ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs.

Research output: Contribution to journalJournal articlepeer-review

Standard

ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. / Xing, Dezhi; Kjølbye, Anne Louise; Nielsen, Morten S; Petersen, Jørgen S; Harlow, Kenneth W; Martins, James B; Holstein-Rathlou, N.-H.

In: Cardiovascular Electrophysiology, Vol. 14, No. 5, 2003, p. 510-20.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Xing, D, Kjølbye, AL, Nielsen, MS, Petersen, JS, Harlow, KW, Martins, JB & Holstein-Rathlou, N-H 2003, 'ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs.', Cardiovascular Electrophysiology, vol. 14, no. 5, pp. 510-20.

APA

Xing, D., Kjølbye, A. L., Nielsen, M. S., Petersen, J. S., Harlow, K. W., Martins, J. B., & Holstein-Rathlou, N-H. (2003). ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. Cardiovascular Electrophysiology, 14(5), 510-20.

Vancouver

Xing D, Kjølbye AL, Nielsen MS, Petersen JS, Harlow KW, Martins JB et al. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. Cardiovascular Electrophysiology. 2003;14(5):510-20.

Author

Xing, Dezhi ; Kjølbye, Anne Louise ; Nielsen, Morten S ; Petersen, Jørgen S ; Harlow, Kenneth W ; Martins, James B ; Holstein-Rathlou, N.-H. / ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. In: Cardiovascular Electrophysiology. 2003 ; Vol. 14, No. 5. pp. 510-20.

Bibtex

@article{4127e060ab6211ddb5e9000ea68e967b,
title = "ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs.",
abstract = "INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +/- 0.2 nM: 6/12 vs 0/12; 7.7 +/- 0.6 nM: 7/13 vs 1/12; and 69.2 +/- 5.4 nM: 9/13 vs 1/13. The preventive effect of ZP123 on reentrant VT was closely correlated to reversal of functional, unidirectional conduction block. ZP123 did not affect effective refractory period, surface ECG parameters, mean arterial pressure, or infarct size. CONCLUSION: The stable AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT.",
author = "Dezhi Xing and Kj{\o}lbye, {Anne Louise} and Nielsen, {Morten S} and Petersen, {J{\o}rgen S} and Harlow, {Kenneth W} and Martins, {James B} and N.-H. Holstein-Rathlou",
note = "Keywords: Animals; Blood Pressure; Cell Membrane; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Electrocardiography; Female; Gap Junctions; Heart Block; Heart Conduction System; Incidence; Infusions, Intravenous; Male; Models, Cardiovascular; Myocardial Ischemia; Myocytes, Cardiac; Oligopeptides; Reproducibility of Results; Statistics as Topic; Tachycardia, Ventricular",
year = "2003",
language = "English",
volume = "14",
pages = "510--20",
journal = "Journal of Cardiovascular Electrophysiology",
issn = "1045-3873",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs.

AU - Xing, Dezhi

AU - Kjølbye, Anne Louise

AU - Nielsen, Morten S

AU - Petersen, Jørgen S

AU - Harlow, Kenneth W

AU - Martins, James B

AU - Holstein-Rathlou, N.-H.

N1 - Keywords: Animals; Blood Pressure; Cell Membrane; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Electrocardiography; Female; Gap Junctions; Heart Block; Heart Conduction System; Incidence; Infusions, Intravenous; Male; Models, Cardiovascular; Myocardial Ischemia; Myocytes, Cardiac; Oligopeptides; Reproducibility of Results; Statistics as Topic; Tachycardia, Ventricular

PY - 2003

Y1 - 2003

N2 - INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +/- 0.2 nM: 6/12 vs 0/12; 7.7 +/- 0.6 nM: 7/13 vs 1/12; and 69.2 +/- 5.4 nM: 9/13 vs 1/13. The preventive effect of ZP123 on reentrant VT was closely correlated to reversal of functional, unidirectional conduction block. ZP123 did not affect effective refractory period, surface ECG parameters, mean arterial pressure, or infarct size. CONCLUSION: The stable AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT.

AB - INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +/- 0.2 nM: 6/12 vs 0/12; 7.7 +/- 0.6 nM: 7/13 vs 1/12; and 69.2 +/- 5.4 nM: 9/13 vs 1/13. The preventive effect of ZP123 on reentrant VT was closely correlated to reversal of functional, unidirectional conduction block. ZP123 did not affect effective refractory period, surface ECG parameters, mean arterial pressure, or infarct size. CONCLUSION: The stable AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT.

M3 - Journal article

C2 - 12776869

VL - 14

SP - 510

EP - 520

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 5

ER -

ID: 8420263