PMID- 11078407
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 36
IP  - 5 Suppl 1
DP  - 2000 Nov
TI  - The selective endothelin-A-receptor antagonist LU 135.252 inhibits the direct 
      arrhythmogenic action of endothelin-1.
PG  - S314-6
AB  - Besides being a strong vasoconstrictor, endothelin-1 (ET-1) also causes severe 
      ventricular arrhythmias. The aim of our study was to differentiate between the 
      vasoconstrictor and arrhythmogenic actions of ET-1 by using the selective 
      endothelin-A-(ETA) receptor antagonist LU 135.252 (LU). A bolus injection of 5 
      mg/kg LU was administered to 10 anesthetized mongrel dogs in group A. The 30 min 
      intracoronary ET-1 infusion was started 20 min after the LU bolus at a rate of 60 
      pmol/min. In the control group (group B, n = 8) only ET-1 was administered (60 
      pmol/min). The left anterior descending coronary artery blood flow (CBF), cardiac 
      output, electrocardiograph (ECG) and arterial blood pressure were monitored. Two 
      monophasic action potential duration (MAPD) catheters were placed onto the left 
      ventricular epicardium (LVEP) and into the right ventricular endocardium (RVEND) 
      to follow electrophysiologic changes. No significant changes were observed in 
      blood pressure (0 min vs 30 min: group A, 99.0 +/- 4.5 vs 90.0 +/- 5.2 mmHg, p = 
      NS; group B, 103 +/- 6 vs 104 +/- 3 mmHg, p = NS), cardiac output (0 min vs 30 
      min: group A, 3.5 +/- 0.7 vs 3.2 +/- 0.8 l/min, p = NS; group B, 3.6 +/- 0.4 vs 
      3.3 +/- 0.3 l/min, p = NS), and MAPD90 (0 min vs 30 min: group A, LVEP, 241 +/- 
      11 vs 260 +/- 14 ms; RVEND, 233 +/- 5 vs 239 +/- 8 ms, p = NS), whereas a 
      significant decrease was observed in CBF (deltaCBF 30 min: group A, -28 +/- 2%, p 
      < 0.05; group B, -32 +/- 3%, p < 0.05). In group A ventricular fibrillation (VF) 
      occurred once. Ventricular premature contractions (VPCs) and short, nonsustained 
      ventricular tachycardias (nsVTs) were observed in seven cases. Early after 
      depolarizations and a MAPD90 increase were observed in the control group B (0 min 
      vs 30 min: LVEP, 244 +/- 10 vs 292 +/- 12 ms; RVEND, 255 +/- 9 vs 290 +/- 8 ms) 
      accompanied by VPCs, incessant nsVTs. Sustained VT and VF were evident in seven 
      cases. Our results indicate, that the applied single bolus injection of LU 
      effectively prevents ET-1-induced major ventricular arrhythmias, whereas it has 
      no effect on coronary vasoconstriction. These data support the notion that ET-1 
      possesses a direct arrhythmogenic action.
FAU - Merkely, B
AU  - Merkely B
AD  - Department of Cardiovascular Surgery, Semmelweis Medical University, Budapest, 
      Hungary. merkbel@hermes.sote.hu
FAU - Szabo, T
AU  - Szabo T
FAU - Geller, L
AU  - Geller L
FAU - Kiss, O
AU  - Kiss O
FAU - Horkay, F
AU  - Horkay F
FAU - Raschack, M
AU  - Raschack M
FAU - Juhasz-Nagy, A
AU  - Juhasz-Nagy A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Endothelin-1)
RN  - 0 (Phenylpropionates)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptor, Endothelin A)
RN  - 33JD57L6RW (darusentan)
SB  - IM
MH  - Animals
MH  - Arrhythmias, Cardiac/chemically induced/*prevention & control
MH  - Dogs
MH  - *Endothelin Receptor Antagonists
MH  - Endothelin-1/*antagonists & inhibitors
MH  - Phenylpropionates/*pharmacology
MH  - Pyrimidines/*pharmacology
MH  - Receptor, Endothelin A
EDAT- 2000/11/15 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/11/15 11:00
PHST- 2000/11/15 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/11/15 11:00 [entrez]
AID - 10.1097/00005344-200036051-00091 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S314-6. doi: 
      10.1097/00005344-200036051-00091.