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Biomedical subjects

S Einzig

Publications and source records attributed to S Einzig.

At least 37 records · Page 2Linked to original sources

Reduced lipid peroxidation in dilated hearts of cardiomyopathic turkeys.

Adverse pulmonary reactions to some nitrofuran antibiotics are thought, in part, to involve production of reactive oxygen radicals. Furazolidone, a nitrofuran antibiotic, causes a dilated cardiomyopathy in domestic turkeys. The mechanism of this drug induced cardiomyopathy is unknown. We investigated the possible role of free radical injury in this heart failure model. Left ventricular lipid peroxidation capacity, assessed by two methods (the thiobarbituric acid reactive substances and lipid hydroperoxides assays respectively), was investigated in five 5-8 week old cardiomyopathic turkeys with severe cardiac dilatation, left ventricular dysfunction and systemic hypotension, and in five control birds. Superoxide dismutase activity, total and manganese, was also measured in the crude left ventricular homogenates. Both lipid peroxidation products were reduced in the myopathic hearts: thiobarbituric acid reactive substances (malondialdehyde) 70(SEM 4) v 86(3) nmol.100 mg protein-1 in controls, p less than 0.02; and lipid hydroperoxides 29(7) v 74(14) nmol.100 mg protein-1, p less than 0.02. Total superoxide dismutase activity was similar in cardiomyopathic and control hearts: 670(26) v 657(105) nitrite units.100 mg protein-1. Although total superoxide dismutase activity was unchanged, we found decreased manganese superoxide dismutase in the dilated hearts compared with controls (54% v 84% of total activity, p less than 0.02). In separate in vitro experiments furazolidone (2-10 mg.g wet weight-1) did not increase malondialdehyde production in turkey (or rat) left ventricular homogenates. These results indicate that cardiomyopathy induced by furazolidone is associated with decreased myocardial lipid peroxidation. Although as yet unexplained, the decrease may be due to a diminished amount of heart lipid susceptible to peroxidation accompanying the process of cardiac hypertrophy and dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of coronary artery anatomy in patients with tetralogy of Fallot by two-dimensional echocardiography.

A major coronary artery crossing the right ventricular outflow tract in patients with tetralogy of Fallot interferes with a transannular patch, and preoperative detection of this artery is important. We evaluated the ability of two-dimensional echocardiography to define noninvasively the coronary artery anatomy in 37 consecutive patients (age range, 1 day to 18 years; mean age, 40.9 months). The origin and distribution of the right anterior descending and circumflex coronary arteries, as well as any anteriorly coursing vessel, were examined from parasternal views. Complete studies were obtained in 29 (78%) of the 37 patients. Coronary artery anatomy was determined to be normal by echocardiography in 20 (69%) of the 29 patients. An anterior vessel across the right ventricular outflow tract was detected in the remaining nine patients. Six patients had an anterior descending artery from the left main coronary artery (paired anterior descending arteries in three patients, a right anterior descending artery from the left main coronary artery in two patients, and a right coronary-to-pulmonary artery fistula in one patient). Three patients had no anterior descending artery from the left main coronary artery (anterior descending artery from the right main coronary artery in two patients, and anterior descending and circumflex arteries from the right main coronary artery in one patient). Angiography, surgery, or autopsy confirmed the diagnoses in all but the final patient in whom the anterior descending artery arose from the right main coronary artery as observed at surgery, but the circumflex artery was not seen. Accurate evaluation of coronary artery anatomy is possible by echocardiography in the majority of patients with tetralogy of Fallot. Noninvasive identification of a major coronary artery coursing anteriorly can influence the timing of cardiac catheterization and surgery and the need for angiography.

Adolescent↗

Echocardiographic versus cardiac catheterization diagnosis of infants with congenital heart disease requiring cardiac surgery.

The success of noninvasive preoperative evaluation of infants with congenital heart disease using cardiac ultrasound depends not only on diagnostic accuracy, but also on risk of morbidity and mortality as compared with infants who undergo cardiac catheterization. Fifty-six infants (age 10 weeks or younger) with coarctation of the aorta (n = 16), coarctation with ventricular septal defect (n = 12), valvar aortic stenosis (n = 10) or total anomalous pulmonary venous connection (n = 18) were examined. Thirty-one underwent noninvasive preoperative assessment and 25 underwent evaluation including cardiac catheterization. Age, level and duration of support, pH, renal function, mortality, complications of cardiac catheterization and errors of diagnosis were compared. Significant differences between the 2 groups were more frequent preoperative use of prostaglandin E1 and shorter hospital stay in the noninvasively evaluated coarctation group. Of the infants with coarctation and ventricular septal defect, 1 who had cardiac catheterization required renal transplantation and 1 evaluated noninvasively required surgery at age 3 months for mitral stenosis not discovered on preoperative evaluation. One noninvasively evaluated infant with total anomalous pulmonary venous connection had a stenotic communication between the pulmonary venous confluence and the left atrium not detected by ultrasound. Surgery was successful in the latter 2 infants. Noninvasive preoperative diagnosis of some infants with congenital heart disease can be performed without increasing the risk of operative morbidity and mortality. Eliminating cardiac catheterization reduces hospital costs, decreases total numbers of catheterizations performed and influences the structure of training programs.

Cardiac Catheterization↗

Exercise reduces persistent ductus arteriosus shunting in piglets.

To determine the effects of dynamic exercise on ductal left to right shunting and skeletal and myocardial blood flow distribution, a persistent ductus arteriosus was created by balloon catheters in neonatal piglets. At 8-10 weeks of age, aortic, pulmonary artery, and left atrial catheters were placed and radiolabelled microspheres injected for measuring left ventricular output, organ blood flows, and ductus left to right shunting at rest and during treadmill exercise (1.6 mph). At rest, effective left ventricular output and myocardial and skeletal muscle blood flows were similar in the study group and controls. Exercise increased skeletal muscle and left ventricular blood flows similarly in the control and study group and did not accentuate the exercise induced small reduction in the left ventricular subendocardial to subepicardial blood flow ratio. This was due to a significant reduction in the ductus left to right shunt during exercise (mean(SD) 34(15) vs 18(7)%, p less than 0.02) and maintenance of effective left ventricular output in the study group (447(144) vs 446(98) ml.min-1.kg-1 in controls). The reduction in ductus shunting during exercise was due to a significant decrease in systemic vascular resistance and a small increase in pulmonary vascular and ductus resistance. Thus, reduced persistent ductus arteriosus shunting and maintenance of effective left ventricular output prevents myocardial perfusion abnormalities during dynamic exercise in swine with a persistent ductus and small to moderate left to right shunts.

Animals↗

Beta-adrenergic function in a congestive cardiomyopathy model.

We investigated the cardiac beta-adrenergic-adenylate cyclase (AC) system in turkeys inbred for congestive cardiomyopathy (CCM) and the relation of this system to echocardiographically determined left ventricular shortening fraction (LVSF) in individual 56-day-old birds. The isoproterenol (Iso)-stimulated, NaF-stimulated, and basal AC activities in CCM birds were decreased to 69, 72, and 86%, respectively, of control values, P less than 0.05. By linear regression analysis there was significant direct correlation of initial LVSF in CCM birds with each of the following: change in heart rate (HR) after Iso function; Iso-stimulated, NaF-stimulated, and basal AC activities, and density of beta-adrenergic receptors. In addition, we investigated the effect of Iso infusion (0.4 microgram X kg-1 X min-1) on systemic hemodynamics. In CCM birds the initial LVSF was 72% of the control value, P less than 0.01; the initial HR was 112% of the control value, P less than 0.01. During Iso infusion both the LVSF and HR in control birds were increased, whereas in CCM turkeys with marked cardiac dilatation neither of these parameters changed. In 10-day-old CCM turkeys, which show no cardiac dilatation, NaF-stimulated AC activity was reduced to 70% of the control values, whereas basal and Iso-stimulated AC activities were unchanged. Thus an abnormality in the beta-adrenergic-adenylate cyclase system is present in CCM birds before development of cardiac dilatation; when cardiac dilatation is severe, a global defect in this system can be directly related to depressed inotropic and chronotropic responsiveness to Iso infusion in individual turkeys.

Adenylyl Cyclases↗

Morphine suppression of digitalis-induced ventricular arrhythmias.

The purpose of the study was to investigate the effect of morphine on digitalis-induced arrhythmias. Seventeen normokalemic dogs [serum potassium 3.9 +/- 0.3 mEg/L (+/- 1 S.D.)] and 19 hypokalemic dogs (serum potassium 2.2 +/- 0.3 mEg/L) were allocated to a morphine pretreatment group (morphine sulfate 3 mg/kg) or to a control group without morphine. Ouabain was administered by a constant infusion of 150 micrograms/kg/hr following an initial bolus of 20 micrograms/kg until animals developed ventricular tachycardia. In hypokalemic dogs, morphine pretreatment significantly (p less than 0.05) increased the digitalis dose required to initiate ventricular tachyarrhythmias (66 +/- 14 vs 37 +/- 11 micrograms ouabain/kg). In normokalemic dogs morphine did not affect the relationship between digitalis dose and arrhythmias. Thus, morphine pretreatment reduces the tendency for hypokalemia to potentiate digitalis-induced ventricular arrhythmias.

Animals↗

Innervation of periosteum and bone by sympathetic vasoactive intestinal peptide-containing nerve fibers.

Neural control of bone metabolism and growth has been suggested, although the identity of participating neurons and neurotransmitters effecting this control has not been established. Immunohistochemical studies demonstrated a system of vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers that innervate periosteum and bone in several mammalian species. Thoracic sympathetic chain ganglionectomy resulted in an ipsilateral loss of VIP-immunoreactive fibers in the periosteum of ribs, whereas dorsal root ganglionectomy had no effect. Injection of fast blue into rib periosteum labeled a population of VIP-immunoreactive sympathetic postganglionic neurons. Thus, postganglionic sympathetic neurons may provide an important means by which VIP regulates bone mineralization.

Animals↗

Long term model for evaluation of myocardial metabolic recovery following global ischemia.

Myocardial ATP levels remain depressed following significant periods of ischemia (Isc) despite reperfusion (Rpf). Neither the rate of in vivo ATP return following global Isc nor the factors which influence recovery have been defined. In order to determine the time course to complete the return of ATP levels and evaluate methods of enhancing recovery of ATP levels, we have devised a chronic canine model of global Isc. In this model serial ventricular biopsies can be taken in the awake animal over several days without reoperation which allows an investigation of the recovery of the myocardium following a uniform global insult to be performed. Recovery of ATP levels has been shown to depend, at least in part, on the availability of precursors and the activity of the ATP regenerating enzymes. Because complete recovery of ATP levels takes days, short term (hours) models have limitations. Previous attempts at enhancing ATP recovery following Isc have been only partially successful because either the degree of depression was not great or the period of observation was short, resulting in incomplete return. To identify the best precursor choice, we previously measured the activity of the AMP regenerating enzymes, adenosine kinase (AdK) (adenosine----AMP) and adenine phosphoribosyl transferase (APRT) (adenine----AMP). Because APRT activity was 20 fold higher than AdK with similar Km values for substrates, it appeared that adenine (A) is preferred to adenosine for AMP regeneration in the dog's myocardium. The formation of 5-phosphoribosyl 1-pyrophosphate (PRPP) may also be rate limiting and, therefore, the effect of ribose (R) on ATP recovery was also evaluated. Recovery of ATP levels was assessed in three groups: (1) normal saline (NS), (2) A (20 mM) in normal saline (A/NS) or (3) A with R (80 mM) in normal saline (A/R) were infused (1.0 ml/min) into the right atrium of dogs for 48 hours following Isc. In all groups, ATP levels fell to between 46-60% of pre-Isc levels during Isc. In the NS dogs, ATP levels continued to fall slightly to 46% pre-Isc levels during the first four hours of Rpf after Isc. By 24 hours no appreciable recovery had occurred and the measured ATP was only 51% of the pre-Isc value. Even by seven days, ATP had not returned fully, and by extrapolation, complete recovery required 9.9 +/- 1.4 days. Treated dogs showed, however, that ATP recovery could be significantly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

Myocardial high-energy phosphate levels in cardiomyopathic turkeys.

A congestive cardiomyopathy (CCM) model occurs in inbred broad-breasted turkeys and is manifested by reduced hatchability and a high mortality within a week of hatching. In the survivors, cardiac dilation begins by 3-4 weeks of age and further mortality occurs from chronic congestive heart failure. The mechanisms behind these changes is unknown, and, therefore, we investigated what role, if any, myocardial energy metabolism might play in these events. Ventricular myocardial samples were obtained for analysis of adenine nucleotides (ATP, ADP, AMP) and creatine phosphate (CP) in control and CCM turkeys, 1-31 days old. The adenine nucleotide energy charge (EC) was calculated using the formula EC = ATP + 1/2ADP/(ATP + ADP + AMP). We found the myocardial ATP levels and EC in CCM hearts at 1-2 days were reduced. In control turkeys, no significant age-related differences were found in myocardial high-energy phosphate compounds or in the EC. This depression in the energy metabolism of CCM turkeys may also be reflected in their poor hatchability. By 6-10 days, however, ATP levels had recovered and remained normal despite the onset of cardiac dilation and failure at 3-4 weeks of age in CCM turkeys. Because CP levels in control and CCM turkey hearts were similar in all age groups, significant ischemia did not appear to be present after hatching in CCM turkeys. Our results suggest, therefore, that an insult probably prior to hatching produced depressed myocardial energy levels in CCM turkeys and led to reduced hatchability. This early insult appears to be significant, in that late cardiac dysfunction resulted despite the recovery of myocardial ATP levels.

Adenine Nucleotides↗

Flow in the aorta and patent ductus arteriosus in infants with aortic atresia or aortic stenosis: a pulsed Doppler ultrasound study.

We used pulsed Doppler ultrasound to determine the flow dynamics of the aorta and patent ductus arteriosus (PDA) in 21 infants (ages 1 to 16 days) with PDA and aortic atresia (n = 15) or aortic stenosis (n = 6). The flow within the PDA was recorded in 19, and was right-to-left during systole in all. There was a diastolic left-to-right PDA shunt in 11 patients with aortic atresia and in three with aortic stenosis, and the shunt was associated with large (3 to 11 mm in diameter) interatrial communications. In two patients with aortic atresia and three with aortic stenosis, however, the diastolic PDA shunt was from right to left, and the interatrial communications were small (0 to 2 mm in diameter). The right-to-left diastolic PDA shunting may be best explained by the relative pulmonary (high with left-sided inflow obstruction and a small interatrial communication) and systemic resistances. All patients with aortic atresia and three with aortic stenosis had retrograde systolic flow in the transverse aortic arch, probably resulting from inadequate left ventricular output. Antegrade diastolic flow in the transverse aortic arch toward the PDA was observed in all infants with aortic atresia and a left-to-right PDA shunt. Ascending aortic flow was recorded in 11 patients with aortic atresia, and was retrograde during diastole in each, the result of coronary perfusion. Application of pulsed Doppler ultrasound can lead to a better understanding of the hemodynamics and physiology of patients with congenital cardiovascular disease.

Aorta↗

Rest and exercise hemodynamics in pulmonary stenosis: comparison of children and adults.

To better understand the hemodynamics of pulmonary stenosis (PS), 24 adults and 53 children with similar degrees of PS who had undergone cardiac catheterization at rest and during supine exercise were retrospectively studied. Three groups were defined. Group I consisted of 9 adults and 18 children with a pulmonary valve area of less than 0.5 cm2/m2; group II, 6 adults and 25 children with a pulmonary valve area of 0.5 to 1.0 cm2/m2; and group III, 9 adults and 10 children with pulmonary valve area of more than 1.0 cm2/m2. The mean ages of the adults were 29, 26 and 22 years for groups I, II, and III, respectively. The mean ages of the children were 11, 10 and 9 years for groups I, II and III, respectively. The pertinent data collected from catheterization included oxygen consumption, cardiac rate and index, arterial venous oxygen difference, stroke index, right ventricular (RV) systolic pressure and RV end-diastolic pressure. Adults and children in groups II and III had an appropriate response to exercise. Group I children responded abnormally by increasing their RV end-diastolic pressure and decreasing their stroke index. In group I adults both of these variables increased. Group I adults exhibited a significantly lower cardiac index at rest and exercise secondary to a significantly lower absolute cardiac rate. Long-standing severe PS results in hemodynamic compromise. Hence, early relief of PS is recommended.

Adolescent↗

Arachidonic acid metabolism in thrombocytes and vascular tissues of turkeys.

Turkeys are hypertensive compared to mammals of similar size. In vitro synthesis of thrombocyte thromboxane B2 (TxB2), 12L-hydroxy-5,8,10 heptadecatrienoic acid (HHT), 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) and aortic prostaglandin (PG) production was studied in one to ten month old domestic white turkeys. Compared to normal human platelets, TxB2 production was increased (55.4 vs. 31.4%) and HETE production was markedly reduced (6.5 vs. 34.6%) in control thrombocytes. Similar to human platelets in which cyclooxygenase inhibition with aspirin results in an increase in HETE production, block of the thrombocyte enzyme with aspirin doubled the production of HETE. In vitro conversion of radiolabeled arachidonic acid (AA) showed that the primary PG produced by turkey aorta was PGE2. A 6-keto immunoreactive PG was present which comigrated with authentic 6-keto PGF1 alpha, but failure of the aortic supernatant to inhibit adenosine diphosphate or AA induced platelet aggregation suggested that PGI2 was not produced. The vasodepressor potency of PGE1, PGE2 and PGI2 was altered in awake turkeys with PGE1 and PGE2 having five times the hypotensive effect as PGI2. In addition, conversion of AA to PGE2 by aorta in one month turkeys was greater (17.3 vs. 9.2%) than in ten month old turkeys. Systemic arterial pressure was increased in the ten month old turkeys (188 mmHg) compared to one month old turkeys (143 mmHg). Thus, both vascular AA metabolism and the vasodepressor potencies of PGE2 and PGI2 are altered and the activity of the lipoxygenase pathway in thrombocytes is limited in the turkey.

Animals↗

Carnitine alterations in spontaneous and drug-induced turkey congestive cardiomyopathy.

Carnitine and acylcarnitines were measured in plasma and tissues of control turkeys, turkeys with an inbred spontaneous cardiomyopathy, and turkeys with furazolidone-induced cardiomyopathy. Heart failure was evident in both types of cardiomyopathy from decreased systemic blood pressure and cardiac dilatation compared to controls. Plasma free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine were significantly elevated by 76 to 614% (p less than 0.01) in the two cardiomyopathy models compared to control. The highest carnitine levels were found in the most hypotensive turkeys. Liver free carnitine and short-chain acylcarnitine levels were also elevated by 45 to 537% (p less than 0.05) in both types of cardiomyopathy. Free carnitine was elevated by 126% in left ventricle and by 54% in skeletal muscle of the furazolidone-treated turkeys (p less than 0.05). We speculate that hepatic synthesis of carnitine may be increased in response to hypotension and progressive cardiac dysfunction in cardiomyopathic turkeys. Such an increase may be useful to promote beta-oxidation of fatty acids as a cardiac energy source.

Animals↗

Adequacy of ascending aorta-descending aorta shunt during cross-clamping of the thoracic aorta for prevention of spinal cord injury.

The effectiveness of various sized shunts placed between the ascending and the descending aorta to prevent paraplegia in dogs with the thoracic aorta cross-clamped for 1 hour was tested. Three tapered shunts sizes were used with tip dimensions of 3.8, 5.2, and 6.3 mm inner diameter, with cross-sectional areas of 11.34, 21.23, and 33.18 mm2, respectively, and with an equal midportion diameter of 10 mm (3/8 inch). These shunts carried 40%, 60%, and 72% respectively, of baseline descending aortic flow during the cross-clamping period. Flow distribution was measured with radioactive microspheres in the spinal cord (gray and white matter) and kidneys. All dogs without shunts (Group I) developed paraplegia, severe proximal circulatory embarrassment, and severe ischemia of the spinal cord (mainly gray matter) that was followed by marked hyperemia persisting up to 24 hours following the experiment. Mortality was 33%. Only animals treated with large shunts (Groups III and IV) avoided paraplegia and postischemic injury. An effective shunt was characterized as carrying 60% or more of baseline descending aortic flow, having a cross-sectional area at its tip equal to or larger than 29% of the descending aorta, and equaling at least 54% of its diameter. Porportionately, the size of the tridodecylmethylamonium-heparin shunts being used in human beings (even the largest 9 mm inner diameter) is significantly inadequate to maintain distal flows and pressures for the prevention of spinal cord injury. Four clinical options are discussed.

Adrenal Glands↗

Inducible ventricular arrhythmias in a naturally occurring model of cardiomyopathy.

This study examined inducibility of ventricular tachyarrhythmias in turkeys with and without naturally occurring dilated cardiomyopathy. Using a transvenously positioned electrode catheter, 32 cardiomyopathy and 12 control unsedated turkeys aged 2 to 4 months were studied by right ventricular endocardial extrastimulus testing at basic pacing cycle lengths of 200 and 170 ms with both 1 and 2 extrastimuli and burst pacing at progressively shorter cycle lengths (200 to 100 ms). Following study, a dilatation index (determined as the ratio of left ventricular endocardial and epicardial diameter at level of the apex-base midpoint) was utilized to assess the functional severity of cardiomyopathy. All control turkeys had a dilatation index less than 0.3. In cardiomyopathic turkeys, dilatation index was normal (less than 0.3) in 3/32, showed mild to moderate dilatation in 25/32 (0.3 to 0.6), and severe dilatation in 4/32 (greater than 0.6). Results showed no difference in right ventricular effective or functional refractory periods between control and cardiomyopathic turkeys. Control turkeys had no inducible ventricular tachyarrhythmias, but 16/32 cardiomyopathic turkeys (p less than 0.005) had inducible ventricular tachyarrhythmias, consisting most frequently of two beats of rapid ventricular tachycardia supervened by ventricular fibrillation. In the cardiomyopathic turkeys, inducible tachyarrhythmias occurred in 1/3 with normal dilatation index, in 11/25 with mild to moderate dilatation, and in 4/4 with severe dilatation. Thus, inducibility of ventricular tachyarrhythmias in cardiomyopathic turkeys is closely associated with increasing ventricular dilatation, but does not correlate with altered right ventricular refractoriness. This model may be suitable for studying the relationship between ventricular tachyarrhythmias and cardiomyopathy.

Animals↗