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Biomedical subjects

R Polikar

Publications and source records attributed to R Polikar.

17 recordsLinked to original sources
PubMed2000

Connexin37 in normal and pathological development of mouse heart and great arteries.

Cx37 is a member of the connexin family of gap junction proteins, whose distribution in heart remains controversial. We have generated novel antibodies against Cx37 to investigate this distribution during normal and pathological development in mouse. Using these affinity-purified antibodies, we have detected Cx37 in hearts and aortas of mouse embryos from day 11 ed. onwards. Immunostaining revealed that during prenatal development Cx37 predominated in endothelial and endocardial cells but was also detectable in small amounts in the trabeculated and compact layers of ventricular myocardium, as well as in the mesenchyme of conotruncal ridges and atrioventricular cushions. Cx37 was also differentially expressed in the ascending and descending portions of the embryonic aorta, according to a pattern which differed in the three layers of the vessel wall. Cx37 distribution was altered in both heart and aorta of mice that had been exposed to all-trans retinoic acid at the beginning of foetal development, whether or not these animals subsequently developed a transposition of great arteries. The data indicate that Cx37 is widely distributed in multiple compartments of cardiovascular system, in patterns which are modulated during development, by retinoic acid.

Animals↗
PubMed1993

The thyroid and the heart.

Cardiovascular manifestations are a frequent finding in hyperthyroid and hypothyroid states. In this review, potential mechanisms by which thyroid hormones may exert their cardiovascular effects and pathophysiological consequences of such effects are briefly discussed. Two major concepts have emerged about how thyroid hormones exert their cardiovascular effects. First, there is increasing evidence that thyroid hormones exert direct effects on the myocardium, which are mediated by stimulation of specific nuclear receptors, which in turn leads to specific mRNAs production. Furthermore, there is some evidence that thyroid hormones may also activate extranuclear sites and may directly alter plasma membrane function. Second, thyroid hormones interact with the sympathetic nervous system by altering responsiveness to sympathetic stimulation presumably by modulating adrenergic receptor function and/or density. Pathophysiological consequences of such direct and indirect thyroid hormone effects include increased myocardial contractility and relaxation that may be related to stimulation by T3 of specific myocardial enzymes. However, when left ventricular hypertrophy occurs in association with hyperthyroidism, it may be related to either direct thyroid hormone-induced stimulation of myocardial protein synthesis or to thyrotoxicosis-induced increases in cardiac work load. Although hyperthyroidism generally has little or no effect on mean arterial blood pressure, hypothyroidism is often associated with increases in diastolic blood pressure that are reversible after hormone substitution and may be mediated in part by sympathetic activation. Moreover, there is increasing evidence that thyroid hormones have direct chronotropic effect on the heart that are independent of the sympathetic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Circadian rhythmicity of rate-normalized QT interval in hypothyroidism and its significance for development of class III antiarrhythmic agents.

Lengthening of repolarization and refractoriness occurs in hypothyroidism; it is associated with a reduced probability of arrhythmias, with the converse occurring in hyperthyroidism. Because the QT interval and its circadian rhythmicity relative to heart rate is poorly defined in man, we used our new computer-assisted technique to measure QT interval in our analysis of 24-hour Holter tapes before and after (8 to 12 weeks) thyroxine (T4) replacement in 10 patients with hypothyroidism; the findings were compared to those in 6 normal control subjects. QTc interval was prolonged (p less than 0.02) and heart rate decreased (p less than 0.005) during the hypothyroid state. Data were analyzed for circadian rhythmicity by repeated-measures analysis. Circadian variation in QTc and heart rate was statistically significant during hypothyroid and euthyroid states (p less than 0.001) as well as in control subjects, but the circadian rhythmicity of QTc interval and heart rate were out of phase; the maximum prolongation of QTc occurred between midnight and 6 A.M., at a time when heart was at its lowest. QTc interval remained significantly prolonged after 8 to 12 weeks of T4 replacement, when biochemical indexes of hypothyroidism had returned to normal values. The computer-assisted QTc interval determination technique that we used, and our data on the circadian rhythmicity of QTc and heart rate, have significant implications for the development of new class III antiarrhythmic agents.

Adult↗
PubMed1990

Decreased adrenergic sensitivity in patients with hypothyroidism.

Cardiovascular sensitivity to catecholamines was assessed in 15 patients with hypothyroidism (mean [+/- SEM] thyroxine [T4] index 2.7 +/- 0.5 micrograms/100 ml, thyroid stimulating hormone [TSH] 136.9 +/- 48.3 microU/ml), aged 45 +/- 4 years and in 8 healthy control subjects. The study was repeated in 10 patients with hypothyroidism 4.0 +/- 0.5 months after thyroid replacement therapy (T4 index 9.9 +/- 2.1 micrograms/100 ml, TSH 3.5 +/- 1.3 microU/ml). In addition, basal, average and maximal heart rates were measured using 24 h ambulatory electrocardiographic (ECG) monitoring, and plasma levels of epinephrine and norepinephrine were determined before and after thyroid replacement. Heart rate increased less after bolus injection of 0.8, 1.6 and 3.2 micrograms of isoproterenol in the hypothyroid (10 +/- 2, 15 +/- 2 and 21 +/- 4 beats/min, respectively) than in the euthyroid (16 +/- 3, 22 +/- 3 and 30 +/- 4 beats/min, respectively) state (p less than 0.05). Control subjects reacted similarly to patients receiving thyroid replacement. Basal heart rate (64 +/- 3 versus 68 +/- 3 beats/min, p less than 0.05) and maximal heart rate (116 +/- 5 versus 133 +/- 5 beats/min, p less than 0.05) were lower on 24 h ambulatory ECG monitoring in the hypothyroid than euthyroid state despite higher basal plasma norepinephrine levels (394 +/- 45 versus 315 +/- 45 pg/ml, p less than 0.05). Thus, patients with hypothyroidism display a decreased cardiac chronotropic response to beta-adrenergic stimulation. This may contribute in part to the decreased basal and maximal daily heart rates seen in patients with hypothyroidism, which occurs despite elevated plasma norepinephrine levels.

Adrenergic beta-Agonists↗
PubMed1990

Age-induced decreases in the messenger RNA coding for the sarcoplasmic reticulum Ca2(+)-ATPase of the rat heart.

Age-associated slowing of cardiac relaxation related to the decline in the Ca2+ pump function of cardiac sarcoplasmic reticulum (SR) has been previously described. It is unclear if the decreased Ca2+ pump function results from a lower amount of Ca2(+)-ATPase protein or a decreased pumping activity of the enzyme. To determine if these alterations could be mediated by changes in the amount of the protein itself, the level of the messenger RNA (mRNA) coding for the Ca2(+)-ATPase of the SR of Fischer rat hearts (4- and 30-month-old rats) were quantitated with a Northern blotting technique. We observed that the levels of SR Ca2(+)-ATPase mRNA were 60% lower in old rats as compared with young rats, suggesting that a quantitative reduction in the levels of the corresponding protein could occur during aging to explain the delayed diastolic relaxation documented in old animals as opposed to a change in the specific activity of this enzyme. The thyroid hormone responsiveness of SR Ca2(+)-ATPase mRNA has been previously established. We have found in this study that the thyroxine levels were consistently lower in old rats; however, this difference was relatively small (4.3 +/- 0.7 and 3.1 +/- 0.8 micrograms/dl [mean +/- SD), respectively, in young and old rats). In addition, no age-induced decrease in 3,5,3'-triiodothyronine levels was observed, suggesting that the aging process itself may be responsible for the changes in SR Ca2(+)-ATPase mRNA levels.

Aging↗
PubMed1990

Plasma norepinephrine kinetics, dopamine-beta-hydroxylase, and chromogranin-A, in hypothyroid patients before and following replacement therapy.

Whether the increased plasma norepinephrine level reported in hypothyroidism is the result of impaired norepinephrine (NE) clearance or increased NE release by nerve terminals is unknown. We, therefore, measured plasma NE levels and clearance in 11 hypothyroid patients before [T4 index, 41.2 +/- 7.7 nmol/L (mean +/- SEM); TSH, 71.4 +/- 23.0 mU/L] and 4 +/- 0.5 months after thyroid replacement (T4 index, 136.4 +/- 24.4 nmol/L; TSH, 3.2 +/- 1.2 mU/L) and in 8 healthy volunteers. Plasma dopamine-beta-hydroxylase and chromogranin-A, which are coreleased with NE by sympathetic nerve endings, were also measured. Plasma NE was higher in the hypothyroid (2.37 +/- 0.24 nmol/L) than in the euthyroid state (1.86 +/- 0.24 nmol/L; P less than 0.02) or in the controls (1.87 +/- 0.27 nmol/L). Plasma clearance of NE, however, was not affected after thyroid replacement (hypothyroid, 2.08 +/- 0.31 L/min; euthyroid, 1.94 +/- 0.21 L/min; controls, 1.86 +/- 0.15 L/min). There was no significant change in plasma dopamine-beta-hydroxylase (hypothyroid, 720 +/- 139 nmol/mL.h; euthyroid, 553 +/- 97 nmol/mL.h) or plasma chromogranin-A (hypothyroid, 48.9 +/- 7.1 ng/mL; euthyroid, 42.9 +/- 5.3 ng/mL) after thyroid replacement. We conclude that the increased plasma NE in hypothyroid patients is not due to a change in plasma clearance, but is more likely secondary to increased NE release.

Adult↗
PubMed1990

Decreased sensitivity to alpha-adrenergic stimulation in hypothyroid patients.

Nine hypothyroid patients had blood pressure and pulse rate responses to the alpha-adrenergic agonist phenylephrine measured before [T4 index, 45.045 +/- 9.009 nmol/L (mean +/- SEM); TSH, 57.1 +/- 23.6 mU/L] and after 4 +/- 0.5 months of thyroid replacement therapy (T4 index, 141.570 +/- 29.601 nmol/L; TSH, 2.6 +/- 1.0 mU/L). Hypothyroid patients had a smaller blood pressure increment and heart rate decrement at both 66.7 and 100 micrograms/min infusion rates of phenylephrine. Furthermore, the slope of the dose-response curves for systolic (2.06 +/- 0.22 vs. 1.32 +/- 0.19; P less than 0.01) and diastolic (1.04 +/- 0.18 vs. 0.62 +/- 0.08; P less than 0.01) blood pressures were significantly greater after thyroid replacement therapy. Pulse rate changes remained proportional to blood pressure changes in hypothyroid patients, so there was no change in baroreflex sensitivity. Plasma norepinephrine levels were higher before than after thyroid replacement (2.41 +/- 0.28 vs. 1.82 +/- 0.29 nmol/L, respectively; P less than 0.01). Thus, hypothyroid patients have diminished pressor sensitivity to an alpha-adrenergic agonist and increased plasma levels of the alpha-adrenergic neutrotransmitter norepinephrine.

Adult↗
PubMed1989

Familial aortic dissecting aneurysm.

A family is described in which nine members over two generations had an aortic dissecting aneurysm or aortic or arterial dilation at a young age. The family has been followed up since 1977 after the death of a second teenager from a kindred of 11. None of the patients had the Marfan syndrome or a history of systemic hypertension. Three members died of ruptured aortic dissecting aneurysm and acute hemopericardium at 14, 18 and 24 years of age, respectively; a fourth member died suddenly at age 48 years, a few years after aortic repair for aneurysmal dilation. One member underwent surgical repair of an ascending aortic dissecting aneurysm at age 18 years and is still alive. Four members are currently under close medical observation for aortic or arterial dilation. Histologic examination of the aortic wall at autopsy or surgery in three patients revealed a loss of elastic fibers, deposition of mucopolysaccharide-like material in the media and cystic medial changes. Types I and III collagen from cultured fibroblasts appeared normal on gel electrophoresis. Results of indirect immunofluorescent studies of the elastin-associated microfibrillar fiber array in skin and fibroblast culture from multiple family members were also normal. This dramatic familial cluster of aortic dissecting aneurysm and aortic or arterial dilation suggests a genetically determined disease of autosomal dominant inheritance although the basic defect remains unknown.

Adolescent↗
PubMed1989

Effect of thyroid replacement therapy on the frequency of benign atrial and ventricular arrhythmias.

Whether thyroid replacement therapy can trigger cardiac arrhythmias in patients with hypothyroidism is not known. In this prospective study, 24 h ambulatory electrocardiographic (ECG) monitoring was used to assess the frequency of atrial and ventricular premature beats in 25 patients with hypothyroidism (5 men and 20 women, aged 56 +/- 3 years) before and 3.5 +/- 0.5 months (mean +/- SEM) after thyroid replacement therapy. Plasma thyroid-stimulating hormone was 73.6 +/- 12.3 and 3.1 +/- 0.6 microU/ml and free thyroxine index was 2.4 +/- 0.4 and 9.8 +/- 0.9 micrograms/100 ml at baseline and after thyroid replacement therapy, respectively. The frequency of ventricular premature beats was not affected by thyroid replacement therapy (from 273 +/- 221 at baseline to 352 +/- 235 beats/24 h after therapy), even in patients with frequent baseline arrhythmias. In contrast, the frequency of atrial premature beats was slightly increased after thyroid replacement therapy (from 47 +/- 17 to 279 +/- 197 beats/24 h), largely as a result of changes seen in three patients. No patient developed new onset of sustained ventricular or supraventricular arrhythmias. Average, basal and maximal heart rates during ECG monitoring increased significantly after thyroid replacement therapy (average 72 +/- 2 to 80 +/- 2; basal 64 +/- 2 to 70 +/- 2; maximal 114 +/- 3 to 130 +/- 3 beats/min, respectively, p less than 0.001). In conclusion, thyroid replacement therapy is safe in patients with common benign cardiac arrhythmias, and does not trigger an increase in arrhythmia frequency except in rare patients with baseline atrial premature beats. It is, however, associated with an increase in basal, average and maximal heart rates.

Adult↗
PubMed1989

Short- and long-term clinical outcome after Q wave and non-Q wave myocardial infarction in a large patient population.

Prognosis for patients with non-Q wave myocardial infarction is controversial although a number of studies have shown a less favorable outlook after hospital discharge for patients with non-Q wave than for those with Q wave infarction. Therefore, the in-hospital and 1-year prognosis was investigated in a sufficiently large patient population (n = 2,024) to allow stratification by subgroups, in particular by age and previous myocardial infarction. Patients with non-Q wave infarction (n = 444; 22% of the total study population) were somewhat older (65 vs. 63 years, p less than 0.001) and had an increased incidence of previous myocardial infarction (46% vs. 24%, p less than 0.001) and congestive heart failure (21% vs. 8%, p less than 0.001) than patients with Q wave infarction. In-hospital mortality of patients with non-Q wave infarction was lower (8.1% vs. 11.5%; p less than 0.06), whereas their 1-year mortality after hospital discharge was significantly higher (13.7% vs. 9.2%, p less than 0.05) than for patients with Q wave infarction. However, total mortalities at 1 year were nearly equal. When patients were subgrouped by presence or absence of a previous myocardial infarction, patients in both subgroups exhibited mortality patterns typical of the entire population with Q wave or non-Q wave infarction. However, when stratified by age and previous infarction, in-hospital mortality for patients with non-Q wave infarction was significantly lower only in patients older than 70 years of age. Similarly, the higher mortality after hospital discharge in patients with non-Q wave infarction occurred only in patients older than 70 years of age without previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

Long-term outcome in patients with inferior myocardial infarction and complete atrioventricular block.

Some studies have reported increased short-term mortality and higher incidence of multivessel coronary artery disease in patients with inferior myocardial infarction and complete heart block, but information is lacking on clinical outcome after hospital discharge. Therefore, data were obtained and analyzed in 749 patients who were admitted with inferior myocardial infarction to four different centers and followed up for 1 year. Six hundred fifty-four patients (Group 1) did not have complete heart block and 95 (Group 2) had complete heart block during their hospital stay (incidence rate 12.8%). Compared with Group 1, Group 2 patients were older (66 versus 61 years, p less than 0.01), more often had signs of left ventricular failure (p less than 0.001) and had higher peak creatine kinase values (1,840 versus 1,322 IU/liter, p less than 0.001). The in-hospital mortality rate was higher in Group 2 than in Group 1 (24.2 versus 6.3%, p less than 0.001). However, at discharge there was no difference between Group 1 and Group 2 in clinical characteristics, left ventricular ejection fraction (0.52 +/- 0.12 versus 0.52 +/- 0.11) or incidence of complex ventricular arrhythmias on ambulatory electrocardiographic monitoring. Furthermore, during the year after hospital discharge, patients in Groups 1 and 2 did not have significantly different mortality rates (6.4 versus 10.1%, p = NS). The incidence rate of reinfarction (4%) was the same in Groups 1 and 2. The incidence of coronary artery bypass surgery was slightly but not significantly higher in Group 1 compared with Group 2 (11 versus 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effect of oral triiodothyronine during amiodarone treatment for ventricular premature complexes.

Whether there is a link between the antiarrhythmic efficacy of amiodarone and its blocking effect on the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) is uncertain. If such a link exists, oral intake of T3 during amiodarone treatment could reverse, at least partially, the antiarrhythmic efficacy of amiodarone. To assess the safety of oral intake of T3 during amiodarone treatment and gain further insight into the relation between the antiarrhythmic action of amiodarone and its metabolic effect on T4, 7 patients (aged 32 to 62 years) with multiple ventricular premature complexes (VPCs) but no underlying heart disease were studied. Antiarrhythmic treatment was indicated for symptomatic relief only. Each patient underwent a 48-hour ambulatory electrocardiographic recording, electrocardiography and thyroid function tests, including plasma T4, T3, reverse T3 (rT3), free T4, free T3 and thyroid-stimulating hormone without treatment (baseline) after 1 month of amiodarone therapy and after a second month of amiodarone therapy with increasing doses of oral T3 (up to 75 micrograms/day). Treatment with amiodarone resulted in a decrease in plasma T3 and free T3, an increase in plasma rT3, a marked diminution in the frequency of VPCs and a prolongation of the corrected QT interval (QTc). During treatment with amiodarone and T3, plasma T3 and free T3 increased and plasma T4, free T4 and rT3 levels decreased; the frequency of VPCs remained low despite shortening of the QTc to values not different from baseline. Thus, in patients with frequent VPCs and no underlying heart disease, oral intake of T3 during amiodarone treatment is safe and does not abolish the antiarrhythmic efficacy of amiodarone, despite a shortening of the QTc.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Hormonal, global, and regional haemodynamic responses to a vascular antagonist of vasopressin in patients with congestive heart failure with and without hyponatraemia.

The pathophysiological role of an increase in circulating vasopressin in sustaining global and regional vasoconstriction in patients with congestive heart failure has not been established, particularly in patients with hyponatraemia. To assess this further, 20 patients with congestive heart failure refractory to digoxin and diuretics were studied before and 60 minutes after the intravenous injection (5 micrograms/kg) of the vascular antagonist of vasopressin [1(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-(0-methyl) tyrosine] arginine vasopressin. Ten patients were hyponatraemic (plasma sodium less than 135 mmol/l) and 10 were normonatraemic. In both groups of patients the vascular vasopressin antagonist did not alter systemic or pulmonary artery pressures, right atrial pressure, pulmonary capillary wedge pressure, cardiac index, or vascular resistances. Furthermore, there was no change in skin and hepatic blood flow in either group after the injection of the vascular antagonist. Only one patient in the hyponatraemic group showed considerable haemodynamic improvement. He had severe congestive heart failure and a high concentration of plasma vasopressin (51 pmol/l). Plasma renin activity, vasopressin, or catecholamine concentrations were not significantly changed in response to the administration of the vasopressin antagonist in either the hyponatraemic or the normonatraemic groups. Patients with hyponatraemia, however, had higher baseline plasma catecholamine concentrations, heart rate, pulmonary pressure and resistance, and lower hepatic blood flow than patients without hyponatraemia. Plasma vasopressin and plasma renin activity were slightly, though not significantly, higher in the hyponatraemic group. Thus the role of vasopressin in sustaining regional or global vasoconstriction seems limited in patients with congestive heart failure whether or not concomitant hyponatraemia is present. Vasopressin significantly increases the vascular tone only in rare patients with severe congestive heart failure and considerably increased vasopressin concentrations. Patients with hyponatraemia do, however, have raised baseline catecholamine concentrations, heart rate, pulmonary arterial pressure and resistance, and decreased hepatic blood flow.

Adult↗
PubMed1984

[The place of kidney biopsies in the diagnosis of isolated hematuria].

Twenty-six patients with idiopathic hematuria, i.e. with normal intravenous pyelography, without arterial hypertension, renal failure or significant proteinuria, underwent renal biopsy in our institution between 1973 and 1981. Segmental proliferative endocapillary glomerulonephritis was diagnosed in 13 cases; in the other 13 patients the renal tissue was either normal (6) or presented only minor lesions of the mesangium (5) or interstitial tissue (2). Twenty-two patients underwent a follow-up examination after a mean of 51 months (range 12-120). The hematuria had disappeared in half of them and no patients had developed hypertension or renal failure. These results suggest that in cases of idiopathic hematuria renal biopsy is not indicated for prognostic or therapeutic reasons, though in some cases it may avoid repeated and potentially dangerous investigations.

Adolescent↗