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PubMed2001

LV systolic performance improves with development of hypertrophy after transverse aortic constriction in mice.

Transverse aortic constriction (TAC) is an effective technique for inducing left ventricular (LV) hypertrophy in mice. With the use of transthoracic echocardiography and Doppler measurements, we studied the effects of an acute increase in pressure overload on LV contractile performance and peak systolic wall stress index (WSI) at early time points after TAC and the time course of the development of LV hypertrophy in mice. The LV mass index was similar between TAC and sham-operated mice at postoperative day 1 but progressively increased in TAC mice by day 10. There was no further increase in the LV mass index between postoperative days 10 and 20. On day 1, whereas peak systolic WSI increased significantly, the LV ejection fraction (LVEF) and percent fractional shortening (%FS) decreased in TAC mice compared with sham-operated mice. By day 10, peak systolic WSI, LVEF, and %FS had recovered to baseline levels and were not significantly different between postoperative days 10 and 20. Thus LV systolic performance in mice declines immediately after TAC, associated with increased peak systolic WSI, but recovers to baseline levels with the development of compensatory LV hypertrophy over 10-20 days.

Animals↗
PubMed1990

Effects of baroreceptor denervation on endocrine and drinking responses to caval constriction in dogs.

Plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake (H2OIN) are increased by thoracic inferior vena caval constriction (TIVCC). To assess the role of the cardiac and sinoaortic baroreceptors in these responses, 9 sham-, 10 cardiac-(CD), 6 sinoaortic-(SAD), and 4 combined cardiac and sinoaortic-(CD + SAD) denervated conscious dogs were studied. All animals were studied while normally hydrated 1) with no access to water (H2O-) and 2) while drinking was permitted (H2O+). TIVCC caused similar reductions (P less than 0.001) of mean arterial (-32 +/- 4 mmHg), left atrial pressure (-6.5 +/- 1.1 cmH2O), and right atrial pressure (-4.2 +/- 0.8 cmH2O) in all groups. After TIVCC in sham dogs with H2O-, AVP increased from 3.6 +/- 0.7 to 72.8 +/- 12.6 pg/ml (P less than 0.001). AVP was similar with SAD (57.1 +/- 6.9) but was reduced with CD (30.9 +/- 3.0) and CD + SAD (17.7 +/- 4.0). In all groups, PRA increased from 4.5 +/- 0.7 to 23.8 +/- 3.0 ng.ml-1 x 3 h-1 and plasma angiotensin II (ANG II) increased from 14.0 +/- 2.8 to 59.5 +/- 13.0 pg/ml (P less than 0.001). Plasma adrenocorticotropic hormone (ACTH) increased similarly in all groups (55 +/- 5 to 128 +/- 25 pg/ml). Plasma norepinephrine (NE) levels increased similarly in all groups (298 +/- 61 to 654 +/- 88 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Biological actions of brain natriuretic peptide in thoracic inferior vena caval constriction.

Brain natriuretic peptide (BNP) shares structural and functional similarities to atrial natriuretic peptide (ANP). Although BNP and ANP interact with the same biologically active guanylate cyclase-coupled receptor, recent reports conflict with regard to the biological actions of exogenous BNP in sodium-retaining and edematous states. We studied the biological actions of BNP in normal dogs (n = 5) and sodium-avid dogs with chronic thoracic inferior vena caval constriction (TIVCC) (n = 6). In normal dogs BNP increased glomerular filtration rate, renal blood flow, and urinary sodium excretion and decreased proximal and distal fractional reabsorption of sodium with activation of urinary guanosine 3',5'-cyclic monophosphate (cGMP). These renal actions occurred in association with marked hypotensive actions and activation of systemic cGMP. In TIVCC, a state characterized by chronic reductions of cardiac output, avid sodium retention, edema, and activation of the renin-angiotensin-aldosterone system (RAAS), the renal actions of BNP were absent in association with marked attenuation of the urinary cGMP response. In contrast, an enhanced hypotensive response with preserved activation of systemic cGMP was observed. In neither normal dogs nor TIVCC dogs did BNP inhibit the RAAS. These studies report that BNP is a potent vasoactive and natriuretic peptide with potent proximal and distal tubular actions in normal dogs. These studies also demonstrate that in TIVCC, a model of low cardiac output and congestive failure that results in marked sodium retention with edema in which there is activation of the RAAS, the renal actions of BNP are attenuated while the vasoactive actions are enhanced.

Absorption↗
PubMed1987

Effects of aortic constriction and renal denervation in DOCA-hypertensive swine.

The autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) was examined in normal and deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine (YMS). Aortic constriction (AC) was used to vary renal perfusion pressure (RPP) from 158 to 90 mmHg for DOCA-YMS and 124 to 50 mmHg for normals. DOCA animals had calculated RBF autoregulatory indexes demonstrating less effective autoregulation compared with controls. Over the pressure range of RBF autoregulation, control animals also autoregulated their GFR, whereas most DOCA animals did not. When renal function in DOCA-YMS was evaluated at the normotensive RPP of 115 mmHg, GFR, urine volume, and sodium excretion were decreased by approximately 60, 70, and 80%, respectively. In DOCA-YMS, after the normalization of RPP to 115 mmHg, renal denervation significantly increased RBF. In DOCA animals the relative decrease in sodium and water excretion in relation to decreased RPP was not altered by renal denervation. In this hypertensive model the excretion of water and sodium are closely linked to RPP. At a normotensive RPP the sodium retention in the DOCA animals may be even further exaggerated by their inability to autoregulate GFR.

Animals↗
PubMed1990

Interpretation of interrupter resistance after histamine-induced constriction in the dog.

The interrupter method for measuring respiratory system resistance involves interrupting flow at the airway opening and measuring the resultant changes in pressure. We have recently shown (J. Appl. Physiol. 65: 408-414, 1988) that in open-chest mongrel dogs, under control conditions, the initial rapid pressure change (delta Pinit) reflects conducting airway resistance and the subsequent gradual pressure change (delta Pdif) reflects stress recovery of the tissues. We questioned whether the same interpretation would apply after induced constriction. Accordingly, we performed interruption experiments on anesthetized, paralyzed, tracheostomized, open-chest mongrel dogs during passive expiration, measuring pressure at the trachea and in three different alveolar regions with alveolar capsules. We recorded measurements before and after the administration of increasing concentrations of histamine aerosol (0.1-30.0 mg/ml). We found a significant increase in the heterogeneity of alveolar pressures during the relaxed expiration with increasing concentrations of histamine. Despite the introduction of significant mechanical heterogeneities, delta Pinit still reflected the pressure drop as the result of the resistance of the conducting airways. delta Pdif, however, reflected a combination of the stress recovery of the tissues and pendelluft.

Airway Resistance↗
PubMed1997

Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening.

During a bronchial challenge, much of the observed response of lung tissues is an artifactual consequence of inhomogeneous airway constriction. Inhomogeneities, in the sense of time constant inequalities, are an inherently linear phenomenon. Conversely, if lung tissues respond to a bronchoagonist, they become more nonlinear. On the basis of these distinct responses, we present an approach to separate real tissue changes from airway inhomogeneities. We developed a lung model that includes airway inhomogeneities in the form of a continuous distribution of airway resistances and nonlinear viscoelastic tissues. Because time domain data are dominated by nonlinearities, whereas frequency domain data are most sensitive to inhomogeneities, we apply a combined time-frequency domain identification scheme. This model was tested with simulated data from a morphometrically based airway model mimicking gross peripheral airway inhomogeneities and shown capable of recovering all tissue parameters to within 15% error. Application to our previously measured data suggests that in dogs during histamine infusion 1) the distribution of airway resistances increases widely and 2) lung tissues do respond but less so than previously reported. This approach, then, is unique in its ability to differentiate between airway and tissue responses to an agonist from a single broadband measurement made at the airway opening.

Airway Resistance↗
PubMed2002

Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats.

To investigate the effects of colchicine on left ventricular (LV) function and hypertrophy (LVH) of rats subjected to constriction of transverse aorta (TAoC), we evaluated SO (sham operated, vehicle; n = 25), SO-T (sham operated, colchicine 0.4 mg/kg body wt ip daily; n = 38), TAoC (vehicle; n = 37), and TAoC-T (TAoC, colchicine; n = 34) on the 2nd, 6th, and 15th day after surgery. Colchicine attenuated LVH of TAoC-T compared with TAoC rats, as evaluated by ratio between LV mass (LV(M)) and right ventricular mass, LV wall thickness, and average diameter of cardiac myocytes. Systolic gradient across TAoC ( approximately 45 mmHg), LV systolic pressure, LV end-diastolic pressure, and rate of LV pressure increase (+dP/dt) were comparable in TAoC-T and TAoC rats. However, the baseline and increases of LV systolic pressure-to-LV(M) and +dP/dt-to-LV(M) ratios induced by phenylephrine infusion were greater in TAoC-T and SO-T compared with SO rats. Baseline and increases of +dP/dt-to-LV(M) ratio were reduced in TAoC compared with SO rats. TAoC rats increased polymerized fraction of tubulin compared with SO, SO-T, and TAoC-T rats. Our results indicate that colchicine treatment reduced LVH to pressure overload but preserved LV function.

Animals↗
PubMed2006

Sciatic chronic constriction injury produces cell-type-specific changes in the electrophysiological properties of rat substantia gelatinosa neurons.

Peripheral nerve injury increases spontaneous action potential discharge in spinal dorsal horn neurons and augments their response to peripheral stimulation. This "central hypersensitivity, " which relates to the onset and persistence of neuropathic pain, reflects spontaneous activity in primary afferent fibers as well as long-term changes in the intrinsic properties of the dorsal horn (centralization). To isolate and investigate cellular mechanisms underlying "centralization," sciatic nerves of 20-day-old rats were subjected to 13-25 days of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model). Spinal cord slices were then acutely prepared from sham-operated or CCI animals, and whole cell recording was used to compare the properties of five types of substantia gelatinosa neuron. These were defined as tonic, irregular, phasic, transient, or delay according to their discharge pattern in response to depolarizing current. CCI did not affect resting membrane potential, rheobase, or input resistance in any neuron type but increased the amplitude and frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in delay, transient, and irregular cells. These changes involved alterations in the action potential-independent neurotransmitter release machinery and possible increases in the postsynaptic effectiveness of glutamate. By contrast, in tonic cells, CCI reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such changes may relate to the putative role of tonic cells as inhibitory GABAergic interneurons, whereas increased synaptic drive to delay cells may relate to their putative role as the excitatory output neurons of the substantia gelatinosa. Complementary changes in synaptic excitation of inhibitory and excitatory neurons may thus contribute to pain centralization.

Animals↗
PubMed2004

Microarray analysis of gene expression after transverse aortic constriction in mice.

Cardiac hypertrophy is a compensatory response initially beneficial to heart function but can ultimately lead to cardiac decompensation. It is an integrated process involving multiple cellular signaling pathways and their cross talk. Microarray GeneChip technology is a powerful new tool to identify gene expression profiles of cardiac hypertrophy. To identify well-characterized as well as novel adaptive mechanisms, we utilized a murine model of compensated pressure overload hypertrophy (transverse aortic constriction, TAC). At 48 h, 10 days, and 3 wk, hearts were harvested and total RNA hybridized to Affymetrix U74Av2 GeneChips, which contain a 12,488-gene/EST probe set. Verification of gene expression was performed by SYBR quantitative real-time RT-PCR (QRT-PCR) for selected genes. A rigorous evaluation of the adequacy of the control condition was also performed. For statistical analysis we generated a four-step filtering criteria. Our results show an upregulation of 38 genes (48 h), 269 genes (10 days), and 203 genes (3 wk) and downregulation of 15 genes (48 h), 160 genes (10 days), and 124 genes (3 wk). Transcripts differentially expressed after TAC were categorized into 12 functional groups and revealed the presence of several intriguing transcripts, e.g., cell proliferation-related Ki-67 and several apoptosis-related genes. Overall changes in QRT-PCR were in accordance with GeneChip data, with the highest correlation for genes with the largest up- or downregulation with TAC. Thus TAC results in altered expression of genes in several pathways regulating both cardiac structure and function. However, for in vivo gene microarray experiments, it is critical to define adequate controls, perform rigorous statistical analysis, and provide validation by alternative methods.

Acute Disease↗
PubMed1999

A case of constrictive pericarditis with local thickening of the pericardium without manifest ventricular interdependence.

This is the first case report of postsurgical constrictive pericarditis confined to the left ventricle in which the majority of diagnosis tests were not indicative of the disease. A 50-year-old woman with a past history of mitral valve replacement was admitted for right heart failure. Cardiac catheterization showed impaired diastolic filling but lacked the characteristic ventricular interdependence recently reported to be specific for the disease, without manifest radiological appearance of pericardial thickening. However, a new technique using magnetic resonance tagging cine revealed pericardial adhesion, limited to the left ventricle, which was confirmed during pericardiectomy. After the surgery, right heart failure and diastolic filling abnormality disappeared with restoration of normal heart pressures.

Blood Flow Velocity↗
PubMed2003

Reformation of the posterior atlanto-occipital membrane following posterior fossa decompression with subsequent constriction at the craniocervical junction.

The posterior atlanto-occipital membrane (PAO) contributes little to craniocervical stability and is generally underappreciated and incised with most suboccipital craniectomies. We report a case of a child who underwent posterior fossa decompression for Chiari I malformation with syringomyelia whose symptoms had not resolved months after surgery. A secondary exploratory operation revealed a healed constricting PAO which had been incised linearly at the initial operation. This patient's symptoms improved soon after the second surgery. We propose that attention be given to this membrane, and if it is incised with underlying dura mater as in a standard posterior fossa decompression, it should be removed or cauterized separately and laterally to inhibit its reformation.

Arnold-Chiari Malformation↗
PubMed2004

Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist CP-101,606 in a rat chronic constriction injury model.

In order to examine the site of action of an NR2B subtype-selective NMDA antagonist CP-101,606, we investigated its analgesic effect in a rat model of neuropathic pain at various routes of administration. Mechanical allodynia was induced by chronic constriction injury (CCI) of the sciatic nerve in male Sprague-Dawley rats. Subcutaneous treatment of the animals with CP-101,606 at 10 mg/kg significantly inhibited CCI-induced mechanical allodynia. Intracerebroventricular injection of CP-101,606 at 10, 30 and 100 nmol also inhibited the mechanical allodynia in a dose-dependent manner, the statistically significant effect being achieved at the highest dose tested (100 nmol) without producing any behavioral abnormalities. However, intrathecal injection of CP-101,606 at a dose of 300 nmol failed to inhibit CCI-induced allodynia. A receptor binding assay using rat forebrain and spinal cord membrane preparations demonstrated that [3H]CP-101,606 bound to the brain NR2B receptor with a greater extent compared to the spinal cord one. These findings suggest that the anti-allodynia effect of CP-101,606 is ascribable to blockade of NR2B receptors at the brain, but not at the spinal cord. In contrast, intrathecal injection of a non-selective NMDA antagonist, memantine, significantly inhibited CCI-induced mechanical allodynia at a dose of 300 nmol, indicating the difference in the site of action between the non-selective NMDA antagonist and the NR2B-specific NMDA antagonist.

Analgesics↗
PubMed2006

Clozapine-induced effuso-constrictive pericarditis. Case report and review of the literature.

Clozapine is a widely used antipsychotic medication and is effective against both positive and negative symptoms of schizophrenia. However, clozapine use should be monitored closely due to its side effects profile. The main side effects include cardiorespiratory symptoms, seizures and agranulocytosis. We report a case of effuso-constrictive pericarditis soon after being started on clozapine therapy, whose symptoms improved after discontinuation of clozapine. The literature is reviewed and importance of monitoring is discussed.

Antipsychotic Agents↗
PubMedDate not supplied

In situ morphology of fetal aortic isthmus following ductal constriction in rats.

To clarify the effect of experimentally increased blood flow to the aortic isthmus, in situ cross-sectional morphology of the aortic isthmus and the juxta-ductal descending aorta was studied in fetal rats. Indomethacin (10 mg/kg) was administered to 10 near-term pregnant rats, and fetuses were studied 4 and 24 h later with cesarean section, rapid whole-body freezing, sectioning on a freezing microtome in a plane perpendicular to the aortic isthmus, and photographing cross-sections. Fetuses without treatment served as controls. The ductus was constricted and its cross-sectional area was 12 +/- 3% (mean +/- SEM, % of control; p < 0.05 vs. control) at 4 and 24 h. The aortic isthmus was enlarged and the cross-sectional area was 146 +/- 5% at 24 h in response to the increased flow. These results support the concept that the size of the fetal aortic isthmus can change rapidly depending on the flow in late gestation.

Animals↗
PubMed2003

Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits.

OBJECTIVE: The redox pathophysiology of vascular repair is incompletely understood. We assessed the role of vascular superoxide dismutase (SOD) activity in oxidative/nitrative stress and caliber loss postinjury (PI). METHODS AND RESULTS: Rabbits submitted to iliac artery balloon overdistension were followed for 14 days PI. Significant decrease in vascular SOD activity occurred at 7 and 14 days PI (by 45% and 34%, respectively, versus control, 96+/-1 U/mg, P<0.05). Separation in concanavalin-A column showed that both extracellular SOD (ecSOD) and CuZn SOD activities were reduced, whereas Western analysis showed normal or augmented protein expression. Immunoreactivity to nitrotyrosine, neuronal NO synthase (NOS), and inducible NOS (iNOS) increased in media and neointima PI; iNOS mRNA also augmented. Administration of ecSOD from days 7 to 14 PI corrected the SOD activity decrease and minimized caliber loss by 59% (P=0.007) despite unaltered neointima. Nitrate levels markedly increased with ecSOD in injured artery homogenates (26+/-5 versus 4+/-0.3 micromol/L per mg, P=0.001). Such increase was 70% inhibited by specific iNOS antagonist 1400w. Nitrotyrosine and neuronal NOS expression decreased after ecSOD. CONCLUSIONS: Sustained low vascular SOD activity has a key role in constrictive remodeling after injury, promoting oxidative/nitrative stress and impairment of iNOS-derived NO bioavailability. SOD function may critically determine whether iNOS induction is beneficial or deleterious in vivo.

Animals↗
PubMed1999

Constrictive pericarditis in the modern era: evolving clinical spectrum and impact on outcome after pericardiectomy.

BACKGROUND: The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy. METHODS AND RESULTS: The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%, P = 0.011), but late survival was inferior to that of an age- and sex-matched US population (57+/-8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6+/-0.7 at baseline versus 1.5+/-0.8 at latest follow-up [P<0.0001]), with 83% being free of clinical symptoms. CONCLUSIONS: The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.

Adolescent↗
PubMed2000

Differentiation between restrictive cardiomyopathy and constrictive pericarditis by early diastolic doppler myocardial velocity gradient at the posterior wall.

BACKGROUND: The differential diagnosis between restrictive cardiomyopathy (RCM) and constrictive pericarditis (CP) is challenging and, despite combined information from different diagnostic tests, surgical exploration is often necessary. METHODS AND RESULTS: A group of 55 subjects (mean age, 63+/-11 years; 36 men and 19 women) were enrolled in the study; 15 had RCM, 10 had CP, and 30 were age-matched, normal controls. The diagnosis of RCM was supported by a biopsy; in the CP group, the diagnosis was confirmed either surgically or at autopsy. All patients underwent a transthoracic echocardiogram that included the assessment of Doppler myocardial velocity gradient (MVG), as measured from the left ventricular posterior wall during the predetermined phases of the cardiac cycle. MVG was lower (P<0.01) in RCM patients compared with both CP patients and normal controls during ventricular ejection (2. 8+/-1.2 versus 4.4+/-1.0 and 4.7+/-0.8 s(-1), respectively) and rapid ventricular filling (1.9+/-0.8 versus 8.7+/-1.7 and 3.7+/-1.4 s(-1), respectively). Additionally, during isovolumic relaxation, MVG was positive in RCM patients and negative in both CP patients and normal controls (0.7+/-0.4 versus -1.0+/-0.6 and -0.4+/-0.3 s(-1), respectively; P<0.01). During atrial contraction, MVG was similarly low (P<0.01) in both RCM and CP patients compared with normal controls (1.6+/-1.7 and 1.7+/-1.8 versus 3.8+/-0.9 s(-1), respectively). CONCLUSIONS: Doppler myocardial imaging-derived MVG, as measured from the left ventricular posterior wall in early diastole during both isovolumic relaxation and rapid ventricular filling, allows for the discrimination of RCM from CP.

Aged↗