PMID- 31461671
OWN - NLM
STAT- MEDLINE
DCOM- 20200813
LR  - 20200813
IS  - 1532-8414 (Electronic)
IS  - 1071-9164 (Linking)
VI  - 25
IP  - 10
DP  - 2019 Oct
TI  - Hemodynamic Effects of Late Sodium Current Inhibitors in a Swine Model of Heart 
      Failure.
PG  - 828-836
LID - S1071-9164(18)31232-6 [pii]
LID - 10.1016/j.cardfail.2019.08.015 [doi]
AB  - OBJECTIVES: To evaluate possible treatment-related hemodynamic changes, we 
      administered ranolazine or mexiletine to swine with heart failure (HF) and to 
      controls. BACKGROUND: Ranolazine and mexiletine potently inhibit depolarizing 
      late Na(+) current (I(Na,late)) and Na(+) entry into cardiomyocytes(.) Blocking 
      Na(+) entry may increase forward-mode Na/Ca exchange and reduce cellular Ca(+2) 
      load, further compromising systolic contraction during HF. METHODS AND RESULTS: 
      Anesthetized tachypaced HF swine received ranolazine (n = 9) or mexiletine 
      (n = 7) as boluses, then as infusions; the same experiments were performed in 10 
      nonpaced controls. The swine with HF had characteristic elevated left ventricular 
      end-diastolic pressure (LVEDP) and reduced maximal left ventricular pressure rise 
      (+dP/dt(max)) and left ventricular peak systolic pressure (LVSP). No significant 
      change occurred after ranolazine dosing for any parameter: LVEDP, +dP/dt(max), 
      LVSP, heart rate, maximal LV pressure fall rate (-dP/dt(max)), or time constant 
      for isovolumic relaxation. Similar results seen in additional swine with HF: 7 
      were given mexiletine, and 7 others were given ranolazine after a 27% rate 
      decrement to maximize I(Na,late). Patch-clamped HF cardiomyocytes confirmed 
      drug-induced I(Na,late) blockade. CONCLUSIONS: Ranolazine or mexiletine blocking 
      I(Na,late) neither worsened nor improved hemodynamics during advanced HF. 
      Although results must be clinically confirmed, they suggest inhibition of 
      I(Na,late) by ranolazine or mexiletine may not exacerbate HF in patients.
CI  - Published by Elsevier Inc.
FAU - Goldstein, Robert E
AU  - Goldstein RE
AD  - Department of Medicine, Division of Cardiology, Uniformed Services University of 
      the Health Sciences, Bethesda, Maryland 20814. Electronic address: 
      robert.goldstein@usuhs.edu.
FAU - Klein, Michael G
AU  - Klein MG
AD  - Department of Medicine, Division of Cardiology, Uniformed Services University of 
      the Health Sciences, Bethesda, Maryland 20814.
FAU - Ouimet, Sean P
AU  - Ouimet SP
AD  - Department of Medicine, Division of Cardiology, Uniformed Services University of 
      the Health Sciences, Bethesda, Maryland 20814.
FAU - Shou, Matie
AU  - Shou M
AD  - Department of Medicine, Division of Cardiology, Uniformed Services University of 
      the Health Sciences, Bethesda, Maryland 20814.
FAU - Hood, Maureen N
AU  - Hood MN
AD  - Department of Radiology, Uniformed Services University of the Health Sciences, 
      Bethesda, Maryland 20814.
FAU - Flagg, Thomas P
AU  - Flagg TP
AD  - Department of Anatomy, Physiology, & Genetics, Uniformed Services University of 
      the Health Sciences, Bethesda, Maryland 20814.
FAU - Haigney, Mark C
AU  - Haigney MC
AD  - Department of Medicine, Division of Cardiology, Uniformed Services University of 
      the Health Sciences, Bethesda, Maryland 20814.
LA  - eng
PT  - Journal Article
DEP - 20190825
PL  - United States
TA  - J Card Fail
JT  - Journal of cardiac failure
JID - 9442138
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Voltage-Gated Sodium Channel Blockers)
RN  - 0 (Voltage-Gated Sodium Channels)
RN  - 1U511HHV4Z (Mexiletine)
RN  - A6IEZ5M406 (Ranolazine)
SB  - IM
MH  - Animals
MH  - Cardiovascular Agents/pharmacology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Drug Monitoring/methods
MH  - *Heart Failure/metabolism/physiopathology
MH  - Hemodynamics/drug effects
MH  - Mexiletine/*pharmacology
MH  - Myocardial Contraction/drug effects
MH  - Ranolazine/*pharmacology
MH  - Swine
MH  - Voltage-Gated Sodium Channel Blockers/pharmacology
MH  - Voltage-Gated Sodium Channels/physiology
OTO - NOTNLM
OT  - Ranolazine
OT  - action potential
OT  - mexiletine
OT  - systolic dysfunction
EDAT- 2019/08/29 06:00
MHDA- 2020/08/14 06:00
CRDT- 2019/08/29 06:00
PHST- 2018/11/14 00:00 [received]
PHST- 2019/08/03 00:00 [revised]
PHST- 2019/08/20 00:00 [accepted]
PHST- 2019/08/29 06:00 [pubmed]
PHST- 2020/08/14 06:00 [medline]
PHST- 2019/08/29 06:00 [entrez]
AID - S1071-9164(18)31232-6 [pii]
AID - 10.1016/j.cardfail.2019.08.015 [doi]
PST - ppublish
SO  - J Card Fail. 2019 Oct;25(10):828-836. doi: 10.1016/j.cardfail.2019.08.015. Epub 
      2019 Aug 25.