cardiac function to a greater extent in adult than in aged rats. These results provide important information regarding the potential effects of chronic beta-agonist use on cardiac function and the future development of safe and effective treatments for sarcopenia.

Maternal central hemodynamics in hypertensive disorders of pregnancy

Objective: To document maternal central hemodynamics during the preclinical and clinical phases of nonproteinuric gestational hypertension and preeclampsia. Methods: We conducted a longitudinal study of 400 primigravidas who were monitored throughout pregnancy using Doppler echocardiography. Multinomial logistic regression was used to identify variables associated with risk of hypertension. Results: Gestational hypertension developed in 24 women and preeclampsia developed in 20. Compared with normotensive controls, women who had preeclampsia had significantly elevated cardiac outputs before clinical diagnosis, but total peripheral resistance was not significantly different during this latent phase. During the clinical phase of preeclampsia, there was a marked reduction in cardiac output and increase in peripheral resistance. All women who had gestational hypertension had significantly elevated cardiac outputs before and during the clinical course of the condition. Conclusion: Our data support the concept of a hyperdynamic disease model for preeclampsia, with a subsequent hemodynamic crossover to low cardiac output and high resistance circulation coinciding with the onset of the clinical syndrome. Women with gestational hypertension had no such hemodynamic crossover and maintained hyperdynamic circulation throughout pregnancy.

Echocardiographic and Survival Studies in Mice Undergoing Endotoxic Shock: Effects of Genetic Ablation of Inducible Nitric Oxide Synthase and Pharmacologic Antagonism of Platelet-Activating Factor

Evidence implicating inducible nitric oxide synthase (iNOS) in the alterations of cardiac function characteristic of septic shock has come mostly from studies on anesthetized animals, isolated hearts, cultured myocytes, or hosts treated with pharmacologic inhibitors that lack complete specificity for iNOS. Platelet-activating factor (PAF) can participate in the induction of iNOS and has also been implicated in cardiac dysfunction in sepsis. The present studies assessed cardiac function in a model of sepsis in awake mice in which the gene for iNOS was either normal or selectively disrupted. Mice of each genotype were treated with parenteral fluids or with a highly specific antagonist of PAF. Endotoxic shock was induced by challenge with bacterial lipopolysaccharide (LPS) after priming with heat-killed Propionobacterium acnes. Wild-type mice increased stroke volume and cardiac output in response to LPS. These changes were absent in iNOS-deficient mice. When treated with parenteral fluids, LPS-challenged wild-type and iNOS-deficient mice both had a marked reduction in cardiac output. Antagonism of PAF had no effect on echocardiographic indices in wild-type mice, but selectively overcame the bradycardia and reduced cardiac output elicited by fluid administration in LPS-shocked, iNOS-deficient mice. Thus, there are major cardiovascular effects of PAF that are shared by rather than mediated by iNOS. Neither complete iNOS deficiency nor antagonism of PAF improved survival, whether tested as single or combined intervention. On the contrary, complete deficiency of iNOS was detrimental to survival. Finally, we tested the hypothesis that iNOS deficiency might improve survival if the deficiency were specific but partial. For this, we used mice with one normal and one disrupted gene for iNOS. No survival advantage was evident for these iNOS heterozygotes. Thus, partial or complete inhibition of iNOS, with or without antagonism of PAF, afforded no evident benefit beyond the previously demonstrated reduction in hypotension. Finally, these studies demonstrate that echocardiography preceded by acclimatization is feasible in unanesthetized mice, a finding which should expand the value of genetically manipulated animals for analysis of cardiac function.

Cardiopulmonary effects of positive end-expiratory pressure in anesthetized, mechanically ventilated ponies

Summary To investigate the cardiopulmonary effects of positive end-expiratory pressure (peep), values of 10, 20, and 30 cm of H2O, were applied to anesthetized, dorsally recumbent, ventilated ponies. After iv induction of general anesthesia, peep was superimposed on controlled ventilation with 100% oxygen, and changes in gas exchange and cardiac function were measured. Increasing values of peep in these ponies caused a linear increase in the mean (± SEM) functional residual capacity, from a control value (zero end-expiratory pressure) of 1.7 ± 0.24 L to 2.2 ± 0.31, 2.9 ± 0.32 and 3.4 ± 0.3 L at peep of 10, 20, and 30 cm of H2O, respectively (P < 0.05). Paralleling these changes, intrapulmonary shunt fraction decreased significantly (P < 0.05) from a control value of 12.9 ± 0.5%, to 7.5 ± 1.1 and 2.1 ± 0.6%, at peep of 20 and 30 cm of H2O, respectively. Cardiac output was decreased by increasing values of peep, from control value of 11.7 ± 1.56 L/min to 9.9 ± 1.51, 8.8 ± 1.33 and 5.62 ± 0.56 L/min at peep of 10, 20, and 30 cm of H20, respectively. Related to decreasing cardiac output, tissue oxygen delivery also decreased as peep was increased, from control value of 2.0 ± 0.09 L/min to 1.8 ± 0.07, 1.6 ± 0.06, and 1.03 ± 0.04 L/min at peep of 10, 20, and 30 cm of H2O, respectively. Thus, the effects of increasing values of peep in these ponies included increased functional residual capacity and arterial oxygenation, but marked reduction in cardiac output, resulting in no improvement or decrease in total oxygen delivery. Although peep is useful for improving arterial oxygenation, the deleterious cardiovascular effects should be anticipated or ameliorated by use of volume loading and/or inotrope administration.

Prophylactic and delayed treatment with indomethacin in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia.

The effects of prophylactic and delayed treatment with indomethacin were evaluated in a porcine model of early adult respiratory distress syndrome (ARDS) induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with indomethacin i.v., 5 mg . kg-1 in 30 min, followed by further infusion at a rate of 2 mg . h-1 . kg-1. Ten animals received the same dosage of indomethacin beginning 2 h after the start of endotoxin infusion. Pretreatment with indomethacin inhibited the endotoxin-induced impairment in pulmonary gas exchange, but did not prevent pulmonary oedema. The pulmonary hypertension was counteracted. Oxygen delivery did not improve, because of a marked reduction in cardiac output (Qt). Systemic vascular resistance (SVR) increased markedly, and mean arterial pressure (MAP) was higher. Survival was improved. Delayed indomethacin treatment prevented a further deterioration in pulmonary gas exchange and restored it towards the baseline level. The pulmonary oedema was not counteracted, while the pulmonary hypertension was reduced. O2 delivery was not restored, owing to the greater decrease in Qt compared with the untreated endotoxin group. SVR increased considerably, and MAP was better maintained. Survival was not improved. These results indicate that cyclo-oxygenase inhibitors might benefit pulmonary gas exchange in human ARDS. Drugs which interfere with arachidonate metabolism will probably be of great importance in the prophylaxis, in particular, and also in the treatment of ARDS.

Effects of Food Restriction on Cardiac Output and Blood Flow to the Uterus and Placenta in the Pregnant Rat

Cardiac output and blood flow to the uterus, ovary and placenta were determined at day 21 of gestation in rats fed ad libitum a standard diet or 50% of control intake from day 5 of gestation. Restricted rats had lower body weights, smaller fetuses and placentas and a marked reduction in blood flow to ovary and placenta but not to endometrium and myometrium. These animals also had a marked reduction in cardiac output. However, the percent distribution of cardiac output in the whole uterus, ovary and placenta was similar in control and restricted rats. Results suggest that food restriction decreases expansion in uterine and placental blood flow by interfering with the expansion in cardiac output which normally occurs in pregnancy.

Use of the bovine with an artificial heart as an experimental pharmacologic model. Peripheral vascular and direct cardiac effects of a large dose of dopamine.

ABSTRACTPeripheral vascular and direct cardiac effects of a single intravenous injection of a large dose of dopamine (50μg/Kg) were determined in ten unanesthetized calves before and after replacement of their natural hearts (NH) with pneumatically driven artificial hearts (AH). Data were recorded before and three minutes after injection of dopamine, when alpha adrenergic effects were maximal. Dopamine markedly increased systemic vascular resistance (from 919 to 1490 dyne ˙ sec/cm5 in NH calves and 896 to 1420 dyne ˙ sec/cm5 in AH calves), mean aortic pressure (from 105 to 144 torr in NH calves and 109 to 129 torr in AH calves), mean pulmonary artery pressure (from 20 to 25 torr in NH calves and 18 to 30 torr in AH calves), and mean right atrial pressure (from 5 to 8 torr in NH calves and 6 to 10 torr in AH calves). Dopamine significantly decreased stroke volume (from 100 to 90 ml in NH calves and 101 to 74 ml in AH calves) and cardiac output (from 8.7 to 7.3 L/min in NH calves and 9.2 to 6.7 L/min in AH calves). Heart rate was significantly reduced by dopamine in NH calves (from 87 to 81 beats/min) but was fixed (91 beats/min) in AH animals. Changes in stroke volume, cardiac output and mean pulmonary artery pressure were significantly greater in AH calves while mean aortic pressure was increased significantly more in NH calves. Increases in right atrial pressure and systemic vascular resistance after dopamine were similar in both groups of animals.Dopamine also produced marked changes in respiratory dynamics. The compound significantly decreased tidal volume (from 612 to 344 ml in NH calves and 582 to 236 ml in AH calves), minute volume (from 19.6 to 10.3 L/min in NH calves and 20.4 to 6.6 L/min in AH calves) and minute oxygen uptake (from 488 to 430 ml in NH calves and 507 to 355 ml in AH calves). Dopamine also reduced respiratory rate, but only in AH calves (from 35 to 28 breaths/min). Changes in respiratory rate, minute ventilation and oxygen uptake were significantly greater in AH than NH animals. These data demonstrate that large bolus injections of dopamine can produce significant decreases in cardiac output and respiratory dynamics. They also indicate that an animal with an artificial heart, or at least an artificial heart which is unable to respond to the positive inotropic effect of dopamine, will experience a more marked reduction in cardiac output and minute ventilation than an animal with its natural heart.

Regional distribution of blood flow during arterial hypertension produced by lesions of the nucleus tractus solitarii in rats.

Changes in the fractional distribution of cardiac output (FF), organ blood flow, and regional vascular resistance were measured by the isotope dilution technique of Sapirstein using 86Rb as indicator in unanesthetized rats during acute arterial hypertension produced by bilateral lesions of the nucleus tractus solitarii (NTS). After NTS lesions, the FF was significantly reduced in skin, muscle, and colon, increased in ventricular myocardium, spleen, and adrenal glands, and was unchanged elsewhere. Because of a marked reduction in cardiac output (CO) during hypertension, the absolute organ blood flow (FF X CO) was reduced in lesioned rats to 30-40% of control in skin, muscle, and colon and between 60% and 75% of control in most of the remainder of the gastrointestinal tract and renal cortex; it was unchanged in myocardium and endocrine glands. Resistance was substantially increased (4- to 6-fold) in skin, muscle and colon but was only moderately increased (1.5- to 2.5-fold) in the remaining organs. The results indicate that, while NTS lesions will increase resistance in most vascular beds, the response is unequally distributed, influencing skin, muscle, and colon disproportionately to other tissues. Because of an interaction between a reduction in CO and little autoregulation, blood flow is reduced primarily in skin, muscle, and colon. The pattern of redistribution of CO was consistent with the interpretation that NTS hypertension results from interrupting baroreceptor reflexes centrally. The pattern of redistribution of blood flow in rats with NTS lesions differs from that produced by deoxycorticosterone acetate-salt and renal ischemia.

CIRCULATORY INFLUENCES OF ARTIFICIAL VENTILATION DURING NITROUS OXIDE ANAESTHESIA IN MAN: II: RESULTS: THE RELATIVE INFLUENCE OF MEAN INTRATHORACIC PRESSURE AND ARTERIAL CARBON DIOXIDE TENSION

SUMMARY In nineteen normal patients, anaesthesia was induced with thiopentone and maintained with nitrous oxide, oxygen and a muscle relaxant, supplementary analgesia being produced with small doses of phenoperidine. Under these conditions, cardiac output and other haemodynamic variables were measured during spontaneous and artificial ventilation. The relative circulatory influence of independent and alternated changes of mean intrathoracic pressure and arterial Pco2 were studied during established artificial ventilation. Although a marked reduction in cardiac output occurred in every patient during the transition from spontaneous to artificial ventilation, this could not be correlated with changes in arterial Pco2 or mean intrathoracic pressure. There was a linear relationship between cardiac output and arterial Pco2 over a wide range of the latter and this relationship was independent of the pattern of ventilation. At a mean arterial Pco2 of 23 mm Hg, cardiac output was reduced to a mean of 72 per cent of the value during spontaneous ventilation. Alterations of mean intrathoracic pressure produced by changes from intermittent positive pressure ventilation to intermittent positive-negative pressure ventilation and vice versa, did not produce significant changes in cardiovascular function either at low or normal values of arterial Pco2.

STUDIES ON LIVER CIRCULATION DURING HEMORRHAGIC SHOCK; THE RELATION BETWEEN LIVER CIRCULATION AND CARDIAC OUTPUT AND OXYGEN CONSUMPTION IN THE INTERNAL ORGANS

Recently, the hepatic circulation in hemorrhagic shock has been investigated by HEINEMANN, BRADLEY, SELKURT, FRANK and others. However, the opinions among the authors have not yet been in agreement but rather controversial, par icularly, as to the relationship between hepatic blood flow and cardiac output. HEINEMANN reported that hepatic blood flow fell sharply following hemorrhage and then returned spontaneously the control level in absence of the restoration of blood pressure. While, the others reported that hepatic blood flow did not recovered and remained in decreased level, having the same trend in blood pressure change. It seems likely that such a controversy will be partly due to the difference of the methods employed in measuring hepatic blood flow and partly to the confusion in recognizing the stage of shock, because the sequence of respective hemodynamic phenomenon is considerably different at the period of observation in this condition. The purpose of the present paper is to classify the relationship of hepatic blood flow and cardiac output throughout the entire course of hemorrhagic shock and its bearing on the irreversibility of shock. Oxygen utilization in the splanchnic viscera was also studied. The Relationship between Hepatic Blood Flow and Cardiac Output 1) Methods : Hepatic blood flow was measured by modified Frank's method. Twenty-two dogs ranging in weight from 8 to 20 kg were used and anesthetized with intravenous pentobarbital sodium of 25 mg/kg. A polyethylene catheter was passed through a right external jugular vein into the hepatic vein and then wedged into one of hepatic lobar veins. The outer end of the catheter in the hepatic vein was fixed at the level of the vena cava and allowed to drain continuously. The rate of hepatic outflow was measured by a graduated cylinder and stop watch. The blood collected was returned by transfer to an elevated burette draining into a left external jugular vein. Heparin (3-5 mg/kg) was given intravenously during the experiments. Cardiac output was calculated from indicator dilution curves according to the STEWART-HAMILTON principle. Two different procedures were used. In one method 32P labelled red cells were used as an indicator and injected intravenously. Blood samples were collected successively from the femoral artery. In another cases, radio-iodinated serum albumin (RISA) was injected as an indicator. Cardiac output was calculated from radio-cardiograms by using a scintillation detector at the heart region and a rate-meter. 2) Results : We could distinguish the following two stages in hemorrhagic shock in relation to hepatic blood flow and cardiac output. a) The first stage : In the early stage of shock, hepatic blood flow decreases in parallel with the changes in cardiac output. b) The second stage : After same delay from the initial bleeding, hepatic blood flow decreases progressively without marked reduction in cardiac output. Consequently, a difference or "gap" appears in percentile changes of hepatic blood flow and cardiac output. c) Effects of transfusion : Complete recovery of arterial pressure, cardiac output and hepatic blood flow can be obtained by a transfusion performed in the first stage. Whereas, the transfusion made in the second stage give rise only transient recovery of arterial pressure and cardiac output.

Role of venous return in the cardiovascular response following injection of ganglion-blocking agents.

The reduction of arterial pressure in anesthetized dogs following the injection of ganglion-blocking agents is dependent primarily upon a reduction in arterial vasomotor activity and secondarily upon a reduction in venous return associated with an increase in vascular capacity. When venous return is maintained at control levels, the administration of the blocking agents of this study invariably produce a decrease in total peripheral resistance (TPR). Ordinarily in the intact animal such a decrease in TPR is not observed due to a marked reduction in cardiac output which produces a secondary increase in TPR. The results of this study further suggests that the venous and arterial systems may differ in their sensitivity to the effects of ganglion-blocking agents.