No substantial excess all-cause mortality among cardiac implantable electronic device patients during the first COVID­19 lockdown in the Leiden area.

In the Netherlands, the coronavirus disease 2019 (COVID­19) pandemic has resulted in excess mortality nationwide. Chronic heart disease patients are at risk for a complicated COVID­19 course. The current study investigates all-cause mortality among cardiac implantable electronic device (CIED) patients during the first peak of the pandemic and compares the data to the statistics for the corresponding period in the two previous years. Data of adult CIED patients undergoing follow-up at the Leiden University Medical Centre were analysed. All-cause mortality between 1 March and 31 May 2020 was evaluated and compared to the data for the same period in 2019 and 2018. At the beginning of the first peak of the pandemic, 3,171 CIED patients (median age 70 years; 68% male; 41% ischaemic aetiology) were alive. Baseline characteristics of the 2019 (n = 3,216) and 2018 (n = 3,169) cohorts were comparable. All-cause mortality during the peak of the pandemic was 1.4% compared to 1.6% and 1.4% in the same period in 2019 and 2018, respectively (p = 0.84). During the first peak of the COVID­19 pandemic, there was no substantial excess mortality among CIED patients in the Leiden area, despite the fact that this is group at high risk for a complicated course of a COVID­19 infection. Strict adherence to the preventive measures may have prevented substantial excess mortality in these vulnerable patients.

Redesigning healthcare: The 2.4 billion euro question? : Connecting smart technology to improve outcome of patients.

Although it has been possible to transfer electrocardiograms via a phone line for more than 100 years, use of internet-based patient monitoring and communication systems in daily care is uncommon. Despite the introduction of numerous health-monitoring devices, and despite most patients having internet access, the implementation of individualised healthcare services is still limited. On the other hand, hospitals have invested heavily in massive information systems offering limited value for money and connectivity. However, the consumer market for personal healthcare devices is developing rapidly and with the current healthcare-related investments by tech companies it can be expected that the way healthcare is provided will change dramatically. Although a variety of initiatives under the banner of 'e-Health' are deployed, most are characterised by either industry-driven developments without proven clinical effectiveness or individual initiatives lacking the embedding within the traditional organisations. However, the introduction of numerous smart devices and internet-based technologies facilitates the fundamental redesign of healthcare based on the principle of achieving the best possible care for the individual patient at the lowest possible cost. Conclusion The way healthcare is delivered will change, but to what degree healthcare professionals together with patients will be able to redesign healthcare in a structured manner is still a question.

Heart failure admissions in adults with congenital heart disease; risk factors and prognosis.

BACKGROUND: Heart failure (HF) is a serious complication and often the cause of death in adults with congenital heart disease (CHD). Therefore, our aims were to determine the frequency of HF-admissions, and to assess risk factors of first HF-admission and of mortality after first HF-admission in adults with CHD. METHODS: The Dutch CONCOR registry was linked to the Hospital Discharge Registry and National Mortality Registry to obtain data on HF-admissions and mortality. Risk factors for both HF-admission and mortality were assessed using Cox regression models. RESULTS: Of 10,808 adult patients (49% male), 274 (2.5%) were admitted for HF during a median follow-up period of 21 years. The incidence of first HF-admission was 1.2 per 1000 patient-years, but the incidence of HF itself will be higher. Main defect, multiple defects, and surgical interventions in childhood were identified as independent risk factors of HF-admission. Patients admitted for HF had a five-fold higher risk of mortality than patients not admitted (hazard ratio (HR)=5.3; 95% confidence interval 4.2-6.9). One- and three-year mortality after first HF-admission were 24% and 35% respectively. Independent risk factors for three-year mortality after first HF-admission were male gender, pacemaker implantation, admission duration, non-cardiac medication use and high serum creatinine. CONCLUSIONS: The incidence of HF-admission in adults with CHD is 1.2 per 1000 patient-years. Mortality risk is substantially increased after HF-admission, which emphasises the importance to identify patients at high risk of HF-admission. These patients might benefit from closer follow-up and earlier medical interventions. The presented risk factors may facilitate surveillance.

Integration of data from remote monitoring systems and programmers into the hospital electronic health record system based on international standards.

Remote follow-up of implanted ICDs may offer a solution to the problem of overcrowded outpatient clinics. All major device companies have developed a remote follow-up solution. Data obtained from the remote follow-up systems are stored in a central database system, operated and owned by the device company and accessible for the physician or technician. However, the problem now arises that part of the patient's clinical information is stored in the local electronic health record (EHR) system in the hospital, while another part is only available in the remote monitoring database. This may potentially result in patient safety issues. Ideally all information should become available in the EHR system. IHE (Integrating the Healthcare Enterprise) is an initiative to improve the way computer systems in healthcare share information. To address the requirement of integrating remote monitoring data in the local EHR, the IHE Implantable Device Cardiac Observation (IDCO) profile has been developed. In our hospital, we have implemented the IHE IDCO profile to import data from the remote databases from two device vendors into the departmental Cardiology Information System. Data are exchanged via an HL7/XML communication protocol, as defined in the IHE IDCO profile.

Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) associated with congenital heart disease is usually the result of a large systemic-to-pulmonary shunt, and often leads to right ventricular failure and early death. The purpose of this study was to determine the prevalence of PAH among adult patients included in a national registry of congenital heart disease and to assess the relation between patient characteristics and PAH. METHODS: Patients with PAH associated with a septal defect were identified from the registry. Gender, age, underlying diagnosis, previous closure, age at repair and NYHA classification were recorded. PAH was defined as a systolic pulmonary arterial pressure (sPAP) greater than 40 mm Hg, estimated by means of echocardiographical evaluation. RESULTS: The prevalence of PAH among all 5970 registered adult patients with congenital heart disease was 4.2%. Of 1824 patients with a septal defect in the registry, 112 patients (6.1%) had PAH. Median age of these patients was 38 years (range 18-81 years) and 40% were male. Of these patients, 58% had the Eisenmenger syndrome. Among the patients with a previously closed septal defect, 30 had PAH (3%). Ventricular septal defect (VSD) was the most frequent underlying defect (42%) among patients with PAH and a septal defect. Female sex (Odds ratio=1.5, p=0.001) and sPAP (Odds ratio=0.04, p<0.001) were independently associated with a decreased functional class. CONCLUSION: PAH is common in adult patients with congenital heart disease. In our registry the prevalence of PAH in septal defects is around 6%. More than half of these patients have the Eisenmenger syndrome, which accounts for 1% of the total population in the CONCOR registry. Whether the prevalence of PAH will decrease in the future as a result of early detection and intervention remains to be awaited.

CONCOR, an initiative towards a national registry and DNA-bank of patients with congenital heart disease in the Netherlands: rationale, design, and first results.

INTRODUCTION: Survival of patients with congenital heart disease has dramatically improved after surgical repair became available 40 years ago. Instead of a mortality of 85% during childhood following the natural course, over 85% of these infants are now expected to reach adulthood. However, data on long-term outcome is scarce due to the lack of large, national registries. Moreover, little is known about the genetic basis of congenital heart defects. In 2000, the Interuniversity Cardiology Institute of the Netherlands and the Netherlands Heart Foundation have taken the initiative to develop a national registry and DNA-bank of patients with congenital heart disease in the Netherlands named CONCOR. OBJECTIVES: The aims of the CONCOR project are to facilitate investigation of the prevalence and long-term outcome of specific congenital heart defects and their treatment, to develop an efficient organisational structure for the improvement of healthcare for patients with congenital heart disease, and to allow investigation of the molecular basis of congenital heart defects. METHODS: After informed consent, research nurses enter data of participating patients into the CONCOR database using a web application. Data is transferred over the Internet via a secure connection. About 20 ml blood is withdrawn from the patient, and the DNA is isolated and stored. From each participating patient family history on congenital heart disease is obtained. RESULTS: Within two and a half years more than 4200 patients have agreed to participate. More than 99% of the patients that were asked have given their consent to participate in CONCOR. From 60% of these patients DNA has already been obtained. Mean age of the patients included is 34 years; more than 85% of the patients are younger than 45 years. Late complications occur frequently and the incidence increases with advancing age. 18% of the patients are known with supraventricular or ventricular arrhythmias. 2% of the included patients suffered a cerebrovascular accident, 139 (3%) had endocarditis. 6% of the patients has pulmonary hypertension or Eisenmenger syndrome. More than 15% of the patients reported an affected family member with congenital heart disease in the first, second, or third degree. 6% has an affected first-degree relative, and 4% a second-degree relative. Already 10 research projects have started using the CONCOR data and DNA. CONCLUSION: The population of patients with congenital heart disease is young and rapidly growing. Late complications occur frequently and the incidence increases with advances age. The CONCOR registry and DNA-bank facilitates research on prevalence and long-term outcome and allows investigation of the molecular basis of congenital heart disease.

[National registry and DNA-bank of patients with congenital heart disease: the CONCOR-project]. / Landelijke registratie en DNA-bank van patiënten met aangeboren hartafwijkingen, het CONCOR-project.

Although survival of patients with congenital heart disease has dramatically improved since surgical repair has become available, cure is seldom achieved. Exact data on long-term outcome are not available, however, because a national registry is lacking. Furthermore, little is known about the role of genetic defects in the development of congenital heart disease. The CONCOR-project (CONgenital CORvitia) has been set up to facilitate the investigation of the long-term outcome and molecular basis of specific congenital heart defects and their treatment. It will also facilitate the development of an efficient organisational structure for the improvement of healthcare for patients with congenital heart disease.

The volume-dependency of parallel conductance throughout the cardiac cycle and its consequence for volume estimation of the left ventricle in patients.

OBJECTIVE: To study the hypothesis that the electrical conductance of tissues and fluids (parallel conductance (G(p))) around the ventricle depends on left ventricular volume throughout the cardiac cycle. METHODS: We extended a recently developed method to determine G(p) throughout the cardiac cycle. First, we compared the estimates of parallel conductances obtained with the new method (G(a)(p)) with those of the conventional one (G(1)(p)), both averaged over the cardiac cycles. Secondly, G(a)(p) was determined throughout the cardiac cycle and its volume dependency was assessed. Thirdly, the factor alpha was calculated as the ratio between stroke volume, obtained by the conductance method using G(1)(p), and that obtained by a thermodilution method. Because the non-homogeneous field was indicated to be the reason for the dependency of G(p) on left ventricular volume as well as for the need for alpha, we tested whether the hypothesis implies that a correction with alpha is not needed if G(p) is determined throughout the cardiac cycle. RESULTS: We found a negative linear relation between G(p) and left ventricular volume. This relation appeared to be reproducible within each patient. Furthermore, we found that alpha deviates from 1 primarily due to the dependency of G(p) on left ventricular volume. CONCLUSION: To obtain stroke volume or to determine absolute left ventricular volume continuously within a cardiac cycle, G(p) should be determined throughout each cardiac cycle and if a constant G(p) throughout the cardiac cycle is used a correction with the factor alpha should be made to correct for a possible influence of electrical field heterogeneity.

A new approach to determine parallel conductance for left ventricular volume measurements.

OBJECTIVES: To determine absolute ventricular volume with the conductance catheter technique, the electrical conductance of tissues and fluids (parallel conductance) around the ventricle should be determined precisely. METHODS: A new objective method to estimate parallel conductance based on analysis of the dilution curve of hypertonic saline was investigated. The parallel conductances obtained with the new method (G(a)(p)) were compared to those obtained with the conventional method (G(l)(p)). The study was performed in the left ventricle of 12 patients. RESULTS: G(a)(p) was not significantly different from G(l)(p). For the G(l)(p) method the average percentage difference between duplicate values, both taken as absolute values, was 15.06% and for the G(a)(p) method it was 4. 01%. Thus the reproducibility of the method is a factor four better than that of the method. This difference appeared to be significant. CONCLUSION: We conclude that a smaller number of injections will be required to obtain the same precision using our method.

Three-dimensional catheter positioning during radiofrequency ablation in patients: first application of a real-time position management system.

INTRODUCTION: Precise localization of target sites for radiofrequency catheter ablation (RFCA) of arrhythmias is hampered by the relative inaccuracy of X-ray localization procedures. This study evaluated the efficacy of a three-dimensional (3D) real-time position management system in guiding RFCA procedures in patients. METHODS AND RESULTS: Patients (n = 30, age 59+/-20 years) referred for ablation of either atrial flutter (n = 10), ventricular tachycardia (n = 15), or accessory pathways (n = 5) were studied. The real-time position management system uses ultrasound ranging techniques to track the position of an ablation catheter relative to two multitransducer reference catheters, positioned in the right atrium or coronary sinus and the right ventricle. Each catheter contains three or four ultrasound transducers. The distance between the transducer(s) is determined by calculating the time necessary for an ultrasound pulse to reach other transducers, assuming the speed of sound in blood is 1,550 m/sec. The proximal His bundle was marked at the beginning and the end of the procedure as an electrical landmark to verify reproducibility. After identification of target sites, the position of each lesion created with the ablation catheter was marked. Successful ablation was achieved in 94% of the patients. The distance between the location of the proximal His bundle as marked at the beginning and at the end of the procedure was 2.0+/-1.2 mm (range 1.5 to 3.5). CONCLUSION: The new 3D real-time position management system facilitated RFCA procedures as it allowed accurate and reproducible 3D tracking of the mapping and ablation catheter.

Evaluation of a new transcardiac conductance method for continuous on-line measurement of left ventricular volume.

OBJECTIVE: To evaluate a new, less invasive, conductance method to measure continuous on-line left ventricular volume. End-systolic and end-diastolic volumes obtained with this transcardiac conductance method were compared with simultaneous measurements using the conventional intracardiac conductance catheter. DESIGN: Controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Six sheep. INTERVENTIONS: Anesthetized sheep were instrumented and inotropic condition was varied by beta-receptor stimulation (5 microg/kg/min of dobutamine) and beta-receptor blockade (1 mg/kg of propranolol). In each condition (control, dobutamine, repeat control, propranolol), ventricular volume was varied over a wide range by gradual preload reduction using a vena caval balloon catheter. MEASUREMENTS AND MAIN RESULTS: We compared the two methods by performing linear regression analysis on simultaneous end-systolic and end-diastolic volumes obtained during gradual caval occlusions. We statistically analyzed the intercepts, slopes, and correlation coefficients of the regression equations relating the transcardiac and conductance catheter measurements to determine the effects of interanimal variability, inotropic condition, and cardiac phase on the relationship between the two methods. The results show an excellent linear correlation between the two methods (mean intercept, -1.82+/-1.24 mL; mean slope, 0.787+/-0.024 and r2 = .94). Both slope and intercept of the relationship between the two methods show a significant interanimal and cardiac phase related variability but no significant dependence on inotropic condition. CONCLUSIONS: The significant interanimal variability indicates that the new method requires individual calibration in each subject. However, the small variability of the regression coefficients with changes in condition indicates that after initial calibration, end-systolic and end-diastolic volume can be followed accurately even in the presence of large changes in volume and inotropic state. This new method may facilitate quantitative continuous assessment of cardiac function in clinical practice, for example, in the intensive care unit.

Correlated neurocardiologic and fitness changes in athletes interrupting training.

PURPOSE: We studied nine male Dutch top marathon skaters during a 1-month interruption of their training schedules after their last contest in the winter to investigate a possible decline in baroreflex sensitivity. METHODS: Before and after this period, a maximal exercise test was done, and at days 0, 4, 7, 14, and 28 neurocardiologic measurement sessions--heart rate and noninvasive baroreflex sensitivity, recumbent and tilt--were performed. RESULTS: Interruption of training resulted in a significant and relevant decrease in the maximal oxygen uptake (from 65.7 +/- 5.8 to 61.6 +/- 4.7 mL O2 x kg(-1) x min(-1); P = 0.03), most likely associated with decreased competitive possibilities. Resting heart rate modestly increased (from 54.6 +/- 7.2 to 58.8 +/- 7.5 bpm), however, not significantly. Heart rate during 60 degrees tilt increased considerably (from 70.1 +/- 6.1 to 80.1 +/- 9.1 bpm; P = 0.01), possibly due to a decrease in blood volume and an increase in cardiopulmonary baroreflex gain. Arterial baroreflex sensitivity decreased significantly in the recumbent (from 13.3 +/- 5.4 to 9.8 +/- 3.8 ms x mm Hg(-1), P = 0.04), but not in the 60 degrees tilt position (from 6.7 +/- 2.0 to 6.0 +/- 2.5 ms x mm Hg(-1)). The relative decrease in baroreflex sensitivity and maximal oxygen uptake correlated significantly (r = 0.71, P = 0.02). CONCLUSIONS: In summary, our data show that correlated detrimental changes in fitness and baroreflex sensitivity are measurable in these athletes after a month of interruption of training.

Pretreatment with allopurinol in cardiac hypoxic-ischemic reperfusion injury in newborn lambs exerts its beneficial effect through afterload reduction.

The aim of this study was to determine whether allopurinol (ALLO) reduces reperfusion injury inflicted upon the heart resulting from excess production of free oxygen radicals after hypoxia and ischemia (HI) in newborn animals. We, therefore, produced severe HI in 13 newborn lambs by low O2-ventilation and blood volume reduction. One hour before HI seven lambs received ALLO (20 mg/kg i.v.), six received a placebo (CONT). Cardiac function and hemodynamic parameters were assessed by sequential measurement of left ventricular (LV) contractility through the end-systolic pressure-volume relation (ESPVR) using the conductance catheter method. Stroke volume (SV), cardiac output (CO), and aortic pressure (Pao) were measured and ejection fraction and total peripheral resistance (TPR) were calculated before HI, upon resuscitation (UR), and at 60 and 120 min post-HI. To estimate the effect of ALLO on redox status and anti-oxidative capacity, we measured concentrations of uric acid, sulfhydryl (SH), malondialdehyde (MDA), ascorbic acid (AA), and dehydroxylated ascorbic acid (DHAA) in plasma obtained from the coronary sinus and calculated the AA/DHAA ratio. Compared to CONT lambs, TPR in ALLO treated lambs decreased significantly, accompanied by a rise in CO and SV. ALLO did not affect myocardial contractility, because the ESPVR showed no significant differences between groups. AA/DHAA and SH showed a significant decrease in ALLO animals vs pre-HI, but not in CONT animals. Uric acid was significantly decreased in ALLO as compared to pre-HI and CONT animals. MDA was significantly increased in CONT animals at 15 min post-HI as compared to pre-HI, whereas in ALLO animals MDA showed a significant increase at 120 min post-HI vs CONT. We conclude that pretreatment with ALLO has a beneficial effect on the pump function by afterload reduction but not by changes in contractility. Furthermore, ALLO inhibited uric acid formation with a consequent decrease in anti-oxidative capacity.

Effect of deferoxamine on post-hypoxic-ischemic reperfusion injury of the newborn lamb heart.

UNLABELLED: Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (Ees) and volume intercept of the end-systolic P-V relationship (V10). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither Ees nor EF changed significantly in either group, the volume intercept V10 in the DFO-treated group was significantly smaller (0.25 +/- 0.03 vs. 0.70 +/- 0.09, p < 0.05), whereas SV was larger (3.6 +/- 0.6 vs. 2.2 +/- 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. IN CONCLUSION: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.

Endocardial activation mapping of ventricular tachycardia in patients : first application of a 32-site bipolar mapping electrode catheter.

BACKGROUND: Localization of early activated endocardial areas during ventricular tachycardia (VT) is mandatory for performance of surgical or radiofrequency catheter interventions. The use of a multielectrode catheter may shorten the procedure time and increase the accuracy of the procedure compared with single-electrode mapping techniques. This study was performed to evaluate the safety and efficacy of a 32-bipolar-electrode mapping catheter in patients. METHODS AND RESULTS: The basket-shaped mapping catheter (BMC), integrated with a computerized mapping system, allowed on-line reconstruction of endocardial activation maps. Twenty patients with VT were studied before surgery (n=4) or radiofrequency catheter ablation (n=16). End-diastolic left ventricular (LV) volume was 280+/-120 mL, with an LV ejection fraction of 33+/-14%. The volume encompassed by the BMC was 164+/-27 mL (130 to 200 mL); the deployment time was 46+/-11 minutes. Endocardial activation time during sinus rhythm was 105+/-34 ms; 14+/-5 electrodes could be used to stimulate the heart. Cycle length of VT was 325+/-83 ms. Earliest endocardial activation was recorded 58+/-42 ms before the onset of the surface ECG. Complications were pericardial effusion (n=2) and transient cerebral disorientation (n=1). CONCLUSIONS: Percutaneous multielectrode endocardial mapping in patients with VT is feasible and relatively safe. The use of this technique shortens the time patients have to endure VT.

Effects of critical coronary stenosis on global systolic left ventricular function quantified by pressure-volume relations during dobutamine stress in the canine heart.

OBJECTIVES: In this study we quantified the effects of a critical coronary stenosis on global systolic function using pressure-volume relations at baseline and during incremental dobutamine stress. BACKGROUND: The effects of coronary stenosis have previously been analyzed mainly in terms of regional (dys)function. Global hemodynamics are generally considered normal until coronary flow is substantially reduced. However, pressure-volume analysis might reveal mechanisms not fully exposed by potentially load-dependent single-beat parameters. Moreover, no systematic analysis by pressure-volume relations of the effects of dobutamine over a wide dose range has previously been presented. METHODS: In 14 dogs left ventricular volume and pressure were measured by conductance and micromanometer catheters, and left circumflex coronary flow by Doppler probes. Measurements in control and with left circumflex stenosis were performed at baseline and at five levels of dobutamine (2.5 to 20 microg/kg/min). The end-systolic pressure-volume relation (ESPVR) dP/dtMAX vs. end-diastolic volume (dP/dtMAX - V(ED)) and the relation between stroke work and end-diastolic volume (preload recruitable stroke work [PRSW]) were derived from data obtained during gradual caval occlusion. RESULTS: In control, dobutamine gradually increased heart rate up to 20 microg/kg/min, the inotropic effect blunted at 15 microg/kg/min. With stenosis, the chronotropic effect was similar, however, contractile state was optimal at approximately 10 microg/kg/min and tended to go down at higher levels. At baseline, the positions of ESPVR and PRSW, but not of dP/dtMAX - V(ED), showed a significant decrease in function with stenosis. No differences between control and stenosis were present at 2.5 microg/kg/min; the differences were largest at 15 microg/kg/min. CONCLUSIONS: Pressure-volume relations and incremental dobutamine may be used to quantify the effects of critical coronary stenosis. The positions of these relations are more consistent and more useful indices than the slopes. The positions of the ESPVR and PRSW show a reduced systolic function at baseline, normalization at 2.5 microg/kg/min and a consistent significant difference between control and stenosis at dobutamine levels of 5 microg/kg/min and higher.

Left ventricular pressure-volume relationships before and after cardiomyoplasty in patients with heart failure.

BACKGROUND: The aim of this study was to elucidate whether beneficial effects of cardiomyoplasty (CMP) in patients with dilated cardiomyopathy are the result of a decrease in existing ventricular dilatation or a prevention of further dilatation. METHODS AND RESULTS: Combined micromanometer-conductance catheters were used to evaluate left ventricular pressure-volume relationships in six patients with dilated cardiomyopathy before and at 6 and 12 months after CMP. Acute changes in preload and afterload were induced by a standardized leg-tilting intervention and a bolus infusion of nitroglycerin. After CMP, end-diastolic volume (EDV) decreased from 138+/-10 to 103+/-18 mL/m2 (P<.01) at 6 months and to 83+/-17 mL/m2 (P<.01) at 12 months. End-diastolic pressure (EDP) decreased from 20.2+/-6.4 to 13.9+/-7.7 mm Hg (P<.01) at 6 months after CMP. Peak ejection rate and ejection fraction increased at 6 months after CMP from 594+/-214 to 799+/-214 mL/s (P<.05) and from 26.6+/-4.7% to 40.1+/-8.3% (P<.05), respectively. Peak dP/dt decreased at 12 months after CMP from -842+/-142 to -712+/-168 mm Hg/s (P<.05). Leg-tilting before CMP increased EDP from 20.2+/-6.4 to 25.6+/-5.2 mm Hg (P<.01), end-systolic pressure (ESP) from 118+/-17 to 122+/-17 mm Hg (P<.05), and tau from 50.8+/-2.8 to 53.8+/-2.3 ms (P<.05). Six months after CMP, leg-tilting also increased EDV from 103+/-18 to 110+/-22 mL/m2 (P<.05) and ESV from 62+/-14 to 66+/-14 mL/m2 (P<.05). Before CMP, nitroglycerin decreased EDP from 20.2+/-6.4 to 10.4+/-3.8 mm Hg (P<.01), ESP from 118+/-17 to 96+/-11 mm Hg (P<.05), ESV from 100+/-11 to 89+/-7 mL/m2 (P<.05), and tau from 50.8+/-2.8 to 44.5+/-3.7 ms (P<.05). Six months after CMP, nitroglycerin decreased EDP, ESP, and tau to similar values. CONCLUSIONS: Our findings show that up to 1 year after CMP, marked decreases in left ventricular volume are present. Our measurements suggest that CMP actively reduced the dilated ventricle but did not prevent a higher EDV on an increased venous return. The latissimus dorsi muscle wrap contraction results in better synchronization of contraction and more rapid emptying of the left ventricle.

Effect of post-hypoxic-ischemic inhibition of nitric oxide synthesis on cerebral blood flow, metabolism and electrocortical brain activity in newborn lambs.

Since an excessive production of nitric oxide upon reperfusion/reoxygenation may play an important role in post-hypoxic-ischemic (HI) brain injury, we investigated whether immediate post-HI blockade of nitric oxide synthesis by N-omega-nitro-L-arginine (NLA) may reduce this injury. In 18 newborn lambs, subjected to severe HI, changes from pre-HI values were measured for carotid blood flow (Qcar [ml/min]) as a measure of changes in brain blood flow, (relative) cerebral metabolic rate of oxygen (CMRO2), and electrocortical brain activity (ECBA) at 15, 60, 120 and 180 min after HI. Upon completion of HI, at the onset of reperfusion and reoxygenation, 6 lambs received a placebo (control group), 6 low-dose NLA (10 mg/kg i.v., NLA-10 group), and 6 high-dose NLA (40 mg/kg i.v., NLA-40 group). Histological damage to cerebellar Purkinje cells was assessed after termination of the experiment. Only the control group showed a distinct initial post-HI cerebral hyperperfusion. From 60 min after HI onward Qcar was decreased to about 75% of pre-HI Qcar in all 3 groups, although none of these changes in Qcar reached statistical significance. Despite the decreased Qcar in all 3 groups, only the control group showed a significantly decreased CMRO2. ECBA and its bandwidth decreased in all groups, but only recovered in the NLA-10 group 180 min after HI. The brain to body mass ratio (%) and percentage necrotic Purkinje cells were, respectively: 15.3 +/- 0.8 and 56 +/- 10 (control group); 12.5 +/- 1.2 and 36 +/- 9 (NLA-10 group), and 11.3 +/- 1.0 (p < 0.05 vs. the control group) and 35 +/- 14 (NLA-40 group). Since post-HI reperfusion injury of the brain has been characterized by a decreased CMRO2 and electrical brain activity, we conclude that preservation of CMRO2 in both NLA groups, but a recovery of ECBA and its bandwidth only in the NLA-10 group, suggests that NLA, and especially low-dose NLA, may reduce post-HI brain injury.

Nitric oxide inhibition after hypoxia-ischemia elevates pulmonary arterial pressure and increases oxygen need.

Inhibition of nitric oxide (NO) production may reduce post-hypoxic-ischemic (HI) neonatal brain damage, but may also induce pulmonary hypertension by inhibiting endogenous NO production in the pulmonary vascular bed. The aim of this study was to evaluate the effect of nitric oxide inhibition on pulmonary artery pressure and oxygen need after hypoxic ischemia. Severe HI was produced in 18 newborn lambs. After completion of HI the lambs were divided into three groups of 6 animals receiving either placebo (Cont), low dose N omega-nitro-L-arginine (10 mg/kg i.v., NLA-10) or high dose (40 mg/kg i.v., NLA-40) to block NO production. Pulmonary artery pressure (Pap), aortic pressure, blood gases, inspiratory oxygen concentration and ventilator settings were recorded before and 15, 60, 120 and 180 min after HI. Mean Pap rose initially significantly as compared to baseline in all groups at 15 min post-HI, decreased to normal in Cont but not in treated animals; 180 min post-HI mean Pap was significantly higher in both treated groups as compared to control (NLA-10: 32 mm Hg, NLA-40: 34 mm Hg, Cont: 25 mm Hg, p < 0.05 for NLA-10 and NLA-40 vs. Cont). Moreover, in both NLA-treated groups the oxygenation index was significantly elevated 120 and 180 min post-HI as compared to those of the Cont group. NO synthase inhibition after HI causes a prolonged increase in pulmonary artery pressure leading to a higher oxygen need.