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J L Guerrero

Publications and source records attributed to J L Guerrero.

At least 19 recordsLinked to original sources
PubMed2001

Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction: insights from three-dimensional and contrast echocardiography with strain rate measurement.

BACKGROUND: Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. METHODS AND RESULTS: We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2+/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2+/-0.3 to 1.4+/-0.3 mL; +3.8+/-0.5 mm to -2.2+/-0.7 mm axially relative to baseline; P<0.001) as PM strain rate decreased from +0.78+/-0.07 per second (contraction) to -0.42+/-0.06 per second (elongation, P<0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with inferior ischemia and recurred with PM ischemia. CONCLUSIONS: PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy.

Animals↗
PubMed2001

Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. METHODS AND RESULTS: In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8+/-0.2 to 7.1+/-0.5 mL/beat after infarction and then decreased to 0.9+/-0.1 mL/beat with chordal cutting (P<0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). CONCLUSIONS: Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.

Animals↗
PubMed2001

Cessation of platelet-mediated cyclic canine coronary occlusion after thrombolysis by combining nitric oxide inhalation with phosphodiesterase-5 inhibition.

OBJECTIVES: We sought to evaluate the ability of type 5 phosphodiesterase (PDE5) inhibitors to augment the antithrombotic effects of inhaled nitric oxide (NO) in a canine model of platelet-mediated coronary thrombosis after thrombolysis. BACKGROUND: Type 5 phosphodiesterase inhibitors potentiate the ability of NO to inhibit platelet aggregation in vitro by preventing platelet cyclic guanosine monophosphate catabolism. We previously reported that breathing low concentrations of NO gas attenuated, but did not prevent, cyclic flow reductions (CFRs) in a canine model of coronary thrombosis after thrombolysis. METHODS: Cyclic flow reductions were induced after creation of a left anterior descending coronary artery stenosis, endothelial injury, thrombus formation and thrombolysis. Dogs were either untreated or treated with inhaled NO (20 ppm by volume), intravenous zaprinast, intravenous dipyridamole or the combination of inhaled NO with either PDE5 inhibitor (n = 4 per group). RESULTS: Cyclic flow reductions ceased, and complete coronary patency was achieved in all dogs after they breathed NO combined with zaprinast (by 12.0+/-4.7 min [mean +/- SEM]) or dipyridamole (by 9.8+/-4.7 min). The frequency of CFRs was unaffected by NO, dipyridamole or zaprinast alone. Systemic arterial blood pressure and bleeding time were unchanged with any treatment. Ex vivo thrombin-induced platelet aggregation in dogs breathing NO and receiving dipyridamole was reduced by 75+/-7% (p < 0.05). CONCLUSIONS: The PDE5 inhibitors potentiated the antithrombotic properties of inhaled NO in a canine model of platelet-mediated coronary artery thrombosis after thrombolysis, without prolonging the bleeding time or causing systemic hypotension.

Administration, Inhalation↗
PubMed2001

Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation.

OBJECTIVES: This study aimed to separate proposed mechanisms for segmental ischemic mitral regurgitation (MR), including left ventricular (LV) dysfunction versus geometric distortion by LV dilation, using models of acute and chronic segmental ischemic LV dysfunction evaluated by three-dimensional (3D) echocardiography. BACKGROUND: Dysfunction and dilation-both mechanisms with practical therapeutic implications-are difficult to separate in patients. METHODS: In seven dogs with acute left circumflex (LCX) coronary ligation, LV expansion was initially restricted and then permitted to occur. In seven sheep with LCX branch ligation, LV expansion was also initially limited but became prominent with remodeling over eight weeks. Three-dimensional echo reconstruction quantified mitral apparatus geometry and MR volume. RESULTS: In the acute model, despite LV dysfunction with ejection fraction = 23 +/- 8%, MR was initially trace with limited LV dilation, but it became moderate with subsequent prominent dilation. In the chronic model, MR was also initially trace, but it became moderate over eight weeks as the LV dilated and changed shape. In both models, the only independent predictor of MR volume was increased tethering distance from the papillary muscles (PMs) to the anterior annulus, especially medial and posterior shift of the ischemic medial PM, measured by 3D reconstruction (r2 = 0.75 and 0.86, respectively). Mitral regurgitation volume did not correlate with LV ejection fraction or dP/dt. CONCLUSIONS: Segmental ischemic LV contractile dysfunction without dilation, even in the PM territory, fails to produce important MR. The development of MR relates strongly to changes in the 3D geometry of the mitral apparatus, with implications for approaches to restore a more favorable configuration.

Animals↗
PubMed2000

The power-velocity integral at the vena contracta: A new method for direct quantification of regurgitant volume flow.

BACKGROUND: Noninvasive quantification of regurgitation is limited because Doppler measures velocity, not flow. Because backscattered Doppler power is proportional to sonified blood volume, power times velocity should be proportional to flow rate. Early studies, however, suggested that this held only for laminar flow, not for regurgitant jets, in which turbulence and fluid entrainment augment scatter. We therefore hypothesized that this Doppler power principle can be applied at the proximal vena contracta, where flow is laminar before entrainment, so that the power-times-velocity integral should vary linearly with flow rate and its time integral with stroke volume (SV). METHODS AND RESULTS: This was tested in vitro with steady and pulsatile flow through 0.07- to 0.8-cm(2) orifices and in 36 hemodynamic stages in vivo, replacing the left atrium with a rigid chamber and column for direct visual recording of mitral regurgitant SV (MRSV). In 12 patients, MRSV was compared with MRI mitral inflow minus aortic outflow and in 11 patients with 3D echo left ventricular ejection volume-Doppler aortic forward SV. Vena contracta power in the narrow high-velocity spectrum from a broad measuring beam was calibrated against that from a narrow reference beam of known area. Calculated and actual flow rates and SV correlated well in vitro (r=0.99, 0.99; error=-1.6+/-2.5 mL/s, -2. 4+/-2.9 mL), in vivo (MRSV: r=0.98, error=0.04+/-0.87 mL), and in patients (MRSV: r=0.98, error=-2.8+/-4.5 mL). CONCLUSIONS: The power-velocity integral at the vena contracta provides an accurate direct measurement of regurgitant flow, overcoming the limitations of existing Doppler techniques.

Animals↗
PubMed2000

Design of a new surgical approach for ventricular remodeling to relieve ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

BACKGROUND: Mechanistic insights from 3D echocardiography (echo) can guide therapy. In particular, ischemic mitral regurgitation (MR) is difficult to repair, often persisting despite annular reduction. We hypothesized that (1) in a chronic infarct model of progressive MR, regurgitation parallels 3D changes in the geometry of mitral leaflet attachments, causing increased leaflet tethering and restricting closure; therefore, (2) MR can be reduced by restoring tethering geometry toward normal, using a new ventricular remodeling approach based on 3D echo findings. METHODS AND RESULTS: We studied 10 sheep by 3D echo just after circumflex marginal ligation and 8 weeks later. MR, at first absent, became moderate as the left ventricle (LV) dilated and the papillary muscles shifted posteriorly and mediolaterally, increasing the leaflet tethering distance from papillary muscle tips to the anterior mitral annulus (P<0.0001). To counteract these shifts, the LV was remodeled by plication of the infarct region to reduce myocardial bulging, without muscle excision or cardiopulmonary bypass. Immediately and up to 2 months after plication, MR was reduced to trace-to-mild as tethering distance was decreased (P<0.0001). LV ejection fraction, global LV end-systolic volume, and mitral annular area were relatively unchanged. By multiple regression, the only independent predictor of MR was tethering distance (r(2)=0.81). CONCLUSIONS: Ischemic MR in this model relates strongly to changes in 3D mitral leaflet attachment geometry. These insights from quantitative 3D echo allowed us to design an effective LV remodeling approach to reduce MR by relieving tethering.

Acute Disease↗
PubMed2000

Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure.

In human and experimental models of heart failure, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling. The disturbances in calcium metabolism have been shown to contribute significantly to the contractile dysfunction observed in heart failure. We investigated whether increasing SERCA2a expression can improve ventricular function in an animal model of heart failure obtained by creating ascending aortic constriction in rats. After 19-23 wk of banding during the transition from compensated hypertrophy to heart failure (documented by >25% decrease in fractional shortening), rats were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a, n = 13) or beta-galactosidase (Ad.betagal, n = 14) by using a catheter-based technique. The failing hearts infected with Ad. betagal were characterized by a significant decrease in SERCA2a expression and a decrease in SERCA2a activity compared with nonfailing sham-operated rats (n = 11). In addition, these failing hearts had reduced left-ventricular systolic pressure, maximal rate of left-ventricular pressure rise and decline (+dP/dt, -dP/dt), and rate of isovolumic relaxation (tau). Overexpression of SERCA2a restored both SERCA2a expression and ATPase activity to nonfailing levels. Furthermore, rats infected with Ad.SERCA2a had significant improvement in left-ventricular systolic pressure, +dP/dt, -dP/dt, and rate of isovolumic relaxation (tau) normalizing them back to levels comparable to sham-operated rats. In this study, we show that in an animal model of heart failure where SERCA2a protein levels and activity are decreased and severe contractile dysfunction is present, overexpression of SERCA2a in vivo restores both systolic and diastolic function to normal levels.

Adenoviridae↗
PubMed2000

Myocardial perfusion and wall motion in infarction border zone: assessment by myocardial contrast echocardiography.

Several mechanisms have been proposed to explain the decreased wall motion (WM) at the borders of myocardial infarction (MI). We used myocardial contrast echocardiography (MCE) to investigate the relation of perfusion to WM in infarcted border zones (BZs) 6 weeks after MI in 5 sheep. After quantifying the extent of WM abnormality and the perfusion defect, normal (NL), infarcted, and BZs were defined. Peak intensity after contrast was measured in acoustic units (AU). Radiolabeled microspheres were injected to measure regional blood flow. The heart was stained with 2,3, 5-triphenyltetrazolium chloride (TTC). The perfusion defect on MCE was 33% +/- 7% of the total myocardial area and correlated well with TTC (r = 0.92, P <.03). The BZ was 8% +/- 5% of the total myocardial area. Peak intensity after contrast was decreased in MI compared with BZ and NL (MI: 2.5 +/- 1.9 AU, BZ: 8.0 +/- 3.8 AU, P <.005; NL: 10.2 +/- 6.9 AU, P <.02) and comparable in NL and BZ. The blood flow measured by microspheres was not different in NL and BZ but was decreased in MI (NL: 1.6 mL/g/min, BZ: 1.5 +/- 0.5 mL/g/min, MI: 0.7 +/- 0.5 mL/g/min; P <.0001). In this model of chronic ovine MI, the BZ was small and its perfusion was preserved. These findings support the hypothesis that tethering of normal myocardial segments explains the abnormal wall motion noted at the borders of MI.

Animals↗
PubMed2000

Emergency department visits associated with traumatic brain injury: United States, 1995-1996.

The purposes of this study were to provide a national estimate of the incidence of traumatic brain injuries (TBIs) seen in emergency departments (EDs), but not requiring hospitalization and to determine the causes of these injuries. Using the Centers for Disease Control and Prevention case definition of TBI, ED data was analysed from the National Hospital Ambulatory Medical Care Survey (1995-1996). The average overall incidence rate of TBI-related ED visits for persons who were not hospitalized was 392/100,000 population per year, or 1,027,000 visits to hospital EDs in the US each year. This estimate is nearly twice (392 vs. 216) the previously estimated incidence rate, which was based on data from the 1991 National Health Interview Survey Injury Supplement. It was found that the highest incidence rate occurred among children aged 0-14 years, the rate for males was higher than for females, and the primary reported causes of these injuries were 'falls', motor vehicle-related causes, and 'struck by an object'. Although often considered 'mild' TBIs, these injuries can lead to significant cognitive and emotional impairment. Thus, continued surveillance of TBI-related ED visits is an important part of a comprehensive TBI prevention strategy.

Adolescent↗
PubMed1999

Surveillance for injuries and violence among older adults.

PROBLEM/CONDITION: Injuries and violence are major causes of disability and death among adults aged > or =65 years in the United States. Injuries impair older adults' quality of life and result in billions of dollars in health-care expenditures each year. REPORTING PERIOD: This report reviews 1987-1996 data regarding fall-related deaths, 1988-1996 data on hospitalizations for hip fracture, 1990-1997 data regarding motor vehicle-related injuries, 1990-1996 data on suicides, and 1987-1996 data on homicides. DESCRIPTION OF SYSTEMS: Data on fall-related deaths, suicides, and homicides are from the National Center for Health Statistics annual mortality data tapes for 1987-1996. Homicide data are supplemented with information from the Federal Bureau of Investigation's Supplemental Homicide Reports for 1987-1996. Data on hospitalizations for hip fracture are from the 1988-1996 National Hospital Discharge Surveys. Information regarding motor vehicle-related injuries for 1990-1997 is from the National Highway Traffic Safety Administration's Fatality Analysis Reporting System and General Estimates System. RESULTS: Rates of fall-related deaths for older adults increased sharply with advancing age and were consistently higher among men in all age categories. Men were 22% more likely than women to sustain fatal falls. A trend of increasing rates of fall-related deaths was observed from 1987 through 1996 in the United States, although rates were consistently lower for women throughout this period. Rates of hospitalizations for hip fracture differed by age and were higher for white women than for other groups. Rates increased with advancing age for both sexes but were consistently higher for women in all age categories. U.S. hospitalization rates for hip fracture increased for women from 1988 through 1996 while the rates for men remained stable. Rates of motor vehicle-related injuries increased slightly from 1990 through 1997, and marked variations in state-specific death rates were observed; in most states, older men had death rates approximately twice those for older women. Although suicide rates remain higher among older adults than among any other age group, rates of suicide among adults aged > or =65 years decreased 16% during the study period. Suicide rates among older adults varied by sex and age group. Homicide rates declined 36% among older adults. Homicide rates were highest for black men, followed by black women and white men; the homicide risk for blacks relative to whites decreased from 4.8 to 3.9 per 100,000 persons, indicating that the gap between rates for blacks and whites is closing. Half of the older homicide victims were killed by someone they knew. INTERPRETATION: The increase in rates of fall-related deaths and hip fracture hospitalizations from 1988 through 1996 might reflect a change in the proportion of adults aged > or =85 years compared with those aged 65-84 years - a change that results, in part, from reduced mortality from cardiovascular and other chronic diseases. Fall-related death rates might be higher among older men because they often have a higher prevalence of comorbid conditions than women of similar age. Racial differences in hospitalization rates might have some underlying biologic basis; the prevalence of osteoporosis, a condition that contributes to reduced bone mass and increased bone fragility, is greatest among older white women. Compared with whites aged > or =65 years, blacks of comparable ages have greater bone mass and are less likely to sustain fall-related hip fractures. Additional studies are needed to determine why rates of motor vehicle-related injury have increased slightly among older adults and why these rates vary by state. Declining rates of suicide among older adults might be related to changes in the effect or type of risk factors traditionally observed in this age group. Research is needed to identify reasons for variations in suicide rates among older persons. Homicides among olde

Accidental Falls↗
PubMed1999

Epidemiological approach to quality assessment in echocardiographic diagnosis.

OBJECTIVES: This study sought to determine whether statistical analysis of a computerized clinical diagnostic database can be used as a tool for quality assessment by determining the contribution of reader bias to variance in diagnostic output. BACKGROUND: In industry, measurement of product uniformity is a key component of quality assessment. In echocardiography, quality assessment has focused on review of small numbers of cases, or prospective determination of reader variability in selected and relatively small subsets. However, diagnostic biases in clinical practice might be discerned utilizing large computerized databases to determine interreader differences in diagnostic prevalence and, with use of appropriate statistical methods, to determine the association of reader selection with diagnostic prevalence independently of other covariates. METHODS: We analyzed 6,026 echocardiograms in a computerized database, read by one of three level 3 (American Society of Echocardiography) readers, for differences in frequency among four coded echocardiographic diagnoses: mitral valve prolapse, valvular vegetations, left ventricular (LV) thrombus, and LV regional wall-motion abnormality. RESULTS: Significant differences (up to fourfold) were found between readers, which persisted after statistical adjustment for those population characteristics, which differed slightly between readers. The low population prevalence of these conditions would have made it unlikely that these interreader differences could be detected by nonstatistical methods. Additionally, chamber dimensions differed between readers and were not normally distributed. CONCLUSIONS: Statistically based quality assessment analysis of computerized clinical databases facilitates ongoing monitoring of interreader bias despite low diagnostic prevalence, and targets opportunities for subsequent quality improvement.

Diagnostic Errors↗
PubMed1999

Abnormal global left ventricular relaxation occurs early during the development of pharmacologically induced ischemia.

In animal and human models, left ventricular (LV) diastolic function has been observed to be highly sensitive to myocardial ischemia. The response of LV diastolic parameters to pharmacologically induced ischemia, however, has not been characterized and might be important in the interpretation of dobutamine stress echocardiography. Eight mongrel dogs, in which were inserted a high-fidelity micromanometer LV catheter, coronary sinus sampling catheter, and ultrasonic coronary artery flow probe, underwent intravenous dobutamine infusion at escalating doses both before (control protocol) and after (ischemia protocol) creation of left anterior descending coronary artery stenosis with a hydraulic cuff occluder adjusted to maintain resting coronary artery flow but attenuate reactive hyperemia. At each dobutamine dose, epicardial short-axis 2-dimensional echocardiographic images and hemodynamic measurements were obtained. LV diastolic function was examined by calculation of peak (-)dP/dt and the time constant of isovolumic relaxation (tau). The dobutamine infusion protocol was terminated on the earliest recognition of an anterior wall motion abnormality. Peak (+)dP/dt normalized for developed isovolumetric pressure was calculated as a relatively load-independent index of global LV contractile function. Dobutamine infusion with and without ischemia resulted in comparable changes in heart rate and (+)dP/dt/IP, with no change in LV end-diastolic or -systolic pressure. The magnitude of peak (-)dP/dt increased less during the ischemia (1231 +/- 109 to 1791 +/- 200 mm Hg/sec) versus the control (1390 +/- 154 to 2432 +/- 320 mm Hg/sec) protocol (P <.05). Similarly, the observed decrease in tau was less during the ischemia (53 +/- 3 to 38 +/- 4 msec) than the control (51 +/- 5 to 23 +/- 3 msec) protocol, corresponding to a slower rate of relaxation (P <.05). In addition, the smaller decrease in tau was observed at the dobutamine dose before the dose at which an echocardiographic wall motion abnormality was first recognized. Dobutamine-induced ischemia is associated with abnormal LV diastolic function. In addition, these abnormalities seem to occur early in the development of ischemia. These observations extend to pharmacologically induced ischemia prior findings from other models of ischemia, suggesting the high sensitivity of LV diastolic function to the development of myocardial ischemia.

Animals↗
PubMed1999

The prevalence of disability from chronic conditions due to injury among adults ages 18-69 years: United States, 1994.

PURPOSE: To describe the causes and determine the prevalence of disability from chronic conditions due to injury among US civilian non-institutionalized persons aged 18-69 years. METHODS: Data from the National Health Interview Survey Disability (NHIS-D) Supplement Phase I, United States 1994 were analysed and six disability categories were examined: activities of daily living (ADL), instrumental activities of daily living (IADL), functional activities (FA), sight, hearing, and communication. RESULTS: In 1994, 5.6 million persons aged 18-69 years reported a disability because of a chronic condition that was caused by injury. The prevalence of ADL disability due to chronic conditions caused by injury was 370 per 100000 population; IADL disability was 1256; FA disability was 2512; sight was 231; hearing was 339; and communication was 91 per 100000 population. Fifty per cent of ADL, IADL, and FA disabilities were attributed to motor vehicle crashes and falls, as were 31% of sight, 19% of hearing, and 23% of communication disabilities. CONCLUSIONS: Though these estimates may be conservative, this study indicates that injury is a major cause of disability in addition to a leading cause of death in the US.

Adolescent↗
PubMed1999

Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH(2)-terminal kinases.

Cardiac hypertrophy often presages the development of heart failure. Numerous cytosolic signaling pathways have been implicated in the hypertrophic response in cardiomyocytes in culture, but their roles in the hypertrophic response to physiologically relevant stimuli in vivo is unclear. We previously reported that adenovirus-mediated gene transfer of SEK-1(KR), a dominant inhibitory mutant of the immediate upstream activator of the stress-activated protein kinases (SAPKs), abrogates the hypertrophic response of neonatal rat cardiomyocytes to endothelin-1 in culture. We now report that gene transfer of SEK-1(KR) to the adult rat heart blocks SAPK activation by pressure overload, demonstrating that the activity of cytosolic signaling pathways can be inhibited by gene transfer of loss-of-function mutants in vivo. Furthermore, gene transfer of SEK-1(KR) inhibited pressure overload-induced cardiac hypertrophy, as determined by echocardiography and several postmortem measures including left ventricular (LV) wall thickness, the ratio of LV weight to body weight, cardiomyocyte diameter, and inhibition of atrial natriuretic factor expression. Our data suggest that the SAPKs are critical regulators of cardiac hypertrophy in vivo, and therefore may serve as novel drug targets in the treatment of hypertrophy and heart failure.

Adenoviridae↗
PubMed1999

Myocardial perfusion and right ventricular function.

OBJECTIVE: Maximal right ventricular (RV) performance is influenced by left heart hemodynamics and hence coronary perfusion. We examined the role of myocardial perfusion of the right ventricle as potential determinant of maximal RV function. MATERIALS AND METHODS: In 6 canine isovolumic right heart preparations, incremental volumes were introduced into a high compliance RV balloon until RV failure occurred. Maximal RV developed pressure (RVDP) and maximal positive RV dP/dt were determined at a constant controlled left ventricular (LV) output of 2 l/min and at controlled mean arterial pressures of 50, 80 and 120 mmHg. Right coronary artery (RCA) flow was measured. RESULTS: Maximal RVDP increased significantly with increasing mean arterial pressures (44.8+/-11.2 vs 57.2+/-15.5 vs 75.4+/-2.5 mmHg for systemic pressures of 50, 80 and 120 mmHg respectively, p < 0. 05). With increasing mean arterial pressures RCA flow increased significantly (33.1+/-11.0 vs 46.1+/-20.4 vs 79.6+/-35.3 ml/min). At the onset of RV failure, RCA blood flow significantly decreased in all preparations compared to the maximal flow in the RCA (1.9+/-1.0 vs 33.1+/-11.0 ml/min at 50 mmHg; 13.6+/-10.2 vs 46.1+/-20.4 ml at 80 mmHg and 18.7+/-8.0 vs 79.6+/-35.3 ml/min at 120 mmHg; p < 0.05). CONCLUSIONS: These results suggest that coronary perfusion is a major determinant of maximal RV function. The coronary artery driving pressure must be sufficient to avoid the onset of RV failure. Maintaining systemic pressure and hence RV myocardial blood flow may thus extend RV function.

Animals↗
PubMed1999

[Adequacy of continuous ambulatory peritoneal dialysis in children].

When the use of dialytical therapy is decided after a careful assessment of clinical and laboratory variables, the close supervision of the procedure, that allows a feedback between our indications and its clinical efficacy, is essential. The correct and routine use of validated adequacy tools such as Kt/V and the Peritoneal Equilibration Test (PET) is mandatory. We compare the adequacy figures for adult and pediatric populations, mentioning the Kt/V and PET values obtained in eight patients followed during 12 months in a Nephrology Unit. An initial Kt/V of 2.04 and of 2.14 after 12 months of procedure are values that adjust to the general recommendations discussed in this paper. According to PET results, this group of patients were classified as low average for ultrafiltration and high average for creatinine clearance. Based on the local experience and literature review, some recommendations are made for the management of peritoneal dialysis in children.

Adult↗
PubMed1998

Modulation of ventricular function through gene transfer in vivo.

We used a catheter-based technique to achieve generalized cardiac gene transfer in vivo and to alter cardiac function by overexpressing phospholamban (PL) which regulates the activity of the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a). By using this approach, rat hearts were transduced in vivo with 5 x 10(9) pfu of recombinant adenoviral vectors carrying cDNA for either PL, beta-galactosidase (beta-gal), or modified green fluorescent protein (EGFP). Western blot analysis of ventricles obtained from rats transduced by Ad.PL showed a 2.8-fold increase in PL compared with hearts transduced by Ad.betagal. Two days after infection, rat hearts transduced with Ad.PL had lower peak left ventricular pressure (58.3 +/- 12.9 mmHg, n = 8) compared with uninfected hearts (92.5 +/- 3.5 mmHg, n = 6) or hearts infected with Ad.betagal (92.6 +/- 5.9 mmHg, n = 6). Both peak rate of pressure rise and pressure fall (+3, 210 +/- 298 mmHg/s, -2, 117 +/- 178 mmHg/s, n = 8) were decreased in hearts overexpressing PL compared with uninfected hearts (+5, 225 +/- 136 mmHg/s, -3, 805 +/- 97 mmHg/s, n = 6) or hearts infected with Ad.betagal (+5, 108 +/- 167 mmHg/s, -3, 765 +/- 121 mmHg/s, n = 6). The time constant of left ventricular relaxation increased significantly in hearts overexpressing PL (33.4 +/- 3.2 ms, n = 8) compared with uninfected hearts (18.5 +/- 1.0 ms, n = 6) or hearts infected with Ad.betagal (20.8 +/- 2.1 ms, n = 6). These differences in ventricular function were maintained 7 days after infection. These studies open the prospect of using somatic gene transfer to modulate overall cardiac function in vivo for either experimental or therapeutic applications.

Adenoviruses, Human↗