VATS management of an enlarging multicystic pneumatocele.

A multicystic pneumatocele progressively enlarged when the patient required positive pressure ventilation for an intercurrent respiratory syncytial virus infection. Video Assisted Thoracoscopic Surgery was used to visualize the pneumatocele for cannulation. One chamber of the pneumatocele was cannulated with a pigtail catheter and another large chamber ruptured, without cannulation. The multicystic pneumatocele resolved with this therapy.

Loss of high affinity cardiac beta adrenergic receptors in dogs with heart failure.

We studied the alterations in myocardial beta-adrenergic receptor-adenylate cyclase activity and muscarinic receptor density in a canine model of left ventricular (LV) failure. LV failure was characterized by a doubling of LV weight/body weight ratio (3.3 +/- 0.1 to 6.9 +/- 0.4 g/kg) and an elevation of LV end-diastolic pressure, 32 +/- 4.5 mmHg, compared with 7.7 +/- 0.6 mmHg in normal dogs. Despite a 44% increase in receptor density as measured by antagonist binding studies with [3H]dihydroalprenolol, there was a twofold decrease in receptor affinity, i.e., an increase in the dissociation constant (Kd) (5.6 +/- 0.7 to 12 +/- 1.6 nM) in heart failure. Agonist displacement of [3H]dihydroalprenolol binding with isoproterenol in the presence and absence of 5'-guanylylimidodiphosphate [Gpp(NH)p] demonstrated a striking loss of high affinity binding sites in heart failure (51 +/- 16 to 11 +/- 5%). Beta-Adrenergic receptor-mediated stimulation of adenylate cyclase and maximal stimulation with Gpp(NH)p or sodium fluoride was reduced in heart failure. There was a concomitant marked, P less than 0.01, reduction in muscarinic receptor density (242 +/- 19 vs. 111 +/- 20 fmol/mg). Thus, while muscarinic receptor density fell, beta-adrenergic receptor density actually increased in LV failure. However, a larger portion of the beta-adrenergic receptors are not functionally coupled to the GTP-stimulatory protein (Ns), as evidenced by a decrease in the fraction of receptors that bind agonist with high affinity.

Impaired cardiac muscarinic receptor function in dogs with heart failure.

Prior physiological studies have suggested that parasympathetic control is altered in heart failure. The goal of our studies was to investigate the influence of heart failure on the muscarinic receptor, and its coupling to adenylate cyclase. Ligand binding studies using [3H]quinuclidinyl benzilate and enriched left ventricular (LV) sarcolemma, demonstrated that muscarinic receptor density in heart failure declined 36% from a control of 5.6 +/- 0.6 pmol/mg, with no change in antagonist affinity. However, agonist competition studies with both carbachol and oxotremorine showed that it was a loss of high affinity agonist binding sites in the sarcolemma from failing LV that accounted for this difference. The functional efficacy of the muscarinic receptor was also examined. When 1 microM methacholine was added to 0.1 mM GTP and 0.1 mM isoproterenol, adenylate cyclase stimulated activity was inhibited by 15% in normal LV but only 5% in LV sarcolemma from animals with heart failure even when the reduced adenylate cyclase in these heart failure animals was taken into account. Even at 100-fold greater concentrations of methacholine, significantly less inhibition of adenylate cyclase activity was observed in LV failure as compared with normal LV sarcolemma. Levels of the GTP-inhibitory protein known to couple the muscarinic receptor to adenylate cyclase, as measured with pertussis toxin labeling, were not depressed in LV failure. Thus, the inhibitory pathway regulating LV adenylate cyclase activity is defective in heart failure. The decrease in muscarinic receptor density, and in particular the specific loss of the high affinity agonist binding component of this receptor population, appears to be the major factor underlying this abnormality.

Effects of chronic heparin administration on coronary vascular adaptation to hypertension and ventricular hypertrophy in sheep.

BACKGROUND: Hypertension decreases myocardial perfusion capacity in adults for several reasons, including insufficient coronary angiogenesis with left ventricular (LV) hypertrophy, arteriolar hypertrophy, and altered vasomotion. Heparin influences growth factors that promote angiogenesis and vasodilation and inhibit arteriolar wall thickening. METHODS AND RESULTS: Adult sheep were given heparin 200 U/kg body wt SC twice daily throughout 6 weeks of LV and coronary hypertension from a progressively constricted ascending aortic band (n=14). They were compared with untreated sheep with (n=13) and without (n=13) aortic stenosis. After 6 weeks, maximum myocardial perfusion was measured during adenosine infusion in the conscious state by the microsphere method. Sheep with aortic stenosis had less maximum coronary flow per gram, less conductance reserve, and thicker arteriolar walls in the LV and nonhypertrophied right ventricle. Capillary density decreased in the LV endomyocardium and remained unchanged in the right ventricle. Heparin-treated sheep had significant partial normalization of coronary conductance reserve and maximum perfusion in both ventricles and capillary density in the LV endomyocardium. Arteriolar wall thickness was unchanged. Compared with untreated sheep with aortic stenosis, in heparin-treated sheep LV FGF-2 protein increased 2-fold, whereas FGF-2 mRNA remained unchanged. VEGF mRNA and protein increased 3-fold and 1.4-fold, respectively, whereas TGF-beta(1) mRNA declined 3-fold. CONCLUSIONS: Heparin administration during LV hypertension increases heparin-binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decreases in LV perfusion capacity and capillary density.

Preload dependence of fiber shortening rate in conscious dogs with left ventricular hypertrophy.

Employing the new concept of systolic myocardial stiffness, this study addresses the questions of linearity of the end-systolic stress-strain relations in left ventricular hypertrophy and the preload dependence of fiber shortening rate. Pressure overload hypertrophy was induced in six puppies by banding the ascending aorta. Ultrasonic crystals were implanted for measurement of short axis and wall thickness in the six dogs with hypertrophy and in five control dogs. A pressure catheter was inserted through the apex for left ventricular pressure measurement. Load was altered by graded infusions of phenylephrine in the setting of beta-adrenergic blockade. Linearity of the end-systolic stress-strain relations was observed in all cases, and preload-corrected shortening rate-afterload relations were derived from these stress-strain relations. Without preload correction, mid wall and endocardial shortening rate were depressed (p less than 0.05 and p less than 0.005, respectively) in the hypertrophy group. However, with preload correction at 35 g/cm2, there was no significant difference in shortening rate between the control and hypertrophy groups at afterloads of 150, 200 and 250 g/cm2. Endocardial shortening rate at a preload of 25 versus 35 g/cm2 demonstrated a preload dependence in both the control (p less than 0.04) and the hypertrophy group (p less than 0.01). Mid wall shortening rate displayed a preload dependence only in the hypertrophy group (p less than 0.05). It is concluded that end-systolic stress-strain relations are linear in control conditions and in hypertrophy, fiber shortening rate is preload-dependent and, thus, shortening rate-afterload relations currently used to assess myocardial contractility need to be modified to account for these preload effects.

Effect of young age on coronary adaptations to left ventricular pressure overload hypertrophy in sheep.

OBJECTIVES: This study attempted to determine the effect of young age on changes in coronary conductance and capillary density with left ventricular pressure overload hypertrophy. Mechanisms responsible for age differences in perfusion capacity were examined. BACKGROUND: Hypertension in adults causes alterations in the coronary vasculature, resulting in diminished coronary perfusion capacity and myocardial ischemia. These processes are worsened in adults by advanced age. Young age may provide advantages in coronary adaptation to hypertension. METHODS: Coronary conductance was examined in conscious chronically instrumented 10-week old lambs and adult sheep with progressive ascending aortic stenosis of 6-week's duration and age-matched control sheep by means of the microsphere technique and vasodilators. Capillary density was measured post-mortem. RESULTS: Adult sheep with aortic stenosis had a decrease in left ventricular subendomyocardial capillary density by 17% and maximal coronary conductance with adenosine by 67%. In the nonhypertrophied right ventricle, maximal coronary conductance was depressed by 47%, whereas capillary density was normal, implying an effect of coronary hypertension on resistance vessels. In contrast, lambs with aortic stenosis maintained normal left ventricular capillary density, maximal coronary conductance and coronary reserve and had relatively little impairment of conductance in the right ventricular coronary bed (-15%, p = NS). Similar responses were found with other vasodilators, isoproterenol and chromonar. CONCLUSIONS: Young age confers advantages to coronary adaptation to left ventricular pressure overload, including angiogenesis proportionate to hypertrophy, resulting in normal capillary density and coronary conductance. There is also less hypertension-induced impairment of coronary conductance distinct from the effects of hypertrophy.

Autonomic mechanisms regulating myocardial contractility in conscious animals.

In this review some of the issues and controversies involved in the neural control of the myocardial inotropic response to stress have been discussed. For example, it is surprising that either direct or reflex activation of the sympathetic nerves induces a relatively small increase (20-40%) in the left ventricular inotropic state when compared with the three-five-fold increase associated with maximal dynamic exercise. Studies contrasting the levels of circulating catecholamines with the left ventricular inotropic responses induced by hemorrhage, exercise and exogenously administered catecholamines, suggest that the catecholamine concentration at the synaptic cleft is the primary determinant of the left ventricular inotropic response. Although parasympathetic neural activation alone appears to have little direct influence on the left ventricular inotropic state and central nervous system integration of the autonomic nervous system usually insures there is a reciprocal relationship between sympathetic and parasympathetic neural activity, the potential for parasympathetic inhibition of the response to sympathetic or sympathomimetic augmentation of the intropic response exists. The importance of sympathetic-parasympathetic nervous system interaction in physiologic and pathologic conditions has yet to be defined. It is this type of knowledge of the interactions of reflex pathways which will be critical to the full understanding of autonomic reflex control of myocardial performance under physiologic and pathologic conditions.

Effect of young sibling visitation on respiratory syncytial virus activity in a NICU.

OBJECTIVE: To determine whether the restriction of young sibling (<13 years) visitation in the neonatal intensive care unit (NICU) during the respiratory syncytial virus (RSV) season was associated with a reduction in the rate of RSV infection among NICU patients. STUDY DESIGN: A retrospective chart review of all RSV positive infants from the 2001-2010 RSV seasons. The 2001-2006 RSV seasons (group 1) contained 639 admissions and the 2007-2010 (group 2, with sibling restriction) contained 461 admissions. Groups were compared by using the Fisher's Exact Test. RESULTS: There was a reduction of RSV positive infants from 6.7% in Group 1 to 1.7% in Group 2 (P<0.0001). There was a reduction of symptomatic infants from the number of infants with symptomatic RSV infection from 23/639 infants with young sibling visitation to 2/461 (P<0.001). CONCLUSION: Exclusion of young sibling visitors <13 years of age during RSV season was associated with a significant reduction in the number of RSV positive infants in the NICU.

Direct versus indirect pressor and vasoconstrictor actions of angiotensin in conscious dogs.

To determine the importance of the direct and the indirect pressor and vasoconstrictor actions of angiotensin II (ANG II), experiments were conducted in conscious dogs 2 to 8 weeks after instrumentation with aortic catheters and aortic electromagnetic flow probes to measure arterial pressure and cardiac output. Total peripheral resistance was calculated by an on-line digital computer. Pretreatment with propranolol eliminated complicating inotropic effects of norepinephrine, released by the indirect actions of ANG II. The pressor and vasoconstrictor responses after ganglionic blockade, in either the presence or absence of arterial baroreceptor nerves, were considered to be the direct effects of ANG II. In conscious dogs, systemically administered ANG II (32 ng/kg bolus) increased mean arterial pressure by 38 +/- 3 mm Hg, total peripheral resistance by 37 +/- 2 mm Hg/L/minute, and decreased heart rate by 15 +/- 2 beats/minute. After arterial baroreceptor denervation, administration of ANG II increased mean arterial pressure by 88 +/- 7 mm Hg, total peripheral resistance by 54 +/- 4 mm Hg/L/minute, and heart rate by 12 +/- 2 beats/minute. After arterial baroreceptor denervation and ganglionic blockade with hexamethonium, administration of ANG II increased mean arterial pressure by 53 +/- 8 mm Hg, total peripheral resistance by 27 +/- 3 mm Hg/L/minute, and left heart rate unchanged. These results indicate that in the conscious dog without baroreflex buffering nearly one-half of the pressor and vasoconstrictor actions of angiotensin are not direct, but are mediated by the autonomic nervous system.

Radionuclide angiocardiographic assessment of pulmonary vascular reactivity in patients with left to right shunt and pulmonary hypertension.

Radionuclide angiocardiography was used to assess pulmonary vascular reactivity in eight patients (nine studies) with a large, relatively unrestrictive intracardiac defect and pulmonary arterial hypertension. Radionuclide angiocardiograms, using technetium-99m pertechnetate, were performed first with the patient breathing room air and then after 10 minutes of breathing a mixture containing 90 percent or more of oxygen. The pulmonary to systemic flow ratios obtained by gamma variate analysis of the radionuclide time-activity curves were compared with those calculated with the Fick principle at the time of cardiac catheterization. There was a good correlation between the two methods both in room air studies (r = 0.88) and in those obtained with 90 percent or more of oxygen (r = 0.94). All six studies (in five patients) with a reactive pulmonary vasculature (judged by a pulmonary vascular resistance at cardiac catheterization of less than 6 units/m2 with oxygen or after tolazoline) had a radionuclide pulmonary to systemic flow ratio of 3.0 or greater with oxygen. The three patients with a nonreactive pulmonary vasculature had a radionuclide pulmonary to systemic flow ratio of 2.3 or less with oxygen, a value that was unchanged from the room air value. These data suggest that radionuclide angiocardiography may be a useful, relatively noninvasive method of assessing pulmonary vascular reactivity in patients with a large, relatively unrestrictive intracardiac defect.

Age-dependent ventricular response to pressure overload. Considerations for the arterial switch operation.

Success with the arterial switch operation for D-transposition of the great arteries and the concept of left ventricular suitability for systemic work stimulated this literature review of the age-dependent mechanisms in normal cardiac growth and pressure-induced left ventricular hypertrophy. Normal postnatal myocardial growth is markedly influenced by hemodynamic factors. It consists of an early hyperplastic phase of both myocytes and capillaries that is followed by a myocyte hypertrophic phase. Similarly, imposition of a pressure overload induces both myocyte hyperplasia/hypertrophy and increased angiogenesis in neonates, but only myocyte hypertrophy at a later age. The functional consequences of ventricular hypertrophy are the result of adaptive and nonadaptive changes resulting from the overload stimulus, for example, induction of protooncogene expression, myosin isoenzyme shifts, degree of coronary perfusion, responsiveness to beta-adrenergic stimulation, and myocyte capacity to re-accumulate or sequester cytosolic calcium. Strikingly, both the capacity and the rapidity of left ventricular hypertrophy decrease with increasing age. This experimental information supports the current use of primary arterial switching for neonates with D-transposition of the great arteries and the use of "rapid" two-stage arterial switching in infants more than 3 to 4 weeks of age; it raises some concern about the practice of late retraining of the left ventricle in cases of failed atrial inversion operation.

A time-course study of the effects of pentobarbital, fentanyl, and morphine chloralose on myocardial mechanics.

Cardiovascular physiological studies in anesthetized animals may be confounded by the hemodynamic actions of the anesthetic agents themselves. To identify an anesthetic regimen that does not significantly influence cardiovascular physiology, the hemodynamic responses of 28 dogs were studied. Animals were equally divided among groups with 1) no anesthesia (i.e., trained conscious preparation), 2) pentobarbital sodium, 3) fentanyl citrate, and 4) a combination of morphine sulfate and alpha-chloralose. Anesthesia was maintained for 3 h. Data were acquired with the use of ultrasound imaging of the heart in conjunction with invasive pressure measurements. Left ventricular ejection phase indexes and end-systolic force-velocity relations were used to evaluate the effects of each anesthetic agent on overall systolic performance and myocardial contractility. Compared with the conscious animals, pentobarbital profoundly depressed systolic performance (P less than 0.05 vs. control) because of a reduction in myocardial contractility (P less than 0.01) and an increase in left ventricular afterload (end-systolic wall stress, P less than 0.05). Fentanyl increased myocardial contractility (P less than 0.05) but also tended to increase afterload with the net result that overall systolic performance remained unchanged. Morphine-chloralose did not affect overall ventricular systolic performance or its individual determinants. Pentobarbital and fentanyl also caused progressive time-dependent deteriorations in all parameters of systolic function during prolonged anesthesia. In contrast, cardiac function was stable for greater than or equal to 3 h after induction of morphine-chloralose anesthesia. The hemodynamic profile of dogs anesthetized with morphine-chloralose most closely resembled that of the conscious animals. Morphine-chloralose is recommended when prolonged anesthesia is required for studies of cardiovascular physiology.

Diagnostic ionizing radiation exposure in premature patients.

OBJECTIVE: Concern regarding the magnitude and consequences of diagnostic radiation exposure in premature infants in neonatal intensive care units (NICUs) has increased as survival of premature infants has improved. Radiation exposure is not often rigorously monitored in NICU patients. The purpose of this observational study was to quantify the amount of ionizing radiation exposure in infants <33 weeks gestational age and to identify the indications for diagnostic imaging. STUDY DESIGN: We conducted a retrospective review of 215 premature infants who were <33 weeks gestation and who received central venous line (CVL) placement during their NICU stay during the period from 2006 to 2011. Absorbed ionizing radiation was estimated using the method of Puch-Kapst and colleagues (2009) and compared with recommended radiation exposure limits. All infants were 29.2±2.3 weeks (mean±s.d.) and 1262±433 g birth weight. RESULT: Subjects received 15±15 radiographs (4.4±2.9 for CVL placement, 5.7±9.8 for gastrointestinal (GI) evaluations and 5.2±9.3 for respiratory indications). Eleven infants (5.1%) received more than the maximum recommended radiation from radiographs (>1000 µSv). Inclusion of fluoroscopic procedures increased to 26 the number of infants (12.1%) who received more than the maximum recommended 1000 µSv. CONCLUSION: Ionizing radiation exposure that exceeded the recommended maximum in premature infants at high risk for long-term sequelae occurred in 12.1% of infants who were <33 weeks gestation and who were cared for in our NICU over the past 5 years. CVL placement accounted for 22% of this radiation exposure. GI evaluations accounted for the greatest amount of ionizing radiation exposure. We suggest that the increased use of other imaging strategies may reduce total ionizing radiation exposure in this vulnerable population.

Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome.

OBJECTIVE: Comparison of the differences between availability of animal-derived surfactant preparations used to treat premature infants is incomplete. The objective of this study was to assess the short-term treatment efficacy of the two most commonly used surfactant preparations in the United States, beractant (100 mg kg(-1) initial and subsequent doses) and poractant alfa (200 mg kg(-1) initial and 100 mg kg(-1) subsequent doses), in very premature, mechanically ventilated infants <30 weeks gestation with respiratory distress syndrome (RDS). STUDY DESIGN: Inborn infants at two institutions, open label, 1:1, randomized controlled trial. Level of respiratory support for first 72 h of life. Morbidities of prematurity observed during the neonatal intensive care unit hospitalization. RESULT: We studied 52 infants 24 0/7 to 29 6/7 weeks gestation; 25 received poractant alfa (27.1±1.6 weeks, birth weight of 930±231 g) and 27 received beractant (26.7±1.7 weeks, P=0.343 and birth weight 900±271 g, P=0.668). Respiratory support for the first 72 h of life was lower in the poractant alfa than beractant group for mean airway pressure (MAP, P=0.003) and respiratory index (MAP × FiO(2), P=0.032). Infants in the poractant alfa group had a greater number of infants extubated at 48 (13/25 vs 6/27, P=0.027) and 72 h (15/25 vs 8/27, P=0.029) than the beractant group. Although the study was not powered to detect morbidities of prematurity, the prevalence of PDA and air leaks was less in the infants treated with poractant alfa than in those treated with beractant. Rates of bronchopulmonary dysplasia (8/23 vs 11/22, P=0.303) or death (2/25 [corrected] vs 5/27, P=0.272) were similar in the infants treated with poractant alfa and beractant, respectively. CONCLUSION: This study suggests significant short-term benefits to the use of the larger initial dose of poractant alfa than beractant in very premature infants with RDS. Further studies involving a larger number of preterm infants are needed to assess long-term effects.

Baroreflex mechanisms buffering alpha-adrenergic agonists in conscious dogs.

To determine the relative importance of the mechanisms utilized by the arterial baroreflex in buffering the pressor and vasoconstrictor responses to alpha-adrenergic receptor agonists, we studied responses to norepinephrine and phenylephrine in conscious dogs. The dogs were studied 2-8 wk after instrumentation with aortic catheters and aortic electromagnetic flow probes to measure arterial pressure and cardiac output. Total peripheral resistance was calculated on-line by a digital computer. The dogs were studied after beta-adrenergic receptor blockade (propranolol 1.0 mg/kg) to eliminate the complicating inotropic effects of the agonists studied. Norepinephrine (0.2 microgram/kg bolus) increased mean arterial pressure by 30 +/- 3 mmHg, total peripheral resistance by 51 +/- 4 mmHg . l-1 . min-1, and decreased heart rate by 26 +/- 3 beats/min. After arterial baroreceptor denervation, norepinephrine increased mean arterial pressure by 69 +/- 8 mmHg, total peripheral resistance by 48 +/- 6 mmHg . l-1 . min-1, and heart rate did not change. After ganglionic blockade (hexamethonium 40 mg/kg), norepinephrine increased mean arterial pressure by 76 +/- 3 mmHg, total peripheral resistance by 47 +/- 4 mmHg X l-1 X min-1, and heart rate did not change. Only after elimination of the buffering by heart rate by use of cholinergic receptor blockade (atropine 0.1 mg/kg) or ventricular pacing could buffering of the vasoconstrictor responses to alpha-adrenergic receptor agonists be demonstrated. Thus in conscious dogs the primary mechanism for buffering increases in arterial pressure induced by alpha-adrenergic receptor agonists is compensatory changes in heart rate and cardiac output with little buffering of total peripheral resistance.

Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy.

To determine the extent to which the hypertrophied left ventricle responds to the chronotropic stress induced by graded atrial pacing rates, we studied conscious, chronically instrumented dogs with severe compensated pressure overload left ventricular (LV) hypertrophy induced by aortic banding in puppies 8-10 weeks of age. At 1-2 years, dogs with severe LV hypertrophy (LV free wall/body wt ratio 6.8 +/- 0.6 g/kg) and sham-operated littermates (LV free wall/body wt ratio 4.0 +/- 0.3 g/kg) were instrumented with ultrasonic dimension crystals to measure LV short axis internal diameter and wall thickness, miniature LV pressure transducers, and aortic and LV catheters. During atrial pacing (240 beats/min) in eight control dogs, LV pressure did not change from 119 +/- 2 mm Hg, and mean velocity of circumferential fiber shortening (VCF) did not change from 1.25 +/- 0.09/sec. In seven dogs with LV hypertrophy, atrial pacing (240 beats/min) decreased systolic LV function; that is, LV systolic pressure decreased (p less than 0.01) by 65 +/- 12 from 254 +/- 14 mm Hg, and VCF decreased (p less than 0.01) by 0.19 +/- 0.03 from 0.97 +/- 0.15/sec. Diastolic dysfunction was also observed in the dogs with LV hypertrophy. In the control dogs during atrial pacing (240 beats/min), LV end-diastolic pressure decreased (p less than 0.01) by 8 +/- 1 from 9 +/- 1 mm Hg, end-diastolic stress decreased (p less than 0.01) by 18 +/- 2 from 22 +/- 2 g/cm2, and the radial myocardial stiffness constant did not change from 5.6 +/- 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Different responses of extent and velocity of contraction to dobutamine in conscious sheep.

The shortening- and shortening rate-preload-afterload relations, based on the concept of the myocardial end-systolic stress-strain relation (ESSSR), are a newly developed load- and size-independent assessment of myocardial contractility. The purpose of this study was to apply this assessment to compare extent and velocity of myocardial contraction during graded infusions of dobutamine. Seven chronically instrumented unsedated sheep were studied at rest and during graded infusions of dobutamine (2.5-20 micrograms.kg-1.min-1). The ESSSR were linear over a wide range of load alterations, whereas the end-systolic pressure-diameter relations (ESPDR) were generally nonlinear. Midwall shortening rate (SRm) at common preload and afterload representing contraction extent increased with each dose of dobutamine through 20 micrograms.kg-1.min-1. In contrast, midwall shortening (Sm) increased through dobutamine 5 micrograms.kg-1.min-1 but not at higher dobutamine infusion rates. Conventional endocardial shortening and the slope of the ESPDR, fitted to a linear model, exhibited responses similar to Sm. The velocity of circumferential endocardial fiber shortening (Vcf,c), Vcf,c-afterload relation, and maximum first derivative of left ventricular pressure exhibited responses similar to SRm. Thus both the extent and velocity of contraction increased at low doses of dobutamine, whereas only the velocity increased at high doses. Potential mechanisms for the saturated response of the extent of contraction include 1) shorter systolic time for contraction due to earlier onset of relaxation and 2) the utilization of myocardial contractile energy for left ventricular wall deformation at small cavity volumes at high doses of dobutamine.

Mechanical and inotropic reserve in conscious dogs with left ventricular hypertrophy.

We studied the left ventricular (LV) responses to infusions of norepinephrine and prenalterol, a specific beta 1-adrenergic receptor agonist, in conscious, chronically instrumented adult dogs with severe LV hypertrophy. The goal of this study was to determine the extent of compensation induced by LV hypertrophy in an animal model in which the pressure overload was gradually increased, as occurs in human pathological states. One to 2 yr after banding the ascending aorta of puppies, six dogs with severe LV hypertrophy (LV free-wall weight-to-body weight ratio 7.0 +/- 0.4 g/kg), and nine sham-operated littermates (LV free-wall weight-to-body weight ratio 4.0 +/- 0.2 g/kg) were studied. The dogs were instrumented with ultrasonic dimension crystals (to measure LV short-axis diameter and wall thickness), miniature LV pressure transducers, and LV and aortic catheters. In the control dogs norepinephrine (0.4 micrograms X kg-1 X min-1) increased LV systolic/diastolic pressure from 121 +/- 2/9 +/- 1 to 177 +/- 9/20 +/- 2 mmHg, mean arterial pressure from 97 +/- 2 to 143 +/- 9 mmHg, LV dP/dt from 3,363 +/- 123 to 5,174 +/- 343 mmHg/s, and mean systolic wall stress from 194 +/- 14 to 299 +/- 22 g/cm2, while mean velocity of circumferential fiber shortening (Vcf), (dD/dt/D)max, and heart rate did not change from base line. In dogs with LV hypertrophy norepinephrine increased LV pressure from 224 +/- 16/11 +/- 1 to 305 +/- 22/19 +/- 1 mmHg, mean arterial pressure from 90 +/- 2 to 132 +/- 4 mmHg, LV dP/dt from 3,246 +/- 156 to 5,619 +/- 345 mmHg/s, and mean systolic wall stress from 224 +/- 11 to 307 +/- 24 g/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)