• Korean Circulation Journal
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• v.52 no.3
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• pp.173-197
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• 2022

Treatment options for patients with heart failure (HF) with reduced ejection fraction (HFrEF) have expanded considerably over the past few decades. Whereas neurohormonal modulation remains central to the management of patients with HFrEF, other pathways have been targeted with drugs that have novel mechanisms of action. The angiotensin receptor-neprilysin inhibitors (ARNIs) which enhance levels of compensatory molecules such as the natriuretic peptides while simultaneously providing angiotensin receptor blockade have emerged as the preferred strategy for inhibiting the renin angiotensin system. Sodium glucose cotransporter 2 (SGLT2) inhibitors which were developed as hypoglycemic agents have been shown to improve outcomes in patients with HF regardless of their diabetic status. These agents along with beta blockers and mineralocorticoid receptor antagonists are the core medical therapies for patients with HFrEF. Additional approaches using ivabradine to slow heart rate in patients with sinus rhythm, the hydralazine/isosorbide dinitrate combination to unload the heart, digoxin to provide inotropic support and vericiguat to augment cyclic guanosine monophosphate production have been shown in well-designed trials to have beneficial effects in the HFrEF population and are used as adjuncts to the core therapies in selected patients. This review provides an overview of the medical management of patients with HFrEF with focus on the major developments that have taken place in the field. It offers prospective of how these drugs should be employed in clinical practice and also a glimpse into some strategies that may prove to be useful in the future.

• Journal of Chest Surgery
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• v.51 no.2
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• pp.109-113
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• 2018

Background: Low cardiac output syndrome (LCOS) after cardiac surgery usually requires inotropes. In this setting, critical illness-related corticosteroid insufficiency (CIRCI) may develop. We aimed to investigate the clinical features of CIRCI in the presence of LCOS and to assess the efficacy of steroid treatment. Methods: We reviewed 28 patients who underwent a rapid adrenocorticotropic hormone (ACTH) test due to the suspicion of CIRCI between February 2010 and September 2014. CIRCI was diagnosed by a change in serum cortisol of <$9{\mu}g/dL$ after the ACTH test or a random cortisol level of <$10{\mu}g/dL$. Results: Twenty of the 28 patients met the diagnostic criteria. The patients with CIRCI showed higher Sequential Organ Failure Assessment (SOFA) scores than those without CIRCI ($16.1{\pm}2.3$ vs. $11.4{\pm}3.5$, p=0.001). Six of the patients with CIRCI (30%) received glucocorticoids. With an average elevation of the mean blood pressure by $22.2{\pm}8.7mm\;Hg$ after steroid therapy, the duration of inotropic support was shorter in the steroid group than in the non-steroid group ($14.1{\pm}2.3days$ versus $30{\pm}22.8days$, p=0.001). Three infections (15%) developed in the non-steroid group, but this was not a significant between-group difference. Conclusion: CIRCI should be suspected in patients with LCOS after cardiac surgery, especially in patients with a high SOFA score. Glucocorticoid replacement therapy may be considered to reduce the use of inotropes without posing an additional risk of infection.

• Neonatal Medicine
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• v.18 no.2
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• pp.365-369
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• 2011

Tetralogy of Fallot (TOF) assumes its' most severe form when accompanied by pulmonary atresia (PA). Preserving the patent ductus arteriosus to maintain pulmonary blood flow is life-saving for patients with this congenital heart disease. Milrinone, a selective phosphodiesterase III inhibitor, is a potent vasodilator. Here, we report the successful use of milrinone for a newborn infant with TOF and PA for keeping the ductus arteriosus open and thereby maintaining pulmonary circulation. Milrinone is a useful drug because of its inotropic, lusitropic, and pulmonary vasodilating effects, in addition to its ability to keep the ductus arteriosus open and its relatively mild side-effects. Case series and comparative studies will be needed in the future to verify the effectiveness of this drug.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.41-48
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• 1992

A concentration of 0.01 mM bupivacaine was necessary to maintain approximately 50% depression of contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4 at $30^{\circ}C$. Sodium pyruvate, sodium acetate, and fructose partially restored the contractility of the bupivacaine-depressed atria. However, 20 mM glucose had no effect on the bupivacaine-depressed atria, although this concentration of glucose markedly increased the contractility of normal atria not to be exposed to bupivacaine. Contractility of normal atria was not significantly influenced by sodium pyruvate, sodium acetate, and fructose. The results suggested that at least part of the negative inotropic action of bupivacaine is the result of inhibition of glucose uptake or utilization in the glycolytic pathway, and further pinpoint the blockade as an early step in the glycolytic sequence prior to the phosphofructokinase step.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.75-79
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• 1992

Higenamine, which is one of active component of Aconiti tuber, has been known to have positive inotropic effect through adrenergic beta-receptor. The effect of higenamine on norepinepharine or potassium induced contraction of pulmonary aorta in rabbit were studies. 1. The contraction of aortic strips induced by norepinephrine was suppressec by pre-or post-treatment of higenamine dose dependently and those effects of higenamine were prevented by propranolol. The $pA_2$ value of higenamine against propranolol calculated as 8.25. 2. The effect of higenamine was not affected by phentolamine. 3. Isoprotrenol has shown 10 times stronger vasodiatory effect on norepinephrine induced cntracture than that of higenamine but high concentration $(3.3{\times}10^{-6}\;M)$ of isoproterenol produce intrinsic activity. 4. Vasodilatory effect of higenamine or isoproterenol was not observed in potassium induced contacture of pulmonary aortic strips. These results strongly suggest that higenamine dilated the pulmonary vascular smooth muscle through stimulation of adrenergic beta-receptor.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.209-213
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• 2002

Diltiazem inhibits calcium channels and Iεads to vascular smooth muscle rεlaxation and negative inotropic and chronotropic effects in the hεart. Diltiazem is almost completely absorbεd after oral administration, but its extent of absolute oral bioavailability is reduced because of considerable first-pass hepatic metabolism. Diltiazem is able to dilate renal vasculature and can increase the glomerular filtration rate and renal sodium excretion. The purpose of this study was to report the pharmacokinetic changes of diltiazem after oral administration of diltiazem, 20 mg/kg, in rabbits coadministered with cimetidine, 20 mg/kg and pretreated twice per day for 3 days at cimetidine dose of 20 mg/kg. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly higher in rabbits pretreated with cimetidine than that in control rabbits (p<0.01), showing about 149% increased relative bioavailability. The peak plasma concentration $(C_{max})$ and elimination half-life of diltiazem were increased significantly (p<0.05) in rabbits pretreated with cimetidine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant by pretreated with cimetidine. The effects of cimetidine on the pharmacokinetics of oral diltiazem were more considerable in rabbits pretreated with cimetidine compared with those in control rabbits. The results suggest that the dosage of diltiazem should be adjusted when the drug would be co-administerεd chronically with cimetidine in a clinical situation.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.61-69
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• 1983

Hypothermia is an essential preparatory procedure for cardiac surgery, which lows the metabolic rate and myocardial oxygen demand. However, hypothermia itself is a stress enough to change the tonus of sympathoadrenal system, especially the cardiovascular responses to the catecholamines. It is reported that the positive chronotropic and inotropic response of catecholamines is exaggerated during hypothermia because of decreased norepinephrine uptake at the junctional cleft or decreased catecholamine metabolism. On the other hand, there are evidences of diminished catecholamines responses in low temperature ana further, interconversion of adrenergic receptors is also suggested. Present investigation was planned to observe the cardiovascular changes and its responses to catecholamines during surface hypothermia in cat. Healthy mongrel cats, weighing $2{\sim}3\;kg$, anesthetized with secobarbital(30 mg/kg), were permitted to hypothermia by external cooling technic. Esophageal temperature, ECG (lead II), heart rate, left ventricular pressure with dP/dt, carotid artery pressure and left ventricular contractile force were monitored with Polygragh (Model 7, Grass), and the respiration was maintained with artificial respirator (V 5 KG, Narco). Followings are summarized results. 1) Surface cooling caused progressive decrease of body temperature and reached $l8.8{\pm}0.8^{\circ}C$ and $16.9{\pm}0.6^{\circ}C$ in 120 and 150 min respectively, after immersion into ice water, and ventricular fibrillation was developed at $20.4{\pm}0.65^{\circ}C$. 2) Heart rate, blood pressure and myocardial contractility were decreased after initial increase as the body temperature falls. 3) Systolic and diastolicdd P/dt of left ventricular pressure were decreased and that the decrement of diastolic dP/dt was more marked. 4) On ECG, ST depression, Twave inversion and prolongation of PR interval were prominent in hypothermia, and moreover, the prolongation of PR interval was marked just prior to the development of ventricular fibrillation. 5) The cardiovascular responses to catecholamines, especially to isoproterenol, were suppressed under hypothermia.

• The Korean Journal of Physiology
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• v.9 no.1
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• pp.69-76
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• 1975

Cardiac performances were analyzed in intact turtle heart(Amyda japonica), perfusing with turtle Ringer-Locke's solution containing various hydrogen ion concentration, at several levels of arterial and venous pressure. 1. Ventricular work increased when venous pressure, or venous filling pressure increased, and also increased when arterial pressure increased. 2. The higher the arterial pressure, the lower the cardiac to output, for arterial pressure is the resistance to the ventricular blood flow. On the other hand, in specific arterial pressure, cardiac output was proportional to the venous filling pressure. 3. Heart rates did not change significantly during the perfusion with Ringel· solution of various pH. 4. In the heart Perfused with Ringer solution of various pH, ventricular work was the highest at PH 7.6 (at 6 $cmH_2O$ arterial pressure and 8 $cmH_2O$ venous pressure, the ventricular work was 63.09m$\cdot$cm). However, within the range of pH $7.1{\sim}7.6$, there were no significant changes in cardiac output and ventricular work. Below the level of pH 7.0, ventricular work decreased to less than 56% of maximium value (at $6cmH_2O$ arterial pressure and $8cmH_2O$ venous Pressure, ventricular work was 36.0$gm{\cdot}$ at pH 7.0). At pH 7.7 ventricular work decreased to less than 48% of maximum value (ventricular work: 30.0 $gm{\cdot}$). The nature of the cardiac performance at the various arterial and venous pressures was similar to that of normal heart. 5. Turtle heart seemed to be relatively insensitive to acid-base disturbances. The mechanism of negative inotropic effect of hydrogen ion was discussed.

• Journal of Chest Surgery
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• v.40 no.7 s.276
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• pp.512-516
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• 2007

A mechanical circulatory support system is a life-saving option for treating acute severe respiratory failure or cardiac failure. There are currently a few types of assist devices and the Twin-Pulse Life Support (T-PLS) system is a kind of pulsatile pump. We report here on three patients with severe life threatening cardiopulmonary dysfunction who had the T-PLS system used as an assist device. The indications for applying the T-PLS system were continuing respiratory or cardiac failure in spite of maximal ventilatory and inotropic support. There were two patients with acute respiratory failure due to infection and one patient with cardiac failure due to acute myocarditis. One respiratory failure patient and one cardiac failure patient survived after applying the T-PLS system for 3 days and 5 days, respectively. The T-PLS system is useful as an assist device and it should be considered before multi-organ failure occurs.