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Effects of thiopental and ketamine on cardiac function during moderate hemorrhage in chronically instrumented rats.

This study was designed to assess the effects of thiopental and ketamine on cardiac function after a blood loss of 2 ml/100 g of body weight. In nine Sprague-Dawley rats, a catheter was placed in the abdominal aorta, a pulsed Doppler probe was positioned around the thoracic aorta, and a wall-thickness probe was sutured onto the left ventricle. On three occasions, all rats were studied awake, during thiopental anesthesia, and during ketamine anesthesia. In awake rats, a 30% blood loss resulted in an immediate, transient hypotension (49%) and a prolonged decrease in cardiac output (39%) and stroke volume (28%). No significant changes were observed in the wall-thickening fraction, which is an index of cardiac contractility, and in the heart rate. The effect of thiopental on cardiovascular responses to moderate hemorrhage was minimal. Although ketamine did not affect the hypotensive response to moderate hemorrhage, it did accentuate systemic vasoconstriction and cardiac depression as indicated by a decrease in cardiac output (57%), stroke volume (49%), and wall thickness (47%).

Animals↗

MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction.

Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myocardium is beneficial for cardiac function over time, nor which regulatory pathways play a crucial role in this process. To address these questions, transgenic (TG) mice engineered to overexpress modulatory calcineurin-interacting protein-1 (MCIP1) in the myocardium were used to achieve cardiac-specific inhibition of calcineurin activation. MCIP1-TG mice and their wild-type (WT) littermates, were subjected to MI and analyzed 4 weeks later. At 4 weeks after MI, calcineurin was activated in the LV of WT mice, which was significantly reduced in MCIP1-TG mice. WT mice displayed a 78% increase in LV mass after MI, which was reduced by 38% in MCIP1-TG mice. Echocardiography indicated marked LV dilation and loss of systolic function in WT-MI mice, whereas TG-MI mice displayed a remarkable preservation of LV geometry and contractility, a pronounced reduction in myofiber hypertrophy, collagen deposition, and beta-MHC expression compared with WT-MI mice. Together, these results reveal a protective role for MCIP1 in the post-MI heart and suggest that calcineurin is a crucial regulator of postinfarction-induced pathological LV remodeling. The improvement in functional, structural, and molecular abnormalities in MCIP1-TG mice challenges the adaptive value of post-MI hypertrophy of the remote myocardium. The full text of this article is available online at http://circres.ahajournals.org.

Animals↗

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.

Adult↗

Differential effects of OPC-18790, amrinone and dobutamine on cardiac function and energy metabolism in the guinea-pig isolated ischaemic heart.

1. The effects of OPC-18790, a novel positive inotropic agent, on cardiac function and myocardial energy metabolism in the guinea-pig isolated heart with ischaemia were studied by 31P-magnetic resonance spectroscopy (MRS) and compared with those of amrinone and dobutamine. 2. Cardiac ischaemia was induced by intracoronary infusion of 15 microns microspheres to reduce coronary perfusion flow (CPF) by 50%. Microsphere embolisation caused a 40% decrease in left ventricular systolic pressure (LVSP), cardiac contractility measured by peak of ventricular pressure development (LVdP/dt) and slightly reduced heart rate. There was also a decrease in ATP and creatine phosphate (PCr) by 20%, an increase in inorganic phosphate (Pi) by 25% and an acidic shift of intracellular pH in the ischaemic heart. 3. In the ischaemic heart, OPC-18790, amrinone and dobutamine were applied at concentrations which increased LVdP/dt by about 60%. These compounds increased LVP by 15% to 30% and increased CPF by about 10%. Amrinone and dobutamine but not OPC-18790 increased heart rate. When these drugs produced the haemodynamic changes described above, amrinone and dobutamine reduced ATP and PCr, increased Pi and produced further intracellular acidosis, whereas, OPC-18790 did not change these parameters. 4. Cardiac pacing at 285 beats min-1 produced decreases in LVP, LVdP/dt and CPF by about 30%, 20%, 5%, respectively and an increase in Pi, decreases in PCr and ATP, and intracellular acidosis. 5. These results suggest that degradation of high energy phosphate compounds closely relates to increase in heart rate in the ischaemic heart. Positive inotropic agents without chronotropic action seem to be beneficial in support of the ischaemic heart.

Adenosine Triphosphate↗

Hypertonic saline dextran resuscitation fails to improve cardiac function in neonatal and senescent burned guinea pigs.

Our previous studies suggested that the greater diminution in burn-induced cardiac contractile function which occurs in young and elderly subjects compared with adult subjects is related to differences in intracellular calcium availability to the myofilaments. We recently showed that improved cardiac function after hypertonic saline dextran (HSD) resuscitation from burn injury in adults was related to enhanced intracellular calcium content. In the study presented here, 126 hearts isolated from neonatal, adult, and senescent guinea pigs were used to evaluate age-related differences in cardiac contractile response to HSD resuscitation from burn injury. Scald burn was induced in 30 adult, 18 neonatal, and 30 senescent guinea pigs; within each age group, half of the burned animals were resuscitated with lactated Ringer's (Parkland formula, 4 mL/kg/% burn for 24 hours); half received an initial bolus of HSD (4 mL/kg, IV) plus lactated Ringer's (1 mL/kg/% burn for 24 hours). An additional 16 animals from each age group served as sham burn controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Effects of wrapping tightness on acute cardiac function in dynamic cardiomyoplasty.

BACKGROUND: It has not been clarified how tightly the heart should be wrapped for maximal augmentation of cardiac function in cardiomyoplasty. METHODS: Hearts in acute failure induced by propranolol were wrapped with the left latissimus dorsi muscle, loosely (loose CMP), moderately (moderate CMP), and tightly (tight CMP) in each of 5 pigs. To measure the pressure between the latissimus dorsi muscle and the left ventricle (LV), a Millar pressure catheter with a latex balloon was placed on the anterior wall of the LV. Left ventricular wall tension was calculated according to Laplace's law, using the difference between the LV pressure and the balloon pressure. RESULTS: In the loose CMP, moderate CMP, and tight CMP groups, the mean balloon pressures during unassisted beats were 8.2, 10.4, and 13.2 mm Hg, respectively. During unassisted beats, the mean LV wall tension values were 38,683, 29,938 (p < 0.05 versus loose CMP), and 26,652 (p < 0.05 versus loose CMP) dynes/cm, respectively, the peak LV pressures were 76.8, 73.8, and 65 (p < 0.05 versus loose CMP) mm Hg, respectively, and the stroke volumes were 12.8, 9.2, and 8.5 (p < 0.05 versus loose CMP) mL, respectively. During assisted beats, the mean LV wall tension values were 20,059, 11,290, and 7,893 (p < 0.05 versus loose CMP) dynes/cm, respectively, the peak LV pressures were 94.1, 98.1, and 92.0 mm Hg, respectively, and the stroke volumes were 13.8, 11.6, and 9.4 (p < 0.05 versus loose CMP) mL, respectively. CONCLUSIONS: During unassisted beats, tight CMP (13 mm Hg) had the advantage of diminishing LV wall tension, but the disadvantage of diminishing LV pressure and stroke volume, compared with loose CMP (8 mm Hg). Moderate CMP (10 mm Hg), however, had the advantage of diminishing LV wall tension without a decrease in LV pressure and stroke volume.

Animals↗

Pharmacologic interventions for the neonate with compromised cardiac function.

The developmental aspects of myocardial performance must be considered when pharmacologic agents are used to support the neonate with compromised cardiac function. Neonatal cardiovascular function is characterized by a limited preload reserve, decreased ventricular compliance, limited contractile reserve, and CO that is primarily dependent on the HR. Nurses caring for these neonates need a baseline understanding of normal cardiovascular physiology to evaluate the effectiveness of pharmacologic interventions to augment CO. Neonatal nurses play a pivotal role in the therapeutic management of pharmacologic interventions to provide safe, high quality care for the sick neonate.

Cardiovascular Agents↗

The effects of burn injury and fluid resuscitation on cardiac function in vitro.

The effects of a 30% full-thickness total body surface area scald burn on in vitro mechanical cardiac function was studied in Sprague-Dawley rats. The findings were a 50% decrease in tension development and velocities of contraction and relaxation, when papillary muscle functions from sham and unresuscitated burned animals were compared. Fluid resuscitation synchronous with burning completely reversed the defects in papillary muscle function. This defect in function was partially transferable to normal muscles incubated in serum from burned rats.

Animals↗

Adaptive mechanisms that preserve cardiac function in mice without myoglobin.

Mice lacking myoglobin survive to adulthood and meet the circulatory demands of exercise and pregnancy without cardiac decompensation. In the present study, we show that many myoglobin-deficient embryos die in utero at midgestation with signs of cardiac failure. Fetal mice that survive to gestational day 12.5, however, suffer no subsequent excess mortality. Survival in the absence of myoglobin is associated with increased vascularity and the induction of genes encoding the hypoxia-inducible transcription factors 1alpha and 2, stress proteins such as heat shock protein 27, and vascular endothelial growth factor. These adaptations are evident in late fetal life, persist into adulthood, and are sufficient to maintain normal myocardial oxygen consumption during stressed conditions. These data reveal that myoglobin is necessary to support cardiac function during development, but adaptive responses evoked in some animals can fully compensate for the defect in cellular oxygen transport resulting from the loss of myoglobin.

Adaptation, Physiological↗

Disturbed cardiac function possibly associated with mianserin therapy.

Two patients, who were receiving therapy with mianserin for depressive disorders, developed signs of disturbed cardiac function which resolved after mianserin therapy was discontinued. One of the patients also developed hypokalaemia which was probably caused by the drug. It is felt that these side effects warrant further research.

Aged↗

Childhood cardiac function after prenatal diagnosis of intracardiac echogenic foci.

OBJECTIVE: To determine whether prenatally diagnosed intracardiac echogenic foci are associated with childhood cardiac dysfunction and persistence. METHODS: Children in whom intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center underwent echocardiography at ages 2 to 7 years. A single pediatric cardiologist, blinded to the prenatal sonographic intracardiac echogenic focus locations, assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid and mitral valve regurgitation was also sought. The secondary outcome was intracardiac echogenic focus persistence. RESULTS: Twenty-five children, 14 (56%) male and 11 (44%) female, were examined at a mean age +/- SD of 3.0 +/- 1.0 years. Prenatally, 18 children (72%) had left ventricular intracardiac echogenic foci, and 7 (28%) had right ventricular intracardiac echogenic foci. The left ventricular shortening fraction was normal in all children. The overall mean left ventricular myocardial performance index (reference value, 0.36 +/- 0.06), was normal for both children with left ventricular intracardiac echogenic foci (0.36 +/- 0.06) and those with right ventricular intracardiac echogenic foci (0.36 +/- 0.04). Two children with left ventricular intracardiac echogenic foci had an isolated left ventricular myocardial performance index of greater than 2.5 SD above the mean. Trace tricuspid valve regurgitation and mitral valve regurgitation were noted in 13 (52%) and 2 (8%) of the children, respectively, similar to the general population. Left ventricular intracardiac echogenic foci persisted in 16 children (89%), whereas right ventricular intracardiac echogenic foci persisted in 2 (29%) (P = .007). CONCLUSIONS: Prenatally diagnosed intracardiac echogenic foci are often persistent but not associated with childhood myocardial dysfunction.

Child↗

Effect of "living high-training low" on the cardiac functions at sea level.

Living high-training low (LHTL), living at high altitude and training at sea level, is reported to be beneficial in enhancing physical performance. Effect of LHTL on cardiac function which is one of major determinants in performance, however, was not examined. To address this issue, 21 well-trained triathletes divided into control (n = 10, living and training at sea level) and LHTL group (living at 1980 m altitude > or = 12 hrs/day and training at sea level) were Doppler echocardiographically examined before and at the end of the two-week program. Heart rate and blood pressure did not change in both groups. At end of the training, left ventricular endsystolic diameter of LHTL group was smaller than that of controls (32 vs 34 mm, P < 0.05). Shortening fraction and ejection fraction in LHTL group increased by 9% and 17 %, respectively, P < 0.05. Preejection period/ejection time was more greatly reduced in LHTL group (P < 0.05). Stroke volume and cardiac output in LHTL increased. Diastolic function was not significantly affected by LHTL. These results suggest that LHTL produced an improvement of systolic function underlined by incremented left ventricular contractility, which might be associated with increased beta-adrenergic receptor or an improved myocardial energy utilization.

Adult↗

Doppler echocardiographic studies of diastolic cardiac function in the human fetal heart.

Fetal echocardiography has been used for the noninvasive evaluation of human fetal cardiac anatomy, function, and hemodynamics. The purpose of the present study was to use Doppler echocardiographic methods to measure diastolic flow velocity patterns across the tricuspid and mitral valves in human fetuses during gestation. Fifty normal fetuses, 35 fetuses with intrauterine growth retardation (IUGR), and 30 fetuses of diabetic mothers (DM) were studied. Peak flow velocities during early diastole (peak E wave) and peak flow velocities during atrial contraction (peak A wave) were measured, and the peak E/A ratio was calculated. The peak E/A ratio of the left ventricle in fetuses increased gradually with increasing gestational age (r = 0.57, p < 0.05), and the peak E/A ratio of the right ventricle in fetuses increased linearly with increasing gestational age (r = 0.48, p < 0.05). In early gestational age, the peak E/A ratios of both the left and right ventricle in fetuses with IUGR and of DM were not significantly different from those in the controls. However, in late gestational age, the peak E/A ratios of both the left and right ventricle in fetuses with IUGR and of DM were significantly smaller than those in the controls. This gradual decrease in the peak E/A ratio during gestation may represent the maturational or developmental alteration of diastolic cardiac properties in utero. Fetuses with IUGR and of DM may have abnormal diastolic cardiac function in later gestation.

Diastole↗

Myocardial signaling defects and impaired cardiac function of a human beta 2-adrenergic receptor polymorphism expressed in transgenic mice.

A threonine to isoleucine polymorphism at amino acid 164 in the fourth transmembrane spanning domain of the beta 2-adrenergic receptor (beta 2AR) is known to occur in the human population. The functional consequences of this polymorphism to catecholamine signaling in relevant cells or to end-organ responsiveness, however, are not known. To explore potential differences between the two receptors, site-directed mutagenesis was carried out to mimic the polymorphism. Transgenic FVB/N mice were then created overexpressing wild-type (wt) beta 2AR or the mutant Ile-164 receptor in a targeted manner in the heart using a murine alpha myosin heavy chain promoter. The functional properties of the two receptors were then assessed at the level of in vitro cardiac myocyte signaling and in vivo cardiac responses in intact animals. The expression levels of these receptors in the two lines chosen for study were approximately 1200 fmol/mg protein in cardiac membranes, which represents a approximately 45-fold increase in expression over endogenous beta AR. Myocyte membrane adenylyl cyclase activity in the basal state was significantly lower in the Ile-164 mice (19.5 +/- 2.7 pmol/min/mg) compared with wt beta 2AR mice (35.0 +/- 4.1 pmol/min/mg), as was the maximal isoproterenol-stimulated activity (49.8 +/- 7.8 versus 77.1 +/ 7.3 pmol/min/mg). In intact animals, resting heart rate (441 +/- 21 versus 534 +/- 17 bpm) and dP/dtmax (10,923 +/- 730 versus 15,308 +/- 471 mmHg/sec) were less in the Ile-164 mice as compared with wt beta 2AR mice. Similarly, the physiologic responses to infused isoproterenol were notably less in the mutant expressing mice. Indeed, these values, as well as other contractile parameters, were indistinguishable between Ile-164 mice and nontransgenic littermates. Taken together, these results demonstrate that the Ile-164 polymorphism is substantially dysfunctional in a relevant target tissue, as indicated by depressed receptor coupling to adenylyl cyclase in myocardial membranes and impaired receptor mediated cardiac function in vivo. Under normal homeostatic conditions or in circumstances where sympathetic responses are compromised due to diseased states, such as heart failure, this impairment may have important pathophysiologic consequences.

Adenylyl Cyclases↗

Pulsed Doppler and two-dimensional echocardiography: comparison of halothane and isoflurane on cardiac function in infants and small children.

The combination of two-dimensional and pulsed Doppler echocardiography was used to measure determinants of cardiac function in 20 ASA physical status I infants and small children (9 days-32 months of age) during equipotent halothane (n = 10) or isoflurane (n = 10) anesthesia in oxygen. Five sets of cardiovascular data were recorded in each patient. In the awake, unmedicated state prior to induction, at three different anesthetic levels, 0.75, 1.0, and 1.25 MAC (corrected for age) and a final measurement repeated at 1.25 MAC after the intravenous infusion of 15 ml X kg-1 of Lactated Ringers solution. The study was completed prior to intubation and surgery. Results are expressed as mean +/- SEM. Isoflurane and halothane decreased mean blood pressure from the awake level (isoflurane 76.6 +/- 2.3 to 60.6 +/- 3.1 mm, halothane 72.2 +/- 3.9 to 60.6 +/- 3.1 mm at 1.25 MAC). Isoflurane increased heart rate at all anesthetic levels (128.7 +/- 4.2 to 142.5 +/- 6.0 beats/min at 0.75 MAC). Halothane decreased heart rate at 1.25 MAC (124.6 +/- 4.6 to 119.4 +/- 3.5 beats/min). Isoflurane and halothane decreased cardiac index at 1.25 MAC. Stroke volume index decreased at 1.0 and 1.25 MAC with both isoflurane (36.9 +/- 3.8 to 30.2 +/- 3.5 ml/m2) and halothane (32.7 +/- 2.5 to 28.9 +/- 2.5 ml/m2). Ejection fractions also decreased significantly at 1.0 and 1.25 MAC in both groups of patients (22 +/- 6% at 1.25 MAC halothane and 28 +/- 8% at 1.25 MAC isoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Evaluation of size and dynamics of the inferior vena cava as an index of right-sided cardiac function.

To define normal criteria of size and dynamics of the inferior vena cava (IVC) and its clinical value in assessing right-sided cardiac function, 2-dimensional (2-D) and M-mode echocardiography (echo) were performed in 175 subjects, who were classified into 3 groups: group 1-80 normal subjects; group IIA--65 patients with documented right-sided cardiac disease, and group IIB--30 patients with cardiac disease but no right-sided abnormality. The IVC was adequately imaged in 175 of 185 subjects (95%). There was good correlation between M-mode and 2-D echo (r = 0.84) and long- and short-axis (r = 0.88) measurements. The IVC diameter during expiration was: group 1-9 to 28 mm (mean 18.2 +/- 4.6); group IIA--15 to 40 mm (mean 23.1 +/- 4.8) and group IIB-8-24 mm (mean 15.6 +/- 3.7). Collapsibility index (inspiratory decrease in diameter) was: group I-37 to 100% (mean 55.8 +/- 15.9); group IIA--0 to 39% (mean 13.5 +/- 10.5); and group IIB--44 to 100% (mean 60.4 +/- 13.1). A and V waves could be measured in 120 of 151 cases (79%). Both A and V waves were less than 125% of its diameter in group I. The A wave was absent in 34 patients; 30 (88%) were in atrial fibrillation. Among 8 patients with tricuspid regurgitation, 5 (63%) had V waves greater than 125%. There was no correlation between diameter or collapsibility index and age, sex, rhythm or body surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Augmentation of cardiac function by elevation of intrathoracic pressure.

We studied the cardiovascular effects of increasing intrathoracic pressure in an acute pentobarbital-anesthetized canine model of acute ventricular failure induced by large doses of propranolol. Left ventricular (LV) function curves were generated by volume loading from LV filling pressures of 5-20 Torr. The animals were ventilated by using intermittent positive-pressure ventilation with large tidal volumes (30 ml/kg). Chest and abdominal pneumatic binders were used to increase intrathoracic pressure. When compared with the control state, acute ventricular failure was associated with a decrease in the slope of the LV function curves (P less than 0.01). After binding the increase in intrathoracic pressure (1.1 +/- 1.6 to 12.1 +/- 2.4 Torr, P less than 0.01) was associated with an improvement in both right ventricular and LV function. Our study demonstrates that in this model of acute ventricular failure, increasing intrathoracic pressure improves cardiac function. We postulate that this observed improvement with increased intrathoracic pressure is due to reduced LV wall stress in a manner analogous to that seen with arterial vasodilator therapy in congestive heart failure.

Acute Disease↗

Cardiac function: evaluation with fast-echo MR imaging.

Magnetic resonance (MR) imaging of the heart has, to date, been limited in its ability to evaluate cardiac function. The authors have implemented a technique for functional assessment of the heart using shorter echo times than those generally used for conventional spin-echo imaging. With these short echo times, multiple images can be obtained in a multisection mode approximately within the isovolumetric phases of the cardiac cycle. This permits a pair of image stacks to be obtained, one in end systole and the other in end diastole. With the use of a modified Simpson rule, left ventricular volume and ejection fraction were calculated and compared with results obtained from contrast material-enhanced ventriculography. Preliminary results indicate that this method has promise for the evaluation of a variety of functional parameters in the heart. The short acquisition times for this functional study permit it to be combined with a tissue characterization study within the time constraints of a clinical MR imaging session.

Heart Function Tests↗