A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study.

BACKGROUND: Previous metoprolol studies in myocardial infarction patients were performed with immediate-release (IR) metoprolol. This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar ß-blockade over 24 h compared to multiple dosing of metoprolol IR. METHODS: After 2 days of routine metoprolol treatment, 27 patients with suspected acute myocardial infarction were randomized to open-label treatment with metoprolol IR (50 mg four times daily or 100 mg twice daily) or metoprolol CR/XL 200 mg once daily for 3 days. RESULTS: Metoprolol CR/XL 200 mg once daily gave more pronounced suppression of peak heart rate, with lower peak and less variation in peak to trough plasma levels. There were no differences in AUC between the CR/XL and IR formulations, although the trough plasma metoprolol levels were comparable for metoprolol CR/XL 200 mg once daily and metoprolol IR 50 mg four times daily, but lower for metoprolol IR 100 mg twice daily. Both treatments were well tolerated. CONCLUSIONS: Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC. This was accompanied by a more uniform ß-blockade over time, which was reflected by heart rate, and a more pronounced suppression of peak heart rate with similar tolerability. This suggests metoprolol CR/XL may be used as an alternative to metoprolol IR in patients with myocardial infarction.

Maintained normalization of cardiovascular dysfunction 5 years after parathyroidectomy in primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (pHPT) has been associated with premature death in cardiovascular diseases. Short-term prospects for normalization of cardiovascular derangements have been described after parathyroidectomy. This study explores long-term effects of parathyroidectomy on cardiovascular functions in pHPT. METHODS: Thirty consecutive patients with pHPT were reexamined 1 and 5 years after parathyroidectomy, together with 30 matched controls, with echocardiography and a bicycle exercise test. RESULTS: Serum calcium was normal in all patients and control subjects at follow-up. The maximal blood pressure during the exercise was higher before parathyroidectomy (median 223 [range, 200-268] mm Hg vs 202 [165-277] mm Hg, P < .05) but not 5 years after (230 [155-270] mm Hg vs 219 [165-252] mm Hg. The ST-segment depression diminished from -1.4 (-8.3-0) to -0.8 (-3.3-0) mm 1 year after parathyroidectomy and further to -0.1 (-3.3-0.0) mm after 5 years but was unchanged in the control group. The number of ventricular extrasystolic beats at exercise testing in the pHPT group before parathyroidectomy was higher than in the control group (1 [0-340] vs 0 [0-3]). The isovolemic relaxation time at rest was prolonged before parathyroidectomy (mean 100 +/- 17 ms [SD] vs 89 +/- 14 ms, P < .05). CONCLUSION: Parathyroidectomy can induce long-lasting improvement in regulation of blood pressure, left ventricular diastolic function, cardiac irritability (ventricular extrasystolic beats), and other signs of myocardial ischemia, with potential implications for the postoperative life expectancy of patients with pHPT who have undergone parathyroidectomy.

Circadian cardiac autonomic nerve dysfunction in primary hyperparathyroidism improves after parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism has been associated with premature death in cardiovascular diseases, but reversibility and background mechanisms are uncertain. This study investigates autonomic nervous function in hyperparathyroidism because disturbances in this respect have been related to increased cardiovascular morbidity. METHODS: Twenty-one consecutive patients with hyperparathyroidism and 23 matched control subjects without interfering medication underwent electrocardiographic recordings and ambulatory blood pressure (ABP) determination during a 24-hour period. Patients were re-examined at normocalcemia 1 year after parathyroidectomy. Heart rate variability was analyzed in subjects with sinus rhythm and normal atrioventricular conduction; time domain measures were calculated from the RR-intervals, and frequency domain variables were obtained with an autoregressive algorithm, which expressed power distribution (high, low, or very low frequency). RESULTS: Nocturnal increase in low frequency was blunted in cases versus control subjects (103+/-128 m(2) vs 430+/-171 m(2); P=.03). Very low frequency at nighttime correlated inversely with serum parathormone (r=-0.33; P<.05) and increased postoperatively (P=.03). ABP was higher both at daytime and nighttime (P<.05) in patients and remained unchanged after surgery. Systolic ABP correlated with the parathormone (r=0.47; P<.01). CONCLUSION: Results suggest altered circadian autonomic function in hyperparathyroidism that can improve after parathyroidectomy. Despite elevated blood pressure, ABP shows retained diurnal rhythm, which indicates different pathophysiologic mechanisms behind the 2 predictors of cardiovascular death in hyperparathyroidism.

A comparison of the carbon balances of a natural lake (L. Orträsket) and a hydroelectric reservoir (L. Skinnmuddselet) in northern Sweden.

Carbon balances were calculated for the summer stratification period of 2001 for the hydroelectric reservoir L. Skinnmuddselet (created in 1989) and the natural L. Orträsket, and estimated on annual basis for both lakes. The reservoir and the lake have similar chemical characteristics and are located in adjacent catchments in the northern part of Sweden. Our main hypothesis was that the CO(2) production and emissions from the reservoir, L. Skinnmuddselet, would be greater than in the natural L. Orträsket, due to the decomposition of flooded vegetation and peat. The carbon balances showed that the total production of CO(2) per unit lake surface area during the summer was very similar in the natural lake and the reservoir (31.3 g Cm(-2) in L. Orträsket and 25.3 g Cm(-2) in L. Skinnmuddselet). The sediments were the major CO(2) source in the reservoir, while most of the mineralization in the natural lake occurred in the water column. On annual basis the natural L. Orträsket produced and emitted more CO(2) per unit of lake surface area than the reservoir L. Skinnmuddselet since mineralization proceeded during winter when L. Skinnmuddselet was emptied for electricity production. Therefore, the potential for CO(2) emission was not greater in the reservoir than in the natural lake.