Long-term beta-blocker treatment prevents chronic creatine kinase and lactate dehydrogenase system changes in rat hearts after myocardial infarction
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1Würzburg University, Germany.
Insights
Long-term bisoprolol treatment prevented changes in creatine kinase (CK) and lactate dehydrogenase (LDH) systems after myocardial infarction in rats. Early intervention with bisoprolol improved cardiac function and enzyme levels, suggesting a protective mechanism.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- The precise mechanisms underlying the cardioprotective effects of beta-blocker therapy remain incompletely understood.
- Investigating the impact of beta-blockers on specific biochemical markers post-myocardial infarction is crucial for elucidating their therapeutic benefits.
Purpose of the Study:
- To test the hypothesis that long-term bisoprolol treatment prevents alterations in creatine kinase (CK) and lactate dehydrogenase (LDH) systems following chronic myocardial infarction.
- To evaluate the efficacy of early versus late administration of bisoprolol in mitigating these biochemical changes and preserving cardiac function.
Main Methods:
- A rat model of myocardial infarction was established using left anterior descending coronary artery ligation.
- Six groups of rats were studied: sham-operated, untreated myocardial infarction, and myocardial infarction treated early (30 min post-infarction) or late (14 days post-infarction) with bisoprolol.
- Cardiac function was assessed, and enzyme activities (CK, LDH), isoenzyme profiles, and total creatine levels were measured in myocardial tissue after 8 weeks of treatment.
Main Results:
- Early bisoprolol treatment significantly preserved left ventricular developed pressure compared to untreated myocardial infarction hearts.
- Bisoprolol prevented the reduction in total CK activity and normalized altered CK and LDH isoenzyme profiles in infarcted hearts.
- Early treatment was more effective than late treatment in preventing biochemical system changes and preserving cardiac function; sham hearts showed increased creatine levels.
Conclusions:
- Bisoprolol effectively prevented detrimental changes in CK and LDH systems after myocardial infarction in a rat model.
- These findings suggest that preserving the integrity of these enzyme systems may contribute to the beneficial long-term effects of beta-blocker therapy in patients with chronic myocardial infarction.
Objectives:
We tested the hypothesis that long-term beta-blocker treatment with bisoprolol prevents creatine kinase (CK) and lactate dehydrogenase system changes that occur after chronic myocardial infarction.
Background:
The mechanism of the beneficial effect of beta-blocker therapy is still unclear.
Methods:
Six groups of rats were studied. Sham operated (sham) and hearts with ligated left anterior descending coronary artery (myocardial infarction) were untreated, treated early (beginning 30 min after infarction) or treated late (beginning 14 days after infarction). After 8 weeks, hearts were isolated and buffer perfused isovolumetrically. With a left ventricular balloon, mechanical function was recorded at an end-diastolic pressure of 10 mm Hg. Biopsy samples of noninfarcted left ventricular tissue were taken. Enzyme activities were measured spectrophotometrically; isoenzymes were separated by agar gel electrophoresis; and total creatine levels were measured with high performance liquid chromatography.
Results:
The decrease in left ventricular developed pressure in untreated hearts (120 +/- 9 vs. 104 +/- 5 mm Hg [mean +/- SE], p < 0.05, sham vs. myocardial infarction) after myocardial infarction was prevented by early treatment (118 +/- 9 vs. 113 +/- 4 mm Hg). Late treatment failed to improve mechanical function. Reduction of CK activity occurring in untreated infarcted hearts (6.4 +/- 0.3 vs. 5.1 +/- 0.3 IU/mg protein, p < 0.05, sham vs. myocardial infarction) was prevented by early beta-blocker therapy. The increase in CK isoenzyme BB and MB levels, decrease in mitochondrial CK isoenzyme levels and increase in anaerobic lactate dehydrogenase isoenzyme levels in untreated infarcted hearts did not occur during bisoprolol treatment. The decrease in total creatine levels after myocardial infarction (74.2 +/- 4.9 vs. 54.9 +/- 3.3 nmol/mg protein, p < 0.05, sham vs. myocardial infarction) was prevented by bisoprolol treatment. Early treatment was more effective than late therapy in preventing CK and lactate dehydrogenase system changes. In addition, in sham hearts, a 40% increase of creatine levels above normal levels was detected.
Conclusions:
Bisoprolol prevented changes in CK and lactate dehydrogenase system that occur after myocardial infarction. These observations may be related to the beneficial effects of long-term beta-blocker treatment in patients with chronic myocardial infarction.