Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor.

Exercise protects against myocardial ischemia-reperfusion (I-R) injury but the mechanism remains unclear. Protection can be transferred from a remotely preconditioned human donor to an isolated perfused rabbit heart using a dialysate of plasma. We hypothesized that physical exercise preconditioning also confers cardioprotection through a humorally mediated effector dependent on opioid receptor activation. Thirteen male volunteers performed vigorous exercise (four 2-minute bouts of high-intensity exercise) and 1 week later they underwent remote ischemic preconditioning (four cycles of 5 min upper limb ischemia and reperfusion). Dialysates were prepared from blood collected before (control) and after the two interventions. Isolated rabbit hearts were perfused with the dialysates without and with co-administration of naloxone (opioid receptor antagonist) prior to 40 min regional ischemia and 2 h reperfusion. Exercise and remote ischemic preconditioning (rIPC) reduced infarct size from 60 ± 5 to 35 ± 5 % and from 57 ± 7 to 27 ± 3 % of the area at risk, respectively (p < 0.05 and < 0.01). Furthermore, post-ischemic left ventricular developed pressure was improved compared with controls (p = 0.08 for exercise and p = 0.04 for rIPC). Co-perfusion with naloxone abrogated the protective effects of exercise and remote ischemic preconditioned dialysates. In conclusion, high-intensity exercise preconditioning elicits cardioprotection through a humorally mediated dependent on opioid receptor activation, similar to rIPC.

The neonatal but not the mature heart adapts to acute tachycardia by beneficial modification of the force-frequency relationship.

The force-frequency relationship (FFR) reflects alterations in intracellular calcium cycling during changing heart rate (HR). Tachycardia-induced heart failure is associated with depletion of intracellular calcium. We hypothesized (1) that the relative resistance to tachycardia-induced heart failure seen in neonatal pigs is related to differences in calcium cycling, resulting in different FFR responses and (2) that pretreatment with digoxin to increase intracellular calcium would modifies these changes. LV +dP/dt was measured during incremental right atrial pacing in 16 neonatal and 14 adult pigs. FFR was measured as the change in +dP/dt as HR was increased. Animals were randomized to control or intravenous bolus digoxin (n = 8 neonate pigs in the 0.05 mg/kg group and n = 7 adult pigs in the 0.025 mg/kg group) and paced for 90 min at 25 bpm greater than the rate of peak +dP/dt. Repeat FFR was then obtained. The postpacing FFR in neonatal control pigs shifted rightward, with peak force occurring 30 bpm greater than baseline (P < 0.03). There was no vertical shift; thus, force at 150 bpm decreased (P < 0.03) and force at 300 beats/min increased (P < 0.08). In adult control pigs, FFR shifted downward (P < 0.01), with decreased force generation at all HRs. In both neonates and adult pigs, digoxin increased +dP/dt at all HRs; however, in neonate pigs digoxin decreased the contractile reserve by abrogation of the rightward shift of FFR. An adaptive response to tachycardia in the neonate pig leads to improved force generation at greater HRs. Conversely, the response of the mature pig heart is maladaptive with decreased force generation. Pretreatment with digoxin modifies these responses.

Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs.

AIM: Intermittent limb ischaemia prior to cardiac ischaemia is a cardioprotective stimulus. This study was to investigate whether this peripheral stimulus had any effects on basal coronary blood flow and resistance, and to explore its potential mechanisms by studying the effect of femoral nerve transection and Katp blockade by glibenclamide. METHODS: Remote ischaemic preconditioning (rIPC) was induced by four 5-min cycles of lower limb ischaemia. Coronary resistance was measured using standard formulae and coronary blood flow in the left anterior descending artery (LAD) by a flow probe. In experiment 1, coronary ischaemia was induced by inflation of a cuff placed around the mid-LAD, and inflated until cessation of flow. Left ventricular (LV) function was assessed using dp/dt and Tau at 1 and 30 min of ischaemia. Experiment 1: 20 pigs were randomized to control (n = 6), rIPC (n = 7) or femoral nerve transection + rIPC (n = 7) groups. The femoral nerve was transected before the rIPC protocol. All data were collected at fixed heart rates of 120 bpm. Coronary resistance was decreased and flow was increased significantly by the rIPC stimulus (P = 0.003, P = 0.016, paired t-test), and these changes were preserved after femoral nerve transection. Experiment 2: 19 pigs were randomized to control (n = 5), rIPC (n = 8) or glibenclamide-treated rIPC (n = 6) groups. Data were collected at baseline, and during incremental pacing between 120 and 180 bpm. RESULTS: Experiment 1: Coronary resistance was decreased and flow was increased significantly by rIPC stimulus (P = 0.003, P = 0.016, paired t-test), and these changes were preserved after femoral nerve transaction. rIPC was associated with superior LV function (dp/dt(max)) at 30 min, compared with controls and the rIPC + femoral nerve transaction group. Experiment 2: Coronary resistance was significantly lower, and LAD flow was significantly higher in rIPC group (P < 0.0001, P = 0.0008, two-way anova). These effects were reversed in the glibenclamide group. CONCLUSION: The rIPC stimulus leads to reduced coronary resistance and increased flow. This effect, while modified by glibenclamide appears to be a generic effect of remote ischaemia rather than a direct preconditioning effect.

Systemic and myocardial oxygen transport responses to brain death in pigs.

BACKGROUND: Brain death is associated with profound disturbances of systemic and myocardial oxygen transport, but little is known regarding the acute response of systemic oxygen consumption (VO(2)). METHODS: Brain death was induced in 6 pigs (30.6 +/- 3.0 kg) by balloon inflation into the cranial cavity. VO(2) was continuously measured by respiratory mass spectrometry. Blood pressures and gases were measured from the aorta, superior vena cava, and coronary sinus, with arterial epinephrine and norepinephrine, prior to brain death, at 1, 10, and 90 minutes after brain death. Cardiac output (CO), systemic vascular resistance (SVR), oxygen delivery (DO(2)), oxygen extraction (EO(2)), and myocardial oxygen (mEO(2)) and lactate extractions (mE(1ac)) were calculated. Left ventricular contractility was assessed by micromanometer tipped catheters. RESULTS: VO(2) increased from 4.8 +/- 0.9 to 6.3 +/- 0.9 mL/min/kg 1 minute after brain death (P < .001), and subsequently decreased to below baseline at 90 minutes (P < .001). Left ventricular contractility, CO, and DO(2) increased 1 minute after brain death (P < .001), followed by a rapid decrease to baseline within 10 minutes (P < .001). SVR and EO(2) decreased after brain death (P < .01) and remained low. Lactate remained unchanged. mE(1ac) decreased after brain death despite a decrease in mEO(2) (P < .01), and returned to baseline at 90 minutes. CONCLUSIONS: The initial surge in VO(2) after brain death is offset by the greater increase in DO(2), thus tissue perfusion remains adequate. The lower than baseline VO(2) and SVR at the end of the study period may indicate general metabolic and hemodynamic compromise. The information regarding the profound metabolic alterations imposed by brain death may have implications for management of brain death donors.

Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning.

Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K(+)-dependent ATP (K(ATP)) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 +/- 14.3 vs. 38.3 +/- 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion (P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 +/- 6% and 3 +/- 5% in control and PerC, respectively (P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group (P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion (P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.

Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study.

OBJECTIVES: To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB). DESIGN: Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h. INTERVENTION: rIPC was induced by four 5 min cycles of lower limb ischaemia before CPB. MAIN OUTCOME MEASURES: Troponin I, glial protein S-100B, lactate concentrations, load-independent indices (conductance catheter) of systolic and diastolic function, and pulmonary resistance and compliance were measured before and for 6 h after CPB. RESULTS: Troponin I increased after CPB in both groups but during reperfusion the rIPC group had lower concentrations than controls (mean area under the curve -57.3 (SEM 7.3) v 89.0 (11.6) ng.h/ml, p = 0.02). Lactate increased after CPB in both groups but during reperfusion the control group had significantly more prolonged hyperlactataemia (p = 0.04). S-100B did not differ between groups. Indices of ventricular function did not differ. There was a tendency to improved lung compliance (p = 0.07), and pulmonary resistance changed less in the rIPC than in the control group during reperfusion (p = 0.02). Subsequently, peak inspiratory pressure was lower (p = 0.001). CONCLUSION: rIPC significantly attenuated clinically relevant markers of myocardial and pulmonary injury after CPB. Transient limb ischaemia as an rIPC stimulus has potentially important clinical applications.

Assessment of the relationship between cerebral and splanchnic oxygen saturations measured by near-infrared spectroscopy and direct measurements of systemic haemodynamic variables and oxygen transport after the Norwood procedure.

OBJECTIVES: To evaluate the clinical utility of near-infrared spectroscopic (NIRS) monitoring of cerebral (ScO2) and splanchnic (SsO2) oxygen saturations for estimation of systemic oxygen transport after the Norwood procedure. METHODS: ScO2 and SsO2 were measured with NIRS cerebral and thoracolumbar probes (in humans). Respiratory mass spectrometry was used to measure systemic oxygen consumption (O2). Arterial (SaO2), superior vena caval (SvO2) and pulmonary venous oxygen saturations were measured at 2 to 4 h intervals to derive pulmonary (Qp) and systemic blood flow (Qs), systemic oxygen delivery (DO2) and oxygen extraction ratio (ERO2). Mixed linear regression was used to test correlations. A study of 7 pigs after cardiopulmonary bypass (study 1) was followed by a study of 11 children after the Norwood procedure (study 2). RESULTS: Study 1. ScO2 moderately correlated with SvO2, mean arterial pressure, Qs, DO2 and ERO2 (slope 0.30, 0.64. 2.30, 0.017 and -32.5, p < 0.0001) but not with SaO2, arterial oxygen pressure (PaO2), haemoglobin and O2. Study 2. ScO2 correlated well with SvO2, SaO2, PaO2 and mean arterial pressure (slope 0.43, 0.61, 0.99 and 0.52, p < 0.0001) but not with haemoglobin (slope 0.24, p > 0.05). ScO2 correlated weakly with O2 (slope -0.07, p = 0.05) and moderately with Qs, DO2 and ERO2 (slope 3.2, 0.03, -33.2, p < 0.0001). SsO2 showed similar but weaker correlations. CONCLUSIONS: ScO2 and SsO2 may reflect the influence of haemodynamic variables and oxygen transport after the Norwood procedure. However, the interpretation of NIRS data, in terms of both absolute values and trends, is difficult to rely on clinically.

Non-invasive assessment of ventricular force-frequency relations in the univentricular circulation by tissue Doppler echocardiography: a novel method of assessing myocardial performance in congenital heart disease.

OBJECTIVE: To describe the first clinical application of a novel tissue Doppler derived index of contractility, isovolumic acceleration (IVA), in the assessment of the ventricular myocardial force-frequency relation (FFR) in the univentricular heart (UVH). DESIGN: Prospective study. SETTING: Tertiary referral centre. INTERVENTIONS: Non-invasive assessment of the myocardial FFR by tissue Doppler echocardiography during atrial pacing. RESULTS: IVA was used to measure the FFR of the systemic ventricle in patients with structurally normal hearts and in patients with UVHs. Basal IVA of the normal hearts (mean (SD) 1.9 (0.3) m/s2) was significantly greater than that of UVHs in patients with a dominant right ventricle (RV) (1.0 (0.3) m/s2) or left ventricle (LV) (0.8 (0.7) m/s2; p < 0.05 for both). Neither the absolute nor percentage change from basal to peak values of IVA with pacing differed between the three groups. Peak force developed by the normal LV was significantly greater than that of the UVH, dominant LV group but not different from that of the UVH, dominant RV group. CONCLUSION: Contractility at basal heart rate is depressed in patients with UVH compared with the normal LV. Analysis of ventricular FFRs exposes further differences in myocardial contractility. There is no evidence that contractile function of the dominant RV is inferior to that of the dominant LV over a physiological range of heart rates.

Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot.

BACKGROUND: Evaluation of right ventricular (RV) function in patients with pulmonary regurgitation (PR) after tetralogy repair remains challenging because of abnormal RV loading conditions. METHODS AND RESULTS: We examined 124 patients, aged 21+/-11.4 years, who had tetralogy repair at 3.7+/-3.5 years. By Doppler echocardiography, 33 patients had mild, 22 moderate, and 69 severe PR; 55 had significant tricuspid regurgitation (TR). Myocardial velocities, myocardial acceleration during isovolumic contraction (IVA), strain, and strain rate were measured at RV and LV base. Tricuspid valve annulus was measured in a 4-chamber view. QRS, QT, and JT intervals and their dispersions were measured from 12-lead electrocardiogram. IVA in the RV was lower in all patients compared with controls (0.8+/-0.4 versus 1.8+/-0.5, P<0.0001) and correlated with the severity of PR (r=-0.43, P<0.0001), whereas myocardial velocities, and strain/strain rate did not. LV IVA correlated with PR (r=-0.32, P<0.001) and with RV IVA (r=0.28, P<0.003). Patients with severe PR had a higher incidence of TR (r=0.69, P<0.0001) and lower RV IVA (1.0+/-0.4 versus 0.6+/-0.3, P<0.0001), a larger tricuspid valve ring diameter (P<0.0001), and prolonged electrical depolarization (P<0.001). Age at surgery or examination did not correlate with PR and with RV function assessed by IVA. In the RV, IVA correlated inversely with QRS duration (P<0.01). CONCLUSIONS: Although load-dependent myocardial velocities and strain are not influenced by the severity of PR and presence of significant TR, IVA demonstrates reduced contractile function in relation to the degree of PR and may be an early, sensitive index for selecting patients for valve replacement.

Maternal hyperglycemia improves fetal cardiac function during tachycardia-induced heart failure in pigs.

BACKGROUND: Fetal tachycardia often leads to cardiac failure, which in experimental settings can be prevented by direct fetal glucose-insulin administration. In this study, we hypothesize that similar effects can be obtained indirectly by inducing maternal hyperglycemia. METHODS AND RESULTS: Systolic and diastolic indices (dP/dt(max) and tau) of left ventricular function were measured by use of high-fidelity catheters during 180 minutes of aggressive atrial pacing ( approximately 300 bpm) in 12 preterm porcine fetuses. In 6 fetuses, maternal hyperglycemia (15 mmol/L) was induced for the last 120 minutes of pacing. The remaining fetuses served as controls. Glucose, insulin, and free fatty acid levels were determined, as was fetal myocardial glycogen content. Maternal glucose infusion led to significant fetal hyperglycemia and hyperinsulinemia but did not change the inherently low fetal levels of free fatty acids. There were no differences between groups with regard to dP/dt(max) (1025+/-226 and 1037+/-207 mm Hg, P=NS) and tau (20.6+/-2.0 and 21.4+/-1.6 ms, P=NS) at baseline (100%). During the 180 minutes of pacing, systolic function (dP/dt(max)) and diastolic function (tau) deteriorated more in the control group than in the hyperglycemic group (P<0.001 for both). At 180 minutes, dP/dt(max) was 62+/-18% of baseline in controls and 85+/-11% in hyperglycemic fetuses (P=0.03), and tau was 117+/-12% and 98+/-4%, respectively (P=0.004). CONCLUSIONS: Induced maternal hyperglycemia improves fetal cardiac function during fetal tachycardia and suggests a possible additional therapeutic option to improve the function of the failing fetal heart before or during antiarrhythmic therapy. The findings may be relevant in fetal heart failure in general.

Bedside balloon atrial septostomy on neonatal units.

Traditionally, neonates with transposition of the great arteries are immediately transferred to a cardiac centre. Travelling to the bedside to perform a balloon atrial septostomy and allowing the child to remain there for a few days before transfer is safe, effective, and a good use of medical resources.

Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation.

BACKGROUND: The pulsatile nature of pulmonary blood flow is important for shear stress-mediated release of endothelium-derived nitric oxide (NO) and lowering pulmonary vascular resistance (PVR) by passive recruitment of capillaries. Normal pulsatile flow is lost or markedly attenuated after Fontan-type operations, but to date, there are no data on basal pulmonary vascular resistance and its responsiveness to exogenous NO at late follow-up in these patients. METHODS AND RESULTS: We measured indexed PVR (PVRI) using Fick principle to calculate pulmonary blood flow, with respiratory mass spectrometry to measure oxygen consumption, in 15 patients (median age, 12 years; range, 7 to 17 years; 12 male, 3 female) at a median of 9 years after a Fontan-type operation (6 atriopulmonary connections, 7 lateral tunnels, 2 extracardiac conduits). The basal PVRI was 2.11+/-0.79 Wood unit (WU) times m2 (mean+/-SD) and showed a significant reduction to 1.61+/-0.48 (P=0.016) after 20 ppm of NO for 10 minutes. The patients with nonpulsatile group in the pulmonary circulation dropped the PVRI from 2.18+/-0.34 to 1.82+/-0.55 (P<0.05) after NO inhalation. CONCLUSIONS: PVR falls with exogenous NO late after Fontan-type operation. These data suggest pulmonary endothelial dysfunction, related in some part to lack of pulsatility in the pulmonary circulation because of altered flow characteristics. Therapeutic strategies to enhance pulmonary endothelial NO release may have a role in these patients.

Transient limb ischemia induces remote ischemic preconditioning in vivo.

BACKGROUND: Ischemic preconditioning reduces local tissue injury caused by subsequent ischemia-reperfusion (IR), but may also have a salutary effect on IR injury of tissues remote from those undergoing preconditioning. We tested the hypothesis that limb ischemia induces remote preconditioning, reduces endothelial IR injury in humans, and reduces experimental myocardial infarct size. METHODS AND RESULTS: Endothelial IR injury of the human forearm was induced by 20 minutes of upper limb ischemia (inflation of a blood pressure cuff to 200 mm Hg) followed by reperfusion. Remote preconditioning was induced by three 5-minute cycles of ischemia of the contralateral limb. Venous occlusion plethysmography was used to assess forearm blood flow in response to acetylcholine at baseline and 15 minutes after reperfusion. Experimental myocardial infarction was achieved by 40 minutes of balloon occlusion of the left anterior descending artery in 15-kg pigs. Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Triphenyltetrazolium staining was used to assess the extent of myocardial infarction. In the human study, the response to acetylcholine was significantly attenuated in the control group after 15 minutes' reperfusion, but remote preconditioning prevented this reduction. Limb ischemia caused a significant reduction in the extent of myocardial infarction relative to the area at risk compared with control (26+/-9% versus 53+/-8%, P<0.05). CONCLUSION: Remote ischemic preconditioning prevents IR-induced endothelial dysfunction in humans and reduces the extent of myocardial infarction in experimental animals. Transient limb ischemia is a simple preconditioning stimulus with important potential clinical applications.

Hybrid approaches to complex congenital cardiac surgery.

OBJECTIVES: A hybrid operation is a joint procedure involving the interventional cardiologist and the cardiac surgeon concomitantly to optimise surgical management. The aim of our study was to demonstrate the conceptual development and the feasibility of a hybrid approach to complex congenital cardiac surgery. METHODS: Descriptive study of two different indications for concomitant intervention by the cardiologist and the cardiac surgeon. Seven patients with complex congenital heart defects requiring high risk operative interventions were included in the study. The indications were: (1) intraoperative stenting of a pulmonary artery stenosis with concomitant additional surgical procedures (n=4). (2) Balloon occlusion of Blalock-Taussig shunts or major aorto-pulmonary collateral artery to control pulmonary blood flow during surgical repair (n=3). RESULTS: All patients had successful hybrid procedures. There were no important complications related to the temporal proximity of the interventional procedure and cardiac surgery, the latter being significantly facilitated by the former. CONCLUSIONS: Intraoperative stenting of pulmonary artery stenosis with additional surgical repair and balloon occlusion on cardiopulmonary bypass can be performed safely and may be complementary in patients with complex lesions by providing a better result in combination than either alone can offer.

Arterial distensibility in children and teenagers: normal evolution and the effect of childhood vasculitis.

BACKGROUND: Polyarteritis nodosa is a necrotising vasculitis of the medium sized and small muscular arteries. The inflammatory and subsequent reparative processes may alter the arterial mechanical properties. The effect of vasculitic damage on arterial distensibility has never been explored however. AIM: To determine the normal values and the effect of childhood vasculitis on arterial distensibility in children and teenagers. METHODS: Distensibility of the brachioradial arterial segment was studied using pulse wave velocity (PWV proportional, variant 1/ radical distensibility), in 13 children with polyarteritis nodosa at a median age of 11.8 (range 4.9-16) years. As a control group, 155 healthy schoolchildren (6-18 years, 81 boys) were studied. PWV was assessed using a photoplethysmographic technique; blood pressure was measured by an automatic sphygmomanometer (Dinamap). Data from patients were expressed as z scores adjusted for age and compared to a population mean of 0 by a single sample t test. Determinants of PWV in normal children were assessed by univariate and multivariate linear regression analyses. RESULTS: Age, height, weight, and systolic blood pressure correlated individually with the brachioradial PWV. Multivariate analysis identified age as the only independent determinant. Ten of the patients were in clinical remission, while three had evidence of disease activity at the time of study. The PWV in the patient group as a whole was significantly greater than those in healthy children (mean z score +0.99). Raised C reactive protein concentration (>2 mg/dl) in the three patients with active disease was associated with a higher PWV when compared to those in remission (z score +2.78 v +0.45). The diastolic blood pressure of the patients was higher than those of the controls (z score +1.04) while the systolic pressure was similar (z score -0.36). CONCLUSIONS: PWV in the brachioradial arterial segment increases gradually during childhood independent of body weight, height, mass, and blood pressure. Increased PWV, and hence decreased distensibility, in this peripheral arterial segment occurs in polyarteritis nodosa and is amplified during acute inflammatory exacerbation.

Influence of the introduction of Amplatzer device on the interventional closure of defects within the oval fossa in children.

Since June 1998, we have used an Amplatzer device whenever considered appropriate in patients with isolated defects within the oval fossa. The aim of this study was to define the total cohort of patients with isolated defects in the oval fossa seen at this hospital, so as to assess the impact of this policy on contemporary management. In the two-year period commencing 1st June 1998, 116 patients older than 6 months were seen with an isolated septal defect within the oval fossa. Mean age at closure or last review was 5.8 years, with a range from 0.5 to 20 years. In total, 42 (36%) patients were assigned to surgical closure, 25 (22%) to closure using an Amplatzer device, and 49 (42%) remained under clinical follow up. Direct referral for surgical closure occurred in 24 (21%) patients, in whom transcatheter closure was considered not appropriate after transthoracic echocardiography. Transoesophageal echocardiography was performed in 45 (39%) patients to assess suitability for closure using the Amplatzer device. Of these, 20 (44% of the group undergoing transoesophageal echocardiography) were considered unsuitable for closure in this fashion. Of these, 18 were referred for surgery and 2 with small defects were considered not to require closure. Patients undergoing closure with the device were older than the group referred for surgical closure, having a median age of 7.8 versus 3.6 years, and stayed for a shorter period in hospital. Those closed using the device stayed for 2 days, as opposed to a median of 5 days, with a range from 4 to 10 days for those undergoing surgical closure. Closure was complete as assessed by echocardiography after follow up of 1-3 months in both groups. There were no recognised complications related to insertion of the device, whereas transient postoperative morbidity occurred in 38% of those closed surgically. Insertion of an Amplatzer device was considered to be appropriate in 37% of patients older than 6 months requiring closure of an atrial septal defect in the oval fossa.

Right ventricular distension alters monophasic action potential duration during pulmonary arterial occlusion in anaesthetised lambs: evidence for arrhythmogenic right ventricular mechanoelectrical feedback.

Abnormal loading and distension of the right ventricle may induce arrhythmia through the process of mechanoelectrical feedback. Nonetheless, the electrophysiological effects of right ventricular distension are ill-defined and the mechanisms which underpin mechanoelectrical feedback in the right ventricle are unknown. We examined the effects of changes in right ventricular load (complete occlusion of both caval veins or the main pulmonary artery) in 14 anaesthetised lambs, instrumented with right ventricular surface electrodes and strain gauges for recording monophasic action potential and segment length, and an integrated conductance and micromanometer-tipped catheter for measurement of right ventricular pressure and volume. Caval occlusion did not alter right ventricular segment length and monophasic action potential duration. By contrast, pulmonary arterial occlusion increased the segment length and decreased the monophasic action potential duration at 25, 50 and 70% repolarisation by 29 +/- 6, 22 +/- 4 and 17 +/- 3 ms, respectively (all P < 0.01). Of the 42 pulmonary arterial occlusions, 38 were associated with early afterdepolarisations (EADs) which increased progressively in magnitude as the occlusion was maintained until, in 32, overt arrhythmia was observed. By contrast, none of the four occlusions in which EADs were not observed resulted in arrhythmia. As a result, the proportion of occlusions which resulted in arrhythmia were greater in those associated with EADs than in those which were not (P = 0.002). Right ventricular distension alters the pattern of repolarisation, precipitates early afterdepolarisations and results in a variety of ventricular arrhythmia, including ventricular tachycardia.

Abnormalities of right ventricular long axis function after atrial repair of transposition of the great arteries.

BACKGROUND: While volume derived global indices of right ventricle (RV) function are frequently abnormal after the Mustard procedure, the mechanism for these abnormalities is poorly understood. RV muscle fibres are predominantly arranged longitudinally and thus indices derived in the long axis may better describe RV function. METHODS: 20 survivors of the Mustard operation were studied (age 7.8-37.3 years, median 14.2 years). Long axis recordings from the apical four chamber view were obtained with the M mode cursor positioned through the lateral angle of the tricuspid valve annulus. M mode traces were recorded on paper and later digitised to derive total atrioventricular ring excursion, peak lengthening rate, and peak shortening rate. These data were averaged and compared with control data for the normal RV and left ventricle (LV). RESULTS: RV total atrioventricular ring excursion was lower than that for the RV (p < 0.0001) or LV (p < 0.005) of controls. Peak lengthening rate was lower than the normal RV (p < 0.0001) and LV (p < 0.0001) rates. Furthermore, peak shortening rate was less than that of normal RV (p < 0.0001) and normal LV (p < 0.005) controls. CONCLUSION: Systemic RV long axis function is notably reduced compared with that of either the normal subpulmonary RV or the systemic LV. This presumably reflects the response of the predominantly longitudinally arranged myocardial fibres to increased afterload. However, such measurements may provide a more sensitive marker for progressive changes in global function during long term follow up.

Effect of fenestration on the sub-diaphragmatic venous hemodynamics in the total-cavopulmonary connection.

OBJECTIVE: To understand differences in the sub-diaphragmatic venous physiology between patients with fenestrated and non-fenestrated total-cavopulmonary connections (TCPC). METHODS: We studied the effects of respiration, retrograde flow, and gravity on the sub-diaphragmatic venous flows in 20 normal healthy volunteers (control), 25 Fontan patients with non-fenestrated TCPC, and 21 with fenestrated TCPC. Subhepatic inferior vena cava (IVC), hepatic vein (HV), and portal vein (PV) flow rates were measured with Doppler ultrasonography during inspiration and expiration in both supine and upright positions. The supine inspiratory-to-expiratory flow rate ratio was calculated to reflect the effect of respiration, the supine-to-upright flow rate ratio was calculated to assess the effect of gravity, and the magnitude of retrograde flow was evaluated with respect to total antegrade flow. Mean IVC, HV, and wedged hepatic venous (WHV) pressures were measured during cardiac catheterization in four TCPC patients before and after fenestration closure. The transhepatic venous pressure gradient (TVPG) was calculated as the difference between the HV and WHV pressure. RESULTS: Compared with control, HV flow in TCPC was heavily dependent on respiration; this inspiratory capacity was greater in fenestrated than non-fenestrated subjects (inspiratory-to-expiratory flow ratio 1.7, 4.4, and 3.0, respectively P<0.001). Normal retrograde HV flow was diminished in TCPC patients, furthermore, fenestrated subjects had less flow reversal than non-fenestrated (retrograde as percent of antegrade flow 43, 19, and 30%, respectively P<0.001). Gravity decreased IVC and HV flows more in TCPC subjects than control, but this effect was not different between the two TCPC groups. Closure of the fenestration resulted in higher IVC and HV pressures (pre-closure versus post-closure pressures [mmHg]: 11.2 +/- 4.0 vs. 12.3 +/- 3.9, and 11.5 +/- 3.8 vs. 12.4 +/- 3.8, respectively P< or =0.001). The normal TVPG was reduced in fenestrated TCPC, and worsened after fenestration closure (0.9 +/- 0.3 and 0.7 +/- 0.4, respectively P < 0.04). CONCLUSIONS: Fenestration of the inferior venous connection has important influences on sub-diaphragmatic venous return in TCPC patients. Although fenestration lowers venous pressures and partially restores TVPG, its beneficial effects on flow in TCPC patients are mediated primarily by an increase in inspiration-derived forward HV flow and reduced flow reversal. These observations suggest fenestration results in a more efficient and less congested splanchnic circulation in TCPC patients, and may have important implications in the early and late management of Fontan patients.