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Biomedical subjects

S Einzig

Publications and source records attributed to S Einzig.

At least 73 records · Page 4Linked to original sources

Association of varicella, myocarditis, and congestive cardiomyopathy.

A retrospective study of children dying with active varicella revealed 11 of 17 cases who had unsuspected interstitial myocarditis at the time of their death. In addition, a prospective study of 6 children, consecutively admitted to the hospital with active varicella, were evaluated for evidence of cardiac dysfunction by echocardiography, ECG, and serum enzyme levels. All 6 children had Reye's syndrome in association with active varicella. Evidence of myocardial involvement, consistent with acute congestive cardiomyopathy, was documented in 4 of the 6 children. This study suggests that the heart is commonly involved in varicella infections and that cardiac involvement should be considered in children with this disease.

Adolescent↗

Effects of dopamine and dobutamine on the myocardial and systemic circulation during and following cardiopulmonary bypass in dogs.

The effect of dopamine (Dp) and dobutamine (Db) on myocardial and systemic blood flow (BF) distribution was compared in dogs being weaned from cardiopulmonary bypass (CPB) after 20 min of normothermic global myocardial ischemia. Drug infusions (10 mcg/kg/min) were begun and BF was measured (radiolabeled microspheres) prior to weaning and 60 min off CPB. On CPB: Pump flows, by design, were similar (100 ml/kg/min) in Dp, Db, and saline control (NS) dogs. Dp and Db significantly (p less than 0.05) increased myocardial BF. Dp did not alter renal, visceral, and skeletal muscle BF and only increased BF to the cervical spinal cord and medulla. Db, however, significantly reduced renal (-49%), splenci (-58%), pancreatic (-27%), and colonic (-47%) BF but increased perfusion in essentially all of the central nervous system. Off CPB: Cardiac output during Dp and Db infusions was significantly greater than NS dogs (107 +/- 7 vs 152 +/- 12 vs 82 +/- 10 ml/kg/min resp.); the greater increase for Db resulting from a larger stroke volume. Dp and Db significantly increased myocardial BF. Dp increased splenic (+77%), gastric (+139%), and gallbladder (+125%) BF but had no effect on renal, hepatic, skeletal muscle, and intestinal BF. Db infusion maintained renal BF similar to NS and elevated BF to most visceral organs. The results of this study show that the myocardium responded to inotropic stimulation despite the previous ischemic insult but the BF changes varied among regional vascular beds with Dp and Db infusions during and following CPB. Of the 2 drugs, Db showed the greater inotropic response off CPB, a similar increase in myocardial perfusion and greater visceral organ bloodflow.

Animals↗

Nulceoprotein changes in the hearts of cardiomyopathic turkeys.

The possible involvement of nuclear proteins in the pathogenesis of a spontaneously occurring model of congestive cardiomyopathy in turkeys was examined. This model is characterised by cardiac hypertrophy and dilatation, reduced cardiac output and depressed contractility. The protein composition of myocardial nuclei was compared in normal (n = 9) and cardiomyopathic (n = 18) turkeys, 70 to 140 days old. Myopathic hearts as a group have a higher histone content (1.75 +/- 0.09 (SD) mg . mg DNA-1 vs 1.65 +/- 0.07 in controls, P less than 0.01) and histone/nonhistone protein (NHP) ratio (1.07 +/- 0.07 vs 0.95 +/- 0.02 in controls, P less than 0.01). The latter was independent of age and correlated well with the degree of cardiac dilatation. The electrophoretic patterns of chromatin proteins was decreased in myopathic hearts. This decrease was primarily accounted for by lower NHP phosphorylation (5.78 +/- 1.38 pmol 32P . mg prot-1 . 15 min-1 vs 8.33 +/- 0.81 in controls, P less than 0.01). DEAE-Sephacel chromatography separated cyclic AMP-dependent and -independent nuclear protein kinases with similar substrate specificities but lower specific activities in myopathic hearts. SDS-polyacrylamide similar substrate specificities but lower specific activities in myopathic hearts. SDS-polyacrylamide gel electrophoresis of phosphorylated nucleoproteins revealed differences in the lower molecular species of NHPs between control and myopathic hearts. There was a significant correlation between NHP phosphorylation and degree of cardiac dilatation (r = -0.78) or contractility as reflected by left ventricular systolic time intervals (r = -0.57). These results suggest that development of this model of spontaneous cardiomyopathy is associated with, and may, in part, be secondary to changes in the composition and function of myocardial nucleoproteins.

Animals↗

Contrasting effects of spontaneous and induced cardiomyopathy on the nucleoproteins of turkey hearts.

The possible involvement of nuclear proteins in the pathogenesis of cardiomyopathy was studied in a spontaneously occurring and a furazolidone-induced model of turkey cardiomyopathy. Both models are characterised by cardiac hypertrophy and dilatation, systemic hypotension and depressed contractility. The protein composition of myocardial nuclei was compared in normal (n = 9) and cardiomyopathic (spontaneous n = 6, furazolidone-induced n = 21) turkeys. Cardiac nuclei from spontaneously myopathic animals had a higher histone content (1.827 +/- 0.058 (mean +/- SD) mg . mg DNA-1 vs 1.688 +/- 0.187 in controls, P less than 0.05) and histone/nonhistone protein ratio (1.122 +/- 0.020 vs 0.882 +/- 0.128 in controls, P less than 0.01). Nuclear protein phosphorylation was lower in spontaneously cardiomyopathic turkeys primarily because of decreased nonhistone protein phosphorylation (5.100 +/- 0.759 pmol 32 P . mg prot-1 .15 min-1 vs 8.456 +/- 0.886 in controls, P less than 0.01). In contrast, furazolidone-induced cardiomyopathy of similar severity to the spontaneously occurring model was not associated with changes in nucleoprotein composition or degree of phosphorylation. These results indicate that development of spontaneous cardiomyopathy in turkeys may be related to the composition and function of nuclear nonhistone proteins. These changes are not secondary to the cardiac hypertrophy/dilatation accompanying the myopathic process.

Animals↗

Acute effects of amrinone on regional myocardial and systemic blood flow distribution in the dog.

The effect of bolus intravenous injections of amrinone (1-2 mg/kg) on abdominal organ, central nervous system, and myocardial blood flow distribution was examined in 15 anesthetized dogs. Blood flows were measured during control conditions and 5 and 60 min following drug administration using left atrial injection of 15-micrometers radionuclide-labeled spheres. Analysis of variance revealed that blood flow changes were similar in dogs receiving either drug dose (P greater than 0.10). Five minutes following injection, blood flow was increased (all P less than 0.05) in the renal cortex (+20.4%), spleen (+40.4%), and liver (+47.1%); flow was unchanged in other abdominal organs (pancreas, gallbladder, small and large intestine, and fundic and antral gastric mucosa) and the central nervous system (cervical spinal cord, pons, medulla, dorsal thalamus, cerebellum, caudate nucleus, and cerebral cortical gray and white matter); and flow was reduced in the triceps muscle (-23.7%). At this time, left ventricular flow was increased (+25.0%) and the left ventricular subendocardial/subepicardial (Endo/Epi) flow ratio was reduced (1.09 +/- 0.02 (SE) vs. 0.90 +/- 0.02, P less than 0.001). Sixty minutes following injection, renal and hepatic flows had returned to control values while splenic flow remained increased (+61.6%); intestinal, gastric mucosal, gallbladder, and triceps flows were reduced by values ranging from 26.7 to 38.9% and central nervous system perfusion was reduced by values ranging from 11.8 to 19.4% in all regions except the caudate nucleus. Although left ventricular flow had returned to control values, the Endo/Epi ratio (1.02 +/- 0.02) remained minimally reduced at this time (P less than 0.001). These results suggest that vascular responsiveness to intravenous amrinone is not uniform in different circulatory beds and that relative subendocardial under-perfusion of the left ventricular myocardium occurs following bolus intravenous amrinone injections in the dog.

Aminopyridines↗

Transcutaneous angioplasty of experimental aortic coarctation.

A dilatable form of juxtaductal aortic coarctation was surgically created in 29 newborn lambs. Of the 17 long-term survivors, four lambs served as controls and 13 underwent transcutaneous balloon dilation angioplasty with either polyvinylchloride or polyethylene catheters after 7--10 weeks of recovery. During growth before dilation, there was little change in the systolic gradient across the coarctation (36.6-35.3 mm Hg) despite an increase in animal weight from 3.8 to 19.3 kg. This systolic gradient remained constant in undilated lambs throughout a 6-month follow-up. Dilation produced an immediate 65% increase in the diameter of the coarctation and a 68% decrease in the systolic gradient across the coarctation site. Successful dilation required very high (6--8 atmospheres) dilating pressures. This gradient relief persisted throughout a follow-up of up to 1 year. Although no late sequelae could be attributed to the angioplasty, one lamb suffered an anterior aortic tear (associated with a difficult postdilation wire passage across the dilation site), which resulted in fatal intrathoracic hemorrhage. Cross pathologic inspection demonstrated intimal and medial tears in successfully dilated lambs in the first 3 days after dilation; on late pathologic examination, the intima appeared completely healed, without evidence of aneurysm or accelerated atheroma formation, within 2 months. These results, in conjunction with previous human in vitro studies, support the hypothesis that human aortic coarctation may be a dilatable lesion, although the safe limits and optimal protocols for dilating human coarctations are not known.

Angioplasty, Balloon↗

Pharmacokinetics of digoxin in the turkey and comparison with other species.

Digoxin was administered by bolus intravenous injection to seven broad-breasted white turkey poults at doses of 0.1, 0.15, or 0.2 mg/kg. Plasma digoxin concentrations were measured by a 125I radioimmunoassay at selected times over the subsequent 24 hr. The data were fitted to a two compartment open pharmacokinetic model. Overall mean values for kinetic variables were: distribution halflife, 38.96 min; elimination halflife, 11.03 hr; volume of distribution in the central compartment, 1.54 liters/kg; total body clearance, 5.81 ml/min/kg. Different doses did not appear to have a significant effect on the identifiable pharmacokinetic variables, suggesting that digoxin disposition is dose independent in the turkey. The results obtained in turkeys were compared with data reported for rats, cats, dogs, and humans. The value for total body clearance of digoxin in the turkey was similar to values found in man, dogs, and cats but considerably less than values reported for rats. The value for elimination halflife in turkeys was somewhat less than values reported for infants and dogs; however, it was considerably different than values reported for rats and cats.

Adult↗

Effect of Amrinone, a cardiotonic drug, on hemodynamics and platelet function.

In the present study we have investigated the effect of Amrinone on the hemodynamics, platelet counts, prostacyclin and thromboxane synthesis and platelet function. Results show that infusion of the drug increased the heart rate and lowered left atrial, aortic and pulmonary artery pressures within five minutes after a single bolus injection of 2 mg/kg IV dose. Platelet counts made from the blood obtained from anesthetized dogs after the drug infusion showed severe loss of platelets. However, infusion of a similar dose in awake dogs showed no such detrimental effect on platelets. Examination of formalin fixed blood for aggregates showed no more clumps in the treated samples than in the control. Platelets obtained from canine blood drawn at 30 minutes post infusion of the drug showed no aggregatory response to arachidonate. However, the response of these platelets to ADP was quite normal. Amrinone infusion had no inhibitory effect on the ability of vascular tissue to convert arachidonic acid to prostacyclin. Similarly, no inhibitory action could be observed on platelet cyclo-oxygenase activity at this concentration (2 mg/kg). In vitro studies on human platelets showed significant inhibition of cyclo-oxygenase at high concentrations (0.5 mg/ml). Therefore it is unlikely that the drug caused inhibition of the platelet response to arachidonate by the inhibition of prostaglandin synthesis during infusion, as the dose used was quite low (2 mg/kg) compared to what is required for the inhibition of cyclo-oxygenase.

Adenosine Diphosphate↗

Cellular electrophysiological changes in "round heart disease" of turkeys: a potential basis for dysrhythmias in myopathic ventricles.

Arrhythmias are commonly recorded in "round heart disease", a presumed viral, congestive cardiomyopathy of turkeys. To assess whether cellular electrophysiological changes may be associated with arrhythmia susceptibility, we compared transmembrane action potential characteristics in left and right ventricular endocardial muscle fibres from 19 inbred myopathic turkeys with findings in 13 normal control turkeys (age 1 to 74 days). In left ventricular tissue, as a group, action potential duration at 50% repolarisation (APD50) was reduced in myopathic hearts (201+/-6(SEM) vs 228+/-9 ms in controls. P less than 0.01), while the maximum rate of phase 0 (dV/dtmax) action potential amplitude, diastolic resting membrane potential and action potential duration at 90% repolarisation (APD90) did not differ from control turkeys. By contrast, in myopathic right ventricular tissue, as a group, both APD50 (186+/-5 vs 206+/-4 ms in controls) and APD90 (208+/-4 vs 228+/-3 ms in controls) were shorter (P less than 0.01). The plateau potential in both right and left ventricular tissue was significantly higher in inbred turkeys. Since a spectrum of cardiac dilatation and hypertrophy is present in myopathic turkeys, we examined the effect of hypertrophy on action potential characteristics. In "round heart disease" turkeys, left ventricular hypertrophy was characterised by reduced dV/dtmax (98+/- vs 274+/-26 V.s-1, P less than 0.01) and right ventricular hypertrophy by further shortening of both APD50 (174+/-7 vs 202+/-6 ms, P less than 0.01) and APD90 (193+/- vs 224+/-5 ms, P less than 0.01), but no change in dV/dtmax (105+/-13 vs 120+/-9 V.s-1, P = NS). These results indicate that certain electrophysiological differences (eg reduced action potential duration), may, in part, contribute to dysrhythmia susceptibility in this presumed viral cardiomyopathy model.

Action Potentials↗

Changes in regional myocardial blood flow and variable development of hypertrophy after aortic banding in puppies.

Supravalvar aortic banding was performed in 6 to 12 week puppies. Sixteen animals were studied 7.3 (3.5 to 10) months later, closed-chested under morphine-chloralose, catheters being positioned in the great vessels and heart, including the left atrium for microsphere injection. Compared with 11 controls, eight dogs developed biventricular hypertrophy, four isolated left ventricular hypertrophy and four had no hypertrophy. The left ventricular systolic pressure was similar (P greater than 0.05) in these 3 banded groups (mean, 30 +/- 2 [SEM] kPa, [222 +/- 16 mmHg], n = 16). The left ventricle was divided into three coronal slices with approximately 59 samples being taken from subendocardial, midwall, and subepicardial layers and additional samples from the atria and right ventricle for regional myocardial flow measurement. As left ventricular hypertrophy increased, the subendocardial/subepicardial flow ratio decreased (r = -0.8). Heterogeneity of left ventricular regional myocardial flow, including a base-to-apex decrease in flow, present in controls, was markedly reduced in the banded dogs. Analysis of variance was found to be the most sensitive test for detecting left ventricular perfusion abnormalities since in banded dogs without hypertrophy, total and regional subendocardial/subepicardial flow ratios were not significantly different from control values, whereas the subendocardial circumferential flow pattern determined by analysis of variance was significantly different from control in these dogs (P less than 0.05).

Animals↗

Early alterations in the function of sarcoplasmic reticulum in a naturally occurring model of congestive cardiomyopathy.

In a naturally occurring model of congestive cardiomyopathy-round heart disease of turkeys, Ca2+ transport of isolated cardiac sarcoplasmic reticulum was evaluated at 1, 10, 28, and 56 days of age. Ca2+ binding in round heart disease birds was reduced to between 55% and 75% of values measured in age-matched commercial control turkeys (P less than 0.05 to less than 0.01). Similarly, Ca2+ uptake in round heart disease birds was reduced to between 52% and 87% of values measured in age-matched commercial control turkeys (P less than 0.05 and less than 0.01). Ca2+-stimulated ATPase values were similar in 1-, 10-, and 28-day-old round heart disease and commercial control turkeys. However at 56 days of age, when all round heart disease birds showed moderate to marked left ventricular dilatation. Ca2+-stimulated ATPase was reduced to 75% of control values (P less than 0.05). Depression of Ca2+ binding and Ca2+ uptake preceded the appearance of cardiac dilatation and may contribute to the pathogenesis of round heart disease. Depression of Ca2+-stimulated ATPase, present only after cardiac dilatation developed, appears to be secondary to cardiac failure. Sarcoplasmic reticulum function in round heart disease birds immunosuppressed by cyclophosphamide treatment (40 mg . kg-1 . d-1 for the first 4 days of age) was evaluated at 10 days of age. This treatment increased Ca2+ binding by 73% (P less than 0.05), and Ca2+-uptake by 58% (P less than 0.01) over values measured in untreated round heart disease birds. Reversal of the altered Ca2+ transport in sarcoplasmic reticulum by early immunosuppression supports the hypothesis that the immune system plays an integral part in the development of the congestive cardiomyopathy of round heart disease.

Aging↗

Transvenous angioplasty of experimental branch pulmonary artery stenosis in newborn lambs.

A dilatable form of bilateral branch pulmonary artery stenosis was created in 27 newborn lambs. Nine lambs were long-term survivors and were dilated with modified Grüntzig balloon dilation catheters. They were allowed to recover for 6-9 weeks, during which time there was no significant change in the mean systolic gradients across the narrowed sites. Thirteen arteries underwent dilation. Dilation was associated with a decrease in the systolic gradient in all cases (from 34.9 mm Hg to 8.1 mm Hg) and an increase in the diameter of the narrowed site (from 4.6 to 7.6 mm) as estimated by angiography. Flows and flow distribution were measured in four lambs before and after unilateral dilation using 15-mu radiolabeled microspheres; in each case, the fraction of total flow to the dilated lung rose after dilation (19.2 to 45.4%), as did the total flow to the dilated lung (30.0 to 69.2 ml/kg-min). Four lambs were catheterized every 2-4 weeks for an average of 16 weeks after dilation; the average gradient in these lambs remained below 10 mm Hg despite considerable growth (from 9.6 to 25.9 kg). Gross pathologic examination showed an intact vascular adventitia in all cases; there were multiple linear tears in the intima in recently (less than 7 days) dilated cases, but complete intimal healing had occurred by 2 months after dilation. No significant morbidity could be attributed to the dilation procedure. These results indicate that clinical trials are warranted.

Angioplasty, Balloon↗

Regional myocardial blood flow and cardiac function in a naturally occurring congestive cardiomyopathy of turkeys.

Round heart disease, a presumed viral myocarditis of turkeys, provides a unique opportunity for the study of congestive cardiomyopathy. Regional myocardial blood flow and cardiac output measurements were made in nine, 19 to 34 day old anaesthetised birds using 141Ce labelled microspheres (15 micron diameter). Atrial, right ventricular and weighted-average left ventricular myocardial blood flow values were similar in control (n = 5) and round heart disease (n = 4) turkeys. The left ventricular subendocardial/subepicardial blood flow ratio of 0.89 +/- 0.02 (mean +/- SE) in round heart disease birds was, however, reduced compared with the value of 1.19 +/- 0.09 in the control birds (P < 0.05). Round heart disease turkeys also had lower systemic pressures and lower cardiac outputs when compared with control birds. M-mode echocardiograms were obtained in 42 unanaesthetised 17 to 37 day old turkeys, 34 control and eight with round heart disease. Echocardiographic evidence of left ventricular dysfunction characterised by left atrial and left ventricular dilation and a markedly reduced left ventricular shortening fraction was found in round heart disease turkeys. Paradoxical motion of the interventricular septum was present in two of eight round heart disease turkeys but in none of the control turkeys. The interventricular septum/left ventricular posterior wall ratio in control and round heart turkeys were similar. Although the body weight of control and round heart disease turkeys were similar, and the diastolic thickness of the left ventricular wall were not substantially different, the ventricular weight/body weight ratio in round heart disease turkeys was increased approximately 52%. The increased ventricular weight was not due to myocardial oedema, as myocardial water content was similar in control and round heart disease turkeys. The features which characterise round heart disease in turkeys: left atrial and left ventricular dilatation, reduced left ventricular shortening fraction, systemic hypotension, low cardiac output, relative subendocardial underperfusion, and an increase in ventricular mass, make it a useful model for congestive cardiomyopathy.

Animals↗

Myocardial perfusion abnormalities in carbon monoxide poisoned dogs.

The effect of carbon monoxide inhalation on the regional distribution of right and left ventricular myocardial blood flow was studied in 12 closed-chest anesthetized dogs. Dogs were exposed to a nonhypoxic mixture of oxygen (21-40%) and carbon monoxide (1.5-2.0%) for 10 min. Myocardial blood flow was measured (15 micron radionuclide-labeled spheres) during control conditions, and 10 and 60 min following discontinuation of carbon monoxide corresponding to carboxyhemoglobin levels (COHb) of 41.6 +/- 2.8 and 26.5 +/- 1.6% (mean +/- SE), respectively. At COHb level of 26.5%, right and left ventricular blood flows were increased to approximately 1.8-1.9 times the control values (1.06 +/- 0.10 vs 0.64 +/- 0.08 mL/min per gram and 1.72 +/- 0.12 vs. 0.91 +/- 0.07 mL/min per gram, respectively, P less than 0.002). At a COHb level of 41.6%, both right and left ventricular vascular beds were maximally or near maximally dilated as right ventricular and left ventricular myocardial blood flow values were increased approximately fivefold. The right and left ventricular subendocardial-subepicardial flow ratios were reduced at both COHb levels (P less than 0.05). Thus, in addition to the global myocardial hypoxia that occurs following elevation of the COHb level, relative subendocardial underperfusion is a component of carbon monoxide poisoning in the intact dog.

Animals↗

Differential sensitivity of regional vascular beds in the dog to low-dose prostacyclin infusion.

The effects of low-dose prostacyclin (PGI2) infusion on abdominal organ, regional central nervous system, and regional myocardial blood flow distribution was studied in 14 open-chested, anesthetized dogs. Blood flow was measured using the radioactive microsphere technique and left atrial (LA) injection of 15-micron spheres. Continuous LA PGI1 infusion (25-35 ng/kg per minute) significantly (P less than 0.05 to P less than 0.005) increased renal cortical (+13%), splenic (+20%), small intestinal (+41%), large intestinal (54%), fundic mucosal (+53%), and antral mucosal (+65%) blood flows whereas pancreatic, gallbladder, and hepatic (arterial) flow remained unchanged. Within the central nervous system blood flow increased in the medulla (+18%) and cerebral cortical gray matter (+17%) but was unchanged in the cervical spinal cord, pons, dorsal thalamus, cerebellum, caudate nucleus, and cerebral white matter. Atrial and ventricular myocardial blood flows and masseter muscle blood flow were unchanged during PGI2 administration. Thus blood flow changes are variable between and within regional vascular beds during low-dose PGI2 infusion in the dog.

Abdomen↗

Effect of low dose prostacyclin infusion on blood flow in acutely ischemic canine myocardium.

The effect of low dose prostacyclin (PGI2) infusion (0.025 to 0.035 microgram/kg per min) on regional blood flow distribution in acutely ischemic left ventricular myocardium was studied in nine open-chest anesthetized dogs. Blood flow was measured using left atrial injection of "15" micron radioactive microspheres 30 minutes following ligation of one to four branches of the left anterior descending coronary artery and again 7 to 9 minutes later during continuous PGI2 infusion when mean aortic pressure was reduced by 11 mmHg (P < 0.005). Heart rate, cardiac output, left atrial and pulmonary artery pressures and coronary sinus PO2 were unchanged during PGI2 administration. PGI2 had no effect on transmural flow in either ischemic (0.32 +/- 0.05 (SE) ml/min per g) or non-ischemic (0.82 +/- 0.06 ml/min per g) myocardium. The regional distribution of blood flow in ischemic and non-ischemic myocardium was also unchanged during PGI2 administration. Specifically, ischemic tissue subendocardial flow (0.21 +/- 0.05 ml/min per g) was not increased (0.20 +/- 0.06 ml/min per g). We conclude that low dose PGI2 infusion reduces systemic pressure but has no effect on either the transumral or regional distribution of blood flow in acutely ischemic canine myocardium.

Animals↗