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Biomedical subjects

M H Gewitz

Publications and source records attributed to M H Gewitz.

At least 19 recordsLinked to original sources

Role of cGMP mechanisms in response of rat pulmonary arteries to hypoxia.

We have demonstrated previously that in response to hypoxia, isolated rat pulmonary arteries show an initial endothelium-dependent relaxation followed by an endothelium-independent transient contraction. In the presence of increased extracellular Ca2+, both of these responses were enhanced in endothelium-intact arteries. Nitro-L-arginine, a blocker of the biosynthesis of endothelium-derived relaxing factor (EDRF), abolished the initial endothelium-dependent relaxation and Ca(2+)-induced enhancement of hypoxic contraction in endothelium-intact arteries but did not alter responses in endothelium-denuded vessels. Inhibition of prostaglandin formation with indomethacin had no effect on the hypoxia-elicited responses. Preincubation with LY 83583, an inhibitor of guanylate cyclase activation, abolished the initial hypoxia-elicited relaxation and subsequent contraction. M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, decreased tone under O2 but not under N2, causing an apparent enhancement of the contraction to hypoxia. Thus the modulation of hypoxic responses by the endothelium is dependent on changes in EDRF production, and a decrease in smooth muscle cGMP not involving an EDRF mechanism appears to mediate the endothelium-independent hypoxic contraction observed in the isolated rat pulmonary artery.

Aminoquinolines

Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs.

The atrial appendages contain most of the atrial natriuretic factor (ANF) in the mammalian heart, and atrial appendage mechanical function predicts ANF secretion during volume loading. To demonstrate the crucial role of the atrial appendages in ANF release, we first measured hemodynamics and changes in plasma ANF after injection of 1,000 ml i.v. normal saline in conscious dogs and again after bilateral atrial appendectomy; we next measured changes in renal function using infusions of atriopeptin 24 to achieve plasma levels corresponding to levels achieved during volume loading; and we lastly measured renal function during acute volume expansion and also after atrial appendectomy. Plasma ANF increased from 65 +/- 11 to 246 +/- 54 pg/ml after volume loading but did not increase after atrial appendectomy. Atrial appendectomy did not alter the tachycardia or hemodynamic effects of volume loading. Infusion of 10 ng/kg/min atriopeptin 24 increased plasma ANF from 50 +/- 9 to 234 +/- 54 pg/ml, increased urine output 34 +/- 10%, and increased sodium excretion 62 +/- 10% in dogs with intact atrial appendages. Renal function was compared in dogs before atrial appendectomy: 20, 40, and 60 minutes after volume loading, urine flow rate increased by 5.9 +/- 0.5, 6.9 +/- 0.4, and 4.4 +/- 0.8 ml/min, while sodium excretion increased by 717 +/- 60, 839 +/- 84, and 582 +/- 57 mueq/min. After atrial appendectomy urine flow rate increased 2.1 +/- 0.7, 2.7 +/- 0.7, and 2.0 +/- 0.6 ml/min, and sodium excretion increased only by 327 +/- 110, 324 +/- 77, and 340 +/- 92 mueq/min (p less than 0.01) during volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Noncardiac chest pain in adolescents and children with mitral valve prolapse.

Chest pain in adolescents and children is usually not of cardiac origin. Of cardiac conditions commonly linked to chest pain in childhood, mitral valve prolapse (MVP) is the most prevalent, but this association has recently been questioned. In light of recent reports of gastroesophageal sources of chest pain in adults with MVP, we performed a comprehensive gastroesophageal evaluation of 17 preadolescents and adolescents with mitral valve prolapse who had chest pain as their presenting symptom. Evaluation consisted of esophageal manometry, Bernstein test, esophageal pH probe, and/or esophagogastroscopy. Fourteen of the 17 patients had at least one abnormal finding. Five patients had esophagitis, five had gastritis, one had high-amplitude esophageal contractions, one had abnormal esophageal manometry with positive Bernstein test, one had esophageal reflux and positive Bernstein test, and one had abnormal manometry with esophageal reflux. The 13 patients with esophagitis, gastritis, reflux, or positive Bernstein test were treated with antacid, with resolution of chest pain in 12 patients. Two of these patients underwent follow-up endoscopy with documentation of improvement. The patient with high-amplitude esophageal contractions was treated with dicyclomine, which resulted in resolution of chest pain. The observation that the chest pain was not related to mitral valve prolapse is important in clinical practice and raises further questions as to whether mitral valve prolapse causes chest pain.

Adolescent

Atrial compliance determines the nature of passive atrial stretch and plasma atrial natriuretic factor in the conscious dog.

STUDY OBJECTIVE: The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. DESIGN: Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. EXPERIMENTAL MATERIAL: Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters. MEASUREMENTS AND MAIN RESULTS: During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1. CONCLUSIONS: Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.

Animals

Electrocardiographic findings in children with Lyme disease.

The incidence of cardiac involvement in Lyme disease (LD) has been estimated to be 4 to 10% in adults, with conduction and rhythm disturbances noted most frequently. To assess the frequency of electrocardiographic abnormalities in children with LD, we prospectively performed 12-lead electrocardiograms in 32 randomly selected children presenting with LD between May and September 1989. No patient had symptoms of cardiac involvement. Using defined diagnostic criteria, combining symptoms, signs, serology, and residence in or travel to an endemic area, 14 patients were classified as having definite LD and 10 were categorized as probable. The incidence of electrocardiographic abnormalities in the definite group was 29% (4/14), including two patients with 1 degree atrioventricular block, one with left axis deviation, and one with ventricular ectopy. Thirty percent (3/10) of the probable group had abnormal ECGs, including one with ST-T wave abnormalities, one with prominent sinus arrhythmia, sinus bradycardia, and wandering atrial pacemaker, and one with ectopic atrial bradycardia. No patient required cardiac therapy. The incidence of abnormal ECG findings in this group of children with either probable or definite LD was thus 29%, with 1 degree atrioventricular block noted most frequently. When the diagnosis of LD is highly suspected, an electrocardiogram may be a useful screening test for cardiac involvement.

Adolescent

O2 and rat pulmonary artery tone: effects of endothelium, Ca2+, cyanide, and monocrotaline.

The present study examines the influence of the endothelium (E), Ca2+ concentration, cyanide and monocrotaline (MCT) pretreatment on the responses of isolated rat hilar pulmonary arterial rings (PA) to hypoxia. In PA precontracted with phenylephrine, hypoxia induced an initial E-dependent relaxation phase followed by an E-independent transient contraction and a final relaxation. An increase in Ca2+ concentration from 1.5 to 2.5 mM produced an E-dependent reduction in tone generation under O2 and a significant enhancement of the hypoxia-elicited initial relaxation and the transient contractile responses. Addition of cyanide (0.1 mM) to precontracted PA produced a transient contraction similar to that caused by hypoxia. Preincubation with cyanide led to inhibition of tone generation and abolition of the contraction to hypoxia. However, the final relaxation response to hypoxia was not inhibited by cyanide. Thus, hypoxia produces an E-independent contraction via a mechanism that appears also to be activated by cyanide, and this response is not altered by MCT. The endothelium alters the response to hypoxia in a Ca(2+)-dependent manner.

Acetylcholine

The role of vasopressin and atrial natriuretic factor in postoperative fluid retention after the Fontan procedure.

The Fontan procedure results in right atrial distention and is complicated by fluid retention. Since systemic fluid balance may be hormonally mediated in part and related to right atrium size, we measured plasma atrial natriuretic factor and plasma arginine vasopressin levels in 19 patients undergoing the Fontan procedure and in 12 control patients undergoing other types of heart operations. Preoperative plasma atrial natriuretic factor levels were higher in patients undergoing the Fontan procedure than in control patients (95 +/- 16 pg/ml preoperatively versus 50 +/- 8 pg/ml; p less than 0.05) and increased in patients undergoing the Fontan procedure to 330 +/- 48 pg/ml by postoperative day 2 (p less than 0.05) but not in control patients. Increased plasma atrial natriuretic factor levels could enhance capillary transudation, but elevated plasma atrial natriuretic factor levels should also enhance diuresis and prevent fluid retention. Vasopressin levels, however, were also increased in patients undergoing the Fontan procedure (from 9 +/- 2 pg/ml preoperatively to 144 +/- 37 pg/ml at end of operation) and were higher and remained elevated longer than in control patients undergoing heart operations (37 +/- 7, 20 +/- 4, 16 +/- 6 pg/ml on postoperative days 1, 2, and 3 to 10 for the Fontan group compared with 15 +/- 4, 4 +/- 1, 4 +/- 2 pg/ml for control patients). Vasopressin levels were highest in the Fontan group with the most severe fluid retention and effusions (for example, 51 +/- 10 pg/ml versus 23 +/- 4 pg/ml, on postoperative day 1). Increased vasopressin and atrial natriuretic factor could act synergistically to result in the development of effusions after the Fontan procedure when atrial natriuretic factor-induced capillary transudation is combined with vasopressin-induced antidiuresis.

Atrial Natriuretic Factor

Regulation of plasma ANF after increases in afterload in conscious dogs.

Although atrial stretch is the primary stimulus for atrial natriuretic factor (ANF) secretion, hormones may directly affect ANF secretion or may indirectly influence ANF by changing left ventricular afterload, thereby altering atrial stretch. To determine whether direct effects are important for the release of ANF in vivo, we measured changes in plasma ANF and in atrial wall function in the conscious dog after the administration of vasopressin, angiotensin II, and phenylephrine and by mechanically increasing left ventricular afterload by partial aortic occlusion. Injections of phenylephrine, angiotensin II, and arginine vasopressin (AVP) that were chosen to cause similar changes in systemic arterial pressure resulted in similar changes in atrial pressure and diameter. Maximum V wave atrial wall stress increased to 283 +/- 12, 311 +/- 41, 327 +/- 24, and 277 +/- 22 g/cm2 for AVP, angiotensin, phenylephrine, and occlusion, respectively, and plasma ANF increased to 242 +/- 81, 248 +/- 62, 299 +/- 95, and 190 +/- 53 pg/ml. There were significant linear correlations between left ventricular afterload and left atrial pressure, and each method for increasing left ventricular afterload shifted the position to the left on an atrial pressure-diameter, compliance curve, by a similar degree. Thus changes in left ventricular afterload result in changes in atrial wall function and similar changes in plasma ANF. No hormonal-specific increase in plasma ANF was found in conscious dogs after increases in afterload.

Angiotensin II

Enteral nutrition in infants with congenital heart disease and growth failure.

To determine an effective nutritional regimen for management of growth failure in infants with congenital heart disease and congestive heart failure, the authors studied 19 infants with cardiac anomalies who were not candidates for early corrective surgery. Patients were randomly assigned to one of three feeding groups: group 1 (n = 7) received continuous, 24-hour nasogastric alimentation; group 2 (n = 5) received overnight, 12-hour nasogastric infusions plus daytime oral feedings as tolerated; and group 3 (n = 7) received oral feedings alone. For all patients, commercial infant formula (cow's milk or soy protein) was supplemented to a calorie density of approximately 1 kcal/mL. During a 5.25 +/- 0.45 month study period, only group 1 infants achieved intakes greater than 140 kcal/kg per day (mean = 147 kcal). Serial anthropometric measurements demonstrated that only 24-hour infusions (group 1) were associated with significantly improved nutritional status, when assessed by z scores for weight (P less than .01) and length (P less than .05). Group 1 infants also showed marked increases in midarm muscle circumference and triceps and subscapular skinfold thicknesses (P less than .01, compared with groups 2 and 3). These data suggest that infants with congenital cardiac defects complicated by malnutrition manifest increased nutrient requirements for growth and weight gain. Continuous, 24-hour, nasogastric alimentation is a safe and effective method for achieving both increased nutrient intake and improved overall nutritional status in these infants.

Anthropometry

Acrocallosal syndrome: additional manifestations.

The acrocallosal syndrome (ACS) is a probable autosomal recessive condition of macrocephaly, craniofacial and hand and foot abnormalities, absence of the corpus callosum, and mental retardation. This patient had characteristics of the ACS but also had a severe congenital heart defect and other visceral malformations. After comparing the ACS with and contrasting it to other disorders, we concluded that the internal organ abnormalities found in this patient probably represent further manifestations of the ACS.

Abnormalities, Multiple

Infants with apparent life threatening events. Cardiac rhythm and conduction.

The role of cardiac dysrhythmias in the pathogenesis of Sudden Infant Death Syndrome (SIDS) is uncertain, but there have been several reports of infants with Apparent Life Threatening Events (ALTE) due to significant dysrhythmias. To further characterize the cardiac rhythm and conduction of these "at-risk for SIDS" infants, we performed 24-hour continuous (Holter) electrocardiograms on 100 full term, healthy infants with ALTE. Sixty-two patients (62%) had one or more dysrhythmias on Holter monitor. Twenty-five patients (25%) had premature ventricular depolarizations (PVD), including five with couplets. Thirty (30%) had QTc greater than 2 SD above the mean, and, of these, 40 percent had PVD's. Fifteen (15%) had premature atrial depolarizations and 39 (39%) had evidence of moderate or marked sinus node irregularity. There was no prexcitation, supraventricular tachycardia, ventricular tachycardia, or atrioventricular block. Two patients with marked sinus node dysfunction were treated with propantheline and did well. All patients were monitored at home, with no deaths or clinically significant dysrhythmias on follow-up (1-32 months (mean = 18]. In summary, when Holter monitoring was performed, a high incidence of dysrhythmia was found in infants with ALTE. Most dysrhythmias were clinically insignificant. The incidence of ventricular dysrhythmias and long QTc are consistent with previously advanced theories of cardiac electrical instability in some of these patients, but no patient with ventricular dysrhythmias required therapy. The incidence of sinus node dysfunction requiring therapy was 2 percent. Although Holter monitoring of infants with ALTE only infrequently determines therapy, it may provide data linking theories of cardiac etiology of SIDS with actual clinical events.

Arrhythmia, Sinus

Variable arginine vasopressin levels in neonatal congestive heart failure.

Arginine vasopressin levels in 17 neonates with cardiac disease were compared with control levels in 10 healthy newborn infants. Infants with congestive heart failure who were free of left ventricular outflow tract obstruction had a mean level of 80 +/- 18 pg/ml, which was significantly greater than the mean control level (p less than 0.001). Infants with congestive heart failure and left ventricular outflow tract obstruction had a mean vasopressin level of 3 +/- 0.7 pg/ml, which was lower than the mean control level of 6 +/- 0.7 pg/ml (p less than 0.05). The data suggest that impaired forward flow to high pressure sinoaortic and ventricular baroreceptors is necessary for vasopressin release in congestive heart failure. In left ventricular outflow tract obstruction with heart failure these receptors may be impaired or absent, leading to decreased vasopressin release. Low plasma arginine vasopressin may adversely affect circulatory homeostasis.

Acute Disease

Life-threatening dysrhythmias in varicella myocarditis.

Varicella myocarditis is an unusual complication of a common childhood disease. Two patients with life-threatening dysrhythmias and circulatory failure are reported. One patient required permanent pacemaker implantation for acquired complete heart block, not previously described with varicella infection. Previously reported cases of varicella myocarditis are reviewed.

Arrhythmias, Cardiac

In utero thickening of the chordae tendinae. A cause of intracardiac echogenic foci.

Asymptomatic hyperechoic foci were noted within the left cardiac ventricular chamber on the prenatal sonograms of 26 patients between 16 and 20 weeks of gestation. Their range of occurrence, the prenatal follow-up in 12 patients and postnatal echocardiograms in six patients, indicate a clinically insignificant congenital anomaly associated with the chordae tendinae.

Adult

Elevated atrial natriuretic peptide after the Fontan procedure.

To assess the response of atrial natriuretic peptide (ANP) to rapidly changing right atrial pressures in vivo, we measured ANP levels in 15 patients undergoing the Fontan procedure and compared them with control levels in nine patients undergoing cardiac surgery for lesions not associated with atrial hypertension. There were no significant differences in preoperative ANP levels: 57 +/- 15 pg/ml for patients undergoing the Fontan procedure, 43 +/- 8 pg/ml for control patients. There was no significant change in ANP during surgery or in the postoperative period in control patients. In contrast, ANP increased significantly to 333 +/- 70 pg/ml (p less than .0025) after establishment of right atrial-pulmonary artery continuity with the Fontan procedure and was related to right atrial pressure, which increased from 5 mm Hg before to 14 mm Hg after the Fontan procedure (p less than .001). There was no significant change in left atrial pressure. During the first postoperative day, ANP levels fell to 141 +/- 34 pg/ml (p less than .01) but later increased to 290 +/- 80 pg/ml (p less than .025), a finding that may suggest depletion of a readily releasable intracellular pool of ANP before mobilization of a storage pool. There was no direct relationship between ANP levels and effusions in patients undergoing the Fontan procedure. Pharmacologically significant increases in ANP occur in patients undergoing the Fontan procedure, correlating with increased right atrial pressures, but the relationship between ANP and the fluid derangements after the procedure remains unclear.

Atrial Natriuretic Factor

Cardiac involvement in cystic fibrosis: early noninvasive detection and vasodilator therapy.

Cardiac involvement in cystic fibrosis (CF) occurs commonly but may remain undetected by usual evaluation in its early stages when right ventricular dysfunction (RVD) may be treatable. To assess the role of vasodilator therapy for early RVD in CF, we performed a prospective study in 23 ambulatory CF patients with mild CF (clinical score m = 79 +/- 8, range 61 to 90). Echocardiography (echo) and radionuclide angiography (RA) were performed at rest and with exercise stress testing (EST) in all 23 to select patients with early RVD. Thirteen of twenty-three had RVD on echo or RA evidenced by increased RV dimensions (P less than 0.001) on echo and decreased RV ejection fraction (EF) on RA (P less than 0.01) but 30% of these patients were abnormal only with EST. All 13 with RVD underwent inpatient double-blinded randomization to receive placebo or hydralazine orally without changing other standard therapy. Nine of thirteen received hydralazine (2 mg/kg/day) for 3 days. With hydralazine no change from placebo was seen on any echo or RA measurement at rest or with EST other than left ventricular STI which fell (P less than 0.05). These data indicate: 1) EST with echo and RA detects RVD in CF earlier than resting studies, 2) patients with mild CF (clinical score less than 85) frequently have RVD on EST, and 3) hydralazine does not improve RVD in CF even very early in its development.

Adolescent