Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Sep 2011
Management of acute cardiac failure by intracoronary administration of levosimendan.
Acute cardiac failure caused by myocardial infarction or inadequate cardioprotection during heart surgery is associated with increased mortality and morbidity. Levosimendan is a new drug used in heart failure though it is limited by the systemic hypotension, which develops with intravenous administration. Intracoronary (IC) administration however should affect systemic circulation less while maintaining the beneficial cardiac effects of the drug. ⋯ Better myocardial perfusion improved metabolic requirements, with myocardial oxygen extraction and glucose uptake increasing by 72% and 74%, respectively, whereas lactate production was reduced by 64%. Echocardiography demonstrated additional ventricular segment recruitment. Therefore, IC Levosimendan administration in acute heart failure is safe and efficacious producing improved cardiac function without significant detrimental hypotension.
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J. Cardiovasc. Pharmacol. · Sep 2011
Reactivation of peroxisome proliferator-activated receptor alpha in spontaneously hypertensive rat: age-associated paradoxical effect on the heart.
Prevention of left ventricular hypertrophy remains a challenge in the prevention of hypertension-induced adverse cardiac remodeling. Cardiac hypertrophy is associated with a shift in energy metabolism from predominantly fatty acid to glucose with a corresponding reduction in the expression of fatty acid oxidation enzyme genes. Although initially adaptive, the metabolic switch seems to be detrimental in the long run. ⋯ It is inferred that the stimulation of PPARα before the initiation of metabolic remodeling may prevent cardiac hypertrophy, but reactivation after the metabolic adaptation aggravates hypertrophy. Whether the downregulation of CD36 is mediated by decreased substrate availability remains to be explored. Age-dependent paradoxical effect on the heart in response to fenofibrate, used as a lipid-lowering drug, can have therapeutic implications.
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J. Cardiovasc. Pharmacol. · Aug 2011
ReviewPediatric cardiovascular drug dosing in critically ill children and extracorporeal membrane oxygenation.
Cardiovascular disease in children is common and results in significant morbidity and mortality. The sickest children with cardiovascular disease may require support with extracorporeal membrane oxygenation (ECMO), which provides life-saving assistance for children with refractory cardiorespiratory failure. Many classes of cardiovascular drugs are used in children, but very few of these agents have been well studied in children. ⋯ Esmolol, amiodarone, nesiritide, bumetanide, sildenafil, and prostaglandin E1 seem to require dosing modifications in children supported by ECMO, whereas it seems that hydralazine, nicardipine, furosemide, epinephrine, and dopamine can be dosed similarly to children not supported by ECMO. However, trials evaluating the PK of these drugs in patients supported by ECMO are extremely limited (ie, case reports), and therefore, definitive dosing recommendations are not plausible. Research efforts should focus on evaluating the PK of drugs in patients on ECMO to avoid therapeutic failures or unnecessary toxicities.
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J. Cardiovasc. Pharmacol. · Aug 2011
ReviewManagement of hypertension in the young: role of antihypertensive medications.
Traditionally, antihypertensive medications were used in few children or adolescents, usually just those with underlying renal or other organ system disease. However, with recent data suggesting that the incidence of primary hypertension may be increasing in the young, it is possible that more children and adolescents will be prescribed antihypertensive agents. This article will review currently available pediatric data on the use of calcium channel blockers, agents affecting the renin-angiotensin-aldosterone system and other classes of antihypertensive medications in children, highlighting appropriate indications and safety considerations. Guidelines for use of antihypertensive medications, including choice of initial agent and how to prescribe appropriately, will be presented.
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J. Cardiovasc. Pharmacol. · Aug 2011
Effects of sepiapterin infusion on renal oxygenation and early acute renal injury after suprarenal aortic clamping in rats.
Acute kidney injury (AKI) can occur after aortic clamping due to microvascular dysfunction leading to renal hypoxia. In this rat study, we have tested the hypothesis that the administration of the precursor of the nitric oxide synthase essential cofactor tetrahydrobiopterin (BH4) could restore renal oxygenation after ischemia reperfusion (I/R) and prevent AKI. We randomly distributed rats into 4 groups: sham group; ischemia-reperfusion group; I/R + sepiapterin, the precursor of BH4; and I/R + sepiapterin + methotrexate, an inhibitor of the pathway generating BH4 from sepiapterin. ⋯ Finally, treatment with sepiapterin prevented renal infiltration by inflammatory cells and decreased urine neutrophil gelatinase-associated lipocalin levels indicating a decrease of renal injury. These effects were blunted when adding methotrexate, except for myeloperoxidase. In conclusion, the administration of sepiapterin can prevent renal hypoxia and AKI after suprarenal aortic clamping in rats.