Browsing by Subject "levosimendaani"

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  • Berghäll, Minna (University of Helsinki, 1994)
  • Korpi, Anna (Helsingfors universitet, 2011)
    Heart failure is a complex and severe syndrome caused by different kinds of cardiovascular diseases. Pathophysiology of heart failure involves, for example, activation of sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), insufficiently contracting left ventricle, cardiac remodeling, myocyte mishandling of Ca2+ and myocyte loss owing to apoptosis. Despite advances in the management of patients with heart failure, the mortality of patients with heart failure remains high. The use of classic inotropic agents is hampered by poor prognosis due to increase in [Ca2+]i, induction of arrhytmias and increase in the myocardial oxygen consumption. Levosimendan is an inotropic agent that has positive inotropic and anti-stunning effects mediated by the calcium sensitization of the contractile proteins and vasodilatory, anti-ischemic and cardioprotective effects mediated by opening of sarcolemmal and mitochondrial KATP channels. Levosimendan also inhibits cardiac PDE3 predominately at higher concentrations. Levosimendan is currently used only as 24-hour infusion to improve symptoms of acute decompensated heart failure. However, other promising indications have also been discovered. For example, chronic use of oral levosimendan improves survival and protects cardiovascular system in vivo. In the present study, the effects of oral levosimendan, valsartan and their combination use on survival, blood pressure and cardiac remodeling were examined in Dahl/Rapp rats on a high salt diet (8 %). Levosimendan improved the survival in Dahl/Rapp rats on a high-salt diet, although not statistically significantly when compared to control group. The drug combination prevented completely salt-induced cardiovascular mortality. The combination therapy also produced a blood pressure-dependent protection against hypertension-induced hypertrophy measured by heart weight-to-body weight ratio (HW/BW) and echocardiographic parameters. Interestingly, the combination use of levosimendan and valsartan had an additive antihypertensive effect in Dahl/Rapp rats. Levosimendan slightly improved systolic function. However, echocardiography revealed increased IVRT in Dahl/Rapp control rats when compared to control group on low salt diet (0,2 %) indicating impaired diastolic relaxation in Dahl/Rapp rats. In the present study, levosimendan, alone and in combination with valsartan, also corrected hypertension-induced diastolic dysfunction.
  • Kortejärvi, Hanna-Sisko (University of Helsinki, 1997)
  • Matikainen, Heikki (Helsingfors universitet, 2011)
    Chronic heart failure is a major worldwide health problem. It is a complex and severe syndrome caused by different kinds of cardiovascular diseases. Cardiac hypertrophy is frequently caused by hypertension and can lead to abnormality in heart contraction, activation of many neurohumoral mechanism and heart failure. The most important neurohormonal mechanisms of heart failure are activation of sympathetic nervous system and the renin-angiotensin-aldosterone system, insufficiently contracting left ventricle, cardiac remodeling and myocyte loss owing to apoptosis. Antihypertensive drug treatment is often used to prevent or decelerate progression of cardiac hypertrophy. Activation of the renin-angiotensin-aldosterone system plays a major role in heart failure. During the past decades angiotensin converting enzyme inhibitors (ACEIs) have been used as firstline treatment of heart failure. ACEI treatment has been shown to reduce mortality associated with chronic heart failure and improve prognosis of the disease. Angiotensin receptor blockers (ARBs) were expected to replace ACEIs in the treatment of heart failure but for the present they are only an alternative to ACEIs. Beta-blocking agents which reduce activation of sympathetic nervous system have established themself as the second most important treatment of heart failure. Diuretics are widely used as the treatment of heart failure but only aldosterone antagonists has been shown to improve prognosis of the disease. Also digoxin is still used in the treatment of chronic heart failure. In the future renin inhibitors, neutral endopeptidase inhibitors, vasopressin antagonists and molecules that affect inflammatory cytokines could potentially be capable of improving the prognosis of chronic heart failure patients. The major object in the present study was to investigate development of left ventricular hypertrophy induced by abdominal aorta banding in male Wistar rats and prevention of hypertrophy by calcium sensitizer levosimendan and angiotensin II receptor blocker valsartan. Also functionality of abdominal aorta banding as a rodent model of cardiac hypertrophy and heart failure was estimated. Abdominal aorta was constricted above the right renal arteries. That leads to pressure overload and increase in cardiac load. Heart response to pressure overload by hypertrophy in the form of wall thickening. 64 rats were assigned to different groups, each having eight rats. Three of the groups were treated with levosimendan with different daily doses (0,01 mg/kg; 0,10 mg/kg; 1,00 mg/kg) and three of the groups were treated with valsartan with different daily doses (0,10 mg/kg; 1,00 mg/kg; 10,00 mg/kg) via drinking water for eight weeks after the surgery. Sham-operated group underwent the same surgical procedures without constriction of the aorta. All the groups were compared to abdominal aorta banded group without any medical treatment. Cardiovascular parameters such as isovolumic relaxation time (IVRT), left ventricle end-systolic (ESD) and end-diastolic (EDD) dimensions, ejection fraction (EF), fractional shortening (FS), cardiac output (CO), stroke volume (SV), interventricular septum (IVS) and posterior wall (PW) thickness were measured eight weeks after the surgery by using cardiac ultrasound. In the present study levosimendan slightly improved systolic function of the heart. Improvement of the systolic function was seen in a tendency to improve ejection fraction and fractional shortening in abdominal aorta banded rats compared to abdominal aorta banded rats without medical treatment. Neither levosimendan nor valsartan affected diastolic function of heart. Diastolic function was measured by isovolumic relaxation time. Neither levosimendan nor valsartan had significant effect on development of cardiac hypertrophy. Cardiac hypertrophy was estimated by measuring heart weight-to-body weight ratio (HW/BW), left ventricular wall thicknesses and left ventricular internal dimensions in systole and diastole. The present study indicates that outflow constriction by aortic banding is clearly a model of cardiac hypertrophy but not of heart failure.