Thesis (PhD)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: The reperfusion injury after myocardial ischemia is relevant in the clinical setting,
after cardiopulmonary bypass for cardiac surgery, after PTCA and stenting and
after cardiopulmonary resuscitation. The components of the reperfusion injury
considered in this study were myocardial stunning and reperfusion arrhythmias.
Calcium antagonists have been shown to be beneficial in attenuating the
myocardial reperfusion injury in the in vitro and in vivo laboratory setting
(Lamping, Gross 1985, Przyklenk and Kloner 1988, Taylor 1990, Ehring 1992,
Gross and Piper 1992). However systemic administration of a dose of calcium
antagonist, large enough to attenuate the myocardial reperfusion injury in the
clinical setting, would inevitably lead to unwanted systemic side effects of the
drug.
The aim of this study was to investigate the hypothesis that an adequate dose of
verapamil administered timeously, directly into the ischemic myocardium, would
attenuate the reperfusion injury, either when administered from the onset of
ischemia, or from 3 minutes before reperfusion.
The anesthetized open chest porcine model of myocardial ischemia (15 min total
LAD occlusion) and reperfusion was employed in this study. A low dose of
verapamil (0.5 mg/8mt or 0.0625mg/mt), a high dose of verapamil (2mg/8m or O.25mg/ml), or vehicle (saline) (8ml) was infused over 8 minutes, directly into
the LAD coronary artery supplying the ischemic segment. The infusion was
started either at the onset of ischemia, or from 3 minutes before reperfusion.
The time taken for the various parameters to return to pre ischemic values was
compared between the different groups.
The results showed that the high dose of verapamil (2mg) attenuated the
reperfusion injury both when administered from the onset of ischemia, and when
administered from 3 minutes before reperfusion, compared to either the low dose
of verapamil, or the saline infusions. The high dose of verapamil groups had a
faster recovery of both systolic contractile function and diastolic function and a
lower incidence of ventricular fibrillation on reperfusion. There were no systemic
effects of verapamil infusion in any of the groups.
The clinical setting of cardiac surgery expressly lends itself to the clinical
application of this finding. There is direct access to the coronary arteries both
before ischemia and before reperfusion. A small dose of calcium channel
blocking drug, with no systemic effect can be administered into the aortic root at
the onset of ischemia, just prior to cardioplegia (when the heart is still warm),
and after rewarming a few minutes prior to removal of the aortic cross clamp. / AFRIKAANSE OPSOMMING: Die reperfusie besering na miokardiale isgemie is klinies relevant na
kardiopulmonêre omleiding vir hart chirurgie, na kardiologiese PTKA en stut
prosedures en na kardiopulmonale ressussitasie. Die komponente van die
reperfusie besering wat in hierdie studie oorweeg is, is miokardiale tydelike
omkeerbare onderdrukking (stunning) en reperfusie arritmieë.
Kalsium antagoniste is gewys om effektief te wees in beperking van die
reperfusie besering in beide in vitro en in vivo laboratorium eksperimente
(Lamping, Gross 1985, Przyklenk en Kloner 1988, Taylor 1990, Ehring 1992,
Gross en Piper 1992). Sistemiese toediening van 'n dosis kalsium kanaal
blokker, voldoende om die miokardiale reperfusie besering in die pasiënt te
beperk, lei egter tot ongewenste sistemiese newe effekte van die middel.
Die doel van die studie was om die hipotese te ondersoek dat 'n voldoende dosis
verapamil, wat betyds direk toegedien is aan die isgemiese miokardium, die
reperfusie besering sal beperk, ongeag of dit toegedien is vanaf die begin van
isgemie, of van 3 minute voor reperfusie.
Die vark model van miokardiale isgemie en reperfusie is aangewend in die studie.
Die varke was tydens die eksperiment onder narkose, met die borskas oop, en
15 minute totale LAD okklusie is toegepas. 'n Lae dosis verapamil (0.5mg/8ml of 0.0625 mg/mt), of hoë dosis veraparnil (2mg/8mt of 0.25mg/mt), of saline
(8mt) is oor 8 minute toegedien direk in die LAD arterie wat die isgemiese
segment voorsien. Die infuus is begin direk na die aanvang van isgemie, of 3
minute voor die aanvang van reperfusie. Die tyd geneem vir terugvoer van
parameters na pre isgemiese waardes is tussen die groepe vergelyk.
Die resultate toon dat die hoë dosis veraparnil die reperfusie besering beperk in
vergelyking met die lae dosis veraparnil of saline infusies, ongeag of dit van die
begin van isgemie, of van 3 minute voor reperfusie toegedien word. Die groepe
wat die hoë dosis veraparnil ontvang het, het vinniger herstel van sistoliese en
diastoliese funksie getoon en het'n laer insidensie van reperfusie disritmieë,
gewys. Geen sistemiese effekte van veraparnail infuus is waargeneem nie.
Die kliniese toepassing van hierdie bevinding is by uitstek geskik vir toepassing
tydens kardiopulmonale omleiding by kardiale chirurgie. Daar is direkte toegang
tot koronêre arteries voor isgemie en voor reperfusie. 'n Klein dosis kalsium
antagonis, met weglaatbare sistemiese effekte, kan toegedien word in die aorta
wortel met die aanvang van isgemie, net voor kardioplegie toediening (hart
steeds warm), en na verwarming, 'n paar minute voor verwydering van die aorta
kruis klem.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/50518 |
| Date | January 2005 |
| Creators | Conradie, Suzanne Louise |
| Contributors | Coetzee, A. (Andre), Moolman, J. (Johan), Coetzee, J. (Johan), Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Interdisciplinary Health Sciences. Emergency Medicine. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
| Format | 291 p. : ill. |
| Rights | Stellenbosch University |
Page generated in 0.0029 seconds