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Papers by John Foker

Patients with successfully repaired coarctation of the aorta (CoA) need continued follow-up due t... more Patients with successfully repaired coarctation of the aorta (CoA) need continued follow-up due to risks of restenosis and abnormal arterial compliance, causing early onset hypertension/coronary artery disease. We hypothesize that subtle hemodynamic and structural abnormalities can be predicted in the clinic by an abnormal arm-leg blood pressure (BP) gradient (i.e. arm > leg systolic BP). Design: Uncomplicated CoA patients repaired between 1990 and 2007 with follow-up clinic visits documenting right arm and leg systolic BPs, along with a recent echocardiogram, were studied. Data included the Doppler peak instantaneous (PeakV) and mean velocities (MeanV) in the descending aorta along with measures of the proximal transverse arch (TA) diameter and left ventricular wall (LVPWd) thickness. Measurements were indexed by Z-scores. Patients were grouped by higher systolic BP in the leg (Group 1) or arm (Group 2). Results: Eighty-one patients met the criteria with 52 in Group 1 (median 12.5 years follow-up) and 29 in Group 2 (median 12 years follow-up). Group 2 group had significantly increased arm systolic BP Z-scores (p <0.01), PeakV (p <10-4), MeanV (p <10-6), and LVPWd (p <0.01) compared to Group 1. There was no difference, however, in arm diastolic BP (p =0.7) or TA diameter (p =0.5). These relationships held true even in otherwise "silent" patients without clinical hypertension. Conclusion: Abnormal arm-leg blood pressure gradients accurately identified CoA patients with elevated arch velocities and increased ventricular wall thickness years after repair. The arm-leg pressure measurements could more accurately select patients in need of further imaging studies and therapeutic interventions.

An anastomotic stricture after an apparent satisfactory repair of esophageal atresia (EA) can be ... more An anastomotic stricture after an apparent satisfactory repair of esophageal atresia (EA) can be a vexing problem for all concerned. Post-repair strictures are common and vary widely in severity; nevertheless, they are important enough that their formation and treatment have been studied by pediatric surgeons and GI specialists. The basic science of wound healing and contraction has been a fertile research area, very applicable to the clinical situation. Whether from clinical sources or studies of cellular events, the information can provide helpful guidance for the treatment of strictures.

Circulation Research, Dec 9, 2011

Objectives The signal for ventricular growth has not been defined. This basic developmental quest... more Objectives The signal for ventricular growth has not been defined. This basic developmental question was studied using infants with congenital heart lesions as models. Our first hypothesis was that clinical ventricular hypoplasia is a developmental rather than a primarily genetic defect and, therefore, catch-up growth can be induced. Our clinical observations also led to the hypothesis that forward flow across the atrioventricular (AV) valve (mitral or tricuspid) is what generates the growth signal. To test these hypotheses we analyzed clinical data from infants with a variety of congenital defects including three groups of patients with a hypoplastic ventricle in whom a procedure was carried out to increase flow across the AV valve. Methods Infants with one of several congenital heart problems had right and left ventricular volumes (RV, LV) assessed by biplane echo and indexed to body surface area (m 2 ). The degree of hypoplasia was calculated using nomograms to determine the number of standard errors of the mean (SEM) below the expected volume (Table 1). Hypoplasia was considered significant when the SEM &lt; −2.0. The three groups were studied before and after (3–6 months) procedures which increased AV flow. Results Other possible growth mechanisms were assessed. (1) High wall stress with systemic or supra-systemic pressures produced no net cavitary growth unless AV valve flow was increased. (2) Significant retrograde flow from semilunar valve regurgitation did not increase ventricular size until failure developed. Therefore, no evidence was found for other growth mechanisms. Conclusions 1) Patients with congenital heart disease have a variety of defects, some of which can serve as models to answer basic developmental questions. 2) Increased AV valve flow provides the signal which induces ventricular growth. 3) Operations which increased AV valve flow induced catch-up growth of hypoplastic ventricles and allowed beneficial two-ventricle repairs in these patients.

American Journal of Physiology-heart and Circulatory Physiology, Aug 1, 1991

The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff... more The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff-perfused rat hearts were investigated by 31P nuclear magnetic resonance spectroscopy during total global normothermic ischemia while the left ventricular pressure was recorded continuously via an intraventricular balloon. Glucose-perfused hearts (n = 63) were divided into five groups based on the time of onset of contracture (TOC), and three other groups of hearts were treated to vary the ischemic glycogen availability. ATP levels, which showed no evidence of accelerated ATP depletion during contracture, were significant and variable at TOC. Intracellular pH initially declined and then leveled off at TOC, with lower final pH in hearts with later TOC. We conclude that contracture began when anaerobic glycolysis (and thus glycolytic ATP synthesis) stopped. These results, though consistent with the concept that ischemic contracture in normal hearts results from rigor bond formation due to low ATP levels at the myofibrils, suggest that TOC is more closely related to glycolytic ATP production than to total cellular ATP content, thus providing evidence of some degree of subcellular compartmentation or metabolite channeling. In glycolytically inhibited hearts, the quite early contracture may have a Ca2+ component.

Circulation Research, Jul 18, 2014

Objectives: Congenital heart disease may include hypoplastic heart valves, ventricles or great ar... more Objectives: Congenital heart disease may include hypoplastic heart valves, ventricles or great arteries. Infants with coarctation of the aorta (CoA) often have a hypoplastic transverse aortic arch (TAA) which can greatly complicate surgical repairs. Although these defects are often considered to be genetic in origin, our hypothesis was that they are problems of development which are potentially reversible. We tested the corollary hypothesis that hypoplastic TAAs retain normal developmental potential and the increased aortic flow after CoA repair provides the biomechanical signal for catch-up growth. Methods: Infants (N = 19) with TAA hypoplasia who underwent surgical CoA repair were studied for TAA growth by echocardiography done prior to and at intervals up to 13 years later. The TAA diameters were indexed using nomograms and calculated as standard deviations from expected size (SDE). Normal range is ± 2 SDE and &lt; −2 indicates hypoplasia. Results: 1) TAA growth was rapid and significant within 3 months. 2) The initial average TAA SDE = −3.7 (range: −7.6 to −2.1) (0/19 normal); 3 months = −1.5 (-4.1 to 0.9) (12/17); 1 year = −1.0 (-4.2 to 1.3) (15/19); 5 to 13 years = −0.6 (-2.1 to 0.9) (16/17 normal). Conclusions: 1) Hypoplastic aortic arches grew rapidly to normal size with increased flow following CoA repair. 2) The results suggest the cause of hypoplasia was underdevelopment from low flow and, when increased, flow provided the biomechanical signal to induce catch up growth. 3) Infants were a relevant model for demonstrating the aortic growth signal. 4) Growth induction by increased blood flow could be used to reverse aortic underdevelopment in other selected patients.

Journal of Surgical Research, Feb 1, 2009

Journal of Surgical Research, Feb 1, 2010

Early Human Development, Jun 1, 2009

Objectives: To determine the pattern of feeding milestones following primary repair of long-gap e... more Objectives: To determine the pattern of feeding milestones following primary repair of long-gap esophageal atresia (EA). Method: A questionnaire based upon well established feeding milestones was used. Children after long-gap EA repair, n = 40, were compared from after primary repair to healthy children from birth, n = 102. Results: The age when surveyed of the EA group and controls was different: 6.2 ± 4.7 (mean ± standard deviation) years, range 1.1-20.9, versus 2.5 ± 2.4 years, range 0.0-12.1, p = 0.00. The esophageal gap length in the EA group was 5.1 ± 1.2 cm and age at repair was 5.5 ± 5.0 months. There was no statistically significant difference between the atresia group and controls for feeding milestones; Self feeding finger foods approached significance. There was, however, greater variability in the timing of milestones in the atresia group compared to controls. Feeding milestones were negatively correlated with age at primary repair: drinking with a covered sippy cup, ρ = − 0.51, p = 0.01 and self feeding finger foods, ρ = − 0.36, p = 0.04 were statistically significant. Drinking from a cup correlated with gestational age, ρ = 0.38, p = 0.04, and negatively correlated to esophageal gap length, ρ = − 0.45, p = 0.01. Conclusions: Despite delayed onset of feeding, major milestones after EA repair occurred in similar pattern to normal infants. An early referral for primary repair is beneficial for earlier acquisition of milestones for infants with long-gap EA.

Journal of Surgical Research, 2009

Early Human Development, 2009

Circulation Research, 2011

Objectives The mechanism underlying heart failure (HF) after an index cardiac event is unknown bu... more Objectives The mechanism underlying heart failure (HF) after an index cardiac event is unknown but should have several characteristics. HF is a modern problem, so it will likely be a general response and be able to encompass the variety of initiating cardiac lesions as well as significant stress (e.g. exertion). The consequences should lead to the many alterations found in HF. [ATP] falls when energy demand outstrips supply (e.g. ischemia) but do not recover promptly with reperfusion because AMP is quickly catabolized and unavailable for recharging. [ATP] recovery is slow and limited by the availability of ribose-5-P. Ribose is not used as fuel and is channeled into nucleotide (ATP) synthesis allowing the effects of [ATP] recovery on function to be studied. Our hypothesis was that HF results from these responses of energy metabolism to stress which lower [ATP[ and affect the numerous myocardial reactions whose activity depends on [ATP]. The ability of ribose to quickly increase [ATP...

The Journal of Thoracic and Cardiovascular Surgery, 1984

The acute metabolic and hemodynamic effects of dopamine, dobutamine (both at 10 micrograms . kg-1... more The acute metabolic and hemodynamic effects of dopamine, dobutamine (both at 10 micrograms . kg-1 . min), and isoproterenol (at 0.05 or 0.1 micrograms . kg-1. min) were determined in dogs following 20 minutes of normothermic global myocardial ischemia. The catecholamines were started 10 minutes before cardiopulmonary bypass (CPB) was discontinued and were continued for 1 hour after bypass. Regional myocardial and systemic blood flow distribution was measured by means of the radioactive microsphere technique. On bypass all catecholamines sharply increased heart rate, myocardial oxygen consumption, and left ventricular blood flow (p less than 0.01). Because the hearts were unloaded, these data suggest that velocity of contraction is an important component of myocardial oxygen consumption. Although these drugs did not lower myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels, the significant rise in oxygen consumption suggested that inotropic treatment on bypass may not be beneficial. Furthermore, renal blood flow was diminished in dobutamine-treated dogs (p less than 0.01) and tended to decrease with isoproterenol infusion. No change was seen with dopamine infusion. After bypass, dobutamine treatment increased cardiac output (p less than 0.01) and stroke volume (p = 0.017) with no change in heart rate, myocardial oxygen consumption, high-energy phosphate levels, and total or transmural distribution of left ventricular blood flow. Dopamine infusion did not change cardiac output but did increase oxygen consumption (p less than 0.01). Isoproterenol showed a slight inotropic effect, but frequent ventricular arrhythmias were present during weaning from bypass. In all treatment groups, blood flow in the other systemic beds (cerebral, gastrointestinal, and renal) was similar to that in control dogs. These data suggest that dobutamine is the most efficient of the drugs tested for support of the heart following global myocardial ischemia but, when given during bypass, it appears to decrease renal blood flow.

The Journal of Thoracic and Cardiovascular Surgery, 1980

Adenosine metabolism and myocardial preservation Consequences of adenosine catabolism on myocardi... more Adenosine metabolism and myocardial preservation Consequences of adenosine catabolism on myocardial high-energy compounds and tissue blood flow The nature of the metabolic events leading to irreversible damage of the ischemic myocardium are not known. We tested the hypothesis that catabolism of adenosine triphosphate precursors limits the regeneration of this high-energy compound following ischemic insult. Dogs on cardiopulmonary bypass (CPB) had the aorta cross-clamped for 20 minutes at normothermia and 30 minutes later CPB was discontinued. Mean pre-CPB values (pmoleslgm) in left ventricular biopsies for ATP, creatine phosphate (CP), ADP, and AMP were 5.30,6.18, 1.32 and 0.43, respectively. Adenosine (Ad), inosine, and hypoxanthine lxanthine were not detectable. At the end of cross-clamping, ATP had fallen to 2.80 and CP to 0.57; however, the predicted rise in the levels of ADP, AMP, and Ad was not found. The levels of inosine (1.23) and hypoxanthine /xanthine (0.24) increased, an indication that ADP, AMP, and Ad had been further catabolized. Following release of the cross-clamp, ATP levels did not increase; even 60 minutes after termination ofCPB this level was only 3.07. CP levels rose to 10.2 within 5 minutes after cross-clamp release, indicating high-energy bonds could be formed. EHNA (10 mg/kg), an inhibitor of adenosine deaminase, was used to test the effect of blocking Ad catabolism. At the end of cross-clamping, tissue Ad, previously unmeasurable, was 1.30 umolestgm, Nevertheless, ATP levels did not rebound after release of the cross-clamp; the reason was found to be cellular loss. and the coronary sinus blood contained high levels of Ad. Ad (20 mg lkg} infusion alone increased myocardial blood flow fivefold compared to flow in control dogs, but did not alter subsequent ATP levels. Combined EHNA /Ad treatment similarly increased flow but, more importantly, resulted in recovery of ATP levels to 88% of pre-CPB values. We conclude that ATP regeneration after ischemia is limited by the availability of ADP, AMP, and Ad. Inhibition of Ad catabolism and infusion of Ad will enhance ATP return from ischemia. Current preservation methods, chiefly hypothermia and cardioplegia, are designed to decrease ATP utilization. Our approach. by providing precursors for ATP recovery, may further improve myocardial preservation.

American Journal of Physiology-Heart and Circulatory Physiology, 1991

The newborn has an attenuated response to saline fluid challenge. We studied the response of endo... more The newborn has an attenuated response to saline fluid challenge. We studied the response of endogenous atrial natriuretic peptides (ANF) to 10% body weight graded isotonic saline volume expansion (VE) in 14 anesthetized neonatal lambs which were either 1 day old or 7 days old. Plasma ANF values were unchanged at 3.3% and 10% VE compared with control values (56 +/- 28 vs. 66 +/- 17 and 66 +/- 37 pg/ml, not significant) in the 1-day-old lambs, whereas values increased significantly at both 3.3% and 10% VE (47 +/- 40 vs. 99 +/- 57 and 96 +/- 73, P = 0.022 and P = 0.018, respectively) in the 7-day-old lambs. No relationship existed between right atrial (RAP) or pulmonary capillary wedge pressures (PCWP) and plasma ANF in the 1-day-old lambs; however, a significant correlation existed (RAP, P = 0.015; PCWP, P = 0.022) in the 7-day-old lambs. In general, renal function was improved in the 7-day-old lambs compared with the 1-day-old lambs, but only changes in fractional sodium excretion w...