Tyrosine hydroxylase activity in the heart of the cardiomyopathic syrian hamster.
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Animals↗
Biomedical subjects
M J Sole
Publications and source records attributed to M J Sole.
A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster.
The development of heart failure in the cardiomyopathic hamster is associated with a decrease in norepinephrine stores and parallel increases in cardiac sympathetic tone and tyrosine hydroxylase activity. Despite the increase in tyrosine hydroxylase, cardiac norepinephrine synthesis does not increase in heart failure. In this study, we have shown that an accumulation of cardiac dopamine accompanies the decline of cardiac norepinephrine. The abnormal content of norepinephrine and of dopamine in the decompensating hamster heart is restored to normal by peripheral ganglionic blockade. The acute increase in cardiac sympathetic tone induced by immobilization stress in control hamsters mimics the alterations in cardiac catecholamine distribution found in heart failure. Other investigators have demonstrated similar alterations in the catecholamine content of the rat submaxillary gland and adrenal medulla following an increase in sympathetic input to these organs. We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. There is evidence that this shift which results in an accumulation of dopamine in the noradrenergic nerve terminals of the heart is a general manifestaion of augmented sympathetic nerve traffic rather than a peculiarity of hamster cardiomyopathy.
Animals↗
Echocardiographic features of an unusual case of aortic valve endocarditis.
In a patient with aortic valve endocarditis a myocardial abscess, complete heart block and acute aortic regurgitation developed. Echocardiography gave evidence of large aortic valve vegetations, and at operation vegetations were found to have destroyed the right coronary cusp and part of the noncoronary cusp. Following surgery the patient recovered. Echocardiography may prove to be a useful noninvasive technique to aid in the timing of surgical therapy in patients with valvular vegetations.
Adult↗
Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster.
Although a reduction in myocardial norepinephrine stores in cardiac hypertrophy and congestive failure is well documented, norepinephrine turnover has been inadequately studied in such hearts. We compared norepinephrine turnover in control and cardiomyopathic hamsters by following the decline in specific activity of myocardial norepinephrine after labelling with an intraperitoneal tracer dose of 3H-norepinephrine. Adult myocardial norepinephrine concentrations were not attained until 4 weeks of age in both strains. There was no difference in the rate of constant (K) for myocardial norepinephrine turnover (0.107+/-0.004 hours-1 vs. 0.100+/-0.005 hours-1) in the two strains of hamsters during the neonatal period. In young control hamsters, K fell to 0.064+/-0.004 hours-1, but that for age-matched hamsters with mild cardiac hypertrophy was 0.102+/-0.001 hours-1 (P less than 0.001). There was little change in K as control hamsters aged. With the development of more severe hypertrophy in cardiomyopathic hamsters, cardiac norepinephrine decreased and resting K rapidly increased to approach the value obtained when hamsters were subjected to immobilization stress (0.302+/-0.013 hours-1). The maximum achievable K remained the same for both control and dystrophic hamsters even during terminal disease. Prolonged immobilization led to a reduction in cardiac norepinephrine in both strains. Ganglionic blockade of failing hamsters completely restored the levels of both cardiac norepinephrine and K to control values. Splenic noradrenergic nerves showed no change in K, norepinephrine content, or maximum K during cardiac decompensation. We conclude that, in the late stages of hamster cardiomyopathy, there is a progressive and possibly specific increase in cardiac sympathetic tone which leads to a concomitant decrease in cardiac norepinephrine. With the loss of sympathetic reserve, congestive failure supervenes.
Animals↗
The effect of peritoneovenous shunting on catecholamine metabolism in patients with hepatic ascites.
The elevated catecholamine levels in cirrhotic patients with ascites have been proposed to be due to sympathetic overactivity secondary either to reduced intravascular volume or to an underlying cardiovascular abnormality such as reduced pressor responsiveness. Furthermore, these elevated catecholamine levels have been proposed to be involved in the pathogenesis of salt and water retention. Therefore, the effect of peritoneovenous shunting on the circulating levels and renal excretion of catecholamines were studied in six patients with massive refractive ascites preoperative within the first 8 hr postoperative and by 2 weeks postoperative under metabolic conditions. The recirculation of ascites into the intravascular compartment resulted perioperatively in significant rises in cardiac output (p = 0.001), para-amino-hippurate clearance (p = 0.08), creatinine clearance, diuresis (p = 0.05) and natriuresis (p = 0.06). Systemic blood pressure remained unchanged while systemic vascular resistance decreased (p less than 0.05). Preoperative circulating levels of free catecholamine were highly elevated, and renal vein concentrations were about 25% higher than renal arterial levels. Perioperatively, there was little change in circulating catecholamine levels or distribution of renal blood flow although renal artery and vein concentrations tended to equalize. In contrast by 2 weeks postoperatively, free catecholamine levels had fallen to within the normal ranges: mean norepinephrine from 1,477.6 +/- 194.6 to 395 +/- 62.9 pg per ml (p less than 0.05); epinephrine from 276 +/- 74.2 to 65.7 +/- 15.0 pg per ml (p less than 0.02), and dopamine from 325.6 +/- 175.2 to 47.9 +/- 5.3 pg per ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A biochemical, histochemical, and electron microscopic study on the effects of iron-loading on the hearts of mice.
Acute iron poisoning and chronic iron overload are well-known causes of myocardial failure. Although the exact mechanism is not known, excess iron-catalyzed free radical generation is conjectured to play a role in damaging the myocardium and altering cardiac function. We report here on the effects of acute and chronic iron-loading on the total iron concentration, glutathione peroxidase activity, and cytotoxic aldehyde production in the heart of a murine model (n = 35). Light microscopic examination for the presence of ferrous and ferric iron was undertaken following histochemical staining for these species. In addition, examination of representative samples by transmission electron microscopy was performed. Our findings show that iron-loading can result in significant increases in total iron concentrations, alterations to glutathione peroxidase activity, and increases in cytotoxic aldehyde concentrations in the hearts of mice. Furthermore, we observe that iron-loading can significantly alter and damage various cellular constituents (e.g., mitochondria, lysosomes, sarcoplasmic reticulum) and this may have bearing on the mechanism of iron-induced heart failure.
Animals↗
Chronic dietary tyrosine supplements do not affect mild essential hypertension.
The blood pressure and plasma norepinephrine response to oral tyrosine, the precursor of norepinephrine, supplementation (2.5 g t.i.d.) of regular meals was examined in 13 untreated patients with mild essential hypertension. Using a randomized double-blind crossover design, each 2-week treatment was followed by a 2-week supplement-free interval. Supine and standing blood pressure and plasma norepinephrine levels were measured at the beginning and end of each 2-week treatment. Plasma tyrosine levels increased (p less than 0.001) from 71.2 +/- 8.0 nM/ml at baseline to 152.8 +/- 17.4 nM/ml 2 hours after the tyrosine supplement. Blood pressure under control conditions was 144 +/- 3 Hg systolic, 91 +/- 2 mm Hg diastolic (109 +/- 2 mm Hg mean) after 30 minutes in the supine position and 148 +/- 4 mm Hg systolic, 102 +/- 3 mm Hg diastolic (117 +/- 3 mm Hg mean) after 5 minutes of standing. Plasma norepinephrine levels were 191 +/- 18 pg/ml in the supine subjects and 390 +/- 33 pg/ml in the standing subjects. No difference in systolic, diastolic, or mean blood pressure, heart rate, or plasma norepinephrine levels were seen between the beginning and end of each period or between groups. Individual changes in blood pressure showed no correlation with individual changes in norepinephrine levels. These results indicate that the addition of a tyrosine supplement to the usual diet of mild hypertensive subjects has no beneficial effect on blood pressure.
Administration, Oral↗
Plasma norepinephrine in stroke.
Cardiac arrhythmias, myocardial necrosis and ECG abnormalities in stroke may result from abnormally high levels of sympathetic activity. To examine this possibility, plasma norepinephrine, epinephrine and dopamine were measured in 74 patients with cerebral infarction, 18 with transient ischemic attacks and 33 non-stroke controls. Mean norepinephrine, epinephrine and dopamine values (pg/ml) in cerebral infarction (433.2, 81.6, 75.6 were higher (p less than 0.01) than in controls (281.1, 60.1, 40.5, respectively). Transient ischemic attacks produced values intermediate to these two groups (391.3, 80.9, 54.9). The elevated catecholamine concentrations in cerebral infarction could not be explained by differences in age, blood pressure, heart rate, stress, type or severity of stroke. The high plasma norepinephrine in the stroke group is consistent with an increase in peripheral sympathetic activity which could produce the cardiac abnormalities of cerebral infarction.
Aged↗
Cardiac sequelae of acute stroke.
The possibility that acute stroke produces an increase in sympathetic tone with resultant cardiac abnormalities was examined in 100 stroke patients admitted to a stroke ICU and in 50 controls found to have diagnoses other than stroke or TIA after admission to the Unit. Continuous 24 hour Holter ECG tapings were performed and serum cardiac enzymes and plasma norepinephrine concentrations were measured within 48 hours after admission. Significantly, (p less than .001) more serious arrhythmias were observed during 24 hour Holter ECG monitoring in stroke patients compared with controls and the difference remained (p less than .01) after matching for age and co-existing heart disease. Arrhythmias were more common in older stroke (p less than .001) and older control (p = .05) patients and with infarction of the cerebral hemispheres (p less than .05) as compared to brainstem lesions. Arrhythmia occurrence was independent of the presence of co-existing heart disease and the level of sympathetic activity. However, the 15 stroke patients with abnormally high CK values (mean 34.3 units) had a higher (p less than .02) mean plasma norepinephrine concentration (650.4 pg/ml) than stroke patients with normal CK (427.7 pg/ml). Acute stroke may cause cardiac arrhythmias and myocardial cell damage, the latter through stroke induced increases in sympathetic tone.
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